Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

Trends in management and outcomes of colon cancer in the United States over 15 years: Analysis of the National Cancer Database.

Management of colon cancer has changed over the last few decades. We assessed the trends in management and outcomes using the US National Cancer Database (NCDB). A retrospective analysis of all patients with colonic adenocarcinoma between 2005 and 2019 was conducted. The cohort was divided into three equal time periods: Period 1 (2005-2009), Period 2 (2010-2014), and Period 3 (2015-2019) to examine treatment and outcomes trends. The primary outcome was 5-year overall survival (OS). The study included 923,275 patients. A significant increase in patients with stage IV disease was noted in Period 3 compared to Period 1 (47.9% vs. 27.9%, respectively), whereas a reciprocal reduction was seen in patients with locally advanced disease (stage II: 20.8%-12%; stage III: 14.5%-7.7%). Use of immunotherapy significantly increased from 0.3% to 7.6%. Mean 5-year OS increased (43.6 vs. 42.1 months) despite the increase in metastatic disease and longer time from diagnosis to definitive surgery (7 vs. 14 days). A reduction in 30-day readmission (5.1%-4.2%), 30- (3.9%-2.8%), and 90-day mortality (7.1%-5%) was seen. Laparoscopic and robotic surgery increased from 45.8% to 53.1% and 2.9% to 12.7%, respectively. Median postoperative length of hospital stay decreased by 2 days. Rate of positive resection margins (7.2%-6%) and median number of examined lymph nodes (14-16) also improved. Minimally invasive surgery and immunotherapy for colon cancer significantly increased in recent years. Patient outcomes including OS improved over time.

Outcomes of Early Versus Standard Closure of Diverting Ileostomy After Proctectomy: Meta-analysis and Meta-regression Analysis of Randomized Controlled Trials.

OBJECTIVE: We aimed to compare outcomes of early and standard closure of diverting loop ileostomy (DLI) after proctectomy and determine risk factors for anastomotic leak (AL) and complications. BACKGROUND: Formation of DLI has been a routine practice after proctectomy to decrease the incidence and potential adverse sequela of AL. METHODS: PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) that compared outcomes of early versus standard closure of DLI after proctectomy. Main outcome measures were postoperative complications, AL, ileus, surgical site infection, reoperation, readmission, and hospital stay following DLI closure. RESULTS: Eleven RCTs (932 patients; 57% male) were included. Early closure group included 474 patients and standard closure 458 patients. Early closure was associated with higher odds of AL [odds ratio (OR): 2.315, P =0.013] and similar odds of complications (OR: 1.103, P =0.667), ileus (OR: 1.307, P =0.438), surgical site infection (OR: 1.668, P =0.079), reoperation (OR: 1.896, P =0.062), and readmission (OR: 3.431, P =0.206). Hospital stay was similar (weighted mean difference: 1.054, P =0.237). Early closure had higher odds of AL than standard closure when early closure was done ≤2 weeks (OR: 2.12, P =0.047) but not within 3 to 4 weeks (OR: 2.98, P =0.107). Factors significantly associated with complications after early closure were diabetes mellitus, smoking, and closure of DLI ≤2 weeks, whereas factors associated with AL were ≥ American Society of Anesthesiologists II classification and diabetes mellitus. CONCLUSIONS: Early closure of DLI after proctectomy has a higher risk of AL, particularly within 2 weeks of DLI formation. On the basis of this study, routine early ileostomy closure cannot be recommended.

Accuracy of Clinical Staging of Localized Colon Cancer: A National Cancer Database Cohort Analysis.

BACKGROUND: This study aimed to assess concordance between clinical and pathologic assessment of colon cancer. PATIENTS AND METHODS: A retrospective cohort analysis of patients with stage I-III colon cancer in the National Cancer Database (2010-2019) was conducted. Concordance between clinical and pathologic assessment of colon cancer was calculated using Kappa coefficients and 95% confidence intervals (CIs). RESULTS: A total of 125,473 patients (51.2% female; mean age 68.2 years) were included. There was moderate concordance between clinical and pathologic T stage (Kappa = 0.606, 95%CI: 0.602-0.609) and between clinical and pathologic N stage (Kappa = 0.506, 95%CI: 0.501-0.511). For right-sided colon cancer, there was moderate agreement between clinical and pathologic T stage (Kappa = 0.594, 95%CI: 0.589-0.599) and N stage (Kappa = 0.530, 95%CI: 0.523-0.537). For left-sided colon cancer, there was substantial agreement between clinical and pathologic T stage (Kappa = 0.624, 95%CI: 0.619-0.630) and moderate agreement between N stage (Kappa 0.472, 95%CI: 0.463-0.480). Sensitivity of clinical assessment of T and N stage ranged from 64.3% to 77.2% and 41.6% to 54.5%, respectively. Specificity ranged from 96.7% to 97.7% for T stage and 95.7% to 97.3% for N stage. CONCLUSIONS: Clinical assessment of T and N stages of colon cancer had good diagnostic accuracy with moderate concordance with the final pathologic stage. While clinical assessment was highly specific with < 3% of patients being over-staged, it had modest sensitivity, especially for detection of nodal involvement. Diagnostic accuracy of clinical assessment of right and left colon cancers was similar, except for higher sensitivity and accuracy of assessment of nodal involvement in right than left colon cancers.

