Relationship Between Baseline Rectal Tumor Length and Magnetic Resonance Tumor Regression Grade Response to Chemoradiotherapy: A Subanalysis of the TRIGGER Feasibility Study.

BACKGROUND: It is widely believed that small rectal tumors are more likely to have a good response to neoadjuvant treatment, which may influence the selection of patients for a 'watch and wait' strategy. OBJECTIVE: The aim of this study was to investigate whether there is a relationship between baseline tumor length on magnetic resonance imaging (MRI) and response to chemoradiotherapy. METHOD: The 96 patients with locally advanced rectal cancer randomised (2:1-intervention:control) in the TRIGGER feasibility study where eligible. Baseline tumor length was defined as the maximal cranio-caudal length on baseline MRI (mm) and was recorded prospectively at study registration. Magnetic resonance tumor regression grade (mrTRG) assessment was performed on the post-chemoradiotherapy (CRT) MRI 4-6 weeks (no later than 10 weeks) post completion of CRT. This was routinely reported for patients in the intervention (mrTRG-directed management) arm and reported for the purposes of this study by the central radiologist in the control arm patients. Those with an mrTRG I/II response were defined as 'good responders' and those with an mrTRG III-V response were defined as 'poor responders'. RESULTS: Overall, 94 patients had a post-CRT MRI performed and were included. Forty-three (46%) patients had a good response (mrTRG I/II) and 51 (54%) patients had a poor response (mrTRG III/IV). The median tumor length of good responders was 43 mm versus 50 mm (p < 0.001), with considerable overlap in tumor lengths between groups. CONCLUSION: Baseline tumor length on MRI is not a clinically useful biomarker to predict mrTRG tumor response to CRT and therefore patient suitability for a deferral of surgery trial.

Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales.

AIM: To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer. METHODS: A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included "tumour regression", "mrTRG", "poor response" and "colorectal cancers". Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures. RESULTS: Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR 0%-1.8%, DR 0%-11.6%, DFS 78.4%-86.7%, and OS 77.4%-88.2%. A poor response on MRI (mrTRG 4,5) resulted in 5-year LR 4%-29%, DR 9%, DFS 31%-59% and OS 27%-68%. The 5-year outcomes with a good response on MRI (mrTRG 1,2 and 3) were LR 1%-14%, DR 3%, DFS 64%-83% and OS 72%-90%. CONCLUSION: For histopathology regression assessment, Mandard 1, 2/Dworak 3, 4 should be used for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5, respectively.

Double-Gloving Impairs the Quality of Surgical Knot Tying: A Randomised Controlled Trial.

BACKGROUND: Double-gloving is endorsed by a number of healthcare authorities worldwide, on the basis that it promotes patient and surgeon safety; adoption of this practice amongst surgeons remains limited, based upon anecdotal reporting that double-gloving may compromise surgical technique due to impaired dexterity and sensation. The aim of this study is to formally investigate and demonstrate the effect of double-gloving upon the quality of knot tying, an essential surgical skill. METHODS: An international cohort of practising general surgeons hand tied surgical knots, under both single-gloved and double-gloved conditions, using monofilament and braided sutures, at two different gauges. Half of the participants tied single-gloved first. The mechanical strength of the knots was determined by tensile testing, and each knot was given a knot quality score (KQS), a validated assessment of knot quality. RESULTS AND CONCLUSIONS: 1466 knots were tested. Double-gloving was shown to reduce KQS for all suture types, compared to knots tied under single-gloved conditions (p = 0.001). There was no difference in the KQS of the double-gloved ties between those who routinely double-gloved and those who did not (p = 0.640). The OR showed that double-gloving reduced the KQS by 24 % overall, with the effect being much more prominent when the finer 4.0 suture was used, as knot quality was reduced by almost 50 % (95 % CI 13-93 %). Double-gloving impairs the quality of knot tying, and therefore, surgeons should consider other precautions to ensure patient and surgeon safety. These findings also question the validity of recommendations that surgeons should double-glove as a routine.

Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study.

