A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas

We hypothesized that delivering adjuvant radiotherapy (RT) preoperatively with chemotherapy might enhance local control of the cancer and patient tolerance for the intervention. Thirty-four patients with localized pancreatic cancer (24 head, 8 head
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  A Pilot Study of Preoperative Chemoradiation for Patients With Localized Adenocarcinoma of the Pancreas John P. Hoffman, MD, James L. Weese, MD, Lawrence J. Solin, MD, Paul Engstrom, MD, Pasha Agarwal, MD, Locke W. Barber, DO, Marlane C. Guttmann, MD, Samuel Litwin, PhD, Hernando Salazar, MD, Burton L. Eisenberg, MD, Philadelphia, Pennsylvania BACKGROUND: We hypothesized that delivering adjuvaut radiotherapy (RT) preoperatively with chemotherapy might enhance local control of the cancer and patient tolerance for the intervention. METHODS: Thirty-four patients with localized pancreatic cancer (24 head, 8 head and body, 2 body and tail) were treated during the past 6 years with an intramural protocol consisting of Sfluorouracil (1,000 mg/m’ on days 2 to 5 and 29 to 32) and mitomycin-C (10 mg/m” on day 2) given with preoperative external beam RT (median 5,040 cGy). Nine patients did not have surgery: 1 refused, 1 died of cholangitis, and 7 were noted to have distant (5) or unresectable local cancer (2) after RT. Of the 25 patients who underwent celiotomy, 11 had liver (8) or peritoneal (3) metastases and 3 had palliative pancreatectomies (2 with liver metastasectomy and 1 with hepatic artery and portal vein re- placement). The remaining 11 patients (44 of the cohort with surgery, 32 of all patients) had potentially curative (PC) resections (5 total panereatectomy, 5 Whipple, 1 distal pancreatec- tomy). Median tumor diameter by computed to- mographic scan was 3.75 cm (range 3 to S) for the 11 patients who received PC resections aud 4.5 cm (range 3 to 7.5) for all patients. Of the 11 patients with PC resections, 8 had evidence of superior mesenteric, portal or splenic venous involvement and 4 had been deemed unre- sectable at previous celiotomies. RESI.LTS: One patient developed respiratory fail- ure and one died postoperatively, yielding a 9 rate of major morbidity and mortality. Median follow-up of the surviving patients with curative resection is 33 months (range 14 to 70). Their median survival from the time of tissue diagnosis is 45 months with a median disease-free survival of 27 months. The product limit estimate of S- year survival is 40 (95 confidence bounds +29 , -30 ). One patient had a microseopi- tally positive resection margin, which was a From the Departments of Surgical Oncology, Radiation Oncology. Medical Oncology. Diagnostic Radiology, Pathology and Biostatistics, Fox Chase Cancer Center and Temple University School of Medicine, Philadelphia, Pennsylvania. Requests for reprints should be addressed to John P. Hoffman. MD, Fox Chase Cancer Center, 7701 Burhohne Avenue. Philadelphia, Pennsylvania 19111. Presented at the 35th Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans. Louisiana. May 16-1X. 1994. falsely negative frozen section margin at the pancreatic neck. Two patients had positive re- gional lymph nodes. Five patients have been di- agnosed with recurrent cancer. Only 1 has had a local/regional component to the recurrence. CONCLUSIONS: Preoperative RT and chemother- apy followed by resection is well tolerated and safe for patients with locally advanced pancreatic cancer. This approach provides tumor free re- section margins and offers prolonged survival to patients with truly localized pancreatic cancer. T he concept of preoperative radiation therapy (RT) for patients with localized pancreas adenocarcinoma was developed 2 decades ago. -3 n the first clinical trials, when experience was still very limited, 2 of 6 patients with pan- creatic resection survived longer than 5 years after surgery and several responded with decreases in tumor size and cellularity.‘~” The theoretical advantages of the new tech- nique included a reduction in the number of viable cells being shed into the circulation at the time of surgery and a possible increase in resectability.? Subsequent authors felt that presurgical irradiation de- creased the ability of tumor cells to implant upon the sur- gical incisions at the time of operation and reduced the in- cidence of positive margins and pancreaticojejunostomy leaks. Administration of RT at a time when there is no re- cent operation from which to recover and no tixed small bowel in the RT portal should improve tolerance of RT and the ability to deliver the planned RT dose as well as rates of late complications. In addition, preoperative RT guarantees