Background ERCP can be associated with serious complications. Difficulty in common bile duct (CBD) cannulation is one of the main risk factors for post-ERCP pancreatitis. The double-guidewire ...technique (DGT) has been considered a promising alternative approach in difficult cannulation situations. Objective To compare the performance of DGT with the standard cannulation technique (SCT) in patients in whom CBD cannulation is difficult to perform. Design Multicenter randomized, controlled trial. Setting Six tertiary referral centers. Patients A total of 188 patients with difficult CBD cannulation defined by completion of 5 unsuccessful cannulation attempts were enrolled. Interventions Ninety-seven patients were assigned to the DGT group and 91 to the SCT group. Both techniques were compared for an extra 10 cannulation attempts. Main Outcome Measurements CBD cannulation rate, number of attempts required to cannulate, and ERCP-related complications. Results Successful CBD cannulation was achieved in 46 of 97 (47%) patients in the DGT group compared with 51 of 91 (56%) in the SCT group (OR 0.85; 95% CI, 0.64-1.12). The median number of attempts required for each group was 9 and 7, respectively ( P = .128). The incidence of post-ERCP pancreatitis was 17% in the DGT group and 8% in the SCT group (OR 2.13; 95% CI, 0.89-5.05). Limitations Reduced number of enrolled subjects and a lack of detailed information regarding the number and extent of pancreatic duct contrast injections. Conclusions In patients with difficult CBD cannulation, DGT was not superior to SCT in achieving CBD cannulation. DGT might be associated with a higher risk of post-ERCP pancreatitis. (This study has been registered in ClinicalTrials.gov with identifier NCT00270868 .)
We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus platinum-based chemotherapy (pembrolizumab-combination) ...for NSCLC among patients in the phase 3 KEYNOTE-189 (ClinicalTrials.gov, NCT02578680; nonsquamous) and KEYNOTE-407 (ClinicalTrials.gov, NCT02775435; squamous) trials.
This retrospective exploratory analysis evaluated prevalence of high tTMB and STK11, KEAP1, and KRAS mutations in patients enrolled in KEYNOTE-189 and KEYNOTE-407 and the relationship between these potential biomarkers and clinical outcomes. tTMB and STK11, KEAP1, and KRAS mutation status was assessed using whole-exome sequencing in patients with available tumor and matched normal DNA. The clinical utility of tTMB was assessed using a prespecified cutpoint of 175 mutations/exome.
Among patients with evaluable data from whole-exome sequencing for evaluation of tTMB (KEYNOTE-189, n = 293; KEYNOTE-407, n = 312) and matched normal DNA, no association was found between continuous tTMB score and overall survival (OS) or progression-free survival for pembrolizumab-combination (Wald test, one-sided p > 0.05) or placebo-combination (Wald test, two-sided p > 0.05) in patients with squamous or nonsquamous histology. Pembrolizumab-combination improved outcomes for patients with tTMB greater than or equal to 175 compared with tTMB less than 175 mutations/exome in KEYNOTE-189 (OS, hazard ratio = 0.64 95% confidence interval (CI): 0.38‒1.07 and 0.64 95% CI: 0.42‒0.97, respectively) and KEYNOTE-407 (OS, hazard ratio = 0.74 95% CI: 0.50‒1.08 and 0.86 95% CI: 0.57‒1.28, respectively) versus placebo-combination. Treatment outcomes were similar regardless of KEAP1, STK11, or KRAS mutation status.
These findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the utility of tTMB, STK11, KEAP1, or KRAS mutation status as a biomarker for this regimen.
We present a case report of a 15-year-old girl with right-side endocarditis, which presented with multiple large masses located on both right chambers mimicking the appearance of a tumor. There were ...no predisposing factors other than an infected navel piercing. Piercing-associated infective endocarditis has occasionally been reported, and usually occurs in patients with an underlying cardiac condition. We briefly discuss the main features of piercing-related endocarditis and also some aspects of cardiac tumors as differential diagnosis of large cardiac masses.
Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ...(NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m2 on day 1 plus docetaxel (75 mg/m2 on day 1) or gemcitabine (1250 mg/m2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m2 or AUC 5 with gemcitabine 1000 mg/m2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov , number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p<0·0001). Main grade 3 or 4 toxicities were rash (11 13% of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 22%), anaemia (one 1% vs three 4%), and increased amino-transferase concentrations (two 2% vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.
Abstract Objective The addition of androgen deprivation therapy (ADT) to conventional radiation therapy improves overall survival (OS) in intermediate- and high-risk prostate cancer. The benefit of ...ADT to added to dose-escalated radiotherapy is less clear. The aim of this study was to report disease control outcomes and to identify prognostic variables associated with favorable outcomes in patients with intermediate- and high-risk prostate cancer treated with dose-escalated radiation therapy without ADT. Methods and materials From September 2001 to March 2010, 127 patients with intermediate- or high-risk prostate cancer were treated with dose-escalated radiation otherapy without ADT. Biochemical recurrence-free survival (bRFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality, and OS were assessed. Univariate and multivariate analyses using Cox regression modeling were performed. Results The median follow-up was 6.5 years, and the 5-year estimated bRFS, DMFS, prostate cancer–specific mortality, and OS for all patients was 89%, 96.1%, 98.4%, and 96.9% respectively. On multivariate analysis, factors that predict bRFS include risk group and PSA nadir, and factors that predict DMFS include perineural invasion, risk group, and PSA nadir. Conclusions Patients with favorable intermediate-risk cancer could likely be treated with dose-escalated radiation therapy without ADT. Patients with high-risk and unfavorable intermediate-risk cancer, perineural invasion, and PSA nadir ≥1ng/dL had worse outcomes and likely need distinct therapeutic approaches.
Background Few studies have analyzed the tangible impact of global, philanthropic medical missions. We used qualitative methods to analyze the work of one such mission, Operation Walk Boston, which ...has made yearly trips to a Dominican Republic hospital since 2008. Methods We interviewed twenty-one American and Dominican participants of the Operation Walk Boston team to investigate how the program led to changes at the host Dominican hospital and how the experience caused both mission protocols and U.S. practices to change. Transcripts were analyzed with the use of content analysis. Results Participants noted that Operation Walk Boston’s technical knowledge transfer and managerial examples led to sustainable changes at the Dominican hospital. Additionally, participants observed an evolution in nursing culture, as the program inspired greater independence in decision-making. Participants also identified barriers such as language and organizational hierarchy that may limit bidirectional knowledge transfer. U.S. participants noted that their practices at home changed as a result of better appreciation for different providers’ roles and for managing cost in a resource-constrained environment. Conclusions Operation Walk Boston catalyzed sustainable changes in the Dominican hospital. Cultural norms and organizational structure are important determinants of program sustainability.
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