Pancreatic resection of isolated metastases from nonpancreatic primary cancers.

BACKGROUND: The goal of this study is to report the safety and efficacy of pancreatic resection for isolated metastatic cancers from nonpancreatic primary disease. METHODS: We retrospectively identified patients from a single institution's prospectively gathered pancreaticobiliary database from 1970 to 2007 who underwent a pancreatic resection for metastatic disease. RESULTS: Forty-nine patients were identified with metastatic lesions to the pancreas. Pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy were performed in 31, 14, and 4 patients, respectively. Pathology distribution was as follows: 21 renal cell carcinoma (RCC), 6 gallbladder cancer, 4 lung cancer, 4 ovarian cancer, 4 sarcoma, 3 melanoma, 2 colon cancer, 1 breast cancer, 1 hepatocellular carcinoma, 1 seminoma, 1 Langerhans cell histiocytosis, and 1 nonpancreatic endocrine cancer. Postoperative morbidity was 48%. There were no perioperative deaths. A statistically significant difference in survival was found between cancer types (P = .007) with median survivals ranging from 4.8 years for RCC to .9 years for melanoma. Univariate analysis demonstrated a survival disadvantage for patients with perineural (hazard ratio [HR] = 5.4, P = .004) and vascular invasion (HR = 4.4, P = .002). The most commonly resected metastatic lesion of the pancreas was RCC. Eighteen of the 23 patients with RCC had a metachronous lesion with a median length between initial operation and pancreatic resection of 9.3 years. Metachronous lesions had a survival similar to that of synchronous lesions (HR = 1.0, P = .98). Vascular invasion (HR = 2.4, P = .007) and lymph node metastases (HR = 24.1, P = .01) were associated with greater mortality. CONCLUSION: Long-term survival can be achieved in patients undergoing resection of isolated metastases to the pancreas.

Duodenojejunostomy leaks after pancreaticoduodenectomy.

BACKGROUND: A duodenojejunostomy (DJ) or gastrojejunostomy (GJ) leak is a potentially fatal complication after pancreaticoduodenectomy (PD). However, due to its rarity, this complication has not been fully characterized. METHODS: We reviewed 3,029 PDs performed at our institution over a 26-year period and identified patients who suffered a leak at the DJ or GJ anastomosis. Perioperative data from patients with such a leak were examined in detail and were compared to patients who did not experience such a leak after PD. RESULTS: A total of 13 patients experienced a DJ or GJ leak after PD, amounting to a 0.4% leak rate. Common clinical signs of a leak included an acute abdomen, enterocutaneous fistula, and a fever. Twelve of thirteen patients also had a leukocytosis, with five patients having a peak white blood cell count exceeding 30,000 cells/mm(3). The median time interval between surgery and diagnosis of the DJ or GJ leak was 10 days; three patients were diagnosed after being discharged from the hospital and one patient was diagnosed on the day of their planned discharge. In a multivariate model, perioperative risk factors for a DJ or GJ leak included a preoperative BUN-to-creatinine ratio > 20 (odds ratio = 6, p = 0.01), intraoperative blood loss > or =1 l (odds ratio = 6, p = 0.03), and a total pancreatectomy (odds ratio = 7, p = 0.005). In the DJ or GJ leak group, 12 of 13 patients were managed operatively. The median postoperative length of stay was 35 days after PD, and four patients died within 4 months of surgery as a result of their complicated postoperative course. CONCLUSION: DJ or GJ leaks occur infrequently after PD, but are associated with substantial morbidity. The clinical presentation is usually delayed, and surgical management is the preferred approach. Early diagnosis, attention to preoperative volume status, and continued efforts to control blood loss may minimize the impact of DJ or GJ leaks in some instances.

Acinar cell carcinoma of the pancreas: an institutional series of resected patients and review of the current literature.

INTRODUCTION: Acinar cell carcinoma (ACC) is a rare, malignant neoplasm with a generally poor prognosis. We report our institutional series of 14 patients with ACC to determine current guidelines for their evaluation and treatment. MATERIALS AND METHODS: The Johns Hopkins pathology prospective database was reviewed from 1988 to 2006 to identify patients with pancreatic neoplasms possessing features of acinar cell differentiation. Retrospective review and follow-up was performed for each patient. RESULTS: Fourteen patients with ACC were identified with a median age of 57 years. All patients presented with abdominal pain or discomfort with none showing evidence of lipase hypersecretion syndrome. Each patient underwent surgical resection, including nine pancreaticoduodenectomies and five distal pancreatectomies. Median tumor size was 3.9 cm with 12 patients found to have stage IIB disease or worse. Four patients underwent neoadjuvant chemoradiation. Eight of the fourteen patients developed recurrent disease. Overall median survival and disease-free survival were 33 and 25 months, respectively, as compared to a median survival of 18 months for pancreatic adenocarcinoma. CONCLUSION: Acinar cell carcinomas are rare, aggressive neoplasms that are difficult to diagnose and treat. Operative resection represents the best first-line treatment. These lesions have a better prognosis than the more common pancreatic adenocarcinomas.

Biochemical markers predict morbidity and mortality after pancreaticoduodenectomy.

