SCOPE - medicina.uaslp.mx 1 - Number 2.pdf · mariana salgado bustamante md, phd christian a....

SCOPE

Our mission is to give the opportunity to develop critical thinking skills needed to carry out a well- sustained investigation in order to spread knowledge with great responsibility in the constant search for academic scientific and research excellence that science demands world-

wide

Journal of Medical Students Reviews is a student-founded student-administered and student managed digital and free Access journal under guidance of faculty and staff Created to give opportunity to develop the critical thinking skills needed to carry out a well- sustained investigation

THE JOURNAL OF MEDICALS STUDENTS REVIEWS is a quarterly publication of the Faculty of Medicine Universidad Autoacutenoma de San Luis Potosiacute Av Venustiano Carranza 2405 Col los Filtros CP 78210 San Luis Potosiacute SLP 8 26 23 00 ext 6688 Web page wwwmedicinauaslpmxPublicacionesJMSR Chief Editor Mauricio Pierdant Peacuterez Reserva de derechos al autor exclusivo and Inter-national Estaacutendar Serial Number in process both awarded by the Instituto Nacional del Derecho del Autor Responsible for the latest

update of this issue Date of last updateThe opinions expressed in the content of the articles are the responsibility of the authors and do not necessarily reflect the point of view of the reviewers or the publisher It is totally forbidden the total or partial reproduction of the content of this magazine by any means

even electronic nor translated into other languages without written authorization of its publishers Journal of Medical Students Reviews by Facultad de Medicina UASLP is licensed under a Creative Commons Reconocimiento-NoCo-

mercial-SinObraDerivada 40 Internacional License

MISSION

VALUES

By 2023 we will be an international magazine included in the most important indexes of quality and quotation in the area of health in constant growth and with publications of the

highest quality

VISION

HonestyMedical student empowerment

Compromise Responsibility

DIRECTIVE COMMITTEE

RECTOR OF THE UNIVERSITYDIRECTORCHIEF EDITORASSOCIATE EDITOR

MANUEL FERMIacuteN VILLAR RUBIO M ARCH

ALEJANDRO JAVIER ZERMENtildeO GUERRA MDMAURICIO PIERDANT PEacuteREZ MD MSC

MARIacuteA ISABEL PATINtildeO LOacutePEZ MLIS

LILIANA ITAMAR CARRILLO BARBA MSANDREacuteS CASTILLO DIMAS MSALEJANDRA DE LA TORRE SOTO MSROCIacuteO DANIELA OCHOA VALTIERRA MSLIZETH GUADALUPE ORTIZ VAacuteZQUEZ MS

AREA EDITORS

BLANCA ARIADNA CARRILLO AacuteVALOS MD MARIANA SALGADO BUSTAMANTE MD PhDCHRISTIAN A GARCIacuteA SEPUacuteLVEDA MD PhDSERGIO SAacuteNCHEZ-ARMASS ACUNtildeA MD PhDESTHER LAYSECA ESPINOSA MD PhDUCIEL RENEacute OCHOA PEacuteREZ MD MSC

ANTONIO A GORDILLO MOSCOSO MD PhD EMMANUEL RIVERA LOacutePEZ MDDAVID DE DANIEL ESMER SAacuteNCHEZ MDRAUacuteL ROQUE SAacuteNCHEZ MDJUAN CARLOS TORO ORTIZ MDAMADO NIETO CARAVEO MD MSC

MARISOL OROCIO CONTRERAS MD PhD

EDITORIAL COMMITTEE

MORPHOLOGYBIOCHEMISTRYMOLECULAR BIOLOGYPHYSIOLOGYIMMUNOLOGYMICROBIOLOGYPHARMACOLOGYINTERNAL MEDICINESURGERYPEDIATRICSGYNECOLOGYPUBLIC HEALTHMENTAL HEALTH

INDEX

Editorial The role of academic journals in medical educational settingsMAURICIO PIERDANT PEREZ

CHIEF EDITOR

Effectivity of Suprathelreg on second degree burns

ALEJANDRO AGUILAR LLAMAS MS CHRISTIAN ADRIAacuteN ALEMAacuteN ALVARADO MS

JUAN CARLOS ALVARADO DE ALBA MS MAYRA DANIELA BANDA VILLEDA MS

KARLA CANTUacute FLORES MS BRENDA CAacuteRDENAS GONZAacuteLEZ MS DENISSE CAacuteRDENAS

GONZAacuteLEZ MS

Pediatric Esophageal Achalasia report of a case and an integrative

review of the pediatric surgical treatmentIVAacuteN LEDEZMA BAUTISTA MS

Genetic predisposition in the etiology and pathogenesis of AchalasiaMARIacuteA OA VALENZUELA ALMADA MS HEacuteCTOR SALVADOR AacuteLVAREZ MANZO MS

ALEJANDRO QUINTERO VILLEGAS MS

1-2 p

3-11p

12-18 p

19-37p

Guide for authors JMSR

ARTICLES

38-40p

EDITORIAL

ThE ROLE Of ThE AcADEmIc jOuRnALs In mEDIcAL EDucATIOnAL sETTIngs

Pierdant-Peacuterez Mauricio1

1Chief Editor

Facultad de Medicina Universidad Autoacutenoma de San Luis PotosiacuteAv Venustiano Carranza 2405 San Luis Potosiacute SLP ZP 78210 Mexico

1

According to the definition posted in Wikipedia an academic or scholarly journal is ldquoa periodical publication in which scholarship relating to a particular academic discipline is published

Academic journals serve as permanent and transparent forums for the presentation scrutiny and

discussion of research

They are usually peer-reviewed or refereed Content typically takes the form of articles presenting

original research review articles and book reviews The purpose of an academic journal according to

the first editor of the worlds oldest academic journal Henry Oldenburg is to give researchers a venue

to impart their knowledge to one another and contribute what they can to the Grand design of

improving natural knowledge and perfecting all Philosophical Arts and Sciences1

So this definition was taken into account when we decided to create The Journal of Medical Students Reviews an academic journal made by students for students open free access that permits and encourages the students not only from our faculty but from everywhere to make integrative research on any medical subject This effort makes a perfect introduction for medical research in the way that it creates the basis for the understanding of complex medical problems and states the current information to start prospective research

22

This means that this journal not only tries to serve as a presentation of medical information for the undergraduate students but it can also serve as an inspirational reading of ideas for research that seasoned and novel investigators can take to iniciate well sustained research

Another advantage of the JMSR is that we act as a facilitator to learn and practice interaction with the world of journals and scientific publications we do not reject articles recieved from medical students what our editorial comittee (formed by medical students well trained in integrative research) does is that it gives advice to the students to make their integrative research well sustained supervised by the area editors and the chief editor

These qualities may help students engage into research in our medical school we introduce students to research in the second year of medical school by teaching them the principles of research articles (what we call the ldquoanatomyrdquo and ldquophisiologyrdquo of a scientific article) then we introduce them to the basic and complex forms of documentary search in the web and finally they get to practice by means of creating an integrative search of a scientific question or a theme wich in many times is the result of issues not stated or not well comprehended in the formal lectures with their proffessors Once they get their integrative research done they can publish it in the JMSR and others start persuing a

side research program with members of our research academy

In this issue of the JMSR we present two articles on Achalasia one of them associated with children and the other makes an integrative aproach to the genetic predisposition of Achalasia from students of the Universidad Panamericana School of Medicine in Mexico City the third article is about the Effectivity of suprathelreg on second degree burns this article adresses the research up to date of a novel dreessing on the treatment of second degree burns

We at JMSR hope our readers find well sustained information and that this academic journal fullfills the objetives planned to encourage research in all of the modalities

BIBLIOGRAPHY

1 Academic journal In Wikipedia [Internet] 2018 [cited 2018

Feb 14] Available from httpsenwikipediaorgwindex

phptitle=Academic_journalampoldid=824340753

2 Abu-Zaid A Alkattan K Integration of scientific research

training into undergraduate medical education a reminder call

Med Educ Online 2013 Jan18(1)22832

3 Murdoch-Eaton D Drewery S Elton S Emmerson C

Marshall M Smith JA et al What do medical students

understand by research and research skills Identifying

research opportunities within undergraduate projects Med

Teach 201032(3)e152-e160

How to cite this article Pierdant-Peacuterez M The role of academic journals in medical educational settings JMSR 2017 Oct-Dic1(2)1-2


Aguilar-Llamas Alejandro1 Alemaacuten-Alvarado Crhistian Adriaacuten1 Alvarado-de-Alba Juan Carlos1 Banda-Villeda Mayra Daniela1 Cantuacute-Flores Karla1

Caacuterdenas-Gonzaacutelez Brenda1 Caacuterdenas-Gonzaacutelez Denisse11Facultad de Medicina Universidad Autoacutenoma de San Luis Potosiacute

Av Venustiano Carranza 2405 San Luis Potosiacute SLP ZP 78210 Meacutexico

Abstract

Key Words MEMBRANE ASYMMETRY LIPID BILAYER AUTOIMMUNITY APOPTOSIS AUTOIMMUNE DISEASES

Corresponding autor

Cantuacute-Flores Karlakarlacantufloreshotmailcom

How to cite this article Aguilar-Llamas A Alemaacuten-Alvarado CA Alvarado-de-Alba JC Banda-Villeda MD Cantuacute-Flores K Caacuterdenas-Gonzaacutelez B et al Effectivity of Suprathelreg on second degree burns JMSR 2017 Oct-Dic1(2)3-11

3

Introduction A burn is an injury to the skin or other organic tissue caused mainly by heat or radiation radioactivity electricity friction or contact with chemicals Depending on its duration and intensity the thermal insult can affect both the epidermal and dermal layers of the skin The basic objective of wound treatment is to obtain such tissue regeneration that would involve the reconstitution of structural and functional properties of the damaged skin layers Standard treatment involves immediate debridement of nonviable tissue and coverage of the wound with dressings that provide favorable conditions for repithelialization One of such dressings which displays the properties of the natural epithelium is Suprathelreg Methods The following metasearchers were used to retrieve the articles quoted PubMed and Trip Database As well as SpringerLink Wiley Online Library Web of Science Scopus Science Direct Academic Search Complete Biblioteca Virtual en Salud and Nature data bases all of them from health area Results Suprathelreg is an absorptive synthetic wound covering which consists of a copolymer-foil of DL-laktidtri-methylencarbonate and e-caprolakton It offers high plasticity with an immediate adaptability to the wound bed at body temperature The moisture permeability prevents the accumulation of wound secretion and avoids the dehydration of the wounds Many authors report the advantages of this product in small expenditure of care rapid mobilization short hospitalization time fast dismissals and additionally a reduction of medical costs significantly less pain reduced number of intravenous narcotic doses No significant difference in healing time of the grafts donor sites was detected between Suprathelreg and other treatments Conclusion It is important to know the most effective treatment for patients with partial-thickness burns since this way we can reduce costs and hospitalization times in addition to a quick recovery helping to reduce bleeding and pain and favoring reepithelialization According to the comparative articles analyzed in this review Suprathelreg it turns out to comply with these characteristics placing itself as one of the best options

44

In our hospital service performing the internship in the burn unit in contact with patients and getting involved in their care treatment and evolution we studied and investigated different treatment modalities and we perceived that Suprathelreg was an innovative treatment so we decided to go deeper into the theme starting from the question How effective is the use of Suprathelreg in second degree burns

The skin is the largest organ of the human body consisting of several layers which possess different properties and perform different physiological functions The most important task of the skin is the creation of a barrier between the external environment and the body Its other functions include immune protection of the body the sense of sensation and the ability to conduct regeneration and healing processes(1)

The loss of skin integrity caused by a trauma or disease may result in acute physiological and immune disorders that may even be fatal One of the most common causes of skin loss is a burn trauma

A burn is an injury to the skin or other organic tissue caused mainly by heat or radiation radioactivity electricity friction or contact with chemicals Thermal burns occur when some or all of the skin cells or other tissues are destroyed by hot liquids (scalds) hot solid objects (contact burns) flames (flame burns)According to the most recent data burn death rates are slightly higher in women than in men Children are especially vulnerable to burns Burns are the fifth most common cause of non-fatal injuries during childhood(2)

Partial-thickness burns typically cover a relatively small percentage of total burn surface area (TBSA) and are a common occurrence in emergency and trauma as well as in specialized burn care (3) Depending on its duration and intensity the thermal insult can affect both the epidermal and dermal layers of the skin it may extend superficially into the papillary dermis or deep into the reticular dermis and characteristically causes severe pain(45)

Healing of the resulting wounds typically occurs within 2 to 3 weeks after injury and significant scarring is not expected in superficial partial thick-ness burns(6)

The following metasearchers were used to retrieve the articles quoted PubMed and Trip Database As well as SpringerLink Wiley Online Library Web of Science Scopus Science Direct Academic Search Complete Biblioteca Virtual en Salud and Nature data bases all of them from health area The criteria implemented for the selection was essential text which revealed significant information in the summary comply with indicated limits (human 10 years)

The ldquohumanrdquo limit was stablished since the main purpose of the study was to search the evidence for the effectiveness of Suprathelreg as a treatment in second degree burns evaluating its behavior on human skin

The ldquo10 yearsrdquo boundary is owing to the fact that most representative articles for this review which include prospective human trials started to publish at the year 2007 Exclusion criteria were do not meet the terms with the general theme and articles with different typology than the established

