Outcomes of Patients Undergoing Elective Bowel Resection Before and After Implementation of an Anemia Screening and Treatment Program.

BACKGROUND: Patients with anemia undergoing elective colorectal cancer surgery are known to have significantly higher rates of postoperative complications and worse outcomes. OBJECTIVE: This study aimed to improve rates of anemia screening and treatment in patients undergoing elective colon and rectal resections through a quality improvement initiative. DESIGN: We compared a historical cohort of patients before implementation of our anemia screening and treatment quality improvement program to a prospective cohort after implementation. SETTINGS: This study was conducted at a tertiary care hospital. PATIENTS: This study included all adult patients with a new diagnosis of colon or rectal cancer without evidence of metastatic disease between 2017 and 2019. INTERVENTIONS: The interventions include the anemia screening and treatment quality improvement program. MAIN OUTCOME MEASURES: The primary outcome was hospital cost per admission. RESULTS: This study includes a total of 84 patients who underwent elective colon or rectal resection before implementation of our anemia quality improvement project and 88 patients who underwent surgery after. In the preimplementation cohort 44 of 84 patients (55.9%) were anemic compared to 47 of 99 patients (54.7%) in the postimplementation cohort. Rates of screening (25%-86.4%) and treatment (27.8%- 63.8%) were significantly increased in the postimplementation cohort. Mean total cost per admission was significantly decreased in the postimplementation cohort (mean cost $16,827 vs $25,796; p = 0.004); this significant reduction was observed even after adjusting for relevant confounding factors (ratio of means: 0.74; 95% CI, 0.65-0.85). The mechanistic link between treatment of anemia and reductions in cost remains unknown. No significant difference was found in rates of blood transfusion, complications, or mortality between the groups. LIMITATIONS: The study limitation includes before-after design subjected to selection and temporal biases. CONCLUSIONS: We demonstrate the successful implementation of an anemia screening and treatment program. This program was associated with significantly reduced cost per admission. This work demonstrates possible value and benefits of implementation of an anemia screening and treatment program. See Video Abstract at http://links.lww.com/DCR/C15 .RESULTADOS DE LOS PACIENTES SOMETIDOS A RESECCIÓN INTESTINAL ELECTIVA ANTES Y DESPUÉS DE LA IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN Y TRATAMIENTO DE ANEMIA. ANTECEDENTES: Se sabe que los pacientes anémicos que se someten a una cirugía electiva de cáncer colorrectal tienen tasas significativamente más altas de complicaciones posoperatorias y peores resultados. OBJETIVO: Mejorar las tasas de detección y tratamiento de la anemia en pacientes sometidos a resecciones electivas de colon y recto a través de una iniciativa de mejora de calidad. DISEO: Comparamos una cohorte histórica de pacientes antes de la implementación de nuestro programa de detección de anemia y mejora de la calidad del tratamiento con una cohorte prospectiva después de la implementación. ENTORNO CLINICO: Hospital de atención terciaria. PACIENTES: Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019. INTERVENCIONES: Detección de anemia y programa de mejora de la calidad del tratamiento. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue el costo hospitalario por ingreso. RESULTADOS: Un total de 84 pacientes se sometieron a resección electiva de colon o recto antes de la implementación de nuestro proyecto de mejora de calidad de la anemia y 88 pacientes se sometieron a cirugía después. En la cohorte previa a la implementación, 44/84 (55,9 %) presentaban anemia en comparación con 47/99 (54,7 %) en la cohorte posterior a la implementación. Las tasas de detección (25 % a 86,4 %) y tratamiento (27,8 % a 63,8 %) aumentaron significativamente en la cohorte posterior a la implementación. El costo total medio por admisión se redujo significativamente en la cohorte posterior a la implementación (costo medio $16 827 vs. $25 796, p = 0,004); esta reducción significativa se observó incluso después de ajustar los factores de confusión relevantes (proporción de medias: 0,74, IC del 95 %: 0,65 a 0,85). El vínculo mecánico entre el tratamiento de la anemia y la reducción de costos sigue siendo desconocido. No hubo diferencias significativas en las tasas de transfusión de sangre, complicaciones o mortalidad entre los grupos. LIMITACIONES: El diseño de antes y después está sujeto a sesgos temporales y de selección. CONCLUSIONES: Demostramos la implementación exitosa de un programa de detección y tratamiento de anemia. Este programa se asoció con un costo por admisión significativamente reducido. Este trabajo demuestra el valor y los beneficios posibles de la implementación de un programa de detección y tratamiento de la anemia. Consulte Video Resumen en http://links.lww.com/DCR/C15 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Surgery and the Subtype of Inflammatory Bowel Disease Impact the Risk of Venous Thromboembolism After Hospital Discharge.

