QS36. Nitric Oxide-Mediated Radiosensitization to Ionizing Radiation-Induced Apoptosis of Colon...
2
pancreatic adenocarcinoma. However, a more detailed analysis con- sidering outcomes without surgery for each primary tumor site is needed before the value of this aggressive surgical approach can be completely assessed. QS33. EXTENDED LEFT-SIDED PANCREATECTOMY WITH SPLEEN PRESERVATION. Arash Mohebati 1 , Roderich E. Schwarz 2 ; 1 UMDNJ - Robert Wood Johnson Medical School, New Brunswick, NJ; 2 UT Southwestern Medical Center, Dal- las, TX Background: Left-sided or distal pancreatectomy (DP) is frequently performed in conjunction with splenectomy, although splenectomy can be linked to various untoward effects, and sparing of the main splenic vessels (SV) is not necessary for successful spleen preserva- tion (SP). Methods: We reviewed clinical records of all patients undergoing DP in a single-surgeon practice to assess feasibility and outcomes of SP. Results: Between 1997 and 2007, 41 of 177 pancre- atic resections involved a DP (23%). There were 14 men (34%) and 27 women (66%), with a median age of 60 years (range: 34-86). Resec- tion indications included 26 solid masses, 10 cysts, 4 combinations thereof, and one diffuse process. Four procedures were en bloc resec- tions, 2 total pancreatectomies, while 8 of the remaining 35 DPs were performed laparoscopically. SP was accomplished in 33 of 34 possible cases (spleen preservation rate 97%), despite SV resection in 27 of these (82%). The postoperative complication rate was 24%, and there was no postoperative death. The median length of stay was 6 days (4-24). Pancreatic fistulae occurred in 2 patients (5% of patients at risk), and one SPDP led to splenic infarct. At a median follow-up of 16 months (2.5-89), no other clinically relevant problems specific to SP have become apparent. One patient after DP with splenectomy expired from postsplenectomy sepsis. Conclusions: Pancreatic fis- tula rate and other outcomes in this small DP experience compare favorably to many other DP series. Few spleen-specific complications and the radicality of resection support the liberal use of SP with SV resection, irrespective of an open or laparoscopic approach. QS34. PREOPERATIVE DIAGNOSIS OF TUMOR EXTENT OF BILE DUCT CANCER BY INTRADUCTAL ULTRA- SONOGRAPHY. Jun Ienaga, Yoshihiko Sadakari, Reiko Tanabe, Norihiro Sato, Shunichi Takahata, Hiroki Toma, Toshinaga Nabae, Masafumi Nakamura, Koji Yamaguchi, Masao Tanaka; Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Backgrounds: For bile duct cancer, it is important to evaluate the vertical and horizontal extent correctly. Aim: To determine the useful- ness of intraductal ultrasonography (IDUS) for diagnosis of tumor ex- tent of bile duct cancer. Patients and Methods: Between July 2001 and September 2007, 54 patients with bile duct cancer were studied by IDUS. Among them, 25 patients underwent surgical resection. IDUS findings with respect to vertical invasion to the subserosal layer, pan- creatic parenchyma, right hepatic artery and portal vein, and horizon- tal spread along the bile duct wall were compared with pathological findings in these 25 patients. All pathological descriptions were based on the General Rules for Surgical and Pathological Studies on Cancer of the Biliary Tract (5th edition) published by the Japanese Society of Biliary Surgery. Results: Subserosal invasion was correctly diagnosed by IDUS in 20 patients (80%). Pancreatic parenchymal invasion was accurately determined in 20 patients (80%). Although there were no patients who had histological invasion to the right hepatic artery in this study population, IDUS diagnosis was correlated well with surgical diagnosis in this regard (accuracy: 88%). One patient who had histolog- ical invasion to the portal vein could be diagnosed as having the inva- sion preoperatively by IDUS; all other patients without portal vein invasion were diagnosed correctly. Horizontal spread to the hepatic side was accurately determined in 22 patients (88%). Those who had biliary drainage performed either by the percutaneous transhepatic method or endoscopic retrograde method tended to show low accuracy compared with those who did not received biliary drainage (71% (5/7), 