Influence of Klebsiella pneumoniae and quinolone treatment on prognosis in patients with pancreatic cancer.

BACKGROUND: An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. METHODS: This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001). CONCLUSION: K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

Risk of malignancy in small pancreatic cysts decreases over time.

BACKGROUND: Pancreatic cysts <15 mm without worrisome features have practically no risk of malignancy at the time of diagnosis but this can change over time. Optimal duration of follow-up is a matter of debate. We evaluated predictors of malignancy and attempted to identify a time to safely discontinue surveillance. METHODS: Bi-centric study utilizing prospectively collected databases of patients with pancreatic cysts measuring <15 mm and without worrisome features who underwent surveillance at the Massachusetts General Hospital (1988-2017) and at the University of Verona Hospital Trust (2000-2016). The risk of malignant transformation was assessed using the Kaplan-Meier method and parametric survival models, and predictors of malignancy were evaluated using Cox regression. RESULTS: 806 patients were identified. Median follow-up was 58 months (6-347). Over time, 58 (7.2%) cysts were resected and of those, 11 had high grade dysplasia (HGD) or invasive cancer. Three additional patients had unresectable cancer for a total rate of malignancy of 1.7%. Predictors of development of malignancy included an increase in size ≥2.5 mm/year (HR = 29.54, 95% CI: 9.39-92.91, P < 0.001) and the development of worrisome features (HR = 9.17, 95% CI: 2.99-28.10, P = 0.001). Comparison of parametric survival models suggested that the risk of malignancy decreased after three years of surveillance and was lower than 0.2% after five years. CONCLUSIONS: Pancreatic cysts <15  mm at the time of diagnosis have a very low risk of malignant transformation. Our findings indicate the risk decreases over time. Size increase of ≥2.5 mm/year is the strongest predictor of malignancy.

An elevated CA 19-9 is associated with invasive cancer and worse survival in IPMN.

BACKGROUND: Current guidelines for IPMN include an elevated serum carbohydrate antigen (CA) 19-9 among the worrisome features. However, the correlation of CA 19-9 with histological malignant features and survival is unclear. Serum CEA is also currently used for preoperative management of IPMN, although its measurement is not evidence-based. Accordingly, we aimed to assess the role of these tumor markers as predictors of malignancy in IPMN. METHODS: IPMN resected between 1998 and 2018 at Massachusetts General Hospital were analyzed. Clinical, pathological and survival data were collected and compared to preoperative levels of CA 19-9 and CEA. Receiver operating characteristic (ROC) and Cox regression analyses were performed considering cut-offs of 37 U/ml (CA 19-9) and 5 µg/l (CEA). RESULTS: Analysis of 594 patients showed that preoperative CA 19-9 levels > 37 U/ml (n = 128) were associated with an increased likelihood of invasive carcinoma when compared to normal levels (45.3% vs. 18.0%, P < 0.001), while there was no difference with respect to high-grade dysplasia (32.9% vs 31.9%, P = 0.88). The proportion of concurrent pancreatic cancer was higher in patients with CA 19-9 > 37 U/ml (17.2% vs 4.9%, P < 0.001). An elevated CA 19-9 was also associated with worse overall and disease-free survival (HR = 1.943, P = 0.007 and HR = 2.484, P < 0.001 respectively). CEA levels did not correlate with malignancy. CONCLUSION: In patients with IPMN, serum CA19-9 > 37 U/ml is associated with invasive IPMN and concurrent pancreatic cancer as well as worse survival, but not with high-grade dysplasia. Serum CEA appears to have minimal utility in the management of these patients.

Major Complications Independently Increase Long-Term Mortality After Pancreatoduodenectomy for Cancer.

BACKGROUND: Postoperative major morbidity has been associated with worse survival gastrointestinal tumors. This association remains controversial in pancreatic cancer (PC). We analyzed whether major complications after surgical resection affect long-term survival. METHODS: Records of all PC patients resected from 2007 to 2015 were reviewed. Major morbidity was defined as any grade-3 or higher 30-day complications, per the Clavien-Dindo Classification. Patients who died within 90 days after surgery were excluded from survival analysis. RESULTS: Of 616 patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal pancreatectomy (DP). Major complications occurred in 19.1% after PD and 15.9% after DP. In patients who survived > 90 days, the likelihood of receiving adjuvant treatment was 43.9% if major complications had occurred, vs. 68.5% if not (p < 0.001), and those who received it started the treatment median 10 days later compared with uncomplicated patients (median 60 days (50-72) vs. 50 days (41-61), p = 0.001). By univariate analysis, in addition to the conventional pathology-related prognostic determinants and the receipt of adjuvant treatment, major complications worsened long-term survival after PD (median OS 26 months vs. 15, p = 0.008). A difference was also seen after DP, but it did not reach statistical significance, likely related to the small sample size (median OS 33 months vs. 18, p = 0.189). At multivariate analysis for PD, major postoperative complications remained independently associated with worse survival [HR 1.37, 95%CI (1.01-1.86)]. CONCLUSIONS: Major surgical complications after pancreaticoduodenectomy are associated with worse long-term survival in pancreatic cancer. This effect is independent of the receipt of adjuvant treatment.

