Gallbladder Cancer Surgery in the United States: Lymphadenectomy Trends and Impact on Survival.

BACKGROUND: Gallbladder cancer has a poor prognosis, and surgery is the only curative treatment. However, lymphadenectomy has been underperformed. We evaluate the trend of lymphadenectomy in the United States and its impact on survival. METHODS: This is a cohort study of patients who underwent gallbladder cancer surgery between 2004 and 2016. Trend analysis of the rate of lymphadenectomy and the number of lymph nodes (LNs) removed were examined. The impact of lymph node status and different LN staging systems on survival was examined. RESULTS: Of the 4577 patients identified, 69.9% were female, the mean age was 71.0 (±12.4), 87.2% had ≥ T2, and only 50.3% (n = 2302) received lymphadenectomy. Although the rate of lymphadenectomy and the number of LNs removed increased during the study period, both with P < 0.0001, the rate of patients who received examination of ≥6 LNs remained low, 13.6% in 2016. Adjusted regression analysis showed that patients without LN examination had worse overall survival than patients with LN positive disease, HR: 1.11 (95% CI: 1.01, 1.22). Concordance index analysis revealed that LN ratio (LNR) and Log odds of positive LN (LODDS) did not improve the ability of the American Joint Commission on Cancer (AJCC) staging in predicting 5-y survival rate. CONCLUSIONS: Lack of LN examination is associated with worse survival than LN positive disease. Although the rate of LN examination and number of LNs retrieved have increased from 2004 to 2016, they remained low. LNR and LODDS staging systems added no benefit to AJCC staging ability in predicting a 5-y survival rate.

Abdominal lymphangiomas in adults.

Abdominal lymphangiomas are rare benign cystic tumors that can become locally invasive and often require resection. They arise in all ages and have a variable presentation. We performed a retrospective review of a single institution surgical experience with this lesion in adults. The pathology prospective database was reviewed to identify patients with surgically resected abdominal lymphangiomas from January 1986 to May 2004. Retrospective review and follow-up was performed for each patient. The six patients with abdominal lymphangiomas ranged in age from 38 to 66 years. They presented with a variety of signs and symptoms. All underwent CT scan that demonstrated a cystic lesion, but in only one third was the diagnosis made preoperatively. Tumors were located in the retroperitoneum, small bowel mesentery, liver, and pancreas. Five of the six tumors were completely resected. Two of the six required resection of adjacent or involved organs. Follow-up ranged between 6 months and 18 years. All had symptomatic relief after resection, and no patient showed evidence of recurrence in this time period. Abdominal lymphangiomas are rare. The correct diagnosis often remains elusive until tissue is obtained. The treatment of choice is complete surgical resection. When completely resected, these lesions seem not to recur, and the overall prognosis is excellent.

Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms.

Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3sigma and ERM protein expression. Expression of 14-3-3sigma and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.

Pancreaticobiliary cancers with deficient methylenetetrahydrofolate reductase genotypes.

BACKGROUND & AIMS: Methyl group deficiency might promote carcinogenesis by inducing DNA breaks and DNA hypomethylation. We hypothesized that deficient methylenetetrahydrofolate reductase (MTHFR) genotypes could promote pancreatic cancer development. METHODS: First, we performed a case-control study of germline MTHFR polymorphisms (C677T, A1298C) in 303 patients with pancreatic cancer and 305 matched control subjects. Pancreatic neoplasms frequently lose an MTHFR allele during tumorigenesis; we hypothesized that such loss could promote carcinogenesis. We therefore evaluated the cancer MTHFR genotypes of 82 patients with pancreaticobiliary cancers and correlated them to genome-wide measures of chromosomal deletion by using 386 microsatellite markers. Finally, MTHFR genotypes were correlated with global DNA methylation in 68 cancer cell lines. RESULTS: Germline MTHFR polymorphisms were not associated with an increased likelihood of having pancreatic cancer. Fractional allelic loss (a measure of chromosomal loss) trended higher in cancers with 677T genotypes than in cancers with other genotypes (P = .055). Among cancers with loss of an MTHFR allele, cancers with 677T MTHFR alleles had more deletions at folate-sensitive fragile sites (36.9%) and at tumor suppressor gene loci (68.5%) than 677C cancers (28.7% and 47.8%, P = .079 and .014, respectively). LINE1 methylation was lower in cancers with less functional 677T/TT genotypes (24.4%) than in those with 677CT (26.0%) and CC/C genotypes (32.5%) (P = .014). CONCLUSION: Cancers with defective MTHFR genotypes have more DNA hypomethylation and more chromosomal losses. Deficient MTHFR function due to loss of an MTHFR allele by an evolving neoplasm might, by promoting chromosomal losses, accelerate cancer development.