BACKGROUND: The association between routinely ordered perioperative laboratory tests and postoperative morbidity and mortality after pancreaticoduodenectomy has not been well characterized. STUDY DESIGN: Routine perioperative laboratory data were analyzed for 2,894 patients who underwent a pancreaticoduodenectomy over a 25-year period. Laboratory values were initially categorized as being above or below the 75th percentile for the study population, and biochemical markers of morbidity and mortality were identified using multivariate logistic regression. The most significant biochemical markers were studied in greater detail by regrouping patients into low, intermediate, and high categories. RESULTS: Significant multivariate predictors of a postoperative complication included preoperative blood urea nitrogen> or =18 mg/dL, preoperative albumin< or =3.5 g/dL, and postoperative amylase> or =292 U/L. Significant multivariate predictors of a postoperative death included preoperative albumin< or =3.5 g/dL and postoperative aminotransferase> or =187 U/L. Postoperative hyperamylasemia was found to be associated, in particular, with an increased pancreatic fistula rate. Pancreatic fistula rates in the low (0 to 99 U/L), intermediate (100 to 399 U/L), and high (> or = 400 U/L) postoperative amylase groups were 4%, 14%, and 20%, respectively. Postoperative mortality rates in patients with low (0 to 499 U/L), intermediate (500 to 1,999 U/L), and high (> or = 2,000 U/L) postoperative aminotransferase groups were 0.9%, 5%, and 29%, respectively. Postoperative mortality rates in the high (> 3.5 g/dL), intermediate (2.6 to 3.5 g/dL), and low (0 to 2.5 g/dL) albumin groups were 0.9%, 3%, and 7%, respectively. CONCLUSIONS: Routine perioperative laboratory tests can help surgeons identify patients who are at increased risk for morbidity and mortality after pancreaticoduodenectomy.

Resected serous cystic neoplasms of the pancreas: a review of 158 patients with recommendations for treatment.

BACKGROUND: Serous cystic neoplasms of the pancreas are regarded as a benign entity with rare malignant potential. Surgical resection is generally considered curative. OBJECTIVE: To perform the largest single institution review of patients who underwent surgical resection for serous cystic neoplasms of the pancreas in the hopes of guiding future management. METHODS: Between June 1988 and January 2005, 158 patients with serous cystic neoplasms of the pancreas underwent surgical resection. A retrospective analysis was performed. Univariate and multivariate models were used to determine factors influencing perioperative morbidity and mortality. Major complications were defined as pancreatic fistula or anastomotic leak, postoperative bleed, retained operative material, or death. Minor complications were defined as wound infection, postoperative obstruction/ileus requiring total parenteral nutrition (TPN), delayed gastric emptying, arrhythmia, or other infection. RESULTS: The mean age of the patients was 62.1 years, with 75% being female. The majority of patients were symptomatic at presentation (63%), with abdominal pain as the most common symptom. Of the 158 patients, 75 underwent distal pancreatectomy, 65 underwent pancreaticoduodenectomy, nine underwent central pancreatectomy, five underwent local resection or enucleation, and four underwent total pancreatectomy. Mean tumor diameter was 5.1 cm. Mean operative time was 277 min. Mean postoperative length of hospital stay was 11 days. One patient was diagnosed at presentation with serous cystadenocarcinoma. The remaining 157 patients were initially diagnosed with benign serous cystadenoma. One of three patients with locally aggressive benign disease later presented with metastatic disease. Resection margins for all 158 patients were negative for tumor, and only one (0.6%) showed lymph node involvement. There was one intraoperative death. The incidence of major perioperative complications was 18%, whereas the incidence of minor complications was 33%. Men were significantly more likely to experience minor perioperative complications (OR = 3.74, P = 0.008), whereas patients greater than 65 years showed a trend toward fewer major complications (OR = 0.36, P = 0.09). CONCLUSIONS: Surgically resected serous cystic neoplasms of the pancreas are typically seen in asymptomatic women as 5 cm neoplasms and are predominantly benign. Most are resected via either a left- or right-sided pancreatectomy with low mortality risk, but with notable major or minor morbidity. Cystadenocarcinoma is a rare finding on initial resection of serous cystic neoplasms. However, initial pathology specimens exhibiting benign but locally aggressive neoplasia may indicate an increased likelihood of recurrence or metachronous metastasis, although this claim is limited by a small patient subpopulation in this study and warrants further review.

Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up.

