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Case series describing excellent outcomes for patients with dMMR GI cancer after resection of a single progressive lesion under immunotherapy.
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Reparación de la Incompatibilidad de ADN , Inhibidores de Puntos de Control Inmunológico , Terapia Recuperativa , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Gastrointestinales/cirugía , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/tratamiento farmacológico , AncianoRESUMEN
BACKGROUND AND AIMS: During early phases of inflammation, activated neutrophils extrude neutrophil extracellular traps (NETs) in a PAD4-dependent manner, aggravating tissue injury and remodelling. In this study, we investigated the potential pro-fibrotic properties and signalling of NETs in Crohn's disease (CD). METHODS: NETs and activated fibroblasts were labelled on resected ileum from CD patients by multiplex immunofluorescence staining. NETs-treated human primary intestinal fibroblasts were analysed by bulk RNA-sequencing to uncover cell signalling pathways, and by high-throughput imaging to assess collagen production and migratory activity. Consequentially, TLR2/NF-kB pathway was evaluated by transfection of CCD-18Co fibroblasts with NF-kB-luciferase reporter plasmid, incorporating C29 to block TLR2 signalling. A chronic DSS mouse model was used to define the specific role of PAD4 deletion in neutrophils (MRP8-Cre, Pad4fl/fl). RESULTS: Immunofluorescence showed spatial co-localisation of NETs and activated fibroblasts in ileal ulcerations of CD patients. Transcriptomic analysis revealed upregulation of pro-fibrotic genes and activation of TLR-signalling pathways in NETs-treated fibroblasts. NETs treatment induced fibroblast proliferation, diminished migratory capability, and increased collagen release. Transfection experiments indicated a substantial increase in NF-kB expression with NETs, whereas C29 led to decreased expression and release of collagen. In line, a significantly reduction in collagen content was observed in the colon of MRP8-Cre, Pad4fl/fl mice subjected to chronic DSS colitis. CONCLUSIONS: NETs potentially serve as an initial stimulus for pathological activation of fibroblasts within the intestine via the TLR2/NF-kB pathway. Given their early involvement in inflammation, inhibition of PAD4 might offer a strategy to modulate both inflammation and fibrogenesis in CD.
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BACKGROUND & AIMS: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia. RESULTS: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION: This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD.
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Inflammatory bowel diseases (IBD), encompassing conditions like Crohn's disease and ulcerative colitis, present multifaceted challenges requiring a comprehensive management approach. Patients often necessitate a combination of medical therapy, surgical interventions, and nutritional support. Despite advancements in medical and dietary therapies, the prevalence of surgery remains high among the IBD population, alongside the persistent risk of malnutrition. Preoperative nutritional optimization has thus become a critical element in the perioperative pathway, given its association with improved surgical outcomes. However, standardized protocols for preoperative optimization of IBD patients are lacking, and available data are mainly retrospective. This review provides an overview of the current knowledge on preoperative nutritional screening and optimization in IBD patients and identifies avenues for future research and clinical practice. Interdisciplinary collaboration among healthcare professionals, including gastroenterologists, surgeons, dietitians, physiotherapists, and psychologists, is crucial for comprehensive preoperative nutritional management in IBD patients. By addressing the interplay between inflammation, malnutrition, and surgical risk, clinicians can strive to enhance surgical care and postoperative outcomes. In conclusion, while recognizing the importance of preoperative nutritional optimization in improving surgical outcomes for IBD patients, challenges persist in standardizing management protocols. Prospective studies are needed to establish such protocols and evaluate the effectiveness of different nutritional strategies.
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Enfermedades Inflamatorias del Intestino , Evaluación Nutricional , Cuidados Preoperatorios , Humanos , Cuidados Preoperatorios/métodos , Enfermedades Inflamatorias del Intestino/dietoterapia , Apoyo Nutricional/métodos , Desnutrición/diagnóstico , Desnutrición/terapia , Estado NutricionalRESUMEN
Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.
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Enfermedad de Crohn , Fibroblastos , Fibrosis , Monocitos , Proteína 1 Relacionada con Twist , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Enfermedad de Crohn/inmunología , Humanos , Fibroblastos/metabolismo , Fibroblastos/patología , Proteína 1 Relacionada con Twist/metabolismo , Proteína 1 Relacionada con Twist/genética , Monocitos/metabolismo , Monocitos/patología , Monocitos/inmunología , Masculino , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Femenino , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Íleon/patología , Íleon/metabolismo , Íleon/inmunología , Comunicación Celular , Adulto , Endopeptidasas/metabolismo , Endopeptidasas/genética , Animales , RatonesRESUMEN
AIM: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short-term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. METHOD: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. RESULTS: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). CONCLUSION: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.