QUESTION AND CONTEXT

METHODS

INTRODUCTION

55

limits Obtaining the following results with the different combinations of keywords where the first number are the articles obtained and the second are those that were used discarded articles were those that did not meet the inclusion and exclusion criteria or that were repeated in the searches made ((ldquoSuprathelregrdquo OR ldquocopolymer-foil of D L-lactide-co-trimethylene carbonate and D-caprolactonerdquo AND Burn) 19419 another form of search was (ldquoSuprathelregrdquo AND Burn) 1104 (Figure I)

The basic objective of wound treatment is to obtain such tissue regeneration that would involve the reconstitution of structural and functional properties of the damaged skin layers to a level which is as close as possible to the pre-traumatic local condition(1) Standard treatment involves immediate debridement of nonviable tissue and coverage of the wound with dressings that provide favorable conditions for reepithelialization(4)

RESULTS

Figure 1 Search strategy

66

An ideal wound dressing serves as a barrier to prevent transdermal fluid loss mitigates the risk of infection allows reepithelialization of the wound surface is cost-effective easy to use and controls pain While a wide variety of dressings are currently available conclusive data on the most favorable treatment option for partial- thickness burns in an outpatient setting are sparse (7)

One of such dressings which display the properties of the natural epithelium is Suprathelreg Our objetive was to search the evidence for the effectiveness of Suprathelreg as a treatment in second degree burns describing its characteristics and uses as well as the determination of advantages and disadvantages it has against other treatments

The early closure of debrided superficial partial-thickness burns is one of the primary focuses in treatment of burns patients Biosynthetic wound dressings or bioengineered alternative tissue are designed to cover the wounds in order to temporarily restore an impaired barrier and allow a better prognosis (8) Biological substitutes such as amnion or xenogenic materials have a non-negligible viral risk (9 10) Thus biosynthetic wound dressings exclude these risks

Suprathelreg is an absorptive synthetic wound covering which consists of a copolymer-foil of DL-laktidtri-methylencarbonate and e-caprolakton It offers high plasticity with an immediate adaptability to the wound bed at body temperature The moisture permeability prevents the accumulation of wound secretion and avoids the dehydration of the wounds(11)

Elasticity makes it possible to apply the dressing to the wound at the sites which are difficult to treat and also ensures

that the dressing will closely adhere to all the curves and depressions on the damaged skin surface (1213)

Dressing transparency enables constant control of the healing process whereas the biodegradability eliminates the need for dressing removal before the end of the burn wound epithelialization process (14)

Many authors report the advantages of this product in small expenditure of care rapid mobilization short hospitalization time fast dismissals and additionally a reduction of medical costs significantly less pain reduced number of intravenous narcotic doses(81213151617) No significant difference in healing time of the grafts donor sites was detected between Suprathelreg and other treatments (11 13 18) Keck et al in 2011 found that at day 15 after the event Suprathelreg had a closure rate of 444 while autologous slip-thickness skin grafts had a 889 rate with total closure in both groups at the day 30 (19)

The way of use is different according to the author Madry et al in 2011 20 stated that before Suprathelreg application the wound was washed with water and a detergent and debridement was performed so as to apply Suprathelreg directly onto the undamaged skin layers A single layer of paraffin soaked gauze and then a dressing of sterile gauze creating an absorptive layer were applied on top of Suprathelreg

The absorptive layer of the dressing was changed daily and the condition of the remaining layers and the burn wound was inspected on a daily basis Suprathelreg was removed at places where it peeled off from the wound by itself Highton et al in 2012 (14) stated that the wounds were thoroughly

77

debrided and cleaned with chlorhexidine antiseptic solution under opiate or general anesthesia and reassessed Suprathelreg was applied to the wounds followed by a layer of Vaseline gauze dry gauze and crepe bandage

The outer dressings were changed every 5ndash10 days unless clinical problems dictated otherwise If the previous treatment of the wound is not the adequate will be consequences in the same study of Highton et al (14) thirty-three children with burns were treated with Suprathelreg Ten patients took longer than 21 days to heal of whom four developed hypertrophic scarring which was strongly associated with wound infection

The cost is one of the most important criteria for the wound dressing selection Indeed the ultimate cost of any dressing includes not only the product but also the length and complexities of patient care including the expenses of dressing changes complications and hospital stay A study realized in Austria in 2017(21) compared Biobrane and Suprathelreg for the cost situation in partial-thickness burn patients with a TBSA of 15 It could be demonstrated that Suprathelreg was cost-effective over Biobrane The study was limited due to the fact that only few micro costing data available for burns injuries in both countries Thus further research will be needed to confirm this result (Table I)

The treatment of partial-thickness burns demands several qualities from modern wound dressings pain minimization promotion of reepithelization ease of care and cost-effectiveness Both biological and synthetic bandaging have been developed to meet these objectives This study compared the quality and efficiency of different materials to answer one question how effective is the

use of Suprathelreg in second degree burnsThe data evaluated in the majority of the studies was pain using a 10-point Visual Analogue Scale duration of healing with the days of treatment until complete reepithelialization ease of care taking the total number of necessary dressing changes until complete reepithelization duration of single dressing change reduces difficulty of material application and removal dressingrsquos management of wound fluids cost effectiveness with total material costs (investigated wound dressings additional dressing material) costs for nursing and physician care and finally the scar assessment using in almost all of the studies the Vancouver scar scale 3 to 6 months after harvesting the graft

In partial-thickness burns pain represents a common complaint In accordance with the results of all the reviewed studies we observed significant pain reduction in patients treated with Suprathelreg using a 10-Point Visual Analogue Scale in all of them This pain reduction has been assumed to be related to the immediate release of incorporated analgesics together with a moist wound environment Markl et al described surprisingly that patients treated with Suprathelreg experienced particular pain increase on the fifth day of treatment particularly if starting mobilization compared with Mepitel they hypothesized that the increased pain scores on the fifth postoperative day may be related to patient mobilization that induces untimely detachments from wound surfaces because of the development of material rigidity in addition similar to Mepitel Biatain-Ibu occasionally severely adhered to wound surfaces (after 48ndash72 hours) thus causing painful material removal with elevated pain scores

88

Table 1 Results

99

Table 1 Continuation

1010

The mean time to reepithelialization in randomized controlled trials (RCT) that used other (semi)synthetic dressings varied between 75 and 236 days In adults no difference in reepithelialization was found when Suprathelreg was compared to other (semi)synthetic dressings (Biobrane and Omiderm) or split thickness skin graft (STSG)

Suprathelreg showed best ease of care easy and precise initial application with excellent material elasticity and no necessary material removal from wound surfaces Schwarze et al described as the wound heals Suprathelreg becomes transparent and offering constant wound monitoring

Because it peels off (detachment through absorption) it allows pain-free removal without manipulating the healing process Pain reduction together with the lower number of dressing changes represents the major advantages of this synthetic skin substitute

All Suprathelreg-treated patients presented excellent healing results with good skin texture and full mobility of the affected anatomic areas In some studies follow-up was longer than 3 months and all of these patients demonstrated excellent healing results

A comparison of overall treatment costs showed that Suprathelreg represented the most expensive dressing material with the highest treatment costs Although this dressing significantly minimizes the amount of nursing and physician care its high prize makes treatment least cost-effective This may represent a limiting factor for its application however after acquiring approval of Suprathelreg it was possible to treat numerous light and medium burns and split skin donor sites very successfully and with significantly less pain

Outpatient treatment of second degree burns demand special considerations regardless of the dressing utilized According to the articles analyzed in this review the use of synthetic dressings such as Suprathelreg comparing it with paraffin gauze or autologous grafts is recommended It is remarkable to mention that most clinical trials do not have a significant number of patients The only disadvantage found in Suprathelreg was its expensiveness comparing with diverse medical options However the effectiveness of Suprathelreg relies on the benefits which include decreased disturbance of the wound bed favoring reepithelialization without many apposition changes and reduced pain especially in the pediatric patient population although most of the dressings share equivalent healing times

POINTS TO REMEMBER

bull A burn is an injury to the skin or other organic tissue caused mainly by heat or radiation radioactivity electricity friction or contact with chemicals bull A second degree burn is one that involves the epidermis and part of the dermisbull It is vital to take into account factors such as age extent of the burn cause and place of the burn at the time of choosing the treatmentbull Suprathelreg supposes a good option of treatment due to the reduction of pain and bleeding as well as favoring reepithelialization but we do not have to set aside its high cost

Conflict of interest There was no conflict of interest in the realization of this review the authors respond to no organization financial disclosure or company

CONCLUSIONS

1111

Acknowledgements

This publication is addressed with an expression of gratitudeTo Dr Mario Aurelio Martiacutenez Jimeacutenez for his support and motivation in carrying out this project for his enthusiasm and knowledge transmitted throughout the undergraduate course

BIBLIOGRAPHY1 Kamolz LP Lumenta DB Kitzinger HB Frey M Tissue

engineering for cutaneous wounds an overview of current

standards and possibilities Eur Surg 200840(1)19-26

2 Organizacioacuten Mundial de la Salud Quemaduras [Internet]

Organizacioacuten Mundial de la Salud 2017 [cited 2018 Feb 14]

Available from httpwwwwhointmediacentrefactsheets

fs365es

3 American Burn Association 2016 ABA Annual Burn

Repository [Internet] Available from httpwwwameri- burn

orgNBRphp Accessed January 5 2018

4 Lewis GM Heimbach DM Gibran NS Evaluation of the burn

wound management decisions En Herndon DN Total Burn

Care 4th ed Philadelphia Elsevier 2012 p 125-30

5 Gee Kee E Kimble RM Cuttle L Stockton K Comparison of

three different dressings for partial thickness burns in children

study protocol for a randomised controlled trial Trials 2013

Nov 2514(403)1-8

6 Cubison TC Pape SA Parkhouse N Evidence for the link

between healing time and the development of hypertrophic

scars (HTS) in paediatric burns due to scald injury Burns 2006

Dec32(8)992-999

7 Wasiak J Cleland H Campbell F Spinks A Dressings for

superficial and partial thickness burns Cochrane Database

Syst Rev 2013 Mar28(3) CD002106

8 Uhlig C Hierlemann H Dittel K-K Actual strategies

in thetreatment of severe burnsmdashconsidering modern

skinsubstitutes Osteo Trauma Care 2007152-7

9 Brusselaers N Pirayesh A Hoeksema H Verbelen J Blot

S Monstrey S Burn scar assessment A systematic review of

objective scar assessment tools Burns 201036(8)1157-1164

10 Cua AB Wilhelm KP Maibach HI Elastic properties

ofhuman skin relation to age sex and anatomical region Arch

Dermatol Res 1990 Aug282(5)283-288

11 Rahmanian-Schwarz A Beiderwieden A Willkomm L Amr

A Schaller H-E Lotter O A clinical evaluation of Biobranereg

and Suprathelreg in acute burns and reconstructive surgery

Burns 2011 Dec37(8)1343-1348

12 Uhlig C Rapp M Hartmann B Hierlemann H Planck H Dittel

K SuprathelregmdashAn innovative resorbable skin substitute for

the treatment of burn victims Burns 2007 Mar33(2)221-229

13 Schwarze H Kuumlntscher M Uhlig C Hierlemann H

Prantl L Noack N et al Suprathelreg a new skin substitute in

the management of donor sites of split-thickness skin grafts

Results of a clinical study Burns 2007 Nov33(7)850-854

14 Highton L Wallace C Shah M Use of Suprathelreg for partial

thickness burns in children Burns 2013 Feb39(1)136-141

15 Schwarze H Kuumlntscher M Uhlig C Hierlemann H Prantl

L Ottomann C et al Suprathelreg a New Skin Substitute in

the Management of Partial-Thickness Burn Wounds Ann Plast

Surg 2008 Feb60(2)181-185

16 Everett M Massand S Davis W Burkey B Glat P Use of a

copolymer dressing on superficial and partial-thickness burns

in a paediatric population J Wound Care 2015 Jul24(7)S4-S8

17 Kaartinen IS Kuokkanen HO Suprathelregcauses less

bleeding and scarring than MepilexregTransfer in the treatment

of donor sites of split-thickness skin grafts J Plast Surg Hand

Surg 2011 Sep45(4-5)200-203

18 Markl P Prantl L Schreml S Babilas P Landthaler M Schwarze

H Management of Split-Thickness Donor Sites With Synthetic

Wound Dressings Ann Plast Surg 2010 Nov65(5)490-496

19 Keck M Selig HF Lumenta DB Kamolz LP Mittlboumlck M

Frey M The use of Suprathelreg in deep dermal burns First

results of a prospective study Burns 2012 May38(3)388-395

20 Mądry R Strużyna J Stachura-Kułach A Drozdz Ł Bugaj

M Effectiveness of Suprathelreg Application in Partial Thickness

Burns Frostbites and Lyell Syndrome Treatment Pol Przegl

Chir 201183(10)541-548

21 Wahler S Wurzer P Kamolz L Muumlller A Cost-Effectiveness

Comparison Between Biobrane and Suprathelreg for Partial

Thickness Burn Treatment for Austria Value in Health 2017

Oct-Nov20(9)A802

22 Selig HF Keck M Lumenta DB Mittlboumlck M Kamolz LP

The use of a polylactide-based copolymer as a temporary skin

substitute in deep dermal burns 1-year follow-up results of a

prospective clinical noninferiority trial Wound Repair Regen

2013 May-Jun21(3)402-409

23 Rashaan ZM Krijnen P Allema JH Vloemans AF Schipper IB

Breederveld RS Usability and effectiveness of Suprathelreg in

partial thickness burns in children Eur J of Trauma Emerg Surg

2017 Aug43(4)549-556

24 Hundeshagen G Collins VN Wurzer P Sherman W Voigt

CD Cambiaso-Daniel J et al A Prospective Randomized

Controlled Trial Comparing the Outpatient Treatment of

Pediatric and Adult Partial-Thickness Burns with Suprathelreg

or Mepilex Ag J Burn Care Res 2017 May23

25 Glik J Kawecki M Kitala D Klama-Baryła A Łabuś W

Grabowski M et al A new option for definitive burn wound

closure-pair matching type of retrospective case-control

study of hand burns in the hospitalised patients group in the

Dr Stanislaw Sakiel Centre for Burn Treatment between 2009

and 2015 Int Wound J 2017 Oct14(5)849-855

Genetic predisposition in the etiology and pathogenesis of Achalasia

Valenzuela-Almada Mariacutea Oa1 Quintero-Villegas Alejandro1 Aacutelvarez-Manzo Heacutector1

