Faculty Bibliography

INTRODUCTION/BACKGROUND:National Comprehensive Cancer Network (NCCN) guidelines recommend hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA). We sought to evaluate compliance with these recommendations and to assess trends in the management and survival of patients with GBA. METHODS:Using Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data, we identified 2,955 patients with GBA who underwent cancer-directed surgery from 1991 to 2005. We assessed clinicopathologic data, trends in surgical management, and survival. RESULTS:From 1991 to 2005, preoperative evaluation included CT (62%), MRI (6%), and PET (2%). Only 383 (13%) patients underwent radical resection/hepatectomy with a temporal increase over the study period (1991-1995, 12%; 1996-1999, 10%; 2000-2002, 12.0%; 2003-2005, 16%; P < 0.001). For patients undergoing radical resection/hepatectomy, LND ≥ 3 nodes was performed in 96 (3%) patients. Among patients who had LND, 47% had nodal metastasis. The overall 1-, 3-, and 5-year survival was 56%, 30%, and 21%. On multivariate analysis, radical resection/hepatectomy (hazard ratio (HR) = 0.71) and LND ≥ 3 nodes (HR = 0.56) were independently associated with increased survival. There was no significant improvement in survival over time (P = 0.60). CONCLUSIONS:Compliance with NCCN guidelines for GBA remains poor. Survival of patients with surgically managed GBA has not improved over time.

BACKGROUND:Precise localization of small pancreatic tumors during laparoscopic distal pancreatectomy (LDP) can be difficult because of decreased tactile ability of laparoscopy and the homogeneous appearance of the pancreas and surrounding retroperitoneal fat. Precise localization of the lesion is critical to achieving adequate margins of resection and preserving healthy pancreatic tissue. EUS-guided fine-needle tattooing (EUS-FNT) of a pancreatic lesion before LDP has been described in single case reports, but no large series have reported its effectiveness in patients undergoing LDP. OBJECTIVE:To assess the feasibility, safety, and efficacy of EUS-FNT in consecutive patients undergoing LDP. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary-care referral hospital. PATIENTS/METHODS:This study involved 30 consecutive patients who underwent LDP from 2008 to 2010. Thirteen had EUS-FNT followed by LDP, and 17 had LDP alone. INTERVENTIONS/METHODS:LDP or EUS-FNT with a sterile carbon-particle tattoo followed by LDP. MAIN OUTCOME MEASUREMENTS/METHODS:The following features were examined: the technical success and complication rates of EUS-FNT, visibility of the tattoo at the time of laparoscopy, durability of the tattoo, and pathologic absence of tumor at the resection margin. RESULTS:The final pathology of pancreatic lesions of patients who had EUS-FNT was similar to those who had LDP alone. The median resected tumor size was significantly larger for the LDP-alone patients (median 4.0 cm vs 1.3 cm; P = .03). Thirty-one percent (4/13) of lesions in the EUS-FNT group were not visualized by prior preoperative pancreatic protocol CT. EUS-FNT was feasible in all 13 patients at laparoscopy, with R0 resection and negative final pathology margins in all cases. The tattoo was visible in all 13 EUS-FNT cases, with mean time from EUS-FNT to surgery of 20.3 days (range, 3-69 days). There were no significant complications associated with EUS-FNT. LIMITATIONS/CONCLUSIONS:Small, retrospective, single-center study. CONCLUSIONS:Preoperative EUS-FNT of lesions was technically feasible and safe, and it assisted in the localization of lesions in patients before LDP. The carbon particle tattoo was durable and visible in all cases.

