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.

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.

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.

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.

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.

Outcomes of laparoscopic versus robotic-assisted resection of T4 rectal cancer: propensity score-matched analysis of a national cancer database.

BACKGROUND: T4 rectal cancer is a challenging condition owing to the highly invasive nature of the tumour that may compromise R0 resection. The present study aimed to assess the outcomes of laparoscopic versus robotic-assisted resection of non-metastatic T4 rectal adenocarcinoma. METHODS: This was a retrospective propensity score-matched analysis using the National Cancer Database between 2010 and 2019. Patients with pathological T4 non-metastatic rectal adenocarcinoma who underwent laparoscopic or robotic-assisted resection were compared and a propensity score-matched analysis was performed in a 1:1 manner. The main outcome measures were conversion to open surgery, mortality, readmission, resection margins, and overall survival. RESULTS: After propensity score matching, 235 patients were included in each group. There were 260 (55.3 per cent) men and 210 (44.7 per cent) women, with a mean (s.d.) age of 61 (13.2) years. Patients in the robotic group had a statistically significantly lower conversion rate (8.9 per cent versus 17.9 per cent; P = 0.006), shorter median duration of hospital stay (5 versus 6 days; P = 0.007), higher overall survival rate (56.2 per cent versus 43.4 per cent; P = 0.007), and a longer median survival (60.8 versus 43.2; P = 0.025). There were no significant differences between the two groups with regard to positive resection margins, examined lymph nodes, 30-day and 90-day mortality rates, and 30-day readmission rate. CONCLUSIONS: Robotic resections of T4 rectal cancer were associated with a significantly lower conversion rate and shorter duration of hospital stay than laparoscopic resections. The two approaches were comparable with regard to positive resection margins, short-term mortality, and readmission.

Propensity-score matched analysis of the pathologic outcomes and survival benefits of neoadjuvant therapy in stage II-III anal adenocarcinoma.

BACKGROUND: Anal adenocarcinomas are a rare condition which account for less than 10% of anal cancers. The present study aimed to assess the impact of neoadjuvant therapy on the clinical and pathologic outcomes and overall survival (OS) of patients with stage II-III anal adenocarcinomas after abdominoperineal resection (APR). METHODS: A retrospective cohort study of patients with anal adenocarcinoma in the US National Cancer Database (NCDB) (2010-2020) was conducted. Propensity-score matching was used to compare patients who received neoadjuvant therapy (neoadjuvant therapy group) to the no-neoadjuvant group. The primary outcome was 5-year OS whereas secondary outcomes included conversion to open surgery, hospital stay, surgical margins, 30-day mortality, 90-day mortality, and 30-day readmission. RESULTS: A total of 742 patients (56% male) with a mean age of 63.6 ± 12.4 years were included. A total of 214 patients in the neoadjuvant group were matched with 107 in the no-neoadjuvant group. The mean OS was similar between the two groups (47.5 vs. 44.8 months, p = 0.253). Patients who received neoadjuvant therapy had a longer median time between diagnosis and surgery (151 vs. 54 days, p < 0.001), lower 90-day mortality (1.9% vs. 6.7%, p = 0.046), more pT0 tumors (15.7% vs. 0%), less pT3-4 tumors (28.4% vs. 36.4%, p = 0.001), less pN1-2 tumors (22.9% vs. 34.7%, p < 0.001), and less lymphovascular invasion (16.2% vs. 40%, p < 0.001) than the no-neoadjuvant group. Both groups had similar conversion rates, hospital stay, 30-day mortality, 30-day readmission, and positive surgical margins. CONCLUSIONS: Neoadjuvant therapy before APR was associated with significant downstaging of anal adenocarcinomas and lower 90-day mortality, yet similar OS to patients who were surgically treated without neoadjuvant treatment.

Serum matrix metalloproteinase-7: a potential biomarker in patients with Lynch Syndrome.

BACKGROUND AND AIMS: The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer. METHODS: This was a case control study. Baseline serum MMP-7 levels were determined by ELISA in 40 colon cancer patients, 62 LS-carriers and 60 healthy controls. Retrieved data from medical files included demographics, background diseases, clinical data regarding tumor characteristics and genetic data. We assessed the association of serum MMP-7 levels with different variables in the study cohort using linear regression model adjusted for potential confounders. RESULTS: In crude analysis, serum MMP-7 levels were significantly higher in colon cancer group compared to LS-carriers and controls [median (IQR) 4.1 ng/ml (2.7-6.0), 2.3 ng/ml (1.7-3.1), 2.5 ng/ml (1.5-3.7), respectively; p value - p < 0.001) while there was no difference between the two last groups (p value = 0.583). However, after adjusting for age and gender, LS-carriers' patients had 18% higher concentrations of serum MMP-7 compared to healthy controls (p value = 0.037), while colon cancer patients had 50% higher serum MMP-7 level in comparison to healthy controls (p value < 0.001). Additionally, age was positively associated with higher serum MMP-7 levels across all study groups (r = 0.67, p value < 0.001). In contrast, no correlation was observed between serum MMP-7 and either tumor staging and gene mutation. CONCLUSIONS: Age-adjusted serum MMP-7 levels in asymptomatic LS carriers are higher than its levels in healthy population. While in colon cancer, MMP-7 higher level probably reflects the tumor burden and may have a prognostic effect, its significance and clinical applicability as a biomarker for tumorigenesis in LS is less clear and should be elucidated.

