Results of pancreatic resection. Patients undergoing total pancreatectomy for adenocarcinoma had a significantly worse survival than patients undergoing other pancreatic resections or total pancreatectomy for nonadenocarcinoma pathologic findings.
Karpoff HM, Klimstra DS, Brennan MF, Conlon KC. Results of Total Pancreatectomy for Adenocarcinoma of the Pancreas. Arch Surg. 2001;136(1):44-47. doi:10.1001/archsurg.136.1.44
Total pancreatectomy for infiltrating ductal adenocarcinoma is not superior to pancreaticoduodenectomy or distal pancreatectomy.
A retrospective analysis of a prospective database of patients.
Memorial Sloan-Kettering Cancer Center, New York, NY.
All patients (n = 488) undergoing pancreatic resection.
Main Outcome Measures
Duration of operation, estimated blood loss, complications, length of stay, number of positive lymph nodes, presence of a positive margin, and survival times were analyzed.
Thirty-five patients were identified who underwent total pancreatectomy, 28 of whom had adenocarcinoma. Median length of stay was 32 days; 19 (54%) developed postoperative complications, of which 63% were infectious. Thirty-day mortality was 3% (1 patient). Median survival was 9.3 months (range, 0.6-172 months). There was no significant difference between patients with and without adenocarcinoma in terms of duration of operation, estimated blood loss, complications, length of stay, or number of readmissions. In patients with adenocarcinoma, margin or nodal status were not significant survival variables. Patients undergoing total pancreatectomy for adenocarcinoma had a significantly worse overall survival than those undergoing total pancreatectomy for other reasons (P<.001), or compared with a contemporaneous cohort with adenocarcinoma undergoing pancreaticoduodenectomy (n = 409) and distal pancreatectomy (n = 51) (7.9 vs 17.2 months; P<.002).
Total pancreatectomy can be performed safely with low mortality; survival is predicted by the underlying pathologic findings: patients undergoing total pancreatectomy for adenocarcinoma have a uniformly poor outcome. Those undergoing total pancreatectomy for benign disease or nonadenocarcinoma variants can have long-term survival. In patients who require total pancreatectomy for ductal adenocarcinoma, the survival is so poor as to bring into question the value of the operation.
ALTHOUGH THERE have been substantial improvements in morbidity and mortality for surgical resection of cancer of the pancreas, improvements in survival have been small,1- 4 with the majority of patients dying in less than 2 years after "curative resection."5 A number of adverse prognostic factors have been identified, including lymph node status, tumors with poor histologic differentiation, and tumor size.6 While the extent of operation has not been shown to be a significant predictor of outcome, some have suggested that pancreatic adenocarcinoma is a multicentric disease and resections less than total are suboptimal. Thus, the concept of total pancreatectomy with wide regional lymphadenectomy is intellectually appealing.
The first total pancreatectomy was reported in 1943 by Rockey,7 who performed the procedure for carcinoma. Unfortunately, the patient died within 1 month of resection. Priestly et al,8 in 1944, performed the procedure for hyperinsulinism, resulting in long-term survival; Ross,9 in a 1954 report of a total pancreatectomy for carcinoma, was a strong advocate of the procedure. Support for the procedure grew in the early 1970s because the results of pancreaticoduodenectomy were so poor. The results of total resection, however, were not significantly better, with few long-term survivors.10,11 Further interest in total pancreatectomy has been generated because of the literature on extended lymphadenectomy for pancreatic resections.12 A recent randomized trial from Italy showed a trend toward a survival benefit from extended lymphadenectomy.11,13
The true role of total pancreatectomy for adenocarcinoma is controversial. Advocates have suggested that the increased morbidity associated with total pancreatectomy is compensated for by a potential improvement in survival.9 Detractors have reported that the morbidity and brittle diabetes subsequent to complete resection of the gland overshadow any marginal benefits. To clarify the role of total pancreatectomy, we examined the outcome of patients undergoing total pancreatectomy, analyzing the safety of the procedure and factors associated with long-term survival.
We analyzed a prospective database of patients undergoing pancreatic resection at Memorial Sloan-Kettering Cancer Center, New York, NY, from October 15, 1983, to November 30, 1998. Clinical and operative details were recorded, and pathologic findings were reviewed. Resections were performed by experienced pancreatic surgeons. The extent of nodal dissection was at the surgeon's discretion. Patients undergoing total pancreatectomy for infiltrating ductal adenocarcinoma were compared with those undergoing total pancreatectomy for other tumors or benign diseases. We also compared survival of patients undergoing total pancreatectomy for adenocarcinoma with those undergoing either distal pancreatectomy or pancreaticoduodenectomy (Whipple) for adenocarcinoma. Follow-up was obtained by patient interview or hospital charts and correspondence with the attending physician.
