Faculty Bibliography

PURPOSE/OBJECTIVE:Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. METHODS AND MATERIALS/METHODS:Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes, including median survival, overall survival, and complication rates were assessed for both groups. RESULTS:Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-oclusive disease or graft failure/leakage. CONCLUSION/CONCLUSIONS:In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.

Pancreatic adenosquamous carcinoma is a rare morphological variant of pancreatic adenocarcinoma with an especially poor prognosis. The purpose of this study is to identify clinicopathologic features associated with prognosis, assess whether the percentage of squamous differentiation in pancreatic adenosquamous carcinoma is associated with an inferior prognosis, and examine the impact of adjuvant chemoradiation therapy on overall survival. Forty-five (1.2%) of 3651 patients who underwent pancreatic resection at the Johns Hopkins Hospital, Baltimore, MD, between 1986 and 2007 were identified with adenocarcinoma of the pancreas with any squamous differentiation. All pathologic specimens were re-reviewed. Statistical analyses were performed on the 38 patients amenable to adjuvant chemoradiation therapy for whom clinical outcome data could be obtained. Median age was 68 years (61% male). Sixty-one percent underwent pancreaticoduodenectomy. Median tumor size was 5.0 cm. Seventy-six percent of carcinomas were node positive, 37% were margin-positive resections, and 68% had 30% or more squamous differentiation. Median overall survival of the pancreatic adenosquamous carcinoma cohort was 10.9 months (range, 2.1-140.6 months; 95% confidence interval, 8.2-12.5 months). Adjuvant chemoradiation therapy was associated with superior overall survival in patients with pancreatic adenosquamous carcinoma (P = .005). Adjuvant chemoradiation therapy was associated with improved survival in patients with tumors 3 cm or larger and vascular or perineural invasion (P = .02, .03, .02, respectively). The proportion of squamous differentiation was not associated with median overall survival (< 30% versus > or = 30%, P = .82). Survival after pancreatic resection of pancreatic adenosquamous carcinoma is poor. Treatment with adjuvant chemoradiation therapy is associated with improved survival. The proportion of squamous differentiation in resected pancreatic adenosquamous carcinoma specimens does not appear to impact overall survival.

BACKGROUND:Multiple reports have demonstrated pancreatic cancer patients undergoing surgery have superior outcomes at high-volume hospitals. This study noted trends in access to high-volume centers for pancreatic resection and identified gaps in improving access. STUDY DESIGN/METHODS:We performed a retrospective analysis of the Nationwide Inpatient Sample (NIS 2000 to 2005) linked to the Area Resource File (ARF). Inclusion criteria were patients with primary diagnosis of pancreatic cancer who received pancreatic resection. The primary outcomes variable was treatment at high-volume hospitals (average annual case volume greater than 20). Independent variables included age, gender, race, Charlson Comorbidity Index score, insurance status, calendar year, and region, obtained from the Nationwide Inpatient Sample; community poverty level and density of all physicians, gastroenterologists, surgeons, and radiation oncologists were data obtained from the Area Resource File. RESULTS:A total of 8,370 patients were identified. A minority (38.51%) were referred to high-volume hospitals. A significant increase in overall referral and odds of referral to a high-volume center was observed over time (22.2% in 2000 to 44.4% in 2005). Patients referred to high-volume centers were younger (61.9 versus 63.2 years, p < 0.001) and more likely to be Caucasian (81.7% versus 73.6%, p < 0.001). Patients greater than 85 years old, African Americans, Hispanics, and Asians were less likely to be referred, relative to their younger, Caucasian counterparts (p < 0.01). The overall trend toward improved referral over time was driven by improved referral among Caucasians. In multivariate analysis, access to high-volume centers was associated with calendar year, patient age, and race. In addition, increase in density of gastroenterologists or radiation oncologists in the population was also associated with higher likelihood of referral. CONCLUSIONS:This study demonstrated that less than half of pancreatic cancer patients are being referred to high-volume centers. Unlike referral in Caucasians, improvement in referral for minorities has not occurred.

Brunner's gland hamartomas (BGH) are uncommon benign tumors of the duodenum forming mature Brunner's glands. We report here an unusual case of a giant BGH that was not amenable to endoscopic or surgical local resection thus requiring a pancreaticoduodenectomy for extirpation. The relevant literature is discussed.

BACKGROUND AND PURPOSE/OBJECTIVE:To examine the role of adjuvant chemoradiation (CRT) in patients with resected ampullary adenocarcinoma. MATERIALS AND METHODS/METHODS:The records of patients who underwent curative surgery for ampullary adenocarcinoma at a single institution between 1992 and 2007 were reviewed. Final analysis included 111 patients, 45% of which also received adjuvant CRT. RESULTS:Median overall survival (OS) was 36.2 months for all patients. Adverse prognostic factors for OS included T stage (T3/4 vs. T1/T2, p=0.046), node status (positive vs. negative, p<0.001), and histological grade (grade 3 vs. 1/2, p=0.09). Patients receiving CRT were more likely to have advanced T-stage (p=0.001), node positivity (p<0.001), and poor histologic grade (p=0.015). Patients who received CRT were also significantly younger (p=0.001). On univariate analysis, adjuvant CRT failed to result in a significant difference in survival when compared to surgery alone (median OS: 33.4 vs. 36.2 months, p=0.969). Patients with node-positive resections who underwent CRT had a non-significant improvement in survival (median OS: 21.6 vs. 13.0 months, p=0.092). Thirty-three percent of patients developed distant metastasis. Common sites of distant metastasis included liver (23%) and peritoneum (7%). CONCLUSIONS:Adjuvant chemoradiation following curative resection for ampullary adenocarcinoma did not lead to a statistically significant benefit in overall survival. A significant proportion of patients still developed distant metastatic disease suggesting a need for more effective systemic adjuvant therapy.