BACKGROUND: Many studies have reported 5-year survival data after pancreaticoduodenectomy for periampullary adenocarcinoma. This study evaluates 10-year survival in patients surviving 5 years after initial surgery. METHODS: We reviewed all patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma from April 1970 to July 1999 at a single institution. All 5-year survivors were identified, and their subsequent 5-year survival was compared with the actuarial survival of the general population starting at 70 years of age. RESULTS: Nine hundred fifteen patients underwent pancreaticoduodenectomy for periampullary adenocarcinoma. Follow-up was complete on 890 patients. There were 201 (23%) 5-year survivors with a median age of 65 years at initial surgery; 51% were male and 92% were Caucasian. For the 5-year survivors, the carcinoma origin was pancreatic in 46%, ampullary in 25%, distal bile duct in 17%, and duodenal in 12%. For all 5-year survivors, the subsequent 5-year actuarial survival rate was 65%, with a median survival after achieving the 5-year landmark of 7.9 additional years. The subsequent 5-year survival by site of tumor origin was 55% for pancreatic, 66% for ampullary, 74% for bile duct, and 85% for duodenal cancer. For the age-matched population, the 5-year survival rate was 87% (P<.001 when compared with those with all periampullary cancers). CONCLUSIONS: While the 5-year survival rate for all patients with resected periampullary adenocarcinoma is only 23%, these data imply that attainment of the 5-year survival landmark carries with it an improved survival for the subsequent 5 years. While the survival rate was less than that of the age-matched population, 65% of 5-year survivors survived 5 more years, bringing them to the 10-year postresection landmark.

Pancreaticoduodenectomy in the very elderly.

It is estimated that by 2050, there will be a 300% increase in the elderly population (> or =65 years) and a corresponding increase in elderly patients presenting for surgical evaluation. Surgical decision-making in this population can be difficult because outcomes in the elderly are poorly defined. We reviewed 2698 consecutive pancreaticoduodenectomies (PDs) at our institution over a 35-year period (April 1970 through March 2005), with the last 1000 resections being done in the last 4 years. Data collected included surgical indication, mortality (defined as 30-day or in-hospital mortality), complications, and survival. Patients were divided by age into three groups (<80, 80-89, and > or =90 years) and evaluated using multiple logistic regression. Two hundred seven patients > or =80 years old underwent a PD (7.7% of 2698). Patients 80-89 years of age had a mortality rate of 4.1% (8 of 197) and a complication rate of 52.8% (99 of 197), whereas patients < or =79 years of age had a mortality of 1.7% and a complication rate of 41.6% (P < 0.05). There were no perioperative deaths among the 10 patients > or =90 years of age, and their complication rate was 50% (5 of 10). One-year survival for patients 80-89 years of age was 59.1%, and that for patients > or =90 years was 60%. Age was not an independent risk factor for perioperative mortality and morbidity following PD after adjusting for preoperative comorbidities. We demonstrate that PD can be safely performed in patients over 80 years of age and conclude that age alone should not be a contraindication to pancreatic resection. The advent of improved surgical outcomes and an aging population will likely result in a significant increase in the number of PDs performed in the next few decades.

1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience.

Pancreaticoduodenectomy (PD) with the possible addition of neoadjuvant or adjuvant therapy is the standard of care in the United States for adenocarcinoma originating in the pancreatic head, neck, and uncinate process. We reviewed 1423 patients who underwent a PD for a malignancy originating in the pancreas at our institution between 1970 and 2006. We examined 1175 PDs for ductal adenocarcinomas in greater detail. Eighteen different histological types of pancreatic cancer were identified; the most common diagnoses included ductal adenocarcinoma, neuroendocrine carcinoma, and IPMN with invasive cancer. Patients with ductal adenocarcinoma were analyzed in detail. The median age was 66 years, with patients in the present decade significantly older (68 years), on average, than patients in the three prior decades (e.g., 60 years in 1970, P = 0.02). The median tumor diameter was 3 cm; 42% of the resections had positive margins and 78% had positive lymph nodes. The perioperative morbidity was 38%. The median postoperative stay declined over time, from 16 days in the 1980s to 8 days in the 2000s (P < 0.001). The perioperative mortality declined from 30% in the 1970s to 1% in the 2000s (P < 0.001). The median survival for all patients with ductal adenocarcinoma was 18 months (1-year survival = 65 %, 2-year survival = 37%, 5-year survival = 18%). In a Cox proportional hazards model, pathological factors having a significant impact on survival included tumor diameter, resection margin status, lymph node status, and histologic grade. This is the largest single-institution experience with PD for pancreatic cancer. Patients who have cancers with favorable pathological features have a statistically significant improved long-term survival.

Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial.

Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy (PD) with encouraging results in both retrospective and prospective studies. We performed a prospective randomized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD. Two hundred thirty-eight patients were randomized to either receive a pancreatic stent (S) or no stent (NS), and stratified according to the texture of the pancreatic remnant (soft/normal versus hard). Four patients were excluded from the study; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed. Patients who randomized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis. In patients with a soft pancreas, 57 randomized to the S group and 56 randomized to the NS group. In patients with a hard pancreas, 58 randomized to the S group and 63 randomized to the NS group. The S and NS groups for the entire study population, as well as for the subgroup of high-risk patients with soft pancreata, were similar as regard to demographics, past medical history, preoperative symptoms, preoperative procedures, and intraoperative data. The pancreatic fistula rate for the entire study population was 9.4%. The fistula rates in the S and NS subgroups with hard pancreata were similar, at 1.7% and 4.8% (P = 0.4), respectively. The fistula rates in the S and NS subgroups with soft pancreata were also similar, at 21.1% and 10.7% (P = 0.1), respectively. A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation (e.g., anastomotic technique, anastomotic orientation, pancreatic duct size, and number of intra-abdominal drains placed). In patients with soft pancreata, 63% percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway (including two deaths), compared to 47% of the pancreatic fistulas in patients in the NS group (P = 0.3). Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas.

Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma--part 3: update on 5-year survival.

The study objective was to update the survival analysis at the 5-year mark of patients undergoing standard versus radical (extended) pancreaticoduodenectomy (PD) for periampullary adenocarcinoma (cancers of the pancreas, ampulla, common bile duct, and duodenum). A prospective randomized trial was performed (April 1996 through June 2001) comparing survival after pylorus-preserving PD resection (standard) to survival after PD with distal gastrectomy and retroperitoneal lymphadenectomy (radical). An interim report (Ann Surg 1999;229:613) and report after closing the trial (Ann Surg 2002;236:355) showed no differences in survival between the standard and radical groups. Two hundred ninety-nine patients were randomized to either the standard or radical group. Five patients were excluded from final analysis because final pathology failed to reveal adenocarcinoma. The 5-year survival of the two groups was evaluated. The median live patient follow-up is now 64 months (5.33 years). For all periampullary cancer patients, those undergoing standard resection had 1- and 5-year survival rates of 78% and 25%, respectively, compared with 76% and 31% (P = 0.57) for those patients in the radical group. For pancreatic adenocarcinoma patients, the 1- and 5-year survival rates in the standard group were 75% and 13%, respectively, compared with 73% and 29% in the radical group (P = 0.13). The increased morbidity rate, longer operative time, and similar survival for radical PD led us to conclude that pylorus-preserving PD without retroperitoneal lymphadenectomy should be the procedure of choice for most patients with resectable periampullary adenocarcinoma. While there is an intriguing trend toward improved survival in patients with pancreatic adenocarcinoma in the radical group, this trend may be largely accounted for by the higher incidence of microscopically margin positive resections in the standard resection group (21%) compared with a 5% incidence in the radical group (P = 0.002).

Enhanced trauma program commitment at a level I trauma center: effect on the process and outcome of care.

HYPOTHESIS: With advances in surgical care, the occurrences of major adverse outcomes have become a rare event. The effect of a surgical service can be more comprehensively evaluated by following the Donabedian model, looking at the triad of structure, process, and outcome. It is hypothesized that the implementation of a focused program commitment at a trauma center is associated with improvements in process of care and patient outcomes. DESIGN: Evaluation of prospectively collected information in a trauma registry for the 3-year periods immediately before (1995-1997) and after (1999-2001) the implementation (in 1998) of the full-time trauma service. SETTING: Level I university-affiliated trauma center. PATIENTS: Patients meeting criteria for major trauma. INTERVENTION: The implementation of a full-time trauma service, featuring 24-hour in-house attending coverage, dedicated trauma admitting unit, regular trauma core curriculum, regular multidisciplinary quality assurance meetings, and state designation for level I status. MAIN OUTCOME MEASURES: Process of care measures, including time in the emergency department (ED) and trauma "bypass" hours (ie, time spent in the trauma resuscitation area). Outcome measures, including lengths of stay, overall mortality and mortality, excluding ED deaths. RESULTS: The total number of patients with major trauma increased from 2240 (1995-1997) to 2513 (1999-2001). The average time in the ED for patients going to the operating room, intensive care unit, and observation wards all decreased significantly (84 vs 52 minutes, 197 vs 118 minutes, and 300 vs 140 minutes, respectively; all with P<.01). The number of hours that the trauma center was closed owing to ED overcrowding also decreased significantly, from 56 to 2.7 hours per month (P<.01). After excluding ED deaths, there was a trend on bivariate analyses toward lower overall mortality rates (4.5% vs 3.4%, P =.07) and mortality rates among patients with severe head injury (23.8% vs 17.2%, P =.07). On further analyses with multiple logistic regression, controlling for age, Injury Severity Score, Abbreviated Injury Score (for a head injury), and admission blood pressure, the later period is associated with a 31% decrease in overall odds of death (P =.047) and a 42% decrease in odds of death among patients with severe head injury (an Abbreviated Injury Score, >or=3; P =.03). CONCLUSION: The implementation of a full-time trauma service is associated with improved timeliness of triage and therapeutic interventions and improved patient outcomes.

Does fibrin glue sealant decrease the rate of pancreatic fistula after pancreaticoduodenectomy? Results of a prospective randomized trial.

