Association of sporadic and familial Barrett's esophagus with breast cancer.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.

Systematic review with meta-analysis: selective serotonin reuptake inhibitors for noncardiac chest pain.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are used to treat noncardiac chest pain (NCCP) symptoms, however, data regarding their efficacy remains inconclusive. AIM: To conduct a meta-analysis of randomised controlled trials (RCT) comparing SSRIs to placebo in patients with NCCP, and rate the quality of evidence. METHODS: Electronic databases were searched using the terms 'noncardiac chest pain', 'atypical chest pain' and 'selective serotonin reuptake inhibitors'. Data were extracted from RCTs of ≥8 weeks. Standardised mean differences (SMD), weighted mean differences (WMD) or risk ratios (RR) were used as summary statistics for pooled outcomes. GRADE methodology was used to rate the quality of evidence. RESULTS: Four RCTs (184 patients) met the inclusion criteria. Compared to placebo, patients on SSRIs showed a nonsignificant change in chest pain of 3½ points decrease on a 100 mm visual analogue scale (184 patients, 95% CI, -9.5 to 2.5; I(2)  = 0%). Change in depression scores was not significantly different between the two groups (88 patients; WMD = 0.7; 95% CI, -1.81 to 3.20; I(2)  = 64%). Treatment discontinuations were not significantly different between groups (154 patients, RR = 2.08; 95% CI, 0.77-5.60; I(2)  = 0%). The quality of evidence was rated as moderate for change in chest pain symptoms, low for change in depression scores and moderate for treatment discontinuation due to adverse events. CONCLUSIONS: Selective serotonin reuptake inhibitors are not superior to placebo in improving chest pain or depression symptoms in patients with noncardiac chest pain. Larger trials with longer follow-up periods are necessary to assess the benefits and drawbacks of SSRIs for the treatment of noncardiac chest pain.

Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis.

BACKGROUND: Treatment options for constipation-predominant irritable bowel syndrome (IBS-C) are limited. While linaclotide improved IBS-C symptoms in randomized controlled trials (RCTs), results vary among studies and the magnitude of benefit is unclear. METHODS: Two investigators independently extracted data on study participants, methods and outcomes (i.e., symptoms, quality of life, and adverse events) from eligible articles i.e., RCTs comparing linaclotide with placebo in adult patients with IBS-C with a follow-up of 12 weeks or longer. The grading of recommendations assessment, development and evaluation (GRADE) methodology was used to rate the quality of evidence. KEY RESULTS: Of 182 identified citations, three RCTs enrolling 1773 patients met the inclusion criteria. Compared with placebo, fewer patients on linaclotide failed to achieve responses i.e., FDA endpoint (1604 patients, risk ratio [RR] = 0.80; 95%CI 0.76-0.85), adequate IBS symptom relief (1773 patients, RR = 0.73; 95%CI 0.65-0.82), and clinically meaningful improvement in IBS-QOL (1659 patients, RR = 0.78; 95%CI 0.72-0.86). The incidence of diarrhea leading to discontinuation of treatment was higher for linaclotide (1773 patients, RR = 14.75; 95%CI 4.04-53.81). The quality of evidence was rated as moderate for FDA endpoint and adequate relief response, high for diarrhea, and low for IBS-QOL. Generalizability may be limited by the study population (i.e., predominantly white female patients), lack of data regarding prior therapy, and availability of few RCTs. The number of patients is insufficient to identify rare adverse events. CONCLUSIONS & INFERENCES: Linaclotide is moderately effective in improving symptoms of IBS-C with diarrhea being the major side effect. Further studies are needed to evaluate the long-term efficacy and safety of linaclotide for IBS-C.