Reza F. Saidi

Is There a Role for Palliative Gastrectomy in Patients with Stage IV Gastric Cancer

Patients with metastatic gastric cancer are currently not considered operative candidates and are most often offered systemic therapy. Palliative resection of the primary tumor has been considered irrelevant to the outcome and has been recommended only for palliation of symptoms. We have examined the role of palliative gastrectomy and its impact on survival in patients with stage IV gastric cancer at initial diagnosis between 1990 and 2000. A total of 105 patients with stage IV disease were identified during this period; 81 of them (77.1%) had no resection, and 24 (22.9%) underwent palliative gastric resection. Mean survival in those without resection who received chemotherapy (with or without radiation) treatment was 5.9 months (95% confidence interval 4.2–7.6). For those with resection and adjuvant therapy, mean survival time was 16.3 months (95% confidence interval 4.3–28.8 months). Kaplan-Meier survival analysis showed significantly better survival in those with resection and adjuvant therapy (log-rank test, P = 0.01). Mortality and morbidity rates associated with palliative resection were 8.7% and 33.3%, respectively, which did not differ statistically from the 3.7% and 25.3% in patients who underwent curative gastrectomy during same period of time. However, the length of hospitalization (22 versus 16 days) was significantly higher compared with those without stage IV disease. These data suggest that palliative resection combined with adjuvant therapy may improve survival in a selected group of patients with stage IV gastric cancer. Palliative gastrectomy plus systemic therapy should be compared with systemic therapy alone in a randomized trial.

Surgical resection for gastric cancer in elderly patients: Is there a difference in outcome?

BACKGROUNDnEarly and long-term outcome of gastrectomy for gastric cancer in elderly adults has been a subject of controversy and debate.nnnMATERIALS AND METHODSnClinical information was reviewed for patients undergoing gastrectomy for gastric cancer during an 11-year period (1990-2000) at the University of Tennessee Medical Center at Knoxville. Patient demographics, tumor characteristics, operative mortality and morbidity, survival, and length of hospitalization were reviewed.nnnRESULTSnOf 48 patients who underwent gastric resection for gastric adenocarcinoma, 24 were older than 70 and 24 younger than 70. There were no differences between the two groups regarding tumor characteristics, including location, tumor size, grade, gross pathology, lymph node involvement, lymphovascular invasion, and stage. In the elderly group, 75% underwent subtotal gastrectomy and 25% had total gastrectomy with or without resection of adjacent organs. In the younger patients, these numbers were 66.6% and 33.3%, respectively, which was statistically insignificant (P = 0.5). Five-year survival was 16.6% among elderly patients compared to 20.8% in the younger patients (P = 0.45). Half of the elderly patients and 39% of young patients had other comorbidities (P = 0.45). Postoperative mortality and morbidity was 8.33% and 33.3% in elderly patients, compared to 4.2% and 33.3%, respectively, in the younger group. These results were statistically insignificant (P = 0.4). The median postoperative length of stay was 15 days (95 percent confidence interval, 11-19 days) in younger patients compared to 18 days (95 percent confidence interval, 13-22 days) in the elderly group (P = 0.3).nnnCONCLUSIONnThis study suggests that gastrectomy can be carried out safely in elderly patients. The early and long-term outcomes in elderly patients (over age 70) are comparable to younger patients (under age 70). Age alone should not preclude gastric resection in elderly patients.

Interferon receptor alpha/beta is associated with improved survival after adjuvant therapy in resected pancreatic cancer

AIMnInterferons (IFNs) are known to have antiproliferative and immunoregulatory activities that are modulated through specific cell surface ligands, known as IFN-alpha, -beta, and -gamma receptors. The presence of these receptors and their impact on response to adjuvant therapy in patients with pancreatic cancer has not been determined.nnnPATIENTS AND METHODSnSlides were prepared from 46 patients with pancreatic adenocarcinoma. Immunohistochemistry (IHC) was subsequently used to determine the expression of IFN- alpha/beta receptor-chain 2 (IFN-alpha/betaR) and IFN-gamma receptor-chain 1 (IFN-gammaR). The correlation between IFN receptor expression, tumor characteristics, and the overall patient response to adjuvant therapy were determined analytically.nnnRESULTSnThe IHC performed for pancreatic adenocarcinoma demonstrated a high IFN-alpha/betaR expression in 4% (2/46) of patients, moderate expression in 20% (9/46) of patients, and faint or no expression in 76% (35/46) of patients. IHC confirmed a high expression of IFN-gammaR in 52% (24/46) of patients, moderate expression in 35% (16/46) of patients, and faint or no expression in the remaining 13% (6/46) of patients. Thirty-two (69.7%) patients received adjuvant therapy. Clinicopathological survey did not demonstrate any significant correlation between IFN-alpha/betaR and IFN-gammaR expression with regard to tumor size, vascular invasion, perineural invasion, lymph node metastases, or stage of disease. Use of adjuvant therapy was associated with increased survival in patients with IFN-alpha/betaR-positive tumors compared with patients with IFN-alpha/betaR-negative tumors (24 months versus 14.7 months in log rank test, p=0.012). The expression of IFN-gammaR, however, had no impact on patient survival (20 months vs 17 months; p=0.656, log rank test).nnnCONCLUSIONnIFN-alpha/betaR is associated with improved survival for patients with resectable pancreatic cancer who received adjuvant therapy.

