PeritonectomyPeritonectomyIs this a realistic, safe and viable option for Is this a realistic, safe and viable option for

improving ovarian cancer cytoreductive improving ovarian cancer cytoreductive surgery?surgery?

Alex J CrandonAlex J Crandon&&

Marcelo Carraro Nascimento Marcelo Carraro Nascimento Qld Centre for Gyn. CancerQld Centre for Gyn. Cancer

AdvantagesAdvantages of Cytoreductive of Cytoreductive SurgerySurgery

Generally accepted as the corner stone for Generally accepted as the corner stone for treating advanced ovarian cancertreating advanced ovarian cancer

Gives most accurate diagnosis & stagingGives most accurate diagnosis & staging Rapidly improves symptoms and QOLRapidly improves symptoms and QOL Optimises response to chemotherapyOptimises response to chemotherapy May improve host immune responseMay improve host immune response Improves survivalImproves survival

Residual Disease –v- Survival in Residual Disease –v- Survival in Advanced EOCAdvanced EOC

16 (>2cm)45 (<2cm)Delgado, G 1984

16 (>2cm)45 (<2cm)Pohl, R 1984

14 (>2cm)25+ (<2cm)Conte, P 1985

8 (>1cm)19 (≤1cm)Zang, RY 2000

18 (>2cm)30+ (<2cm)Posada, JG 1985

15 (≥2cm)24 (<2cm)Louie, KG 1986

21 (>3cm)72 (≤3cm)Hainsworth, J 1988

21 (>1cm)48 (≤1cm)Piver, MS 1988

23 (≥3cm)45 (<3cm)Sutton, GP 1989

15 (>2cm)25 (≤2cm)Munkarah 1997

10 (>1cm)38 (≤1cm)Bristow, RE 1999

Suboptimal debulking Survival (months)

Optimal debulking Survival (months)

Study

Optimal DebulkingOptimal Debulking

Variously defined in the literature Variously defined in the literature from <0.5cm (Hacker, NF 1983) to from <0.5cm (Hacker, NF 1983) to ≤3cm (Hainsworth, 1988 & Sutton, ≤3cm (Hainsworth, 1988 & Sutton, 1989)1989)

Consistently associated with better Consistently associated with better survivalsurvival

Most studies are retrospectiveMost studies are retrospective

QCGC DatabaseQCGC Database

New database commissioned in 1994New database commissioned in 1994 Prospectively accumulated data on Prospectively accumulated data on

701 patients with stage 3C epithelial 701 patients with stage 3C epithelial ovarian cancerovarian cancer

Stratified residual disease left at the Stratified residual disease left at the end of surgery into 6 categories: nil end of surgery into 6 categories: nil residuum, <1cm, 1-2cm, >2cm but residuum, <1cm, 1-2cm, >2cm but not gross residuum, gross residuum & not gross residuum, gross residuum & unknown.unknown.

Stage 3C EOC BreakdownStage 3C EOC Breakdown

100701Total

24.1169Unknown

9.365Gross

6.445>2cm

8.6601-2cm

32.4227<1cm

19.3135Nil

PercentNumberResidual Disease

Stage IIIC EOC Stage IIIC EOC Residual Disease –v- Disease Specific Residual Disease –v- Disease Specific

SurvivalSurvival

100

90

80

70

60

50

40

30

20

10

0

% S

UR

VIV

AL

12 24 36 48 60 MONTHS

47% (135-32) Nil

95% CI MedianNil 135 102 80 62 45 32 37, 57[ ] 57 Mths

26% (227-26) <1cm

95% CI Median

<1cm 227 192 118 75 38 26 19, 33[ ] 32 Mths

16% (170-10) 1+cm

95% CI Median

1+cm 170 115 62 39 22 10 8, 23[ ] 23 Mths

Ovary 3c - Residual disease

Stage IIIC EOCStage IIIC EOCResidual Disease and Relapse Free SurvivalResidual Disease and Relapse Free Survival

100

90

80

70

60

50

40

30

20

10

0

% R

ELA

PS

E F

RE

E

12 24 36 48 60 MONTHS

27% (135-18) Nil

95% CI MedianNil 135 89 47 31 21 18 18, 36[ ] 23 Mths

13% (227-14) <1cm

95% CI Median

<1cm 227 145 51 31 19 14 8, 18[ ] 13 Mths

6% (170-3) 1+cm

95% CI Median

1+cm 170 82 21 12 5 3 1, 10[ ] 12 Mths

Ovary 3c - Residual disease

ConclusionsConclusions

Nil residuum have a statistically Nil residuum have a statistically significantly better overall and significantly better overall and relapse free 5 year survival, relapse free 5 year survival, p<0.001p<0.001

Once the residuum gets to Once the residuum gets to ≥1cm ≥1cm then it doesn’t matter how much then it doesn’t matter how much residuum you leave behindresiduum you leave behind

The proportion left with nil residuum The proportion left with nil residuum needs to be increasedneeds to be increased

Management of Advanced Management of Advanced DiseaseDisease

Pelvic & omental disease well Pelvic & omental disease well managedmanaged

Tendency to leave paracolic, Tendency to leave paracolic, abdominal wall, sub-diaphragmatic, abdominal wall, sub-diaphragmatic, retro-hepatic and para-splenic disease retro-hepatic and para-splenic disease to be dealt with by chemotherapyto be dealt with by chemotherapy

This last decision is obviously This last decision is obviously detrimental to patient survivaldetrimental to patient survival

Peritonectomy StudyPeritonectomy Study

This is a prospective feasibility study This is a prospective feasibility study into the techniques of peritonectomy into the techniques of peritonectomy to determine its transferability to to determine its transferability to surgery for ovarian and primary surgery for ovarian and primary peritoneal carcinomaperitoneal carcinoma

During the course of the study During the course of the study patients with other peritoneal patients with other peritoneal carcinomatoses have been referred carcinomatoses have been referred for surgeryfor surgery

Peritonectomy MethodologyPeritonectomy Methodology

Very careful selection of patients for Very careful selection of patients for this procedurethis procedure Relatively fit and wellRelatively fit and well Three day pre-operative inpatient Three day pre-operative inpatient

assessment by anaesthetist, intensivist, assessment by anaesthetist, intensivist, medical oncologist & surgeonmedical oncologist & surgeon

Reservations involving 2 or more and the Reservations involving 2 or more and the patient doesn’t get donepatient doesn’t get done

Peritonectomy WorkupPeritonectomy Workup

Full blood countFull blood count Blood group and antibody screenBlood group and antibody screen Coagulation screenCoagulation screen Biochemistry and liver function testsBiochemistry and liver function tests EchocardiogramEchocardiogram Full lung function testsFull lung function tests Nutritional assessmentNutritional assessment Visit ICU and wardVisit ICU and ward Pathology liaises with Red Cross blood bankPathology liaises with Red Cross blood bank Immunise for possible splenectomy Immunise for possible splenectomy

(pneumococcus, haemophilus influenzae & (pneumococcus, haemophilus influenzae & meningococcal C)meningococcal C)

One Patient RejectedOne Patient Rejected

One woman aged 43 with peritoneal mesothelioma One woman aged 43 with peritoneal mesothelioma was rejected for surgerywas rejected for surgery

Previous left pneumonectomyPrevious left pneumonectomy On admission for work up was found to have a On admission for work up was found to have a

resting tachycardia ~100bpmresting tachycardia ~100bpm Echocardiogram showed pulmonary hypertension Echocardiogram showed pulmonary hypertension

and tricuspid incompetenceand tricuspid incompetence Patients father took her to Boston where Patients father took her to Boston where

peritonectomy & HIPC performedperitonectomy & HIPC performed Returned to Brisbane 12 weeks later Returned to Brisbane 12 weeks later Died of right heart failure 10 days after returningDied of right heart failure 10 days after returning

Peritonectomy AdmissionPeritonectomy Admission

Admitted at least 1 day prior to Admitted at least 1 day prior to surgerysurgery

High nitrogen low residue diet High nitrogen low residue diet continued (started at home)continued (started at home)