BACKGROUND: Surgery for inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolism (VTE) during hospitalization. It is unclear whether this association persists after hospital discharge. AIMS: We assessed the association between surgery and VTE following hospital discharge in IBD. METHODS: We conducted a population-based cohort study between 2002 and 2016 in Ontario, Canada. Adults with IBD hospitalized for ≥ 72 h who underwent an intra-abdominal surgery were compared to hospitalized, nonsurgical IBD patients. Multivariable Cox proportional hazard models were used to compare VTE risk within 12 months of discharge. RESULTS: A total of 80,445 hospital discharges were analyzed: 60% Crohn's disease (CD) and 40% ulcerative colitis (UC). The median time to VTE was three times longer for nonsurgical patients with CD and 1.6 times longer for nonsurgical patients with UC. Compared with nonsurgical patients, surgery for CD was associated with a lower cumulative risk of VTE in the 2 weeks after discharge and persisted through to 12 months after discharge (adjusted HR 0.24; 95% CI 0.15-0.40). In contrast, urgent surgery for UC was associated with an increased risk of VTE. The increased risk was greatest at 2 weeks after discharge (aHR, 1.80; 95% CI 1.26-2.57) and declined progressively over the course of 12 months. CONCLUSIONS: Surgery was associated with a greater risk of VTE after hospital discharge in UC but not CD. In patients with UC who have undergone urgent surgery, healthcare providers should consider an extended period of prophylaxis after hospital discharge.

Quality indicator selection for the Canadian Partnership against Cancer rectal cancer project: A modified Delphi study.

AIM: It is well established that (i) magnetic resonance imaging, (ii) multidisciplinary cancer conference (MCCs), (iii) preoperative radiotherapy, (iv) total mesorectal excision surgery and (v) pathological assessment as described by Quirke are key processes necessary for high quality, rectal cancer care. The objective was to select a set of multidisciplinary quality indicators to measure the uptake of these clinical processes in clinical practice. METHOD: A multidisciplinary panel was convened and a modified two-phase Delphi method was used to select a set of quality indicators. Phase 1 included a literature review with written feedback from the panel. Phase 2 included an in-person workshop with anonymous voting. The selection criteria for the indicators were strength of evidence, ease of capture and usability. Indicators for which ≥90% of the panel members voted 'to keep' were selected as the final set of indicators. RESULTS: During phase 1, 68 potential indicators were generated from the literature and an additional four indicators were recommended by the panel. During phase 2, these 72 indicators were discussed; 48 indicators met the 90% inclusion threshold and included eight pathology, five radiology, 11 surgical, six radiation oncology and 18 MCC indicators. CONCLUSION: A modified Delphi method was used to select 48 multidisciplinary quality indicators to specifically measure the uptake of key processes necessary for high quality care of patients with rectal cancer. These quality indicators will be used in future work to identify and address gaps in care in the uptake of these clinical processes.

Implementation of a systematic tobacco treatment protocol in a surgical outpatient setting: a feasibility study.

