Increased Pathologic Downstaging with Induction versus Consolidation Chemotherapy in Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy-A National Cancer Database Analysis.

Total neoadjuvant therapy (TNT) is the recommended treatment for locally advanced rectal cancer. The optimal sequence of TNT is debated: induction (chemotherapy first) or consolidation (chemoradiation first)? We aim to evaluate the practice patterns and clinical outcomes of total neoadjuvant therapy with either induction or consolidation regiments in the United States for patients with locally advanced rectal cancer. METHODS: This is a retrospective analysis of the National Cancer Database for patients with clinical stage II or stage III rectal cancer, diagnosed between 2006 and 2017, who underwent total neoadjuvant therapy followed by surgery. RESULTS: From 2006 to 2017, we identified 8999 patients and found that the utilization of induction chemotherapy increased from 2.0% to 35.0%. TNT resulted in pathologic downstaging 46.7% of the time and a pathologic complete response 11.6% of the time. Induction chemotherapy lead to higher pathologic downstaging (58% vs. 44.7%, p < 0.001) and pathologic complete responses (16.8% vs. 10.7%, p < 0.001). Similar trends held true in a multivariate analysis and subset analysis of stage II and III disease. CONCLUSIONS: These findings suggest that induction chemotherapy may be preferred over consolidation chemotherapy when downstaging prior to oncologic resection is desired. The optimal treatment plan for total neoadjuvant therapy is multi-factorial and requires further elucidation.

Cancer in Anal Fistulas.

Fistula-associated anal cancer in Crohn's disease (CD) can be challenging to diagnose and treat. Patients with longstanding fistulas in the setting of CD who present with a sudden change in their symptoms should undergo biopsy under anesthesia with extensive sampling, followed by staging imaging. Pelvic magnetic resonance imaging (MRI) can be helpful in identifying the extent of the disease locally. Patients often present in the later stages due to the challenges associated with diagnosing these patients. Two subtypes of this disease include squamous cell carcinoma and adenocarcinoma, and treatment depends on diagnosis. Small sample size and lack of uniform data on treatments make it difficult to say which treatment modalities are optimal, but aggressive combined therapy is likely the best approach for survival. This will include chemotherapy and radiation and often radical resection as well. Despite this, survival is poor, although more recent data suggest that outcomes are improving.

Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn's Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis.

BACKGROUND AND AIMS: We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohn's disease [CD], focusing on outcomes in the biologic era. METHODS: Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity. RESULTS: Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28-41%; 37% in biologic era], 6-18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54-71%] had successful restoration of bowel continuity, and 26% [20-34%] required re-diversion. Overall, 21% patients [17-27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30-39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies. CONCLUSION: In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.

Sex-Based Differences in IBD Surgical Outcomes.