that patients who develop prolonged operative complications that necessitate delay or abandonment of postoperative RT will not miss out altogether on this ther- apeutic modality. Preoperative RT should also be more ef- fective than postoperative RT because the cancer cells in the target area presumably will have better vascularity and be relatively less hypoxic than after pancreaticoduo- denectomy. Finally, preoperative RT entails a 113 to 12- week observation period before pancreatectomy. This de- lay should improve patient selection for attempts at curative resection by allowing detection of clinically ob- vious distant metastases hat develop in the intervaL3-” Because work in the past decade demonstrated the supe- riority of chemotherapy and RT (CTRT) over RT alone for patients having unresectable pancreas cancers, it has been hypothesized that such combination therapy might also im- prove the adjuvant treatment of localized pancreas can- cer.“‘.” Accordingly, in late 1986. we began a trial at the Fox Chase Cancer Center (FCCC) using a chemoradiation program that had been tested extensively in esophageal can- THE AMERICAN JOIJRNAL OF SURGERY” VOLUME 169 JANUARY 1995 71  cer at our institution and in patients with unresectable pan- creas cancer at Thomas Jefferson University Medical Center (Philadelphia, Pennsylva&a).L”~‘s Our goals were to examine the resectability, local control, and survival of pa- tients with advanced but localized periampullary cancer who were treated with this regimen followed by extirpa- tion of the cancerous lesion if it was still localized and re- sectable after completion of the treatment. PATIENTS AND METHODS At the start of the study, patients were declared eligible if their tumors were biopsy-proven adenocarcinoma or adenosquamous carcinoma with no distant metastases. Patients with islet-cell tumors and cystadenocarcinomas were excluded. While the study included patients with all periampullary cancers, only those with pancreatic carci- nomas are described here. Eligibility was amended in 1988 to allow only patients considered by the surgeons to have potentially resectable lesions. Patients were entered into the trial from November 1986 to August 1993. After November 1990, patients were preferentially entered into the Eastern Cooperative Oncology Group (ECOG) trial EST PD-289, which tested the same treatment regimen as this pilot trial. Subsequently, the only patients entered into the present trial had cancers other than adenocarcinoma (2 adenosquamous), cancers greater than 5 cm in diameter (n = 3), cancers not proven preoperatively to arise from the pancreas (2 thought possibly to be duodenal, 2 possibly bile duct), and cancers treated with CTRT in institutions outside FCCC or its network hospitals (n = 3). The patients were 21 females and I3 males aged 4 I to 79 years (median 63). Their cancers were 22 adenocarci- nomas and 2 adenosquamous carcinomas of the head of the pancreas, 8 adenocarcinomas involving both the head and body of the pancreas, and 2 adenocarcinomas arising from the pancreatic body and tail. Thirteen patients (38 ) had previous celiotomies, at which time their tumors were felt to be unresectable. Of the 13, 2 had transduodenal core needle biopsies that confimled the presence of an adenocarcinomd of the pancreas, 6 had inci- sional biopsies of the tumor, and 3 had biopsies of positive regional lymph nodes. One patient had positive biopsies of the primary tumor, a regional node, and an omental nodule. Another had no biopsies taken at surgery because positive computed tomography (CT)-directed fine needle aspiration (FNA) biopsies had been obtained preoperatively. The op- erating surgeons had judged the cancers unresectable either because of nodal involvement (n = 3). central vascular in- volvement (n = 9). or omental metastasis (n = I ). The remaining 21 patients had positive biopsies obtained by CT directed FNA (n = 13) ultrasound guided FNA (n = 2), fluoroscopically directed FNA (n = 2), endoscopic biopsy (n = 2), or bile duct brushings from transhepatic stent tracts (n = 2). Eight of 19 patients with at least one FNA required a second biopsy-3 a second FNA, 3 a third FNA, 1 a duo- denal biopsy, and 1 a bile brushing-to confvm the diag- nosis. Patients with obstructive jaundice routinely were treated with transhepatic or endoscopically placed stems. Tumor sizes were estimated from CT scan images, The tumor size estimates represented the largest tumor diame- ters, and were the average of the readings of two radiolo- gists who were unaware of each others’ interpretations. The estimates ranged from 3 to 7.5 cm (median 4.5). Thirty patients had splanchnic arteriography, of whom only 4 ( 13 ) had entirely normal