A Propensity Score-Matched Analysis of the Impact of Neoadjuvant Radiation Therapy on the Outcomes of Stage II and III Mucinous Rectal Carcinoma.

BACKGROUND: Patients with mucinous rectal carcinoma tend to present in advanced stage with a poor prognosis. OBJECTIVE: This study aimed to assess the effect of neoadjuvant radiation therapy on outcomes of patients with stage II and III mucinous rectal carcinomas using data from the National Cancer Database. DESIGN: Retrospective analysis of prospective national databases. SETTING: National Cancer Database between 2004 and 2019. PATIENTS: Patients with mucinous rectal carcinoma. INTERVENTION: Patients who did or did not receive neoadjuvant radiation therapy were matched using the nearest-neighbor propensity score method for age, clinical stage, neoadjuvant systemic treatment, and surgery type. MAIN OUTCOME MEASURES: Main outcomes of the study were numbers of total harvested and positive lymph nodes, disease downstaging after neoadjuvant radiation, and overall survival. Other outcomes were hospital stay, short-term mortality, and readmission. RESULTS: A total of 3062 patients (63.5% men) with stage II and III mucinous rectal carcinoma were included, 2378 of whom (77.7%) received neoadjuvant radiation therapy. After 2:1 propensity score matching, 143 patients in the no neoadjuvant group were matched to 286 patients in the neoadjuvant group. The mean overall survival was similar (77.3 vs 81.9 months; p = 0.316). Patients who received neoadjuvant radiation therapy were less often diagnosed with pathologic T3 and 4 disease (72.3% vs 81.3%, p = 0.013) and more often had pathologic stage 0 and 1 disease (16.4% vs 11.2%, p = 0.001), yet with a higher stage III disease (49.7% vs 37.1%, p = 0.001). Neoadjuvant radiation was associated with fewer examined lymph nodes (median: 14 vs 16, p = 0.036) and positive lymph nodes than patients who did not receive neoadjuvant radiation. Short-term mortality, readmission, hospital stay, and positive surgical margins were similar. LIMITATIONS: Retrospective study and missing data on disease recurrence. CONCLUSIONS: Patients with mucinous rectal carcinoma who received neoadjuvant radiation therapy had marginal downstaging of disease, fewer examined and fewer positive lymph nodes, and similar overall survival to patients who did not receive neoadjuvant radiation. See Video Abstract . UN ANLISIS EMPAREJADO POR PUNTUACIN DE PROPENSIN DEL IMPACTO DE LA RADIOTERAPIA NEOADYUVANTE EN LOS RESULTADOS DEL CARCINOMA MUCINOSO DE RECTO EN ESTADIO IIIII: ANTECEDENTES:Los pacientes con carcinoma mucinoso de recto tienden a presentarse en estadio avanzado con mal pronóstico.OBJETIVO:Este estudio tuvo como objetivo evaluar el efecto de la radioterapia neoadyuvante en los resultados de pacientes con carcinomas mucinosos de recto en estadio II-III utilizando datos de la Base de Datos Nacional del Cáncer.DISEÑO:Análisis retrospectivo de bases de datos nacionales prospectivas.PACIENTES:Pacientes con carcinoma mucinoso de recto.AJUSTE:Base de datos nacional sobre el cáncer entre 2004 y 2019.INTERVENCIÓN:Los pacientes que recibieron o no radioterapia neoadyuvante fueron emparejados utilizando el método de puntuación de propensión del vecino más cercano por edad, estadio clínico, tratamiento sistémico neoadyuvante y tipo de cirugía.PRINCIPALES MEDIDAS DE VALORACIÓN:Los principales resultados del estudio fueron el número total de ganglios linfáticos extraídos y positivos, la reducción del estadio de la enfermedad después de la radiación neoadyuvante y la supervivencia general. Otros resultados fueron la estancia hospitalaria, la mortalidad a corto plazo y el reingreso.RESULTADOS:Se incluyeron 3.062 pacientes (63,5% hombres) con carcinoma mucinoso de recto estadio II-III, de los cuales 2.378 (77,7%) recibieron radioterapia neoadyuvante. Después de un emparejamiento por puntuación de propensión 2:1, 143 pacientes del grupo sin neoadyuvancia fueron emparejados con 286 del grupo neoadyuvante. La supervivencia global media fue similar (77,3 vs 81,9 meses; p = 0,316). A los pacientes que recibieron radiación neoadyuvante se les diagnosticó con menos frecuencia enfermedad pT3-4 (72,3% frente a 81,3%, p = 0,013) y con mayor frecuencia tenían enfermedad en estadio patológico 0-1 (16,4% frente a 11,2%, p = 0,001), aunque con una enfermedad en estadio III superior (49,7% vs 37,1%, p = 0,001). La radiación neoadyuvante se asoció con menos ganglios linfáticos examinados (mediana: 14 frente a 16, p = 0,036) y ganglios linfáticos positivos que los pacientes que no recibieron radiación neoadyuvante. La mortalidad a corto plazo, el reingreso, la estancia hospitalaria y los márgenes quirúrgicos positivos fueron similares.LIMITACIONES:Estudio retrospectivo y datos faltantes sobre recurrencia de la enfermedad.CONCLUSIONES:Los pacientes con carcinoma mucinoso de recto que recibieron radioterapia neoadyuvante tuvieron una reducción marginal de la enfermedad, menos ganglios linfáticos examinados y positivos, y una supervivencia general similar a la de los pacientes que no recibieron radiación neoadyuvante. (Traducción- Dr Ingrid Melo ).

A Prospective, Single-Arm Study to Evaluate the Safety and Efficacy of an Autologous Blood Clot Product in the Treatment of Anal Fistula.

BACKGROUND: Surgical treatment of complex perianal fistula is technically challenging, associated with risk of failure, and may require multiple procedures. In recent years, several biologic agents have been developed for permanently eradicating anal fistulous disease with variable success. In this study, the treatment is an autologous whole-blood product created from the patients' blood. It forms a provisional matrix that was found to be safe and effective in healing acute and chronic cutaneous wounds. OBJECTIVE: The study aimed to assess the efficacy and safety of an autologous blood clot product as a treatment for transsphincteric perianal fistulas. DESIGN: A prospective single-arm study. SETTINGS: A single tertiary medical center. PATIENTS: Patients with simple or complex transsphincteric fistulas confirmed by MRI were included in the study. Cause was either cryptoglandular or Crohn's disease related (in the absence of active luminal bowel disease). INTERVENTION: The outpatient procedure was performed under general anesthesia and consisted of: 1) physical debridement and cleansing of the fistula tract; 2) suture closure of the internal opening; and 3) instillation of the autologous blood clot product into the entire tract. MAIN OUTCOME MEASURES: Safety and efficacy at 6- and 12-months after surgery. RESULTS: Fifty-three patients (77% men) with a median age of 42 (20-72) years were included in the study. Three patients withdrew consent, and 1 patient was lost to follow-up. At the time of this interim analysis, 49 and 33 patients completed the 6- and 12-month follow-up period. Thirty-four of the 49 patients achieved complete healing (69%) at 6 months, but 20 of the 33 patients (60%) achieved healing after 1 year. All patients who achieved healing at 6 months remained healed at the 1-year mark. In a subgroup analysis of patients with Crohn's disease, 7 of 9 patients completed 1-year follow-up, with 5 patients (71%) achieving clinical remission. No major side effects or postoperative complications were noted, but 2 adverse events occurred (admission for pain control and coronavirus 2019 infection). LIMITATIONS: Noncomparative single-arm pilot study. CONCLUSIONS: Treatment with an autologous blood clot product in perianal fistular disease was found to be feasible and safe, with an acceptable healing rate in both cryptoglandular and Crohn's disease fistula-in-ano. Further comparative assessment is required to determine its potential role in the treatment paradigm of fistula-in-ano. See Video Abstract . BRAZO PARA EVALUAR LA SEGURIDAD Y EFICACIA DE RDVER, UN COGULO DE SANGRE AUTLOGO, EN EL TRATAMIENTO DE LA FSTULA ANAL: ANTECEDENTES:El tratamiento quirúrgico de la fístula perianal compleja es técnicamente desafiante, se asocia con riesgo de fracaso y puede requerir múltiples procedimientos. En los últimos años, se han desarrollado varios agentes biológicos con el fin de erradicar permanentemente la enfermedad fistulosa anal con éxito variable. El tratamiento RD2-Ver.02 es un producto de sangre total autólogo creado a partir de la sangre de los pacientes, que forma una matriz provisional que resultó segura y eficaz para curar heridas cutáneas agudas y crónicas.OBJETIVO:Evaluar la eficacia y seguridad de RD2-Ver.02 como tratamiento para las fístulas perianales transesfinterianas.DISEÑO:Un estudio prospectivo de un solo brazo.LUGARES:Un único centro médico terciario.PACIENTES:Se incluyeron en el estudio pacientes con fístulas transesfinterianas simples o complejas confirmadas mediante resonancia magnética. La etiología fue criptoglandular o relacionada con la enfermedad de Crohn (en ausencia de enfermedad intestinal luminal activa).INTERVENCIÓN:El procedimiento ambulatorio se realizó bajo anestesia general y consistió en: 1) desbridamiento físico y limpieza del trayecto fistuloso; 2) cierre con sutura de la abertura interna; y 3) instilación de RD2-Ver.02 en todo el tracto.PRINCIPALES MEDIDAS DE VALORACIÓN:Seguridad y eficacia a los 6 y 12 meses después de la cirugía.RESULTADOS:Se incluyeron en el estudio 53 pacientes (77% varones) con una mediana de edad de 42 (20-72) años. Tres pacientes retiraron su consentimiento y un paciente se perdió durante el seguimiento. En el momento de este análisis intermedio, 49 y 33 pacientes completaron el período de seguimiento de 6 y 12 meses, respectivamente. Treinta y cuatro (34) pacientes lograron una curación completa (69%) a los 6 meses, mientras que 20 de 33 pacientes (60%) lograron una curación después de un año. Todos los pacientes que lograron la curación a los 6 meses permanecieron curados al año. En un análisis de subgrupos de pacientes con enfermedad de Crohn, 7/9 pacientes completaron un seguimiento de un año y 5 pacientes (71%) alcanzaron la remisión clínica. No se observaron efectos secundarios importantes ni complicaciones postoperatorias, mientras que ocurrieron 2 eventos adversos (ingreso para control del dolor e infección por COVID-19).LIMITACIONES:Estudio piloto no comparativo de un solo brazo.CONCLUSIONES:Se encontró que el tratamiento con RD2-Ver.02 en la enfermedad fístula perianal es factible y seguro, con una tasa de curación aceptable tanto en la fístula criptoglandular como en la de Crohn en el ano. Se requiere una evaluación comparativa adicional para determinar su papel potencial en el paradigma de tratamiento de la fístula anal. (Pre-proofed version ).