Comparison between staple and vessel sealing device for parynchemal transection in laparoscopic liver surgery in a swine model

BACKGROUNDnAdvancements in technology have allowed laparoscopic surgery to expand into advanced procedures such as liver resection; however, the transection method is debatable. This study was designed to evaluate the feasibility and outcome of laparoscopic liver resection comparing the vessel sealing device (VSD) versus endomechanical stapling devices for parenchymal transection in a swine model.nnnMATERIALS AND METHODSnLaparoscopic left hepatectomy was performed in two groups (n=7 in each group) comparing the stapler device with the VSD. The cut surfaces of the liver were evaluated for bleeding and biliary leakage at the time of the operation and 1 week later. The animals were sacrificed 1 week after the operation to determine hemorrhage and bile leakage, and to allow histological evaluation of the liver. Serum liver enzymes were checked before, after, and 1 week postoperatively.nnnRESULTSnNo evidence of biliary leakage or hemorrhage was noted at the time of the operation and 1 week later for both groups. There was a trend toward an increase in blood loss in the stapled group compared with LigaSure (40+/-16.4 cc vs 17+/-3.7 cc, p>0.05). There was also a trend toward shorter transection time in the stapled group compared with the LigaSure group (15+/-4.1 min vs 21.8+/-5.3, p>0.05). The instrument cost was significantly higher in the stapled group (720+/-110 vs 400+/-50; p<0.05). There was no difference in serial liver enzymes and liver histopathology in the two groups.nnnCONCLUSIONSnThe VSD and endomechanical stapler can be safely and effectively used for parenchymal transection during laparoscopic liver resection. However, using endomechanical staplers is associated with an increase in cost.

Intrahepatic cholangiocarcinoma masked as fever of unknown origin

Intrahepatic cholangiocarcinoma is a rare malignancy that often presents in an advanced stage. For many patients, early diagnosis is often delayed, secondary to vague symptoms and a lack of physical findings. Herein, we report an unusual case of fever of unknown origin secondary to intrahepatic cholangiocarcinoma.

