SAR user guide to the rectal MR synoptic report (primary staging).

Rectal MR is the key diagnostic exam at initial presentation for rectal cancer patients. It is the primary determinant in establishing clinical stage for the patient and greatly impacts the clinical decision-making process. Consequently, structured reporting for MR is critically important to ensure that all required information is provided to the clinical care team. The SAR initial staging reporting template has been constructed to address these important items, including locoregional extent and factors impacting the surgical approach and management of the patient. Potential outputs to each item are defined, requiring the radiologist to commit to a result. This provides essential information to the surgeon or oncologist to make specific treatment deisions for the patient. The SAR Initial Staging MR reporting template has now been officially adopted by the NAPRC (National Accreditation Program for Rectal Cancer) under the American College of Surgery. With the recent revisions to the reporting template, this user guide has been revamped to improve its practicality and support to the radiologist to complete the structured report. Each line item of the report is supplemented with clinical perspectives, images, and illustrations to help the radiologist understand the potential implications for a given finding. Common errors and pitfalls to avoid are highlighted. Ideally, rectal MR interpretation should not occur in a vacuum but in the context of a multi-disciplinary tumor board to ensure that healthcare providers use common terminology and share a solid understanding of the strengths and weaknesses of MR.

Asymptomatic Clostridium difficile carriage rate post-fecal microbiota transplant is low: a prospective clinical and stool assessment.

OBJECTIVES: We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT). METHODS: All patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8 weeks post FMT. Assessments occurred at 1 week and 4 weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well. RESULTS: 167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C. difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129). CONCLUSIONS: Asymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary.

Linkage of clinical trial and administrative data: a survey of cancer patient preferences.

BACKGROUND: Personal health information, including diagnoses and hospital admissions, is routinely collected in administrative databases. Patients enrolling on clinical trials consent to separate collection and storage of their personal health information. We evaluated patient preferences for linking long-term data from administrative databases with clinical trials. METHODS: Adults with cancer attending outpatient clinics at 3 Ontario hospitals were surveyed about their willingness, when faced with the hypothetical scenario of participating in a clinical trial, to provide potentially identifying information such as initials and date of birth to facilitate long-term research access to normally deidentified publicly collected databases. RESULTS: Of 569 patients surveyed, 335 (59%) were women, 452 (79%) were white, 385 (68%) had a post-secondary education, and 386 (68%) had never participated in a clinical trial. Median age in the group was 59 years. Most participants (93%, cohort 1) would allow long-term access to their information and allow personal information to be used to match clinical trial with administrative data. At the time of clinical trial closure, two thirds of participants (68%, cohort 2) preferred to make additional clinical information available through linkage with administrative databases, and 8 (9%) preferred to have no further information made available to researchers. No significant differences were found in the subset of patients who were part of a clinical trial and those who had never participated (p = 0.65). INTERPRETATION: Almost all patients would allow a clinical trial research team to access their confidential information, providing a more comprehensive assessment of an intervention's long-term risks and benefits.

Clostridium difficile associated risk of death score (CARDS): a novel severity score to predict mortality among hospitalised patients with C. difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is a public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. AIM: To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile associated risk of death score (CARDS). METHODS: We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalisations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilised to identify independent predictors of mortality. Clostridium difficile associated risk of death score was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. RESULTS: We identified 77 776 hospitalisations, yielding an estimate of 374 747 cases with an associated diagnosis of CDI in the US, 8% of whom died in the hospital. The eight severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from -1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. CONCLUSION: Clostridium difficile associated risk of death score is a promising simple severity score to predict mortality among those hospitalised with C. difficile infection.

The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema.

Clostridium difficile infection (CDI) is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. The management of CDI has become a major challenge, given growing rates of recurrences and failures with standard antibiotic therapy. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is a paucity of data with regard to repeat FMT for primary non-response to this treatment, this study examined the outcome of multiple FMTs for recurrent CDI. Case records were reviewed for 94 patients who underwent FMT via retention enema for recurrent or refractory CDI during the period 2008-2012. Demographic information, treatment data, and clinical resolution rates were examined for single FMT and cumulative resolution was assessed for multiple FMTs in the context of ongoing symptoms. The cumulative clinical resolution following four or more FMTs was 86%. When antibiotic therapy was used between FMTs, the clinical resolution rate increased to 92%. There were no reported adverse events and no patients who were cured with FMT had further episodes of CDI at 6-24 months follow-up. Multiple FMTs administered through enemas is an effective, safe, and simple therapy for the management of recurrent or refractory CDI.

