Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN+ versus IFN- pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types.

The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection.

Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial, and more studies are needed to understand their orchestration. In the present study, we characterize in depth and link pDC activation states in animals infected by mouse cytomegalovirus by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially in time and in different micro-anatomical locations. In addition, we show that pDC commitment to IFN-I production was marked early on by their downregulation of leukemia inhibitory factor receptor and was promoted by cell-intrinsic tumor necrosis factor signaling. We propose a new model for how individual pDCs are endowed to exert different functions in vivo during a viral infection, in a manner tightly orchestrated in time and space.

pH and ROS Responsiveness of Polymersome Nanovaccines for Antigen and Adjuvant Codelivery: An In Vitro and In Vivo Comparison.

The antitumor immunity can be enhanced through the synchronized codelivery of antigens and immunostimulatory adjuvants to antigen-presenting cells, particularly dendritic cells (DCs), using nanovaccines (NVs). To study the influence of intracellular vaccine cargo release kinetics on the T cell activating capacities of DCs, we compared stimuli-responsive to nonresponsive polymersome NVs. To do so, we employed "AND gate" multiresponsive (MR) amphiphilic block copolymers that decompose only in response to the combination of chemical cues present in the environment of the intracellular compartments in antigen cross-presenting DCs: low pH and high reactive oxygen species (ROS) levels. After being unmasked by ROS, pH-responsive side chains are exposed and can undergo a charge shift within a relevant pH window of the intracellular compartments in antigen cross-presenting DCs. NVs containing the model antigen Ovalbumin (OVA) and the iNKT cell activating adjuvant α-Galactosylceramide (α-Galcer) were fabricated using microfluidics self-assembly. The MR NVs outperformed the nonresponsive NV in vitro, inducing enhanced classical- and cross-presentation of the OVA by DCs, effectively activating CD8+, CD4+ T cells, and iNKT cells. Interestingly, in vivo, the nonresponsive NVs outperformed the responsive vaccines. These differences in polymersome vaccine performance are likely linked to the kinetics of cargo release, highlighting the crucial chemical requirements for successful cancer nanovaccines.

Perioperative outcomes of ileorectal anastomosis - an analysis of 823 patients.

AIM: Ileorectal anastomosis (IRA) following total abdominal colectomy (TAC) allows for resortation of bowel continuity but prior studies have reported rates of anastomotic leak (AL) to be as high as 23%. We aimed to report rates of AL and complications in a large cohort of patients undergoing IRA. We hypothesized that AL rates were lower than previously reported and that selective use of diverting loop ileostomy (DLI) is associated with decreased AL rates. METHOD: Patients undergoing TAC or end-ileostomy reversal with IRA, with or without DLI, between 1980 and 2021 were identified from a prospectively maintained institutional database and retrospectively analysed. Redo IRA cases were excluded. Short-term (30-day) surgical outcomes were collected using our database. AL was defined using a combination of imaging and, in the case of return to the operating room, intraoperative findings. RESULTS: Of 823 patients in the study cohort, DLI was performed in 27% and performed more frequently for constipation and inflammatory bowel disease. The overall AL rate was 3% (1% and 4% in those with and without DLI, respectively) and diversion was found to be protective against leak (OR 0.28, 95% CI 0.08-0.94, p = 0.04). However, patients undergoing diversion had a higher overall rate of postoperative complications (51% vs. 36%, p < 0.001) including superficial wound infection, urinary tract infection, dehydration, blood transfusion and portomesenteric venous thrombosis (all p < 0.04). CONCLUSION: Our study represents the largest series of patients undergoing IRA reported to date and demonstrates an AL rate of 3%. While IRA appears to be a viable surgical option for diverse indications, our study underscores the importance of careful patient selection and thoughtful consideration of staging the anastomosis and temporary faecal diversion when necessary.

Fact or fiction? Does the position of the end-to-end (EEA) stapler spike matter for colorectal anastomoses using a double-stapled technique?

AIM: Surgeons often have strong opinions about how to perform colorectal anastomoses with little data to support variations in technique. The aim of this study was to determine if location of the end-to-end (EEA) stapler spike relative to the rectal transection line is associated with anastomotic integrity. METHOD: This study was a retrospective analysis of a quality collaborative database at a quaternary centre and regional hospitals. Patients with any left-sided colon resection with double-stapled anastomosis were included (December 2019 to August 2022). Our primary endpoint was a composite outcome including positive air insufflation test, incomplete anastomotic donut, or thin/eccentric donut. Our secondary endpoint was clinical leak. RESULTS: Overall, 633 patients were included and stratified by location of the stapler spike relative to the rectal transection line. Of note, 86 patients had an end-colon to anterior rectum ("reverse Baker") anastomosis with no crossing staple lines. The rates of the composite endpoint based on position of the stapler spike were 12.4% (anterior), 8.1% (through), 12.8% (posterior), 5.1% (corner), and 2.3% for the "reverse Baker" (p = 0.03). The overall rate of clinical leak was 3.8% and there were no differences between methods. In a multivariate analysis, the "reverse Baker" anastomosis was associated with decreased odds of poor anastomotic integrity when compared to anastomoses with crossing staple lines (OR 0.20, 95% CI: 0.05-0.87, p = 0.03). CONCLUSIONS: For anastomoses with crossing staple lines, the position of the stapler spike relative to the rectal staple line is not associated with differences in anastomotic integrity. In contrast, anastomoses with no crossing staple lines resulted in significantly lower rates of poor anastomotic integrity, but no difference in clinical leaks.

Outcome of incidental versus preoperatively diagnosed colorectal cancer during total proctocolectomy with ileal pouch-anal anastomosis for inflammatory bowel disease.