Despite substantial improvements in perioperative mortality, complications, and specifically the development of a pancreatic fistula, remain a common occurrence after pancreaticoduodenectomy. It was the objective of this study to evaluate the role of fibrin glue sealant as an adjunct to decrease the rate of pancreatic fistula after pancreaticoduodenectomy. One hundred twenty-five patients were randomized after pancreaticoduodenal resection only if, in the opinion of the surgeon, the pancreaticojejunal anastomosis was at high risk for development of a pancreatic anastomotic leak. After completion of the pancreaticojejunal anastomosis, the patients were randomized to topical application of fibrin glue sealant to the surface of the anastomosis or no such application. The primary postoperative end points in this study were pancreatic fistula, total complications, death, and length of hospital stay. A total of 59 patients were randomized to the fibrin glue arm, whereas 66 patients were randomized to the control arm and did not receive fibrin glue application. The pancreatic fistula rate in the fibrin glue arm of the study was 26% vs. 30% in the control group (p = not significant [NS]). The mean length of postoperative stay for all patients randomized was similar (fibrin glue = 12.2 days, control = 13.6 days) and the mean length of stay for patients in whom pancreatic fistula developed was also not different (fibrin glue = 18.9 days, control = 21.7 days). There were no differences with respect to total complications or specific complications such as postoperative bleeding, infection, or delayed gastric emptying. These data demonstrate that the topical application of fibrin glue sealant to the surface of the pancreatic anastomosis in this patient population undergoing high-risk pancreaticojejunal anastomosis did not reduce the incidence of pancreatic fistula or total complications after pancreaticodudodenectomy. There seems to be no benefit regarding the use of this substance in this setting.

Standard vs. radical pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective, randomized trial evaluating quality of life in pancreaticoduodenectomy survivors.

This study was designed to assess the health-related quality of life (QOL) of patients who had been randomly assigned to either standard or radical pancreaticoduodenectomy for periampullary adenocarcinoma. Pancreaticoduodenectomy has been performed in increasing numbers for periampullary adenocarcinoma. The appropriate extent of resection (standard vs. radical [extended]) remains controversial, particularly as concerns survival benefit. Past reports comparing standard vs. radical resection have suggested that the more extensive resection is attended by negative functional outcomes (diarrhea and weight loss) and poorer QOL, diminishing the impact of any possible survival advantage of the radical resection. A prospective, randomized single-institution trial comparing standard pancreaticoduodenectomy (pylorus preservation preferred) to radical pancreaticoduodenectomy (including distal gastrectomy and retroperitoneal lymphadenectomy) evaluated 299 patients with periampullary adenocarcinoma between April 1996 and June 2001. A standard Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) QOL survey designed for hepatobiliary cancer was sent to 150 of these patients surviving pancreaticoduodenectomy. QOL and functional status were assessed via a series of subscale scores for physical, social, emotional, and functional well-being. A total of 105 QOL surveys (70%) were returned and analyzed, with 55 of the patients having been randomized to the standard group and 50 to the radical group. The patients were evaluated at a mean of 2.2 years after pancreaticoduodenectomy. The two groups were statistically similar with regard to multiple parameters including age at operation (64.6 years), race, intraoperative blood transfusions, pathologic diagnosis and staging, and perioperative complications. The radical group had a significantly higher percentage of men (66% vs. 44%; P = 0.02), a longer operative time (369 minutes vs. 327 minutes; P < 0.001), and a longer postoperative length of hospital stay (13.6 days vs. 10.1 days; P < 0.01). The FACT-Hep total QOL scores were similar between the standard and radical groups: 143.5 vs. 147.3, respectively. Additionally, the individual FACT-G subscale scores evaluating physical (22.1 vs. 23.3), social (24.5 vs. 24.4), emotional (19.2 vs. 19.6), and functional well-being (20.6 vs. 22.4) were comparable between the standard and radical groups. Subgroup analyses based on pathologic diagnosis (pancreatic, ampullary, distal bile duct, etc.) failed to reveal any differences in QOL assessment between the standard and radical pancreaticoduodenectomy groups. Finally, QOL measures were similar when comparing time since operation (<2 years' follow-up vs. >2 years' follow-up) and age (< or =65 years vs. >65 years). This is the largest report comparing QOL assessment in survivors of pancreaticoduodenectomy randomized between standard and radical resection. These data demonstrate no differences in long-term QOL between standard and radical resection. These results imply that no negative long-term QOL measures are associated with radical pancreaticoduodenectomy (as performed in this study) for periampullary adenocarcinoma.

Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital.

PURPOSE: To examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) in patients undergoing resection at Johns Hopkins Hospital (JHH; Baltimore, MD). PATIENTS AND METHODS: Between August 30, 1993, and February 28, 2005, a total of 908 patients underwent PD for PC at JHH. A prospective database was reviewed to determine which patients received fluorouracil (FU) -based CRT. Excluded patients had metastatic disease, died 60 or fewer days after PD, received preoperative therapy, an experimental vaccine, adjuvant chemotherapy or radiation alone. The final cohort includes 616 patients. RESULTS: The median follow-up was 17.8 months (interquartile range, 9.7 to 33.5 months). Overall median survival was 17.9 months (95% CI, 16.3 to 19.5 months). Groups were similar with respect to tumor size, nodal status, and margin status, but the CRT group was younger (P < .001), and less likely to present with a severe comorbid disease (P = .001). Patients with carcinomas larger than 3 cm (P = .001), grade 3 and 4 (P < .001), margin-positive resection (P = .001), and complications after surgery (P = .017) had poor long-term survival. Patients receiving CRT experienced an improved median (21.2 v 14.4 months; P < .001), 2-year (43.9% v 31.9%), and 5-year (20.1% v 15.4%) survival compared with no CRT. After controlling for high-risk features, CRT was still associated with improved survival (relative risk = 0.74; 95% CI, 0.62 to 0.89). CONCLUSION: These data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT. These data support the use of combined adjuvant CRT for PC.