Full bowel prep with IV infusion Full bowel prep with IV infusion runningrunning

Repeat FBC, Biochem & LFT’s, Repeat FBC, Biochem & LFT’s, MagnesiumMagnesium

Possible stoma sites markedPossible stoma sites marked

Day of SurgeryDay of Surgery

Transfer to OT by 0700 hrTransfer to OT by 0700 hr General anaestheticGeneral anaesthetic Arterial lineArterial line Central lineCentral line Oesophageal temperature probeOesophageal temperature probe Indwelling urinary catheterIndwelling urinary catheter Patient positioned for surgery on Patient positioned for surgery on

warming air mattresswarming air mattress Intra-operative “echo” Intra-operative “echo”

Peritonectomy PositioningPeritonectomy Positioning

Peritonectomy MethodologyPeritonectomy Methodology

LongLong midline incision – assess and decide if proceed midline incision – assess and decide if proceed to peritonectomyto peritonectomy

Total omentectomy up to spleen and splenic flexure Total omentectomy up to spleen and splenic flexure +/- splenectomy+/- splenectomy

Excise falciform ligament and ligamentum teres, Excise falciform ligament and ligamentum teres, mobilise liver and do right upper quadrant; left mobilise liver and do right upper quadrant; left upper quadrant; abdominal wall and paracolic upper quadrant; abdominal wall and paracolic gutters; pelvis with retrograde hysterectomy, BSO, gutters; pelvis with retrograde hysterectomy, BSO, pelvic peritonectomy +/- low restorative rectal pelvic peritonectomy +/- low restorative rectal resection; finish mesentry & small bowel.resection; finish mesentry & small bowel.

Insertion naso-jejunal feeding tubeInsertion naso-jejunal feeding tube All surgery performed by QCGC staffAll surgery performed by QCGC staff

Important AspectsImportant Aspects

Harmonic shears for omentectomy Harmonic shears for omentectomy and splenectomy saves time & and splenectomy saves time & bleedingbleeding

The whole surgical team needs to The whole surgical team needs to stop every 4 hours and take a break; stop every 4 hours and take a break; rehydration and food is importantrehydration and food is important

Peritoneal stripping should be done Peritoneal stripping should be done either with electrodiathermy using either with electrodiathermy using 3mm ball on pure cut or Argon 3mm ball on pure cut or Argon plasma coagulatorplasma coagulator

Peritonectomy PatientsPeritonectomy Patients

Died of bowel obstruction

FOD

?PD

?PD

FOD

FOD

FOD

DOD

SD

FOD

Recurrence (L & H)

FOD

Status

27.53C ROvary77PP

3143CPeritoneum53SW

7 10.253C ROvary66ES

417D RAppendix61VM

8133C ROvary57SM

010.254 RMesothelioma40KC

3103COvary60SD

35.754 RMesothelioma59ML

053C RPeritoneum59IK

38.53CPeritoneum74MT

053COvary65VW

05.53C ROvary54SB

Intra-op Transfusion

(units)

Operative Time (hrs)

StagePrimary Disease Site

AgePatient

PeritonectomyPeritonectomyExtent of SurgeryExtent of Surgery

10 thoracotomies – 6 ICC’s10 thoracotomies – 6 ICC’s 8 significant diaphragmatic resections8 significant diaphragmatic resections 7 subsegmental liver resections7 subsegmental liver resections 3 cholecystectomies3 cholecystectomies 6 splenectomies, 2 distal pancreatectomies6 splenectomies, 2 distal pancreatectomies 3 partial cystectomies, 1 ureteric 3 partial cystectomies, 1 ureteric

implantationimplantation 6 GIT resections; 4 small, 4 large & 1 6 GIT resections; 4 small, 4 large & 1

partial antrectomypartial antrectomy 5 HIPC, 4 post operative IPC.5 HIPC, 4 post operative IPC.