Predictors and survival outcomes of having less than 12 harvested lymph nodes in proctectomy for rectal cancer.

BACKGROUND: Current recommendations suggest that a minimum of 12 lymph nodes (LNs) should be harvested during curative rectal cancer resection. We aimed to assess predictors and survival outcomes of harvesting < 12 lymph nodes in rectal cancer surgery. METHODS: A retrospective case-control analysis of factors associated with harvesting < 12 LNs in rectal cancer surgery was conducted. Data were derived from the National Cancer Database 2010-2019. Univariate and multivariate binary logistic regression analyses were performed to determine predictors of harvesting < 12 LNs. Association between harvesting < 12 LNs and 5-year overall survival (OS) was assessed using Cox regression and Kaplan Meier statistics. RESULTS: 67,529 patients (60.8% male; mean age: 61.2 ± 12.5 years) were included. Median number of harvested LNs was 15 (IQR: 11-20); 27.1% of patients had < 12 harvested LNs. Independent predictors of harvesting < 12 LNs were older age (OR: 1.016;p < 0.001), neoadjuvant systemic treatment (OR: 1.522;p < 0.001), neoadjuvant radiation treatment (OR: 1.367;p < 0.001), longer duration of radiation therapy (OR: 1.003;p < 0.001) and abdominoperineal resection (OR: 1.071;p = 0.017). Higher clinical TNM stage and tumor grade, pull-through coloanal anastomosis, and minimally invasive surgery were independently associated with ≥ 12 harvested LNs. < 12 harvested LNs was independently associated with lower 5-year OS (HR: 1.24;p < 0.001) and shorter mean OS (96.7 vs 102.8 months;p < 0.001) than ≥ 12 harvested LNs. CONCLUSIONS: Older age, open resection, and neoadjuvant therapy were independent predictors of < 12 harvested LNs. Conversely, higher clinical TNM stage and tumor grade, coloanal anastomosis, and minimally invasive surgery were predictive of ≥ 12 harvested LNs. < 12 LNs harvested was associated with lower OS.

The effect of mechanical bowel preparation on postoperative complications in laparoscopic right colectomy: a retrospective propensity score matching analysis.

PURPOSE: To assess whether full bowel preparation affects 30-day surgical outcomes in laparoscopic right colectomy for colon cancer. METHODS: A retrospective chart review of all elective laparoscopic right colectomies performed for colonic adenocarcinoma between Jan 2011 and Dec 2021. The cohort was divided into two groups-no bowel preparation (NP) group and patients who received full bowel preparation (FP), including oral and mechanical cathartic bowel preparation. All anastomoses were extracorporeal stapled side-to-side. The two groups were compared at baseline and then were matched using propensity score based on demographic and clinical parameters. The primary outcome was 30-day postoperative complication rate, mainly anastomotic leak (AL) and surgical site infection (SSI) rate. RESULTS: The original cohort included 238 patients with a median age of 68 (SD 13) and equal M:F ratio. Following propensity score matching, 93 matched patients were included in each group. Analysis of the matched cohort showed a significantly higher overall complication rate in the FP group (28 vs 11.8%, p = 0.005) which was mostly due to minor type II complications. There were no differences in major complication rates, SSI, ileus, or AL rate. Although operative time was significantly longer in the FP group (119 vs 100 min, p ≤ 0.001), length of stay was significantly shorter in the FP group (5 vs 6 days, p = 0.001). CONCLUSIONS: Aside from a shorter hospital stay, full mechanical bowel preparation for laparoscopic right colectomy does not seem to have any benefit and may be associated with a higher overall complication rate.

Immunotherapy in rectal cancer patients-a propensity score matched analysis of the National Cancer Database.

