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BackgroundThe Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures for surgical weight loss. It has been shown that overweight may be associated with an increased risk of gastric cancer. However, the risk of remnant gastric cancer after RYGB has not been defined yet and the development of neoplasm in the excluded stomach remains a matter of concern.MethodsPubMed, EMBASE, and Web of Science databases were consulted. Articles that described the diagnosis and management of remnant gastric cancer after RYGB were considered.ResultsSeventeen patients were included. The age of the patient population ranged from 38 to 71 years. The most commonly reported symptoms were abdominal pain, nausea/vomiting, and anemia. Abdominal computed tomography was used for diagnosis in the majority of patients. The neoplasm was located in the antrum/pre-pyloric region in 70% of cases and adenocarcinoma was the most common tumor histology (80%). An advanced tumor stage (III–IV) was diagnosed in almost 70% of patients and 40% were considered unresectable. Gastrectomy with lymphadenectomy was performed in 9 cases (53%). Post-operative morbidity was 12%. The follow-up ranged from 3 to 26 months and the overall disease-related mortality rate was 33.3%.ConclusionThe development of remnant gastric cancer after RYGB is rare. Surgeons should be aware of this potential event and the new onset of epigastric pain, nausea, and anemia should raise clinical suspicion. Further epidemiologic studies are warranted to deeply investigate the post-RYGB-related risk of remnant gastric cancer development in high-risk populations.

IntroductionThe development of achalasia after Roux-en-Y gastric bypass (RYGB) is rare. Heller myotomy (HM) is the gold standard treatment while peroral endoscopic myotomy (POEM) is an emerging technique with promising results. The aim of this narrative review was to summarize the current knowledge on the treatment of esophageal achalasia after RYGB.MethodsPubMed, EMBASE, and Web of Science databases were consulted. All articles that described the management of achalasia after RYGB were included in this narrative review.ResultsTwelve studies for a total of 28 patients were included. The age of the patient population ranged from 44 to 70 years old and 80% were females. Overall, 61.5% underwent laparoscopic RYGB while 38.5% underwent open RYBG. The elapsed time from the RYGB to myotomy ranged from 14 months to 14 years. Dysphagia (64%) and regurgitation (60.7%) were the most commonly reported symptoms; type I achalasia was diagnosed in 50% of patients. Surgical HM was performed in 17 patients (61%) while POEM was performed in 11 patients (39%). Postoperative morbidity was 3.6% with no differences comparing surgical HM and POEM (6% vs. 0%, p = 0.43). The follow-up time ranged from 1 to 43 months. The overall recurrence rate requiring reoperation was 7% with no differences comparing surgical HM and POEM (12% vs. 0%; p = 0.25).ConclusionBoth HM and POEM seem feasible, safe, and effective in the management of achalasia after RYGB. The role of POEM in the management algorithm of these patients should be further evaluated.

We analysed clinical trials of pharmacological interventions on patients with amyotrophic lateral sclerosis (ALS), and compared study quality and design features. The systematic review included articles published in PubMed and trials registered in ClinicalTrials.gov. Included studies were randomised double-blind placebo-controlled clinical trials assessing a disease-modifying pharmacological intervention. Studies were excluded if primary end points were safety or dose finding. A total of 28 735 articles and 721 current trials were identified. 76 published articles and 23 ongoing trials met inclusion criteria; they referred to distinct populations comprising 22 817 participants with ALS. Most articles and all current trials had parallel group design; few articles had cross-over design. A run-in observation period was included in about 20% of published studies and ongoing trials. Primary end points included functional assessment, survival, muscle strength, respiratory function, biomarkers and composite measures. Most recent trials had only functional assessment and survival. Risk of bias was high in 23 articles, moderate in 35, low in 18. A disease modification effect was observed for 10 interventions in phase II studies, two of which were confirmed in phase III. Three confirmatory phase III studies are currently underway. The present review provides cues for the design of future trials. Functional decline and survival, as single or composite measures, stand as the reference end points. Post hoc analyses should not be performed, particularly in studies using composite end points. There is a general agreement on diagnostic criteria; but eligibility criteria must be improved. Run-in observations may be used for censoring patients but are discouraged for refining participants’ eligibility. The ALS Functional Rating Scale-Revised needs improvement for use as an ordinal measure of functional decline.

A range of different techniques are available for predictive biomarker testing for non-small-cell lung cancer (NSCLC) clinical management. International guidelines suggest next-generation sequencing (NGS) as the preferred procedure, but other reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods are rapidly evolving. In this study, we evaluated the reliability and accuracy of the IdyllaTM GeneFusion assay, a rapid and fully automated platform able to simultaneously detect ALK, ROS1, RET and NTRK1/2/3 and MET ex14 skipping mutations and compared its performance with routine reference methods. The cohort included thirty-seven NSCLCs plus two parotid gland carcinomas, previously characterized for the above alterations through either IHC, FISH, RT-PCR or NGS. In 36 of 39 cases, the Idylla GeneFusion assay and the reference methods were concordant (overall agreement: 92.3%). Tumor sections stored at room temperature for up to 60 days and 17 cases older than 2 years were successfully characterized. Our results suggest that the Idylla GeneFusion assay is a reliable tool to define gene fusion status and may be a valuable stand-alone diagnostic test when time efficiency is needed or NGS is not feasible.

Multiple Myeloma (MM) is driven by clonal plasma cell (PC)-intrinsic factors and changes in the tumorigenic microenvironment (TME). To investigate if residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNAseq and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 18 healthy donors (HDs). Out of n=213,074 CD138pos PCs, 42,717 were genotypically identified as pPCs. Compared to HDs, we detected quantitative and qualitative differences in pPCs of patients showing immunoparesis, where we showed a pro-inflammatory status, driven by specific cellular interactions with TME. Finally, we derived a “hPC signature” that, once inferred in the CoMMpass dataset, was predictive of PFS and OS. Our findings show that genotypic, single-cell identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.