Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes.

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

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.

The spectrum of myelodysplastic syndromes post-solid organ transplantation: a single institutional experience.

An increased incidence of acute myeloid leukemia (AML) has recently been documented in patients post-solid organ transplantation but the incidence and types of myelodysplastic syndromes (MDS) occurring in this patient population are not known. We identified 5 patients (3M, 2F, age 48-64 years) who developed MDS ranging from 1.8 to 25 years (median 4.2 years) post-solid organ transplantation, only 2 patients had received azathioprine. The cumulative incidence of MDS in heart and lung transplant recipients at 15 years was 0.5% and 1.8%, respectively, which is markedly higher compared to the general population. Low-risk types of MDS predominated, 3 of 5 patients are alive (median 3.9 years) since diagnosis. Deletions of chromosome 20q, which have not been previously reported in post-transplant MDS/AML, were identified in 3 cases. Our findings expand the morphologic and cytogenetic spectrum of MDS occurring post-solid organ transplantation and suggest that mechanisms beside azathioprine toxicity might be important in disease pathogenesis.

Substrate specificity and kinetic mechanism of the insect sulfotransferase, retinol dehydratase.

Spodoptera frugiperda retinol dehydratase catalyzes the conversion of retinol to the retro-retinoid anhydroretinol. It shares sequence homology with the family of mammalian cytosolic sulfotransferases and provides the first link between sulfotransferases and retinol metabolism. In this study the enzymatic properties of retinol dehydratase were examined using bacterially expressed protein. We show that retinol dehydratase can catalyze the transfer of the sulfonate moiety to small phenolic compounds and exhibits many functional similarities to the mammalian cytosolic sulfotransferases. The bisubstrate reaction that it catalyzes between retinol and the universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate seems to involve ternary complex formation and to proceed via a Random Bi Bi mechanism. In addition to the low nanomolar Km value for free retinol, retinol dehydratase is strongly inhibited by retinol metabolites, suggesting a preference for retinoids. Conversely, a number of tested mammalian cytosolic sulfotransferases do not utilize retinol, indicating that retinol is not a general substrate for sulfotransferases.