Pancreaticoduodenectomy for nonperiampullary primary tumors

Pancreaticoduodenectomy for NonperiampuUary Primary Tumors Lawrence E. Harrison, MD, Nipun Merchant, MD, Alfred M. Cohen, MD, Murray F. Brennan, MD, New York, New York

INTRODUCTION: This review was performed to evaluate the outcome of patients undergoing pancreaticoduodenectomy (PD) for isolated metastatic or locally advanced nonperiampullary tumors at a single institution over a 13-year period. METHODS: Between 1983 and 1996, patients undergoing PD for metastatic or locally advanced nonperiampullary malignancies were identified. Medical records were reviewed and outcome factorE and survival data analyzed. RESULTS: Eighteen patients were identified. The primary tumor histopathology included colon (n = 7), gastric (n = 4), renal cell (n = 3), lung (n = 2), bladder (n = 1), and melanoma (n = 1). The median length of hospital stay was 15 days (6 to 48) with one perioperative death (5.5%). The median tumor size was 5.5 cm (0.8 to 11.5), and 7 patients had positive peripancreatic lymph nodes. The median survival was 40 months, with a 5-year survival of 35%. CONCLUSIONS: Pancreaticoduodenectomy for nonperiampullary malignancy is infrequently indicated. However, in the absence of widely metastatic disease, PD should be considered for Iocally advanced tumors or isolated metastatic malignancy. Am J Surg. 1997;174:393-395. © 1997 by Excerpta Medica, Inc. he role for surgical resection for periampullary malignancy is well established, with pancreaticoduodenectomy (PD) being the standard of care for localized distal common bile duct, ampullary, duodenal, and head of the pancreas tumors. This role is based on a wellestablished survival benefit for patients able to undergo pancreatic resection compared with patients undergoing bypass only or no operation. I Contributing to this survival advantage after PD is the improved safety of pancreatic resection. Compared with operative mortalities of 25% in the 1960s and 1970s, current series report postoperative fatalities ranging from 1% to 5% in those centers performing a significant number of resections annually. 2'3 Involvement of the pancreas or duodenum by nonperiampullary tumors is rare, and in most cases, is associated with

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From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. Requests for reprints should be addressedto Murray F. Brennan, MD, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. Manuscript submitted December 3, 1996 and accepted in revised form March 28, 1997.

© 1997 by ExcerptaMedica, Inc. All rights reserved.

widely metastatic disease. In these instances, symptomatic patients can be palliated ,~ith endoscopic stenting, operative biliary, and/or gastric bypass. Infrequently, patients may present with isolated metastatic or locally advanced nonperiampullary tumors requiring PD for tumor clearance. While the efficacy of hepatic or pulmonary resection for isolated metastatic tumors or locally advanced malignancy is well established, 4-7 the role of PD for nonperiampullary malignancy is unknown. This review was performed to evaluate the outcome of patients undergoing PD for isolated metastatic or locally advanced nonperiampuUary tumors at a single institution over a 13-year period. METHODS Between 1983 and 1996, patients undergoing PD for metastatic or locally advanced nonperiampullary malignancies were identified by review of the Memorial Sloan-Kettering Cancer Center prospective pancreatic database and hospital tumor registry. A total of 18 patients were identified and comprise the basis of this study. Medical records were reviewed and the following factors analyzed: (1) demographics, (2) symptoms at presentation, (3) primary tumor type, (4) metastatic versus locally advanced presentation, (5) disease-free interval, and (6) intraoperative factors including operative time, blood loss, and transfusion requirements. Outcome measures included length of hospital stay, operative mortality, and overall survival. Data are expressed as median values (range). Survival was calculated by the method of Kaplan-Meier and compared by log rank test with statistical significance defined as P < 0.05. RESULTS Pancreaticoduodenectomy was performed in 589 patients during this study period (1983 to 1996). Eighteen patients underwent PD for nonperiampullary malignancy: 9 for direct extension and 9 for metachronous tumors. The primary tumor histopathology included colon (n = 7), gastric (n = 4), renal cell (n = 3), lung (n = 2), bladder (n = 1), and melanoma (n = 1). The median age of patients at the time of resection was 56 (41 to 76), with a male:female ratio of 13:5. Symptoms at the time of presentation include anemia/ melena (n = 5), abdominal pain (n = 4), gastric outlet obstruction (n = 3), jaundice (n = 2), and none (n = 2). For those patients with metachronous disease, the diseasefree interval was 52 months (11 to 106). The median operating room time for PD for nonperiampullary tumors was 5.8 hours (3.5 to 9), with a blood loss of 1,200 cc (600 to 3,000). The median length of hospital stay was 15 days (6 to 48) with 1 perioperative death 0002-9610/97/$17.00 393 PII S0002-9610(97)00121-9