1 Medical School Universidad PanamericanaAugusto Rodin No 498 Col Insurgentes Mixcoac CP 03920 Del Benito Juaacuterez Ciudad de

Meacutexico

Corresponding autor

Alejandro Quintero-Villegase-mail 0170091upedumx

How to cite this article Valenzuela-Almada MO Quintero-Villegas A Aacutelvarez-Manzo H Genetic predisposition in the etiology and pathogenesis of Achalasia JMSR 2017 Oct-Dic1(2)12-18

12

Abstract

Key Words ESOPHAGEAL ACHALASIA HLA PTPN22 PHYSIOPATHOLOGY CHAGAS HSV-1 GENES

An analysis and comparison of the studies found in the literature about the etiology of idiopathic achalasia is presented in this review with a special focus on the genetic basis of the pathogenesis of this disease specifically the several familiar cases of achalasia are discussed as well as the potential genes implicated in the genetic predisposition for achalasia including HLA (Human Leukocyte Antigen) and PTPN22 (Protein Tyrosine Phosphatase N22 gene) Comprehension of the etiology of this disease is extremely important for future diagnostic and therapeutic strategies

1313

Achalasia is a relatively common disease seen in tertiary centers in Mexicorsquos City Among the different motility disorders of the esophagus achalasia is one of the most frequently diagnosed since the implementation of the high resolution esophageal manometry Being that said we had a special interest in investigating the different causes leading to the disease Furthermore given that in our clinical practice we witnessed a couple of cases with achalasia we focused our research in the genetic predisposition needed for the pathogenesis of the disease

INTRODUCTIONIdiopathic achalasia is an inflammatory disease of unknown etiology characterized by failure of esophageal peristalsis and lack of lower esophageal sphincter (LES) most likely due to loss of inhibitory neurons of the esophageal myenteric plexus (1) Subsequently that causes an obstruction for the food bolus at the level of the LES causing the classic achalasia symptoms such as dysphagia regurgitation thoracic pain heartburn and weight loss A careful clinical history and an upper gastrointestinal tract endoscopy or a barium esophagram will make you suspicious of this disease and an esophageal manometry will confirm it However other entities can mimic the symptoms mentioned above specially malignancy 2

Achalasia was described in 1674 by Sir Thomas Wills and since that time several theories have been proposed regarding the etiology of the disease Some of them include viral infections parasitic infections autoimmune diseases and hereditary and genetic factors 3 In the last years there

have been more research studies trying to elucidate the pathogenesis and etiology of achalasia in order to focus the treatment on the potential causes instead of just treating the consequences Moreover it is generally accepted that a genetic predisposition must be present in order to develop the disease because not all patients with infections or with certain autoimmune diseases end up having achalasia 4

As briefly mentioned before the objective of this review is to state broadly the physiopathology of achalasia to then analyze what is nowadays known about the possible causes The potential genes that have been reported in the literature implicated in generating the predisposition thought to be needed to develop achalasia will further be discussed Hopefully these new findings reported in the literature will lead to new investigations focused on different treatments for specific pathogenic processes hence improving quality of life in patients suffering from this disease

We performed a comprehensive search of English language literature to identify all original research and review articles regarding primary idiopathic achalasia its causes and current known of physiopathology PubMed database We used the following Medical Subject Headings (MeSH) and main keywords for searches achalasia HLA PTPN22 physiopathology Chagas HSV-1 genes inflammation

We also reviewed the reference lists of the papers that we identified during the searches Three authors independently reviewed the selected articles


METHODS

1414

bull(((etiology [TitleAbstract]) AND Achalasia[TitleAbstract])) OR ((etiology [Subheading]) AND Esophageal Achalasia[Mesh])= 2512

PATHOPHYSIOLOGY

It is important to mention that loss of inhibitory neurons of the myenteric plexus can be due to intrinsic factors or extrinsic factors Extrinsic causes are for example lesions involving the vagus nerve fibers or injuries to the central nervous system specially in the dorsal nucleus of vagus nerve which is the origin of the autonomic fibers innervating the myenteric plexus This was demonstrated in post-mortem studies of 3 patients with achalasia in which a loss of 34-43 of dorsal-nucleus neurons was observed 5 However more recently other studies have shown that most of the patients undergoing vagotomy do not develop achalasia hence leading to the thought that the significant loss of neurons in the dorsal nucleus may be a secondary phenomena and not the primary mechanism leading to achalasia 6

On the other side the proposed intrinsic mechanisms explaining the myenteric plexus dysfunction are the disequilibrium of excitatory and inhibitory neurons This was illustrated in a study of 27 patients with achalasia in which cholinergic and anticholinergic medications were randomly administered Anticholinergics effectively decreased the pressure of the LES Other studies suggest that the primary mechanism is the complete absence of inhibitory innervation of the LES muscle these mechanism has been studied while measuring different neurotransmitters such as vasoactive intestinal peptide (VIP)

VIP purpose is to relax the smooth muscle in the gastrointestinal tract and studies had shown that there is a decrease in VIP containing neurons in patients with achalasia 7 Another neurotransmitter demonstrated to be implicated is nitric oxide which is thought to be the principal inhibitor of the myenteric plexus There are studies that prove that its concentration is diminished in patients with the disease 89 Other suggested intrinsic mechanisms include loss of cells in myenteric ganglions 10 inflammation of the myenteric plexus 11 with a subsequent fibrosis of the nerve fibers 12

ETIOLOGY

The probable causes of achalasia which have been linked to the mechanisms observed in the pathophysiology mentioned above will be reviewed in the next paragraphs and afterwards the genetic mechanisms will be more thoroughly explained

Viral Infections

Multiple viruses have been implicated as the initiating factor in the etiopathogenesis of achalasia Some of these viruses are herpes simplex virus (HSV) varicella zoster virus (VZV) measles human papillomavirus (HPV) among others It is well known that HSV has a special tropism for nerve fibers and it has been proposed that this virus persists in the LES neurons during the latent phase of the disease provoking a continuous immune activation which could induce inflammation and neuron death leading to the development of achalasia 13 In the same line there are other studies in which the presence of HSV has been observed through molecular techniques like polymerase chain reaction (PCR) in neurons of the myenteric plexus of the biopsies of patients with achalasia In

RESULTS

1515

addition other studies have found increased number of VZV antibodies when comparing patients with achalasia to healthy individuals 14 However as mentioned before it is probable that all these patients that develop achalasia secondary to viral infections have a genetic predisposition because only a relative small subset of patients acquire the disease 15

Chagas disease

Chagas disease is an infectious disease of parasitic etiology transmitted by a subfamily called Triatominos 16 The parasitic agent is called Trypanosoma cruzi One of the late consequences of this infection is achalasia

The mechanism by which this disease causes achalasia is still not fully known However studies of patients who developed chagasic achalasia have shown that these patients present more frequently than controls higher levels of anti-muscarinic type 2 receptor antibodies 17 Furthermore another possible mechanism by which T cruzi could provoke this complication is a crossed immunological reaction between the flagellar antigen FI-160 of T cruzi and a protein expressed in the neurons of the myenteric plexus producing neurodegeneration and therefore denervation of the esophagus 18

Autoimmunity and inflammation

Some studies have found circulant antibodies in serum against the myenteric plexus nevertheless it has not been determined if these antibodies can cause achalasia or are just a secondary reaction when you have already developed the disease 19 Likewise inflammatory infiltrates have been observed in the surrounding areas of the myenteric plexus with a predominant population of T cells 20 In fact an increase in cytokine

and complement expression has been documented For example proinflammatory cytokines such as IL-22 IFN-γ IL-1β IL-2 and TNF-β are increased in patients 15 The reason why these molecules are increased has not been elucidated yet Eventually these pro-inflammatory and fibrogenic processes lead to an injury to the myenteric plexus with consequent neuronal loss 4

Genetic causes The probable implication of genetic factors in etiology of achalasia was thought in the beginning because of the prevalence of what it is known as familial achalasia Besides achalasia has been associated with many well defined genetic syndromes like Down syndrome Allgrove syndrome Achalasia-microcephaly syndrome and Familial visceral neuropathy Although there is a possibility of a coincidence occurrence of achalasia within the context of these syndromes or that the disease is caused by a secondary pathophysiological mechanism there is strong evidence suggesting that there may be a common genetic alteration that predisposes to the development of achalasia 21 Likewise another fact that supports the genetic theories in the pathogenesis of achalasia is the presence of the disease in monozygotic twins There are few cases reported in the literature The first case was published in 1982 two identical female twins with identical habitus exterior as well as identical blood antigens (ABO Duffy Lewis Kell) without trips to South America nor Central America developed achalasia at different ages one of them was 26 years old and the other 39 22 According to literature the incidence of achalasia is approximately 1 case per 100 000 habitants so it is unlikely that both twins

1616

developed achalasia just by coincidence 22

On the other side of the case mentioned before another case of monozygotic female twins from Mexico was published in 1979 In this case one of the twins developed achalasia at a young age matching clinical criteria for the disease and confirmation with manometry was done while the other one was completely asymptomatic at the time of evaluation and her manometry was normal It is relevant to mention that both twins lived and developed in the same place

The probable explanation for this case is that one of the twins may have had an initiating factor such as an infection from living in an endemic zone for many diseases supporting the idea that genetic alterations are not enough to cause achalasia In addition there was no follow up from the second twin which theoretically could develop the disease in the future 23

Aside this two previously mentioned cases achalasia between siblings has also been reported A case of a family with 9 children 6 of them had achalasia (4 men and 2 women) The 6 children had symptoms of achalasia starting at the age of 6 several molecular genetic studies were carried out without finding any significant alterations 24 Another case was found in the literature about two siblings one of 25 years of age and the other one 6 months old both presenting with clinical criteria of achalasia 25

The existence of familial occurrence of the disease as well as the presentation in monozygotic twins suggests that the transmission pattern may be autosomal recessive although there is still lack of strong evidence to make that conclusion 26

GENES PROPOSED IN THEPATHOGENESIS OF ACHALASIA

Many recent investigations have been made regarding the genes involved in the different syndromes related to achalasia One of them is AAAS gene mutated in Allgrove syndrome In one study that looked for pathological mutations of these gene in 41 patients with achalasia there were not any significant alterations found however more evidence is needed to assume that AAAS is not related to a genetic predisposition for achalasia 21 Alternatively studies of knockout mice have found an implication of genes like RASSf1a NOS1 (mice nNOS deficient) mutated Kit Spry2 in achalasia Also alterations in the molecular cascade mediated by GDNF-RET have been demonstrated 21 This last molecule participates in the development the structure and functioning of the neuroendocrine gut system The majority of animal models with mutations in these genes shown impairment of gastrointestinal tract motility with predisposition to the development of megacolon and megaesophagus with impaired relaxation of the lower esophageal sphincter 27 HLA II As mentioned previously there is an inflammatory response present in patients with achalasia with an important T cell infiltrate mediated by immune activation of not yet determined causes Therefore certain associations have been established between different HLA II haplotypes and the predisposition for achalasia In one study an increased number of anti-myenteric antibodies was seen in patients with HLA-DQA10101 Other associations have been made of achalasia and HLA- DQw1

1717

DQB10502 DQB10601 and DQB10602 The most evident being HLA-DQA10101 On the other hand HLA DQB102 may have a protective effect for the disease In the same way a relationship HLA-DR variants and achalasia has been observed however it has not been consistent in all the studies 27 PTPN22 Another candidate gene involved in pathogenesis of achalasia is PTPN22 gene (protein tyrosine phosphatase N22 gene) which encodes for a specific lymphoid phosphatase that downregulates T lymphocytes Certain alleles for this gene promote an autoimmune response resulting in chronic inflammation Variants of this gene have also been associated to rheumatoid arthritis diabetes mellitus type 1 and other immune diseases 21

Although there has been significantly increasing knowledge in the understanding of the physiopathology of achalasia there are a lot of blank spaces regarding the initiating factors leading to the disease All the probable intrinsic and extrinsic factors that cause the chronic inflammation of the myenteric plexus are not fully established yet These investigations have been difficult because of the wide age range in which this entity can present