superior mesenteric veins (SMV). Eight (27 ) had mild unilateral medial (leftward) SMV compression, 6 (20 ) had portal or superior mesen- teric venous occlusion, 5 (17 ) had bilateral SMV im- pingement, and 4 (13 ) had severe medial SMV com- pression.16 Three others had splenic vein occlusion, 2 with splenic arterial occlusion and 1 with splenic arterial en- casement. Four patients had no arteriogram. CT scans of 29 patients were interpretable for the rela- tionship of the tumor to the superior mesenteric artery (SMA). Eight (28 ) had no abnormal approximation of the tumor to the SMA, while 7 had abnormally dense fat surrounding the SMA, and 11 showed the tumor mass ad- jacent to the SMA without intervening fat. The mass sur- rounded the SM.4 in 3 patients. Radiation treatments delivered at least 6 megavolt (MV) photons, and most commonly 10 MV photons. The pre- scribed total dose was 5,040 cGy in 28 fractions, 180 cGy/fraction, 5 fractions per week. All patients except 3 received a total dose of 5,040 cGy. In general, 3,960 cGy of radiation was delivered to a field encompassing the gross tumor as delineated by CT scanning with a 2- to 3- cm margin, after which an additional 1,080 cGy was ad- ministered to a conedown field including gross tumor with a I- to 2-cm margin. The conedown field sizes were gen- erally no greater than 10 X IO cm. Treatments were indi- vidualized based on the volume and location of disease. Field arrangements were generally delivered using a 3- field or 4-field plan. Careful attention was paid to the dose delivered to the kidneys and spinal cord so that normal tis- sue tolerance was not exceeded. Customized cerrobend blocks and customized wedges were used as indicated. Three patients received either less or more RT than that specified by the protocol. One died of biliary sepsis after the first week of chemotherapy and RT, having received 1 O80 cGy. One received 4,500 cGy over 34 days and then developed nausea and fatigue to the point of refusing fur- ther treatment. A third patient received 6,300 cGy because the referring surgeon and radiotherapist had considered her tumor unresectable by virtue of putative hepatic artery in- volvement. When consultation was obtained with the au- thor after RT was completed and arteriography displayed no major vessel involvement, the patient was accepted for surgery and underwent pancreaticoduodenectomy. Mitomycin, 10 mg/m2 in an intravenous bolus, was given on day 2. On hospital days 2 through 5 and 29 through 32, 5fluorouraci1, 1000 mg/m2/day, was administered as a 96- hour continuous infusion.5 i,n Three to 4 weeks after the completion of RT, patients were again screened with CT scans of the chest, abdomen, and pelvis. If no metastases were noted, they were scheduled for pancreatic resection within 6 weeks of the completion of RT. Seven patients received their chemoradiotherapy (CTRT) according to the same protocol at other institutions, All surgery was performed at FCCC. Standard total, dis- tal, and proximal (Whipple) pancreatectomies were per- formed, with antrectomy for all total and Whipple proce- dures. All but 1 of the patients receiving total pancreatec- CHEMORADIATION IN PANCREATIC CANCER/HOFFMAN ET AL 72 THE AMERICAN JOURNAL OF SURGERY’, VOLUME I 69 JANIJARY ]gy=j  tomies and none undergoing Whipple procedures received total vagotomy. Lymphadenectomy included all tissue to the right side of the SMA and extending just above the superior aspect of the left renal vein. Aortocaval nodes and tissue extending from the right ureter to the left side of the aorta and down to the origin of the inferior mesen- teric artery were removed along with the specimen. One pancreatojejunostomy was intussuscepting while the other 4 were duct-mucosa anastomoses. Transhepatic stents were placed in 8 of the 10 patients with choledochoje- junostomies. Two were removed within 1 week of surgery, the rest 3 to 5 weeks after resection. The pathologists inked all pancreatic, bile duct, retroperi- toneal, and SMV margins in preparation of the resected tissue. Measurements of histologic responses were made independently by two pathologists who examined at least five slides of tissue cut perpendicular to the long axis of what grossly appeared to be the primary tumor. They es- timated the percentage area on each slide composed of tu- mor cells and averaged the percentage involvement among all slides examined. RESULTS Thirteen of 33 patients (39 ) required treatment breaks from 1 to 14 days (median 7). The patient who died of sepsis in the second week of treatment is excluded from this analysis of CTRT toxicity, as her mortality was re- lated to ineffective biliary decompression and subsequent sepsis and multisystem organ failure. Seven treatment breaks were for nausea, vomiting or diarrhea, 5 for throm- bocytopenia and neutropenia, and 1 because the patient misunderstood the treatment schedule. One patient had both low blood counts and gastrointestinal distress. Nine patients had complications-7 gastrointestinal, 2 low platelet and white blood cell counts-but required no treat- ment breaks. Six patients, including 2 who required treatment pauses, required total parenteral nutrition (TPN). Two patients, neither of whom interrupted treatment, were hospitalized for rehydration. Five patients developed thrombocytope- nia and granulocytopenia, 1 thrombocytopenia alone, and 1 granulocytopenia alone, for a total of 7 patients with 6 occurrences of low platelet and white cell counts. Platelet counts among the 6 with thrombocytopenia ranged from 13.000 to 88,000 cells/mm3 (median 27,000). White cell counts among the 6 with granulocytopenia ranged from 800 to 2,300 cells/mm3 (median 1,500). The second course dosage of 5fluorouracil was reduced by half in 3 patients with dyscrasias and omitted in another. There were no treatment-related episodes of sepsis or mortality. In sum, 67 of patients experienced nonlethal complications from this therapy. The majority were nausea and diarrhea. Responses to CTRT were gradable in 31 patients, ex- cluding 1 who died early in treatment and 2 who had no posttreatment imaging studies. Two patients (6 ) demon- strated clear progression in tumor size, 19 (61 ) no change in tumor size, 8 (26 ) decreases of less than 50 in the product of the largest diameter and its perpendicular, and 2 (6 ) decreases of greater than 50 in this product. Thirteen patients, 11 of whom underwent potentially CU- rative and 2 palliative resections, had tissue available for CHEMORADIATION IN PANCREATIC CANCER/HOFFMAN ET AL grading of a histologic response to CTRT. CT measure- ment documented a partial response in 1 and minor re- sponses n 3. Only 2 of these 4 obtained marked histologic responses. Fibrosis and necrosis replaced at least 75 of the tumor area in 6, 60 to 70 in 4, and less than 40 to 50 in 3 (2 of those with radiologic responses were in this last group). No patient had a complete pathologic re- sponse. There were too few patients to correlate radiologic or histologic responses with clinical outcome. However, 3 of the 5 who survived longer than 3 years had a minor or partial radiologic response, and 3 of the 4 patients who survived this long and had tissue available for grading had at least 75 tumor replacement. Nine of 34 patients (26 ) did not go to surgery after CTRT. One died during CTRT and 1 refused an attempt at resection. CT scan restaging after CTRT revealed new liver metastases n 4 patients. One patient with SMV oc- clusion developed ascites and inanition, although para- centesis and peritoneal cytology were not performed. Two patients were noted to have portal or SMV occlusions at post-CTRT studies (one magnetic resonance imaging test, one SMA arteriogram). Neither patient was studied for these abnormalities preoperatively. so it is possible that they developed during the CTRT. Twenty-five patients underwent exploratory celiotomy. Eleven were eliminated as candidates for pancreatectomy, 7 because of liver metastases, 3 because of peritoneal metastases, and 1 because of a liver lesion that was felt to be a possible metastasis by the pathologist but was prob- ably benign. This last patient did not develop further liver metastasis in his remaining 3 years of life. Eleven patients received PC pancreatectomy. Five of them underwent total pancreatectomies, 5 Whipple proce- dures, and 1 a distal pancreatectomy (tail, body, and neck) with resection of the left lateral portion of the SMV. One patient having a Whipple procedure also underwent right lateral SMV resection with lateral venorrhaphy and right colectomy. These patients’ tumor diameters ranged from 3 to 5 cm (median 3.75). Three patients who had pancreatectomies that were not considered PC were included in this analysis. Two of them had total pancreatectomy and wedge resection of a single liver metastasis that was suspected of being an implant from a previous percutaneous biopsy or biliary stent placement. They were noted to have liver metastases 3 and 5 months after their pancreatectornies. A third patient with demonstrated SMV occlusion had total pancreatectomy in conjunction with resection and replacement of SMV and hepatic artery segments. He died 3 days postoperatively of sepsis and multisystem organ failure. At postmortem ex- amination, persistent cancer was found at the hepatic artery and SMV margins. Only 4 of the I I patients who were resected had tumors greater than 4 cm in the widest dimension, while 25 of the 34 patients accrued had tumors that large. Three of the 11 patients whose resections were considered PC had no gross tumor noted in the pathology lab, while tumors in the other 8 ranged from 1 to 4.4 cm (median 3.65). Eight resected patients’ cancers had invaded surrounding structures (duo- denum 6, bile duct 1, stomach I). Two patients had posi- tive nodes. Only 1 had a positive margin, which was at the THE AMERKAN JOURNAL OF SURGERY” VOLUME 169 JANUARY 1995 73  CHEMORADIATION IN PA4NCREATIC CANCERlHOFFBkkN ET Al. divided neck of the pancreas. The frozen section was read as negative, but the permanent sections revealed tumor cells at the margin. This patient with an adenosquamous cancer also had positive peritoneal washings. He died, with liver metastases he only site of recurrence, 20 months af- ter diagnosis and 14 months after Whipple resection. Of the 13 patients with previous celiotomies, 4-all judged unresectable because of central vascular encroachment- had PC resections. One patient died 37 days after PC total pancreatectomy. The cause of death was acquired bacteremia with subse- quent multisystem organ failure. Another patient with to- tal pancreatectomy was hospitalized 144 days after surgery for multiple problems including ascites, hemorrhage from the gastric remnant, sepsis. and adult respiratory distress syndrome. Estimated blood loss for the 11 PC resections ranged from 1.50 o 5,500 mL (median 1,600). Operations took from 6 to 10.4 hours (median 7.4). Hospitalization lasted from 9 to 144 days (median 20). Three other patients with PC resections experienced com- plications. Two developed postoperative ascites that even- tually resolved and 1 postoperative paranoid psychosis for several days. Since the 2 patients who died with multiple complications also had ascites, 4 of the 1 with PC resec- tions, including 3 with total pancreatectomies and 1 with a Whipple procedure, experienced this complication. Two of the 3 with palliative total pancreatectomy also had se- vere ascites. The problem eventually resolved in all with- out the use of peritoneovenous shunting. One of the S pa- tients with a pancreaticojejunostomy experienced a transient postoperative increase in amylase in her drain fluid, but she also had a splenic artery ligation through the superior aspect of the pancreatic tail for a splenic artery aneurysm at the time of pancreaticoduodenectomy. Late complications probably not related to cancer have occurred in 6 patients. Three (1 with PC resection, 1 with Figure 1. KaplanMeier overall survival curve (solid line) and disease-free sur- vival curve (dashed line) for 11 patients with potentially curative resections. Dotted lines represent 95 confidence bounds. Tick marks represent patients still alive. palliative resection, 1 without resection with a transcuta- neous stent) developed cholangitis and liver abscesses hat were eventually fatal. One patient who was not operated on died of an upper gastrointestinal hemorrhage 3 months after CTRT completion. Two long-term survivors have de- veloped myelodysplastic syndromes. One, currently alive without recurrence 69 months after her diagnosis and 67 months after her total pancreatectomy, requires frequent blood transfusions for anemia related to decreased ery- throid precursors in the marrow. The other, also alive with- out recurrence 43 months after her diagnosis and 39 months after a Whipple procedure, has platelet counts of 100,000 cells/mm3 and white blood counts around 3,000 cells/mm”. We have not seen this phenomenon in any of the many patients with esophageal cancer who have been treated with the same regimen. Kaplan-Meier survival and disease-free survival curves for patients with PC resection are shown in Figure 1, and survival curves for those without resection or with pallia- tive resections are shown in Figure 2. Median survival with PC resection is 45 months. Median disease-free sur- vival is 27 months. The product limit estimate of 5year survival is 40 , with 95 confidence bounds of 10 to 79 based on an exponential fit to the survival distribu- tion. The curves for resected patients have large 9.5 con- fidence bounds because of the small number of patients contributing to them. Five patients have been diagnosed with recurrent cancer after PC resection. The new tumors have appeared in the liver in 2 and lung in I. The patient with lung recurrence developed subsequent liver and cutaneous metastases. One of those with liver secondaries died and the other remains alive with liver metastases only. Postmortem examinations were performed on 2 other patients who succumbed with- out known metastases o a liver abscess and a myocardial infarction, respectively. One had liver metastases only and the other had tumors in the pancreatic bed, liver, and lung. 74 THE AMERICAN JOURNAL OF SURGERY” VOLUME 169 JANUARY 1995  CHEMORADIATION IN PANCREATIC CANCER/HOFFMAN ET AL ___ .