BACKGROUND:Erlotinib is approved for the treatment of advanced pancreas cancer. We conducted a prospective trial to determine the safety profile and recommended phase 2 dose of erlotinib and capecitabine given concurrently with intensity-modulated radiation therapy (IMRT) in resected pancreatic cancer patients. The pharmacokinetic profile of this combination was also evaluated. METHODS:Patients with resected pancreatic adenocarcinoma received erlotinib and capecitabine concurrently with IMRT delivered at 1.8 Gy daily in 28 fractions (total = 50.4 Gy). The starting dose level (DL 1) was erlotinib 150mgdaily and capecitabine 800 mg/m(2) twice daily without interruption. The next lower dose level (DL -1) was erlotinib 100 mg daily and capecitabine 800 mg/m(2) twice daily (Monday to Friday). Plasma samples were obtained for pharmacokinetic analysis. RESULTS:Thirteen patients were enrolled in total. At DL 1, six of the seven treated patients were evaluable for toxicities. Four completed planned treatment, but all required treatment interruption or dose reduction. The dose-limiting toxicities were neutropenia, diarrhea, and rash. Six patients were subsequently enrolled to and completed planned treatment in DL-1. Themost common toxicities were fatigue, elevated liver enzymes, and anorexia. The pharmacokinetic parameters of erlotinib and OSI-420 were not significantly different in the presence or absence of capecitabine and were consistent with historical controls. CONCLUSIONS:When administered concurrently with IMRT, erlotinib 100 mg daily and capecitabine 800 mg/m(2) twice daily (Monday to Friday) can be administered safely in resected pancreas cancer patients, and is the recommended regimen for efficacy studies using this regimen.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Many surgeons perceive total pancreatectomy (TP) for pancreatic adenocarcinoma to be associated with inferior outcomes compared to partial pancreatectomy (PP), such as pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). We sought to analyze peri-operative mortality and long-term survival following TP versus PP for pancreatic adenocarcinoma. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with resected pancreatic adenocarcinoma (1998-2004). Survival after TP versus PP was compared by tumor location. RESULTS:Of 3280 patients with resected pancreatic head tumors, 292 underwent TP, and 2988 PD. One-month mortality was 9.0% for TP and 6.5% for PD (P = 0.11). Of 315 patients with resected body/tail tumors, 32 underwent TP, and 283 DP. One-month mortality was 9.3% for TP and 3.9% for DP (P = 0.17). Of 426 patients with resected tumors in unspecified pancreatic locations, 52 underwent TP, and 374 PP. One-month mortality was 5.8% for TP and 6.5% for PP (P = 0.87). Survival analyses demonstrated no difference between TP and PP (hazard ratio (HR) 1.06, P = 0.49 for head; HR 0.84, P = 0.51 for body/tail; HR 1.06, P = 0.79 for unspecified locations). CONCLUSIONS:Peri-operative mortality and long-term survival are similar following TP versus PP for pancreatic adenocarcinoma, supporting the use of TP when oncologically appropriate.

BACKGROUND:There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy. METHODS AND MATERIALS/METHODS:Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available. RESULTS:At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic lymph nodes (HR 1.89, both p < 0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all p < 0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR >or=0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%; p < 0.05). CONCLUSIONS:Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes.

Metastasectomy with curative intent has become standard practice for the management of some malignancies. Resection of isolated metastatic colorectal cancer, gastrointestinal stromal tumours, neuroendocrine cancers, renal-cell cancer and sarcoma is associated with longer survival or even cure. The strongest evidence in favour of metastasectomy exists for colorectal cancer, in which resection of limited metastatic disease in some patients is associated with 5-year survival rates of more than 50%.(1-3) High incidence of the disease, predictable tumour biology, and development of successful chemotherapies have encouraged metastasectomy. Furthermore, improved safety of complex surgeries over the past several decades has lowered the threshold for more aggressive surgical intervention. Most literature on metastasectomy pertains to the resection of disease involving the liver, lung, and brain. However, metastasectomy has been described for almost every organ system, including the pancreas. In this Review, we discuss resection of isolated cancer metastases to the pancreas. Pancreatic metastasectomy is most often done through a formal pancreatic resection such as pancreaticoduodenectomy or distal pancreatectomy. Less often, pancreatic metastasectomy is done by enucleation or a pancreas sparing operation such as a central pancreatectomy.

Cigarette smoking doubles the risk of pancreatic cancer, and smoking accounts for 20% to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provides an unprecedented opportunity to identify mutational patterns associated with smoking. We previously sequenced >750 million bp DNA from 23,219 transcripts in 24 adenocarcinomas of the pancreas (discovery screen). In this previous study, the 39 genes that were mutated more than once in the discovery screen were sequenced in an additional 90 adenocarcinomas of the pancreas (validation screen). Here, we compared the somatic mutations in the cancers obtained from individuals who ever smoked cigarettes (n = 64) to the somatic mutations in the cancers obtained from individuals who never smoked cigarettes (n = 50). When adjusted for age and gender, analyses of the discovery screen revealed significantly more nonsynonymous mutations in the carcinomas obtained from ever smokers (mean, 53.1 mutations per tumor; SD, 27.9) than in the carcinomas obtained from never smokers (mean, 38.5; SD, 11.1; P = 0.04). The difference between smokers and nonsmokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, CDKN2A/p16, and SMAD4), but instead was predominantly observed in genes mutated at lower frequency. No differences were observed in mutations in carcinomas from the head versus tail of the gland. Pancreatic carcinomas from cigarette smokers harbor more mutations than do carcinomas from never smokers. The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer.

We report an adult pancreatic hemangioma diagnosed on pathological specimen review following pylorus preserving pancreaticoduodenectomy for a symptomatic cystic mass in the head of the pancreas. Eight cases of adult pancreatic hemangioma have been reported in literature since 1939. Presenting symptoms, radiographic diagnosis, pathologic characteristics, and treatment of adult pancreatic hemagiomas are discussed following review of all published cases.