AIM: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for colorectal cancer (CRC) in inflammatory bowel disease. CRC may also be discovered incidentally at IPAA for other indications. We sought to determine whether incidentally found CRC at IPAA was associated with worse outcomes. METHODS: Our institutional pouch registry (1983-2021) was retrospectively reviewed. Patients with CRC at pathology after IPAA were divided into two groups: a preoperative diagnosis (PreD) group and an incidental diagnosis (InD) group. Their long-term outcomes (overall survival, disease-free survival and pouch survival) were compared. RESULTS: We included 164 patients: 53 (32%) InD and 111 (68%) PreD. There were no differences in cancer staging, differentiation and location. After a median follow-up of 11 (IQR 3-25) years for InD and 9 (IQR 3-20) years for the PreD group, deaths were 14 (26%) in the InD group and 18 (16%) in the PreD group. Pouch failures were five (9%) in the InD group and nine (8%) in the PreD group, of which two (5%) and four (4%) were cancer related. Ten-year overall survival was 94% for InD and 89% for PreD (P = 0.41), disease-free survival was 95% for InD and 90% for PreD (P = 0.685) and pouch survival was 89% for InD and 97% for PreD (P = 0.80). Pouch survival at 10 years was lower in rectal versus colon cancer (87% vs. 97%, P = 0.01). No difference was found in outcomes in handsewn versus stapled anastomoses. CONCLUSION: Inflammatory bowel disease patients with incidentally found CRC during IPAA appear to have similarly excellent oncological and pouch outcomes to patients with a preoperative cancer diagnosis.

Transanal ileal pouch-anal anastomosis for inflammatory bowel disease: a systematic review and meta-analysis of short-term outcomes.

AIM: Restorative proctocolectomy with transabdominal ileal pouch-anal anastomosis (abd-IPAA) has become the standard surgical treatment for medically refractory ulcerative colitis (UC). However, it requires a technically difficult distal anorectal dissection and anastomosis due to the bony confines of the deep pelvis. To address these challenges, the transanal IPAA approach (ta-IPAA) was developed. This novel approach may offer increased visibility and range of motion compared with abd-IPAA, although its postoperative benefits remain unclear. The aim of this work was to perform a systematic review and meta-analysis to compare and inform the frequency of postoperative outcomes between ta-IPAA and abd-IPAA for patients with UC. METHOD: Several databases were searched from inception until May 2022 for studies reporting postoperative outcomes of patients undergoing ta-IPAA. Reviewers, working independently and in duplicate, evaluated studies for inclusion and graded the risk of bias. Odds ratios (OR), mean differences (MD) and prevalence ratio (PR) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Sensitivity analysis was performed. RESULTS: Ten retrospective studies comprising 284 patients with ta-IPAA were included. Total mesorectal excision was performed in 61.8% of cases and close rectal dissection in 27.9%. There was no difference in the odds of Clavien-Dindo (CD) I-II complications, CD III-IV and anastomotic leak (OR 0.96, 95% CI 0.27-3.40; OR 1.18, 95% CI 0.65-2.16; OR 1.37, 95% CI 0.58-3.23; respectively) between ta-IPAA and abd-IPAA. The ta-IPAA pooled CD I-II complication rate was 18% (95% CI 5%-35%) and for CD III-IV 10% (95% CI 5%-17%), and the anastomotic leak rate was 6% (95% CI 2%-10%). There were no deaths reported. CONCLUSIONS: This meta-analysis compared the novel ta-IPAA procedure with abd-IPAA and found no difference in postoperative outcomes. While the need for randomized controlled trails and comparison of functional outcomes between both approaches remains, this evidence should assist colorectal surgeons to decide if ta-IPAA is a viable alternative.

The role of advanced endoscopy in appendiceal polyp management and outcomes.

BACKGROUND: Appendiceal orifice lesions are often managed operatively with limited or oncologic resections. The aim is to report the management of appendiceal orifice mucosal neoplasms using advanced endoscopic interventions. METHODS: Patients with appendiceal orifice mucosal neoplasms who underwent advanced endoscopic resections between 2011 and 2021 with either endoscopic mucosal resection (EMR), endoscopic mucosal dissection (ESD), hybrid ESD, or combined endoscopic laparoscopic surgery (CELS) were included from a prospectively collected dataset. Patient and lesion details and procedure outcomes are reported. RESULTS: Out of 1005 lesions resected with advanced endoscopic techniques, 41 patients (4%) underwent appendiceal orifice mucosal neoplasm resection, including 39% by hybrid ESD, 34% by ESD, 15% by EMR, and 12% by CELS. The median age was 65, and 54% were male. The median lesion size was 20 mm. The dissection was completed piecemeal in 49% of patients. Post-procedure, one patient had a complication within 30 days and was admitted with post-polypectomy abdominal pain treated with observation for 2 days with no intervention. Pathology revealed 49% sessile-serrated lesions, 24% tubular adenomas, and 15% tubulovillous adenomas. Patients were followed up for a median of 8 (0-48) months. One patient with a sessile-serrated lesion experienced a recurrence after EMR which was re-resected with EMR. CONCLUSION: Advanced endoscopic interventions for appendiceal orifice mucosal neoplasms can be performed with a low rate of complications and early recurrence. While conventionally lesions at the appendiceal orifice are often treated with surgical resection, advanced endoscopic interventions are an alternative approach with promising results which allow for cecal preservation.

Acute colonic pseudo-obstruction: a retrospective review of the surgical outcomes.