~_ -~~~~ ~~~~ -... COMMENTS There are now a number of publications containing end results from various types of preoperative RT with or with- out chemotherapy for patients with adenocarcinoma of the pancreas limited to local and regional sites.2-41’7-‘9 his pi- lot series has the longest follow-up of patients, with a min- imum interval from the time of tissue diagnosis of 14 months and a median of 33 months for patients with pan- creatic resection. However, the small number of patients prohibits any major conclusions regarding the efficacy of the therapy. Other reported studies are also inconclusive because of small numbers of patients treated or short fol- low-up. Reported experience with the treatment program described here will be amplified and more easily judged when the data from the recently closed ECOG trial using the same regimen have matured. Uncertainty clouds the issue of adjuvant radiation therapy and chemotherapy for resectable pancreas cancer. While some data demonstrate that postoperative RT combined with 5’-fluorouracil given both with the RT and for up to 2 years is superior to surgery alone, the sole prospective, ran- domized trial contained only 22 patients in the control group.‘O n this trial, reported by the Gastrointestinal Tumor Study Group (GITSG), the CTRT was the most likely rea- son for the increased survival in the treatment group, but curiously, local recurrence was no greater in the control than in the treatment groups. *’ A relatively low dose of RT was given with a designed treatment break of 2 weeks, all of which may have led to the poor local control. Most subsequent phase II clinical trials have examined higher doses of RT combined with either higher or more prolonged doses of 5fluorouraci1, sometimes combined with mitomycin-C or cisplatin.5.‘7-‘y Similar programs have been used in the post-resectional setting.22 None has demon- strated median survival rates significantly better than the 2 1 months achieved in the treatment arm of the GITSG trial. While our median survival of 4.5 months appears to be Figure 2. Kaplanhrleier survival curves for patients without surgical exploration after radiochemotherapy (dotted linas), patients with surgical exploration but without resection (solid line), and pa tients with palliative resections (dashed lines). Tick marks represents patients still alive. longer, the results will need to be confirmed by much larger numbers of patients, all followed for a minimum of 2 years. Comparisons of end results in the treatment of adeno- carcinoma of the pancreas are particularly difficult because clinical staging is inaccurate and criteria for resectability vary widely. Initial postsurgical pathologic staging is not available for patients treated with preoperative CTRT. Furthermore, it appears that patients with positive lymph nodes may be downstaged by preoperative CTRT.‘,17 It is hoped that the newer imaging modalities will enhance our ability to compare tumors treated with preoperative CTRT, and that surgeons and pathologists will report significant prognostic variables along with end results. In this way, we may be able to better define optimal treatment strate- gies for this malignancy. However, it is doubtful that we will be able to determine the relative value of preopera- tive versus postoperative sequencing without a prospec- tive, randomized trial of the two methods. This pilot trial demonstrates that the CTRT regimen un- der investigation does not cure or even render resectable most tumors that are more than 4 cm in diameter, obstruct the portal vein or SMV, or encase the SMA. Seven of 9 patients with tumors <4 cm in diameter had resections, 4 of 19 with tumors between 4 and 5 cm, and none of 6 with tumors >5 cm (P = 0.01 for 7/9 versus 4/19, P = 0.002 for 719 versus 4125 [Fisher’s exact test, one-sided]). Two of 5 patients with bilateral SMV impingement had resec- tions, but none of 6 with SMV occlusion. Only 2 of the 6 patients with SMV occlusion made it to surgery, while the others all developed ascites and inanition during and after CTRT. One patient underwent a resection requiring both SMV and hepatic artery resection and replacement, yet cancer was present at both remaining vessel margins at postmortem exam. Five of 8 patients with a normal fat plane surrounding the SMA were resected, compared to none of 3 with SMA encasement. Two of 11 with tumor touching SMA had resections. THE AMERICAN JOURNAL OF SURGERP VOLUME 169 JANUARY 1995 75
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