Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2-4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting.

Combining Ketamine and Internet-Based Cognitive Behavioral Therapy for the Treatment of Posttraumatic Stress Disorder: Protocol for a Randomized Controlled Trial.

BACKGROUND: Over one third of patients with posttraumatic stress disorder (PTSD) do not respond to current interventions. Ketamine presents a potential treatment option; however, its effects are temporary. Administering ketamine alongside psychotherapy is one potential means of prolonging its effects; however, only a few studies have investigated this treatment method to date, and none have tested ketamine with internet-based or electronically delivered cognitive behavioral therapy (e-CBT). OBJECTIVE: This open-label randomized controlled trial aims to assess the efficacy of a combined treatment method of subanesthetic intravenous ketamine and e-CBT for treating patients with PTSD. METHODS: In total, 20 patients with refractory PTSD recruited from a community clinic will be randomly assigned to either an experimental group (n=10), receiving a combination of ketamine and therapist-administered e-CBT over 14 weeks, or a waitlist control group (n=10), receiving the experimental treatment after 14 weeks. Both groups will be assessed for the symptoms of PTSD and comorbid disorders before treatment, at two midway points, and at the end of the experiment. RESULTS: PTSD symptoms of participants in the experimental group are expected to improve significantly more than those of participants in the waitlist control group (P=.05) with a large effect size (η2=0.14). CONCLUSIONS: This is the first study to assess the relationship between e-CBT and ketamine and their combined ability to treat refractory PTSD. If successful, this study will open web-based, asynchronous therapeutic options for patients with PTSD and will provide new insights into the functional role of glutamate in trauma-related disorders as well as in learning, memory, and fear extinction. TRIAL REGISTRATION: ClinicalTrials.gov NCT04771767; https://clinicaltrials.gov/ct2/show/NCT04771767. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30334.

Systematic Review of Interventions to Increase Awareness of Ultraviolet Radiation-Induced Harm and Protective Behaviors in Post-Secondary School Adults.

College and university students are a group known for excessive sun exposure and indoor tanning. Health education campaigns for avoidance of ultraviolet (UV) radiation have been relatively unsuccessful in this population. This systematic review examines interventions aimed at post-secondary school young adults on college and university campuses for skin cancer awareness, photoprotection, and change in UV-exposure-related behavior. Fifty-nine studies were identified for inclusion according to predetermined criteria. Study heterogeneity was high; methods of intervention were individual or group-based, and were mostly visually delivered and/or passive learning. Most interventions occurred at a single time point. Intervention success was assessed by evaluating subject behavior, intention, attitudes, knowledge, and emotion. Multicomponent interventions, generally consisting of UV photography and a passively delivered educational component, may be more effective than a single component alone. Overall, study quality was poor. Sample size of the majority of studies was <150 subjects. Most studies used self-report of behavior and had a short follow-up time. Generalizability of findings may be impacted as women, particularly white/Caucasian women, were overrepresented in the studies identified by this systematic review. For this specific target population, themes arising from the review include the importance of self-relevance and message framing. Self-affirmation was identified as a potential challenge in designing interventions for this target group, which can lead to defensiveness and a negative reaction to the health message. The findings of this systematic review may inform future research in this field, as well as guide planning of effective interventions in this target population.

Topical pain control for corneal abrasions: A systematic review and meta-analysis.