PURPOSE: Limited data exist regarding the surgical outcomes of acute colonic pseudo-obstruction (ACPO), commonly referred to as Ogilvie syndrome, in modern clinical practice. The prevailing belief is that surgery should be avoided due to previously reported high mortality rates. We aimed to describe the surgical results of ACPO treated within our institution. METHODS: Our prospectively maintained colorectal surgery registry was queried for patients diagnosed with ACPO, who underwent surgery between 2009 and 2022. Postoperative complications were graded according to Clavien-Dindo (CD) classification. The primary outcome was postoperative mortality. RESULTS: A total of 32 patients who underwent surgery for ACPO were identified. Overall, nonoperative therapy was initially administered to 21 patients (65.6%). The surgeries performed included total abdominal colectomy (15, 43.1%), ascending colectomy with end ileostomy (8, 25%), transverse colostomy (5, 15.6%), ileostomy and transverse colostomy (3, 9.4%), and Hartmann's operation (1, 3.1%). Severe postoperative complications (CD grade 3 or 4) occurred in five patients (15.6%). No recurrence of ACPO was observed and no patient required reoperation. The average postoperative length of stay was 14.5 days, 30-day mortality was 6.3% (n = 2), and 90-day mortality was 15.6% (n = 5) due to complications of underlying comorbidities. CONCLUSIONS: Surgical treatment was effective for patients with ACPO refractory to medical therapy or presenting with acute complications. Although postoperative complications were frequent, both the 30- and 90-day mortality rates were lower than previously documented in the literature. Further investigations are warranted to determine the optimal surgical strategy, which may involve total or segmental colectomy, or diversion alone without resection.

Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV.

We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection - namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels - and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval.

The Learning Curve for Advanced Endoscopy for Colorectal Lesions: A Surgeon's Experience at a High-Volume Center.

BACKGROUND: Advanced endoscopy can be used for the complete removal of large colorectal polyps. To date, few surgeons perform advanced endoscopy, and it is unknown how many procedures are needed to reach proficiency. OBJECTIVE: This study aimed to determine the learning curve for colorectal advanced endoscopy. DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: We queried a prospectively maintained institutional database of advanced endoscopy performed by a high-volume colorectal surgeon between 2011 and 2018. MAIN OUTCOME MEASURES: Advanced endoscopy characteristics were compared for 6 chronological intervals. Primary end points were the rates of complications and polyp recurrence. Secondary end point was the change in polyp removal rate (mm/h) over time. RESULTS: A total of 207 patients underwent advanced endoscopy for a single colorectal polyp. The median polyp size was 30 (4-70) mm, 61.5% were located in the right colon, and 8.8% were malignant. The mean procedure time was 77 (range, 16-320) minutes. Immediate colon resection occurred in 25 patients because of suspicion of cancer or concern for perforation and was excluded from the learning curve analysis. The remaining 182 advanced endoscopy procedures were divided into intervals of 30 procedures. The median removal rate was highest in the last interval and in the endoscopy suite. A removal rate of 30 mm/h was achieved after performing 100 cases. The complication rate (bleeding or return to operating room) was 12.1% and was similar across intervals. The readmission rate was 11.5%, and 6.6% of 6-month follow-up colonoscopies showed polyp recurrence at the resection site. LIMITATIONS: Retrospective design and single surgeon. CONCLUSION: The learning curve for achieving proficiency with advanced endoscopy in the colon and rectum required a minimum of 100 cases with a low complication rate, low polyp recurrence rate, high en bloc resection rate, and a polyp removal rate of 30 mm/h. See Video Abstract at http://links.lww.com/DCR/C162 .LA CURVA DE APRENDIZAJE DE LA ENDOSCOPIA AVANZADA PARA LESIONES COLORRECTALES: LA EXPERIENCIA DE UN CIRUJANO EN UN CENTRO DE ALTO VOLUMENANTECEDENTES:La endoscopia avanzada se puede utilizar para la extirpación completa de pólipos colorrectales grandes. Hasta la fecha, pocos cirujanos realizan endoscopia avanzada y se desconoce cuántos procedimientos se necesitan para alcanzar la competencia.OBJETIVO:Determinar la curva de aprendizaje de la endoscopia colorrectal avanzada.DISEÑO:Retrospectivo.AJUSTE:Centro de referencia terciario.PACIENTES:Consultamos una base de datos institucional mantenida prospectivamente de endoscopia avanzada realizada por un cirujano colorrectal de alto volumen entre 2011 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las características de la endoscopia avanzada en seis intervalos cronológicos. Los puntos finales primarios fueron las tasas de complicaciones y recurrencia de pólipos. El criterio de valoración secundario fue el cambio en la tasa de eliminación de pólipos (mm/h) a lo largo del tiempo.RESULTADOS:Un total de 207 pacientes se sometieron a una endoscopia avanzada por un solo pólipo colorrectal. La mediana del tamaño de los pólipos fue de 30 (4-70) mm, el 61,5% se ubicaron en el colon derecho y el 8,8% fueron malignos. El tiempo medio del procedimiento fue de 77 (rango: 16-320) minutos. La resección inmediata del colon ocurrió en 25 pacientes debido a la sospecha de cáncer o preocupación por la perforación y fueron excluidos del análisis de la curva de aprendizaje. Los restantes 182 procedimientos de endoscopia avanzada se dividieron en intervalos de 30 procedimientos. La mediana de la tasa de extirpación fue más alta en el último intervalo y en la sala de endoscopia. Se logró una tasa de extirpación de 30 mm/hr después de realizar 100 casos. La tasa de complicaciones (sangrado o retorno al quirófano) fue del 12,1% y fue similar en todos los intervalos. La tasa de reingreso fue del 11,5% y el 6,6% de las colonoscopias de seguimiento a los 6 meses mostraron recurrencia de pólipos en el sitio de la resección.LIMITACIONES:Diseño retrospectivo, cirujano único.CONCLUSIÓN:La curva de aprendizaje para lograr el dominio de la endoscopia avanzada en el colon y el recto requiere un mínimo de 100 casos con una baja tasa de complicaciones, baja tasa de recurrencia de pólipos, alta tasa de resección en bloque y una tasa de eliminación de pólipos de 30 mm/h. Consulte el Video Resumen en http://links.lww.com/DCR/C162 . (Traducción-Dr. Yesenia.Rojas-Khalil ).