Background: Smoking cessation programs started as late as 4 weeks before surgery reduce perioperative morbidity and death, yet outpatient clinic interventions are rarely provided. Our aim was to evaluate the feasibility of implementing a tobacco treatment protocol designed for an outpatient surgical setting. Methods: We completed a pre-post feasibility study of the implementation of a systematic, evidence-based tobacco treatment protocol in an outpatient colorectal surgery clinic. Outcomes included smoking prevalence, pre- and postimplementation smoker identification and intervention rates, recruitment, retention, smoking cessation and provider satisfaction. Results: Preimplementation, 15.5% of 116 surveyed patients were smokers. Fewer than 10% of surveyed patients reported being asked about smoking, and none were offered any cessation intervention. Over a 16-month postimplementation period, 1198 patients were seen on 2103 visits. Of these, 950 (79.3%) patients were asked smoking status on first visit and 1030 (86.0%) were asked on at least 1 visit. Of 169 identified smokers, 99 (58.6%) were referred to follow-up support using an opt-out approach. At 1-, 3- and 6-month follow-up, intention-to-quit rates among 78 enrolled patients were 24.4%, 22.9% and 19.2%, respectively. Postimplementation staff surveys reported that the protocol was easy to use, that staff would use it again and that it had positive patient responses. Conclusion: Implementation of our smoking cessation protocol in an outpatient surgical clinic was found to be feasible and used minimal clinic resources. This protocol could lead to increases in identification and documentation of smoking status, delivery of smoking cessation interventions and rates of smoking reduction and cessation.

Contexte: Les programmes d'abandon du tabagisme entamés jusqu'à 4 semaines avant une opération réduisent la morbidité et la mortalité périopératoires, mais les cliniques externes n'en proposent que rarement. L'étude visait à évaluer s'il est faisable d'appliquer un protocole de traitement du tabagisme pensé pour les milieux de soins chirurgicaux extrahospitaliers. Méthodes: Nous avons réalisé une étude de faisabilité pré- et postexpérimentale sur l'application d'un protocole de traitement systématique fondé sur des données probantes à une clinique externe de chirurgie colorectale. Les résultats à l'étude étaient les suivants : prévalence du tabagisme, identification des fumeurs et taux d'intervention avant et après la mise en place du protocole, recrutement, rétention, abandon du tabagisme et satisfaction des fournisseurs. Résultats: Au départ, 15,5 % des 116 patients sondés fumaient. Moins de 10 % des répondants avaient été questionnés sur leur statut tabagique, et aucun ne s'était vu proposer un programme d'abandon. Au cours des 16 mois suivant la mise en place du protocole, 1198 patients ont été rencontrés dans le cadre de 2103 consultations. Parmi eux, 950 (79,3 %) ont été interrogés sur leur statut tabagique à la première rencontre, et 1030 (86 %) l'ont été au moins 1 fois. Des 169 fumeurs identifiés, 99 (58,6 %) ont été orientés vers un programme de soutien selon une approche de consentement présumé. Après 1 mois, 24,4 % des 78 patients participants étaient déterminés à arrêter de fumer; 22,9 % l'étaient toujours après 3 mois, et 19,2 % après 6 mois. Les sondages menés a posteriori auprès du personnel indiquent que le protocole est facile à utiliser, que les employés s'en serviraient de nouveau, et que les patients l'ont accueilli favorablement. Conclusion: Il a été possible de mettre en place notre protocole d'abandon du tabagisme à une clinique externe de chirurgie, et ce en employant un minimum de ressources cliniques. Le protocole pourrait permettre de connaître et de consigner davantage de statuts tabagiques, d'orienter un plus grand nombre de fumeurs vers les programmes d'abandon et d'accroître les taux de réduction et d'abandon du tabagisme.

Isoindoline-Based Nitroxides as Bioresistant Spin Labels for Protein Labeling through Cysteines and Alkyne-Bearing Noncanonical Amino Acids.

Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling (SDSL) is a powerful tool in protein structural research. Nitroxides are highly suitable spin labeling reagents, but suffer from limited stability, particularly in the cellular environment. Herein we present the synthesis of a maleimide- and an azide-modified tetraethyl-shielded isoindoline-based nitroxide (M- and Az-TEIO) for labeling of cysteines or the noncanonical amino acid para-ethynyl-l-phenylalanine (pENF). We demonstrate the high stability of TEIO site-specifically attached to the protein thioredoxin (TRX) against reduction in prokaryotic and eukaryotic environments, and conduct double electron-electron resonance (DEER) measurements. We further generate a rotamer library for the new residue pENF-Az-TEIO that affords a distance distribution that is in agreement with the measured distribution.

