Farnell, Michael B.

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

AbstractBackground and ObjectivesConclusive evidence in favor of neoadjuvant therapy for those with non‐metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non‐metastatic PDAC.MethodsThe study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent‐to‐treat basis.ResultsIn the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001).ConclusionsThe strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non‐metastatic PDAC.

Purpose To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Patients and Methods We performed a retrospective review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT. Results Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio [RR] = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001). Conclusion This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.

AbstractTherapeutic endoscopy (TE) has provided a new means for treating peptic ulcer disease, prompting a reevaluation of surgery's role. The aim of this study was to determine if surgical therapy of bleeding duodenal ulcers has changed since the advent of TE. This retrospective review involved consecutive time periods during which TE was (1985–1990) and was not (1980–1984) widely available. Exclusion criteria were prior gastric surgery, nonpeptic conditions, and untreated ulcers. Inclusion standards were met by 252 patients (180 men, 72 women) whose mean age was 67 years. Patients were grouped by the initial therapeutic intervention. Groups were similar in age, medical condition (mean APACHE II score 16), and morbidity. Seventy‐five patients had surgery alone during 1980–1984 and 38 during 1985–1990. TE was initially performed on 134 patients during 1985–1990. Bleeding (n=30) and perforation (n=1) prompted emergent operation in 23% of cases following TE. Thus 69 (38+31) patients underwent surgery between 1985 and 1990. Preprocedure transfusions averaged 4.1 units in the endoscopic group and 8.2 units in the operative groups (p<0.0001). Disagreement existed between the endoscopic and surgical descriptions of ulcer location in 53% of cases. Emergent surgery was required in 45% of hemodynamically unstable patients versus 14% of stable patients who initially underwent TE (p<0.0001). Sixty‐one percent of incompletely visualized TE‐treated lesions required operation, and 18% of well visualized ulcers underwent operation (p<0.0001). Hospital mortality was similar (8% versus 16%) in the endoscopic and operated groups (p=0.7). Mean follow‐up was 540 days. The number of operations performed for bleeding duodenal ulcer did not change significantly during the TE era, and a significant subset (23%) of endoscopically treated patients required surgical therapy. TE failure was portended by hemodynamic instability or incomplete endoscopic visualization.

Abstract.Although pancreatectomy is still performed in a few patients with pancreatic cancer, and nearly all patients who develop pancreatic cancer eventually die of their disease, significant improvements have been made recently. Pancreatectomy is now safer, with major morbidity (hemorrhage, pancreatic anastomotic leak, intraabdominal sepsis) occurring in only about 20% and operative mortality of less than 5%. Two (seemingly subtle) issues cannot be overemphasized when someone carefully studies the literature: (1) There is a crucial difference between actuarial and actual survival, with the former generally being higher whereas the latter is true; and (2) careful re‐review of pathologic specimens (especially in long‐term survivors) initially diagnosed as pancreatic cancer, preferably by an independent pathologist before publishing long‐term results is essential. (Erroneous inclusion of patients with nonductal carcinoma substantially and artificially increases survival.) After curative resection, 5‐year actual survival is realistically about 10% with median survivals of 12 to 18 months. In certain subgroups with favorable pathologic characteristics (neoplasms < 2 cm without nodal or perineural invasion) the prognosis appears to be significantly better, with the 5‐year survival about 20%. The recent improvements in postoperative morbidity and mortality and long‐term outcome (resulting also in decreased cost of care of such patients) have occurred typically in centers with an invested interest in and proven record with pancreatic surgery. Further improvements in survival should be sought at the areas of earlier diagnosis and novel treatments designed to prevent locoregional recurrences; the role of extended resections must be determined by prospective, randomized trials.