As reviewed in this article there is multiple evidence supporting the genetic basis of achalasia like the reports of familial achalasia monozygotic twin achalasia and the linked-to-genetic syndromes achalasia Still the specific molecular basis of the idiopathic achalasia is yet to be fully investigated More importantly genetic alterations appear to be not enough

for the disease to happen meaning that environmental factors like infections could be the triggering factor for symptomatic disease secondary to damage of the myenteric plexus More studies are needed that focus on these initiating entities for the disease Given the severity of the disease it is extremely important to clarify all possible etiologies in order to develop new diagnostic tools for the purpose of diagnosing the disease earlier than when the clinical manifestations develop In fact the new evidence in the pathogenesis field of this disease will most probably lead to the creation of new directed-to-target treatments that would be more effective in improving quality of life for patients

Conflict of interest We declare that we do not have any conflict of interests

BIBLIOGRAPHY1 Park W Vaezi M Etiology and Pathogenesis of Achalasia

The Current Understanding Am J Gastroenterology 2005

Jun100(6)1404-1414

2 Gallego MP Acalasia Un trastorno de la motilidad esofaacutegica

no tan raro Rev Clin Med Fam 2009 Feb2(6)305-308

3 Niwamoto H Okamoto E Fujimoto J Takeuchi M Furuyama

J Yamamoto Y Are human herpes viruses or measles virus

associated with esophageal achalasia Dig Dis Sci 1995

Apr40(4)859-864

4 Furuzawa-Carballeda J Aguilar-Leoacuten D Gamboa-Domiacutenguez

A Valdovinos MA Nuntildeez-Aacutelvarez C Martiacuten-del-Campo LA et

al Achalasia-An Autoimmune Inflammatory Disease A Cross-

Sectional Study J Immunol Res 2015(2015)729-217

5 Cassella RR Brown AL Jr Sayre GP Ellis FH Jr Achalasia of the

esophagus Pathologic and ethiologic consideration Ann Surg

1964 Sep160(3)474-87

6 Atkinson M Ogilvie AL Roberston CS Smart HL Vagal

function in achalasia of the cardia Q J Med 1987 Apr

63(240)297-303

7 Ates F Vaezi MF The Pathogenesis and Management of

Achalasia Current Status and Future Directions Gut Liver

2015 Jul9(4)449ndash463

8 Yamato S Spechler SJ Goyal RK Role of nitric oxide in esophageal

peristalsis in the oposum Gastroenterology 1992103197-204

9 Sivarao DV Mashimo HL Thatte Hs Goyal RK Lower

CONCLUSIONS

1818

esophageal sphincter is achalasic in nNOS-- and hypotensive

in ww mutant mice Gatroenterology 2001 Jul121(1)34-42

10 Lendrum FC Anatomic features of the cardias

orifice of the stomach with spacial reference to

cardiospasm Arch Intern Med 193759(3)474-511

11 Goldblum JR Whyte RI Orringer MB Appelman

HD Achalasia A morphologic study of 42 resected

specimenes AM J surg Pathol 199418 327-37

12 Cscendes A Smok G Braghetto IRamiacuterez C Velasco

N Herriquez A Gastroesophageal sphicter pressure and

histological changes in distal esophagus in patients with achalasia

of the esophagus Dis Dig Sci 1985 Oct30(10)941-945

13 Boeckxstaens GE Achalasia virus-induced euthanasia of

neurons Am J Gastroenterol 2008 Jul103(7)1610-1612

14 Robertson CS Martin BA Atkinson M Varicella-

zoster virus DNA in the oesophageal myenteric

plexus in achalasia Gut 1993 Mar34(3)299-302

15 Furuzawa-Carballeda J Torres-Landa S Valdovinos

MA Coss-Adame E Martin-Del-Campo LA Torres-

Villalobos G New insights into the pathophysiology

of achalasia and implications for future treatment

World J Gastroenterol 2016 Sep 22(35)7892-907

16 Meneghelli UG Chagasrsquo disease a model

of denervation in the study of digestive tract

motility Braz J Med Biol Res 198518(3)255-264

17 Goin JC Sterin-Borda L Bilder CR Varrica LM Iantorno G

Riacuteos MC et al Functional implications of circulating muscarinic

cholinergic receptor autoantibodies in chagasic patients

with achalasia Gastroenterology 1999 Oct117(4)798-805

18 Andersson J Orn A Sunnemark D Chronic murine

Chagasrsquo disease the impact of host and parasite

genotypes Immunol Lett 2003 Apr86(2)207-212

19 Moses PL Ellis LM Anees MR Ho W Rothstein

RI Meddings JB Sharkey KA et al Antineuronal

antibodies in idiopathic achalasia and gastro-oesophageal

reflux disease Gut 2003 May52(5)629-636

20 Sodikoff JB Lo AA Shetuni BB Kahrilas PJ Yang GY Pandolfino

JE Histopathologic patterns among achalasia subtypes

Neurogastroenterol Motil 2016 Jan28(1)139ndash145

21 Gockel H Schumacher J Gockel I Lang H Haaf

T Noumlthen M Achalasia Will genetic studies provide

insights Hum Genet 2010 Oct128(4) 353-364

22 Stein D Knauer CM Achalasia in monozygotic

twins Dig Dis Sci 1982 Jul27(7)636-640

23 Eckrich J Winans C Discordance for achalasia in identical

twins Digestive Diseases a 1979 Mar24(3) 221-224

24 Bosher LP Shaw A Achalasia in siblings clinical and

genetic aspects Am J Dis Child 1981 Aug135(8)709ndash710

25 Monnig PJ Familial achalasia in children The Annals of

Thoracic Surgery 1990 Jun49(6)1019-1022

26 Frieling T Berges W Borchard F Luumlbke HJ Enck P

Wienbeck M Family occurrence of achalasia and diffuse

spasm of the esophagus Gut 1988 Nov29(11) 1595ndash1602

27 De la Concha EG Fernandez-Arquero M Mendoza

JL Conejero L Figueredo MA Perez de la Sema J et

al Contribution of HLA class II genes to susceptibility

in achalasia Tissue Antigens 1998 Oct52(4)381-384

Pediatric esophageal achalasia report of a case and an integrative review of the pediatric surgical treatment literature

Ledezma-Bautista Ivaacuten1

1 Facultad de Medicina Universidad Autoacutenoma de San Luis PotosiacuteAv Venustiano Carranza 2405 San Luis Potosiacute SLP ZP 78210 Meacutexico

Abstract

Key Words ESOPHAGEAL ACHALASIA CHILD TREATMENT

Corresponding autor

Ivan Ledezma Bautista ivanlblivecom

How to cite this article Ledezma-Bautista I Pediatric esophageal achalasia report of a case and an integrative review of the pediatric surgical treatment literature JMSR 2017 Oct-Dic1(2)19-37

19

INTRODUCTION Esophageal achalasia is a disease with very low incidence in pediatric population (011 per 100000 children) Because of these the management remains in controversy There are no clinical guidelines for the treatment of esophageal achalasia in childMETHODS We reclute all articles related to the surgical and interventional management of pediatric esophageal achalasia Using the main metasearch and data bases with our keywordsRESULTS We found a total of 63 articles that are related belowCONCLUSIONS We consider that the laparoscopic Hellerrsquos myotomy is the actual and best studied surgical and definitive treatment for esophageal achalasia in children Peroral endoscopic myotomy is a promising new therapy but the evidence is limited to small series of cases with low period follow-up We need of multicentric clinical trial comparing the laparoscopic Heller myotomy vs peroral endoscopic myotomy to stablish the best treatment for this disease

2020

Clinic caseIt is a male patient 3 years and 2 months old born and resident of Xilitla San Luis Potosi He is son of a 19 years old mother and a 25 years old father referred as healthy An only son

He is the product of first gestation obtained vaginally at term with a weight of 3400gr spontaneous breathe and cry did not required resuscitation maneuvers and exited with the mother Adequate psychomotor development fed maternal breast exclusively for 6 months then with a continuation formula and ablactating with integration into the family diet at 12 monthsHe went for consultation for a month of evolution with sudden intolerance of the oral route to both solids and liquids with postprandial vomiting of food content up to 6 times a day went to the doctor because of persistent milk intolerance and weight loss of approximately 15kg

They took an abdominal radiography only observing coprostasis refer to General Hospital of Valles City where they take computed tomography scan where esophageal dilatation of the distal third and hidden spina bifida of L5 is observed he is referred for suspicion of achalasia to the Children and Women Hospital in where they placed central venous catheter and initiate parenteral nutrition when they encounter acute malnutrition being managed with fasting

We performed esophageal manometry of 4 channels recording aperistalsis o the three thirds of the esophageal body with pressures less than 30mmHg with cavity phenomenon the passage from the catheter to the stomach was not possible

He is referred to the Central Hospital Dr Ignacio Morones Prieto to be evaluated by the pediatric surgery service upon his admission he was its vital signs of 92 cardiac rate 29 respiratory rate 93 oxygen saturation and 364 C temperature With well-hydrated mucous membranes neck presence of right subclavian central venous catheter rest of normal physical examination It is assessed by pediatric surgery who request and esophagogram observing dilation of the distal two thirds of the esophagus with sudden decrease in distal caliber with pencil point morphology


Image 1 Esophagogram (barium swallow) with the cha-racteristic ldquobird beakrdquo sign compatible with esophageal

achalasia Adapted 4

2121

We report delayed esophageal emptying with filiform passage of the contrast medium into the stomach after 10 minutes no peristaltic waves are seen

INTRODUCTIONEsophageal achalasia is a disease of unknown etiology with a very low incidence in the pediatric population 002 to 011 per 100000 children remaining a controversy in its management attempting to present less invasive treatments Its characterized by the loss of normal distal esophagi peristalsis and with incapacity of the lower esophageal sphincter (LES) to relax after swallow that causes the clinic symptomatology of this diseaseBecause of the very low incidence in this population we make a review of a preschool patient case from Xilitla San Luis Potosi

METHODS PubMed and Trip Database metasearch and SpringerLink Wiley Online Library Web of Science Scopus Science Direct Academic Search Complete Biblioteca Virtual en Salud and Nature data bases were used to retrieve the articles quoted and the criteria used for the selection were relevant information in the summary comply with established limits

The exclusion criteria were not comply with the general theme and contains at least one keyword documents with different typology than the indicated limits Obtaining the following results with the different combinations of keywords where the first number are the articles obtained and the second are those that were used discarded articles were those that did not meet the inclusion and exclusion criteria or that were repeated in the searches made (((((Esophageal Achalasia[MeSH Terms]) OR Achalasia[TitleAbstract]) OR Cardiospasm[TitleAbstract])

OR Megaesophagus[TitleAbstract])) AND ((((((Child[MeSH Terms]) OR Child[TitleAbstract]) OR Children[TitleAbstract]) OR Preschool[TitleAbstract]) OR Infant[MeSH Terms]) OR Infant[TitleAbstract])

RESULTSWe found 63 articles (see Table 1) and the results are presented belowThe first literature report of a pediatric patient with achalasia was in 1961 Raven et al reported the case of 6 month old children The baby had a history of having taken two tablespoons of hot water grains of salt and half-skimmed milk in addition to episodes of pneumonia Episodes of regurgitation were added barium swallow was performed where radiologic characteristics compatible le with achalasia even with barium effusion to the bronchi The patient was prepared for surgery and a Heller operation was performed by paramedial abdominal incision with no complications At 1 year follow-up the patient remained asymptomatic1

In 1981 Boyle et al reported the cases of 10 children the mean age was 123 years (range 10-17) symptoms included dysphagia in all ten patients vomiting in eight weight loss in seven substernal pain in five and nocturnal cough in four The diagnosis was made with radiographic and manometric methods At the moment of endoscopy the pneumatic dilation was performed with no complications Four patients had excellent results with one single dilation the other 6 had variable response due to dysphagia symptoms to certain foods requiring a second or third dilatation The follow-up period was 9 months to 10 years2

In 1985 the first cases series of children with achalasia was made by Lemmer et al Six children had postprandial dysphagia and vomiting three complained of severe

2222

Table 1 Results

2323


2424


2525

retrosternal pain unrelated to food two had nocturnal vomiting and three suffered recurrent pneumonia requiring multiple hospitalizations The average weight loss was 19 pounds Preoperative studies showed dilated esophagus or retrosternal air Two patients aged 6 and 15 years underwent before with pneumatic dilatation with flexible Hurst-Maloney balloon with temporary improvement for less than 3 weeks in each case

A left thoracotomy was performed with posterior esophageal myotomy (modified Hellerrsquos operation) a Hurst-Maloney dilator was inserted orally and dissection was performed to the anterolateral division with a scalpel from the aortic arch to the esophagogastric junction An adequate myotomy requires exposing the submucosa to at least 50 of the circumference The procedure was performed without intra and postoperative complications The average time of follow up was 23 months at that time asymptomatic without reflux findings Swenson pointed out that finding food particles in the childrsquos pillow in the morning may be a clue to the diagnosis This disease in young patients can be confused with psychological disorders Payne et al reported the transthoracic approach of myotomy in 1961 3

In 1996 the first laparoscopic esophagectomy was reported in a pediatric patient bye Holcomb et al There were 2 cases the first with a 12 years old girl with a 4 month history of weight loss of 8 pounds headache and dicinesia in addition to postprandial emesis She was valued by psychiatry for anorexia and depression She was cachectic examinations were performed including chest X-Ray where the dilated esophagus was demonstrated A superior gastrointestinal series demonstrate esophageal achalasia