Comparison of Ligation of the Intersphincteric Fistula Tract and BioLIFT for the Treatment of Transsphincteric Anal Fistula: A Retrospective Analysis.

BACKGROUND: Ligation of the intersphincteric fistula tract is a sphincter-preserving technique for the treatment of anal fistulas. The BioLIFT modification involves the placement of a biologic mesh in the intersphincteric plane. Advocates of this modification state improved healing rates, however evidence for this is lacking, and this approach costs significantly more. OBJECTIVE: The purpose of this study was to compare the healing rates of the ligation of the intersphincteric fistula tract with the BioLIFT. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary care hospital from April 2008 to April 2018. PATIENTS: All adult patients with transsphincteric anal fistulas were included. Patients were excluded if they had IBD, more than 1 fistula tract operated on simultaneously, or a previous attempt at repair. MAIN OUTCOME MEASURES: The primary outcome was primary healing of the fistula tract, and secondary outcomes included overall success, complications, and time to recurrence. RESULTS: There were 119 cases (75 ligation of the intersphincteric fistula tract and 44 BioLIFTs). One surgeon performed 84% of the BioLIFT cases. The primary healing rate was 75.0% versus 58.7% (p = 0.08), and the complication rate was 22.7% versus 17.3% (p = 0.48; BioLIFT vs ligation of intersphincteric fistula tract). After multivariate logistic regression, the BioLIFT had a significantly better healing rate (OR = 2.38 (95% CI, 1.01-5.62); p = 0.048). Median follow-up was 9 versus 29 weeks (BioLIFT vs ligation of intersphincteric fistula tract). Kaplan-Meier analysis demonstrated no difference in the time to recurrence (p = 0.48). LIMITATIONS: This study was limited by the retrospective nature, different lengths of follow-up, and varying case numbers between the surgeons. CONCLUSIONS: The BioLIFT modification is safe and effective for the treatment of anal fistulas but has a higher cost. This modification warrants additional prospective studies to establish its benefits over the ligation of the intersphincteric fistula tract procedure. See Video Abstract at http://links.lww.com/DCR/B139. COMPARACIÓN DE LIFT VERSUS BIOLIFT PARA EL TRATAMIENTO DE LA FÍSTULA ANAL TRANSFINTERÉRICA: UN ANÁLISIS RETROSPECTIVO: Ligadura del tracto de la fístula interesfintérica es una técnica para preservación del esfínter en el tratamiento de las fístulas anales. La modificación BioLIFT implica la colocación de una malla biológica en el plano interesfintérico. Protagonistas de la modificación mejoraron las tasas de curación, sin embargo, carecen evidencias definitivas y la técnica eleva costos significativamente.Comparar las tasas de curación de ligadura del tracto de la fístula interesfintérica con el BioLIFT.Estudio de cohorte retrospectivo.Hospital de atención de tercer nivel desde abril de 2008 hasta abril de 2018.Se incluyeron todos los pacientes adultos con fístulas anales transfinteréricas. Los pacientes fueron excluidos si tenían enfermedad inflamatoria intestinal, más de un tracto fistuloso operado simultáneamente o con un intento previo de reparación.El resultado principal fue la curación primaria del tracto fistuloso y los resultados secundarios incluyeron el éxito en general, las complicaciones y tiempo hasta recurrencia.Se registraron 119 casos (75 ligaduras del tracto de la fístula interesfintérica y 44 BioLIFT). Un cirujano realizó el 84% de los casos de BioLIFT. La tasa de curación primaria fue del 75.0% vs 58.7%, p = 0.08, y la tasa de complicaciones fue del 22.7% vs 17.3%, p = 0.48 comparando BioLIFT vs ligadura del tracto de la fístula interesfintérica. Después de la regresión logística multivariada, el BioLIFT tuvo una tasa de curación significativamente mejor (OR 2.38 [IC 95% 1.01-5.62], p = 0.048). La mediana de seguimiento fue de 9 vs 29 semanas (BioLIFT vs ligadura del tracto de la fístula interesfintérica). El análisis de Kaplan-Meier no demostró diferencias en el tiempo hasta la recurrencia (p = 0,48).Este estudio estuvo limitado por ser retrospectivo, las diferentes duraciones de seguimiento y el número variable de casos entre los cirujanos.La modificación BioLIFT es segura y efectiva para el tratamiento de las fístulas anales pero tiene un costo más alto. Esta modificación amerita más estudios prospectivos para establecer los beneficios sobre ligadura del tracto de la fístula interesfintérica. Consulte Video Resumen en hhttp://links.lww.com/DCR/B139.