OBJECTIVE:To analyze relative perioperative and long-term outcomes of patients undergoing total pancreatectomy versus pancreaticoduodenectomy. BACKGROUND:The role of total pancreatectomy has historically been limited due to concerns over increased morbidity, mortality, and perceived worse long-term outcome. METHODS:Between 1970 and 2007, patients who underwent total pancreatectomy (n = 100) or pancreaticoduodenectomy (n = 1286) for adenocarcinoma were identified. Clinicopathologic, morbidity, and survival data were collected and analyzed. RESULTS:Total pancreatectomy patients had larger median tumor size (4 cm vs. 3 cm; P < 0.001) but similar rates of vascular (50.0% vs. 54.7%) and perineural invasion (90.7% vs. 91.8%) (total pancreatectomy vs. pancreaticoduodenectomy, respectively, both P > 0.05). A similar proportion of total pancreatectomy (74.7%) and pancreaticoduodenectomy (78.3%) patients had N1 disease (P = 0.45). Total pancreatectomy patients had more lymph nodes harvested (27 vs. 16) and were less likely to have positive resection margins (22.2% vs. 43.7%) (total pancreatectomy vs. pancreaticoduodenectomy, respectively, both P < 0.0001). Total pancreatectomy was increasingly used over time (1970-1989, n = 10, 1990-1999, n = 37, 2000-2007, n = 53). Total pancreatectomy was associated with higher 30-day mortality compared with pancreaticoduodenectomy (8.0% vs. 1.5%, respectively; P = 0.0007). However, total pancreatectomy operative mortality decreased over time (1970-1989, 40%; 1990-1999, 8%; 2000-2007, 2%; P = 0.0002). While operative morbidity was higher following total pancreatectomy (69.0% vs. 38.6% for pancreaticoduodenectomy; P < 0.0001), most complications were minor (Clavien Grade 1-2) (59%). Total pancreatectomy and pancreaticoduodenectomy patients had comparable 5-year survival (18.9% vs. 18.5%, respectively, P = 0.32). CONCLUSIONS:Total pancreatectomy perioperative mortality dramatically decreased over time. Long-term survival following total pancreatectomy versus pancreaticoduodenectomy was equivalent. Total pancreatectomy should be performed when oncologically appropriate.

INTRODUCTION/BACKGROUND:Pancreatic leak (PL) remains a major cause of postoperative morbidity in patients undergoing pancreatic resection. We sought to evaluate the incidence of and identify risk factors for the development of PL in patients undergoing distal pancreatectomy (DP) at a single high-volume institution. METHODS:All patients who underwent primary open DP (excluding completion pancreatectomy and debridement) between January 1, 1984 and July 1, 2006 were identified, and their medical records were reviewed. chi and multivariable logistic regression analyses were performed to identify risk factors for PL. RESULTS:In a cohort of 704 patients undergoing primary DP, the indications for DP were benign pancreatic neoplasm (34%), malignant pancreatic neoplasm (31%), other neoplasm (15%), chronic pancreatitis (14%), pseudocyst (3%), and trauma (3%). The pancreatic remnant was sutured alone in 83%, stapled alone in 5%, and both stapled and sutured in 9% of cases. Ligation of the pancreatic duct was performed in 22% of cases. Perioperative mortality was <1%, but overall morbidity was 33%, most commonly PL (12% clinically significant, 21% biochemical). Multivariable logistic regression analysis revealed that neither the method of closure of the pancreatic remnant (P = 0.41) nor ligation of the pancreatic duct (P > 0.05) affected the risk of clinically significant PL. CONCLUSIONS:This largest reported series of DP demonstrates that this procedure can be performed with low mortality but still carries a substantial risk of morbidity, particularly PL. In contrast to some previous studies, this analysis found that surgical management of the pancreatic remnant has no effect on the incidence of clinically significant PL.

PURPOSE/OBJECTIVE:Recently, the majority of protein coding genes were sequenced in a collection of pancreatic cancers, providing an unprecedented opportunity to identify genetic markers of prognosis for patients with adenocarcinoma of the pancreas. EXPERIMENTAL DESIGN/METHODS:We previously sequenced more than 750 million base pairs of DNA from 23,219 transcripts in a series of 24 adenocarcinomas of the pancreas. In addition, 39 genes that were mutated in more than one of these 24 cancers were sequenced in a separate panel of 90 well-characterized adenocarcinomas of the pancreas. Of these 114 patients, 89 underwent pancreaticoduodenectomy, and the somatic mutations in these cancers were correlated with patient outcome. RESULTS:When adjusted for age, lymph node status, margin status, and tumor size, SMAD4 gene inactivation was significantly associated with shorter overall survival (hazard ratio, 1.92; 95% confidence interval, 1.20-3.05; P = 0.006). Patients with SMAD4 gene inactivation survived a median of 11.5 months, compared with 14.2 months for patients without SMAD4 inactivation. By contrast, mutations in CDKN2A or TP53 or the presence of multiple (> or =4) mutations or homozygous deletions among the 39 most frequently mutated genes were not associated with survival. CONCLUSIONS:SMAD4 gene inactivation is associated with poorer prognosis in patients with surgically resected adenocarcinoma of the pancreas.