Laparoscopic myotomy was performed with a 6 port technique as well as endoscopy with intermittent pneumatic dilation without complications After 18 months she remained asymptomatic The second case was 13 years old boy with dysphagia clinic for liquids for 6 months plus a loss of 18 pounds in that period An upper gastrointestinal series showed achalasia the manometry showed a pressure of the 40-45mmHg with incomplete relaxation in response to swallowing with absence of peristalsis

Laparoscopic myotomy was performed without complications After 17 months he remained asymptomatic The same principle of myotomy laparotomy4


2626

In 1997 Robertson et al reported the case of a 13 year old girl with a history of dysphagia was reported Initially she was diagnosed with reflux halitosis and possible bulimia Barium swallowing was performed with findings compatible with achalasia The manometry showed pressure in the lower sphincter of 33mmHg and absence of relaxation with swallowing in addition to the absence of efficient peristalsis Several pneumatic dilatations were performed with partial improvement of short duration Given the refusal of the parents to perform a thoracotomy for possible muscular sequelae they decided to perform a thoracoscopic approach with endoscopic assistance Postoperatively she required chest tube drainage for 48 hours and resumed a regular diet without dysphagia on the second postoperative day She was discharged home on the third postoperative day on prophylactic H2 blockers (because of the potential for gastroesophageal reflux) and remains symptom-free 12 months postoperatively A follow up barium swallow demonstrates a normal esophagus without obstruction or gastroesophageal reflux5

In 1997 a bigger series of cases was published with 19 children Of them 14 had vomiting 13 dysphagia and 1 odynophagia All 19 patients a barium swallow was made for the diagnosis and in 8 of them manometry was also performed The mean age was 10 years range from 13 to 176 and they underwent modified anterior esophagomyotomy of Heller 5 of them also Belsy fundoplication They did not have surgical complications Short-term follow up difficulty to swallow in 2 patients with myotomy alone and in 4 of 5 patients with aggregated fundoplication All patients required dilatation 1 to 4 times in the first year In the long term (mean=9 years) 17 of the 19 patients had complete improvement of symptoms the remaining

2 had occasional mild dysphagia This study and Vane et al show much less success in pneumatic dilation Both the thoracoscopic and laparoscopic routes for Hellerrsquos myotomy seem to have similar efficacy however the days of hospital stay are shorter in laparoscopy (4 days) vs thoracoscopy (8 days)6

In 1997 Khoshoo et al reported the first experiences of botulinum toxin in pediatric patients reporting the case of 3 minors The clinic of children aged 8 11 and 13 years was vomiting dysphagia and weight loss as well as radiological and manometric findings compatible with esophageal achalasia They used an endoscope inject botulinum toxin from Clostridium type A The first patient of 8 years needed a second dose 2 months later which didnrsquot work and balloon dilation was performed which reflected in partial improvement

The second patient had a balloon dilatation for 12 months with temporary improvement for 12 months with temporary improvement for 2 months after injection of botulinum toxin remained totally asymptomatic however released 3 months later returned to treatment with nifedipine remains with partial improvement with mild symptoms In conclusion only 1 of the 3 patients obtained complete and durable improvement of the symptoms

No patients presented adverse events After all botulinum toxin injection offers a safe and less invasive alternative for symptomatic relief of symptoms in children with achalasia and could be used as temporary measure for weight gain priori to surgery It could also be a patient with incomplete response following balloon dilatation or myotomy7

In 1997 Hammond et al reported the cases of 4 pediatric patients with esophageal achalasia treated with tandem balloon dilatation the mean age was 114 years old (range 10-129)

2727

Dysphagia resolved completely in three of the four patients but did not improve significantly in patient 3 One patient needed an additional tandem of 3 dilatation 2 years later There were no complications reported such as perforation or any other8

In 1999 Hamza et al reported the cases of 11 children (8 boys and 3 girls) with ages ranging from 15-14 years (mean 75) with symptoms of achalasia confirmed with manometry endoscopy All underwent pneumatic dilation One patient had excellent results with single dilation and other 7 had them with dilation One patient required Hellerrsquos cardiomyotomy with floppy anti-reflux and no post-operative sequelae9

In 2000 Esposito et al reported the complications incidence for the laparoscopic treatment They reported 10 cases in 10 years in 2 institutions ages between 2 and 13 years old six children received previous treatment with nifedipine with poor results They performed laparoscopic Heller myotomy in 7 cases anterior antireflux Dor was made and Toupet fundoplication in the other 3 The first complication was intraoperative mucosa perforation sutured during procedure The second was a tear of the esophageal mucosa at the level of the left 2 inferior stitches of Toupetrsquos fundoplication founded postoperatively with a computerized tomography The perforation was sutured with methylene The third one was severe dysphagia 1 year after the surgery Five years after the laparoscopic treatment the patient underwent reoperation using the laparotomy approach and 6 month after this he was free of symptoms10

In 2000 Hurwitz et al reported a series of 23 pediatric cases with esophageal achalasia between 2 months and 193 years old treated with botulinum toxin A median duration of

14 months (range 1-36) was followed 83 presented initial improvement or decrease in symptoms in addition weight gain of the remaining 4 1 was given another injection followed by surgery two were performed pneumatic dilation followed by surgery and another missed follow up after 1 month Only 5 patients had complete improvement (22) without the need for additional procedures This represents the lowest report success rate including adults11

In 2000 Ip et al reported the cases of 7 patients agersquos range 2 to 15 years whom underwent botulinum toxin treatment They used Clostridium BTx type A with mild results Only 3 of 7 responded more than 6 months to the treatment the preoperative pressure was significant less in the responder group (38 vs 61mmHg P=005) and found negative correlation with rho -06 between lower esophageal sphincter pressure and the duration of response Two patients required Heller myotomy because of the unsatisfactory response to BTx injection12

In the year 2001 Tashjian et al reported the case of 3 year old boy who presented with a 6 month regurgitation and recurrent upper respiratory tract infection The evaluation included a gastrointestinal series showing a birdrsquos peak image of the lower esophageal sphincter consistent with achalasia Manometry shower poor motility and sphincter pressure of 62mmHg (normal range 10-25mmHg) consistent with achalasia After partial transient improvement by injection of botulinum toxin modified left thoracoscopic left-arm Heller myotomy was performed from the level of inferior pulmonary vein up to 1cm higher than the gastroesophageal junction The endoscopic assistance with illumination and insufflation revealed the intact mucosa without signs of leakage He was discharged on the third

2828

postoperative day without complications The patient presented postoperative dysphagia so temporary cisapride was administered It was also performed manometry with a tone of 19mmHg and barium swallow without evidence of gastroesophageal reflux The patient 16 months later remained asymptomaticEckardt et al do no recommend pneumatic dilation in children under 18 years old In addition this procedure has been associated with esophageal perforation while the results of Hellerrsquos myotomy are excellent the disadvantage is the need for thoracotomy of laparotomy The advantages of performing the thoracic or abdominal procedure have been discussed In the case of thoraroscopy the phrenoessophageal ligament is not divided and there is less mobilization of the esophagus this helps to maintain the anti-reflux mechanism without the need to perform fundoplication In addition pneumatic dilation with endoscope minimizes the possibility of perforation during surgery Albasese et al recently commented that it remains ldquoquestionablerdquo to perform Hellerrsquos myotomy without antireflux procedure The results in pediatric myotomy performed thoracic thoracoscopic laparotomy and laparoscopic indicate that antireflux procedure is not necessary In conclusion thoracoscopy combined with endoscopy represents a definitive surgical treatment without the need for an antireflux procedure13

In 2001 the cases of 9 children was reported by Rothenberg all 9 patients had undergone at least 1 esophageal pneumatic dilatation that improved their dysphagia but all had recurrent symptoms within 6 to 8 weeks One patient presented perforation 1 week after the procedure Another patient developed dysphagia 6

months postoperatively she returned to the operating room for a laparoscopic Heller and Dor fundoplication because of an incomplete myotomy Six patients are relatively asymptomatic with only occasional difficulty swallowing and mild GER14

In 2001 Patti et al reported the cases of 13 children (ages 6 to 17 years) whom underwent laparoscopic Heller myotomy and Dor fundoplication all patients had complete resolution and they considered the results of the operation to be excellent the dysphagia score went from 37 preoperatively to 0 postoperatively with no complications15

In 2001 Babu et al reported a series of cases of pneumatic dilatation in pediatric patient with achalasia confirmed with manometry and barium swallow There were four boys and one girl three patients had only one pneumatic dilatation with full success the other two had subsequent dilatations with temporary improvement16

In 2001 Mehra et al reported a series of cases of 22 pediatric patients who underwent minimally invasive esophagomyotomy for achalasia The media age was 113 years 10 females and 12 males Laparoscopic Heller myotomy with fundoplicationrsquos was made in 18 patients and Thoracoscopic approach in 4 Two of the LHM required conversion to open because of perforation The mean follow-up was 17 months The mean duration of hospitalization was less in the laparoscopic group (27 vs 48 P=005) The results were perfect in all patients with a success rate of 10017

In 2002 Khan et al reported the cases of 12 children with esophageal achalasia with a mean age of 108 years who underwent pneumatic dilatation The balloon dilatation resulted in almost complete relief of symptoms in all children none required

2929

repeated dilatation at 6 moth follow-up18

In 2003 Mattioli et al reported cases series of 20 children with esophageal achalasia mean age was 10 years range was 5 to 14 with diagnostic made with barium swallow or manometry They were treated with laparoscopic Heller myotomy with Dor fundoplication only 2 complications was reported (intraoperative mucosal perforation and esophageal vein bleeding) with no regurgitation symptoms or mortality The successful rate was 19 of 20 with the last patient needing a pneumatic dilatation after 6 months19

In 2004 Fernaacutendez et al reported the case of a 9 year old girl with esophageal achalasia complaining about vomiting for two months immediately after meals in moderate quantities The barium swallow and manometry were the diagnostic tests The management was laparotomy cardiomyomectomy with Dor fundoplication with no intra or post-operative complications In the two year follow-up she remains asymptomatic20

In 2007 Paidas et al reported a large series of 337 patients who underwent laparoscopic Heller myotomy 14 were pediatric with a median age 17 years (range11-19) 6 female and 8 males 2 had Down syndrome No surgery complications was reported and a median of 37 months 77 of pediatric patients symptoms greatly improved21

In 2009 Yin-Zhang et al reported the cases of 13 children 6 boys and 7 girls with an average age of 103 years (range 3-1442) diagnosed with manometry (mean LES pressure was 5398mmHg) and barium swallow with ldquobird peakrdquo sign The symptoms were dysphagia vomitingregurgitation poor growth and respiratory symptoms Of the

13 9 received Hellerrsquos esophagomyotomy 3 with NISSEN antireflux operation Two of the 4 resting underwent pneumatic dilation twice One of the two siblings remained clinically stable after the medical treatment with nifedipine and the other was lost to follow-up after endoscopic dilatation The mean follow-up time was 152 month the outcome was perfect in 66 without any symptoms including 6 patients by surgery and 2 patients by pneumatic dilatation22

Johanna et al reported in 2009 the series of 26 patients the age range was 4 to 18 years and they performed laparoscopic Heller myotomy in all patients with 2 with additional Dor fundoplication and other 23 with Toupet fundoplication Seven patients presented recurrence 3 required reoperation and 3 pneumatic dilatation or botulinum toxin injection23

In 2010 Corda et al reported a 10 year experience series of cases of pediatric achalasia treated with laparoscopic Heller myotomy without fundoplication performed by one surgeon The diagnostic was made with manometry and barium swallow There were 20 patients (13 males and 7 females) with a median age of 12 years (5-15 years) four patients needed open technique and two had mucosal perforation Median length follow-up was 60 months 15 patients remaining asymptomatic with no new intervention (75) 24

In 2010 Jung et al made a retrospective cohort of 22 children with achalasia with an average age of 78 years old they compared the results of Laparotomy and Laparoscopic Heller myotomy vs Pneumatic dilatation Seventeen patients were treated with HM resulting in 58 rate success with four reported complications (Dumping syndrome) In the pneumatic dilatation group

3030

there were nine children with a success rate of 55 with no complications related25

In 2010 Lee et al reported a retrospective cohort study that included 35 pediatric patients with achalasia of which 18 underwent pneumatic balloon dilatation and other 16 underwent Heller myotomy follow up was available for 30 patients (15 PD 15 HM) the mean age was 13 (range 7 weeks to 20 years) 21 males and 9 female the successful rate for esophageal dilation was 7 and for Heller myotomy was 60 with a median follow-up duration of 91 and 73 months (range 06 to 265) with no mortality reported Four patient of the HM group had pneumonia submucosal esophageal leak and small persistent pneumothorax26

In 2010 Tannuri et al reported a series of 15 cases of patients with achalasia treated with laparoscopic Heller myotomy with anterior hemi fundoplication according to Dorrsquos technique Fifteen patients were included in the study There were 8 female and 7 male patients The mean age was 12 years (range 9-17 years) Three patient had one disease (Down Berardinelly and myelomeningocele Mean operating time was 190 minutes with no intraoperative complications but one conversion to open surgery The follow up ranged from 2 months to 8 years (mean 323 months) two patients had recurrence of mild dysphagia that disappeared spontaneously and 1 required a single botulinum toxin injection 4 months after surgery The success rate was 14 of 15 (93)27