Prioritizing resident and patient safety while maintaining educational value: emergency restructuring of a Canadian surgical residency program during COVID-19.

Summary: Surgical programs are facing major and fluctuating changes to the resident workforce because of decreased elective volumes and high exposure risk during the coronavirus disease 2019 pandemic. Rapid restructuring of a residency program to protect its workforce while maintaining educational value is imperative. We describe the experience of the Division of General Surgery at the University of Ottawa in Ontario, Canada. The residency program was restructured to feature alternating "on" and "off" weeks, maintaining a healthy resident cohort in case of exposure. Teams were restructured and subdivided to maximize physical distancing and minimize resident exposure to pathogens. Educational initiatives doubled, with virtual sessions targeting every resident year and incorporating intraoperative teaching. The divisional research day and oral exams proceeded uninterrupted, virtually. A small leadership team enabled fast and flexible restructuring of a system for patient care while prioritizing resident safety and maintaining a commitment to resident education in a pandemic.

The application of incisional negative pressure wound therapy for perineal wounds: A systematic review.

Impaired perineal wound healing is a major source of morbidity after abdominoperineal resection. Incisional negative pressure wound therapy can improve healing, prevent infections, and decrease the frequency of dehiscence. Our objective was to summarise existing evidence on the use of incisional negative pressure wound therapy on perineal wounds after abdominoperineal resection and to determine the effect on perineal wound complications. Electronic databases were searched in January 2017. Studies describing the use of incisional negative pressure wound therapy on primarily closed perineal wounds after abdominoperineal resection were included. Of the 278 identified articles, 5 were retrieved for inclusion in the systematic review (n = 169 patients). A significant decrease in perineal wound complications when using incisional negative pressure wound therapy was demonstrated, with surgical site infection rates as low as 9% (vs 41% in control groups). The major limitation of this systematic review was a small number of retrieved studies with small patient populations, high heterogeneity, and methodological issues. This review suggests that incisional negative pressure wound therapy decreases perineal wound complications after abdominoperineal resection. Further prospective trials with larger patient populations would be needed to confirm this association and delineate which patients might benefit most from the intervention.

Perspectives From Patients and Care Providers on the Management of Fecal Incontinence: A Needs Assessment.

BACKGROUND: A large proportion of Canadians experience fecal incontinence, with no avenue for effective treatments. The Ottawa Hospital has recently started a percutaneous tibial nerve stimulation program for patients who have not improved with conservative efforts. OBJECTIVE: As part of this program implementation, a qualitative needs assessment was undertaken to better define successful outcomes and to identify barriers for program sustainability. DESIGN: This was a cross-sectional, qualitative study involving standardized, semistructured interviews. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: Patients experiencing fecal incontinence, as well as nurses, physical therapists, and physicians, were enrolled in the study. MAIN OUTCOME MEASURES: Interview questions revolved around success definitions, barriers, and promoters of fecal incontinence care. Transcripts were analyzed to develop themes surrounding fecal incontinence care. RESULTS: Twelve interviews were undertaken raising a total of 17 different themes. Barriers to fecal incontinence care included education for both the care provider and patients. Access issues for treatments were also highlighted. Promoters of fecal incontinence care were reflected by the impact that it has on quality of life, personal hygiene, psychological burden, and activity and productivity. The definition of fecal incontinence success was focused on improvements in quality of life rather than a numerical reduction of incontinence episodes. LIMITATIONS: This study was limited in its small number of interviews conducted. We were unable to identify patients who were unable to seek out care for fecal incontinence. CONCLUSIONS: Patient and care provider education surrounding fecal incontinence is lacking. Furthermore, access for effective treatments is a real barrier for Canadians experiencing fecal incontinence. Programs should focus on improvement of overall quality of life rather than a reduction of incontinence episodes.

Real-Time Monitoring of Photoinduced pH Jumps by In Situ Rapid-Scan EPR Spectroscopy.

This work represents the first demonstration of monitoring kinetics upon a light-induced pH jump by in situ rapid-scan (RS) electron paramagnetic resonance (EPR) spectroscopy on the millisecond time scale. Here, we focus on the protonation state of an imidazolidine type radical as a pH sensor under visible light irradiation of a merocyanine photoacid in bulk solution. The results highlight the utility of photoacids in combination with pH-sensitive spin probes as an effective tool for the real-time investigation of biochemical mechanisms regulated by changes in the pH value.

Comparison of BioLIFT versus LIFT for the treatment of trans-sphincteric anal fistula: a protocol for systematic review and meta-analysis.

INTRODUCTION: Identifying the optimal treatment for anal fistula has been challenging. Since first reported in 2007, the ligation of the intersphincteric fistula tract (LIFT) procedure has reported healing rates between 40% and 95% and is being increasingly adopted. The BioLIFT is an augmentation of the LIFT with an intersphincteric bioprosthetic mesh and has reported healing rates between 69% and 94%. Despite increased costs and potential complications associated with mesh, the evidence comparing healing rates between BioLIFT and LIFT is unknown. This study details the protocol for a systematic review and meta-analysis of BioLIFT and LIFT to compare outcomes associated with each procedure. METHODS AND ANALYSIS: MEDLINE, EMBASE and the Cochrane Database will be searched from inception using a search strategy designed by an information specialist. Randomised controlled trials, prospective and retrospective cohort studies, consecutive series, cross-sectional studies and case series with more than five patients will be included. Both comparative and single group studies will be included. The eligible population will be adult patients undergoing BioLIFT or LIFT for trans-sphincteric anal fistula. The primary outcome will be primary healing rate. Secondary outcomes will capture secondary healing rate and complications. Abstract, full text and data extraction will be completed independently and in duplicate by two reviewers. Study risk of bias will be assessed using Risk of Bias In Non-randomized Studies - of Interventions and the Risk of Bias (RoB 2.0) tool. Quality of evidence for outcomes will be evaluated using Grading of Recommendations, Assessment, Development and Evaluations criteria. A meta-analysis will be performed using a random-effects inverse variance model. Subgroup and sensitivity analyses will be explored in relation to complex fistula characteristics and patients who have undergone previous LIFT. Heterogeneity will be assessed using the I2 statistic. ETHICS AND DISSEMINATION: This review does not require research ethics board approval. This study will be completed in September 2022. The findings of this study will be disseminated through peer-reviewed international conferences and journals. PROSPERO REGISTRATION NUMBER: CRD42020127996.

Comparison of non-operative versus operative management of resectable colorectal cancer in elderly patients: study protocol for a systematic review.

BACKGROUND: In the 2021 Statistics Canada census, 18.5% of the Canadian population were senior (65 years and older), among those 1.7 million (4.5%) were aged 80 years and older. Colorectal cancer (CRC) is the third most common cancer in both men and women, with its highest incidence rate in septu- and octogenarians. As clinicians encounter a growing number of very elderly patients (80 years and older) with resectable colorectal cancer, justifying major surgery in a comorbid population with limited life expectancy is difficult. Therefore, this study aims to systemically review the available literature to compare non-operative management to surgical resection with respect to overall survival and quality of life. METHOD: We designed and registered a study protocol for a systematic review. We will include all patients above the age of 80 with resectable colorectal cancer. We will search MEDLINE, EMBASE, and the Cochrane Database of Controlled Trials from January 2000 onwards. We will include randomized, non-randomized controlled trials and observational studies comparing non-operative versus operative management of resectable colorectal cancer in elderly patients. The primary outcomes will be overall survival and mortality. Secondary outcomes will include quality of life, and health services/ resources utilization (e.g., treatments, change of level of care…). Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using the ROB-2 and ROBIN-I tools. If feasible, we will conduct random effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., study design and methodological quality). DISCUSSION: This systematic review will synthesize the existing data on the management of colorectal cancer in the very elderly patients, and identify the gap in the literature for potential future research. More specifically, we aim to streamline non-operative outcome data on resectable colorectal cancers to aid clinicians' decision-making with respect to survival outcomes and quality of life. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, healthcare professionals, and policy makers. Results will be published in a peer-reviewed journal.

