Faculty Bibliography

PURPOSE/OBJECTIVE:Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. METHODS AND MATERIALS/METHODS:Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. RESULTS:The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. CONCLUSION/CONCLUSIONS:Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.

OBJECTIVE:To identify pathologic features that may account for the favorable survival after resection of invasive pancreatic adenocarcinoma arising in the setting of intraductal papillary mucinous neoplasm (IPMN) compared with standard pancreatic ductal adenocarcinoma (PDA) in the absence of IPMN. SUMMARY BACKGROUND DATA/BACKGROUND:The 5-year survival after resection of IPMN-associated invasive adenocarcinoma is reported to be between 40% and 60%, which is superior to the 10-25%, typically cited after resection of standard PDA. It remains unclear whether this represents distinct biology or simply a tendency for earlier presentation of IPMN-associated invasive adenocarcinoma. METHODS:A single institution's prospective pancreatic resection database was retrospectively reviewed to identify patients with invasive pancreatic adenocarcinoma who underwent pancreatectomy with curative intent. Log rank and Cox regression analysis were used to identify factors associated with survival. RESULTS:From 1995 to 2006, 1260 consecutive patients were identified, 132 (10%) with IPMN-associated invasive adenocarcinoma and 1128 (90%) with standard PDA. Actuarial 5-year survival was 42% after resection for IPMN-associated versus 19% for standard PDA (P < 0.001). However, compared with standard PDA, invasive adenocarcinoma arising within an IPMN was associated with a lower incidence of (1) advanced T stage (T2-T4, 96% vs. 73%, P < 0.001); (2) regional lymph node metastasis (78% vs. 51%, P < 0.001); (3) poor tumor differentiation (44% vs. 26%, P < 0.001); (4) vascular invasion (54% vs. 33%, P < 0.001); (5) perineural invasion (92% vs. 63%, P < 0.001); and (6) microscopic margin involvement (28% vs. 14%, P < 0.001). Specifically, in the presence of any one of the aforementioned adverse pathologic characteristics, outcomes after resection for IPMN-associated and standard PDA were not significantly different. CONCLUSION/CONCLUSIONS:The favorable biologic behavior of IPMN-associated compared with standard PDA is based on its lower rate of advanced T stage, lymph node metastasis, high tumor grade, positive resection margin, perineural, and vascular invasion. In the presence of any one of the aforementioned adverse pathologic characteristics, however, survival outcomes after resection of IPMN-associated and after resection of standard pancreatic adenocarcinoma are similar.

BACKGROUND:Whether ampullary neoplasms are best surgically managed by pancreaticoduodenectomy versus local ampullectomy is controversial. We sought to examine the outcome of patients undergoing pancreaticoduodenectomy versus ampullectomy, as well as to identify factors predictive of lymph node metastasis in patients with ampullary neoplasms. METHODS:Between 1970 and 2007, 450 patients who underwent surgical resection of ampullary adenoma or adenocarcinoma were identified from a prospective, single-institution database. Data on clinicopathologic factors, morbidity, mortality, and survival were analyzed. RESULTS:The initial surgical procedure was pancreaticoduodenectomy in 96.7% patients and ampullectomy in 3.3%. Final diagnosis was invasive adenocarcinoma (77.1%) or adenoma (22.9%). Median tumor size was similar for adenomas associated with an adenocarcinoma (2.5 cm) versus adenomas without invasive cancer (2.9 cm; P=0.71). Morbidity was comparable with pancreaticoduodenectomy (52.2%) versus ampullectomy (33.3%; P=0.15), as was 30-day mortality (pancreaticoduodenectomy, 2.1% versus ampullectomy, 0%; P=0.6). Metastatic disease to regional lymph nodes was present in 54.5% patients with adenocarcinoma. Factors associated with presence of lymph node metastasis included tumor size > or = 1 cm (OR 2.1), poor histologicgrade (OR 4.8), perineural invasion (OR 3.0), microscopic vessel invasion (OR 6.6), and depth of invasion > pT1 (OR 4.3; all P<0.05). Specifically, risk of lymph node metastasis increased with T stage (T1, 28.0%; T2, 50.9%; T3, 71.7%; T4, 77.3%; P<0.001). CONCLUSION/CONCLUSIONS:When surgery is indicated, radical resection is required for early invasive adenocarcinoma of the ampulla of Vater, as lymph node metastases are present in nearly 30% of patients with T1 disease. Pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection.

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.