A national database analysis of the evolution of outcomes of surgery for anal melanoma.

BACKGROUND: This study assessed trends in treatment and outcomes of anal melanomas over a 17-year period. METHODS: NCDB was searched for patients with anal melanoma (2004-2020). Receiver-operating characteristic curve analysis was used to determine cutoff year marking increased overall survival (OS) of anal melanoma. Characteristics, treatments, and outcomes in consecutive time periods were compared. RESULTS: A total of 815 patients (mean age: 67.2 years; 59.4% female) were included: 354 in Period 1 (2004-2012) and 461 in Period 2 (2013-2020). Period 2 included fewer abdominoperineal resections (18% vs. 28%, p = 0.002), more local tumor excisions (61.1% vs. 55%, p = 0.002), more often immunotherapy (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 2.22-5.22, p < 0.001) and less often chemotherapy (OR: 0.516, 95% CI: 0.352-0.755, p < 0.001) administered and longer median OS (25.2 vs. 19.8 months, p = 0.006). Independent predictors of worse OS were older age (hazard ratio [HR]: 1.02, p = 0.012), higher Charlson score (HR: 2.32, p = 0.02), and greater number of positive lymph nodes (HR: 1.15, p < 0.001); conversely private insurance (HR: 0.385, p = 0.008) was predictive of increased OS. CONCLUSIONS: Anal melanoma patients diagnosed between 2013 and 2020 underwent fewer abdominoperineal resections and more local excisions than patients diagnosed between 2004 and 2013. Increased immunotherapy and longer median OS were noted in period two. Age and private insurance were significant predictors of OS, remaining constant across time periods.

Factors Associated With Prolonged Operative Times in Laparoscopic Right Hemicolectomy and Its Association With Short-Term Outcomes.

BACKGROUND: This study aimed to investigate factors associated with prolonged operative time in laparoscopic right hemicolectomy for colon cancer. METHODS: This was a retrospective review of patients with colon cancer who underwent laparoscopic right hemicolectomy between 2011 and 2021. Linear and binary logistic regression analyses were performed to determine factors associated with prolonged operative time. The association between longer operative times and complications and hospital stay was assessed. RESULTS: One hundred and ninety-seven patients (52.3% female; mean age: 68.8 ± 14.1 years) were included. Factors independently associated with operative time were male sex (ß = 17.3, 95% CI: 2, 32.5; p = 0.026) and extended hemicolectomy (ß = 67.7, 95% CI: 27.6, 107.9; p = 0.001). American Society of Anesthesiologists (ASA) IV classification had a borderline significant association with operative time (ß = 100.4, 95% CI: -2.05, 202.9; p = 0.055). Male sex (r = 0.158; p = 0.026), body mass index (r = 0.205; p = 0.004), ASA classification (r = 0.232; p = 0.001), extended hemicolectomy (r = 0.256; p < 0.001), and intracorporeal vessel control (r = 0.161; p = 0.025) had significant positive correlation with operative times. Patients with operative times ≥ 160 min had significantly longer hospital stays (5 vs. 4 days; p = 0.043) and similar complication rates to patients with shorter operative times. CONCLUSIONS: Male sex, advanced ASA classification, and extended hemicolectomy were independently and significantly associated with longer operative times in laparoscopic right hemicolectomy. Longer operative times were associated with longer hospital stays and similar complication rates.

Heterogeneity in survival within age groups of early-onset colorectal cancer patients: A National Cancer Database analysis.

BACKGROUND: We aimed to identify predictors of and heterogeneity in survival among different age groups of patients with early-onset colorectal cancer (EOCRC). METHODS: This retrospective cohort study used National Cancer Database data from 2004 to 2019. Differences in survival among CRC patients <50 years, subcategorized into age groups (<20, 20-29, 30-39, 40-49 years) were compared for demographic, clinical, and histologic features by univariate and multivariate analyses. Cox hazard regression and Kaplan Meier survival analysis were performed. RESULTS: 134 219 of the 1 240 787 individuals with CRC (10.8%) were <50 years old; 46 639 (34.8%) had rectal and 87 580 (65.3%) had colon cancer. Within the colon cancer cohort, individuals aged between 30 and 39 years had the highest overall survival rate (66.7%) during a median follow-up of 47.6 months (interquartile range IQR 23.1-89.7). The same age group in the rectal cancer cohort had the lowest survival rate (31%) over a median follow-up of 54.5 (IQR 28.24-97.31) months. Leading factors affecting survival included tumor stage (HR 8.23 [4.64-14.6]; p < 0.0001), lymphovascular invasion (HR 1.88 [1.70-2.06]; p < 0.0001) and perineural invasion (HR 1.08 [1.02-1.15]; p = 0.001). CONCLUSION: Survival trends vary within age groups of patients affected with early onset colon cancer compared to rectal cancer. Tumor stage and unfavorable pathological characteristics are the strongest factors predicting survival.