OBJECTIVE: This study aimed to validate a magnetic resonance imaging (MRI) staging classification that preoperatively assessed the relationship between tumor and the low rectal cancer surgical resection plane (mrLRP). BACKGROUND: Low rectal cancer oncological outcomes remain a global challenge, evidenced by high pathological circumferential resection margin (pCRM) rates and unacceptable variations in permanent colostomies. METHODS: Between 2008 and 2012, a prospective, observational, multicenter study (MERCURY II) recruited 279 patients with adenocarcinoma 6 cm or less from the anal verge. MRI assessed the following: mrLRP "safe or unsafe," venous invasion (mrEMVI), depth of spread, node status, tumor height, and tumor quadrant. MRI-based treatment recommendations were compared against final management and pCRM outcomes. RESULTS: Overall pCRM involvement was 9.0% [95% confidence interval (CI), 5.9-12.3], significantly lower than previously reported rates of 30%. Patients with no adverse MRI features and a "safe" mrLRP underwent sphincter-preserving surgery without preoperative radiotherapy, resulting in a 1.6% pCRM rate. The pCRM rate increased 5-fold for an "unsafe" compared with "safe" preoperative mrLRP [odds ratio (OR) = 5.5; 95% CI, 2.3-13.3)]. Posttreatment MRI reassessment indicated a "safe" ymrLRP in 33 of 113 (29.2%), none of whom had ypCRM involvement. In contrast, persistent "unsafe" ymrLRP posttherapy resulted in 17.5% ypCRM involvement. Further independent MRI assessed risk factors were EMVI (OR = 3.8; 95% CI, 1.5-9.6), tumors less than 4.0 cm from the anal verge (OR = 3.4; 95% CI, 1.3-8.8), and anterior tumors (OR = 2.8; 95% CI, 1.1-6.8). CONCLUSIONS: The study validated MRI low rectal plane assessment, reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy. It also highlights the importance of posttreatment restaging.

Metachronous colorectal cancer: a competing risks analysis with consideration for a stratified approach to surveillance colonoscopy.

BACKGROUND: The incidence of metachronous cancer will become an important clinical consideration as the life expectancy of the population increases and as rates of curative resection improve. OBJECTIVE: To assess the pattern of metachronous cancer development following curative resection of colorectal cancer in an unselected patient population offered postoperative colonoscopic surveillance. METHOD: Prospective clinical follow-up after curative colorectal cancer resection and surveillance colonoscopy with or without polypectomy in accordance with the national guidelines. Actuarial analysis and competing risk analysis were performed to account for death and recurrence and to stratify for age, gender, stage, and tumor site. RESULTS: Five hundred thirty-eight patients with median follow-up 4 years 2 month (0-16) years. Fifteen patients (3%) developed metachronous cancer, at a median time interval of 90 months from primary resection. Thirteen metachronous cancer patients (87%, 13/15) underwent one to five surveillance colonoscopies: nine patients were asymptomatic at time of diagnosis of metachronous cancer. Competing risks analysis suggests that the adjusted cumulative incidence in males aged 55 is 4% at 10 years compared with 1% in females aged 85 years old. CONCLUSIONS: A patient aged under 65 at the time of the primary curative resection carries a 2% 5-year risk of metachronous cancer, implying that 3 year surveillance colonoscopy is justified. Whereas patients aged over 75 carry less than a 2% 10-year risk, implying that it is seldom warranted to repeat the colonoscopy more frequently than every 5 years. A stratified approach to the frequency of surveillance colonoscopy requires further consideration.

Interferon-γ ELISPOT as a biomarker of treatment efficacy in latent tuberculosis infection: a clinical trial.

RATIONALE: Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required. OBJECTIVES: To evaluate ESAT-6 and CFP-10 (EC) IFN-γ ELISPOT as a biomarker for treatment efficacy in LTBI. METHODS: This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants. MEASUREMENTS AND MAIN RESULTS: Participants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT-positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time. CONCLUSIONS: In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen-specific T-cell responses over time. IFN-γ ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI. Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).

Outcomes following oesophageal stent insertion for palliation of malignant strictures: A large single centre series.

BACKGROUND: Self-expanding metal stents (SEMS) are an accepted intervention for malignant dysphagia. Stents vary in ease of insertion, removability, migration and occlusion rates. This series reports the complications, morbidity and mortality associated with several SEMS. METHOD: A prospective database of patients undergoing fluoroscopic guided oesophageal stent insertion for malignancy between June 2001 and June 2009 was analysed. Patient demographics, intervention outcomes and tumour variables were correlated with stent failure and patient survival. Multivariate analysis was performed to evaluate predictors for stent failure. RESULTS: Two hundred and seventy-three stents were deployed using nine different types of SEMS. The median Mellow-Pinkas dysphagia score significantly improved from 3 to 1 post-stent insertion (P < 0.001), with a technical success rate of 98%. Stent complications occurred in 95 (36%) patients [recurrent dysphagia n = 49 (19%), migration n = 24 and occlusion n = 25]. Multivariate analysis demonstrates that the covered Niti S stent fails significantly more than the double-layered Niti S stent (OR = 4, P < 0.005). CONCLUSION: Oesophageal stent insertion provides good palliation for malignant dysphagia, however recurrent dysphagia remains a problem. This major complication occurs more frequently with covered Niti S stents than double-layered Niti S stents. This finding may aid the stent choice used in advanced oesophageal malignancy.