In 2011 Kobayashi et al reported the first case of single-port laraparoscopic Heller myotomy and Dor fundoplication for pediatric achalasia used in a 9-year-old boy with dysphagia and vomiting The barium swallow revealed spindle-type achalasia and a maximum esophageal diameter of

4cm The esophageal manometry revealed an increase lower esophageal sphincter pressure of 26mmHg The technique used a 25cm skin incision on the umbilicus with no complications The symptoms remitted totally with no postoperative problems The follow-up period was no specified28

In 2012 Di Nardo et al reported the cases of 24 patients treated with an initial success rate of 67 of the latter 3 patients (43) Various needed multiple dilatations with no complications occurred The older age was associated with a higher probability to dilatation success (P=00048) and higher pressure They reported an overall effective procedure rate of 87 of 6 years success Young age at presentation seems to be the only independent negative predictive factor for the need for a repeat PD and surgery They suggested that patients younger than 6 years may be referred for surgery earlier29

In 2013 Chatterjee et al reported the cases of 2 children with achalasia The first one was a 9 month female with weight loss vomiting after eat She was treated with open modified Hellerrsquos esophagocardiomyotomy with Toupet posterior partial fundoplication She became asymptomatic The second case was an 11 month-old girl with severe malnourish with a weight of 2kg After anemia correction she underwent LHM with Toupet fundoplication Both babies were followed for a year and are doing well and gaining weight without any problems30

In the 2012 Maselli et al reported the first Peroral endoscopic myotomy in a pediatric patient with esophageal achalasia The patient was 3 year-old female patient with Down syndrome who presented with severe growth retardation Achalasia was suspected because of vomiting recurrent cough aspiration pneumonia and

3131

growth retardation and confirmed with esophagogram and esophageal manometry After failed pneumatic dilatation they decided to make Peroral endoscopic myotomy there were no intra or post-operative complications At 1 year after procedure the patient was asymptomatic and a normal weight for her age31

In 2013 a large series of 31 cases was reported by Esposito et al with a multicentric survey The cases were 31 children (13 girls and 18 boys) with a median age of 84 years who underwent laparoscopic Heller myotomy with Dor fundoplication with a reported success of 90 one patient requiring redo surgery and two requiring pneumatic dilatation There were three perforations sutured with no complications Besides they tested a new hemostatic devices such as Starion LigaSure or the Harmonic scalpel to perform hemostasis and dissection and they proved to shortened the length of surgery (Plt005)32

In 2013 after the report of a case of Maselli Familiari et al reported the first series of cases of 3 children all girls with a median age of 9 (range 9-11) who underwent peroral endoscopic myotomy There were one complication a small perforation of the mucosal repaired with one clip The patients completed 1 year follow-up with no recurrence rate33

In 2013 Lamas-Pinheiro et al reported a series of cases of 6 patients (5 males) with and average age of 122 years (range 08-142) who underwent laparoscopic Heller myotomy with anterior Dor fundoplication The predominant symptoms were dysphagia weight loss vomiting and cough and chest pain With a median follow-up period of 5 years (range 2-10) the success rate was 83 one patient required pneumatic dilation with a notable

improvement in quality of life of all of them34

In 2014 Betancor et al reported the cases of 13 children (median age 12 years range 4-18) there were 7 boys with dysphagia and vomiting as the main symptoms The diagnostics tests were pH-metry and manometry The mean follow-up was 668 months Five patients underwent pneumatic dilatation with a success rate of 60 and two complications (post-operative esophageal perforation) This is the first series of pediatric patients reporting esophageal perforation related to pneumatic dilatation In 6 children they performed tandem pneumatic dilatation and after them open Heller myotomy In the last 2 patients they performed laparoscopic Heller myotomy as first management The complications were broncoaspiration in anesthesia induction and an esophageal tear repaired Both presents mild dysphagia but with no need of another procedure

Pachl et al in 2014 reported a single series of 28 cases of children with esophageal achalasia age range of 32 to 174 years old all with manometry In all cases reported laparoscopic Heller myotomy The complications were one perforation only Of the 28 procedures fundoplication was required in 18 there were no differences in the groups and the overall success rate was 23 of the 28 children with no need of another myotomy36

In 2014 Li et al reported the case of an 8 month-old girl with Allgrove syndrome with persistent vomiting The barium swallow revealed achalasia A botox injection was performed with improvement in feeding for only 3 months Due to continued failure to thrive the patient underwent a laparoscopic Heller myotomy with Toupet fundoplication There were no complications on her last follow-up at 10 years of age she was reported as asymptomatic38

Wei-Feng Chen et al in 2015 reported

3232

the first series of 27 pediatric patients During the procedure the mucosa incision submucosal tunneling and muscular cutting were carried out by using ENDO CUT Q at 50W Minor bleeding was often treated by forced coagulation (60W) by using the knife tip They diagnosed adverse events with a computed tomography 1st after surgery day They did not receive anything by mouth for 24 hours after POEM The successful POEM rate was 963 (2627) the mean operation time was 394plusmn174 minutes Five patients had mucosa injury or small mucosal perforations that were clipped after myotomy Almost half patients had at least one complication (subcutaneous emphysema mediastinal emphysema pneumothorax pneumoperitoneum and pleural effusion pneumonitis and focal atelectasis all minors with no need of more than 5 days in hospital Four patients developed heartburn and regurgitation indicating symptomatic GERD They had to use intermittent medication with standard doses of PPIs The follow up period was 246 months (range 15 to 38)40

In 2015 Chenjie Li et al reported the first series of peroral endoscopic myotomy (POEM) in pediatric population a total of 9 children with a mean age of 141 years old (range 10 to 17) The procedure was previous intubation first they injected indigo carmine plus epinephrine into the right posterior esophageal wall at 6-10cm above esophagogastric junction A 2-3cm longitudinal mucosal incision was made to create tunnel entry and then bilaterally dissection along the submucosal year was made to reduce the tension between mucosal entry and endoscope Myotomy was started from 2 to 3cm below tunnel entry After careful hemostasis several metal clips were applied to close mucosal entry Mean operative time was 567 minutes Treatment success was achieved in 100 cases Postoperative

they decrease statistical significant Eckardt score LES pressure and esophagus diameter and no recurrence of achalasia symptoms They reported 2 complications one patient presented reflux symptoms 6 months after treated with proton-pump inhibitor besides another patient had chest subcutaneous emphysema with no reoperation needed41

In 2015 Tamara Caldaro et al published one of the only comparative study in pediatric with esophageal achalasia They compared the laparoscopic Heller myotomy (LHM) vs peroral endoscopic myotomy (POEM) Eighteen pediatric patients with esophageal achalasia who had undergone LHM or POEM between 2009 and 2014 retrospectively identified The LHM group was mean age of 108 years range 2-17 and the POEM group was 122 years range 6-17 In the results procedure time was different (POEM 62plusmn127minuts vs LHM149plusmn338 minutes Plt001) One major complication occurred in the LHM group which was perforation of the esophageal mucosal layer The average postoperative hospital stay was LHM group 6plusmn49 days vs POEM group 41plusmn14 days Plt001) The follow up was 31 months in the LHM and 127 in the POEM group Both groups experience a marked improvement in symptoms with no statistical differences In the LHM group two children needed esophageal pneumatic dilations one after three months and the other two years after surgery42

In 2015 Filsner et al reported the case of a 10 year old male patient admitted with a 18 month history of dysphagia recurrent vomiting and weight loss with complained about regurgitations appearing immediately after food intake The gastroscopy showed no results but the manometry revealed type I (classic) achalasia The peroral endoscopic myotomy procedure was performed using the technique suggested by Inoue et al the operating

3333

time was 93 minutes with no complications Short term follow up (2 months) showed no clinical improvement with complete control of dysphagia and no sign of reflux43

In 2015 Zagory et al reported a retrospective study of the two center experience They identified all children (0-18 years) with achalasia showing a result of 23 patients (61 male) The most common presenting symptoms were weight lossfailure to thrive (87) emesis (696) and dysphagia (69) Nine patients underwent laparoscopic Heller myotomy with fundoplication (Dor Toupet and Thal) Only one patient had complication (mucosal perforation) The success rate was 842 Fourteen patients underwent pneumatic dilatation as first line therapy ten patients required Heller myotomy49

In 2016 Nabi et al reported a series of 15 cases of children with achalasia treated with peroral endoscopic myotomy There were no complications None of them presented recurrence of achalasia symptoms At 1 year follow-up 3 patients had gastroesophageal reflux with no specified treatment51

Dilation for primary treatment of pediatric achalasiaIn 2016 Tan et al compared the POEM vs PD for pediatric achalasia patients a total of 21 were enrolled and 12 received POEM with no recurrence In the PD group there were 9 patients of them 6 cases presented recurrence (0 vs 66 Plt005)52

In 2016 Altokhais et al reported the first research of robot-assisted Hellerrsquos myotomy with Toupet fundoplication in pediatric population using the DaVinci Si Surgical System They enrolled 6 patients between 2 and 12 years old No intra or post-operative complications and no conversion to laparoscopic or open technique occurred54

In 2017 Meyer et al published a retrospective cohort study involving 42 children with achalasia Of them 17 underwent a myotomy as first-line treatment with a success rate of 35 Twenty-four patients had non-surgical primary treatment (botulinum toxin n=20 and pneumatic dilation n=3) In the BT group all patients required at least a second dose 56

In 2018 Poornachand et al reported the case of a 45 days old infant with regurgitation of feeds noisy breathing and failure to thrive since born Barium swallow study showed dilatation of esophagus with bird beak appearance The manometry showed a LES pressure of 564mmHg confirming the diagnosis of achalasia cardia The infant underwent Hellerrsquos cardiomyotomy along with Nissenrsquos fundoplication with no complications At 1 month follow-up the infant gained weight of 900gr This is the youngest case of achalasia reported59

In 2018 Gugig et al reported a case of 12 year old patient with 1 year history of achalasia whom underwent Heller myotomy with fundoplication and recurred with symptoms 1 week after surgery The decision was made to place a fully covered self-expanding metallic stent for 3 months which resolved the stenosis as confirmed by esophagram The patient has remained asymptomatic since the procedure was performed 2 years ago This could be an alternative treatment of refractory achalasia60

In this year Miao et al published the results of a 21 pediatric patients who underwent peroral endoscopic myotomy their age ranged from 09 to 18 years old The time procedure was 30 to 55 minutes One patient developed subcutaneous emphysema and pneumoperitoneum treated with abdominocentesis Another mediastinal emphysema had spontaneously resolved The follow up period was 3 to 24 months

3434

(mean 132 months) The gastroesophageal reflux rate was 6 of 21 improved with PPIs61

CLINICAL MANIFESTATIONS OF PEDIATRIC ESOPHAGEAL ACHALASIA

Esophageal achalasia in the pediatric population is very uncommon 011100000 patients because of that the diagnosis is frequently delayed The most frequent symptoms are vomiting after meal dysphagia and weight loss or fail to thrive retrosternal pain and recurrent respiratory symptoms such as pneumonia and nocturnal cough In the adolescence age is very common to confuse the diagnosis with psychiatric disorders such as anorexia and bulimia In 1985 Swenson pointed out that finding food particles in the childrsquos pillow in the morning may be a clue to the diagnosis In the toddler age esophageal achalasia is even more infrequent The main clue to the diagnosis in this age group is the vomiting and the fail to thrive The most common finding in the chest radiography is air in the esophagus The definitive diagnosis test are the upper gastrointestinal series (barium swallow) and manometry

CONCLUSIONS

Because of the very low incidence of the esophageal achalasia in child the major evidence to its treatment are report of a case and series of cases with just a few retrospective observational comparative studies The very low success rate of the pneumatic balloon dilatation and botulinum toxin injection with just partial and temporal improvement make us to consider them just as a management for patients whorsquos are not candidates to surgery at that time to help them gain weight and nutrition to the definitive surgical treatment besides its very low complication rate (only 2 esophageal perforation because of the

pneumatic dilatation in the literature)

The definitive surgical treatment is the Heller myotomy There are enough reports to support its laparoscopy and thoracoscopic approach Because of the days of hospital stay are more in the thoracoscopic group (maybe attributed to the need of postoperative chest tube) we prefer the laparoscopic approach The need of antireflux procedure (Dor Toupet Nissen and Thal fundoplication) are reason for controversy even more in pediatric patients The very low incidence of postoperative reflux symptoms in child even without fundoplication indicates that it is probably not absolutely necessary

New therapies are appearing such a peroral endoscopic myotomy with excellent results even 100 success rate with no complications and low reflux symptoms rate but with the problem of small follow-up period The last therapies reported in pediatric population with only one report each are robot assisted Hellerrsquos myotomy or single port laparoscopic are promising managements The only report of endoscopic self-expandable metal stent let us to think that it may be a therapy for refractory achalasia with still no application as first line therapy

The need of multicentric clinical trial comparing the main and new therapies such as laparoscopic Heller myotomy with or without fundoplication vs peroral endoscopic myotomy is clear to stablish the benefits and success rate of each procedure with a long period follow-up

bull Esophageal Achalasia is a very uncommon disease in children younger age more infrequentbull Because of his low incidence the evidence for its management is almost remitted to