OBJECTIVES: Corneal abrasions are common ophthalmic presentations to emergency departments. Among emergency physicians and ophthalmologists, there are highly variable practice patterns with regard to management of resultant pain and discomfort. The goal of this study was to review and analyze the efficacy and safety of topical pain therapies for corneal abrasions, including topical anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), cycloplegics, steroids, pressure patching, and the use of a bandage contact lens (BCL). METHODS: The review followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The protocol was established a priori and published on PROSPERO (CRD42020201288). MEDLINE, EMBASE, CENTRAL, and Web of Science were searched until December 31, 2020. Primary studies comparing topical pain therapies to another therapy or control were included. Primary outcomes included percentage of corneal abrasions healed at 24, 48, and 72 hours, as well as pain control at 24 and 48 hours. Secondary outcomes included use of oral analgesia and incidence of complications. Risk of bias was assessed using validated tools. Quality of evidence was assessed using the GRADE methodology. RESULTS: Overall, 33 studies (31 randomized controlled trials [RCTs], two cohort studies) comprising 4,167 patients with corneal abrasions were analyzed. Only the data for topical NSAIDs were of adequate evidence from which to draw conclusions; topical NSAIDs demonstrated significantly reduced pain scores at 24 hours (standardized mean differences [SMD] -0.69, 95% CI = -0.98 to -0.41) and 48 hours (SMD = -0.56, 95% CI = -1.02 to -0.10) as well as 53% (95% CI = 34% to 67%) lower oral analgesia use compared to control. Based on available data, topical anesthetics, cycloplegics, patching, and the use of a BCL did not result in any significant difference in pain scores or use of oral analgesia, while no studies examined topical steroids. No interventions resulted in healing delays or significantly higher rates of complications compared to controls. CONCLUSIONS: There was strong evidence to support that topical NSAIDs reduce pain associated with corneal abrasions in the first 48 hours and the need for oral analgesia. The existing evidence was insufficient to support or refute the use of topical anesthetics, cycloplegics, steroids, or BCL for pain control in corneal abrasions. Pressure patching was ineffective at pain reduction and may increase the risk of complications. Delays in healing or other complications were not significantly different between any intervention or control for simple, uncomplicated corneal abrasions; however, larger RCTs are required to identify any differences in rare complications.

Predictors of Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer: A Multicenter Study.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective multicenter study involving 5 Canadian cancer centers. PATIENTS AND METHODS: Cancer registries identified consecutive patients with locally advanced rectal adenocarcinoma from the Tom Baker Cancer Centre, Cross Cancer Institute, British Columbia Cancer Agency, Ottawa Hospital Cancer Centre, and the Dr H. Bliss Murphy Cancer Centre who received fluoropyrimidine-based CRT and had curative intent surgery from 2005 to 2012. Patient, tumor, and therapy characteristics were correlated with response. RESULTS: Of the 891 patients included, 885 patients had pCR data available. Of the included patients, 161 (18.2%) had a pCR to CRT, and 724 (81.8%) did not. Patients with a pCR had a lower pretreatment carcinoembryonic antigen (CEA) level, and higher hemoglobin level in univariate analysis. In multivariable analysis, statin use at baseline (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.02-2.92; P = .04), lower pretreatment CEA level (OR, 1.03; 95% CI, 1.01-1.06; P = .03), and distance closer to anal verge (OR, 1.07; 95% CI, 1.01-1.15; P = .04) were significant predictors of pCR. The 3-year disease-free survival was 86% in those with a pCR versus 62.5% in those without a pCR (P < .0001) and pCR was associated with improved overall survival (hazard ratio, 0.29; 95% CI, 0.17-0.51; P < .0001). CONCLUSION: Lower pretreatment CEA level, proximity to anal verge, and statin use are predictors of pCR in our large retrospective cohort. Clinical trials to investigate statins combined with neoadjuvant CRT might be warranted.

Efficacy and safety of single agent or combination adjuvant chemotherapy in elderly patients with colon cancer: a Canadian cancer institute experience.

BACKGROUND: The pattern of adjuvant chemotherapy (AC) use, toxicity profile, and survival benefit in elderly patients with colon cancer (CC) is unclear. We sought to (1) determine whether patients ≥ 65 years with stage III CC were offered single-agent or combination AC, (2) evaluate the reason for selecting single-agent versus combination AC, (3) evaluate the toxicity profile of single-agent and combination AC in the elderly, and (4) determine whether a survival benefit exists for elderly patients receiving combination AC. PATIENTS AND METHODS: A retrospective analysis of records of patients ≥ 65 years diagnosed with stage III CC from 2004 to 2010 was performed to identify baseline characteristics, AC protocols, toxicity, dose intensity, and survival. RESULTS: Two hundred sixty-eight patients ≥ 65 years were diagnosed and treated with AC from 2004 to 2010. Of these patients, 178 were treated with single-agent AC and 90 were treated with combination AC. The most common reasons for choosing single-agent AC were patient preference, comorbidities, and lack of drug coverage. For each year over 65 years, the odds of receiving combination over single-agent AC decreased by 22%. There were more dose delays, dose reductions, and early chemotherapy discontinuation in the combination AC group because of hematologic toxicity. The 5-year overall survival (OS) was 73% in patients who received single-agent AC compared with 84% in those who received combination AC. There was no difference in cancer-related deaths between the groups. CONCLUSION: In elderly patients treated with AC for stage III CC, single-agent AC is used more frequently than combination AC, based on age, comorbidities, and patient choice. Toxicity with combination AC in elderly patients is high. No survival benefit was seen with combination AC over single-agent AC.