Gallbladder cancer: the role of laparoscopy and radical resection.

OBJECTIVES: We assess how laparoscopy has altered the presentation of patients with gallbladder cancer and determine whether radical resection in patients with gallbladder cancer is beneficial. SUMMARY BACKGROUND DATA: The widespread adoption of laparoscopic cholecystectomy has led to an increased frequency of incidentally discovered gallbladder carcinoma. Little data exist to guide surgeons in the optimum management of patients with gallbladder cancer, particularly with respect to the potential advantages of radical resection. METHODS: Records of 107 patients with gallbladder cancer admitted to a tertiary academic medical center between 1995 and 2004 were reviewed. Gallbladder cancer was found incidentally in 53 patients (50%). Fifty-two of these patients underwent a routine laparoscopic cholecystectomy and were found to have gallbladder cancer intraoperatively or following the operation by subsequent pathologic evaluation of the specimen. Gallbladder cancer had been diagnosed preoperatively by radiology in the other 54 patients (50%). These patients did not undergo laparoscopic cholecystectomy and were explored electively. RESULTS: The median age at presentation was 67 years and 66% were female. Patients who were found to have gallbladder carcinoma incidentally at laparoscopic cholecystectomy had a significant increase in survival when compared with those who were admitted electively with a known diagnosis (P < 0.001). All patients who presented with a known diagnosis had stage II or greater disease, and 36% of these were stage IV carcinomas. However, 82% of those patients who were found incidentally were stage I or II. The overall 5-year survival for all patients was 15%; those discovered incidentally at laparoscopic cholecystectomy had a 5-year survival of 33%. This difference was significant among patients with stage II carcinomas. In the laparoscopic group, there was no difference in survival between the patients who were immediately converted to an open resection when identified to have gallbladder cancer intraoperatively (n = 6) and those who had a completed laparoscopic cholecystectomy and were re-explored at a later point when found to have gallbladder cancer by subsequent pathology (n = 33). There was a significant improvement in survival in 50 patients (47%) who underwent some form of radical resection (P < 0.001). Stage for stage comparison showed that this was significant in stage II disease. Patients who underwent hepatic resection along with lymphadenectomy and extra hepatic biliary resection had similar survival compared with those who had hepatic resection and lymphadenectomy alone. CONCLUSIONS: Laparoscopic cholecystectomy appears to have resulted in the earlier discovery of gallbladder cancer in some patients, resulting in increased probability of survival. Patients discovered with gallbladder carcinoma during a laparoscopic cholecystectomy do not have to be converted immediately to an open resection and should be referred to a tertiary care center for further exploration. Adjunctive radical surgical resection, either at the time of cholecystectomy or subsequently, increases survival significantly in early stage disease.

Periampullary and pancreatic incidentaloma: a single institution's experience with an increasingly common diagnosis.

BACKGROUND: While incidental masses in certain organs have received particular attention, periampullary and pancreatic incidentalomas (PIs) remain poorly characterized. METHODS: We reviewed 1944 consecutive pancreaticoduodenectomies (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients (6% of all PDs) presented with an incidental finding of a periampullary or pancreatic mass. The PI patients were analyzed and compared with the rest of the cohort (NI, nonincidentaloma group, n = 1826). RESULTS: Thirty-one percent of the PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P < 0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had little or no risk for malignant progression. The 3 most common diagnoses in the PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall complication rate (55% versus 43%, P = 0.02), due in part to a significantly increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001). Patients in the PI group with malignant disease had a superior long-term survival (median, 30 months, P = 0.01) compared with patients in the NI group with malignant disease (median, 21 months). CONCLUSIONS: Incidentally discovered periampullary and pancreatic masses comprise a substantial proportion of patients undergoing PD. Roughly three fourths of these lesions are malignant or premalignant, and amenable to curative resection. Resected malignant PIs have favorable pathologic features as compared with resected malignant NIs, and resection of these early lesions in asymptomatic individuals is associated with improved survival, compared with patients with symptomatic disease.

Surgical management of bile duct injuries sustained during laparoscopic cholecystectomy: perioperative results in 200 patients.