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(5.5%). The median tumor size was 5.5 cm (0.8 to 11.5), and 7 patients had positive peripancreatic lymph nodes. Seventeen of 18 patients had negative resection margins. The median follow-up time for the entire cohort is 23 months (3 to 108). The median survival was 40 months, with a 5-year survival of 35% (Figure 1). There was no difference in survival comparing local extension versus locally recurrent/metastatic disease (Figure 2). The most common primary tumor type in our series was colon cancer (n = 7). Of these, 5 patients presented with primary T4 lesions requiring en bloc right hemicolectomy and PD. An additional 2 patients recurred 15 months after a curative right hemicolectomy and underwent PD. Two of 7 patients had positive lymph nodes at the time PD. Of these 7 patients, 4 died of recurrence at 14, 16, 21, and 41 months after PD. One patient has no evidence of disease (NED) 61 months after resection. Four patients underwent PD for gastric tumors (3 for a T4 primary, 1 for locally recurrent disease). Two patients died of disease 23 and 27 months after resection, while the other 2 remain NED at 33 and 86 months. Three patients underwent PD for metastatic renal cell carcinoma after a disease-free interval (DFI) of 53, 100, and 106 months after primary resection. An additional 2 patients underwent resection for metastatic lung cancer and 1 patient each for metastatic bladder and melanoma. COMMENTS Pancreaticoduodenectomy is routinely performed for localized periampullary malignancies, with a documented benefit in terms of survival and palliation, l's However, the role of PD for nonperiampullary tumors is unknown. In general, there are three clinical situations where PD may be indicated for nonperiampullary tumors. One situation is for primary T4 colon or gastric tumors that invade the duodenum and pancreas. Similarly, local recurrence from these primaries may also be amenable to resection by PD and constitutes the second presentation. The third clinical scenario that might require PD is isolated metastatic disease from a distant primary site. All three indications are quite rare since isolated tumor in the absence of widespread disease is unusual. The fact that less than 3% of PD performed at our institution over a 13-year period were for nonperiampullary malignancies speaks to the rarity of this clinical situation. This series demonstrates that PD in a select cohort can be performed safely and offers prolonged overall survival. Although large series have not been reported, others have also documented prolonged survival after PD for nonperiampullary primaries. 9-n These encouraging results are related in part to a self-selection process, which reflects the biology of these tumors. By virtue of the fact that these tumors present with single isolated metastatic disease and are technically resectable, it is not surprising that a significant survival can be achieved after PD. Supporting evidence for this favorable biology is noted by the fact that even with relatively large tumors, almost two thirds of the tumors in this series were node negative. This is in contrast to pancreatic adenocarcinoma, where more than 50% of resected specimens are node positive. 1 Patients with locally advanced primary tumors invading the pancreas and duodenum should be considered for PD. Eight patients in our series underwent PD for T4 primary colon (n = 5) and gastric (n = 3) cancers invading the

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pancreas, with a median survival of 27 months. Curley and colleagues9 reported their results for en bloc right hemicolectomy and PD (n = 7) for colon tumors invading the head of the pancreas. They reported a similar median survival of 32 months after resection; however, they included patients requiring only a lateral duodenectomy for complete tumor clearance. Other reports of PD for locally advanced colon cancer also claim long-term survivors. 1° Gastric cancer can also present with locally advanced primary tumors, often invading liver, spleen, or diaphragm, and extended gastric resection for these T4 lesions may provide long-term survival. ~3 However, gastric cancer growing directly into the head of the pancreas, so"as to require a PD for tumor clearance, is rare. In our series, 2 patients remain NED 33 and 86 months after PD for primary T4 tumors. One patient, who initially presented with gastric outlet obstruction from his primary, died of recurrence almost 2 years after resection. Locally recurrent tumors, in the absence of distant metastases, may also be an indication for PD. This is an unusual situation, and only 3 patients in our series underwent PD for locally recurrent colon (n = 2) and gastric (n = 1) [umors. All 3 died of recurrence at 41, 21, and 23 months, respectively.

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I PANCREATICODUODENECTOMY FOR NONPERIAMPULLARY TUMORS/HARRISON ET AL TABLE Series

Pancreaflooduodenectomy for Nonperlampullary Primary Tumors: Review of Literature Colon Renal Cell Melanoma Breast Lung Gastric

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* Review article; includes pancreaticoduodenectomy and total pancreatectomy.