Medical and surgical procedures experienced by young children with cerebral palsy.

PURPOSE: To determine the variation in medical and surgical procedures experienced by children with cerebral palsy (CP) by Gross Motor Function Classification System (GMFCS) levels and geographical region. METHODS: A secondary analysis of an existing database was completed on 386 children with CP (56% male) between the ages of 18 months and 5 years (mean of 38 months, SD = 11.5). The total number of procedures experienced by young children was analyzed using 1-way analyses of variance. RESULTS: Botulinum toxin A (Botox) injections, gastrostomies, shunts, and interventions involving the gastrointestinal tract, respiration, and eyes varied significantly by GMFCS level. No meaningful variations were detected between East, Central, and West regions in North America. CONCLUSIONS: This study describes variations in medical and surgical procedures for children with CP across GMFCS levels. This information is useful for therapists and parents when planning comprehensive services for young children with CP.

Familial Alzheimer's disease presenilin 1 mutation M146V increases gamma secretase cutting of p75NTR in vitro.

The cholinergic neurons of the basal forebrain are amongst the first to degenerate in Alzheimer's disease. These neurons are unique in the brain, expressing the tyrosine kinase receptor TrkA, together with the common neurotrophin receptor p75NTR; both of which bind nerve growth factor. Activation of the TrkA receptor is important in the maintenance of cell viability, whereas the p75NTR receptor has been implicated in apoptosis. Mutations in the gene for presenilin 1, a multi-transmembrane aspartyl protease, are known to cause familial Alzheimer's disease. This is thought to be due to their effect on gamma-secretase-dependent processing of amyloid precursor protein and subsequent formation of amyloid. Since p75NTR was recently shown to undergo gamma-secretase regulated intramembrane proteolysis, this study examines the effect of familial Alzheimer mutations on processing of p75NTR. PC12 cells were stably transfected with familial mutations M146V, A246E and deltaE9 and wild-type presenilin 1 and were examined here for gamma-secretase-dependent proteolysis of p75NTR. Overexpression of wild-type presenilin 1 did not increase gamma-secretase-mediated cleavage of p75NTR. However, by contrast, the presence of the M146V mutation was shown to significantly increase cleavage of p75NTR compared with the other mutations. Survival of cholinergic neurons will depend on the balance between the receptors TrkA and p75NTR, and their respective signalling pathways. Thus alterations in p75NTR proteolysis may influence this equilibrium. The novel finding that a mutation may increase processing of p75NTR may have implications for the pathogenic outcome in Alzheimer's disease.

Development, characterisation, inheritance, and cross-species utility of American lobster (Homarus americanus) microsatellite and mtDNA PCR-RFLP markers.

Effective management of exploited species demands contemporary knowledge of population structure and mating patterns. Genetic markers can prove useful in providing this knowledge. Despite its commercial importance, genetic markers for American lobster (Homarus americanus) are limited. We developed 12 tetra- and 1 trinucleotide microsatellite loci for American lobster that exhibit little stuttering after PCR amplification. Gene diversity of these loci ranged from 0.516 to 0.929. A four-locus multiplex permits rapid genotyping of progeny in parentage experiments with a paternity exclusion probability over the four loci of 97.8%. We examined the loci for conformity to Hardy-Weinberg expectations (HWE) and linkage using individuals from one location and found that four loci deviated from HWE. We also tested inheritance and pairwise linkage using 48 embryos from each of two females. With the exception of two loci that were derived from the same clone and separated by 72 bp, no evidence of linkage was found. We, for the first time, demonstrate the occurrence of multiple paternity in American lobster. We also observed an apparent occurrence of dispermic androgenesis, possibly the first documentation of such an event within a species. Ten of the loci amplified in European lobster (Homarus gammarus), although two were monomorphic and one deviated significantly from HWE. We quantified mitochondrial DNA (mtDNA) sequence variation through the use of PCR amplification of two DNA fragments, followed by digestion with restriction enzymes; eight haplotypes were detected. One of the two fragments amplified in European lobster. Both sets of markers should prove useful for population discrimination purposes, and the microsatellites, in particular the four-locus multiplex, should prove highly amenable to rapidly addressing questions about mating patterns.