Laparoscopic gastrectomy for patients with advanced gastric cancer produces oncologic outcomes similar to those for open resection.

BACKGROUND: Laparoscopic gastrectomy has gained acceptance as treatment for early gastric cancer. However, its role for advanced gastric cancer remains unclear. This study aimed to compare the oncologic outcomes between laparoscopic and open gastrectomy in the management of advanced gastric cancer for patients receiving adjuvant chemoradiotherapy. METHODS: This study reviewed consecutive patients treated with gastric cancer resection and adjuvant chemoradiation (45 Gy/25 with 5-fluorouracil [FU]-based chemotherapy), at a quaternary care comprehensive cancer center between 1 Jan 2000 and 30 Nov 2009. Of 203 patients, 21 were treated with laparoscopic gastrectomy. These patients were compared with patients who had open surgery and evaluated for overall survival, relapse-free survival, and site of first disease recurrence. RESULTS: The 21 patients in the laparoscopic group had a median age of 61.3 years (range, 28.2-76.6 years) and a median follow-up period of 21.3 months (range, 6.7-50.4 months). The majority of the patients (71%) were men. Most of these patients had tumor node metastasis (TNM) v6 stage 2 (33%) or 3 (52%) disease as classified by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). The demographic characteristics of the laparoscopic and open groups were similar. The incidence of recurrence was 38.1% (8/21) in the laparoscopic group and 36.8% (67/182) in the open group. In the laparoscopic group, the site of first recurrence was distant in three patients, peritoneal in four patients, and mixed in one patient (locoregional and distant). The recurrence patterns did not differ significantly between the laparoscopic and open surgery groups. In the open group, recurrence was distant in 26 patients, peritoneal in 12 patients, and locoregional in 15 patients. At presentation, 14 patients showed a mixed pattern. The 3-year relapse-free survival rate was 58% (range, 50-66%), and the difference between the two groups by Gray's test was not significant (P = 0.32). The 3-year overall survival rate was 65.9% (range, 58-73%) and did not differ significantly between the two groups in the univariate (P = 0.92) or multivariate (P = 0.54) analysis. CONCLUSION: The study findings suggest that laparoscopic gastrectomy is an oncologically safe procedure for advanced gastric cancer with outcomes similar to those for open resection.

Adjuvant chemoradiation for gastric cancer with infusional 5-fluorouracil and cisplatin: a phase I study.

OBJECTIVE: This phase I study aimed to determine the maximal tolerated dose of cisplatin administered every 2 weeks with infusional 5-fluorouracil (5FU) and concurrent radiation therapy (RT) in patients after complete resection of gastric adenocarcinoma. METHODS: Patients with resected stage IB to IV (M0) gastric adenocarcinoma were treated with 12 weeks of infusional 5FU (200 mg/m(2) daily) and with RT (45 Gy in 25 fractions starting on day 16). Cisplatin was administered in escalating doses (0, 20, 30, and 40 mg/m(2)) in weeks 1, 3, 5, and 7. In the final cohort, patients received an additional dose of cisplatin (40 mg/m(2)) in week 9. RESULTS: Among the 34 patients [median age: 56 years (range: 31-77 years)] who were assessable for toxicity, 5 experienced dose-limiting toxicities: 1 sepsis (cohort 1), 1 fatigue (cohort 2), 3 upper gastrointestinal toxicity (1 in cohort 2, 2 in cohort 5). Cohort 5 exceeded the maximal tolerated dose. Median follow-up was 2.5 years (range: 0.3-5 years). The 3-year overall and relapse-free survival rates were 86% and 71% respectively; median survival was not reached. CONCLUSIONS: Cisplatin was well tolerated in combination with infusional 5FU and RT, showing promising activity in the adjuvant treatment of gastric cancer. Infusional 5FU 200 mg/m(2) daily for 12 weeks with cisplatin 40 mg/m(2) in weeks 1, 3, 5, and 7 and with concurrent RT 45 Gy in 25 fractions, starting at day 16, is being explored in a phase II study at our institution.

Evaluating the impact on quality of life of chemoradiation in gastric cancer.

OBJECTIVE: Our phase I study prospectively evaluated quality of life (QOL) in patients undergoing adjuvant chemoradiation for gastric adenocarcinoma. METHODS: Thirty-three patients receiving radiotherapy (45 Gy in 25 fractions), together with 12 weeks of infusional 5-fluorouacil and escalating doses of cisplatin every 2 weeks, completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 at five time points: baseline, completion of radiation, 4 weeks after completion of radiation, 6-12 months after completion of chemoradiation, and 2-3 years after completion of chemoradiation. RESULTS: Mean age of the patients was 56 years (range: 31-77 years); 55% of the patients were male. Median follow-up was 2.7 years (range: 0.3-5 years). The 3-year overall survival was 83%. Five patients experienced dose-limiting toxicity (DLT). Median scores on global QOL and on the social, role, emotional, nausea and vomiting, and fatigue scales showed clinically and statistically significant worsening at completion of radiation. Statistical but not clinical worsening was found for the physical and appetite scales. By 6-12 months, no subscale showed a difference, on average, from the baseline score. However, up to 45% of the patients remained below baseline on at least 1 subscale. Patients with DLT had worse scores on the emotional and the nausea and vomiting scales. Scores for global QOL and for nausea and vomiting were significantly associated with chemotherapy dose. CONCLUSIONS: During chemoradiation, QOL is impaired. Although most scores return to baseline, recovery may take 6-12 months, and subscale scores remain below baseline in a significant proportion of patients.

A phase I/II study to evaluate the toxicity and efficacy of accelerated fractionation radiotherapy for the palliation of dysphagia from carcinoma of the oesophagus.

AIMS: We hypothesised that accelerated fractionated radiotherapy may provide a good palliative approach for dysphagia relief in patients with incurable oesophageal cancer, significantly reducing the overall duration of treatment, while providing symptom response with an acceptable toxicity profile. A phase I/II accelerated fractionation study was conducted to evaluate the efficacy and toxicity of this approach. MATERIALS AND METHODS: Patients with incurable oesophageal cancer, symptomatic with dysphagia, Eastern Cooperative Oncology Group performance statusor=6 h apart), 5 days a week, over 2 weeks. RESULTS: Of the 39 evaluable patients, the dysphagia response rate was 69% (27/39) with a median response duration of 5.5 months. The median time to response was 4 weeks. Twenty-eight per cent (11/39) of patients had transient worsening in their dysphagia scores. Acute toxicity (weeks 1-8) occurred in 41% (16/39) of patients. An improvement in global quality of life by week 8 was seen in 42% of patients. There were no late neurological sequelae. The median overall survival was 8 (range 1.7-58+) months. CONCLUSION: The ideal palliative regimen should be relatively short, with minimal toxicity, while offering a favourable response profile. Accelerated fractionation fulfils these criteria and is a suitable treatment alternative for the palliation of dysphagia, especially if the goal is to deliver a higher total biological dose within a shorter (2 week) period of time.

Down-regulation of transforming growth factor-beta receptors: cooperativity between the types I, II, and III receptors and modulation at the cell surface.

The types I, II, and III receptors (RI, RII, RIII) for transforming growth factor-beta (TGF-beta) become down-regulated in response to ligand, presumably via their internalization from the cell surface. This report examines the down-regulation of full-length RI, RII, and RIII in cells endogenously or transiently expressing these receptors. Down-regulation occurred rapidly (within 2 h after TGF-beta1 treatment at 37 degrees C) and showed a dose response, between 10 and 200 pM TGF-beta1, in cells expressing RI, RII, and RIII (Mv1lu and A549 cells). A comparison between Mv1Lu and mutant cell derivatives R-1B (lacking RI) or DR-26 (lacking RII) indicated that all three receptors were necessary for efficient down-regulation. Down-regulation experiments, utilizing TGF-beta-treated 293 cells transiently expressing different combinations of these receptors indicated that neither RII or RIII were down-regulated when expressed alone and that RI was required for maximal down-regulation of RII. RII and RIII were partially down-regulated when these receptors were coexpressed in the absence of RI (in R-1B and 293 cells). Surprisingly, TGF-beta receptors were partially down-regulated in Mv1Lu, A549, and 293 cells treated with TGF-beta1 at 4 degrees C. Microscopic examination of 293 cells coexpressing RI fused to green fluorescent protein (RI-GFP) and RII indicated that, after treatment with TGF-beta1 at 4 degrees C, RI-GFP formed aggregates at the cell surface at this temperature. RI-GFP was not detected at the surface of these cells after TGF-beta1 treatment at 37 degrees C. Our results suggest a two phase mechanism for TGF-beta1 receptor down-regulation involving receptor modulation (aggregation) at the cell surface and internalization.