Post Operative ManagementPost Operative Management

All patients admitted to ICU ventilatedAll patients admitted to ICU ventilated Ventilatory support for 3 to 8 daysVentilatory support for 3 to 8 days ICU stay for 5 to 10 daysICU stay for 5 to 10 days Post-operative hospital stay 16 to 45 daysPost-operative hospital stay 16 to 45 days Naso-jejunal feeding started soon after Naso-jejunal feeding started soon after

admission to ICUadmission to ICU

Total Peritonectomy Total Peritonectomy Post-operative ComplicationsPost-operative Complications

No returns to theatre & No operative No returns to theatre & No operative related deaths (one death at day 34 post-related deaths (one death at day 34 post-op from unresolved functional bowel op from unresolved functional bowel obstruction)obstruction)

One post-op bleed not requiring surgical One post-op bleed not requiring surgical interventionintervention

One left subphrenic haematoma found 4 One left subphrenic haematoma found 4 weeks post peritonectomyweeks post peritonectomy

One wound breakdownsOne wound breakdowns

Modified/Subtotal Modified/Subtotal PeritonectomyPeritonectomy

7 done to date, 7 done to date, All admitted to ICUAll admitted to ICU Ventilation 1 to 3 daysVentilation 1 to 3 days 1 superficial wound breakdown1 superficial wound breakdown One left subphrenic abscess 3 months One left subphrenic abscess 3 months

following surgeryfollowing surgery One recto-vaginal fistula several One recto-vaginal fistula several

months following surgery (2 months months following surgery (2 months after closure of ileostomy)after closure of ileostomy)

Lessons LearntLessons Learnt

Requires a real team approachRequires a real team approach Advantages in having an anaesthetist with Advantages in having an anaesthetist with

cardiac/hepatobiliary experiencecardiac/hepatobiliary experience Extent of peritonectomy dependent on Extent of peritonectomy dependent on

disease distribution & prior chemotherapydisease distribution & prior chemotherapy Liver mobilisation often uncovers covert Liver mobilisation often uncovers covert

diseasedisease Temperature control can be a problem – Temperature control can be a problem –

use an air mattress circulating warm airuse an air mattress circulating warm air

Where could we be?Where could we be?

100

20.2

8.8

8.8

60.3

Modified Peritonectomy

100886Total

20.2179Unknown

8.878Gross

8.878>2cm

10.3921-2cm

34.1302<1cm

17.8158Nil

PercentNumberResidual Disease

ImagineImagine

If over half of our patients with Stage If over half of our patients with Stage 3C EOC were being debulked to nil 3C EOC were being debulked to nil residuum with an overall 5-year residuum with an overall 5-year survival of 47 per cent. survival of 47 per cent.

Conclusion 1 from Conclusion 1 from Peritonectomies Peritonectomies

Peritonectomy is a relatively safe Peritonectomy is a relatively safe procedureprocedure

Conclusion 2 from Conclusion 2 from PeritonectomiesPeritonectomies

If disease can be debulked to 2cm then If disease can be debulked to 2cm then it can be debulked to nil residuum it can be debulked to nil residuum but however long it takes to get to but however long it takes to get to 2cm it will take 1 to 2 times as long 2cm it will take 1 to 2 times as long again to get to nil residuum.again to get to nil residuum.

Conclusion 3 from Conclusion 3 from PeritonectomiesPeritonectomies

At laparotomy if initial assessment indicates At laparotomy if initial assessment indicates that disease cannot be debulked to nil that disease cannot be debulked to nil residuum then limited omentectomy only residuum then limited omentectomy only should be performed with a view to should be performed with a view to interval debulking if good response to interval debulking if good response to Chemo Chemo

On present experience modified On present experience modified peritonectomy is a feasible and viable peritonectomy is a feasible and viable procedure for advanced EO & PP procedure for advanced EO & PP carcinoma and should become the carcinoma and should become the standard of carestandard of care

Conclusion 4 from Conclusion 4 from PeritonectomiesPeritonectomies

Patient selection for modified Patient selection for modified peritonectomy remains the most peritonectomy remains the most difficult issue in planning operating difficult issue in planning operating lists with ovarian cancer caseslists with ovarian cancer cases

Conclusion 5 from Conclusion 5 from PeritonectomiesPeritonectomies

How to train the next generation of How to train the next generation of Gynaecological Oncologists?Gynaecological Oncologists?