Intraoperative Fluid Administration and Surgical Outcomes Following Pancreaticoduodenectomy: External Validation at a Tertiary Referral Center.

BACKGROUND: While intraoperative fluid overload is associated with higher complication rates following surgery, data for pancreaticoduodenectomy are scarce and heterogeneous. We evaluated multiple prior definitions of restrictive and liberal fluid regimens and analyzed whether these affected surgical outcomes at our tertiary referral center. METHODS: Studies evaluating different intraoperative fluid regimens on outcomes after pancreatic resections were retrieved. After application of all prior definitions of restrictive and liberal fluid regimens to our patient cohort, relative risks of each outcome were calculated using all reported infusion regimens. RESULTS: Five hundred and seven pancreaticoduodenectomies were included. Nine different fluid regimens were evaluated. Two regimens utilized absolute volume cutoffs, and the remaining evaluated various infusion rates, ranging from 5 to 15 mL/kg/h. Total volume administration of >5000 mL and >6000 mL was associated with increased complications (RR 1.25 and RR 1.17, respectively) and >6000 mL with increased sepsis (RR 2.14). Conversely, a rate of <5 mL/kg/h was associated with increased risk of postoperative pancreatic fistula (POPF, RR 3.16) and sepsis (RR 3.20), <6.8 mL/kg/h with increased major morbidity (RR 1.64) and sepsis (RR 2.27), and <8.2 mL/kg/h with increased POPF (RR 2.16). No effects were observed on pulmonary complications, surgical site infections, length of stay, or mortality. CONCLUSIONS: In an uncontrolled setting with no standard intraoperative or postoperative care map, the volume of intraoperative fluid administration appears to have limited impact on early postoperative outcomes following pancreaticoduodenectomy, with adverse outcomes only seen at extreme values.

Pancreatic enucleation: improved outcomes compared to resection.

INTRODUCTION: Pancreatic enucleation is associated with a low operative mortality and preserved pancreatic parenchyma. However, enucleation is an uncommon operation, and good comparative data with resection are lacking. Therefore, the aim of this analysis was to compare the outcomes of pancreatic enucleation and resection. MATERIAL AND METHODS: From 1998 through 2010, 45 consecutive patients with small (mean, 2.3 cm) pancreatic lesions underwent enucleation. These patients were matched with 90 patients undergoing pancreatoduodenectomy (n = 38) or distal pancreatectomy (n = 52). Serious morbidity was defined in accordance with the American College of Surgeons-National Surgical Quality Improvement Program. Outcomes were compared with standard statistical analyses. RESULTS: Operative time was shorter (183 vs. 271 min, p < 0.01), and operative blood loss was significantly lower (160 vs. 691 ml, p < 0.01) with enucleation. Fewer patients undergoing enucleation required monitoring in an intensive care unit (20% vs. 41%, p < 0.02). Serious morbidity was less common among patients who underwent enucleation compared to those who had a resection (13% vs. 29%, p = 0.05). Pancreatic endocrine (4% vs. 17%, p = 0.05) and exocrine (2% vs. 17%, p < 0.05) insufficiency were less common with enucleation. Ten-year survival was no different between enucleation and resection. CONCLUSION: Compared to resection, pancreatic enucleation is associated with improved operative as well as short- and long-term postoperative outcomes. For small benign and premalignant pancreatic lesions, enucleation should be considered the procedure of choice when technically appropriate.

Very high serum CA 19-9 levels: a contraindication to pancreaticoduodenectomy?

