Taylor S. Riall

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.

One Thousand Consecutive Pancreaticoduodenectomies

Objective:To trace the evolution of pancreaticoduodenectomy from the decade of the 1960s through the first decade of the new Millenium, through the experience of one surgeon doing 1000 consecutive operations. Summary Background Data:A regional resection of the head of the pancreas was first performed successfully by Kausch in 1909. The operation was popularized by Whipple in 1935, who reported 3 pancreaticoduodenectomies. Because of a hospital mortality of approximately 25%, the operation was performed infrequently until the 1980s. From the 1980s on, experience with this complex alimentary tract operation increased, and high-volume centers developed. This resulted in a significant drop in hospital mortality and allowed institutions and individuals to gain large experiences. Methods:Between March 1969 and May 2003, 1000 consecutive pancreaticoduodenectomies were performed by a single surgeon. A retrospective review of a prospectively maintained database was performed to determine the management and outcome of these patients, as well as to document the evolution of this operative procedure over 5 decades. Results:The median operative time decreased significantly over the decades, being 8.8 hours in the 1970s and 5.5 hours during the 2000s. Postoperative length of stay dropped from a median of 17 days in the 1980s to 9 days in the 2000s. There were only 10 postoperative/hospital deaths, for a mortality of 1%. A total of 405 patients underwent pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Overall 5-year survival was 18%; for the lymph node-negative patients, it was 32%; and for node-negative, margin-negative patients, it was 41%. Conclusions:Pancreaticoduodenectomy has become a commonly performed operation in many tertiary care centers. Operative time, blood loss, and length of stay have dropped substantially. The operation has become safe, with a low hospital mortality. It has become an effective operation for pancreatic cancer in those patients in whom their tumor is margin negative and node negative.

Risk factors and outcomes in postpancreaticoduodenectomy pancreaticocutaneous fistula

A significant fraction of patients undergoing pancreaticoduodenectomy develop a postoperative pancreaticocutaneous fistula. To identify risk factors for this complication and to delineate its impact on patient outcomes, we conducted a retrospective review of 1891 patients undergoing pancreaticoduodenectomy between 1981 and 2002. Overall, 216 patients (11.4%) developed a postoperative pancreaticocutaneous fistula. In univariate analysis, gender, coronary disease, diabetes mellitus, operative times, blood loss, radical lymphadenectomy, gland texture, and specimen pathology correlated with fistula rates. In a multivariate model, however, only gland texture and coronary disease were statistically predictive. A soft gland was associated with a 22.6% fistula rate, a 20.4-fold increase in fistula risk over those patients with a medium or firm gland (95% confidence interval, 4.7–90.9). No patient with a firm gland developed a fistula. Although 30-day postoperative mortality was not different between those patients with and those without fistula (1.4% versus 1.5%), the mean length of stay was longer (26.0 days versus 13.2 days) and the rates of certain complications were increased in those patients with fistula. In this single-institution experience, pancreaticocutaneous fistula was most strongly predicted by pancreatic texture. Choice of anastomotic technique did not correlate with fistula rates. Pancreaticocutaneous fistula increases postoperative length of stay and morbidity but was not directly associated with increased postoperative mortality.

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 pyloruspreserving 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).

A Randomized Prospective Multicenter Trial of Pancreaticoduodenectomy With and Without Routine Intraperitoneal Drainage

Objective:To test by randomized prospective multicenter trial the hypothesis that pancreaticoduodenectomy (PD) without the use of intraperitoneal drainage does not increase the frequency or severity of complications. Background:Some surgeons have abandoned the use of drains placed during pancreas resection. Methods:We randomized 137 patients to PD with (n = 68, drain group) and without (n = 69, no-drain group) the use of intraperitoneal drainage and compared the safety of this approach and spectrum of complications between the 2 groups. Results:There were no differences between drain and no-drain cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, baseline quality of life, or operative technique. PD without intraperitoneal drainage was associated with an increase in the number of complications per patient [1 (0-2) vs 2 (1-4), P = 0.029]; an increase in the number of patients who had at least 1 ≥grade 2 complication [35 (52%) vs 47 (68%), P = 0.047]; and a higher average complication severity [2 (0-2) vs 2 (1-3), P = 0.027]. PD without intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess (10% vs 25%, P = 0.027), severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. The Data Safety Monitoring Board stopped the study early because of an increase in mortality from 3% to 12% in the patients undergoing PD without intraperitoneal drainage. Conclusions:This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