Impact of Total Neoadjuvant Therapy on Postoperative Outcomes After Proctectomy for Rectal Cancer.

BACKGROUND: Total neoadjuvant therapy is an alternative to neoadjuvant chemoradiation alone for rectal cancer and has the benefits of more completion of planned therapy, increased downstaging, earlier treatment of micrometastases, and assessment of chemosensitivity; however, it may increase surgical complications, especially with increased radiation-to-surgery interval. OBJECTIVE: The study aimed to determine the impact of total neoadjuvant therapy on postoperative complications compared with neoadjuvant chemoradiation alone. DESIGN: Retrospective cohort study. SETTINGS: Single tertiary referral center. PATIENTS: The patient included was a stage II/III rectal cancer patient who underwent total neoadjuvant therapy or long-course neoadjuvant chemoradiation followed by surgical resection from 2018-2020. MAIN OUTCOME MEASURES: The main outcome measures included severe postoperative complications (Clavien-Dindo grade ≥3). RESULTS: Of 181 patients, 86 (47.5%) underwent total neoadjuvant therapy and 95 (52.5%) underwent neoadjuvant chemoradiation. There was no difference in severe postoperative complications or any complications. There was also no difference in the rate of complete total mesorectal excision or negative circumferential margin. Total neoadjuvant therapy had a mean operative time of 355.5 minutes and estimated blood loss of 263.6 mL compared with 326.7 minutes and 297.5 mL in the neoadjuvant chemoradiation group. Total neoadjuvant therapy patients had a lower mean lymph node yield than neoadjuvant chemoradiation patients. On multivariable analysis, total neoadjuvant therapy was associated with increased operative time (OR, 1.19; p < 0.001) and estimated blood loss (OR, 1.22; p < 0.001) and decreased lymph node yield (OR, 0.67; p < 0.001). There was no difference in severe complications or any complications. LIMITATIONS: Selection bias uncontrolled by modeling. CONCLUSIONS: We found no difference in risk of postoperative complications between patients who received total neoadjuvant therapy vs neoadjuvant chemoradiation. Total neoadjuvant therapy patients had longer operations and greater estimated blood loss. This may be a reflection of increased operative difficulty because of increased radiation-to-surgery interval and/or the effects of chemotherapy; however, the absolute differences were small and, therefore, should be interpreted cautiously. See Video Abstract at http://links.lww.com/DCR/C44 . IMPACTO DE LA TERAPIA NEOADYUVANTE TOTAL EN LOS RESULTADOS POSOPERATORIOS DESPUS DE UNA PROCTECTOMA POR CNCER DE RECTO: ANTECEDENTES:La terapia neoadyuvante total es una alternativa a la quimiorradiación neoadyuvante sola para el cáncer de recto y tiene los beneficios de una mayor finalización de la terapia planificada, mayor reducción del estadiage, tratamiento más temprano de las micrometástasis y evaluación de la quimiosensibilidad; sin embargo, puede aumentar las complicaciones quirúrgicas, especialmente con un mayor intervalo entre la radiación y la cirugía.OBJETIVO:Determinar el impacto de la terapia neoadyuvante total sobre las complicaciones posoperatorias en comparación con la quimiorradiación neoadyuvante sola.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Centro único de referencia terciario.PACIENTES:Paciente con cáncer de recto en estadio II/III que se sometieron a terapia neoadyuvante total o quimiorradiación neoadyuvante de larga duración seguida de resección quirúrgica entre 2018 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias graves (grado de Clavien-Dindo ≥3).RESULTADOS:De 181 pacientes, 86 (47,5%) se sometieron a terapia neoadyuvante total y 95 (52,5%) se sometieron a quimiorradioterapia neoadyuvante. No hubo diferencia en las complicaciones postoperatorias graves o cualquier otra complicación. Tampoco hubo diferencia en la tasa de escisión mesorrectal total completa o margen circunferencial negativo. La terapia neoadyuvante total tuvo un tiempo operatorio promedio de 355,5 minutos y una pérdida de sangre estimada de 263,6 ml en comparación con 326,7 minutos y 297,5 ml en el grupo de quimiorradiación neoadyuvante. Los pacientes con terapia neoadyuvante total tuvieron una media de ganglios linfáticos más bajo en comparación con los pacientes con quimiorradioterapia neoadyuvante. En el análisis multivariable, la terapia neoadyuvante total se asoció con un mayor tiempo operatorio (OR = 1,19, p < 0,001) y pérdida de sangre estimada (OR = 1,22, p < 0,001) y menor cantidad los ganglios linfáticos (OR = 0,67, p < 0,001). No hubo diferencia en las complicaciones graves o cualquier complicación.LIMITACIONES:Sesgo de selección no controlado por modelado.CONCLUSIONES:No encontramos diferencias en el riesgo de complicaciones postoperatorias entre los pacientes que recibieron terapia neoadyuvante total versus quimiorradiación neoadyuvante. Los pacientes con terapia neoadyuvante total tuvieron operaciones más prolongadas y una mayor pérdida de sangre estimada. Esto puede ser un reflejo de una mayor dificultad quirúrgica como resultado de un mayor intervalo entre la radiación y la cirugía y/o los efectos de la quimioterapia; sin embargo, las diferencias absolutas fueron pequeñas y, por lo tanto, deben interpretarse con cautela. Consulte Video Resumen en http://links.lww.com/DCR/C44 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Leaks From the Tip of the J-pouch: Diagnosis, Management, and Long-term Pouch Survival.