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Enfermedad de Crohn , Íleon , Fenotipo , Complicaciones Posoperatorias , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Femenino , Estudios Retrospectivos , Masculino , Adulto , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Persona de Mediana Edad , Íleon/cirugía , Adulto Joven , Ciego/cirugía , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Laparoscopía/efectos adversos , Tempo Operativo , Tiempo de Internación/estadística & datos numéricos , Factores de TiempoRESUMEN
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.
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Enfermedad de Crohn , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/normas , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSIONS: Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
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INTRODUCTION: Approximately 50% of patients with Crohn's disease (CD) develop intestinal strictures necessitating surgery. The immune cell distribution in these strictures remains uncharacterized. We aimed to identify the immune cells in intestinal strictures of patients with CD. METHODS: During ileocolonic resections, transmural sections of terminal ileum were sampled from 25 patients with CD and 10 non-inflammatory bowel disease controls. Macroscopically unaffected, fibrostenotic, and inflamed ileum was collected and analyzed for immune cell distribution (flow cytometry) and protein expression. Collagen deposition was assessed through a Masson Trichrome staining. Eosinophil and fibroblast colocalization was assessed through immunohistochemistry. RESULTS: The Masson Trichrome staining confirmed augmented collagen deposition in both the fibrotic and the inflamed regions, though with a significant increased collagen deposition in the fibrotic compared with inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells, and monocytes were identified in fibrotic and inflamed CD ileum compared with unaffected ileum of patients with CD as non-inflammatory bowel disease controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased eosinophil cationic protein expression in inflamed deeper layers. Last, no differences in eosinophil and fibroblast colocalization were observed between the different regions. DISCUSSION: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of patients with CD. Immunologic, proteomic, and histological data suggest inflammation and fibrosis are intertwined, with a large overlap between both tissue types. However strikingly, we did identify an increased presence of active eosinophils only in the fibrotic deeper layers, suggesting their potential role in fibrosis development.
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Colágeno , Enfermedad de Crohn , Eosinófilos , Fibrosis , Íleon , Humanos , Enfermedad de Crohn/patología , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/metabolismo , Eosinófilos/patología , Eosinófilos/inmunología , Masculino , Femenino , Adulto , Íleon/patología , Íleon/inmunología , Persona de Mediana Edad , Colágeno/metabolismo , Colágeno/análisis , Fibroblastos/patología , Fibroblastos/metabolismo , Estudios de Casos y Controles , Adulto Joven , Constricción Patológica/patología , Citometría de Flujo , Células Dendríticas/inmunología , Células Dendríticas/patología , Células Dendríticas/metabolismo , InmunohistoquímicaRESUMEN
AIM: Anal fistula is one of the most common anal diseases, affecting between 1 and 3 per 10 000 people per year. Symptoms have a potentially severe effect on a patient's quality of life. Surgery is the mainstay of treatment, aiming to cure the fistula and preserve anal sphincter function. Rectal advancement flap (RAF) is currently the gold standard treatment but has recurrence rates varying between 20% and 50% and might lead to disturbance of continence. The aim of the trial described in this work is to discover if the minimally invasive fistula tract laser closure (FiLaC™) technique could achieve higher healing rates and a better functional outcome than RAF. METHOD: We will perform a randomized prospective multicentre noninferiority study of the treatment of high trans-sphincteric perianal fistulas, comparing FiLaC™ with RAF in terms of fistula healing, recurrence rate, functional outcome and quality of life. Primary and secondary fistula healing will be evaluated at 26 and 52 weeks' follow-up. Quality of life will be evaluated using the SF-36 questionnaire, the Faecal Incontinence Quality of Life Scale questionnaire and the Vaizey score at 3, 6, 12 and 26 weeks postoperatively. CONCLUSION: High trans-sphincteric fistulas have a potentially severe effect on a patient's quality of life. Classical treatment with RAF is a time-consuming invasive procedure. The LATFIA trial aims to compare FiLaC™ with the gold standard treatment with RAF. In case of noninferiority, FiLaC™ treatment could be standardized as a first line treatment for high trans-sphincteric fistulas. Better conservation of the patient's anal sphincter function could possibly be obtained. Likewise, we will report on the postoperative quality of life when applying these two techniques.