Effect of neoadjuvant therapy regimens on lymph nodes yield in rectal cancer.

BACKGROUND AND OBJECTIVES: Pathological nodal staging is relevant to postoperative decision-making and a prognostic marker of cancer survival. This study aimed to assess the effect of different total neoadjuvant therapy (TNT) regimens on lymph node status following total mesorectal excision (TME) for locally advanced rectal cancer (LARC). METHODS: A retrospective cohort study of patients treated for node-positive clinical stage 3 LARC with TNT between January 2015 and August 2022. Patients were stratified into induction therapy and consolidation therapy groups. Variables collated included patient demographics, clinical and radiological characteristics of the tumor, and pathology of the resected specimen. Primary outcome was total harvested lymph nodes. RESULTS: Ninety-seven patients were included (57 [58.8%] males; mean age of 58.5 ± 11.4 years). The induction therapy group included 85 (87.6%) patients while 12 (12.4%) patients received consolidation therapy. A median interquartile range value of 22.00 (5.00-72.00) harvested lymph nodes was recorded for the induction therapy group in comparison to 16.00 (16.00-47.00) in the consolidation therapy arm (p = 0.487). Overall pathological complete response rate was 34%. CONCLUSION: Total harvested nodes from resected specimens were marginally lower in the consolidation therapy group. Induction therapy may be preferrable to optimize postoperative specimen staging.

Association between microsatellite status and characteristics and outcomes of early-onset compared to late-onset rectal cancer.

BACKGROUND: Microsatellite instability (MSI) is an important prognosticator for colorectal cancer (CRC). The present study aimed to assess the impact of MSI status on the characteristics and outcomes of early-onset compared to late-onset rectal cancer. METHODS: This retrospective cohort study used data from the US National Cancer Database (2004-2019) to assess the baseline characteristics, treatment patterns, short-term outcomes, and overall survival (OS) of early-onset rectal adenocarcinoma affecting patients < 50 years compared to late-onset rectal adenocarcinoma according to the MSI status. RESULTS: The present study included 48,407 patients (59.9% male) with rectal cancer, 17.3% of patients were < 50 years and 6.3% had MSI-H tumors. In the early-onset group, patients with MSI-H tumors had a lower mean age (41.5 vs 43 years, p < 0.001) and presented less often with stage IV disease (22.1% vs 17.7%, p = 0.03) and liver metastasis (9.1% vs 13.5%, p = 0.011) than patients with MSS tumors. In the late-onset group, patients with MSI-H and MSS tumors had similar demographics, disease stage, and metastatic pattern, yet MSI-H patients more often received neoadjuvant radiation therapy (58.9% vs 55.1%, p = 0.009) and neoadjuvant systemic therapy (40% vs 36.2%, p = 0.005). In both age groups, MSI-H tumors were associated with more pathologic T3-4 stage and were more likely mucinous and poorly differentiated carcinomas than MSS tumors. The median OS of MSI-H tumors was similar to MSS tumors (108.09 vs 102.31 months, p = 0.1), whether in the early-onset (139.5 vs 134.2 months, p = 0.821) or late-onset groups (106.1 vs 104.3 months, p = 0.236). CONCLUSIONS: In both age groups, MSI-H rectal cancers were more often mucinous and poorly differentiated carcinomas and had pT3-4 stage more often than MSS cancers. MSI-H rectal cancers tend to present less often with distant metastases and nodal involvement than MSS cancers only in early-onset, but not in late-onset rectal cancers. The association between MSI status and survival was not notable in this study, whether in the early-onset or late-onset groups.

Splenic flexure mobilization in left-sided colonic and rectal resections: A meta-analysis and meta-regression of factors associated with anastomotic leak and complications.

AIM: Splenic flexure mobilization (SFM) is commonly performed during left-sided colon and rectal resections. The aim of the present systematic review was to assess the outcomes of SFM in left-sided colon and rectal resections and the risk factors for complications and anastomotic leak (AL). METHOD: This study was a PRISMA-compliant systematic review. PubMed, Scopus and Web of Science were searched for studies that assessed the outcomes of sigmoid and rectal resections with or without SFM. The primary outcomes were AL and total complications, and the secondary outcomes were individual complications, operating time, conversion to open surgery, length of hospital stay (LOS) and pathological and oncological outcomes. RESULTS: Nineteen studies including data on 81 116 patients (49.1% male) were reviewed. SFM was undertaken in 40.7% of patients. SFM was associated with a longer operating time (weighted mean difference 24.50, 95% CI 14.47-34.52, p < 0.0001) and higher odds of AL (OR 1.19, 95% CI 1.06-1.33, p = 0.002). Both groups had similar odds of total complications, splenic injury, anastomotic stricture, conversion to open surgery, (LOS), local recurrence, and overall survival. A secondary analysis of rectal cancer cases only showed similar outcomes for SFM and the control group. CONCLUSIONS: SFM was associated with a longer operating time and higher odds of AL, yet a similar likelihood of total complications, splenic injury, anastomotic stricture, conversion to open surgery, LOS, local recurrence, and overall survival. These conclusions must be cautiously interpreted considering the numerous study limitations. SFM may have only been selectively undertaken in cases in which anastomotic tension was suspected. Therefore, the suboptimal anastomoses may have been the reason for SFM rather than the SFM being causative of the anastomotic insufficiencies.