94% (17/18), respectively, p0.11). The tumor of bile duct and the surrounding structure could be visualized in detail by IDUS. IDUS could accurately evaluate the vertical invasion to the subserosal layer and other organs, and the horizontal extent of mural invasion to the hepatic side. How- ever, once biliary drainage had been introduced, the bile duct wall became thickened and this made it difficult to distinguish between the tumor extent and benign wall thickening in response to a biliary drain- age catheter. Therefore, it seemed to be better to perform IDUS before biliary drainage. Conclusions: IDUS is useful to precisely assess the vertical and horizontal tumor extent of bile duct cancer when performed before biliary drainage. QS35. COLECTOMY FOR COLON CANCER IN PATIENTS WITH A PRIOR VENTRICULOPERITONEAL SHUNT THE DEPARTMENT OF VETERANS AFFAIRS EXPE- RIENCE. Edel M. Doorley 1 , Andrew R. Barina 2 , Katherine S. Virgo 2 , Anil M. Bahadursingh 2 , Frank E. Johnson 2 ; 1 Univer- sity of Liverpool, Liverpool, United Kingdom; 2 Saint Louis University, St. Louis, MO Objective: Many patients have VP shunts implanted for congenital conditions. Subsequent abdominal operations in these patients are reportedly hazardous. We aimed to determine the clinical course of adults with ventriculoperitoneal (VP) shunts for acquired conditions who later required colectomy for colon cancer. Introduction: Ap- proximately 18,000 cerebrospinal fluid shunts, the majority of which are VP, are implanted each year in the USA. These patients may subsequently require colectomy for colon cancer. Whether the risk of adverse events, particularly infection, is increased in such patients is not known. Methods: A search of national Department of Veterans Affairs (DVA) databases was conducted to identify all veterans with a VP shunt from 1989-2003 who later underwent colectomy as curative-intent treatment for colon cancer between 1994-2003. All were healthy upon entry into military service and required shunts for conditions acquired later. Patient medical records were analyzed to determine if the presence of a VP shunt affected the colectomy procedure or the postoperative course. Results: There were 4,219 unique inpatients and 795 unique outpatients with ICD-9 codes for VP shunt and 16,514 with codes for colectomy for colon cancer in the DVA system for the years specified. Fourteen had codes for both colectomy for colon cancer and pre-existing VP shunt. Four met our inclusion criteria and had sufficient data for analysis; all had un- complicated postoperative courses with no instances of extensive adhesions encountered during colectomy, postoperative infection, or postoperative shunt malfunction. Discussion and Conclusions: This is the only English-language report on this topic, to our knowl- edge. Patients who receive VP shunts for acquired hydrocephalus as adults and later receive colectomy as curative treatment for colon cancer in the DVA system appear to experience a postoperative course similar to that of patients without VP shunts. QS36. NITRIC OXIDE-MEDIATED RADIOSENSITIZATION TO IONIZING RADIATION-INDUCED APOPTOSIS OF COLON CANCER CELLS. Derrick Chen, Laura Ortega, David Chen, Edward H. Livingston, Sergio Huerta; Univer- sity of Texas Southwestern, Dallas, TX Background: Metastatic colon cancer cells SW620 are resistant to ionizing radiation (IR)-mediated apoptosis. DETA/NONOate (DETA) is an NO donor, which mimics NO sustained release for over 20 hours. DETA causes mitochondrial permeability resulting in the release of pro-apoptotic mediators, while inhibiting the NFB anti- apoptotic pathway. Methods: SW620 pre-treated with DETA (1000 g X 24 h) and untreated cells were subjected to IR treatment at 0, 1, 2, 3, and 5 Gy. Apoptosis was measured by flow cytometry 283 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
-
Upload
derrick-chen -
Category
Documents
-
view
212 -
download
0
Transcript of QS36. Nitric Oxide-Mediated Radiosensitization to Ionizing Radiation-Induced Apoptosis of Colon...
pancreatic adenocarcinoma. However, a more detailed analysis con-sidering outcomes without surgery for each primary tumor site isneeded before the value of this aggressive surgical approach can becompletely assessed.
QS33. EXTENDED LEFT-SIDED PANCREATECTOMY WITHSPLEEN PRESERVATION. Arash Mohebati1, Roderich E.Schwarz2; 1UMDNJ - Robert Wood Johnson Medical School,New Brunswick, NJ; 2UT Southwestern Medical Center, Dal-las, TX
Background: Left-sided or distal pancreatectomy (DP) is frequentlyperformed in conjunction with splenectomy, although splenectomycan be linked to various untoward effects, and sparing of the mainsplenic vessels (SV) is not necessary for successful spleen preserva-tion (SP). Methods: We reviewed clinical records of all patientsundergoing DP in a single-surgeon practice to assess feasibility andoutcomes of SP. Results: Between 1997 and 2007, 41 of 177 pancre-atic resections involved a DP (23%). There were 14 men (34%) and 27women (66%), with a median age of 60 years (range: 34-86). Resec-tion indications included 26 solid masses, 10 cysts, 4 combinationsthereof, and one diffuse process. Four procedures were en bloc resec-tions, 2 total pancreatectomies, while 8 of the remaining 35 DPs wereperformed laparoscopically. SP was accomplished in 33 of 34 possiblecases (spleen preservation rate 97%), despite SV resection in 27 ofthese (82%). The postoperative complication rate was 24%, and therewas no postoperative death. The median length of stay was 6 days(4-24). Pancreatic fistulae occurred in 2 patients (5% of patients atrisk), and one SPDP led to splenic infarct. At a median follow-up of16 months (2.5-89), no other clinically relevant problems specific toSP have become apparent. One patient after DP with splenectomyexpired from postsplenectomy sepsis. Conclusions: Pancreatic fis-tula rate and other outcomes in this small DP experience comparefavorably to many other DP series. Few spleen-specific complicationsand the radicality of resection support the liberal use of SP with SVresection, irrespective of an open or laparoscopic approach.
QS34. PREOPERATIVE DIAGNOSIS OF TUMOR EXTENTOF BILE DUCT CANCER BY INTRADUCTAL ULTRA-SONOGRAPHY. Jun Ienaga, Yoshihiko Sadakari, ReikoTanabe, Norihiro Sato, Shunichi Takahata, Hiroki Toma,Toshinaga Nabae, Masafumi Nakamura, Koji Yamaguchi,Masao Tanaka; Graduate School of Medical Sciences, KyushuUniversity, Fukuoka, Japan
Backgrounds: For bile duct cancer, it is important to evaluate thevertical and horizontal extent correctly. Aim: To determine the useful-ness of intraductal ultrasonography (IDUS) for diagnosis of tumor ex-tent of bile duct cancer. Patients and Methods: Between July 2001and September 2007, 54 patients with bile duct cancer were studied byIDUS. Among them, 25 patients underwent surgical resection. IDUSfindings with respect to vertical invasion to the subserosal layer, pan-creatic parenchyma, right hepatic artery and portal vein, and horizon-tal spread along the bile duct wall were compared with pathologicalfindings in these 25 patients. All pathological descriptions were basedon the General Rules for Surgical and Pathological Studies on Cancer ofthe Biliary Tract (5th edition) published by the Japanese Society ofBiliary Surgery. Results: Subserosal invasion was correctly diagnosedby IDUS in 20 patients (80%). Pancreatic parenchymal invasion wasaccurately determined in 20 patients (80%). Although there were nopatients who had histological invasion to the right hepatic artery in thisstudy population, IDUS diagnosis was correlated well with surgicaldiagnosis in this regard (accuracy: 88%). One patient who had histolog-ical invasion to the portal vein could be diagnosed as having the inva-sion preoperatively by IDUS; all other patients without portal veininvasion were diagnosed correctly. Horizontal spread to the hepatic sidewas accurately determined in 22 patients (88%). Those who had biliarydrainage performed either by the percutaneous transhepatic method or
endoscopic retrograde method tended to show low accuracy comparedwith those who did not received biliary drainage (71% (5/7), 94% (17/18),respectively, p�0.11). The tumor of bile duct and the surroundingstructure could be visualized in detail by IDUS. IDUS could accuratelyevaluate the vertical invasion to the subserosal layer and other organs,and the horizontal extent of mural invasion to the hepatic side. How-ever, once biliary drainage had been introduced, the bile duct wallbecame thickened and this made it difficult to distinguish between thetumor extent and benign wall thickening in response to a biliary drain-age catheter. Therefore, it seemed to be better to perform IDUS beforebiliary drainage. Conclusions: IDUS is useful to precisely assess thevertical and horizontal tumor extent of bile duct cancer when performedbefore biliary drainage.