POINTS TO REMEMBER

3535

report of a case and series of casesbull Laparoscopic Heller myotomy is currently the best definitive managementbull Antireflux procedure is not clearly bull Treatments as pneumatic endoscopic dilatation and botulinum toxin injection are managements with partial and temporary response useful to weight gain to prepare the definitive procedurebull Peroral endoscopic myotomy is a promising treatment Multicentric clinical trials are required comparing it with laparoscopic Heller myotomy with a similar follow-up timebull New therapies reported in single cases as robot assisted Hellerrsquos myotomy single port laparoscopy and endoscopic self-expandable metal stent had still lack of evidence

AcknowledgmentsTo the pediatric resident of Central Hospital ldquoDr Ignacio Morones Prietordquo Dr Eduardo Caballero who provide me the clinical case of the preschool with esophageal achalasia and PLGA Aacutengela Milaacuten Estrada and Rubiacute Eleane Rodriacuteguez Quiroacutez who help me with the bibliography

BIBLIOGRAPHY

1Lass R Shephard E Mumps Arthritis Br Med J [en liacutenea]1961 Dec 16 [consulta 13 Feb 2018]2(5267)1613-1614 Disponible en httpswwwncbinlmnihgovpmcarticlesPMC19707692 Boyle JT Cohen S Watkins JB Successful treatment of achalasia in childhood by pneumatic dilatation J Pediatr 1981Jul99(1)35-403 Lemmer JH Coran AG Wesley JR Polley TZ Byrne WJ Achalasia in children treatment by anterior esophageal myotomy (modified Heller operation) J Pediatr Surg 1985 Aug20(4)333-3384 Holcomb GW Richards WO Riedel BD Laparoscopic esophagomyotomy for achalasia in children J Pediatr Surg [En liacutenea]1996 May 1 [consulta 13 Feb 2018]31(5)716-718 Disponible en httpwwwjpedsurgorgarticleS0022-3468(96)90685-5fulltext5 Robertson FM Jacir NN Crombleholme TM Moriarty KP Verhave M Thoracoscopic esophagomyotomy for achalasia in a child J Pediatr Gastroenterol Nutr 1997 Feb24(2)215-2176 Lelli JL Drongowski RA Coran AG Efficacy of the transthoracic modified Heller myotomy in children with

achalasia--a 21-year experience J Pediatr Surg 1997 Feb32(2)338-3417 Khoshoo V LaGarde DC Udall JN Intrasphincteric injection of Botulinum toxin for treating achalasia in children J Pediatr Gastroenterol Nutr 1997 Apr24(4)439-441 8 Hammond PD Moore DJ Davidson GP Davies RP Tandem balloon dilatation for childhood achalasia Pediatr Radiol1997 Jul27(7)609-6139 Hamza AF Awad HA Hussein O Cardiac achalasia in children Dilatation or surgery Eur J Pediatr Surg 1999 Oct9(5)299-30210 Esposito C Mendoza-Sagaon M Roblot-Maigret B Amici G Desruelle P Montupet P Complications of laparoscopic treatment of esophageal achalasia in children J Pediatr Surg 2000 May35(5)680-68311 Hurwitz M Bahar RJ Ament ME Tolia V Molleston J Reinstein LJ et al Evaluation of the use of botulinum toxin in children with achalasia J Pediatr Gastroenterol Nutr 2000 May30(5)509-51412 Ip KS Cameron DJ Catto-Smith AG Hardikar W Botulinum toxin for achalasia in children J Gastroenterol Hepatol [En liacutenea] 2000 Oct 1 [consulta 13 Feb 2018]15(10)1100-1104 Disponible enhttponlinelibrarywileycomdoi101046j1440-1746200002341xabstract13 Tashjian DB Moriarty KP Angelides AG Thoracoscopic Heller Myotomy for Achalasia in a 3-Year-Old Child Pediatr Endosurg Innov Tech [En liacutenea] 2001 Mar1 [consulta 13 Feb 2018]5(1)43-47 Disponible en httponlineliebertpubcomdoiabs10108910926410130000916714 Rothenberg SS Partrick DA Bealer JF Chang JH Evaluation of minimally invasive approaches to achalasia in children J Pediatr Surg 2001 May36(5)808-81015 Patti MG Albanese CT Holcomb GW Molena D Fisichella PM Perretta S et al Laparoscopic Heller myotomy and Dor fundoplication for esophageal achalasia in children J Pediatr Surg 2001 Aug36(8)1248-125516 Babu R Grier D Cusick E Spicer RD Pneumatic dilatation for childhood achalasia Pediatr Surg Int 2001 Sep17(7)505-50717 Mehra M Bahar RJ Ament ME Waldhausen J Gershman G Georgeson K et al Laparoscopic and thoracoscopic esophagomyotomy for children with achalasia J Pediatr Gastroenterol Nutr 2001 Oct33(4)466-47118 Khan AA Shah SWH Alam A Butt AK Shafqat F Efficacy of Rigiflex balloon dilatation in 12 children with achalasia a 6-month prospective study showing weight gain and symptomatic improvement Dis Esophagus 200215(2)167-17019 Mattioli G Esposito C Pini Prato A Doldo P Castagnetti M Barabino A et al Results of the laparoscopic Heller-Dor procedure for pediatric esophageal achalasia Surg Endosc 2003 Oct17(10)1650-165220 Fernandez PM Lucio LAG Pollachi F [Esophageal achalasia of unknown etiology in children] J Pediatr (Rio J) 2004 Dec80(6)523-52621 Paidas C Cowgill SM Boyle R Al-Saadi S Villadolid D Rosemurgy AS Laparoscopic Heller myotomy with anterior fundoplication ameliorates symptoms of achalasia in pediatric patients J Am Coll Surg 2007 May204(5)977-983 discussion 983-98622 Zhang Y Xu C-D Zaouche A Cai W Diagnosis and management of esophageal achalasia in children analysis of 13

3636

cases World J Pediatr 2009 Feb5(1)56-5923 Askegard-Giesmann JR Grams JM Hanna AM Iqbal CW Teh S Moir CR Minimally invasive Hellerrsquos myotomy in children safe and effective J Pediatr Surg 2009 May44(5)909-91124 Corda L Pacilli M Clarke S Fell JM Rawat D Haddad M Laparoscopic oesophageal cardiomyotomy without fundoplication in children with achalasia a 10-year experience a retrospective review of the results of laparoscopic oesophageal cardiomyotomy without an anti-reflux procedure in children with achalasia Surg Endosc 2010 Jan24(1)40-4425 Jung C Michaud L Mougenot J-F Lamblin M-D Philippe-Chomette P Cargill G et al Treatments for pediatric achalasia Heller myotomy or pneumatic dilatation Gastroenterol Clin Biol 2010 Mar34(3)202-20826 Lee CW Kays DW Chen MK Islam S Outcomes of treatment of childhood achalasia J Pediatr Surg 2010 Jun45(6)1173-117727 Tannuri ACA Tannuri U Velhote MCP Romatildeo RLP Laparoscopic extended cardiomyotomy in children an effective procedure for the treatment of esophageal achalasia J Pediatr Surg 2010 Jul45(7)1463-146628 Kobayashi M Mizuno M Sasaki A Arisue A Akiyama S Wakabayashi G Single-port laparoscopic Heller myotomy and Dor fundoplication initial experience with a new approach for the treatment of pediatric achalasia J Pediatr Surg 2011 Nov46(11)2200-220329 Di Nardo G Rossi P Oliva S Aloi M Cozzi DA Frediani S et al Pneumatic balloon dilation in pediatric achalasia efficacy and factors predicting outcome at a single tertiary pediatric gastroenterology center Gastrointest Endosc 2012 Nov76(5)927-93230 Chatterjee S Gajbhiye V De A Nath S Ghosh D Das SK Achalasia cardia in infants report of two cases J IMA 201244(1)31 Maselli R Inoue H Misawa M Ikeda H Hosoya T Onimaru M et al Peroral endoscopic myotomy (POEM) in a 3-year-old girl with severe growth retardation achalasia and Down syndrome Endoscopy 201244 Suppl 2 UCTNE285-28732 Esposito C Riccipetitoni G Chiarenza SF Roberti A Vella C Alicchio F et al Long-term results of laparoscopic treatment of esophageal achalasia in children a multicentric survey J Laparoendosc Adv Surg Tech A 2013 Nov23(11)955-9533 Familiari P Marchese M Gigante G Boskoski I Tringali A Perri V et al Peroral endoscopic myotomy for the treatment of achalasia in children J Pediatr Gastroenterol Nutr 2013 Dic57(6)794-79734 Lamas-Pinheiro R Amaral M Campos M Alvarenga A Garcia M Trindade E et al Miotomiacutea de Heller laparoscoacutepica resultados en nintildeos Cir Pediatr 2013 Dec 126(4)173-17635 Betancor L E C Peacuterez G I J Beltraacuten G D O et al La acalasia en la infancia y la adolescencia un reto terapeacuteutico Cir Pediatr [En liacutenea] 2014 Jan [consulta 13 Feb 2018]27(1)6-10 Disponible en httppesquisabvsaludorgportalresourceptibc-120705lang=es36 Pachl MJ Rex D DeCoppi P Cross K Kiely EM Drake D et al Paediatric laparoscopic Hellerrsquos cardiomyotomy A single centre series J Pediatr Surg [En liacutenea] 2014 Feb 1 [consulta 13 Feb 2018]49(2)289-292 Disponible en httpwwwsciencedirectcomsciencearticlepiiS002234681300902037 Franklin AL Petrosyan M Kane TD Childhood achalasia A comprehensive review of disease diagnosis and therapeutic management World J Gastrointest Endosc 2014 Apr

166(4)105-11138 Li Y Fallon SC Helmrath MA Gilger M Brandt ML Surgical treatment of infantile achalasia a case report and literature review Pediatr Surg Int 2014 Jun30(6)677-67939 Zhang X-C Li Q-L Huang Y Miao S-J Zhou P-H Peroral endoscopic myotomy using the posterior approach in an 11-month-old girl with achalasia severe malnutrition and recurrent pneumonia Endoscopy [En liacutenea] 2015 [consulta 13 Feb 2018]47 Suppl 1E480-482 Disponible en httpwwwthieme-connectdeDOIDOI101055s-0034-139315640 Chen W-F Li Q-L Zhou P-H Yao L-Q Xu M-D Zhang Y-Q et al Long-term outcomes of peroral endoscopic myotomy for achalasia in pediatric patients a prospective single-center study Gastrointest Endosc 2015 Jan81(1)91-10041 Li C Tan Y Wang X Liu D Peroral endoscopic myotomy for treatment of achalasia in children and adolescents J Pediatr Surg [En liacutenea] 2015 Jan 1 [consulta 13 Feb 2018]50(1)201-205 Disponible en httpwwwsciencedirectcomsciencearticlepiiS002234681400667842 Caldaro T Familiari P Romeo EF Gigante G Marchese M Contini ACI et al Treatment of esophageal achalasia in children Today and tomorrow J Pediatr Surg [En liacutenea] 2015 May 1 [consulta 13 Feb 2018]50(5)726-730 Disponible en httpwwwsciencedirectcomsciencearticlepiiS002234681500127X43 Filser J Dick A Meyer T Germer C-T von Rahden BHA Peroral Endoscopic Myotomy for the Treatment of Achalasia in a 10-Year-Old Male Patient European J Pediatr Surg Rep 2015 Jun3(1)18-22

44Pandian TK Naik ND Fahy AS Arghami A Farley DR Ishitani MB et al Laparoscopic esophagomyotomy for achalasia in children A review World J Gastrointest Endosc [En liacutenea] 2016 Jan 25 [consulta 13 Feb 2018]8(2)56-66 Disponible en httpswwwncbinlmnihgovpmcarticlesPMC472403145 Erginel B Gun Soysal F Keskin E Celik A Salman T Early myotomy and fundoplication in achalasia in childhood a single-centre experience for 22 years Acta Chir Belg 2016 Feb116(1)16-1846 Miyano G Miyake H Koyama M Morita K Kaneshiro M Nouso H et al Laparoscopic Heller Myotomy for Non-Dilated Esophageal Achalasia in Children with Intraoperative Stepped Dilation Under Image Guidance Attempting Complete Myotomy J Laparoendosc Adv Surg Tech [En liacutenea] 2016 Feb 4 [consulta 13 Feb 2018]26(5)409-412 Disponible en httponlineliebertpubcomdoi101089lap2015021747 Sharp NE Peter SDS Treatment of Idiopathic Achalasia in the Pediatric Population A Systematic Review Eur J Pediatr Surg [En liacutenea] 2016 Apr [consulta 13 Feb 2018]26(02)143-149 Disponible en httpwwwthieme-connectdeDOIDOI101055s-0035-154417448 Huelsen A Oumer R Ashcroft A Roberts RH Coulter GN Kelly SJ et al Achalasia a 13-year single-centre experience comparing endoscopic balloon dilatation and laparoscopic Heller myotomy N Z Med J 2016 Apr 22129(1433)41-5049 Zagory JA Golden JM Demeter NE Nguyen Y Ford HR Nguyen NX Heller Myotomy Is Superior to Balloon Dilatation or Botulinum Injection in Children with Achalasia A Two-Center Review J Laparoendosc Adv Surg Tech A 2016 Jun26(6)483-48750 Gould JL Rentea RM St Peter SD Contemporary Management of Achalasia by Pediatric Surgeons A Survey of