OBJECTIVE: A single institution retrospective analysis of 200 patients with major bile duct injuries was completed. Three patients died without surgery due to uncontrolled sepsis. One hundred seventy-five patients underwent surgical repair, with a 1.7% postoperative mortality and a complication rate of 42.9%. SUMMARY BACKGROUND DATA: The widespread application of laparoscopic cholecystectomy (LC) has led to a rise in the incidence of major bile duct injuries (BDI). Despite the frequency of these injuries and their complex management, the published literature contains few substantial reports regarding the perioperative management of BDI. METHODS: From January 1990 to April 2003, a prospective database of all patients with a BDI following LC was maintained. Patients' charts were retrospectively reviewed to analyze perioperative surgical management. RESULTS: Over 13 years, 200 patients were treated for a major BDI following LC. Patient demographics were notable for 150 women (75%) with a mean age of 45.5 years (median 44 years). One hundred eighty-eight sustained their BDI at an outside hospital. The mean interval from the time of BDI to referral was 29.1 weeks (median 3 weeks). One hundred nine patients (58%) were referred within 1 month of their injury for acute complications including bile leak, biloma, or jaundice. Twenty-five patients did not undergo a surgical repair at our institution. Three patients (1.5%) died after delayed referral before an attempt at repair due to uncontrolled sepsis. Twenty-two patients, having intact biliary-enteric continuity, underwent successful balloon dilatation of an anastomotic stricture. A total of 175 patients underwent definitive biliary reconstruction, including 172 hepaticojejunostomies (98%) and 3 end-to-end repairs. There were 3 deaths in the postoperative period (1.7%). Seventy-five patients (42.9%) sustained at least 1 postoperative complication. The most common complications were wound infection (8%), cholangitis (5.7%), and intraabdominal abscess/biloma (2.9%). Minor biliary stent complications occurred in 5.7% of patients. Early postoperative cholangiography revealed an anastomotic leak in 4.6% of patients and extravasation at the liver dome-stent exit site in 10.3% of patients. Postoperative interventions included percutaneous abscess drainage in 9 patients (5.1%) and new percutaneous transhepatic cholangiography and stent placement in 4 patients (2.3%). No patient required reoperation in the postoperative period. The mean postoperative length of stay was 9.5 days (median 9 days). The timing of operation (early, intermediate, delayed), presenting symptoms, and history of prior repair did not affect the incidence of the most common perioperative complications or length of postoperative hospital stay. CONCLUSIONS: This series represents the largest single institution experience reporting the perioperative management of BDI following LC. Although perioperative complications are frequent, nearly all can be managed nonoperatively. Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results.

Intraductal papillary mucinous neoplasms of the pancreas: an updated experience.

OBJECTIVE: To update the authors' experience with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND DATA: IPMNs are intraductal mucin-producing cystic neoplasms of the pancreas with clear malignant potential. Since the authors' 2001 report, the number of IPMNs resected at our institution has more than doubled, providing an opportunity to define the clinical features of this distinct neoplasm. METHODS: All patients undergoing pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and March 2003 were evaluated. Noninvasive IPMNs were classified as "adenoma," "borderline," or "carcinoma-in situ" (CIS) depending on the degree of dysplasia within the specimen. Invasive cancers were classified as tubular, colloid, mixed, or anaplastic types. Pathology was retrospectively reviewed to identify main-duct or branch-duct origin of the tumors. Long-term overall survival for patients having IPMNs with invasive cancer was compared with those patients having IPMNs without an invasive component. RESULTS: Between January 1987 and March 2003, inclusive, 136 pancreatic resections were performed for patients with IPMNs, with 78 resections performed since January 2001. The mean age of the patients was 66.8 +/- 1.1 years, with 57% being male and 89% white. Pancreaticoduodenectomy was performed in 71% of patients, total pancreatectomy in 15%, distal pancreatectomy in 12%, and central pancreatic resection in 2%. IPMNs without evidence of invasive cancer were identified in 62% (n = 84) of patients (17% adenoma, 28% borderline, or 55% CIS). The remaining 38% (n = 52) of patients had IPMNs with associated invasive cancer (60% tubular, 27% colloid, 7% mixed, and 6% anaplastic). The mean age of patients with IPMN adenoma was 63.2 years, 66.7 years for those with borderline/CIS IPMNs, and 68.1 years for those with invasive cancer (P = 0.08, adenomas vs. invasive cancer). In those patients with invasive cancers, 15% had invasive cancer at the final surgical margin, 23% had IPMN without invasive cancer at the margin, and 54% had lymph node metastases. Residual IPMN was identified at the neck or uncinate margin in 24% of patients with noninvasive IPMNs. The overall 5-year survival for patients having IPMNs without invasive cancer was 77% (several deaths secondary to metachronous invasive cancer), compared with 43% in those patients with an invasive component (P < 0.0001). There were no differences in survival when comparing adenomas, borderline neoplasms, and CIS. Similarly, there were no statistically significant differences in survival when comparing branch-duct, main-duct, and combined variants; however, the branch-duct variants were more often noninvasive. For those patients with invasive IPMNs, 2-year survival was 40% when margins were positive for invasive cancer or for IPMN without invasive cancer, and 60% when margins were tumor-free (P = 0.15). Those patients with colloid carcinomas (n = 14) had improved survival compared with those with tubular carcinomas (n = 31), with 5-year survival rates of 83% and 24%, respectively. IPMN recurrences and deaths from cancer occurred in patients with both invasive and noninvasive IPMNs at initial resection. CONCLUSIONS: IPMNs continue to be recognized with increasing frequency. Five-year survival for those patients following resection of IPMNs with invasive cancer (43%) is improved compared with those patients with resected pancreatic ductal adenocarcinoma in the absence of IPMN (averages 15%-25%). Survival following resection of IPMNs without invasive cancer (regardless of degree of dyplasia) is good, but recurrent disease in the residual pancreas suggests that long-term surveillance is critical. Based on the age at resection data, there appears to be a 5-year lag time from IPMN adenoma (63.2 years) to invasive cancer (68.1 years).

Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality.

OBJECTIVE: To evaluate, in a prospective, randomized single-institution trial, the end points of operative morbidity, operative mortality, and survival in patients undergoing standard versus radical (extended) pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Numerous retrospective reports and a few prospective randomized trials have suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection may improve survival for patients with pancreatic and other periampullary adenocarcinomas. METHODS: Between April 1996 and June 2001, 299 patients with periampullary adenocarcinoma were enrolled in a prospective, randomized single-institution trial. After intraoperative verification (by frozen section) of margin-negative resected periampullary adenocarcinoma, patients were randomized to either a standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the specimen) or a radical (extended) pancreaticoduodenectomy (standard resection plus distal gastrectomy and retroperitoneal lymphadenectomy). All pathology specimens were reviewed, fully categorized, and staged. The postoperative morbidity, mortality, and survival data were analyzed. RESULTS: Of the 299 patients randomized, 5 (1.7%) were subsequently excluded because their final pathology failed to reveal periampullary adenocarcinoma, leaving 294 patients for analysis (146 standard vs. 148 radical). The two groups were statistically similar with regard to age (median 67 years) and gender (54% male). All the patients in the radical group underwent distal gastric resection, while 86% of the patients in the standard group underwent pylorus preservation ( <.0001). The mean operative time in the radical group was 6.4 hours, compared to 5.9 hours in the standard group ( =.002). There were no significant differences between the two groups with respect to intraoperative blood loss, transfusion requirements (median zero units), location of primary tumor (57% pancreatic, 22% ampullary, 17% distal bile duct, 3% duodenal), mean tumor size (2.6 cm), positive lymph node status (74%), or positive margin status on final permanent section (10%). The mean total number of lymph nodes resected was significantly higher in the radical group. Of the 148 patients in the radical group, only 15% (n = 22) had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes, and none had retroperitoneal nodes as the only site of lymph node involvement. One patient in the radical group with negative pancreaticoduodenectomy specimen lymph nodes had a micrometastasis to one perigastric lymph node. There were six perioperative deaths (4%) in the standard group versus three perioperative deaths (2%) in the radical group ( = NS). The overall complication rates were 29% for the standard group versus 43% for the radical group ( =.01), with patients in the radical group having significantly higher rates of early delayed gastric emptying and pancreatic fistula and a significantly longer mean postoperative stay. With a mean patient follow-up of 24 months, there were no significant differences in 1-, 3-, or 5-year and median survival when comparing the standard and radical groups. CONCLUSIONS: Radical (extended) pancreaticoduodenectomy can be performed with similar mortality but some increased morbidity compared to standard pancreaticoduodenectomy. The data to date fail to indicate that a survival benefit is derived from the addition of a distal gastrectomy and retroperitoneal lymphadenectomy to a pylorus-preserving pancreaticoduodenectomy.

Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis.

OBJECTIVE: To compare the presentation and short-term results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis (LPSP) and pancreatic adenocarcinoma (PA) and to provide long-term follow-up on patients undergoing resection for LPSP. SUMMARY BACKGROUND DATA: LPSP is a rare form of chronic pancreatitis characterized by a mixed inflammatory infiltrate centered around pancreatic ducts and ductules, combined with obliterative phlebitis. Its presentation may mimic that of PA. METHODS: Among 1,648 patients undergoing pancreaticoduodenectomy at the authors' institution from January 1992 to May 2002, 37 with LPSP were identified. The demographics, clinical features, and short- and long-term outcomes of these patients were analyzed. Where applicable, comparisons were made to a consecutive group of 45 patients who underwent pancreaticoduodenectomy for PA from July 2001 to December 2001. RESULTS: Twenty-four percent (9/37) of the LPSP patients and none of the PA patients had a history of either atopic or autoimmune disease. The LPSP patients had a similar clinical presentation to the PA patients, but the LPSP patients were less likely to have a discrete pancreatic mass on CT and more likely to have CT findings suggesting a diffusely enlarged pancreas. The LPSP patients were also less likely to have a discrete pancreatic mass at operation, more likely to have a diffusely firm or hard gland, and more likely to have a difficult portal vein/superior mesenteric vein dissection when compared to the PA patients. Transfusion requirement, operative time, postoperative length of stay, and overall complication rate were similar between groups; however, the LPSP patients had a greater operative blood loss. The median length of follow-up for LPSP patients was 33 months. No patients had recurrent jaundice. One patient with LPSP had clinically evident recurrent pancreatitis. Among LPSP patients available for current telephone interview, 68% subjectively rated their quality of life as better, 18% reported no change, and 14% reported diminished quality of life compared to before surgery. CONCLUSION: LPSP mimics PA in clinical presentation, though CT findings of a diffusely enlarged pancreas without a discrete mass may suggest a diagnosis of LPSP. Nevertheless, differentiation from pancreatic neoplasia remains difficult. Patients undergoing pancreaticoduodenectomy for LPSP have durable relief of symptoms and a subjectively improved quality of life.