BACKGROUND: The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from the tip of the J-pouch are a known complication, but there is a paucity of literature regarding this type of leak. OBJECTIVE: We aimed to describe the diagnosis, management, and long-term clinical outcomes of leaks from the tip of the J-pouch at our institution. DESIGN: This was a retrospective study of a prospectively maintained pouch registry. SETTING: This study was conducted at a quaternary IBD referral center. PATIENTS: Patients included those with ileal J-pouches diagnosed with leaks from the tip of the J-pouch. MAIN OUTCOME MEASURES: The main measures of outcomes were pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival. RESULTS: We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, whereas 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3% of patients but only discovered during surgical exploration in 25.6% of patients. Some 63.5% of patients were diagnosed only after loop ileostomy closure, whereas 32.4% of patients were diagnosed before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive nonoperative approach was attempted in 48.6% of patients but was successful in only 10.8% of patients overall. Surgical repair was attempted in 89.2% of patients, whereas 4.5% of patients had pouch excision. Salvage operations (n = 63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair, and reanastomosis (9.5%). Ultimately' 10 patients (13.5%) required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%. LIMITATIONS: This was a retrospective review; referral bias may limit the generalizability. CONCLUSIONS: Leaks from the tip of the J-pouch have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority of patients and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50 . FUGAS DEL EXTREMO DE LA BOLSA EN J DIAGNSTICO, MANEJO Y SUPERVIVENCIA A LARGO PLAZO DE LA BOLSA: ANTECEDENTES:El estándar de atención para el tratamiento quirúrgico de la colitis ulcerosa es la proctocolectomía restauradora con bolsa ileal en J. Las fugas del extremo de la bolsa en J son una complicación conocida, pero hay escasez de literatura sobre este tipo de fuga.OBJETIVO:Describir el diagnóstico, manejo y resultados clínicos a largo plazo de las fugas del extremo de la bolsa en J en nuestra institución.DISEÑO:Estudio retrospectivo de registro de bolsa mantenido prospectivamente.ENTORNO CLINICO:Centro de referencia de enfermedad inflamatoria intestinal cuaternaria.PACIENTES:Pacientes con bolsas ileales en J diagnosticadas con fugas del extremo de la J.PRINCIPALES MEDIDAS DE VALORACIÓN:Tasa de rescate de la bolsa, tipo de procedimientos de rescate y supervivencia a largo plazo de la bolsa Kaplan-Meier.RESULTADOS:Identificamos 74 pacientes con fugas del extremo de la bolsa en J. El dolor (68,9%) y el absceso pélvico (40,9%) fueron las presentaciones más comunes, mientras que el 10,8% de los pacientes presentaron abdomen agudo. La fuga se diagnosticó por imagen y/o endoscopia en el 74,3%, pero solo se descubrió durante la exploración quirúrgica en el 25,6%. El 63,5% fueron diagnosticados solo después del cierre de la ileostomía en asa, mientras que el 32,4% lo fueron antes del cierre de la ileostomía. Los métodos más comunes utilizados para el diagnóstico fueron la endoscopia (31,1%) y el enema de gastrografín (28,4%). Se intentó un abordaje no quirúrgico definitivo en el 48,6%, pero tuvo éxito en solo el 10,8% de los pacientes en general. Se intentó la reparación quirúrgica en el 89,2% de los pacientes, mientras que en el 4,5% se realizó la escisión del reservorio. Las operaciones de rescate (n = 63) incluyeron la reparación con sutura o grapas del extremo de la J (65%), la escisión del reservorio con neo-reservorio (25,4%) y la desconexión, reparación y reanastomosis del reservorio (9,5%). Finalmente, 10 (13,5%) pacientes requirieron la escisión de la bolsa, lo que se asocio con una alta tasa de supervivencia general de la bolsa a los 5 años del 86,3%.LIMITACIONES:Revisión retrospectiva; el sesgo de referencia puede limitar la generalización.CONCLUSIONES:Las fugas del extremo de la bolsa en J tienen presentaciones clínicas variables y requieren un alto índice de sospecha. La cirugía de rescate de la bolsa se requiere en la mayoría y se asocia con una alta tasa de rescate de la bolsa. Consulte Video Resumen en http://links.lww.com/DCR/C50 . (Traducción- Dr. Ingrid Melo ).

Redo Ileocolic Resection Is Not an Independent Risk Factor for Anastomotic Leak in Recurrent Crohn's Disease.