Risk factors for complications following sacral neuromodulation for faecal incontinence: Long-term follow-up.

AIM: Sacral neuromodulation (SNM) has become a standard surgical treatment for faecal incontinence (FI). Prior studies have reported various adverse events of SNM, including suboptimal therapeutic response, infection, pain, haematoma, and potential need for redo SNM. The aim of this study was to identify the risk factors associated with long-term complications of SNM. METHOD: This retrospective cohort reviewed patients who underwent two-stage SNM for FI at our institution between 2011-2021. Preoperative baseline characteristics and follow-up were obtained from the medical record and/or by telephone interview. Management and outcome of each postoperative event were evaluated by univariate and multivariate regression analyses. RESULTS: A total of 291 patients (85.2% female) were included in this study. Postoperative complications were recorded in 219 (75.2%) patients and 154 (52.9%) patients required surgical intervention to treat complications. The most common postoperative event was loss of efficacy (46.4%). Other common adverse events were problems at the implant site (pain, infection, etc.) in 16.5% and pain during stimulation in 11.7%. Previous vaginal delivery (OR 2.74, p = 0.003) and anal surgery (OR = 2.46, p = 0.039) were independent predictors for complications. Previous colorectal (OR = 2.04, p = 0.026) and anal (OR = 1.98, p = 0.022) surgery and history of irritable bowel syndrome (IBS) (OR = 3.49, p = 0.003) were independent predictors for loss of efficacy. CONCLUSION: Postoperative adverse events are frequently recorded after SNM. Loss of efficacy is the most common. Previous colorectal or anal surgery, vaginal delivery, and IBS are independent risk factors for complications.

Stapler size independently predicts postoperative complications following stapled ileocolic anastomosis: A retrospective cohort study.

AIM: Staplers used in ileocolic anastomosis construction differ in length and height. We assessed the impact of stapler type in creating ileocolic anastomoses on postoperative outcomes. METHODS: This retrospective cohort study of an Institutional Review Board approved database included patients who underwent laparoscopic right colectomy for cancer between January 2011 and August 2021. All patients had construction of extracorporeal antiperistaltic stapled ileocolic anastomosis using a linear cutting stapler. Main outcome measures were short-term (<30 day) morbidity and mortality. RESULTS: In all, 270 patients (136 men; median age 70.2 years) were included. A 75 mm stapler was used in 49 (18.1%) patients, 80 mm in 97 (35.9%) and 100 mm in 124 (45.9%). Blue cartridge (stapler height 3.5 mm) was used in 175 (64.5%) and green cartridge (4.8 mm) in 18 (7%) patients; this information was unavailable in 77 (28.5%) cases. Apical enterotomy closure was performed by linear stapler in 54% and linear cutting stapler in 46%. Apical staple line reinforcement or imbrication suturing was used in 26.3%. The overall postoperative complication rate was 28.9%. The anastomotic leak rate was 2.6%. Independent predictors of complications after laparoscopic right colectomy were older age (OR 1.03, 95%CI 1-1.06; P = 0.01), extended colectomy (OR 2.76, 95%CI 1.07-7.08; P = 0.035) and emergency surgery (OR 4.5, 95%CI 1.3-14.9; P = 0.014). A 100-mm linear cutting stapler was an independent protective factor against postoperative complications (OR 0.3, 95%CI 0.18-0.85; P = 0.019). Stapler height and closure technique of apical enterotomy did not affect postoperative complications. CONCLUSION: Independent predictors of complications after laparoscopic right colectomy were older age, extended colectomy and emergency surgery. Using a 100 mm stapler was an independent protective factor against postoperative complications.

The impact of facility type on surgical outcomes in colon cancer patients: analysis of the national cancer database.

BACKGROUND: The type of facility where patients with colon cancer are treated may play a significant role in their outcomes. We aimed to investigate the influence of facility types included in the National Cancer Database (NCDB) on surgical outcomes of colon cancer. METHODS: Retrospective cohort analysis of all patients with stage I-III colon cancer included in the NCDB database between 2010 and 2019 was performed. Patients were grouped based on facility type: Academic/Research Programs (ARP), Community Cancer Programs (CCP), Comprehensive Community Cancer Programs (CCCP), and Integrated Network Cancer Programs (INCP). Study outcomes included overall survival, 30- and 90-day mortality, 30-day readmission and conversion to open surgery. RESULTS: 125,935 patients were included with a median age of 68.7 years (50.5% females). Most tumors were in the right colon (50.6%). Patient were distributed among facility types as ARP (n = 34,321, 27%), CCP (n = 12,692, 10%), CCCP (n = 54,356, 43%), and INCP (n = 24,566, 19%). In terms of surgical approach, laparoscopy was more commonly used in ARP (46%) (p < 0.001). Laparotomy was more common in CCP (58.7%) (p < 0.001), and conversely, CCP had the least amount of robotic surgery (3.9%) (p < 0.001). Median overall survival was highest in ARP (129 months, 95% CI 127.4-134.1) and lowest in CCP (103.7 months, 95% CI 100.1-106.7) (p < 0.001). Conversion rates were comparable between ARP (12%), CCCP (12%) and INCP (11.8%) but were higher in CCP (15.5%) (p < 0.001). 30-day readmission rates and 30-day mortality rates were significantly lower in ARP compared to other facility types (p < 0.001). CONCLUSION: Our findings display differences in surgical outcomes of colon cancer patients among facility types. The findings suggest better outcomes in terms of operative access and survival at ARP as compared to other facilities. These findings underscore the importance of understanding facility-specific factors that may influence patient outcomes and can guide resource allocation and targeted interventions for improving colon cancer care.