Clinical characteristics were compared by means of Fisher exact test and Wilcoxon rank sum test for categorical and continuous data. Survival was analyzed by the Kaplan-Meier method, with differences in survival compared by the log-rank test. Significance was defined at the .05 level.
During the study period, 488 patients underwent exploration and resection for adenocarcinoma of the pancreas: 51 patients underwent distal pancreatectomy, 409 patients underwent pancreaticoduodenectomy, and 28 patients underwent total pancreatectomy. An additional 7 patients underwent total pancreatectomy for other diseases (3 for benign disease, 3 for intraductal papillary-mucinous neoplasms, and 1 for adenocarcinoma of the common bile duct). Of the 28 patients with adenocarcinoma who underwent total pancreatectomy, 15 were men and 13 were women, with a median age of 61 years (range, 45-82 years). Eight patients (29%) had undergone exploration before presentation at our institution. Of these, 6 patients had exploration without resection; 1 patient had a distal pancreatectomy but subsequently developed recurrent disease. Data were unavailable for the remaining patient.
Median duration of the procedure for all patients (n = 35) undergoing total pancreatectomy was 8.1 hours (range, 4.5-12.1 hours), with a median estimated blood loss of 2500 mL (range, 350-7600 mL). Previous exploration correlated with a significantly longer procedure (P<.03) and greater estimated blood loss (P<.02). Nineteen (54%) developed postoperative complications, 12 (63%) of which were infectious. Median length of stay was 32 days. The perioperative mortality (30 days) was 3% (1/35). One patient died at 71 days and 1 died at 131 days postoperatively, without having been discharged. Nineteen patients (55%) who underwent total pancreatectomy were readmitted postoperatively, with a median hospital stay of 22 days (range, 2-136 days).
Despite total pancreatectomy, 18% (5/28) of patients with adenocarcinoma had a positive margin. Positive lymph nodes were seen in 29% (8/28). Histologic examination of the primary tumor demonstrated good differentiation in 25% (7/28), moderate differentiation in 36% (10/28), and poor differentiation in 39% (11/28). Ninety-six percent (27/28) of patients with adenocarcinoma had recurrences, and all died. One patient was alive and free of disease 13 months after operation before becoming unavailable for follow-up. Median survival for this group was 7.9 months (range, 0.63-120 months). In patients with adenocarcinoma, there was no apparent effect of number of positive nodes (P = .97), positive margins (P = .08), or differentiation (P = .30) on outcome.
There was no significant difference between ductal adenocarcinoma and nonadenocarcinoma groups in terms of age, sex, duration of operation, estimated blood loss, complications, length of stay, or number of readmissions (Table 1). However, patients undergoing total pancreatectomy for ductal adenocarcinoma had a significantly worse overall survival than those undergoing total pancreatectomy for other reasons (P<.001).
We then compared survival of patients undergoing total pancreatectomy for ductal adenocarcinoma with a contemporaneous cohort with adenocarcinoma undergoing pancreaticoduodenectomy (n = 409) or distal pancreatectomy (n = 51) and found those undergoing total pancreatectomy to have a significantly worse survival (7.9 vs 17.2 months; P<.002) (Figure 1). When compared separately, patients undergoing total pancreatectomy for adenocarcinoma had a shorter survival than those undergoing pancreaticoduodenectomy (7.9 vs 17.2 months; P<.001) or distal pancreatectomy (7.9 vs 15.8 months; P = .02). Even when patients who underwent total pancreatectomy were compared with the subset of all patients who underwent resection with pancreaticoduodenectomy or distal pancreatectomy with a pathologically positive surgical margin (n = 100) (ie, patients who were not rendered free of disease), survival for total pancreatectomy was worse (7.9 vs 14.2 months; P<.03).
