Variation by stage in the effects of prediagnosis weight loss on mortality in a prospective cohort of esophageal cancer patients.

Cancer cachexia is increasingly recognized as a poor prognostic marker for various tumor types. Weight loss in esophageal cancer is multifactorial, as patients with bulky tumors also have reduced ability to eat. We aimed to investigate the relationship between prediagnosis weight loss and mortality in esophageal cancer and to determine whether these associations vary with tumor stage. We conducted a prospective cohort study of esophageal cancer patients at two tertiary centers. We recorded baseline patient characteristics including medications, smoking, body mass index, and weight loss in the year prior to diagnosis, and collected data on treatment and outcomes. We used Cox regression modeling to determine the associations between percent weight loss and outcomes. The main outcome of interest was all-cause mortality; secondary endpoints were esophageal cancer-specific mortality and development of metastases. We enrolled 134 subjects, the majority of whom had adenocarcinoma (82.1%); median percent weight loss was 4.7% (IQR: 0%-10.9%). Increasing percent weight loss was not associated with all-cause mortality (ptrend = 0.36). However, there was evidence of significant interaction by tumor stage (p = 0.02). There was a strong and significant association between prediagnosis weight loss and mortality in patients with T stages 1 or 2 (adjusted HR 8.26 for highest versus lowest tertile, 95%CI 1.11-61.5, ptrend = 0.03) but not for T stages 3 or 4 (ptrend = 0.32). Body mass index one year prior to diagnosis was not associated with mortality. Prediagnosis weight loss was associated with increased all-cause mortality only in patients with early stage esophageal cancer. This suggests that tumor-related cachexia can occur early in esophageal cancer and represents a poor prognostic marker.

Dietary Inflammatory Index and Risk of Colorectal Adenoma Recurrence: A Pooled Analysis.

No studies have evaluated the association between the dietary inflammatory index (DII) and colorectal adenoma recurrence. DII scores were calculated from a baseline food frequency questionnaire. Participants (n = 1727) were 40-80 years of age, enrolled in two Phase III clinical trials, who had ≥1 colorectal adenoma(s) removed within 6 months of study registration, and a follow-up colonoscopy during the trial. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations were found between DII and odds of colorectal adenoma recurrence [ORs (95% CIs) = 0.93 (0.73, 1.18) and 0.95 (0.73, 1.22)] for subjects in the second and third DII tertiles, respectively, compared to those in the lowest tertile (Ptrend = 0.72). No associations were found for recurrent colorectal adenoma characteristics, including advanced recurrent adenomas, large size, villous histology, or anatomic location. While our study did not support an association between a proinflammatory diet and colorectal adenoma recurrence, future studies are warranted to elucidate the role of a proinflammatory diet on the early stages of colorectal carcinogenesis.

Measurement and validation of frailty as a predictor of outcomes in women undergoing major gynaecological surgery.

OBJECTIVE: Frailty is the loss of physical or mental reserve that impairs function, often in the absence of a defined comorbidity. Our aim was to determine whether a modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing hysterectomy. DESIGN: Retrospective cohort study. SETTING: Hospitals across the USA participating in the National Surgical Quality Improvement Program (NSQIP). SAMPLE: Patients who underwent hysterectomy from 2008 to 2012. METHODS: An mFI was calculated using 11 variables in NSQIP. The associations between mFI and morbidity and mortality were assessed. Model fit statistics (c-statistics) were utilised to evaluate the ability of mFI to distinguish outcomes. MAIN OUTCOME MEASURE: Wound infection, severe complications and mortality. RESULTS: A total of 66 105 patients were identified. Wound complications increased from 2.4% in patients with an mFI of zero to 4.8% in those with mFI ≥ 0.5 (P < 0.0001). Similarly, severe complications increased from 0.98% to 7.3% (P < 0.0001), overall complications rose from 3.7% to 14.5% (P < 0.0001) and mortality increased from 0.06% to 3.2% (P < 0.0001) for patients with a frailty index of zero compared with those with an index of ≥ 0.5. Versus chance, the goodness-of-fit c-statistics suggested that mFI increases the ability to detect wound complications by 11.4%, severe complications by 22.0% and overall complications by 11.0%. CONCLUSIONS: The mFI is easily reproducible from routinely collected clinical data and predictive of outcomes in patients undergoing hysterectomy. Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery. TWEETABLE ABSTRACT: Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery.

Influence of health insurance, hospital factors and physician volume on receipt of immediate post-mastectomy reconstruction in women with invasive and non-invasive breast cancer.

For women with breast cancer who undergo mastectomy, immediate breast reconstruction (IR) offers a cosmetic and psychological advantage. We evaluated the association between demographic, hospital, surgeon and insurance factors and receipt of IR. We conducted a retrospective hospital-based analysis with the Perspective database. Women who underwent a mastectomy for invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS) from 2000 to 2010 were included. Logistic regression analysis was used to determine factors predictive of IR. Analyses were stratified by age (<50 vs. ≥ 50) and IBC versus DCIS. Of the 108,992 women with IBC who underwent mastectomy, 30,859 (28.3 %) underwent IR, as compared to 6,501 (44.2 %) of the 14,710 women with DCIS who underwent mastectomy underwent IR. In a multivariable model for IBC, increasing age, black race, being married, rural location, and increased comorbidities were associated with decreased IR. Odds ratios (OR) of IR increased with commercial insurance (OR 3.38) and Medicare (OR 1.66) insurance (vs. self-pay), high surgeon-volume (OR 1.19), high hospital-volume (OR 2.24), and large hospital size (OR 1.20). The results were identical for DCIS, and by age category. The absolute difference between the proportion of patients who received IR with commercial insurance compared to other insurance, increased over time. Immediate in-hospital complication rates were higher for flap reconstruction compared to implant or no reconstruction (15.2, 4.0, and 6.1 %, respectively, P < .0001). IR has increased significantly over time; however, modifiable factors such as insurance status, hospital size, hospital location, and physician volume strongly predict IR. Public policy should ensure that access to reconstructive surgery is universally available.

Risk of colorectal adenomas and advanced neoplasia in Hispanic, black and white patients undergoing screening colonoscopy.

BACKGROUND: Racial and ethnic differences in the risk of premalignant colorectal neoplasia have not been extensively studied. AIM: To measure adenoma prevalence among asymptomatic white, black and Hispanic patients undergoing screening colonoscopy. METHODS: In this cross sectional cohort study, data from individuals ≥50 years undergoing first-time colonoscopy since 2006 at a single tertiary-care medical centre were obtained from the electronic medical record. Adenoma prevalence among whites, blacks and Hispanics was calculated; multivariate Poisson and logistic regression were used to identify factors independently associated with adenoma rates and the presence of advanced adenomas. RESULTS: We identified 5075 eligible subjects: 3542 (70%) whites, 942 (18%) Hispanics and 591 (12%) blacks. The mean age was 62.2 years with 58% women. At least one adenoma was detected in 19%, 22% and 26% of whites, Hispanics and blacks respectively (Hispanics vs. whites P = 0.09; blacks vs. whites P = 0.0001). Isolated proximal adenomas were present in 9% of whites, 11% of Hispanics (P = 0.03) and 11% of blacks (P = 0.03). In multivariate analyses, a higher rate of adenomas was present in Hispanics (RR: 1.37, 95% CI: 1.20-1.57) and blacks (RR: 1.76, 95% CI: 1.52-2.04) than whites. Hispanics and blacks also had an increased risk of advanced adenomas compared to whites (OR(Hispanics) : 2.25, 95% CI: 1.62-3.11; OR(blacks) : 1.91, 95% CI: 1.27-2.86). CONCLUSIONS: Adenoma prevalence was higher in blacks and Hispanics than in whites. Both groups were at greater risk of having proximal adenomas in the absence of any distal pathology than whites, where these lesions would have only been detected by colonoscopy. Efforts to promote screening are necessary among diverse, under-represented populations.

Risk of colorectal adenomas in patients with coeliac disease.

BACKGROUND: Coeliac disease is associated with an increased risk of lymphoma and small bowel malignancy, but most studies have found no increased risk of colorectal cancer. AIM: To compare the prevalence of colorectal adenomas in coeliac disease patients with that in non-coeliac disease controls. METHODS: We identified all coeliac disease patients who underwent colonoscopy at our institution during a 44-month period. We matched each patient with non-coeliac disease controls by age, gender and endoscopist. We compared the adenoma prevalence between these groups, and used multivariate analysis to assess the independent association of coeliac disease with adenomas. RESULTS: We identified 180 patients with coeliac disease and 346 controls. At least one adenoma was present in 13% of coeliac disease patients and 17% of controls (P = 0.20). On multivariate analysis, age (OR per year 1.04, 95% CI 1.02-1.07) and male gender (OR 2.33, 95% CI 1.36-3.98) were associated with adenomas, while the relationship between coeliac disease and adenomas remained null (OR 0.75, 95% CI 0.41-1.34). CONCLUSIONS: Coeliac disease is not associated with an increased risk of colorectal neoplasia. The lack of increased risk of colorectal cancer observed in population studies is related to a true average risk of colorectal neoplasia, rather than artifactually reflecting increased colonoscopy and associated polypectomies in the coeliac population.

Risk of colorectal neoplasia associated with the adenomatous polyposis coli E1317Q variant.

BACKGROUND: Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting. Using a case-control design, we investigated this relationship within a clinic-based cohort followed through the Integrated Cancer Prevention Center and the Tel-Aviv Sourasky Medical Center. MATERIALS AND METHODS: All study subjects were tested for the APC E1317Q variant at enrollment. Subjects underwent colonoscopic evaluation (+/-biopsy and/or polypectomy) and had cancer history and colorectal neoplasia risk factors assessed. The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated. RESULTS: The prevalence of the E1317Q variant was 1.4% in the entire study sample and 3.2% in Sephardic Jews. E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0-9.6]. When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8-9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8-5.3). After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0-10.8). CONCLUSIONS: The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed. Variant prevalence is elevated in Sephardic Jews.

Predictors of survival after hepatic resection among patients with colorectal liver metastasis.

Studies suggest improved survival following resection of colorectal cancer liver metastases (CLMs). We investigated predictors of survival among patients with CLM who underwent hepatic resection using the SEER-Medicare database to identify patients >/=65 years diagnosed with CLM, 1991-2003, who underwent hepatectomy. Cox proportional hazards models were used to identify factors associated with survival after hepatectomy. Of 923 patients with CLM who underwent hepatectomy, 514 were stages I-III and developed CLM>6 months after diagnosis (metachronous), and 409 were stage IV with CLM at diagnosis (synchronous). From the date of hepatectomy, 5 year survival was 22%; younger age, being married, female gender, surgery in an NCI-designated cancer centre, fewer comorbidities, fewer positive lymph nodes, and lower grade were associated with improved survival. Both 5-fluorouracil (5FU)-based chemotherapy and hepatic arterial infusion (HAI) of floxuridine-based chemotherapy following hepatectomy improved survival (HR=0.62, 95% CI: 0.50-0.78; HR=0.51, 95% CI: 0.28-0.97, respectively) in the synchronous, but not metachronous, group. The HR for overall mortality was higher in hospitals with a high vs low procedure volume (0.75, 95% CI: 0.58-0.94). A substantial subgroup of patients with CLM who undergo hepatectomy experiences long-term survival. High hospital procedure volume and use of 5FU-based or HAI-based chemotherapy after resection were associated with improved prognosis.

Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk.

Isothiocyanates are anticarcinogenic phytochemicals found in cruciferous vegetables that both induce and are substrates for the gluthatione S-transferases (GSTs). The GSTs are phase II metabolizing enzymes involved in metabolism of various bioactive compounds. Functional polymorphisms in GST genes have been identified and may interact with cruciferous vegetable intake to affect cancer risk. We examined this hypothesis using data from the Long Island Breast Cancer Study Project, a population-based case-control study conducted in Long Island, NY, from 1996 to 1997. Cruciferous vegetable intake in the previous year was assessed via modified Block food frequency questionnaire. DNA was extracted from blood samples (n = 1052 cases and n = 1098 controls) and genotyped for GSTM1 deletion, GSTT1 deletion and GSTP1 Ile105Val using multiplex polymerase chain reaction and Taqman assays. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We found an 86% increase in the OR for breast cancer among carriers of the GSTM1 null, GSTT1 null and GSTP 105Ile/Ile genotypes (OR = 1.86, 95% CI = 1.12, 3.08) and a 36% decrease in the OR among carriers of GSTM1 present, GSTT1 null and GSTP1 105Ile/Val + Val/Val genotypes (OR = 0.64, 95% CI = 0.42, 0.97) compared with GSTM1 present, GSTT1 present and GSTP1 105Ile/Ile carriers. We found no joint effects among GST polymorphisms and cruciferous vegetable intake and breast cancer risk. In conclusion, we found associations between specific combinations of three GST gene polymorphisms and breast cancer risk but these did not modify the association between cruciferous vegetable intake and breast cancer. Additional studies are needed to confirm the associations observed.

Risk of duodenal adenoma in celiac disease.

BACKGROUND: There is a 60- to 80-fold increased risk of small-bowel adenocarcinoma in patients with celiac disease. While the adenoma-carcinoma sequence appears to operate in the small bowel as in the large bowel, the risk of duodenal adenomas in celiac patients is unknown. METHODS: The records of 381 patients (245 F, 136 M) with biopsy-proven celiac disease were reviewed to determine the prevalence of duodenal adenoma found during esophagogastroduodenoscopy (EGD). We conducted an extensive literature review to find data for estimates of the prevalence of duodenal adenoma in a comparable general population; we used data from a study at another New York City medical center of 7346 EGDs conducted between 1976 and 1982 (Ghazi et al., 1984). We estimated the relative risk, expressed as a standard morbidity ratio (SMR), by calculating the observed to expected (O/E) ratio. RESULTS: Duodenal adenomas were found in 3 celiac patients (0.78%), with 24 adenomas (0.33%) in the reference population, giving an SMR of 2.39 (95% CI 0.67-8.48). CONCLUSION: We did not find a significantly increased risk of duodenal adenoma in celiac patients compared to a non-celiac endoscoped population. Thus, despite the previously described elevated risk of small-bowel adenocarcinoma in these patients, routine endoscopic examination of the duodenum may not be adequate for screening.

Handheld cellular telephones and risk of acoustic neuroma.

The hypothesis that intracranial energy deposition from handheld cellular telephones causes acoustic neuroma was tested in an epidemiologic study of 90 patients and 86 control subjects. The relative risk was 0.9 (p = 0.07) and did not vary significantly by the frequency, duration, and lifetime hours of use. In patients who used cellular telephones, the tumor occurred more often on the contralateral than ipsilateral side of the head. Further efforts should focus on potentially longer induction periods.

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Increased incidence of colorectal adenomas in follow-up evaluation of patients with newly diagnosed hyperplastic polyps.

BACKGROUND: Although adenomatous polyps have been established clearly as precursor lesions for most cases of colorectal cancer, the role, if any, of hyperplastic polyps remains uncertain. The aim of the current study was to determine whether a patient with an index finding of hyperplastic polyp on colonoscopy is at increased risk for adenomatous polyps. METHODS: We conducted a retrospective cohort study using the records of a single surgeon's colonoscopic experience over a 20-year period (June 1973 to December 1994). Patients found to have hyperplastic lesions on index colonoscopy were compared with those who had "clean" index colonoscopies. The two groups were compared for the subsequent diagnosis of adenomatous polyps on follow-up colonoscopies. Those with cancer or adenomas at index colonoscopy or in their history were excluded. We used Cox proportional hazard modeling with subsequent adenoma or cancer diagnosis at follow-up colonoscopy as the outcome, controlling for age and gender. RESULTS: We identified 42 patients for whom hyperplastic polyps were the only colorectal neoplasms found on the index examination, in contrast to 362 control patients who had a "clean" index examination. In this cohort study, patients found to have only hyperplastic polyps on initial examination had a rate of subsequent adenoma diagnoses (42%) twice that of patients with a clean initial colonoscopy (21%). Mean follow-up time was 4.3 years. The relative rate ratio was 2.0 (95% confidence interval, 1.2-3.4). CONCLUSIONS: This study suggests that patients found to have hyperplastic polyps on initial colonoscopic examination may have twice the risk of adenomas on follow-up colonoscopy, as compared with those who have clean initial examinations. If this finding is borne out in larger prospective studies, surveillance strategies may need to be modified accordingly.

Knowledge, beliefs, and barriers relevant to colorectal cancer screening in an urban population: a pilot study.

A sample of 115 urban, working-class, predominantly minority men and women was interviewed by telephone to assess knowledge, beliefs, and barriers relevant to colorectal cancer (CRC) and CRC screening. More than half (53.9%) were unable to name a CRC screening test. Misconceptions were common. Dispelling inaccurate beliefs, establishing an individual's preference for fecal occult blood tests or flexible sigmoidoscopy, and helping individuals take a proactive role in the receipt of CRC screening are important goals for health education efforts aimed at increasing rates of CRC screening. Participants' willingness to engage in detailed telephone conversations about CRC and CRC screening was encouraging.

Variations in the use of adjuvant chemotherapy for node-positive colon cancer in the elderly: a population-based study.

BACKGROUND: Since 1990, the recommended adjuvant therapy for patients with surgically resected node-positive colon cancer has been 5-fluorouracil (5-FU), usually in combination with leucovorin or levamisole. The purpose of this study is to assess the distribution of adjuvant 5-FU treatment in the elderly. METHODS: The Surveillance, Epidemiology and End Results-Medicare database provides population-based information on cancer patients, representing approximately 14% of the United States population, along with health care utilization data from Medicare claims files. We studied patients with node-positive colon cancer diagnosed between 1992 and 1996 who survived at least 120 days beyond diagnosis (N = 4998). RESULTS: About 50% of elderly patients received 5-FU within 4 months of diagnosis. The proportion of patients treated with 5-FU increased by about 10% from 1992 to 1996. In a multiple logistic regression model, 5-FU treatment was less likely to be given to older patients (compared with those aged 65-69 years, the odds ratio (OR) [95% CI] was 0.82 [0.67-1.00] for ages 70 to 74 years, 0.47 [0.39-0.57] for ages 75 to 79, 0.17 [0.13-0.20] for ages 80 to 84, and 0.04 [0.03-0.05] for ages 85 to 88 years. Non-Hispanic black patients were less likely to be treated than non-Hispanic white patients (OR 0.46 [0.36-0.59]); patients with more than three positive lymph nodes were more likely to be treated than those with three or less, and those with comorbid conditions were less likely to be treated than those without such conditions. CONCLUSIONS: Despite its proven efficacy in reducing colon cancer mortality, 5-FU-based chemotherapy is not widely used among apparently eligible patients over age 65. Efforts are needed to ensure that elderly and non-Hispanic black patients receive appropriate treatment.

Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer.

PURPOSE: Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients. PATIENTS AND METHODS: Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits. RESULTS: Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups. CONCLUSION: Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.

Estimating the effect of an intensive surveillance program on stage of breast carcinoma at diagnosis: a propensity score analysis.

BACKGROUND: The authors used propensity score adjustment to investigate the impact of intensive screening on stage of breast carcinoma at diagnosis in women who were at elevated risk for breast carcinoma. METHODS: The authors compared 58 women participating in a surveillance program at the Columbia Presbyterian Medical Center of New York Presbyterian Hospital who developed breast carcinoma with 3022 nonparticipating breast carcinoma patients. A propensity score was constructed for each woman by using important background covariates, and multivariable regression modeling was used to estimate the association of program membership with disease stage after adjusting for the propensity score. RESULTS: Before propensity score adjustment, nine baseline covariates significantly differed between the two groups (number of pregnancies, number of births, age at first delivery, race, how the tumor was discovered, history of prior breast disease, breast carcinoma in mother, breast carcinoma in maternal aunt, and breast carcinoma in sister), and there was a significant difference in stage at diagnosis. After adjustment, no significant differences remained. Program participants were more likely to have lower stage tumors at diagnosis than nonparticipants, but this association did not reach statistical significance (odds ratio, 1.52; 95% confidence interval, 0.94--2.46). CONCLUSIONS: Propensity score methods can remove bias in treatment comparisons in observational studies. An intensive surveillance program at a major cancer center may have had some effect on improving stage at diagnosis, but this effect was not statistically significant.