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Canal Anal , Terapia por Láser , Calidad de Vida , Fístula Rectal , Colgajos Quirúrgicos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Canal Anal/cirugía , Estudios de Equivalencia como Asunto , Incontinencia Fecal/etiología , Incontinencia Fecal/cirugía , Terapia por Láser/métodos , Estudios Prospectivos , Fístula Rectal/cirugía , Recto/cirugía , Recurrencia , Resultado del Tratamiento , Cicatrización de Heridas , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Care for patients undergoing elective colectomy has become increasingly standardized using Enhanced Recovery Programs (ERP). ERP, encorporating minimally invasive surgery (MIS), decreased postoperative morbidity and length of stay (LOS). However, disruptive changes are needed to safely introduce colectomy in an ambulatory or same-day discharge (SDD) setting. Few research groups showed the feasibility of ambulatory colectomy. So far, no minimum standards for the quality of care of this procedure have been defined. This study aims to identify quality indicators (QIs) that assess the quality of care for ambulatory colectomy. METHODS: A literature search was performed to identify recommendations for ambulatory colectomy. Based on that search, a set of QIs was identified and categorized into seven domains: preparation of the patient (pre-admission), anesthesia, surgery, in-hospital monitoring, home monitoring, feasibility, and clinical outcomes. This list was presented to a panel of international experts (surgeons and anesthesiologists) in a 1 round Delphi to assess the relevance of the proposed indicators. RESULTS: Based on the literature search (2010-2021), 3841 results were screened on title and abstract for relevant information. Nine papers were withheld to identify the first set of QIs (n = 155). After excluding duplicates and outdated QIs, this longlist was narrowed down to 88 indicators. Afterward, consensus was reached in a 1 round Delphi on a final list of 32 QIs, aiming to be a comprehensive set to evaluate the quality of ambulatory colectomy care. CONCLUSION: We propose a list of 32 QI to guide and evaluate the implementation of ambulatory colectomy.
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Hospitales , Indicadores de Calidad de la Atención de Salud , Humanos , Consenso , Atención Ambulatoria , Tiempo de Internación , Técnica DelphiRESUMEN
AIM: The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology. METHODS: Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG. RESULTS: In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations. CONCLUSION: This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.
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Enfermedades del Ano , Fístula Rectal , Adulto , Humanos , Absceso , Revisiones Sistemáticas como Asunto , Fístula Rectal/diagnóstico , Fístula Rectal/cirugía , Cicatrización de Heridas , Resultado del TratamientoRESUMEN
The development of minimally invasive colorectal surgery in the last decades led to a decrease in length of hospital stay. However, readmission and postoperative complications were still observed. Several studies have shown that close postoperative follow-up is required to decrease postoperative morbidity through patient education and by detecting early signs of complications. To help in this task, multiple monitoring programs have been set up to follow patients at home, allowing detection of several complications at an early stage. To evaluate acceptance, satisfaction, usability, compliance and safety of a mobile application following postoperative colorectal patients during the first 15 days post-discharge from hospital. A mobile application enabling the communication between the patient and medical staff during the recovery phase was developed and tested in four hospitals. Patients who underwent a colorectal resection were included in this prospective qualitative study. Questionnaires to assess satisfaction and usability were handed out to patients at the end of the test period. Overall, 118 patients (52% females, median age 52.5 years) were included. Median adherence-rate during 15 days was 89.6%. Satisfaction-rate for the application was 76% and usability was high. Overall, 1220 notifications were collected, of which 722 were orange, 466 red and 32 purple, colours used to rate the severeness of complaints. We analyzed the most common notifications, showing trends in different subgroups of the study with higher risks of complications (pain (409 notifications), abnormal stools (196 notifications), and wound problems (118 notifications)). A mobile application could be used to follow patients at home after colorectal resection. Future studies should evaluate whether these applications can detect complications and prevent readmission.
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Cuidados Posteriores , Neoplasias Colorrectales , Femenino , Humanos , Persona de Mediana Edad , Masculino , Estudios de Seguimiento , Estudios Prospectivos , Alta del Paciente , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Tiempo de Internación , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicacionesRESUMEN
Anal squamous cell carcinoma (ASCC) is the most common histological subtype of malignant tumor affecting the anal canal. Chemoradiotherapy (CRT) is the first-line treatment in nearly all cases, ensuring complete clinical response in up to 80% of patients. Abdominoperineal resection (APR) is typically reserved as salvage therapy in those patients with persistent or recurrent tumor after CRT. In locally advanced tumors, an extralevator abdominoperineal excision (ELAPE), which entails excision of the anal canal and levator muscles, might be indicated to obtain negative resection margins. In this setting, the combination of highly irradiated tissue and large surgical defect increases the risk of developing postoperative perineal wound complications. One of the most dreadful complications is perineal evisceration (PE), which requires immediate surgical treatment to avoid irreversibile organ damage. Different techniques have been described to prevent perineal complications after ELAPE, although none of them have reached consensus. In this technical note, we present a case of PE after ELAPE performed for a recurrent ASCC. Perineal evisceration was approached by combining a uterine retroversion with a gluteal transposition flap to obtain wound healing and reinforcement of the pelvic floor at once, when a mesh placement is not recommended.