AIM: To assess the outcome of patients with resectable pancreatic adenocarcinoma (PA) associated with high serum CA 19-9 levels. METHODS: From 2000 to 2007, 344 patients underwent pancreatoduodenectomy for PA. Fifty-three patients (elevated group) had preoperatively elevated serum CA 19-9 levels (>400 IU/ml) after resolution of obstructive jaundice. Of these, 27 patients had high levels (400-899 IU/ml (HL)) and 26 patients had very high levels >or=900 IU/ml (VHL). Fifty patients with normal preoperative serum CA 19-9 levels (<37 IU/ml) comprised the control group. RESULTS: Median survival of the control group (n = 50) versus elevated group (n = 53) was 22 versus 15 months (p = 0.02) and overall 3-year survival was 32% versus 14% (p = 0.03). There was no statistical difference in the median and 3-year overall survival between patients with HL and VHL. Patients in the elevated group who normalized their CA 19-9 levels after surgery (n = 11) had a survival equivalent to patients in the control group. CONCLUSIONS: Patients who normalized their CA19-9 levels postoperatively had equivalent survival to patients with normal preoperative CA 19-9 levels. Preoperative serum CA 19-9 level by itself should not preclude surgery in patients who have undergone careful preoperative staging.

Evaluation of suspected bile duct injuries.

The proper diagnosis and appropriate treatment are paramount in ensuring a satisfactory outcome after a bile duct injury associated with laparoscopic cholecystectomy. Immediate recognition of a bile duct injury during laparoscopic cholecystectomy can allow proper treatment at that time, averting difficult complications that could occur in the postoperative period should the injury be missed. Unfortunately, most bile duct injuries are not recognized at the time of laparoscopic cholecystectomy. An appropriate level of suspicion followed by prompt and complete evaluation should result in accurate delineation of the biliary anatomy, which is essential for directing appropriate surgical reconstruction.

Surgical techniques for pancreatic cancer.

Surgical resection of pancreatic adenocarcinoma offers the only chance for long-term cure. Over the past 2 decades significant advances have been made in both the surgical techniques and the perioperative care of patients with pancreatic cancer. The operative management of pancreatic cancer involving the head, neck, and uncinate process consists of 2 phases: first, assessing tumor resectability and then, if the tumor is resectable, completing a pancreaticoduodenectomy and restoring gastrointestinal continuity. In this article, we describe our current techniques for resection of pancreatic cancer, review operative palliation for unresectable cancer, and discuss several controversies in the operative management of pancreatic cancer including: 1) the role of extended lymphadenectomy, 2) pylorus preservation and 3) pancreaticojejunostomy versus pancreaticogastrostomy for pancreatic duct reconstruction.

Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity.

OBJECTIVE: To assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). SUMMARY BACKGROUND DATA: Intraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency. METHODS: All patients who underwent pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and December 2000 were studied. The data were compared with those of 702 concurrent patients with infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN resected by pancreaticoduodenectomy. RESULTS: In the 13-year time period, 60 patients underwent pancreatic resection for IPMNs, with 40 patients undergoing resection in the past 3 years. Mean age at presentation was 67.4 +/- 1.4 years. The most common presenting symptom in patients with IPMNs was abdominal pain (59%). Most IPMNs were in the head of the pancreas or diffusely involved the gland, with 70% being resected via pancreaticoduodenectomy, 22% via total pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs immunohistochemically stained for the Dpc4 protein (n = 50), all of the intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all patients with IPMNs (n = 60) was 57%. CONCLUSION: Intraductal papillary mucinous neoplasms represent a distinct clinicopathologic entity being recognized with increasing frequency. IPMNs are clinically, histologically, and genetically disparate from pancreatic ductal adenocarcinomas. The distinct clinical features, the presumably long in situ or noninvasive phase, and the good long-term survival of patients with IPMNs offer a unique opportunity for early diagnosis, curative resection, and further studies of the molecular genetics and natural history of these unusual neoplasms.

Do medical school surgical rotations influence subspecialty choice?

BACKGROUND: A comprehensive exposure to general surgery is essential for medical students pursuing careers in surgery. Occasionally, students applying for surgical residency positions must choose a subspecialty field prior to starting their residency training. Often, this decision is heavily based on their experience on various surgical clerkships. MATERIALS AND METHODS: To determine if surgical clerkships influence subspecialty choice, we surveyed medical students who interviewed for general surgery training over a 2-year period at The Johns Hopkins Hospital. RESULTS: Of 211 surveys sent, 146 were returned (66%). The mean age of the students was 26 +/- 0 years with 21% being female. Students anticipating subspecialization in cardiothoracic, plastic, pediatric, and transplant surgery saw significantly more operations in their respective fields. Similar trends were seen in vascular surgery and surgical oncology. Despite the apparent differences in exposure to subspecialty operations, all students saw equal numbers of hernia repairs and laparoscopic cholecystectomies. CONCLUSIONS: While medical students pursuing careers in surgery have equal exposure to general surgery, their anticipated subspecialty field highly correlated with their operative exposure to that field. Thus, medical school surgical rotations appear to highly influence subspecialty choice.

Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation.

PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF-secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 x 10(7) vaccine cells, three patients received 5 x 10(7) vaccine cells, three patients received 10 x 10(7) vaccine cells, and five patients received 50 x 10(7) vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received >or= 10 x 10(7) vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF-secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.

Occupational exposure to pesticides and pancreatic cancer.

BACKGROUND: An increased risk of exposure to pesticides for pancreatic cancer has been suggested in a number of epidemiologic studies. METHODS: Cases (N = 484), aged 30-79 years, were diagnosed in 1986-1989. Controls (N = 2,095) were a random sample of the general population. Information on usual occupation and potential confounding factors was obtained. A job-exposure matrix (JEM) approach was used to estimate the level of occupational exposure to pesticides. RESULTS: A significant trend in risk with increasing exposure level of pesticides was observed, with ORs of 1.3 and 1.4 for low and moderate/high exposure levels, respectively. Excess risks were found for occupational exposure to fungicides (OR = 1.5) and herbicides (OR = 1.6) in the moderate/high level after adjustment for potential confounding factors. An increased risk for insecticide exposure was disappeared after adjustment for fungicide and herbicide exposures. Results of our occupation-based analysis were consistent with those from the JEM-based analysis. CONCLUSIONS: Our results suggest that pesticides may increase risk of pancreatic cancer, and indicate the need for investigations that can evaluate risk by specific chemical exposures. Published 2001 Wiley-Liss, Inc.

Renal cell carcinoma metastatic to the pancreas: results of surgical management.

Metastatic tumors to the pancreas are uncommon. Renal cell carcinoma is one of the few tumors known to metastasize to the pancreas. The purpose of the current report is to evaluate the surgical management and long-term outcome of patients with metastatic renal cell carcinoma. A retrospective review of patients undergoing pancreatic resection for renal cell carcinomas metastatic to the pancreas or periampullary region between April 1989 and May 1999, inclusive, was performed. Time from initial presentation, other metastatic sites, surgical outcomes, and long-term survival were evaluated. During the 10-year time period, 10 patients underwent pancreatic resection for renal cell carcinoma metastases. Of those, six underwent pancreaticoduodenectomy and two underwent distal pancreatectomy, whereas the two remaining patients underwent total pancreatectomy for extensive tumor involvement throughout the entire gland. The mean time from nephrectomy for resection of the primary tumor to reoperation for periampullary recurrence was 9.8 years (median 8.5 years). The range was 0 to 28 years, with one patient presenting with a synchronous metastasis. The mean age of the patients was 61.2 years with 60% of patients being male and 90% being white. Pathologic findings included histologically negative lymph nodes and negative surgical margins in all patients. One patient had tumor involving the retroperitoneal soft tissue, but final margins were negative. The mean live patient follow-up was 30 months (median = 15 months), with eight patients remaining alive. The Kaplan-Meier actuarial 5-year survival was 75%, with the longest survivor still alive 117 months following resection. The patient with retroperitoneal soft tissue involvement died 4 months after resection. The pancreas is an uncommon site of metastasis for renal cell carcinoma, typically occurring years after treatment of the primary tumor. When the metastatic focus is isolated and the tumor can be resected in its entirety, patients can experience excellent 5-year survival rates. The current report suggests that pancreatic metastases from renal cell carcinoma should be managed aggressively with complete resection when possible.

Intensified adjuvant combined modality therapy for resected periampullary adenocarcinoma: acceptable toxicity and suggestion of improved 1-year disease-free survival.