QS35. COLECTOMY FOR COLON CANCER IN PATIENTSWITH A PRIOR VENTRICULOPERITONEAL SHUNTTHE DEPARTMENT OF VETERANS AFFAIRS EXPE-RIENCE. Edel M. Doorley1, Andrew R. Barina2, Katherine S.Virgo2, Anil M. Bahadursingh2, Frank E. Johnson2; 1Univer-sity of Liverpool, Liverpool, United Kingdom; 2Saint LouisUniversity, St. Louis, MO
Objective: Many patients have VP shunts implanted for congenitalconditions. Subsequent abdominal operations in these patients arereportedly hazardous. We aimed to determine the clinical course ofadults with ventriculoperitoneal (VP) shunts for acquired conditionswho later required colectomy for colon cancer. Introduction: Ap-proximately 18,000 cerebrospinal fluid shunts, the majority of whichare VP, are implanted each year in the USA. These patients maysubsequently require colectomy for colon cancer. Whether the risk ofadverse events, particularly infection, is increased in such patients isnot known. Methods: A search of national Department of VeteransAffairs (DVA) databases was conducted to identify all veterans witha VP shunt from 1989-2003 who later underwent colectomy ascurative-intent treatment for colon cancer between 1994-2003. Allwere healthy upon entry into military service and required shuntsfor conditions acquired later. Patient medical records were analyzedto determine if the presence of a VP shunt affected the colectomyprocedure or the postoperative course. Results: There were 4,219unique inpatients and 795 unique outpatients with ICD-9 codes forVP shunt and 16,514 with codes for colectomy for colon cancer in theDVA system for the years specified. Fourteen had codes for bothcolectomy for colon cancer and pre-existing VP shunt. Four met ourinclusion criteria and had sufficient data for analysis; all had un-complicated postoperative courses with no instances of extensiveadhesions encountered during colectomy, postoperative infection, orpostoperative shunt malfunction. Discussion and Conclusions:This is the only English-language report on this topic, to our knowl-edge. Patients who receive VP shunts for acquired hydrocephalus asadults and later receive colectomy as curative treatment for coloncancer in the DVA system appear to experience a postoperativecourse similar to that of patients without VP shunts.
QS36. NITRIC OXIDE-MEDIATED RADIOSENSITIZATIONTO IONIZING RADIATION-INDUCED APOPTOSIS OFCOLON CANCER CELLS. Derrick Chen, Laura Ortega,David Chen, Edward H. Livingston, Sergio Huerta; Univer-sity of Texas Southwestern, Dallas, TX
Background: Metastatic colon cancer cells SW620 are resistant toionizing radiation (IR)-mediated apoptosis. DETA/NONOate (DETA)is an NO donor, which mimics NO sustained release for over 20hours. DETA causes mitochondrial permeability resulting in therelease of pro-apoptotic mediators, while inhibiting the NF�B anti-apoptotic pathway. Methods: SW620 pre-treated with DETA (1000�g X 24 h) and untreated cells were subjected to IR treatment at 0,1, 2, 3, and 5 Gy. Apoptosis was measured by flow cytometry
283ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
(TUNEL). SW620 cells untreated and pre-treated with DETA(1000�g X 24 h) were subjected to immunohistochemistry with an-tibodies specific for Smac/DIABLO and Apoptosis-inducing factor(AIF). Results: Pre-treatment of SW620 cells with DETA resulted ina 4.8-fold increase in apoptosis at 1 Gy (8.0�1.0 vs. 38.8� 0.2, p �0.001) and a 2.0-fold increase at 2 Gy (10.5�1.0 vs. 18.3�1.4, p �0.05; Figure 1). There was no significant differences at high doses ofIR (3 and 5 Gy). DETA showed no substantial increase in the cellspositive for Smac/DIABLO in cells treated with DETA. A substantialnumber of cells positive for AIF was observed in cells treated withDETA. Conclusions: DETA sensensitizes metastatic cancer cells toIR-induced apoptosis and may provide a therapeutic modality forpatients with rectal cancer who fail to respond to IR. The mechanismresulting in NO-radiosensitization may be mediated by AIF and/orSmac/DIABLO. The NK�B anti-apoptotic pathway following DETApre-treatment with be addressed in IR-induced apoptosis.
