Faculty Bibliography

BACKGROUND:No data on incidence, management, or natural history of chyle leaks following pancreatic resection have been published. We sought to identify possible risk factors associated with chyle leaks following pancreatic resection, as well as determine the natural history of this rare complication. METHODS:Between 1993 and 2008, 3,532 patients underwent pancreatic resection at a single institution. Data on demographics, operative details, primary tumor status, and chyle leak were collected. To identify risk factors associated with chyle leak, a matched 3:1 paired analysis was performed. RESULTS:Of 3,532 patients undergoing pancreatic resection, 47 (1.3%) developed a chyle leak (n = 34, contained chyle leak versus n = 13, diffuse chylous ascites). Chyle leak was identified at median 5 days following surgery. Median drain triglyceride levels were 592 ng/dl. After matching on tumor size, disease etiology, and resection type, the number of lymph nodes harvested and history of concomitant vascular resection predicted higher risk of chyle leak (both P < 0.05). Total parenteral nutrition (TPN) was required in more patients with chylous ascites (92.3%) than those with chyle leaks (44.1%) (P = 0.003). The median time to resolution was shorter for contained chyle leaks (13 days) versus chylous ascites (36 days) (P < 0.001). Patients with chylous ascites tended to have shorter overall survival (3-year, 18.8%) versus patients with no chyle leak (3-year, 46.9%) (P = 0.12). In contrast, patients with a contained chyle leak had a similar survival as patients with no chyle leak (3-year, 53.4% versus 46.9%, respectively) (P = 0.32). CONCLUSION/CONCLUSIONS:Chyle leak was a rare (1.3%) complication following pancreatic resection that was associated with number of lymph nodes harvested and concomitant vascular resection. In general, chyle leaks were successfully managed with TPN with no adverse impact on outcome. Patients with chylous ascites, however, had a more protracted clinical course and tended to have a worse long-term survival.

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/CONCLUSIONS:Long-term survival can be achieved in patients undergoing resection of isolated metastases to the pancreas.

BACKGROUND:The incidence of right-sided colon cancers has been increasing in recent years. It is unclear whether patient prognosis varies by tumor location. In this study, we have compared the survival of right-and left-sided colon cancers in a longitudinal population-based database. METHODS:A retrospective survival analysis was performed using the Surveillance, Epidemiology, and End Results Program (SEER) database between 1988 and 2003 on subjects who underwent surgical resection for the a primary diagnosis of pathologically confirmed invasive colon adenocarcinoma. Cox proportional hazard regression analysis was used to assess long-term survival outcomes comparing right-sided (cecum to transverse colon, excluding appendix) versus left-sided (splenic flexure to sigmoid, excluding rectum) colon cancers. RESULTS:A total of 77,978 subjects were identified with adenocarcinoma of the colon. Overall median survival was 83 months. Median survival for right-sided cancers was 78 vs. 89 months for left-sided cancers (P < .001). By Cox proportional hazard regression analysis, controlling for statistically significant confounders, including age, sex, race, marital status, tumor stage, tumor size, histologic grade, number of lymph nodes examined, and year of diagnosis, right-sided colon cancers were associated with a 5% increased mortality risk compared with left-sided colon cancers (hazard ratio, 1.04; 95% confidence interval, 1.02-1.07). These findings were consistent across subsets of subjects. CONCLUSION/CONCLUSIONS:On the basis of analysis of information from the SEER database, we found that right-sided colon cancers have a worse prognosis than left-sided colon cancers. The reason for this remains unclear but may be due to biological and/or environmental factors and may have particular bearing, given the rising incidence of right-sided colon cancers.

PURPOSE/OBJECTIVE:To evaluate the impact of a multidisciplinary clinic on the clinical care recommendations of patients with pancreatic cancer compared with the recommendations the patients received prior to review by the multidisciplinary tumor board. METHODS:The records of 203 consecutive patients referred to the Johns Hopkins pancreatic multidisciplinary clinic were prospectively collected from November 2006 to October 2007. Cross-sectional imaging, pathology, and medical history were evaluated by a panel of medical/radiation oncologists, surgical oncologists, pathologists, diagnostic radiologists, and geneticists. Alterations in treatment recommendations between the outside institution and the multidisciplinary clinic were recorded and compared. RESULTS:On presentation, the outside computed tomography (CT) report described locally advanced/unresectable disease (34.9%), metastatic disease (17.7%), and locally advanced disease with metastasis (1.1%). On review of submitted imaging and imaging performed at Hopkins, 38 out of 203 (18.7%) patients had a change in the status of their clinical stage. Review of the histological slides by dedicated pancreatic pathologists resulted in changes in the interpretation for 7 of 203 patients (3.4%). Overall, 48 out of 203 (23.6%) patients had a change in their recommended management based on clinical review of their case by the multidisciplinary tumor board. Enrollment into the National Familial Pancreas Tumor Registry increased from 52 out of 106 (49.2%) patients in 2005 to 158 out of 203 (77.8%) with initiation of the multidisciplinary clinic. CONCLUSION/CONCLUSIONS:The single-day pancreatic multidisciplinary clinic provided a comprehensive and coordinated evaluation of patients that led to changes in therapeutic recommendations in close to one-quarter of patients.

PURPOSE/OBJECTIVE: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/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/CONCLUSIONS: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.

INTRODUCTION/BACKGROUND: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/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/CONCLUSIONS: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.

BACKGROUND:The reported incidence of choledochal cyst (CC) disease varies greatly based on geography. Most large series on CC originate from East Asia. So our understanding of the presentation and natural history of CC disease in western societies is less well characterized. Recognition and surgical treatment are important because of the significant longterm risks of developing cholangiocarcinoma. We report here the largest single-institution western experience with CC disease. STUDY DESIGN/METHODS:Ninety-two patients with CC disease who were seen at our institution between 1976 and 2006 were included in this study. Potential differences between children and adults (defined as 16 years old or older) were specifically evaluated. RESULTS:There were 19 children and 73 adults; 90% were girls/women with type I cysts. Adults were more likely to present with abdominal pain (97% versus 63%, p < 0.001), and children were more likely to present with jaundice (71% versus 25%, p=0.001). Surgical management most commonly involved cyst excision and Roux-en-Y hepaticojejunostomy reconstruction. Four adults (three with cholangiocarcinoma and one with gall bladder cancer) and one child (with embryonal rhabdomyosarcoma) had malignancies associated with their CC at the time of excision. Two patients (with type IV and type V disease) developed cholangiocarcinoma after surgical management. Another patient died of pancreatic adenocarcinoma 21 years after excision of her type I cyst. There was no operative or hospital mortality, and no patient who underwent complete cyst excision developed cholangiocarcinoma during a mean followup of 10 years. CONCLUSIONS:Western CC disease has a similar demographic profile as that seen in Asia. CCs are more frequently found in adults and girls/women and are associated with a longterm risk of developing cholangiocarcinoma. Presentation differs between adults and children. After complete cyst excision, no patients developed cholangiocarcinoma.

BACKGROUND:Based on data from other malignancies, the number of lymph nodes evaluated and the ratio of metastatic to examined lymph nodes (LNR) may be important predictors of survival. LNR has never been investigated in a large population-based study of patients with pancreatic adenocarcinoma. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 4005 patients who underwent resection for pancreatic adenocarcinoma from 1988 to 2003. The effect of total lymph node count and LNR on survival was examined using univariate and multivariate analyses. RESULTS:The median number of lymph nodes examined was seven; 390 (10.1%) patients had no lymph nodes examined. Of those patients who had at least one lymph node examined, 1507 (43.3%) had no lymph node metastases (N0) and 1971 (56.7%) had metastatic nodal disease (N1). Overall median survival was 13 months, and 5-year survival was 6.8%. N1 disease was associated with a worse 5-year survival compared with N0 disease (4.3 vs 11.3%, respectively, P < .001). Patients with N0 disease could be further stratified based on the number of lymph nodes evaluated (median survival: 1-11 nodes, 16 months vs 12 or more nodes, 23 months; P < .001). For N1 patients, LNR was one of the most powerful factors associated with survival (LNR > 0-0.2, 15 months; LNR > 0.2-0.4, 12 months; LNR > 0.4, 10 months) (P < .001). CONCLUSIONS:Most patients have an inadequate number of lymph nodes evaluated following pancreatic surgery. N0 patients who have fewer than 12 lymph nodes examined may be understaged. In patients with N1 disease, LNR may better substratify patients with regard to prognosis.