Real-Time Telepathology Is Substantially Equivalent to In-Person Intraoperative Frozen Section Diagnosis.

CONTEXT.­: Intraoperative diagnosis by frozen section is a mainstay of surgical pathology practice, providing immediate feedback to the surgical team. Despite good accuracy with modern methods, access to intraoperative surgical pathology with an appropriate turnaround time (TAT) has been a limiting factor for small or remote surgical centers, with negative impacts on cost and patient care. Telepathology offers immediate expert anatomic pathology consultation to sites without an in-house or subspecialized pathologist. OBJECTIVE.­: To assess the utility of live telepathology in frozen section practice. DESIGN.­: Frozen section diagnoses by telemicroscopy from 2 tertiary care centers with a combined 3 satellite hospitals were queried for anatomic site, TAT per block, pathologist, and concordance with paraffin diagnosis. TAT and concordance were compared to glass diagnoses in the same period. RESULTS.­: For 748 intraoperative diagnoses by telemicroscopy, 694 had TATs with a mean of 18 minutes 56 seconds ± 8 minutes 45 seconds, which was slower than on glass (14 minutes 25 seconds ± 7 minutes 8 seconds, P < .001). Twenty-two (2.89% of available) were discordant, which was not significantly different from the on-glass rate (P = .44) or categorical distribution (P = .31). Two cases (0.27%) had technical failures. CONCLUSIONS.­: Although in-person diagnoses were statistically faster, the great majority of telemicroscopic diagnoses were returned in less than 20 minutes. This remained true through numerous pathologists, pathology assistants and/or technicians, different hospitals, and during a combined 6 years. The concentration of discordant diagnoses among relatively few pathologists suggests individual comfort with telepathology and/or frozen section diagnosis. In rare cases, technical issues prevented telemicroscopic diagnosis. Overall, this justifies continued use and expansion of telemicroscopic services in primary intraoperative diagnoses.

Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay.

UNLABELLED: Primary biliary cirrhosis (PBC) is sometimes diagnosed based on a positive antimitochondrial antibody in the appropriate clinical setting without a liver biopsy. Although a liver biopsy can assess the extent of liver fibrosis and provide prognostic information, serum fibrosis markers avoid biopsy complications and sampling error and provide results as a continuous variable, which may be more precise than categorical histological stages. The current study was undertaken to evaluate serum fibrosis markers as predictors of clinical progression in a large cohort of PBC patients. Serial liver biopsy specimens and serum samples were collected every 2 years in 161 PBC subjects for a median of 7.3 years. Clinical progression was defined as development of one or more of the following events: varices, variceal bleed, ascites, encephalopathy, liver transplantation, or liver-related death. Serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and procollagen III aminopeptide were measured and entered into the previously validated enhanced liver fibrosis (ELF) algorithm. The ability of ELF, histological fibrosis, bilirubin, Model for End-Stage Liver Disease (MELD), and Mayo Risk Score to differentiate between individuals who would experience a clinical event from those who would not was evaluated at different time points. Event-free survival was significantly lower in those with high baseline ELF. Each 1-point increase in ELF was associated with a threefold increase in future complications. The prognostic performance of all tests was similar when performed close to the time of the first event. However, at earlier times in the disease process (4 and 6 years before the first event), the prognostic performance of ELF was significantly better than MELD or Mayo R score. CONCLUSION: The ELF algorithm is a highly accurate noninvasive measure of PBC disease severity that provides useful long-term prognostic information.

Adenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitrite.

We conducted a population-based case-control study of adenocarcinoma of the stomach and esophagus in Nebraska, U.S.A. Nitrate concentrations in public drinking water supplies were linked to residential water source histories. Among those using private wells at the time of the interview, we measured nitrate levels in water samples from wells. Dietary nitrate and nitrite were estimated from a food-frequency questionnaire. Among those who primarily used public water supplies (79 distal stomach, 84 esophagus, 321 controls), average nitrate levels were not associated with risk (highest versus lowest quartile: stomach OR=1.2, 95% CI [0.5-2.7]; esophagus OR=1.3, 95% CI [0.6-3.1]). We observed the highest ORs for distal stomach cancer among those with higher water nitrate ingestion and higher intake of processed meat compared with low intakes of both; however, the test for positive interaction was not significant (p=0.213). We did not observe this pattern for esophagus cancer. Increasing intake of nitrate and nitrite from animal sources was associated with elevated ORs for stomach cancer and with a significant positive trend in risk of esophagus cancer (P-trend=0.325 and 0.015, respectively). Larger studies with higher exposures to drinking water sources of nitrate are warranted to further evaluate N-nitroso compound precursors as risk factors for these cancers.

Dietary patterns and adenocarcinoma of the esophagus and distal stomach.

BACKGROUND: Dietary pattern analysis is a unique approach to studying relations between diet and disease. OBJECTIVE: Our objective was to describe the dietary patterns of an eastern Nebraska population and investigate the associations between those dietary patterns and risks of adenocarcinoma of the esophagus and distal stomach. DESIGN: We recruited 124 subjects with esophageal adenocarcinoma, 124 subjects with distal stomach adenocarcinoma, and 449 control subjects in a population-based, case-control study. RESULTS: Six dietary patterns were identified with the use of cluster analysis. The first dietary pattern represented healthy food choices and had higher energy contributions from fruit and vegetables and grain products and lower energy contributions from red meats, processed meats, and gravy than did the other dietary patterns. In contrast, a second dietary pattern was high in meats and low in fruit and cereals. The other 4 dietary patterns were each characterized by a concentrated energy source: salty snacks, desserts, milk, and white bread, respectively. The test of overall difference in cancer risk across dietary patterns was significant for distal stomach adenocarcinoma (P = 0.04) but not for esophageal adenocarcinoma. Risk of esophageal adenocarcinoma was inversely associated with intakes of dairy products, fish, all vegetables, citrus fruit and juices, and dark bread and was positively associated with gravy intake. Risk of distal stomach adenocarcinoma was positively associated with red meat intake. CONCLUSIONS: Our study suggests that a diet high in fruit and vegetables may decrease the risk of esophageal adenocarcinoma and that a diet high in meats may increase the risk of distal stomach adenocarcinoma.

Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach.

Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer. We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for known risk factors. Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer. Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat.

Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.

Nutrient intakes and adenocarcinoma of the esophagus and distal stomach.

We studied the relationship between nutrient intakes and adenocarcinoma of the esophagus and distal stomach among 124 esophageal adenocarcinoma cases, 124 distal stomach cancer cases, and 449 controls in a population-based case-control study in eastern Nebraska. The residual method was used to adjust nutrient intake quartiles or tertiles for energy intake. We observed significant inverse associations with risk of esophageal adenocarcinoma for dietary intakes of total vitamin A [highest vs. lowest quartile, multivariate odds ratio (OR) = 0.5, P for trend = 0.05], beta-cryptoxanthin (OR = 0.5, P = 0.05), riboflavin (OR = 0.5, P = 0.01), folate (OR = 0.5, P = 0.03), zinc (OR = 0.5, P = 0.05), dietary fiber (OR = 0.5, P = 0.05), protein (OR = 0.5, P = 0.02), and carbohydrate (OR = 0.4, P = 0.02). For distal stomach cancer, only vitamin C (OR = 0.6, P = 0.04), dietary fiber (OR = 0.4, P = 0.007), and carbohydrate (OR = 0.4, P = 0.004) were inversely associated with risk. Our analyses showed significant interaction between dietary fat intake, but not intakes of other nutrients, and respondent type for both cancer sites. Subgroup analyses among self-respondents revealed positive associations between saturated fat intake and risk of esophageal adenocarcinoma (OR = 1.0, 4.1, and 4.6 for intake tertiles, P for trend = 0.02) and risk of distal stomach cancer (OR = 1.0, 1.2, and 3.6, P = 0.03). However, no such associations were found among proxy respondents. Our data suggest that greater intake of dietary fiber, certain carotenoids, and vitamins may decrease the risk of esophageal adenocarcinoma, whereas greater intake of saturated fat may increase the risk of esophageal adenocarcinoma and distal stomach cancer.