Supported by the VISN17 New Investigator Award and theHudson-Penn Surgery Fund.
QS37. DETA/NONOATE CHEMOSENSITIZATION IS MEDI-ATED BY INCREASED LEVELS OF POLY(ADP-RIBOSE) POLYMERASE-1 (PARP-1) LEADING TOAIF-INDUCED APOPTOSIS IN METASTATIC COLONCANCER CELLS. Xiaohuan Gao, Alejandro Millan-Vega,Derrick Chen, Edward H. Livingston, Sergio Huerta; Uni-versity of Texas Southwestern, Dallas, TX
The nitric oxide donor (DETA/NONOate) chemosensitizes metastaticSW620 colon cancer cells to cisplatin (CDDP)-induced apoptosis.SW620 cells have undergone apoptotic gene modifications in proteinproducts involved in the intrinsic pathway of apoptosis leading toapoptosome inactivation. We hypothesized that DETA/NONOatechemosensitization occurs via a caspase independent pathway. Wedemonstrated that AIF protein levels are increased with DETA/NONOate pre-treatment and this effect is attenuated by siRNAspecific for AIF. The mechanism leading to AIF mediated chemosen-sitization by cisplatin remains to be elucidated. PARP-1 activation isrequired for AIF translocation and AIF is a key downstream playerof PARP-1. We subjected SW620 cells to treatments with: CDDP [5mg/ml], DETA/NONOate [0.5 mM and 1.0 mM] and CDDP � DETA/NONOate. Apoptosis was measured by TUNEL as determined byflow cytometry. Total, cytoplasmic and nuclear protein extractsreceiving each treatment underwent Western blot analysis withantibodies specific for AIF and PARP-1. There was a dose dependentincrease of AIF protein band density with each given treatment
compared to control (medium). There is a similar increase in thelevel of protein in SW620 cytoplasmic and nuclear proteinextractswith anti-AIF antibodies. A dose-dependent increase in PARP-1 innuclear extracts of SW620 cells pre-treated with DETA [0.5 mMand 1.0 mM] followed by CDDP [5.0 �g/ml] was observed. Thepresent report demonstrated that the sustained and long actingrelease of nitric oxide chemosensitized metastatic colon cancercells to cisplatin-mediated apoptosis. The synergistic effects ofboth drugs on DNA damage and impaired DNA repair is complexand ill defined. In our system, the combination of pre-treatmentwith DETA/NONOate followed by CDDP showed an increase inAIF-mediated apoptosis. This response was also associated in anincrease in PARP-1 only in SW620 cells exposed to DETA/NONOate pre-treatment emphasizing the close interplay betweenAIF and PARP-1 in DNA repair and cell death. Long acting nitricoxide donors have a substantial potential for chemosensitizationof tumors resistant to conventional treatment modalities.
QS38. HOW SURGEON LOCATION AFFECTS SARCOMA PA-TIENT FOLLOW UP. Katherine S. Virgo1, S. Sarkar2, A. L.Beitler3, J. F. Gibbs3, Keita Sakata2, A. Goel1, M. E. Christy1,Riccardo A. Audisio4, W. G. Kraybill3, Frank E. Johnson1;1Saint Louis University, St. Louis, MO; 2St. Louis VeteransAffairs Medical Center, St. Louis, MO; 3Roswell Park CancerInstitute, Buffalo, NY; 4University of Liverpool, Liverpool,United Kingdom
Introduction: About 1% of all cancers are soft tissue sarcomas(STS); about 60% of these occur in the extremities. Most recurrences(80%) occur within 2 years after potentially curative treatment, butrecurrence at �5 years is not uncommon. Surveillance programs aredesigned to identify recurrence, new primary cancers, and complica-tions of therapy early enough to increase survival duration and
284 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