BACKGROUND: Although there are discrepancies in the development and progression of IBD based on biologic sex, little is known about differences in postoperative outcomes between men and women undergoing surgery for this condition. OBJECTIVE: To compare rates of anastomotic leaks, wound complications, and serious adverse events between men and women undergoing surgery for IBD. DESIGN: This was a retrospective cohort study. SETTINGS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program IBD Collaborative database, which includes 15 high-volume IBD surgery centers. PATIENTS: All adult patients undergoing surgery for IBD were included. Participants with missing data for exposure or outcome variables were excluded. MAIN OUTCOME MEASURES: Rates of anastomotic leaks, wound complications, and serious adverse events were compared between women and men. RESULTS: A total of 3143 patients were included. There was a significant association between sex and BMI, IBD type, and preoperative medication use. Women had decreased odds of serious adverse events compared to men (OR 0.73; 95% CI, 0.55-0.96), but there was no significant association between sex and anastomotic leaks or wound complications. IBD type was found to be an effect measure modifier of the relationship between sex and serious adverse events. Among patients with ulcerative colitis, women had a 54% decrease in the odds of serious adverse events compared to men, whereas there was no significant difference between women and men with Crohn's disease. LIMITATIONS: This study was limited by capturing only 30 days of postoperative outcomes. CONCLUSIONS: Women undergoing surgery for ulcerative colitis had decreased odds of serious adverse events compared to men. Understanding sex-based differences in outcomes allows clinicians to make patient-centered decisions regarding surgical planning and perioperative management for patients with IBD. See Video Abstract . DIFERENCIAS BASADAS EN EL SEXO EN LOS RESULTADOS QUIRRGICOS DE LA ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Aunque existen discrepancias en el desarrollo y la progresión de la enfermedad inflamatoria intestinal según el sexo biológico, se sabe poco sobre las diferencias en los resultados postoperatorios entre hombres y mujeres sometidos a cirugía por esta afección.OBJETIVO:Nuestro objetivo fue comparar las tasas de fugas anastomóticas, complicaciones de las heridas y eventos adversos graves entre hombres y mujeres sometidos a cirugía por enfermedad inflamatoria intestinal.DISEÑO:Este fue un estudio de cohorte retrospectivo.AJUSTES:Los datos se obtuvieron de la base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Americano de Cirujanos para la Enfermedad Inflamatoria Intestinal, que incluye 15 centros de cirugía de enfermedad inflamatoria intestinal de alto volumen.PACIENTES:Se incluyeron todos los pacientes adultos sometidos a cirugía por enfermedad inflamatoria intestinal. Se excluyeron los sujetos a los que les faltaban datos sobre exposición o variables de resultado.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las tasas de fugas anastomóticas, complicaciones de las heridas y eventos adversos graves entre mujeres y hombres.RESULTADOS:Se incluyeron un total de 3.143 pacientes. Hubo una asociación significativa entre el sexo y el índice de masa corporal, el tipo de enfermedad inflamatoria intestinal y el uso de medicación preoperatoria. Las mujeres tuvieron menores probabilidades de sufrir eventos adversos graves en comparación con los hombres (OR = 0,73; IC del 95 %: 0,55 a 0,96), pero no hubo una relacion significativa entre el sexo y las fugas anastomóticas o las complicaciones de las heridas. Se encontró que el tipo de enfermedad inflamatoria intestinal era un modificador de la medida del efecto de la relación entre el sexo y los eventos adversos graves. Entre los pacientes con colitis ulcerosa, las mujeres tuvieron una disminución del 54 % en las probabilidades de sufrir eventos adversos graves en comparación con los hombres, mientras que no hubo diferencias significativas entre mujeres y hombres con enfermedad de Crohn.LIMITACIONES:Este estudio estuvo limitado al capturar solo 30 días de resultados posoperatorios.CONCLUSIONES:Las mujeres sometidas a cirugía por colitis ulcerosa tuvieron menores probabilidades de sufrir eventos adversos graves en comparación con los hombres. Comprender las diferencias en los resultados basadas en el sexo permite a los médicos tomar decisiones centradas en el paciente con respecto a la planificación quirúrgica y el manejo perioperatorio de los pacientes con enfermedad inflamatoria intestinal. (Traducción-Dr Yolanda Colorado).

AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders.

BACKGROUND & AIMS: Pouchitis is the most common complication after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. This American Gastroenterological Association (AGA) guideline is intended to support practitioners in the management of pouchitis and inflammatory pouch disorders. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, conduct an evidence synthesis, and develop recommendations for the prevention and treatment of pouchitis, Crohn's-like disease of the pouch, and cuffitis. RESULTS: The AGA guideline panel made 9 conditional recommendations. In patients with ulcerative colitis who have undergone ileal pouch-anal anastomosis and experience intermittent symptoms of pouchitis, the AGA suggests using antibiotics for the treatment of pouchitis. In patients who experience recurrent episodes of pouchitis that respond to antibiotics, the AGA suggests using probiotics for the prevention of recurrent pouchitis. In patients who experience recurrent pouchitis that responds to antibiotics but relapses shortly after stopping antibiotics (also known as "chronic antibiotic-dependent pouchitis"), the AGA suggests using chronic antibiotic therapy to prevent recurrent pouchitis; however, in patients who are intolerant to antibiotics or who are concerned about the risks of long-term antibiotic therapy, the AGA suggests using advanced immunosuppressive therapies (eg, biologics and/or oral small molecule drugs) approved for treatment of inflammatory bowel disease. In patients who experience recurrent pouchitis with inadequate response to antibiotics (also known as "chronic antibiotic-refractory pouchitis"), the AGA suggests using advanced immunosuppressive therapies; corticosteroids can also be considered in these patients. In patients who develop symptoms due to Crohn's-like disease of the pouch, the AGA suggests using corticosteroids and advanced immunosuppressive therapies. In patients who experience symptoms due to cuffitis, the AGA suggests using therapies that have been approved for the treatment of ulcerative colitis, starting with topical mesalamine or topical corticosteroids. The panel also proposed key implementation considerations for optimal management of pouchitis and Crohn's-like disease of the pouch and identified several knowledge gaps and areas for future research. CONCLUSIONS: This guideline provides a comprehensive, patient-centered approach to the management of patients with pouchitis and other inflammatory conditions of the pouch.

Risk Factors Associated with Postoperative Outcomes in Diverticular Disease Undergoing Elective Colectomy-A Retrospective Cohort Study from the ACS-NSQIP Database.