Palliative Gastrectomy improves survival in metastatic gastric cancer

S: PLENARY and PARALLEL SESSIONS 20 In Vivo Expression of an Adenoviral Vector Encoding Soluble Tie2 Inhibits Metastatic Hepatic Tumor Growth S. Sarraf-Yazdi,* J. Mi, C. Kontos, M. Dewhirst, B. Clary. Surgery, Duke University Medical Cente~ Durham, NC. Introduction: Cumulative evidence has highlighted the importance of the endothelium-specific tyrosine kinase receptor Tie2 (TEK) and its ligands, the angmpoletlns, m normal and pathologic angiogenesis. Preclinical studies targeting Tie2, however, are limited. We examined the effect of AdExTek, an adenoviral vector encoding soluble Tie2 extracellular domain, on growth of hepatic metastases in the mouse. Methods: Murine colon carcinoma cells (CT26) were genetically modified ex vivo to stably express firefly luciferase as a reporter for in vivo bioluminescence detection. These cells were delivered into Balb/C mice via intrasplenic injection. Mice then randomly received 1 x l 0 l l adenoviral particles expressing either lacZ (n = 10), as negative control, or ExTek (n = 10) via tail vein. Tumor burden was detected by in vivo bioluminescence imaging on days 6, 13, and 20 following tumor cell inoculation. Animals were sacrificed twenty days after inoculation. Results: Tumor burden was significantly decreased in mice treated with AdExTek when compared to those treated with the control lacZexpressing adenoviral vector, as determined by bioluminescence imaging on post-inoculation days 13 (p = 0.019, Wilcoxon/Kruskal-Wallis test) and 20 (p = 0.01). All mice eventually developed liver tumors in this single injection approach. Conclusions: Systemic adenoviral delivery of the soluble extracellular domain of the Tie2 receptor reduced liver metastatic burden in this virulent murine model o f metastatic colorectal cancer. These findings suggest that inhibiting either Tie2/Angiopoietin interactions or angiopoietins directly may be a relevant anticancer strategy within the hepatic environment. 21 Efficacy of Isolated Hepatic Perfusion 0HP) in Patients with Progressive Unresectable Colorectal Cancer (CRC) Liver Metastases (LM) after lrinotecan (CPT-11) R. Alexander, 1. S. Libutti, l J. Pingpank, 1 D. Bartlett,: C. Helsabeck, l T. Beresneva. 1 1. Surgery Branch/National Cancer Institute, Bethesda, MD; 2. Division of Surgical Oncology/UPMC, Pittsburgh, PA. Introduction: CPT-11 with 5-FU and leucovorin (LV) is generally considered first line therapy for patients with metastatic CRC. However response duration is less than 1 year and second line systemic chemotherapy has limited efficacy. We analyzed efficacy of IHP for patients with progressive CRC LM after CPT-11. Methods: Between 3/1993 and 2/2003, 118 patients with CRC LM underwent IHP on IRB approved protocols. Overall treatment mortality was 1.7% (2 of 118). Twenty-five patients (F: 10, M: 15; mean age: 53 y) were identified who had progressive LM by CEA and/or CT scan after CPT-11. A 1 h hyperthermic IHP (mean hepatic T: 40.0 ~ C) using 1.5 mg/kg melphalan (mean total dose: 100 mg) was administered via laparotomy. Perfusion, using an oxygenated extraeorporeal circuit, was established with inflow via a cammla in the gastroduodenal artery and common hepatic artery inflow occlusion and outflow was via a cannula in an isolated segment of inferior vena cava (IVC). During IHP, portal and IVC flow were shunted to the axillary vein. Patients were assessed for radiographic response, recurrence pattern, and survival. Results: Mean number of previous CPT11 cycles in 25 patients were 6 (range: 2-14) given alone (n=21) or with 5FU/LV (n=4) as first (n= 6) or second line (n = 19) therapy. Median number of LM prior to IHP was 10 (range: t-50) and median percent hepatic replacement by tumor was 25. Mean operative time was 9 h (range: 6-12) and median hospital stay was 11 d (range: 8-76). There were 1 complete and 15 partial responses in 25 patients (64%) with a median duration of 11 mos (range: 323). Thirteen of 25 patients progressed systemically at a median of 5 mos (range: 3-16). Median overall survival is 11 mos (range: 1-27) and 2-yr survival was 28%. Conclusions: For patients with progressive CRC LM after CPT-I 1, IHP has good efficacy in terms of response rate and duration. Continued evaluation of IHP with melphalan as second line therapy in this clinical setting is justified. 22 Palliative Gastrectomy Improves Survival in Metastatic Gastric Cancer R.E Saidi, ~* N.N. Hanna, 2 P.S. Dudrick. 3 1. Providence Hospital and Medical Centers, Southfield, ML 2. University of Kentucky, Lexington, KY; 3. University of Tennessee, Knoxville, TN. Background. Patients with metastatic gastric cancer are currently considered inoperable and treated with systemic therapy. Palliative resection of the primary tumor is considered irrelevant to the outcome, and is recommended only for palliation of symptoms. Methods. We have examined the use of aggressive Iocat resection, and its impact on survival in patients presenting with stage IV gastric cancer at initial diagnosis, between 1990 and 2000. Results. A total of 110 patients with stage IV disease were identified during this period, of whom 89 (80,9%) received either no operation or bypass procedures, and 21 (19.1%) underwent gastric resection. Patients survival based on type of treatment is shown in Table 1. Mean survival in those without resection who had adjuvant treatment was 5.4 months (95% confidence interval 1.7-9.1) and for those with resection and adjuvant therapy was 23.5 months (95% confidence interval 9.8-37.3 months). Kaplan Mieir survival analysis showed significant better survival in those with resection and adjuvant therapy. Mortality and morbidity of gastric resection were 8.7% and 33.3% respectively, which was not statistically different compared to 3.7% and 25.3% in patients without stage IV disease who underwent gastrectomy. However, the length of hospitalization (22 vs. 16 days) and readmissions for surgery-related problems (45% vs. 27.7%) was significantly higher compared with those without stage IV disease. Conclusions. These data suggest that the palliative resection in patients with stage IV gastric cancer needs to be re-evaluated, and local therapy plus systemic therapy should be compared with systemic therapy alone in a ran-