In general, metastasis from distant primaries to the pancreas is associated with widespread disease and is commonly a preterminal event. However, in a highly select group, metastasis to the pancreas is the sole site of disease and resection can render the patient free of disease. In our series, the longest survivor in our series was a patient with metastatic melanoma, who remains NED 9 years after his PD. For isolated metastatic tumors to the head of the pancreas, PD has been reported for a variety of malignancies (Table), including breast, 14'1srenal cell, 16'~7melanoma, Is and lung. ~° Seven patien~ in our series presented with metastatic tumor to the head of the pancreas. Renal cell carcinoma was the most common metastatic tumor in our series, which is consistent with the literature. A recent review of solitary pancreatic metastasis from renal cell carcinoma cited a total of 33 pancreatic resections in all series, of which 13 patients underwent PD. A mean survival of 14 months was reported after complete resection. ~7 In summary, PD for nonperiampullary malignancy is not frequently indicated. However, in the absence of widely metastatic disease, PD should be considered for primary locally advanced tumors, locally recurrent disease, or isolated metastatic malignancy. With complete resection, long-term survival is possible. REFERENCES 1. Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am ] Surg. 1993;165: 8-73. 2. Lieberman MD, Kilbum H, Lindsey M, Brennan MF. Relation of perioperative deaths to hospital volume among patients undergoing pancreatic resection for malignancy. Ann Surg. 1995; 222:638-645. 3. Cameron JL, Pitt HA, Yeo CJ, et al. One hundred and forty-five consecutive pancreaticoduodenectomies without mortality. Ann Surg. 1993;217:430-438. 4. long Y, Blumgart LH, Cohen AM. Surgical treatment of colorectal metastases to the liver. CA Cancer] C//n. 1995;45:50-62.

5. Harrison LE, Brennan MF, Newman E, et al. Hepatic resection for non-colorecta[ non-neuroendocrine metastases: a fifteen year experience with 96 patients. Surgery. 1977;121:625-632. 6. Bines SD, England G, Deziel DJ, et al. Synchronous, metachmnous and multiple hepatic resections of liver tumots originating from primary gastric tumors. Surge~. 1993;114:799-805. 7. Gadd MA, Casper ES, Woodruff JM, et aL Development and treatment of pulmonary metastases in adult patients with extremity soft tissue sarcoma. Ann Surg. 1993;218:705-712. 8. Lillemoe KD, Cameron JL, Yeo CJ, et al. Pancreaticoduodenectomy: does it have a role in the palliation of pancreatic cancer? Ann Surg. 1996;223:718-728. 9. Curley SA, Evans DB, Ames FC. Resection for cure of carcinoma of the colon directly invading the duodenum or pancreatic head. J Am Co//Surg. 1994;179:587-592. 10. Nakeeb A, Lillemoe KD, Cameron JL. The role of pancreaticoduodenectomy for locally recurrent or metastatic carcinoma to the periampullary region. ] Am Co//Surg. 1995;180:188-192. 11. Smith CD, Behrns KE, van Heerden JA, Sarr MG. Radical pancreaticoduodenectomy for misdiagnosed pancreatic mass. Br] Surg. 1994;81:585-589. 12. Roland CF, van Heerden JA. Nonpancreatic primary tumors with metastasis to the pancreas. Surg G)v~col Obs~t. 1989;168: 345-347. 13. Korenaga D, Okamura T, Baba H, et al. Results of resection of gastric cancer extending to adjacent organs. Br ] Surg. 1988;75: 5-12. 14. Azzarelli A, Clemente C, Quagliuolo V, Baticci F. A case of pancreaticoduodenectomy as resolutive treatment for a solitary metastasis of breast cancer. Tumor/. 1982;68:331-335. 15. Mehta SA, Jagannath P, Krishamurthy SC, De Sotma LJ. Isolated pancreatic metastasis from locally controlled breast cancer: a case report. Indian] Cancer. 1991;28:48-50. 16. Stankard CE, Karl RC. The treatment of isolated pancreatic metastases from renal cell carcinoma: a surgical review. Am] Gasero. 1992;87:1658-1660. 17. Fabre JM, Rouanet P, Dagues F, et al. Various features and surgical approach of solitary pancreatic metastasis from renal cell carcinoma. Fur ] Surg Oncol. 1995;21:683-692. 18. England MD, Sarr MG. Metastatic melanoma: an unusual case of obstructive jaundice. Surgery. 1990;107:595-596.

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