Fecal Diversion for Perianal Crohn Disease in the Era of Biologic Therapies: A Multicenter Study.

BACKGROUND: The natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics. METHODS: We performed a retrospective, multicenter study from 1999 to 2020. Patients who underwent fecal diversion for refractory PCD were stratified by diversion type (ostomy with or without proctectomy). Times to clinical and surgical outcomes were estimated using Kaplan-Meier methods, and the association with biologics was assessed using multivariable Cox proportional hazards models. RESULTS: Eighty-two patients, from 3 academic institutions, underwent a total of 97 fecal diversions: 68 diversions without proctectomy and 29 diversions with proctectomy. Perianal healing occurred more commonly after diversion with proctectomy than after diversion without proctectomy (83% vs 53%; P = 0.021). Among the patients who had 68 diversions without proctectomy, with a median follow-up of 4.9 years post-diversion (interquartile range, 1.66-10.19), 37% had sustained healing, 31% underwent surgery to restore bowel continuity, and 22% underwent proctectomy. Ostomy-free survival occurred in 21% of patients. Biologics were independently associated with avoidance of proctectomy (hazard ratio, 0.32; 95% confidence interval, 0.11-0.98) and surgery to restore bowel continuity (hazard ratio, 3.10; 95% confidence interval, 1.02-9.37), but not fistula healing. CONCLUSIONS: In this multicenter study, biologics were associated with bowel restoration and avoidance of proctectomy after fecal diversion without proctectomy for PCD; however, a minority of patients achieved sustained fistula healing after initial fecal diversion or after bowel restoration. These results highlight the refractory nature of PCD.

Characterization of intact antibody-drug conjugates from plasma/serum in vivo by affinity capture capillary liquid chromatography-mass spectrometry.

Antibody-drug conjugates (ADCs) are designed to facilitate the targeted delivery of cytotoxic drugs to improve their tumor fighting effects and minimize systemic toxicity. However, efficacy and safety can potentially be compromised due to the release of conjugated drugs from the ADC with time while in circulation, resulting in changes in the drug-to-antibody ratio (DAR). Current understanding of this process is limited because existing methods such as immunoassays fail to distinguish ADCs with different DARs. Here we demonstrate a novel method with bead-based affinity capture and capillary liquid chromatography-mass spectrometry to allow direct measurement of drug release by quantifying DAR distributions of the ADC in plasma/serum. This method successfully identified individual intact conjugated antibody species produced due to drug loss from ADCs (e.g., an engineered site-specific anti-MUC16 THIOMAB-drug conjugate) and measured the corresponding DAR distributions in vitro and in vivo. Information obtained can provide insights into the mechanisms involved in drug loss and help to optimize ADC therapeutics. Other potential applications of the method may include characterization of posttranslational modifications, protein adducts, and immunogenicity.

Site-directed attachment of photoexcitable spin labels for light-induced pulsed dipolar spectroscopy.

Photoexcited triplet states are gaining popularity as spin labels in pulsed electron paramagnetic resonance (EPR) spectroscopy. Here, we demonstrate that the fluorophores Eosin Y, Rose Bengal and Atto Thio12 are suitable markers for distance determination by laser-induced magnetic dipole (LaserIMD) spectroscopy in proteins that lack an intrinsic photoexcitable center.

A novel prevention bundle to reduce incisional infections after radical cystectomy.