Trans­anal minimally invasive surgery (TAMIS) versus rigid platforms for local excision of early rectal cancer: a systematic review and meta-analysis of the literature.

BACKGROUND: Available platforms for local excision (LE) of early rectal cancer are rigid or flexible [trans­anal minimally invasive surgery (TAMIS)]. We systematically searched the literature to compare outcomes between platforms. METHODS: PRISMA-compliant search of PubMed and Scopus databases until September 2022 was undertaken in this random-effect meta-analysis. Statistical heterogeneity was assessed using I2 statistic. Studies comparing TAMIS versus rigid platforms for LE for early rectal cancer were included. Main outcome measures were intraoperative and short-term postoperative outcomes and specimen quality. RESULTS: 7 studies were published between 2015 and 2022, including 931 patients (423 females); 402 underwent TAMIS and 529 underwent LE with rigid platforms. Techniques were similar for operative time (WMD 11.1, 95%CI - 2.6 to 25, p = 0.11), percentage of defect closure (OR 0.7, 95%CI 0.06-8.22, p = 0.78), and peritoneal violation (OR 0.41, 95%CI 0.12-1.43, p = 0.16). Rigid platforms had higher rates of short-term complications (19.1% vs 14.2, OR 1.6, 95%CI 1.07-2.4, p = 0.02), although no significant differences were seen for major complications (OR 1.41, 95%CI 0.61-3.23, p = 0.41). Patients in the rigid platforms group were 3-times more likely to be re-admitted within 30 days compared to the TAMIS group (OR 3.1, 95%CI 1.07-9.4, p = 0.03). Rates of positive resection margins (rigid platforms: 7.6% vs TAMIS: 9.34%, OR 0.81, 95%CI 0.42-1.55, p = 0.53) and specimen fragmentation (rigid platforms: 3.3% vs TAMIS: 4.4%, OR 0.74, 95%CI 0.33-1.64, p = 0.46) were similar between the groups. Salvage surgery was required in 5.5% of rigid platform patients and 6.2% of TAMIS patients (OR 0.8, 95%CI 0.4-1.8, p = 0.7). CONCLUSION: TAMIS or rigid platforms for LE seem to have similar operative outcomes and specimen quality. The TAMIS group demonstrated lower readmission and overall complication rates but did not significantly differ for major complications. The choice of platform should be based on availability, cost, and surgeon's preference.

The predicting value of post neoadjuvant treatment magnetic resonance imaging: a meta-analysis.

INTRODUCTION: Neoadjuvant therapy has become standard of care for locally advanced rectal cancer patients. It is correlated with improved clinical and pathological outcomes, including significant tumor downstaging and organ preservation in certain patients. Magnetic resonance imaging (MRI), which has become the standard for pre-operative staging, is also used for clinical and pre-operative restaging following pre-operative treatment. In this meta-analysis, we aimed to evaluate the concordance between restaging MRI (following the completion of neoadjuvant therapy) and postoperative pathology result. METHODS: We conducted a meta-analysis following the PRISMA 2020 guidelines. Two independent reviewers searched PubMed and Google Scholar for studies reporting restaging MRI results compared to pathological outcomes. Outcomes included tumor and nodal staging, circumferential resection margin (CRM) and pathological complete response (pCR). RESULTS: Out of 25,000 studies found on the initial search; 33 studies were included. The studies were published between 2005 and 2023 and included 4100 patients (57.14% males). The median age was 62.45 years. The median interval between the conclusion of neoadjuvant treatment and the subsequent restaging MRI was 6 weeks (range 4.14-8.8 weeks). The pooled concordance rates between the restaging MRI and the pathological outcomes for ypT stage and ypN stage were 63.9% (54.5%-73.3%, I2 = 96.02%) and 60.9% (42.9%-78.9%, I2 = 98.96%), respectively. The pooled concordance for predicting pathological complete response was 70.4% (53.6%-87.1%, I2 = 98.21%). As for the circumferential resection margin (CRM), the pooled concordance was 78.2.% (71.6%-84.8%, I2 = 83.76%). CONCLUSIONS: Our findings suggest that the concordance rates between restaging MRI and pathological outcomes in rectal cancer patients following neoadjuvant therapy are limited. Caregivers should take these results into consideration when making clinical decisions about these patients. More data should be gathered about the predictive value of MRI after total neoadjuvant therapy as well as immunotherapy in rectal cancer patients.

Pathologic Outcomes and Survival in Patients with Rectal Cancer and Increased Body Mass Index.