BACKGROUND: Redo ileocolic resection for recurrent Crohn's disease is associated with increased technical complexity and higher complication rates compared to primary resection. Literature concerning redo surgery for recurrent Crohn's disease is scarce and it is controversial whether a redo is a risk factor for postoperative anastomotic leak. OBJECTIVE: This study aimed to hypothesized that redo ileocolic resection for Crohn's disease is an independent risk factor for anastomotic leak. DESIGN: Retrospective, case-control study from 1994 to 2019 with multivariate analysis and propensity score weighting. SETTING: Quaternary, IBD-referral center. PATIENTS: Adult patients aged >18 years were included in the study. INTERVENTIONS: Primary or redo ileocolic resection with an anastomosis, with or without diverting ileostomy. MAIN OUTCOME MEASURES: Thirty-day anastomotic leak rate. RESULTS: A total of 991 patients (56% primary and 44% redo ileocolic resections) were included. Patients who underwent redo resection were significantly older with more comorbidities, fewer medications, and less fistulizing disease compared to the primary group. On univariate analysis, patients who underwent redo resection had more overall complications (50.5% vs 36.2%, p < 0.001), and the cumulative number of prior ileocolic resections was significantly associated with increased risk for overall morbidity ( p < 0.001). There were 31 (3%) anastomotic leaks; leak rates did not differ between groups ( p = 0.60). Multivariable analysis indicated that extensive adhesiolysis ( p < 0.001), ileostomy omission ( p = 0.009), and intraoperative abscess/fistula ( p = 0.02) were independently associated with leaks but not redo resection ( p = 0.27). Patients with 0, 1, 2, or 3 of these risk factors had observed leak rates of 1.1%, 1.3%, 6.0%, and 11.6.% ( p = 0.03), respectively. LIMITATIONS: The limitations of this study were selection bias, referral bias, and single quaternary center. CONCLUSIONS: Compared to primary procedures, redo ileocolic resection for recurrent Crohn's disease is associated with increased overall morbidity but not anastomotic leak. See Video Abstract at http://links.lww.com/DCR/C132 . LA RESECCIN ILEOCLICA REHECHA NO ES UN FACTOR DE RIESGO INDEPENDIENTE DE FUGA ANASTOMTICA EN LA ENFERMEDAD DE CROHN RECURRENTE: ANTECEDENTES:La resección ileocólica para la enfermedad de Crohn recurrente se asocia con una mayor complejidad técnica y mayores tasas de complicaciones en comparación con la resección primaria. La literatura sobre la reintervención quirúrgica para la enfermedad de Crohn recurrente es escasa y es controvertido si una redo es un factor de riesgo para la fuga anastomótica posoperatoria.OBJETIVO:Tenemos la hipótesis de que rehacer la resección ileocólica para la enfermedad de Crohn es un factor de riesgo independiente para la fuga anastomótica.DISEÑO:Estudio retrospectivo de casos y controles de 1994 a 2019 con análisis multivariado y ponderación de puntuación de propensión.AJUSTE:Centro de referencia de enfermedad inflamatoria intestinal de cuarto nivel.PACIENTES:Pacientes adultos >18 años.INTERVENCIONES:Resección ileocólica primaria o rehecha con una anastomosis, con o sin derivación de ileostomía.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de fuga anastomótica a los 30 días.RESULTADOS:Se incluyeron un total de 991 pacientes (56% resecciones primarias y 44% resecciones ileocólicas rehechas). Los pacientes de reintervención eran significativamente mayores con más comorbilidades, menos medicamentos y menos enfermedad fistulizante en comparación con el grupo primario. En el análisis univariado, los pacientes reoperados tuvieron más complicaciones generales (50,5% frente a 36,2%, p < 0,001) y el número acumulado de resecciones ileocólicas previas se asoció significativamente con un mayor riesgo de morbilidad general ( p < 0,001). Hubo 31 (3%) fugas anastomóticas; las tasas de fuga no difirieron entre los grupos ( p = 0,6). El análisis multivariado indicó que la adhesiolisis extensa ( p < 0,001), la omisión de ileostomía ( p = 0,009) y el absceso/fístula intraoperatorios ( p = 0,02) se asociaron de forma independiente con fugas, pero no con nueva resección ( p = 0,27). Los pacientes con 0, 1, 2 o 3 de estos factores de riesgo observaron tasas de fuga del 1,1%, 1,3%, 6,0% y 11,6% ( p = 0,03), respectivamente.LIMITACIONES:Sesgo de selección, Sesgo de referencia, un centro de cuarto nivelCONCLUSIÓN:En comparación con los procedimientos primarios, la resección ileocólica para la enfermedad de Crohn recurrente se asocia con una mayor morbilidad general, pero no con una fuga anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C132 . (Traducción-Dr. Mauricio Santamaria ).

Effect of Incisional Negative Pressure Wound Therapy on Surgical Site Infections in High-Risk Reoperative Colorectal Surgery: A Randomized Controlled Trial.

