Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

There is increasing evidence supporting the use of preoperative chemoradiotherapy in patients with locally advanced rectal cancer in an attempt to facilitate complete surgical resection with clear margins. We describe our experience of using a 5-day per week regime of preoperative capecitabine chemoradiotherapy. Between November 2004 and September 2006, 70 patients with MRI-defined locally advanced rectal cancer were selected for treatment. Capecitabine was given at a dose of 900 mg m−2 for 5 days per week combined with 45 Gy of radiotherapy in 25 doses. This regime was well tolerated with 89% of our patients receiving the full dose of chemotherapy and 96% receiving the full dose of radiotherapy. Ninety-three per cent proceeded to macroscopically complete surgical resection. The pathological complete response rate was 9.2% with a node-negative rate of 66%. A negative circumferential margin was achieved by 79% of the patients who underwent resection. Compared to studies using a 7-day per week capecitabine schedule, our results show increased compliance and less dose reductions with comparable pathological outcome

Singular Support of a Vertex Algebra and the Arc Space of Its Associated Scheme

Book Subtitle: In Honour of the 75th Birthday of Tony JosephSeries Title: Progress in Mathematics (vol. 330)Attached to a vertex algebra V are two geometric objects. The associated scheme of V isthespectrum of Zhu's Poisson algebra Rv.Thesingular support of V is the spectrum of the associated graded algebra gr(V) with respect to Li's canonical decreasing filtration. There is a closed embedding from the singular support to the arc space of the associated scheme, which is an isomorphism in many interesting cases. In this note we give an example of a non-quasi-lisse vertex algebra whose associated scheme is reduced, for which the isomorphism is not true as schemes but true as varieties

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma

Purpose: To describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiotherapy (IMRT). Materials and methods: A retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardised IMRT technique in five UK cancer centres. Patients were included from the start of UK IMRT guidance in February 2013 to 31st October 2017. Collected data included baseline demographics, treatment details, tumour control, sites of relapse and overall survival. Statistical analysis to calculate outcomes and predictive factors for outcome measures were performed using SPSS and R. Results: The medical records of 385 consecutive patients were analysed. Median follow-up was 24.0 months. 86.7% of patients achieved a complete response (CR) within 6 months of completing chemoradiotherapy. 3yr disease free survival (DFS) and overall survival (OS) were 75.6% and 85.6% respectively. Of all relapses, 83.4% occurred at the site of primary disease. There were two isolated relapses in regional nodes not involved at outset. Predictive factors for cancer recurrence included male sex, high N-stage and failure to complete radiotherapy as planned. Conclusions: The treatment results compare favourably to published outcomes from similar cohorts using 3D conformal CRT. The observed patterns of failure support the current UK IMRT voluming guidelines and dose levels, highlighting our prophylactic nodal dose is sufficient to prevent isolated regional relapse in uninvolved nodes. Further investigation into strategies to optimise CR should remain a priority in ASCC, as the site of primary disease remains the overwhelming site of relapse

High-resolution magic angle spinning 1H nuclear magnetic resonance spectroscopy metabolomics of hyperfunctioning parathyroid glands

Background Primary hyperparathyroidism (PHPT) may be related to a single gland disease or multiglandular disease, which requires specific treatments. At present, an operation is the only curative treatment for PHPT. Currently, there are no biomarkers available to identify these 2 entities (single vs. multiple gland disease). The aims of the present study were to compare (1) the tissue metabolomics profiles between PHPT and renal hyperparathyroidism (secondary and tertiary) and (2) single gland disease with multiglandular disease in PHPT using metabolomics analysis. Methods The method used was 1H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. Forty-three samples from 32 patients suffering from hyperparathyroidism were included in this study. Results Significant differences in the metabolomics profile were assessed according to PHPT and renal hyperparathyroidism. A bicomponent orthogonal partial least square-discriminant analysis showed a clear distinction between PHPT and renal hyperparathyroidism (R2Y = 0.85, Q2 = 0.63). Interestingly, the model also distinguished single gland disease from multiglandular disease (R2Y = 0.96, Q2 = 0.55). A network analysis was also performed using the Algorithm to Determine Expected Metabolite Level Alterations Using Mutual Information (ADEMA). Single gland disease was accurately predicted by ADEMA and was associated with higher levels of phosphorylcholine, choline, glycerophosphocholine, fumarate, succinate, lactate, glucose, glutamine, and ascorbate compared with multiglandular disease. Conclusion This study shows for the first time that 1H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy is a reliable and fast technique to distinguish single gland disease from multiglandular disease in patients with PHPT. The potential use of this method as an intraoperative tool requires specific further studies. © 2016 Elsevier Inc

Does intraoperative neuromonitoring of recurrent nerves have an impact on the postoperative palsy rate? Results of a prospective multicenter study

BACKGROUND: The impact of intraoperative neuromonitoring on recurrent laryngeal nerve palsy remains debated. Our aim was to evaluate the potential protective effect of intraoperative neuromonitoring on recurrent laryngeal nerve during total thyroidectomy. METHODS: This was a prospective, multicenter French national study. The use of intraoperative neuromonitoring was left at the surgeons\u27 choice. Postoperative laryngoscopy was performed systematically at day 1 to 2 after operation and at 6 months in case of postoperative recurrent laryngeal nerve palsy. Univariate and multivariate analyses and propensity score (sensitivity analysis) were performed to compare recurrent laryngeal nerve palsy rates between patients operated with or without intraoperative neuromonitoring. RESULTS: Among 1,328 patients included (females 79.9%, median age 51.2 years, median body mass index 25.6 kg/m), 807 (60.8%) underwent intraoperative neuromonitoring. Postoperative abnormal vocal cord mobility was diagnosed in 131 patients (9.92%), including 69 (8.6%) and 62 (12.1%) in the intraoperative neuromonitoring and nonintraoperative neuromonitoring groups, respectively. Intraoperative neuromonitoring was associated with a lesser rate of recurrent laryngeal nerve palsy in univariate analysis (odds ratio = 0.68, 95% confidence interval, 0.47; 0.98, P = .04) but not in multivariate analysis (oddsratio = 0.74, 95% confidence interval, 0.47; 1.17, P = .19), or when using a propensity score (odds ratio = 0.76, 95% confidence interval, 0.53; 1.07, P = .11). There was no difference in the rates of definitive recurrent laryngeal nerve palsy (0.8% and 1.3% in intraoperative neuromonitoring and non-intraoperative neuromonitoring groups respectively, P = .39). The sensitivity, specificity, and positive and negative predictive values of intraoperative neuromonitoring for detecting abnormal postoperative vocal cord mobility were 29%, 98%, 61%, and 94%, respectively. CONCLUSION: The use of intraoperative neuromonitoring does not decrease postoperative recurrent laryngeal nerve palsy rate. Due to its high specificity, however, intraoperative neuromonitoring is useful to predict normal vocal cord mobility. From the CHU de Nantes, Clinique de Chirurgie Digestive et Endocrinienne, Nantes, France; CHU Lille, Université de Lille, Chirurgie Générale et Endocrinienne, Lille, France; CHU Nancy-Hôpital de Brabois, Service de Chirurgie Digestive, Hépato-Biliaire, et Endocrinienne, Nancy, France; CHU Angers, Chirurgie Digestive et Endocrinienne, Angers, France; CHU de Toulouse-Hôpital Larrey, Chirurgie Thoracique, Pôle Voies Respiratoires, Toulouse; CHU Saint-Etienne-Hôpital Nord, ORL et Chirurgie Cervico-Faciale et Plastique, Saint-Etienne, France; CHU de Limoges-Hôpital Dupuytren, Chirurgie Digestive, Générale et Endocrinienne, Limoges, France; CHU de Besançon-Hôpital Jean Minjoz, Chirurgie Digestive, Besançon, France; Centre Hospitalier du Mans, Service ORL et Chirurgie Cervico-Faciale, Le Mans, France; Centre Hospitalier Lyon-Sud, Chirurgie Générale, Endocrinienne, Digestive et Thoracique, Pierre Bénite, France; AP-HM-Hôpital de La Conception, Chirurgie Générale, Marseille, France; CHU de Rennes-Hôpital Pontchaillou, Service ORL et Chirurgie Maxillo-Faciale, Rennes, France; CHU de Caen, ORL et Chirurgie Cervico-Faciale, Caen, France; CHU d\u27Angers, ORL et Chirurgie Cervico-Faciale, Angers, France; CHU de Nantes, Service ORL, Nantes, France; AP HP URCEco île-de-France, hôpital de l\u27Hôtel-Dieu, Paris, France; DRCI, département Promotion, Nantes, France

Can we <i>S</i>ave the rectum by watchful waiting or <i>T</i>rans<i>A</i>nal microsurgery following (chemo) <i>R</i>adiotherapy versus total mesorectal excision for early <i>RE</i>ctal <i>C</i>ancer (STAR-TREC study)?::protocol for a multicentre, randomised feasibility study

Introduction Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery. Methods and analysis STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2

A new specific succinate-glutamate metabolomic hallmark in SDHx-related paragangliomas

Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with (1)H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones