Optimising surgical anastomosis in ileocolic resection for Crohn's disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES).

BACKGROUND: The most common intestinal operation in Crohn's disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption. METHODS: This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs. DISCUSSION: The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines. TRIAL REGISTRATION: NCT05246917 for HAND2END and NCT05578235 for End2End ( http://www. CLINICALTRIALS: gov/ ).

Case report of unusual synchronous anal and rectal squamous cell carcinoma: clinical and therapeutic lesson.

Synchronous tumors of the rectum and anus are sporadic. Most cases in the literature are rectal adenocarcinomas with concomitant anal squamous cell carcinoma. To date, only two cases of concomitant squamous cell carcinomas of the rectum and anus are reported, and both were treated with up-front surgery and received abdominoperineal resection with colostomy. Here, we report the first case in the literature of a patient with synchronous HPV-positive squamous cell carcinoma of the rectum and anus treated with definitive chemoradiotherapy with curative intent. The clinical-radiological evaluation demonstrated complete tumor regression. After 2 years of follow-up, no evidence of recurrence was observed.

Ileoanal pouch-related fistulae: A systematic review with meta-analysis on incidence, treatment options and outcomes.

BACKGROUND: Ileoanal pouch related fistulae (PRF) are a complication of restorative proctocolectomy often requiring repeated surgical interventions and with a high risk of long-term recurrence and pouch failure. AIMS: To assess the incidence of PRF and to report on the outcomes of available surgical treatments. METHODS: A PRISMA-compliant systematic literature search for articles reporting on PRF in patients with inflammatory bowel diseases (IBD) or familial adenomatous polyposis (FAP) from 1985 to 2020. RESULTS: 34 studies comprising 770 patients with PRF after ileal-pouch anal anastomosis (IPAA) were included. Incidence of PRF was 1.5-12%. In IBD patients Crohn's Disease (CD) was responsible for one every four pouch-vaginal fistulae (PVF) (OR 24.7; p=0.001). The overall fistula recurrence was 49.4%; procedure-specific recurrence was: repeat IPAA (OR 42.1; GRADE +); transvaginal repair (OR 52.3; GRADE ++) and transanal ileal pouch advancement flap (OR 56.9; GRADE ++). The overall failure rate was 19%: pouch excision (OR 0.20; GRADE ++); persistence of diverting stoma (OR 0.13; GRADE +) and persistent fistula (OR 0.18; GRADE +). CONCLUSION: PVFs are more frequent compared to other types of PRF and are often associated to CD; surgical treatment has a risk of 50% recurrence. Repeat IPAA is the best surgical approach with a 42.1% recurrence rate.

Influence of diabetes mellitus on inflammatory bowel disease course and treatment outcomes. A systematic review with meta-analysis.

BACKGROUND: Diabetes Mellitus (DM) may occur in IBD and influence the disease progression. AIM: To compare disease course and treatment outcomes in IBD patients with and without DM. METHODS: This is a systematic review with meta-analysis comparing patients with IBD plus DM with patients with IBD only. PRIMARY ENDPOINTS: need for surgery, IBD-related complications, hospitalizations, sepsis, mortality. Quality of life and costs were assessed. RESULTS: Five studies with 71,216 patients (49.1% with DM) were included. Risk for IBD-related complications (OR=1.12, I2 98% p = 0.77), mortality (OR=1.52, I2 98% p = 0.37) and IBD-related surgery (OR=1.20, I2 81% p = 0.26) did not differ. Risk of IBD-related hospitalizations (OR=2.52, I2 0% p < 0.00001) and sepsis (OR=1.56, I2 88% p = 0.0003) was higher in the IBD+DM group. Risk of pneumonia and urinary tract infections was higher in the IBD+DM group (OR=1.72 and OR=1.93), while risk of C. Difficile infection did not differ (OR=1.22 I2 88% p = 0.37). Mean Short Inflammatory Bowel Disease Questionnaire score was lower in the IBD+DM group (38.9 vs. 47, p = 0.03). Mean health care costs per year were $10,598.2 vs $3747.3 (p < 0.001). CONCLUSION: DM might negatively affect the course of IBD by increasing the risk of hospitalization and infections, but not IBD-related complications and mortality.

SupportiNg operAtive Photographic documentation in ileocolonic CROHN's disease surgery: The SNAPCROHN study.

BACKGROUND: There are reported variations in the intraoperative management of Crohn's disease. This consensus statement aimed to develop a standardised protocol for photographic documentation of intraoperative findings and critical procedural steps in ileocolonic Crohn's disease surgery. METHODS: Colorectal surgeons with a specialist interest in minimally invasive surgery and inflammatory bowel disease were invited as committee members to develop a survey on the use of photo-documentation in Crohn's disease surgery. A 15 item survey was developed on ethical considerations and applications of photo-documentation in audit and quality control, research, and training. RESULTS: There was strong agreement on the potential application of intraoperative photo-documentation in Crohn's disease for training, research, quality control and tertiary referrals. Reviewers agreed that intraoperative staging required photo-documentation of strictures, skip lesions, perforations, fat wrapping and mesenteric disease. The necessary steps to be photo-documented were very specific to Crohn's disease surgery, such as views of anastomosis and strictureplasties, and extent of resection(s). CONCLUSIONS: Our consensus statement identified several items for appropriate intraoperative photo-documentation in Crohn's disease surgery, to be used as an adjunct to accurate annotation of intraoperative findings and procedures.

BNT162b2 mRNA COVID-19 vaccine is safe in a setting of patients on biologic therapy with inflammatory bowel diseases: a monocentric real-life study.

OBJECTIVES: Patients with inflammatory bowel disease were excluded from trials that led to the approval of anti-COVID-19 vaccines and are worthy of real-life studies providing information on the safety of these vaccines in this clinical setting. METHODS: A prospective observational study was performed to estimate BNT162b2 mRNA COVID-19 Vaccine local and systemic adverse events (AEs) incidence related to administration in patients with inflammatory bowel disease through a questionnaire administered at the first, second, and third doses. Disease activity by Mayo Partial Score and Harvey-Bradshaw Index was also evaluated. RESULTS: Eighty patients with a median age of 47.5 years were initially enrolled. The local AEs rate was 26.25%, 58.75%, and 28.37% at the first, second, and third doses of the vaccine, respectively. In contrast, the systemic AEs rate was 52.2%, 48.75%, and 43.24%. Clinic-demographic predictor variables for AEs were not identified. Vaccination did not affect disease activity and no statistically significant difference in disease activity index scores was observed between the three doses. No serious adverse events were observed. CONCLUSION: This vaccine was safe in a population of patients with inflammatory bowel disease and, therefore, could be safely administered in this clinical setting.

Microsatellite Status Detection in Gastrointestinal Cancers: PCR/NGS Is Mandatory in Negative/Patchy MMR Immunohistochemistry.

BACKGROUND: Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers. METHODS: Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS). RESULTS: In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR. CONCLUSIONS: In clinical practice, MMR-IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC.

High complication rate in Crohn's disease surgery following percutaneous drainage of intra-abdominal abscess: a multicentre study.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) present an additional challenge as their presence can contraindicate immunosuppressive treatment whilst emergency surgery is associated with high stoma rate and complications. Treatment options include a conservative approach, percutaneous drainage, and surgical intervention. The current multicentre study audited the short-term outcomes of patients who underwent preoperative radiological drainage of intra-abdominal abscesses up to 6 weeks prior to surgery for ileocolonic CD. METHODS: This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing ileocolic resection for primary or recurrent CD from June 2018 to May 2019. The outcomes of patients who underwent radiological guided drainage prior to ileocolonic resection were compared to the patients who did not require preoperative drainage. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. RESULTS: Amongst a group of 575 included patients who had an ileocolic resection for CD, there were 36 patients (6.2%) who underwent abscess drainage prior to surgery. Postoperative morbidity (44.4%) and anastomotic leak (11.1%) were significantly higher in the group of patients who underwent preoperative drainage. CONCLUSIONS: Patients with Crohn's disease who require preoperative radiological guided drainage of intra-abdominal abscesses are at increased risk of postoperative morbidity and septic complications following ileocaecal or re-do ileocolic resection.

Abdominal versus perineal approach for external rectal prolapse: systematic review with meta-analysis.

BACKGROUND: External rectal prolapse (ERP) is a debilitating condition in which surgery plays an important role. The aim of this study was to evaluate the outcomes of abdominal approaches (AA) and perineal approaches (PA) to ERP. METHODS: This was a PRISMA-compliant systematic review with meta-analysis. Studies published between 1990 and 2021 were retrieved. The primary endpoint was recurrence at the last available follow-up. Secondary endpoints included factors associated with recurrence and function. All studies were assessed for bias using the Newcastle-Ottawa Scale and Cochrane tool. RESULTS: Fifteen studies involving 1611 patients (AA = 817; PA = 794) treated for ERP were included, three of which were randomized controlled trials (RCTs; 114 patients (AA = 54; PA = 60)). Duration of follow-up ranged from 12 to 82 months. Recurrence in non-randomized studies was 7.7 per cent in AA versus 20.1 per cent in PA (odds ratio (OR) 0.29, 95 per cent confidence interval (c.i.) 0.17 to 0.50; P < 0.001, I2 = 45 per cent). In RCTs, there was no significant difference (9.8 per cent versus 16.3 per cent, AA versus PA (OR 0.82, 95 per cent c.i. 0.29 to 2.37; P = 0.72, I2 = 0.0 per cent)). Age at surgery and duration of follow-up were risk factors for recurrence. Following AA, the recurrence rates were 10.1 per cent and 6.2 per cent in patients aged 65 years and older and less than 65 years of age, respectively (effect size [e.s.] 7.7, 95 per cent c.i. 4.5 to 11.5). Following PA, rates were 27 per cent and 16.3 per cent (e.s. 20.1, 95 per cent c.i. 13 to 28.2). Extending follow-up to at least 40 months increased the likelihood of recurrence. The median duration of hospital stay was 4.9 days after PA versus 7.2 days after AA. Overall, incontinence was less likely after AA (OR 0.32), but constipation occurred more frequently (OR 1.68). Most studies were retrospective, and several outcomes from RCTs were not consistent with those observed in non-RCTs. CONCLUSION: The overall risk of recurrence of ERP appears to be higher with PA versus AA. Incontinence is less frequent after AA but at the cost of increased constipation. Age at surgery and duration of follow-up are associated with increased risk of recurrence, which warrants adequate reporting of future studies on this topic.

INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial.

BACKGROUND: The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. METHODS: Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. RESULTS: Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. CONCLUSIONS: Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.

This retrospective chart review of patients treated with darvadstrocel indicates sustained remission and confirms a favorable safety profile up to 156 weeks after a single administration of stem cells for treatment of complex perianal fistulas in patients with Crohn's disease.

Standardization of ileoanal J-pouch surgery technique: Quality assessment of minimally invasive ileoanal J-pouch surgery videos.

BACKGROUND: Ileal pouch anal anastomosis is a complex procedure associated with significant morbidity, with several complications after ileal pouch anal anastomosis surgery leading to pouch failure. The aim of the study is to evaluate the heterogeneity surrounding the technique of ileoanal J-pouch surgery by assessing the safety and quality of published online peer-reviewed surgical videos. METHODS: Ileal pouch anal anastomosis videos published on peer-reviewed surgical journals and video channels were edited and anonymized to demonstrate specific steps of the surgical procedure: mobilization and division of the rectum, formation of the ileoanal J-pouch reservoir, anastomosis, and lengthening techniques. The anonymized videos were presented to a group of reviewers with expertise in ileal pouch anal anastomosis blinded to the names and affiliations of the surgeons performing the procedure. Primary outcome was the rate of interobserver variability in the assessment of specific technical steps of the ileal pouch anal anastomosis surgery procedure. Secondary outcome was the appropriateness of the use of surgical videos review as an assessment tool for ileal pouch anal anastomosis surgery, measured as rate of reviewers being unable to answer for poor video quality. RESULTS: In total, 29 video fragments were distributed, and 13 assessors completed a 60-item survey, organized in 7 major domains. The survey completion rate was 93.4%. Out of a total 729 answers, in 23 (3.2%) the reviewers indicated they were unable to comment due to poor video image, and in 48 (6.5%) were unable to comment due to the particular step not being shown in the procedure. The proportion of assessors rating rectal mobilization technically appropriate ranged from 30.7% to 92.3% and from 7.7% to 69.2% for safety. The level of rectal division was considered appropriate in 0 to 53.8% of the videos, whereas the stapling technique used for rectal division was appropriate in 0 to 70% of the videos. CONCLUSION: Our study assessed published peer-reviewed videos on ileal pouch anal anastomosis surgery and reported heterogeneity in the safety of the demonstrated techniques. Blind assessment of published peer-reviewed ileal pouch anal anastomosis videos reported a high rate of unsafe or inappropriate technique for rectal mobilization and transection in the reviewed videos, with fair interobserver agreement among reviewers. There is a need for consensus on what is considered safe and appropriate in ileal pouch anal anastomosis surgery. Peer review of ileal pouch anal anastomosis surgery videos could facilitate training and accreditation in this complex procedure.

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.

Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn's Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial.

BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn's disease. Safety and efficacy outcomes from the clinical trial known as "Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn's disease," or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn's disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn's disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B812.ClinicalTrials.gov No: NCT01541579. ESTUDIO DE SEGUIMIENTO PARA EVALUAR LA SEGURIDAD Y EFICACIA A LARGO PLAZO DE DARVADSTROCEL TRATAMIENTO CON CLULAS MADRE MESENQUIMALES EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE ENSAYO CONTROLADO ALEATORIZADO DE FASE ADMIRECD: ANTECEDENTES:Darvadstrocel es una terapia con células madre mesenquimales alogénicas expandidas derivadas de tejido adiposo para el tratamiento de fístulas perianales complejas en pacientes con enfermedad de Crohn. Los resultados del ensayo clínico conocido como "Células madre mesenquimales derivadas de tejido adiposo para la inducción de la remisión en la enfermedad de Crohn fistulizante perianal" o ADMIRE-CD (NCT01541579), en cuanto a la seguridad y eficacia hasta 52 semanas después del tratamiento, fueron previamente informados. Seguidamente, se presentan los resultados de un seguimiento extendido de 104 semanas.OBJETIVO:Evaluar la seguridad y eficacia a largo plazo de darvadstrocel a dos años del tratamiento en pacientes con enfermedad de Crohn y fístulas perianales complejas.DISEÑO:Este fue un estudio de fase 3, aleatorizado, a doble ciego, controlado (ADMIRE-CD) en pacientes con enfermedad de Crohn perianal fistulizante.DESARROLLO:Esta extensión del estudio se realizó en varios hospitales de siete países europeos e Israel.PACIENTES:Cuarenta pacientes participaron en la extensión de seguimiento: tratamiento con darvadstrocel (n = 25); grupo control (n = 15).INTERVENCIONES:Se administró Darvadstrocel o solución salina (grupo control) una vez, localmente, tras el legrado del trayecto fístuloso y cierre del orificio interno (con la colocación previa de setón). A todos los pacientes se les permitió continuar con los tratamientos médicos en curso para las fístulas.PRINCIPALES MEDIDAS DE RESULTADO:Los eventos de efectos adversos graves derivados del tratamiento se registraron hasta la semana 104. La remisión clínica, definida como el cierre de todas las aberturas externas tratadas que drenaban al inicio espontáneamente o por compresión suave de los dedos, fue evaluado en la semana 104.RESULTADOS:Del total de 40 pacientes, 37 completaron la extensión de seguimiento. Hasta la semana 104, se reportaron 7 eventos de efectos adversos graves resultantes del tratamiento, de los cuales 4 ocurrieron entre las semanas 52 y 104. En la semana 104, se reportó remisión clínica en 14/25 (56%) pacientes en el grupo de darvadstrocel y 6/15 (40%) pacientes en el grupo de control.LIMITACIONES:Solo una pequeña cantidad de pacientes participaron en el período de seguimiento extendido y no se realizaron exámenes por técnicas de imagen en la visita a 104 semanas.CONCLUSIONES:Darvadstrocel fue bien tolerado y la remisión clínica después del tratamiento con darvadstrocel puede mantenerse hasta 104 semanas en pacientes con enfermedad de Crohn perianal fistulizante. Consulte Video Resumen en http://links.lww.com/DCR/B812. (Traducción-Dr Osvaldo Gauto and Dr Julian Panés.)ClinicalTrials.gov No. NCT01541579.

Colonic Lipoma Causing Bowel Intussusception: An Up-to-Date Systematic Review.

BACKGROUND: Colonic lipomas are rare and can sometimes cause intussusception. The aim of this review was to define the presentation and possible management for colocolic intussusception caused by colonic lipomas. METHODS: A systematic search for patients with colocolic intussusception caused by colonic lipoma, including all available reports up to 2021. Epidemiological, clinical, laboratory, and instrumental data and details about the treatments performed were gathered. RESULTS: Colocolic intussusception caused by lipoma is more frequent in women (57%), occurring between 40 and 70 years of age. Up to 83% of patients report abdominal pain, followed by constipation (18%), rectal bleeding (16%), and diarrhea (12%), with abdominal tenderness (37%), and distension in 16%, whereas 24% have a negative exploration. CT (72%) and colonoscopy (62%) are more commonly able to diagnose the entity. The most common location of intussusception is the transverse colon (28%). The surgical operation varies according to the site. The average dimensions of the lipoma are 59.81 × 47.84 × 38.9 mm3. CONCLUSIONS: A correct preoperative diagnosis of colonic lipoma causing intussusception might not be easy. Despite nonspecific clinical and laboratory presentation, cross-sectional imaging can help differential diagnosis. Surgical treatment depends on the localization.

How Immunotherapy Has Changed the Continuum of Care in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide. The use of local treatment, such as surgical resection, liver transplant, and local ablation, has improved the survival of patients with HCC detected at an early stage. Until recently, the treatment of patients with metastatic disease was limited to the use of the multikinase inhibitor (MKI) sorafenib with a marginal effect on survival outcome. New target approaches, such as the oral MKI lenvatinib in first-line treatment and regorafenib, ramucirumab, and cabozantinib in later lines of therapy, have demonstrated efficacy in patients with preserved liver function (Child-Pugh class A) and good performance status. On the other hand, the implementation of immune checkpoint inhibitors directed against PD-1 (nivolumab and pembrolizumab), PD-L1 (atezolizumab), and anti-CTLA4 (ipilimumab) in the management of advanced HCC has strongly changed the continuum of care of HCC. Future research should include the evaluation of molecular biomarkers that can help patient selection and provide new insight on potential combined approaches. In this review, we provide an overview of the clinical evidence of the use of immune checkpoint inhibitors in HCC, and discuss how immunotherapy has been implemented into the continuum of HCC care.

Endorectal Ultrasound and Magnetic Resonance Imaging for Rectal Cancer Staging: A Modern Multimodality Approach.

Preoperative staging represents a crucial point for the management, type of surgery, and candidacy for neoadjuvant therapy in patient with rectal cancer. The most recent clinical guidelines in oncology recommend an accurate preoperative evaluation in order to address early and advanced tumors to different therapeutic options. In particular, potential pitfalls may occur in the assessment of T3 tumors, which represents the most common stage at diagnosis. The depth of tumor invasion is known to be an important prognostic factor in rectal carcinoma; as a consequence, the T3 imaging classification has a substantial importance for treatment strategy and patient survival. However, the differentiation between tumor invasion of perirectal fat and mesorectal desmoplastic reactions remains a main goal for radiologists. Magnetic resonance imaging (MRI) is actually considered as the best imaging modality for rectal cancer staging. Although the endorectal ultrasound (ERUS) is the preferred staging method for early tumors, it could also be useful in identifying perirectal fat invasion. Moreover, the addiction of diffusion weighted imaging (DWI) improves the diagnostic performance of MRI in rectal cancer staging by adding functional information about rectal tumor and adjacent mesorectal tissues. This study investigated the diagnostic performance of conventional MRI alone, in combination with the DWI technique and ERUS in order to assess the best diagnostic imaging combination for rectal cancer staging.