Although the operative morbidity and mortality of all varieties of pancreatic resection have decreased markedly in the past 2 decades, no inroads have been made in improving overall survival in patients with adenocarcinoma.1,4 The poor survival has been attributed to the advanced disease state at diagnosis, the presence of microscopic positive margins, and positive nodal disease.1,14 Total pancreatectomy offers the theoretical advantage of complete surgical extirpation of the gland and consequent elimination of multicentric disease. It also may allow a wider lymphadenectomy15 and improve the rate of resectability, as indicated in a study by Launois et al.16 Initial reports of total pancreatectomy for hyperinsulinism8 and carcinoma7 demonstrated the feasibility of total resection, and Ross9 in 1954 urged that total pancreatectomy be a standard for resection. Table 2 provides a summary of the larger series of total pancreatectomies.
To be useful, total pancreatectomy must be done safely, and there are differing reports in the literature as to the safety of this procedure. Some reports indicate that total pancreatectomy can be performed safely19,23- 25 and with no different morbidity than with Whipple resection.11,15 Other reports in the literature, however, show significant mortality rates for total pancreatectomy, as high as 28% in one series.18 Another report indicated the complication rate with total pancreatectomy to be 3-fold higher than with pancreaticoduodenectomy.26 Ihse et al10 showed that patients undergoing total pancreatectomy had significantly increased perioperative morbidity and mortality compared with those undergoing less radical surgery, but many of these patients underwent surgery before the "modern" era, and more recent studies have shown total pancreatectomy to be relatively safe. In our study, performed in the modern era of pancreatic surgery, there was only a 3% perioperative (30-day) mortality rate and a 55% morbidity rate. Length of stay was markedly prolonged, emphasizing the greater morbidity associated with total pancreatectomy.
The reported efficacy of total pancreatectomy varies widely, for some have claimed a survival advantage for total pancreatectomy,27 whereas other reports find the results of pancreaticoduodenectomy to be superior.28 Swope et al,15 in a review of the Veterans Affairs database, found an improved survival in patients with stage I and stage II disease undergoing total pancreatectomy compared with Whipple resection (P = .06),15 but this was not seen in stage III and IV disease. These results may simply be due to stage migration. A study by van Heerden et al22 showed a 3-year survival rate of 9% and a 5-year survival rate of 2.3%. In the current study, only 2 of 28 patients survived 5 years.
Most of the theoretical advantages of total pancreatectomy over subtotal resection are not borne out. The advantage resulting from the multicentric nature of the disease is not realized, for studies show that multicentric disease is actually uncommon, seen in only 9% of cases.18,29 In addition, the theoretical advantage of total pancreatectomy in eliminating a pancreatic anastomosis22 is often not realized; although the leak rates after anastomosis are substantial, occurring in 10% to 20%, pancreatic leaks are most often not life threatening.3
Total pancreatectomy has been advocated as an alternative in selected cases of benign pancreatic disease,18,24,30 and these reports indicate favorable outcomes. Dresler et al31 examined the metabolic consequences of total pancreatectomy and found that, although patients become diabetic and have some alterations in lifestyle, most are able to resume a reasonable level of activity. Only 1 of 49 patients died of metabolic disarray, with no other patients having serious diabetic sequelae. Other reports after total pancreatectomy have shown good performance status postoperatively, with intermittent hypoglycemia being the most frequent complication.32 In the current study, all 3 patients with benign disease were alive, with follow-up of 4.5, 12, and 14 years. Two of the 3 patients with intraductal papillary lesions were alive, with a median follow-up of 16 months.
Prognosis of patients undergoing total pancreatectomy appears to be based more on underlying pathologic features than type of resection. In the current series, patients undergoing total pancreatectomy for ductal adenocarcinoma had a significantly worse overall survival than those undergoing total pancreatectomy for other pathologic conditions. In fact, 96% of patients with adenocarcinoma died of their disease, whereas 86% of patients undergoing total pancreatectomy for other disease were still alive at last follow-up. These results are in accord with those of Assan et al,32 who showed long-term survival after total pancreatectomy for benign disease but none for cancer.
Total pancreatectomy for adenocarcinoma offers no survival advantage over less-than-total resection. Furthermore, a positive margin of resection at the time of pancreaticoduodenectomy for adenocarcinoma should not cause the surgeon to perform a total pancreatectomy, as the morbidity is greater and the outcome no better. Total pancreatectomy may play a role in patients with other disease, such as benign disease or intraductal papillary lesions of the pancreas. These patients can have prolonged survival.
This study was supported by the Bernice and Milton Stern Foundation, New York, NY.
Corresponding author and reprints: Kevin C. Conlon, MD, MBA, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021 (e-mail: email@example.com).