INTRODUCTION: We assessed any association between increased body mass index (BMI) and rectal cancer outcomes. METHODS: We included patients who underwent surgery for stage I-III rectal adenocarcinoma who were divided according to BMI at diagnosis: ideal BMI (18.5-24.9 kg/m2) and increased BMI (≥25 kg/m2). Groups were compared using univariate association analyses relative to baseline characteristics, pathologic outcomes, overall survival (OS) and disease-free survival (DFS). Main outcome measures involved circumferential resection margin (CRM), pathologic TNM stage, total mesorectal incision (TME) grade, OS, and DFS. RESULTS: 243 patients (64.6% male; median age 59 years) with median BMI of 26.3 kg/m2 were included. 62.1% had BMI ≥25 kg/m2. Increased BMI patients had similar proportions of males (66.9% vs 60.9%;p=0.407) and comorbidities (ASA III: 47% vs 37.4%;p=0.24) to ideal BMI patients. There were no significant differences in cN1-2 stage (p=0.279) or positive CRM (p=0.062) rates. The groups had similar complete/near-complete TME, pathologic TN stage, and survival rates. Pathologic and survival outcomes were also similar with a BMI cutoff of 30. CONCLUSIONS: There was a trend toward more nodal involvement in preoperative assessment and less CRM involvement in the final pathology of increased BMI patients. Complete/near-complete TME and survival rates were comparable between the groups.

Meta-analysis of Randomized Clinical Trials on Long-term Outcomes of Surgical Treatment of Perforated Diverticulitis.

OBJECTIVE: To assess long-term outcomes of patients with perforated diverticulitis treated with resection or laparoscopic lavage (LL). BACKGROUND: Surgical treatment of perforated diverticulitis has changed in the last few decades. LL and increasing evidence that primary anastomosis (PRA) is feasible in certain patients have broadened surgical options. However, debate about the optimal surgical strategy lingers. METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials (RCT) on surgical treatment of perforated diverticulitis from inception to October 2022. Long-term reports of RCT comparing surgical interventions for the treatment of perforated diverticulitis were selected. The main outcome measures were long-term ostomy, long-term complications, recurrence, and reintervention rates. RESULTS: After screening 2431 studies, 5 long-term follow-up studies of RCT comprising 499 patients were included. Three studies, excluding patients with fecal peritonitis, compared LL and colonic resection, and 2 compared PRA and Hartmann procedures. LL had lower odds of long-term ostomy [odds ratio (OR) = 0.133, 95% CI: 0.278-0.579; P < 0.001] and reoperation (OR = 0.585, 95% CI: 0.365-0.937; P = 0.02) compared with colonic resection but higher odds of diverticular disease recurrence (OR = 5.8, 95% CI: 2.33-14.42; P < 0.001). Colonic resection with PRA had lower odds of long-term ostomy (OR = 0.02, 95% CI: 0.003-0.195; P < 0.001), long-term complications (OR = 0.195, 95% CI: 0.113-0.335; P < 0.001), reoperation (OR = 0.2, 95% CI: 0.108-0.384; P < 0.001), and incisional hernia (OR = 0.184, 95% CI: 0.102-0.333; P < 0.001). There was no significant difference in odds of mortality among the procedures. CONCLUSIONS: Long-term follow-up of patients who underwent emergency surgery for perforated diverticulitis showed that LL had lower odds of long-term ostomy and reoperation, but more risk for disease recurrence when compared with resection in purulent peritonitis. Colonic resection with PRA had better long-term outcomes than the Hartmann procedure for fecal peritonitis.

Robotic and laparoscopic colectomy: propensity score-matched outcomes from a national cancer database.

BACKGROUND: Laparoscopic and robotic approaches to colonic cancer surgery appear to provide similar outcomes. The present study aimed to compare short-term and survival outcomes of laparoscopic and robotic colectomy for colonic cancer. METHODS: This retrospective review of patients with stage I-III colonic cancer who underwent laparoscopic or robotic colonic resection was undertaken using data from the National Cancer Database (2013-2019). Patients were matched using the propensity score matching method. The primary outcome was 5-year overall survival. Secondary outcomes included conversion to open surgery, duration of hospital stay, 30- and 90-day mortality, unplanned readmission, and positive resection margins. RESULTS: The original cohort included 40 457 patients with stage I-III colonic adenocarcinoma, with a mean(s.d.) age of 67.4(12.9) years. Some 33 860 (83.7 per cent) and 6597 (17.3 per cent) patients underwent laparoscopic and robotic colectomy respectively. After matching, 6210 patients were included in each group. Robotic colectomy was associated with marginally longer overall survival for women, and patients with a Charlson score of 0, stage II-III disease or left-sided tumours. The robotic group had a significantly lower rate of conversion (6.6 versus 11 per cent; P < 0.001) and shorter hospital stay (median 3 versus 4 days) than the laparoscopic group. The two groups had similar rates of 30-day mortality (1.3 versus 1 per cent for laparoscopic and robotic procedures respectively), 90-day mortality (2.1 versus 1.8 per cent), 30-day unplanned readmission (3.7 versus 3.8 per cent), and positive resection margins (2.8 versus 2.5 per cent). CONCLUSION: In this study population, robotic colectomy was associated with less conversion to open surgery and a shorter hospital stay compared with laparoscopic colectomy.