Dual inhibition of TGFß and AXL as a novel therapy for human colorectal adenocarcinoma with mesenchymal phenotype.

A subset of colorectal cancer (CRC) with a mesenchymal phenotype (CMS4) displays an aggressive disease, with an increased risk of recurrence after surgery, reduced survival, and resistance to standard treatments. It has been shown that the AXL and TGFß signaling pathways are involved in epithelial-to-mesenchymal transition, migration, metastatic spread, and unresponsiveness to targeted therapies. However, the prognostic role of the combination of these biomarkers and the anti-tumor effect of AXL and TGFß inhibition in CRC still has to be assessed. To evaluate the role of AXL and TGFß as negative biomarker in CRC, we conducted an in-depth in silico analysis of CRC samples derived from the Gene Expression Omnibus. We found that AXL and TGFß receptors are upregulated in CMS4 tumors and are correlated with an increased risk of recurrence after surgery in stage II/III CRC and a reduced overall survival. Moreover, we showed that AXL receptor is differently expressed in human CRC cell lines. Dual treatment with the TGFß galunisertib and the AXL inhibitor, bemcentinib, significantly reduced colony formation and migration capabilities of tumor cells and displayed a strong anti-tumor activity in 3D spheroid cultures derived from patients with advanced CRC. Our work shows that AXL and TGFß receptors identify a subgroup of CRC with a mesenchymal phenotype and correlate with poor prognosis. Dual inhibition of AXL and TGFß could represent a novel therapeutic strategy for patients with this aggressive disease.

Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer.

BACKGROUND: Despite the advancements in new therapies for colorectal cancer (CRC), chemotherapy still constitutes the mainstay of the medical treatment. For this reason, new strategies to increase the efficacy of chemotherapy are desirable. Poly-ADP-Ribose Polymerase inhibitors (PARPi) have shown to increase the activity of DNA damaging chemotherapeutics used in the treatment of CRC, however previous clinical trials failed to validate these results and pointed out dose-limiting toxicities that hamper the use of such combinations in unselected CRC patients. Nevertheless, in these studies little attention was paid to the mutational status of homologous recombination repair (HRR) genes. METHODS: We tested the combination of the PARPi niraparib with either 5-fluorouracil, oxaliplatin or irinotecan (SN38) in a panel of 12 molecularly annotated CRC cell lines, encompassing the 4 consensus molecular subtypes (CMSs). Synergism was calculated using the Chou-Talalay method for drug interaction. A correlation between synergism and genetic alterations in genes involved in homologous recombination (HR) repair was performed. We used clonogenic assays, mice xenograft models and patient-derived 3D spheroids to validate the results. The induction of DNA damage was studied by immunofluorescence. RESULTS: We showed that human CRC cell lines, as well as patient-derived 3D spheroids, harboring pathogenic ATM mutations are significantly vulnerable to PARPi/chemotherapy combination at low doses, regardless of consensus molecular subtypes (CMS) and microsatellite status. The strongest synergism was shown for the combination of niraparib with irinotecan, and the presence of ATM mutations was associated to a delay in the resolution of double strand breaks (DSBs) through HRR and DNA damage persistence. CONCLUSIONS: This work demonstrates that a numerically relevant subset of CRCs carrying heterozygous ATM mutations may benefit from the combination treatment with low doses of niraparib and irinotecan, suggesting a new potential approach in the treatment of ATM-mutated CRC, that deserves to be prospectively validated in clinical trials.