PURPOSE: Our institution implemented a novel intervention bundle to reduce incisional surgical site infections (SSIs) for patients undergoing radical cystectomy. The primary objective of this study was to evaluate the efficacy of the bundle in reducing incisional SSIs post-cystectomy. MATERIAL AND METHODS: A before-after cohort study was performed on all patients who underwent radical cystectomy by urologic oncologists at The Ottawa Hospital from January 2016 to March 2019. Thirty-day postoperative incisional SSIs were identified from the medical record and were compared to institutionally collected National Surgical Quality Improvement Program data. The SSI reduction strategy was implemented as of March 1st, 2018. Adjusted associations between the SSI intervention with the risk of incisional SSI were determined. Cystectomy incisional SSI rates were compared to all other National Surgical Quality Improvement Program-collected surgeries at The Ottawa Hospital during the same time period. RESULTS: One hundred and thirty-two patients were included; 41 following implementation of the SSI reduction bundle. Mean age was 69 years, 104 (79%) were male, and 59 (45%) received neobladders. The risk of incisional SSI decreased from 16.5% preintervention to 2.4% post intervention (risk ratio 0.17; P = 0.004). Intraoperative transfusion and diabetes were independently associated with an increased risk of incisional SSI (P < 0.05). The SSI rate for all other surgical procedures at our institution remained stable during the same time period. CONCLUSIONS: The risk of SSI after radical cystectomy is high. Use of an SSI reduction bundle was associated with a large reduction in incisional SSIs. Further evaluation of this intervention in other centers is warranted.

The Canadian Partnership Against Cancer Rectal Cancer Project: Protocol for a Pan-Canadian, Multidisciplinary Quality Improvement Initiative to Optimize the Quality of Rectal Cancer Care.

BACKGROUND: Over the last 2 decades, the use of multimodal strategies, including total mesorectal excision (TME) surgery, preoperative chemotherapy, multidisciplinary case conference, pelvic magnetic resonance imaging, and pathologic assessment using Quirke method, has led to significant improvements in oncologic outcomes for patients with rectal cancer. Although the literature supports claims on the effectiveness of these multimodal strategies, the uptake of these multimodal strategies varies considerably among centers, suggesting that the best evidence is not always implemented into clinical practice. OBJECTIVE: This study aims to perform a quality improvement initiative to (1) identify existing gaps in care for these multimodal strategies and (2) implement knowledge translation (KT) interventions to close these gaps to optimize quality of care for patients with rectal cancer across high-volume centers in Canada. METHODS: Process indicators for the selected multimodal strategies to optimize rectal cancer care will be selected and prospectively collected for all patients with stages 1 to 3 rectal cancer undergoing TME surgery. KT interventions, including audit and feedback, opinion leaders, and community of practice, will be implemented to increase the uptake of these clinical strategies. RESULTS: The uptake of the process indicators over time and the effect of the uptake of the process indicators on short- and long-term oncologic outcomes will be evaluated for each multimodal strategy. CONCLUSIONS: This quality improvement initiative will identify existing gaps in care for the selected multimodal strategies and implement KT interventions to close these gaps. The results of this study will inform further efforts to optimize rectal cancer care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15535.

Regulation of CDX2 expression in esophageal adenocarcinoma.

Reflux of acidic gastric contents and bile acids into the lower esophagus has been identified to have a central role in esophageal malignancy and is reported to upregulate caudal-related homologue 2 (CDX2), a regulatory gene involved in embryonic development and axial patterning of the alimentary tract. The aim of this study was to characterize the expression of CDX2 in a well-defined series of human esophageal tissues, comprising reflux-induced esophagitis, premalignant Barrett esophagus (BE), and primary esophageal adenocarcinoma (EADC). To explore potential molecular regulatory mechanisms, we also studied the expression of beta-catenin, SOX9, and CDX2 promoter methylation in esophageal tissues, in addition to the effect of bile acids and nitric oxide (NO) on CDX2 expression in the normal human esophageal cell line Het1A. Relative to matched normal esophageal epithelia, CDX2 was overexpressed in esophagitis (37% for RNA; cytoplasmic immunoreactivity in 48% of tissues), a high proportion (91%) of BE tissues, and in EADC (57% for RNA; cell nuclear immunopositivity in 80%). An association with beta-catenin expression was seen, but not with SOX9 or CDX2 promoter methylation. In Het1A cells, CDX2 was upregulated following exposure to bile acids and NO, alone and in combination. These results further implicate CDX2 and beta-catenin in the molecular pathogenesis of human EADC. The observed synergistic effect of NO on the efficacy of bile acid-induction of CDX2 suggests a novel role for NO in modulating the development of the Barrett phenotype and esophageal adenocarcinogenesis.