BACKGROUND: Rectal cancer patients with microsatellite instability (MSI-H) are candidates for immunotherapy. However, there is little evidence on its effect on overall survival (OS). METHODS: Retrospective analysis of stage II-IV rectal adenocarcinoma patients in the National Cancer Database (NCDB) between 2010 and 2019. Propensity score matching was adjusted for baseline and treatment confounders. The cohort was divided into patients who received immunotherapy and matched controls. The primary outcome was OS. RESULTS: 5175/206,615 (2.5%) patients with rectal adenocarcinoma underwent immunotherapy. These patients were younger (58 vs 62 years; p < 0.001), more often male (64.4% vs 61.7%; p < 0.001), were more likely to have private insurance (50.8% vs 43.4%; p < 0.001), more metastatic disease at presentation (clinical TNM stage IV-80.8% vs 23.3%; p < 0.001), presented with larger tumors (median: 5 cm vs. 4.2 cm; p < 0.001) and less often underwent surgery (33.7% vs. 69.9%; p < 0.001), radiation therapy (21.5% vs 57.4%; p < 0.001), and standard chemotherapy (38.1% vs 61%; p < 0.001) than controls. After matching, 488 patients were in each group. OS was significantly shorter in the immunotherapy group (mean survival: 56.4 months (95% CI: -53.03-59.86)) compared to controls (mean survival: 70.5 months (95% CI: -66.15-74.92) (p = 0.004)). Cox regression analysis of factors associated with OS demonstrated that immunotherapy was associated with increased mortality (HR 2.16; 95% CI: 2.09-2.24; p < 0.001). After clinical staging stratification, immunotherapy was associated with improved OS in stage IV (HR 0.91, 95% CI: 0.88-0.95; p < 0.001) but lower survival in stage II (HR 2.38; 95% CI: 2.05-2.77; p < 0.001) and stage III (HR 2.43; 95% CI: 2.18-2.7; p < 0.001) patients. CONCLUSION: Immunotherapy showed modest increase in OS in stage IV metastatic rectal cancer. OS was significantly lower in stage II-III disease treated with immunotherapy.

The value of CA125 in predicting acute complicated colonic diverticulitis.

BACKGROUND: CA125 is a widely used serum marker for epithelial ovarian cancer which levels may also rise in benign conditions involving peritoneal irritation. We aimed to determine if serum CA125 levels can predict disease severity in patients presenting with acute diverticulitis. METHODS: We conducted a single-center prospective observational study, analyzing CA125 serum levels in patients who presented to the emergency department with computerized tomography-proven acute left-sided colonic diverticulitis. Univariate, multivariate, and receiver operating characteristic (ROC) analyses were used to correlate CA125 serum levels at time of initial presentation with the primary outcome (complicated diverticulitis) and secondary clinical outcomes (need for urgent intervention, length of hospital stay (LOS) and readmission rates). RESULTS: One hundred and fifty-one patients were enrolled between January 2018 and July 2020 (66.9% females, median age 61 years). Twenty-five patients (16.5%) presented with complicated diverticulitis. CA125 levels were significantly higher among patients with complicated (median: 16 (7-159) u/ml) vs. uncomplicated (8 (3-39) u/ml) diverticulitis (p < 0.001) and also correlated with the Hinchey severity class (p < 0.001). Higher CA125 levels upon admission were associated with a longer LOS and a greater chance to undergo invasive procedure during the hospitalization. In patients with a measurable intra-abdominal abscess (n = 24), CA125 levels were correlated with the size of the abscess (Spearman's r = 0.46, p = 0.02). On ROC analysis to predict complicated diverticulitis, the area under the curve (AUC) for CA125 (AUC = 0.82) was bigger than for the leukocyte count (AUC = 0.53), body temperature (AUC = 0.59), and neutrophil-lymphocyte ratio (AUC = 0.70) - all p values < 0.05. On multivariate analysis of factors available at presentation, CA125 was found to be the only independent predictor of complicated diverticulitis (OR 1.12 (95% CI 1.06-1.19), p < 0.001). CONCLUSIONS: The results from this feasibility study suggest that CA125 may accurately discriminate between simple and complicated diverticulitis, meriting further prospective investigation.

Risk of colorectal advanced neoplasia in patients with acute diverticulitis with and without previous colonoscopy.

BACKGROUND AND AIM: Guidelines recommend a colonoscopy after an episode of complicated diverticulitis and after a first episode of uncomplicated diverticulitis. The influence of a previous colonoscopy on postdiverticulitis colonoscopic findings has not been studied. The aim of this work was to examine the incidence of adenoma detection rate (ADR), advanced adenoma (AA) and colorectal cancer (CRC) in patients with diverticulitis with and without previous colonoscopy. METHOD: This was a retrospective case-control study of subjects with acute diverticulitis. Subsequent and previous colonoscopies were abstracted for ADR, AA and CRC diagnoses. The incidence of neoplasia was compared between patients with and without previous colonoscopy and also with that of a screening population. RESULTS: Compared with a healthy control group (n = 975), diverticulitis patients without prior colonoscopy (n = 325) had a significantly higher ADR (26.8% vs. 20.5%, p = 0.019) and invasive CRC rate (0.9% vs. 0%, p = 0.016). Risk factors for advanced neoplasia included age ≥ 70 years and complicated diverticulitis. Among subjects with diverticulitis and previous colonoscopy (n = 124), only one patient developed AA and there were no cancer cases. CONCLUSIONS: A previous normal colonoscopy within 5 years before diverticulitis probably overshadows other risk factors for findings of advanced neoplasia and should be considered in the decision to repeat a colonoscopy.