BACKGROUND: Colorectal resections have relatively high rates of surgical site infections causing significant morbidity. Incisional negative pressure wound therapy was introduced to improve wound healing of closed surgical incisions and to prevent surgical site infections. OBJECTIVE: This randomized controlled trial aimed to investigate the effect of incisional NPWT on superficial surgical site infections in high-risk, open, reoperative colorectal surgery. DESIGN: This was a single-center randomized controlled trial conducted between July 2015-October 2020. Patients were randomly assigned to incisional negative pressure wound therapy or standard gauze dressing with a 1:1 ratio. A total of 298 patients were included. SETTINGS: This study was conducted at the colorectal surgery department of a tertiary-level hospital. PATIENTS: This study included patients older than 18 years who underwent elective reoperative open colorectal resections. Patients were excluded who had open surgery within the past 3 months, who had active surgical site infection, and who underwent laparoscopic procedures. MAIN OUTCOME MEASURES: The primary outcome was superficial surgical site infection within 30 days. Secondary outcomes were deep and organ-space surgical site infections within 7 days and 30 days, postoperative complications, and length of hospital stay. RESULTS: A total of 149 patients were included in each arm. The mean age was 51 years, and 49.5% were women. Demographics, preoperative comorbidities, and preoperative albumin levels were comparable between the groups. Overall, most surgeries were performed for IBD, and 77% of the patients had an ostomy fashioned during the surgery. No significant difference was found between the groups in 30-day superficial surgical site infection rate (14.1% in control versus 9.4% in incisional negative pressure wound therapy; p = 0.28). Deep and organ-space surgical site infections rates at 7 and 30 days were also comparable between the groups. Postoperative length of stay and complication rates (Clavien-Dindo grade) were also comparable between the groups. LIMITATIONS: The patient population included in the trial consisted of a selected group of high-risk patients. CONCLUSIONS: Incisional negative pressure wound therapy was not associated with reduced superficial surgical site infection or overall complication rates in patients undergoing high-risk reoperative colorectal resections. See Video Abstract at http://links.lww.com/DCR/B956 . EFECTO DE LA TERAPIA DE HERIDA INSICIONAL CON PRESIN NEGATIVA EN INFECCIONES DEL SITIO QUIRRGICO EN CIRUGA COLORRECTAL REOPERATORIA DE ALTO RIESGO UN ENSAYO CONTROLADO ALEATORIZADO: ANTECEDENTES:Las resecciones colorrectales tienen tasas relativamente altas de infecciones del sitio quirúrgico que causan una morbilidad significativa. La terapia de heridas incisionales con presión negativa se introdujo para mejorar la cicatrización de las heridas de incisiones quirúrgicas cerradas y para prevenir infecciones del sitio quirúrgico.OBJETIVO:El objetivo de este ensayo controlado y aleatorizado fue investigar el efecto de la terapia de herida incisional con presión negativa en infecciones superficiales del sitio quirúrgico en cirugía colorrectal re operatoria, abierta y de alto riesgo.DISEÑO:Ensayo controlado y aleatorizado de un solo centro entre julio de 2015 y octubre de 2020. Los pacientes fueron aleatorizados para recibir tratamiento para heridas incisionales con presión negativa o vendaje de gasa estándar en una proporción de 1:1. Se incluyeron un total de 298 pacientes.AJUSTE:Este estudio se realizó en el departamento de cirugía colorrectal de un hospital de tercer nivel.PACIENTES:Se incluyeron pacientes mayores de 18 años que se fueron sometidos a resecciones colorrectales abiertas, re operatorias y electivas. Se excluyeron aquellos pacientes que tuvieron cirugía abierta en los últimos 3 meses, con infección activa del sitio quirúrgico y que fueron sometidos a procedimientos laparoscópicos.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue infección superficial del sitio quirúrgico dentro de los 30 días. Los resultados secundarios fueron infecciones del sitio quirúrgico profundas y del espacio orgánico dentro de los 7 y 30 días, las complicaciones posoperatorias y la duración de la estancia hospitalaria.RESULTADOS:Se incluyeron un total de 149 pacientes en cada brazo. La edad media fue de 51 años y el 49,5% fueron mujeres. La demografía, las comorbilidades preoperatorias y los niveles de albúmina preoperatoria fueron comparables entre los grupos. En general, la mayoría de las cirugías fueron realizadas por enfermedad inflamatoria intestinal y al 77 % de los pacientes se les confecciono una ostomía durante la cirugía. No hubo diferencias significativas entre los grupos en la tasa de infección del sitio quirúrgico superficial a los 30 días (14,1 % en el control frente a 9,4 % en el tratamiento de herida incisional con presión negativa, p = 0,28). Las tasas de infecciones del sitio quirúrgico profundas y del espacio orgánico a los 7 y 30 días también fueron comparables entre los grupos. La duración de la estancia postoperatoria y las tasas de complicaciones (Clavien-Dindo Graduacion) también fueron comparables entre los grupos.LIMITACIONES:La población de pacientes incluida en el ensayo consistió en un grupo seleccionado de pacientes de alto riesgo.CONCLUSIONES:Video Resumen en http://links.lww.com/DCR/B956 . (Traducción-Dr. Osvaldo Gauto ).

CT vascular territory mapping: a novel method to identify large vessel occlusion collateral.

INTRODUCTION: This descriptive study explores typical patterns of vascular territory mapping (VTM) in ischaemic stroke patients with proximal vessel occlusion. VTM is a novel process using CT perfusion that can identify the source and extent of collateral blood flow in patients with vessel occlusion. It functions by determining which vessel provides dominant blood flow to a brain voxel. METHODS: A total of 167 consecutive patients were analysed from INSPIRE (International Stroke Perfusion Imaging Registry) with their CT perfusion reprocessed through VTM software. We explored the typical territory maps generated by this software relating to common large vessel occlusion location sites (ACA/MCA/PCA). RESULTS/CONCLUSION: In the presence of occlusion, VTM demonstrated a reciprocal increase in collateral vessel territories.

Operative management of anastomotic leak after sigmoid colectomy for left-sided diverticular disease: Ileostomy creation may be as safe as colostomy creation.

AIM: The management of anastomotic leak after sigmoid colectomy for diverticular disease has not been well defined. Specifically, there is a lack of literature on optimal types of reoperations for leaks. The aim of this study was to describe and compare reoperative approaches and their postoperative outcomes. METHODS: We performed a retrospective cohort study using the NSQIP Colectomy Module (2012-2019) and single-institution chart review. Patients with diverticular disease who underwent elective sigmoid colectomy were included. Primary outcomes were anastomotic leak requiring reoperation and management of anastomotic leak. RESULTS: Of 37,471 patients who underwent sigmoid colectomy for diverticular disease, 1003 (2.7%) suffered an anastomotic leak, of whom 583 underwent reoperation. Of the 572 patients who were not initially diverted and underwent reoperation for leak, 302 (52.8%) were managed with stoma creation - 200 (35.0%) with colostomy and 102 (17.8%) with ileostomy. The remaining 47.2% underwent colectomy with reanastomosis, suturing of large bowel, and drainage. There were no differences in length of stay, readmission, or mortality between patients who underwent ileostomy or colostomy at reoperation (p > 0.05). Single-institution analysis demonstrated that 100% of patients with ileostomies underwent subsequent ileostomy closure, compared to 60% of patients with colostomies. CONCLUSIONS: In patients who suffer anastomotic leaks after sigmoid colectomy for diverticular disease and undergo reoperations, ileostomy at the time of reoperation appears to be safe, with comparable results to colostomy. Ileostomies were more frequently closed than colostomies. When faced with a colorectal anastomotic leak, ileostomy creation may be considered.

Assessing prognostic factors of long-term survival after surgery for colorectal gastrointestinal stromal tumours.