3737

the International Pediatric Endosurgical Group J Laparoendosc Adv Surg Tech [En liacutenea] 2016 Jun 20 [consulta 13 Feb 2018]26(7)567-569 Disponible en httponlineliebertpubcomdoi101089lap2016008551 Tan Y Zhu H Li C Chu Y Huo J Liu D Comparison of peroral endoscopic myotomy and endoscopic balloon dilation for primary treatment of pediatric achalasia J Pediatr Surg [En liacutenea] 2016 Oct 1 [consulta 13 Feb 2018]51(10)1613-1618 Disponible en httpwwwsciencedirectcomsciencearticlepiiS002234681630139752 Yamashita K Shiwaku H Hirose R Kai H Nakashima R Kato D et al Long-term outcome of peroral endoscopic myotomy for achalasia treatment in a 9-year-old female patient Asian J Endosc Surg [En liacutenea] 2016 Nov 1 [consulta 13 Feb 2018]9(4)332-5 Disponible en httponlinelibrarywileycomdoi101111ases12296abstract53 Altokhais T Mandora H Al-Qahtani A Al-Bassam A Robot-assisted Hellerrsquos myotomy for achalasia in children Comput Assist Surg (Abingdon) 2016 Dec21(1)127-13154 Grabowski A Korlacki W Pasierbek M Pułtorak R Achtelik F Ilewicz M Pediatric achalasia Single-center study of interventional treatment Prz Gastroenterol [En liacutenea] 2017 [consulta 13 Feb 2018]12(2)98-104 Disponible en httpswwwncbinlmnihgovpmcarticlesPMC549712855 Meyer A Catto-Smith A Crameri J Simpson D Alex G Hardikar W et al Achalasia Outcome in children J Gastroenterol Hepatol [En liacutenea] 2017 Feb 1 [consulta 13 Feb 2018]32(2)395-400 Disponible en httponlinelibrarywileycomdoi101111jgh13484abstract56 Saliakellis E Thapar N Roebuck D Cristofori F Cross K Kiely E et al Long-term outcomes of Hellerrsquos myotomy and balloon dilatation in childhood achalasia Eur J Pediatr [En liacutenea] 2017 Jul 1 [consulta 13 Feb 2018]176(7)899-907 Disponible en httpslinkspringercomarticle101007s00431-017-2924-x57 Nabi Z Ramchandani M Reddy DN Peroral Endoscopic Myotomy in a Child With Achalasia Cardia J Pediatr Gastroenterol Nutr [En liacutenea] 2017 Aug 1 [consulta 13 Feb 2018]65(2)E44 Disponible en httpsinsightsovidcompubmedpmid=2815176958 Islam S Achalasia Semin Pediatr Surg [En liacutenea] 2017 Apr 1 [consulta 13 Feb 2018]26(2)116-120 Disponible en httpwwwsciencedirectcomsciencearticlepiiS105585861730010059 Poornachand V Kumarasamy K Karamath SP Seenivasan V Bavanandam S Dheivamani N Achalasia Cardia in a Young Infant Indian J Pediatr [En liacutenea] 2018 Jan 19 [consulta 13 Feb 2018]1-3 Disponible en httpslinkspringercomarticle101007s12098-018-2610-760 Gugig R Muntildeoz Jurado G Huang C Oleas R Robles-Medranda C Self-expandable metal stent placement in a child for treatment of achalasia after failed Heller myotomy Endosc Int Open [En liacutenea] 2018 Jan [consulta 13 Feb 2018]6(1)E64-6 Disponible en httpswwwncbinlmnihgovpmcarticlesPMC577026961 Miao S Wu J Lu J Wang Y Tang Z Zhou Y et al Peroral Endoscopic Myotomy in Children With Achalasia A Relatively Long-term Single-center Study J Pediatr Gastroenterol Nutr [En liacutenea] 2018 Feb 1 [consulta 13 Feb 2018]66(2)257-262 Disponible en httpsinsightsovidcompubmedpmid=28691974

3838

The research work to be submitted for review should contain the following items organized as shown below

11 Title

It is necessary that you generally reflect the content of your work in an attractive way

12 Name of the authors

It is recommended to analyze how they will be identified because it is necessary to standardize their name for future publications and have a first name must include the full name putting together the surnames with a hyphenExample Mauricio Pierdant-Peacuterez

13 Adscription

Record the degree of studies career to which belong Faculty andor University of which you are student fully registering the name of the institution Separated with semicolons ()Example 2nd year student Medical School Faculty of Medicine Autonomous University of San Luis Potosiacute

14 ORCID

Relate your registration to obtain your Digital Identifier in order to obtain a profile as a researcher and integrate links in each of your works

15 Summary

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16 Keyword

Establish descriptors according to Medical Subject Headings (MeSH) available in the National Library of Medicine (httpswwwncbinlmnihgovmesh) DeCs for Spanish searches

17 Corresponding author

Name and e-Mail

Research questions arise through reading academic or social conversations in classes or in a clinical context so in this section a brief explanation of how your research question and or problem arose guiding to the reader the need that has arisen to carry out the development of his workIn case the origin arises within classes the topic seen in class will be mentioned as well as the degree of information (sufficient or null) that allows to create the question mark

It consists of the following elements

31 Keywords

It is necessary to identify the keywords of the subject that is being sought as well as their synonyms You need to use MeSH to perform searches

32 Boolean operators

Structure the MeSH term conjugations with the boolean operators using AND to join two or three terms OR so that the scope of the search is greater and NOT to exclude unwanted terms

33 Limits

It is important to establish them to delimit our search these tools will be found within each source of electronic information that identifies

InfORmATIOn fOR AuThORs

Journal of Medical Students Reviews

1 MAIN PAGE WHICH WILL CONTAIN 2 QUESTION AND CONTEXT

3 SEARCH STRATEGY

3939

34 Information sources

The electronic sources of information consulted divided intoMeta search engines PuMed BVS Trip database Ovid SPDatabases Medic Latina Science Direct micromedex Springer link Wiley etc

35 Results

The total result of each search will be displayed specifying the total number of articles identified and the total number of articles retrieved (used)Example

No Source of information

No Identified articles

No Recovered items

1 PubMed 200 342 Ovid Sp 140 10

For the analysis of the retrieved literature OPMER will be used a format that allows the methodological evaluation of the articles as well as the selection of those that will be used in the work according to a scale

It gave a general description of the subject the results that you found

In this section you will begin to describe what is found in the literature previously selected the aspects to be considered are

- Authors- Previous research- Results of other similar investigations- Identify Theories- Years in which the selected theme has had a greater impact

4 EVIDENCE EVALUATION

It will include the conclusion reached by the authors about the content of the subject to investigate answering the question concretely coherent and relevant

In this section the students will expose the difficulties with which found developing the topic leading to the development of new research related to the work developedThey can make recommendations within their area to prevent and or treat certain diseases in case of being a clinical issue

It will be in Vancouver-style bibliography based on Citing Medicine the NLM Style Guide for Authors Edithors and Publisers Available in httpswwwncbinlmnihgovbooksNBK7256 As well as the Quick Reference Guide Vancouver Style available at httpsesslidesharenetCICBIguia-rapida- para-la- redaccioacuten-de-referenciasestilo-vancouver

The images tables and graphics will be presented in JPG or PNG format presented at the end of the articleThey should be mentioned within the article at the end of the paragraph in parentheses named and listed consecutively with Arabic numeralsExample (Image 1 Search methodology)For this journal considers as an image that photograph and or figure that support the understanding of a paragraph tables like those figures that are columns and rows that

5 INTRODUCTION

7CONCLUSIONS

6 STATE OF THE ARTRESULTS

8 POINTS TO TAKE HOME

9 BIBLIOGRAPHY

10 TABLES AND GRAPHICS

4040

are recommended for organize and present relevant information in the investigationThe Graphs will be used to represent the numerical data using circles lines or bars the relationship between the data presented

Authors must state that they do not have any type of conflict at the personal institutional that compromise to a secondary benefit nor to be obligatorily committed by third parties and be signed by each of them

10 CONFLICT OF INTEREST

4141

Available in httpwwwmedicinauaslpmxPaginasJMSRManualJMSRpdf

Check our guide How to write a review for the JMSR where you will find more information about how to

publish in our Journal

DIRECTIVE COMMITTEE

RECTOR OF THE UNIVERSITYDIRECTORCHIEF EDITORASSOCIATE EDITOR

MANUEL FERMIacuteN VILLAR RUBIO M ARCH

ALEJANDRO JAVIER ZERMENtildeO GUERRA MDMAURICIO PIERDANT PEacuteREZ MD MSC

MARIacuteA ISABEL PATINtildeO LOacutePEZ MLIS

LILIANA ITAMAR CARRILLO BARBA MSANDREacuteS CASTILLO DIMAS MSALEJANDRA DE LA TORRE SOTO MSROCIacuteO DANIELA OCHOA VALTIERRA MSLIZETH GUADALUPE ORTIZ VAacuteZQUEZ MS

AREA EDITORS

BLANCA ARIADNA CARRILLO AacuteVALOS MD MARIANA SALGADO BUSTAMANTE MD PhDCHRISTIAN A GARCIacuteA SEPUacuteLVEDA MD PhDSERGIO SAacuteNCHEZ-ARMASS ACUNtildeA MD PhDESTHER LAYSECA ESPINOSA MD PhDUCIEL RENEacute OCHOA PEacuteREZ MD MSC

ANTONIO A GORDILLO MOSCOSO MD PhD EMMANUEL RIVERA LOacutePEZ MDDAVID DE DANIEL ESMER SAacuteNCHEZ MDRAUacuteL ROQUE SAacuteNCHEZ MDJUAN CARLOS TORO ORTIZ MDAMADO NIETO CARAVEO MD MSC

MARISOL OROCIO CONTRERAS MD PhD

EDITORIAL COMMITTEE

MORPHOLOGYBIOCHEMISTRYMOLECULAR BIOLOGYPHYSIOLOGYIMMUNOLOGYMICROBIOLOGYPHARMACOLOGYINTERNAL MEDICINESURGERYPEDIATRICSGYNECOLOGYPUBLIC HEALTHMENTAL HEALTH

INDEX


CHIEF EDITOR





GONZAacuteLEZ MS





1-2 p

3-11p

12-18 p

19-37p


ARTICLES

38-40p

EDITORIAL



1Chief Editor


1










22







BIBLIOGRAPHY











Teach 201032(3)e152-e160






Abstract


Corresponding autor



3


44











METHODS

INTRODUCTION

55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




INDEX


CHIEF EDITOR





GONZAacuteLEZ MS





1-2 p

3-11p

12-18 p

19-37p


ARTICLES

38-40p

EDITORIAL



1Chief Editor


1










22







BIBLIOGRAPHY











Teach 201032(3)e152-e160






Abstract


Corresponding autor



3


44











METHODS

INTRODUCTION

55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




EDITORIAL



1Chief Editor


1










22







BIBLIOGRAPHY











Teach 201032(3)e152-e160






Abstract


Corresponding autor



3


44











METHODS

INTRODUCTION

55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




22







BIBLIOGRAPHY











Teach 201032(3)e152-e160






Abstract


Corresponding autor



3


44











METHODS

INTRODUCTION

55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141








Abstract


Corresponding autor



3


44











METHODS

INTRODUCTION

55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




44











METHODS

INTRODUCTION

55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




55



RESULTS


66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




66











77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




77







88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




88

Table 1 Results

99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




99


1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1010







POINTS TO REMEMBER



CONCLUSIONS

1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1111

Acknowledgements








fs365es










Nov 2514(403)1-8




Dec32(8)992-999



Syst Rev 2013 Mar28(3) CD002106













Burns 2011 Dec37(8)1343-1348













Surg 2008 Feb60(2)181-185







Surg 2011 Sep45(4-5)200-203










Chir 201183(10)541-548




Oct-Nov20(9)A802





2013 May-Jun21(3)402-409




2017 Aug43(4)549-556















Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141







Meacutexico

Corresponding autor



12

Abstract



1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1313









METHODS

1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1414


PATHOPHYSIOLOGY




ETIOLOGY


Viral Infections


RESULTS

1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1515


Chagas disease







1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1616








1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1717








Jun100(6)1404-1414






Apr40(4)859-864







1964 Sep160(3)474-87



63(240)297-303



2015 Jul9(4)449ndash463




CONCLUSIONS

1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




1818





























































Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141







Abstract


Corresponding autor



19


2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2020








achalasia Adapted 4

2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2121









2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2222

Table 1 Results

2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2323


2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2424


2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2525







2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2626








2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2727








2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2828








2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




2929










3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3030









3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3131










3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3232






3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3333










3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3434




CONCLUSIONS







POINTS TO REMEMBER

3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3535



BIBLIOGRAPHY



3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3636




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3737


3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3838


11 Title




13 Adscription


14 ORCID


15 Summary


16 Keyword



Name and e-Mail



31 Keywords




33 Limits





3 SEARCH STRATEGY

3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




3939



35 Results




No Recovered items

1 PubMed 200 342 Ovid Sp 140 10










5 INTRODUCTION

7CONCLUSIONS



9 BIBLIOGRAPHY


4040




4141




4040




4141




4141




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