Circulating Tumor DNA After Neoadjuvant Chemotherapy in Breast Cancer Is Associated With Disease Relapse.

PURPOSE: Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy in patients with early-stage breast cancer may allow for early detection of relapse. In this study, we analyzed ctDNA using a personalized, tumor-informed multiplex polymerase chain reaction-based next-generation sequencing assay. METHODS: Plasma samples (n = 157) from 44 patients were collected before neoadjuvant therapy (baseline), after neoadjuvant therapy and before surgery (presurgery), and serially postsurgery including a last follow-up sample. The primary end point was event-free survival (EFS) analyzed using Cox regression models. RESULTS: Thirty-eight (86%), 41 (93%), and 38 (86%) patients had baseline, presurgical, and last follow-up samples, respectively. Twenty patients had hormone receptor-positive/human epidermal growth factor receptor 2-negative, 13 had triple-negative breast cancer, and 11 had human epidermal growth factor receptor 2-positive disease. Baseline ctDNA detection was observed in 22/38 (58%) patients and was significantly associated with Ki67 > 20% (P = .036) and MYC copy-number gain (P = .0025, false discovery rate = 0.036). ctDNA detection at presurgery and at last follow-up was observed in 2/41 (5%) and 2/38 (5%) patients, respectively. Eight relapses (seven distant and one local) were noted (median follow-up 3.03 years [range, 0.39-5.85 years]). After adjusting for pathologic complete response (pCR), ctDNA detection at presurgery and at last follow-up was associated with shorter EFS (hazard ratio [HR], 53; 95% CI, 4.5 to 624; P < .01, and HR, 31; 95% CI, 2.7 to 352; P < .01, respectively). Association between baseline detection and EFS was not observed (HR, 1.4; 95% CI, 0.3 to 5.9; P = .67). CONCLUSION: The presence of ctDNA after neoadjuvant chemotherapy is associated with relapse in early-stage breast cancer, supporting interventional trials for testing the clinical utility of ctDNA monitoring in this setting.

Endoscopic sphincterotomy in patients with "acalculus" cholangitis associated with juxtapapillary diverticula.

BACKGROUND/AIMS: The aim of this study was to investigate patients who underwent endoscopic sphincterotomy for "acalculus" cholangitis associated with juxtapapillary diverticula. METHODOLOGY: In a retrospective study we analyzed 87 patients who underwent endoscopic sphincterotomy for cholangitis; the cholangitis considered "acalculus", when outlining the extra- and intrahepatic bile ducts, we could not observe any intraluminal defect or stricture, and during the clearing of the bile ducts with the balloon, after endoscopic sphincterotomy, there was no evidence of stones, fragments of stones or sludge. Patients who had undergone previous endoscopic sphincterotomy, or who had additional pancreatobiliary diseases were excluded from this study. There were 11 patients with "acalculus" cholangitis associated with juxtapapillary diverticula, and sufficient clinical data available for this study. RESULTS: Nine patients presented pain, fever, and jaundice. In two patients diagnosis was established via the test of abnormal liver biochemistry. Seven patients had positive blood cultures and three of them developed confusion and hypotension. Endoscopic sphincterotomy succeeded in all cases; no evidence of stones, fragments of stones or sludge was recorded during the clearing of bile ducts, after endoscopic sphincterotomy, with the balloon. Five patients presented mild post-endoscopic sphincterotomy complications successfully treated. In the follow-up period, from 4 months to 7 years after endoscopic sphincterotomy, none of the patients developed symptoms of cholangitis. CONCLUSIONS: We recommend endoscopic sphincterotomy in patients with "acalculus" cholangitis associated with juxtapapillary diverticula, despite the absence of obvious obstruction, and the possible morbidity which is inherent with an invasive procedure like endoscopic sphincterotomy.

The natural history of vascular access for hemodialysis: a single center study of 2,422 patients.

BACKGROUND: Our objective is to provide provision of primary and secondary patency rates data and incidence of complications. Despite the publication of some review articles and small prospective trials about vascular accesses, controversy still exists regarding the choice of the outflow conduit and especially the choice of the fistula to be formed in secondary and tertiary access procedures. METHODS: This is a retrospective study of 2,422 consecutive patients who underwent 3,685 vascular access procedures in a tertiary care hospital, including radial-cephalic (RCAVF), brachial-cephalic (BCAVF), brachial-basilic (BBAVF), and prosthetic graft (PTFE) fistulas. Maximum follow-up period was 20 years. Actuarial patency rates were obtained by Kaplan-Meier analysis. RESULTS: The median primary patency (days) of the most common 1st choices for vascular access were 712 (95% CI: 606, 818), 1,009 (95% CI: 823, 1,195), and 384 (95% CI: 273, 945) days for RCAVF, BCAVF, and PTFE, respectively. The median secondary patency was 1809 days (95% CI: 1,692, 1,926) for the RCAVF. The median primary patency of BBAVF (2nd or 3rd choice for vascular access) was 1,582 days (95% CI: 415, 2,749). The cumulative incidence of clinically important complications for the patients who received a RCAVF, BCAVF, BBAVF, and u-PTFE was 0.25, 0.57, 0.33, and 0.61 per patient-year, respectively. CONCLUSION: We advocate maximal use of autogenous conduits, except probably the case of the older diabetic patient, in whom access at the antecubital fossa should be the first choice. BBAVF is an excellent fistula and should probably be constructed before prosthetic graft placement.