Recommendations for elective colectomies after recovery from uncomplicated acute diverticulitis should be individualized. The kinds of associated risk factors that should be considered for this approach remain undetermined. The aim of this study was to identify the risk factors associated with postoperative outcomes in patients with diverticular disease after receiving an elective colectomy. This is a retrospective study using the multi-institutional, nationally validated database of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP). The patients who were diagnosed with diverticular disease and received an elective colectomy were included in our risk factor analyses. Postoperative mortality, morbidity, and overall complications were measured. Univariate and multivariate analyses were used to demonstrate the risk factors. We analyzed 30,468 patients with diverticular disease, 67% of whom received an elective colectomy. The rate of 30-day mortality was 0.2%, and superficial surgical site infection was the most common postoperative morbidity (7.2%) in the elective colectomies. The independent risk factors associated with overall complications were age ≥ 75, BMI ≥ 30, smoking status, dyspnea, hypertension, current kidney dialysis, chronic steroid use, ASA III, and open colectomy. In laparoscopic colectomy, 67.5% of the elective colectomies, the associated risk factors associated with overall complications still included age ≥ 75, smoking, hypertension, chronic steroid use, and ASA III. Identification of patient-specific risk factors may inform the decision-making process for elective colectomy and reduce the postoperative complications after mitigation of those risk factors.

Autologous Fat Grafting: an Emerging Treatment Option for Complex Anal Fistulas.

BACKGROUND: Autologous fat grafting (AFG) has shown promise in the treatment of complex wounds, with trials reporting good healing rates and safety profile. We aim to investigate the role of AFG in managing complex anorectal fistulas. METHODS: This was a retrospective review of a prospectively maintained IRB-approved database. We examined the rates of symptom improvement, clinical closure of fistula tracts, recurrence, complications, and worsening fecal incontinence. Perianal disease activity index (PDAI) was obtained for patients undergoing combination of AFG and fistula plug treatment. RESULTS: In total, 52 unique patients underwent 81 procedures, of which Crohn's was present in 34 (65.4%) patients. The majority of patients previously underwent more common treatments such as endorectal advancement flap or ligation of intersphincteric fistula tract. Fat-harvesting sites and processing technique were selected by the plastic surgeons based on availability of trunk fat deposits. When analyzing patients by their last procedure, 41 (80.4%) experienced symptom improvement, and 29 (64.4%) experienced clinical closure of all fistula tracts. Recurrence rate was 40.4%, and complication rate was 15.4% (7 postoperative abscesses requiring I&D and 1 bleeding episode ligated at bedside). The abdomen was the most common site of lipoaspirate harvest at 63%, but extremities were occasionally used. There were no statistically significant differences in outcomes when comparing single graft treatment to multiple treatments, Crohn's and non-Crohn's, different methods of fat preparation, and diversion. CONCLUSION: AFG is a versatile procedure that can be done in conjunction with other therapies and does not interfere with future treatments if recurrence occurs. It is a promising and affordable method to safely address complex fistulas.

Non-Healing Perianal Fistulas: A Clinical Model of Tissue Senescence Impairing Both Tissue Fibrosis and Regenerative Potential.

Senescent cells and fibrosis are important components that impact the regenerative capacity of skin, particularly when considering chronic non-healing wounds. Anoderm and perianal fistulas in the setting of Crohn's disease are clinically pathophysiological extremes with consequently different healing processes which impact treatment modalities. This study describes the implications of potential senescence reversing techniques including autologous fat grafting and pharmacologic and immunomodulating agents. Given these findings, the authors propose a future direction of study involving exosomes loaded with senolytics as a method for potentially improving chronic wound healing. In conclusion, this manuscript explores the diversity of skin healing and healing outcomes which supports the future investigation of senotherapeutic agents promoting regenerative processes for non-healing wounds.

Conventional Frailty Index Does Not Predict Risk of Postoperative Complications in Patients With IBD: A Multicenter Cohort Study.