PURPOSE: (1) To determine the toxicity of an intensified postoperative adjuvant regimen for periampullary adenocarcinoma (pancreatic and nonpancreatic) utilizing concurrent 5-fluorouracil (5-FU), leucovorin (LV), dipyridamole (DPM), and mitomycin-C (MMC) combined with split-course locoregional external beam radiotherapy (EBRT) to 50 Gy. This was followed by 4 cycles of the same chemotherapy as adjuvant therapy. (2) To determine preliminary estimates of the overall and disease-free survival associated with the use of this regimen. (3) To compare the toxicities and early survival results of patients treated with the current regimen to those of patients who completed our prior trial of concurrent chemoradiation infusion with 5-FU/LV chemotherapy and regional nodal and prophylactic hepatic irradiation. METHODS: Postpancreaticoduodenectomy, patients received every 4 weeks bolus administration of 5-FU, (400 mg/m(2)), and LV, (20 mg/m(2), Days l-3), DPM (75 mg p.o., 4 times per day, Days 0-3, and every 8 weeks), MMC, (10 mg/m(2); maximum of 20 mg, Day l during EBRT). This was followed by 4 months of the same chemotherapy, beginning 1 month following the completion of EBRT. EBRT consisted of split-course 5000 cGy/20 fractions with a 2-week planned rest after the first 10 fractions (2500 cGy). RESULTS: From 4/96 to 6/99, 45 patients were enrolled and treated. Their experience constitutes the basis of this analysis. There were 29 patients with pancreatic cancer and 16 with nonpancreatic periampullary cancer. Seventeen patients had tumors of 3 cm or more, and 39 patients had at least 1 histologically involved lymph node. Thirteen patients had a histologically positive margin of resection. The mean time to start of treatment was 63 days following surgery. During chemoradiation therapy there were no Grade 3 or worse nonhematologic toxicities and 47% Grade 3 or Grade 4 hematologic toxicities of short duration. Following chemoradiation, during chemotherapy treatment only, there was one Grade 3 hepatic and one Grade 3 pulmonary toxicity which was nondebilitating (2% each case) and 42% Grade 3 or 4 hematologic toxicity. There were 2 episodes of neutropenic fever requiring admission and no treatment-related mortalities. One patient developed a mild case of HUS, which responded to standard management. One patient developed persistent shortness of breath (nondebilitating), and another patient had occasional dyspnea on exertion, both occurring after all therapy. The majority of patients complained of increased fatigue (Grade 1-2), greatest during the combined therapy and improving post all treatment. As of 6/23/99, 20 of 45 patients have relapsed, 13 in the liver. Twelve patients have died. Median follow-up for surviving patients is 14.3 months. Disease-free survival at 12 months following surgery is 66% (as compared to 25% in our prior study), and the median disease-free survival is 17 months (as compared to 8. 3 months in our prior study). Median survival has not yet been reached, but will be greater than 17 months. CONCLUSION: With a 14.3-month median follow-up, acute toxicity has been acceptable and manageable. Observed relapses were seen 9-13 months following surgical resection. Early survival analysis suggests a trend toward increased median disease-free survival (8.3 vs. 17 months), especially for patients with nonpancreatic periampullary adenocarcinoma.

Surgery for hilar cholangiocarcinoma: the Johns Hopkins approach.

Carcinoma of the hepatic duct confluence is the most common site of bile duct malignancies. Significant progress has been made in recent years in the diagnosis and treatment of this disease. The diagnosis is generally made in the jaundiced patient with contrast-enhanced spiral computed tomography (CT) scanning followed by cholangiography. Percutaneous transhepatic cholangiography is favored over endoscopic retrograde cholangiography in that it better defines the proximal extent of the tumor involvement and allows placement of percutaneous transhepatic catheters. The preoperative placement of stents facilitates the surgical management, as well as decompressing the obstructed biliary tree. The operative technique at The Johns Hopkins Hospital involves resection of the hepatic confluence and reconstruction over Silastic stents. In patients in whom the hilar cholangiocarcinoma extends along either the right or left hepatic duct into the hepatic parenchyma, appropriate hepatic lobectomy is performed. A recent review of the Johns Hopkins experience has demonstrated that 67% of cholangiocarcinomas are located in the perihilar location. Fifty-six percent of these patients were resectable for potential cure. Of the 109 resected patients, 4 patients (3.6%) died secondary to complications of sepsis. In the 109 patients with resected perihilar tumors, the 1-, 3-, and 5-year survival was 68%, 30% and 11%, respectively. The median survival was 19 months. The addition of hepatic lobectomy did not alter the survival rate. Negative margins and negative lymph node status were associated with improved survival. Postoperative adjuvant radiation therapy did not provide benefit to patients with resected perihilar carcinoma.

Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial.

OBJECTIVE: To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652. METHODS: Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay. RESULTS: Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups. CONCLUSIONS: These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings.