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.

Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

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.

Use of proton pump inhibitors is associated with fractures in young adults: a population-based study.

UNLABELLED: Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture. INTRODUCTION: Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. METHODS: We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ≥ 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. RESULTS: We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and 1.39 (95% CI 1.26 to 1.53) among young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <0.001). CONCLUSIONS: PPI use was associated with fracture in young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.

Depth of resection using two different endoscopic mucosal resection techniques.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been carried out for high-grade dysplasia (HGD) and intramucosal carcinoma (IMCA) in Barrett's esophagus using two different cap-assisted techniques, the "inject, suck, and cut" and the "band and snare." Previous work has demonstrated comparable specimen diameters. However, the two techniques have not been previously compared with respect to depth of resection. PATIENTS AND METHODS: From a database of patients with Barrett's esophagus, we identified 40 consecutive specimens removed using EMR from patients with HGD or IMCA, 20 each from the "inject, suck, and cut" and the "band and snare" techniques. Specimens were evaluated and measured separately by two pathologists for greatest diameter and depth, and for the presence of submucosa and muscularis propria at the deepest margin of resection. Follow-up data were collected regarding clinical outcome and stricture formation. RESULTS: The mean depth of the specimens from the two techniques was not significantly different (0.51 cm vs. 0.50 cm, P = 0.76). All specimens contained substantial submucosa, allowing accurate staging of the neoplastic lesions resected. Muscularis propria was identified at the base of 65% of the "band and snare" and 50% of the "inject, suck, and cut" specimens (P = 0.52). CONCLUSIONS: The "inject, suck, and cut" and "band and snare" techniques both yield equivalent adequate depth of histological specimens from Barrett's esophagus with HGD or IMCA, and both provide accurate pathological staging.

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.

Neoadjuvant therapy in cancer treatment.

Neoadjuvant therapy has come to play an increasingly prominent role in the treatment of cancer. Originally defined as systemic therapy given before local treatment, the concept has been extended to include radiation therapy given before surgery. Potential advantages include improved local and distant control, direct evaluation, and organ-sparing treatment. Potential disadvantages include increased toxicity and cost, potential delay in effective treatment, and obscuring of pathologic staging. Neoadjuvant therapy in cancer treatment may be viewed in three categories: tumors in which neoadjuvant treatment has been shown effective, thus becoming standard therapy; tumors in which it has been shown to facilitate organ-sparing, and tumors in which its utility has not been shown. For patients with osteogenic sarcoma, for example, preoperative chemotherapy and limb salvage therapy have become the standard of care. Response to chemotherapy, ascertained by histologic review of the surgical specimen, can be used to tailor postoperative chemotherapy. In patients with advanced laryngeal squamous cell carcinoma, neoadjuvant chemotherapy followed by radiation has permitted laryngeal preservation in a majority of patients without compromising overall survival. Phase II and III studies conducted in women with breast cancer have demonstrated promising results for neoadjuvant chemotherapy given before radiation therapy and/or surgery. Phase III studies to compare neoadjuvant therapy to standard therapy in patients with breast cancer are underway. For neoadjuvant therapy, as with other innovations in cancer treatment, it is crucial that a new strategy must be compared closely to standard therapy in terms of recurrence, survival, and impact on organ sparing, as well as quality of life and treatment costs.

Evidence of venous stasis after abdominal insufflation for laparoscopic cholecystectomy.

Intraoperative venous stasis may increase the risk for perioperative deep vein thrombosis and pulmonary embolism. To determine if abdominal insufflation during laparoscopic cholecystectomy causes venous stasis, eight patients undergoing this procedure had their left common femoral veins examined by a duplex scanner before and after abdominal insufflation; the veins then were examined again before and after deflation. The right femoral veins were catheterized to measure femoral venous pressures. Abdominal insufflation to 14 millimeters of mercury pressure increased femoral venous pressures (10.2 +/- 4.1 millimeters of mercury to 18.2 +/- 5.1 millimeters of mercury; p < 0.001) and slowed peak blood velocities (24.9 +/- 8.5 centimeters per second to 18.5 +/- 4.5 centimeters per second; p < 0.05) without changing the cross-sectional areas (1.1 +/- 0.4 centimeter squared to 1.2 +/- 1.5 centimeter squared; p = NS) of the common femoral veins. Insufflation also reduced or eliminated pulsatility in the common femoral veins in 75 percent of the patients, indicating that insufflation was causing partial proximal venous obstruction. After 80 +/- 21 minutes of surgery, these changes remained significant. Deflation of the abdomen restored normal venous pulsatility in all patients, reduced femoral venous pressures (18.5 +/- 5.2 millimeters of mercury to 12.2 +/- 9.8 millimeters of mercury; p < 0.001), increased the peak blood velocities (14.2 +/- 6.8 centimeters per second to 28.1 +/- 16 centimeters per second; p < 0.05) and decreased the cross-sectional areas (1.4 +/- 0.6 centimeters squared to 0.9 +/- 0.4 centimeters squared; p < 0.05) of the common femoral veins, indicating venous decompression had occurred. The results suggest abdominal insufflation causes venous stasis during laparoscopic cholecystectomies. Measures shown to reduce intraoperative venous stasis, such as pneumatic compressive stockings, may benefit patients undergoing these procedures.