AIM: Due to their rarity, the management of colorectal gastrointestinal stromal tumours (CR GISTs) is still under debate. The aim of this study was to assess prognostic factors. METHOD: We performed a retrospective review of patients who underwent surgery with curative intent for CR GIST at our centre from 2002 to 2019. Factors associated with overall (OS) and recurrence-free survival (RFS) were analysed. RESULTS: Fifty-six patients were included [median age 63 years, 29 (52%) female, 30 (54%) Miettinen high-risk, 40 (71%) with rectal GIST]. Nineteen (34%) patients received perioperative (neoadjuvant and/or adjuvant) imatinib. All cases of colonic GIST had an R0 resection, compared with 28 (70%) of rectal GISTs. After a median follow-up of 97 months (interquartile range 48-155 months), 14 (25%) deaths and 14 (25%) recurrences occurred. In the high-risk cohort, factors associated with improved RFS were R0 resection (OR 0.19, 95% CI 0.1-0.5, p = 0.002) and perioperative imatinib (OR 0.33, 95% CI 0.42-0.97, p = 0.04). Patients who had received perioperative imatinib had longer RFS (60% vs. 11% at 5 years, p = 0.006) but not OS. In rectal GISTs, 5-year OS was 85% for R0 and 70% for R1 resections (p = 0.164) and 5-year RFS was 85% for R0 and 12% for R1 resection (p < 0.001). When stratifying patients by perioperative imatinib, there were no differences in OS or RFS in the R0 or R1 groups. CONCLUSION: Perioperative imatinib and R0 resection were associated with improved RFS in high-risk patients with CR GIST. In patients with rectal GIST, R1 resection was associated with worse RFS irrespective of perioperative imatinib treatment.

Are large ileocecal valve lesions amenable with advanced endoscopic management to avoid bowel resection?

INTRODUCTION: Mucosal lesions located at the ileocecal valve may be challenging for endoscopic intervention because of angulated anatomy and a thinner wall with narrower lumen when compared to other locations of the bowel. This study aimed to evaluate the management and outcomes of ileocecal valve lesions treated endoscopically. MATERIAL AND METHODS: Patients with mucosal neoplasms involving the ileocecal valve managed with advanced endoscopy at a quaternary care hospital between 2011 and 2021 were included from a prospectively collected database. Patient demographics, lesion characteristics, complications, and outcomes are reported. RESULTS: From 1005 lesions, 80 patients (8%) underwent resection for neoplasms involving ileocecal valve by ESD (n = 38), hybrid ESD (n = 38), EMR (n = 2), and CELS (n = 2). The median age of the study group was 63(37-84) years, and 50% of patients were female. The median lesion size was 34 mm (5-75). The mean procedure time was 66 ± 44 min(range:18-200). The dissection was completed as piecemeal in 41(51%) patients and 35(44%) had en-bloc dissection. Seven(8%) endoscopic interventions required conversion to laparoscopic surgery due to inability to lift the mucosa(n = 4) and perforation(n = 3). No immediate bleeding occurred in the study group. Five patients had late rectal bleeding and two were admitted with post-polypectomy pain within 30 days of intervention. Pathology revealed 4(5%) adenocarcinomas, 33(41.2%) tubular adenomas, 30(37.8%) tubulovillous adenomas, and 5(6.2%) sessile serrated adenomas. Sixty-seven (84.5%) patients completed at least one follow-up colonoscopy and were followed for a median of 11(0-64) months. Six (8.9%) patients had recurrence and were managed with subsequent endoscopic removal. CONCLUSION: Advanced endoscopy can be safely and effectively performed for the management of ileocecal valve polyps with low complication and acceptable recurrence rates. Advanced endoscopy promises an alternative approach to oncologic ileocecal resection while attaining organ preservation. Our study demonstrates the impact of advanced endoscopy for the treatment of mucosal neoplasms involving ileocecal valve.

The use of laparoscopy for T4a and T4b colon cancer: are we playing with fire?

BACKGROUND: The laparoscopic approach for colon cancer has become widely accepted. However, its safety for T4 tumors, and particularly for T4b tumors when local invasion to adjacent structures occurs, remains controversial. This study aimed to compare short and long-term outcomes in patients undergoing laparoscopic vs. open resection for T4a and T4b colon cancers. METHODS: A prospectively maintained, single-institution database was queried to identify patients with pathological stage T4a and T4b colon adenocarcinomas electively operated on between 2000 and 2012. Patients were divided into two groups based on the use of laparoscopy. Patient characteristics, perioperative, and oncologic outcomes were compared. RESULTS: One hundred and nineteen patients [41 laparoscopic (L), 78 open surgeries (O)] met the inclusion criteria. No difference was observed in age, gender, BMI, ASA, and procedure between groups. Tumors treated by L were smaller than O (p = 0.003). No difference was observed in morbidity, mortality, reoperation, or readmission between the groups. Length of hospital stay was shorter in L than O (6 vs. 9 days, p = 0.005). Conversion to open was necessary in 22% of all T4 tumors laparoscopic cases. However, when tumors were subdivided by pT4 classification, conversion was necessary for 4 of 34 (12%) pT4a patients vs. 5 of 7 (71%) pT4b patients (p = 0.003). In the pT4b cohort (n = 37), more tumors were treated by the open approach (30 vs. 7). For pT4b tumors, the R0 resection rate was 94% (86% in L vs. 97% in O, p = 0.249). The use of laparoscopy did not impact overall survival, disease-free survival, cancer-specific survival, or tumor recurrence overall in all T4 or T4a and T4b tumors. CONCLUSIONS: Laparoscopic surgery can be safely performed in pT4 tumors with similar oncologic outcomes as compared to open surgery. However, for pT4b tumors, the conversion rate is very high. The open approach may be preferable.