Overuse of Screening Colonoscopy in the Medicare Population

BACKGROUND All relevant authorities recommend an interval of 10 years between normal screening colonoscopies. We assessed the timing of repeated colonoscopies after a negative screening colonoscopy finding in a population-based sample of Medicare patients. METHODS A 5% national sample of Medicare enrollees from 2000 through 2008 was used to identify average-risk patients undergoing screening colonoscopy between 2001 and 2003. Colonoscopy was classified as a negative screening examination finding if no indication other than screening were in the claims and if no biopsy, fulguration, or polypectomy was performed. Time to repeated colonoscopy was calculated. RESULTS Among 24,071 Medicare patients who had a negative screening colonoscopy finding in 2001 through 2003, 46.2% underwent a repeated examination in fewer than 7 years. In 42.5% of these patients (23.5% of the overall sample), there was no clear indication for the early repeated examination. In patients aged 75 to 79 years or 80 years or older at the time of the initial negative screening colonoscopy result, 45.6% and 32.9%, respectively, received a repeated examination within 7 years. In multivariable analyses, male sex, more comorbidities, and colonoscopy by a high-volume colonoscopist or in an office setting were associated with higher rates of early repeated colonoscopy without clear indication, while those 80 years or older had a reduced risk. There were also marked geographic variations, from less than 5% in some health referral regions to greater than 50% in others. CONCLUSIONS A large proportion of Medicare patients who undergo screening colonoscopy do so more frequently than recommended. Current Medicare regulations intending to limit reimbursement for screening colonoscopy to every 10 years would not appear to be effective.

Pancreaticoduodenectomy in the very elderly

It is estimated that by 2050, there will be a 300% increase in the elderly population (=>65 years) and a cor-responding 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 in-cluded surgical indication, mortality (defined as 30-day or in-hospital mortality), complications, and sur-vival. Patients were divided by age into three groups (<80, 80 89, and =>90 years) and evaluated using multiple logistic regression. Two hundred seven patients =>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 =<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 =>90 years of age, and their com-plication rate was 50% (5 of 10). One-year survival for patients 80 89 years of age was 59.1%, and that for patients =>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 contrain-dication 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.

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.

672 patients with acinar cell carcinoma of the pancreas: a population-based comparison to pancreatic adenocarcinoma

BACKGROUND Acinar cell carcinoma (ACC) is a rare cancer of the pancreas accounting for approximately 1% of nonendocrine tumors. Because no large series of patients with ACC exist, our understanding of this disease comes mainly from small retrospective reports and anecdotal experience. OBJECTIVE Our goal was to evaluate a large population-based cohort of patients with ACC and compare their demographic factors and outcomes to those of patients with pancreatic adenocarcinoma (PA). METHODS Using the Surveillance, Epidemiology, and End Results (SEER) database (1988 to 2003), we identified all patients with ACC or PA. The demographic factors, tumor characteristics, resection status, and long-term survival were compared between the 2 groups. RESULTS A total of 672 patients with ACC and 58,526 with PA were identified. The mean age at the time of diagnosis was significantly lower for ACC than PA (56 years vs 70 years, P < .001). Compared with patients with PA, patients with ACC were more likely to be male (54% vs 48%, P = .007) and white (85% vs 81%, P = .03). Based on SEER clinical staging, patients with ACC were less likely to have unstaged disease (8% vs 18%). Of the 616 patients with staged ACC, 16% had localized disease, 26% had regional disease, and 58% had distant disease. In the 47,896 staged patients with PA, 10% had localized disease, 33% had regional disease, and 57% had distant disease (P < .0001 compared to ACC). Based on clinical extent of disease, 81% of patients with locoregional ACC and 70% of patients with locoregional PA were resectable. However, only 69% of ACC patients with locoregional disease and 27% of PA patients with locoregional disease underwent surgical resection. The overall 5-year survival was 42.8% for ACC (median, 47 months) and 3.8% for PA (median, 4 months, P < .0001). Patients with unresected ACC had a 5-year survival rate of 22% compared to 2% in patients with unresected PA (P < .0001). Surgical resection significantly improved survival. The 5-year survival was 72% in resected ACC and 16.3% in resected PA (P < .0001). Multivariate Cox proportional hazards regression model results suggested patients with ACC were less likely to die (hazard ratio = 0.241; 95% confidence interval, 0.22-0.27) than patients with PA after controlling for gender, race, stage, SEER region of diagnosis, and surgical resection status. CONCLUSIONS Consistent with anecdotal reports and previous retrospective studies, ACC is a more indolent disease than PA. Patients with ACC tend to present at a younger age, are more likely to have resectable disease, and are much more likely to undergo potentially curative resection. The long-term survival for patients with ACC is significantly better when compared to the long-term survival of patients with PA.