BACKGROUND: Frailty has been associated with adverse outcomes in patients with IBD. OBJECTIVE: This study aimed to evaluate the association between health deficit-defined frailty (using the 5-factor modified frailty index) and postoperative outcomes in patients with IBD. DESIGN: Prospective cohort study. SETTING: American College of Surgeons National Surgical Quality Improvement Program, Inflammatory Bowel Diseases Module. PATIENTS: The included patients had IBD and underwent major abdominal surgery between 2016 and 2019. Patients were classified as frail (modified frailty index ≥2), prefrail (modified frailty index = 1), or normal (modified frailty index = 0) based on a validated, 5-factor modified frailty index. MAIN OUTCOME MEASURES: The association was evaluated between frailty and risk of 30-day severe postoperative complications, prolonged hospital stay, and risk of readmission using multivariable logistic regression. RESULTS: Of 3172 patients with IBD who underwent major abdominal surgery (42.7 ± 16.4 y, 49.3% female, 57.7% with Crohn's disease, 43.9% on biologics), 116 (3.7%) were classified as frail and 477 as prefrail (15%). After adjustment for age, sex, race/ethnicity, smoking, BMI, type of surgery, corticosteroid use, and biologic and immunomodulator use, frailty was not associated with increased risk for severe postoperative complications (adjusted OR, 1.24; 95% CI, 0.81-1.90), mortality (adjusted OR, 1.38 [0.44-3.6]), or 30-day readmission (adjusted OR, 1.35 [0.77-2.30]). Nonelective surgery, significant weight loss, corticosteroid use, and need for ileostomy were associated with increased risk of severe postoperative complications. LIMITATIONS: Limited information regarding IBD-specific characteristics. CONCLUSIONS: In patients with IBD undergoing major abdominal surgery, frailty measured by a conventional abbreviated health deficits index is not predictive of adverse postoperative outcomes. Biologic and functional measures of frailty may better risk-stratify surgical candidacy in patients with IBDs. See Video Abstract at http://links.lww.com/DCR/C108 . EL NDICE DE FRAGILIDAD CONVENCIONAL NO PREDICE EL RIESGO DE COMPLICACIONES POSOPERATORIAS EN PACIENTES CON ENFERMEDADES INFLAMATORIAS DEL INTESTINO UN ESTUDIO DE COHORTE MULTICNTRICO: ANTECEDENTES:La fragilidad se ha asociado con resultados adversos en pacientes con enfermedades inflamatorias del intestino.OBJETIVO:Examinamos la asociación entre la fragilidad definida por déficit de salud (utilizando el índice de fragilidad modificado de 5 factores) y los resultados postoperatorios en pacientes con enfermedades inflamatorias del intestino.DISEÑO:Estudio de cohorte prospective.ESCENARIO:Programa Nacional de Mejoramiento de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos, Módulo de Enfermedades Inflamatorias del Intestino.PACIENTES:Pacientes con enfermedades inflamatorias intestinales inscritos en la cohorte que se sometieron a cirugía abdominal mayor entre 2016-19.EXPOSICIÓN:Los pacientes se clasificaron como frágiles (índice de fragilidad modificado ≥2), prefrágiles (índice de fragilidad modificado = 1) o normales (índice de fragilidad modificado = 0) según un índice de fragilidad modificado de 5 factores validado.PRINCIPALES MEDIDAS DE RESULTADO:Examinamos la asociación entre la fragilidad y el riesgo de complicaciones postoperatorias graves a los 30 días, la estancia hospitalaria prolongada y el riesgo de reingreso, mediante regresión logística multivariable.RESULTADOS:De 3172 pacientes con enfermedades inflamatorias intestinales que se sometieron a cirugía abdominal mayor (42,7 ± 16,4 años, 49,3% mujeres, 57,7% con enfermedad de Crohn, 43,9% con biológicos), 116 (3,7%) fueron clasificados como frágiles y 477 como pre- frágil (15%). Después de ajustar por edad, sexo, raza/origen étnico, tabaquismo, índice de masa corporal, tipo de cirugía, uso de corticosteroides, uso de biológicos e inmunomoduladores, la fragilidad no se asoció con un mayor riesgo de complicaciones postoperatorias graves (odds ratio ajustado, 1,24; 95 % de confianza intervalos, 0,81-1,90), mortalidad (odds ratio ajustado, 1,38 [0,44-3,6]) o reingreso a los 30 días (odds ratio ajustado, 1,35 [0,77-2,30]). La cirugía no electiva, la pérdida de peso significativa, el uso de corticosteroides y la necesidad de ileostomía se asociaron con un mayor riesgo de complicaciones posoperatorias graves.LIMITACIONES:Información limitada sobre las características específicas de la enfermedad inflamatoria intestinal.CONCLUSIONES:En pacientes con enfermedades inflamatorias del intestino sometidos a cirugía abdominal mayor, la fragilidad medida por un índice de déficit de salud abreviado convencional no es predictivo de resultados postoperatorios adversos. Las medidas biológicas y funcionales de fragilidad pueden estratificar mejor la candidatura quirúrgica en pacientes con enfermedades inflamatorias del intestino. Consulte el Video Resumen en http://links.lww.com/DCR/C108 . (Traducción-Yesenia Rojas-Khalil ).

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study.

BACKGROUND & AIMS: We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD). METHODS: We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching. RESULTS: As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD. CONCLUSION: In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.