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Neoplasias del Ano , Procedimientos de Cirugía Plástica , Proctectomía , Neoplasias del Recto , Retroversión Uterina , Femenino , Humanos , Retroversión Uterina/complicaciones , Retroversión Uterina/cirugía , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/etiología , Proctectomía/efectos adversos , Neoplasias del Ano/cirugía , Neoplasias del Ano/etiología , Complicaciones Posoperatorias/etiologíaRESUMEN
CD8+ T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against microsatellite stable (MSS) CRC is limited. Little is known about the most critical features of CRC CD8+ T cells that together determine the diverse immune landscapes and contrasting ICB responses. Hence, we pursued a deep single cell mapping of CRC CD8+ T cells on transcriptomic and T cell receptor (TCR) repertoire levels in a diverse patient cohort, with additional surface proteome validation. This revealed that CRC CD8+ T cell dynamics are underscored by complex interactions between interferon-γ signaling, tumor reactivity, TCR repertoire, (predicted) TCR antigen-specificities, and environmental cues like gut microbiome or colon tissue-specific 'self-like' features. MSI CRC CD8+ T cells showed tumor-specific activation reminiscent of canonical 'T cell hot' tumors, whereas the MSS CRC CD8+ T cells exhibited tumor unspecific or bystander-like features. This was accompanied by inflammation reminiscent of 'pseudo-T cell hot' tumors. Consequently, MSI and MSS CRC CD8+ T cells showed overlapping phenotypic features that differed dramatically in their TCR antigen-specificities. Given their high discriminating potential for CD8+ T cell features/specificities, we used the single cell tumor-reactive signaling modules in CD8+ T cells to build a bulk tumor transcriptome classification for CRC patients. This "Immune Subtype Classification" (ISC) successfully distinguished various tumoral immune landscapes that showed prognostic value and predicted immunotherapy responses in CRC patients. Thus, we deliver a unique map of CRC CD8+ T cells that drives a novel tumor immune landscape classification, with relevance for immunotherapy decision-making.
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BACKGROUND: Very few risk factors for postoperative recurrence (POR) of Crohn's Disease (CD) after ileocecal resection have been identified. The aim of the present study was to verify the association between an a priori defined list of intraoperative macroscopic findings and POR. METHODS: This was a prospective observational study including patients undergoing primary ileocecal resection for CD. Four intraoperative factors were independently evaluated by 2 surgeons: length of resected ileum, mesentery thickness, presence of areas of serosal fat infiltration, or abnormal serosal vasodilation on normal bowel proximal to the resected bowel. The primary end point was early endoscopic POR at month 6 and defined as modified Rutgeerts score ≥i2b. Secondary end points were clinical and surgical recurrence. RESULTS: Between September 2020 and November 2022, 83 consecutive patients were included. Early endoscopic recurrence occurred in 45 of 76 patients (59.2%). Clinical and biochemical recurrence occurred in 17.3% (95% confidence interval, [CI], 10.4%-28.0%) and 14.6% of the patients after 12 months. The risk of developing endoscopic and clinical recurrence was 1.127 (95% CI, 0.448;2.834, P = .799) and 0.896 (95% CI, 0.324-2.478, P = .832) when serosal fat infiltration was observed, and 1.388 (95% CI, 0.554-3.476, P = .484), and 1.153 (95% CI, 0.417;3.187, P = .783) when abnormal serosal vasodilation was observed. Similarly, length of the resected bowel and mesentery thickness showed no association with POR. A subgroup analysis on patients who received no postoperative medical prophylaxis did not identify any risk factor for endoscopic POR. CONCLUSIONS: The macroscopic appearance of the bowel and associated mesentery during surgery does not seem to be predictive of POR after ileocecal resection for CD.
Prospective studies investigating risk factors for Crohn's disease recurrence after surgery are scarce. In a prospective cohort of 83 patients undergoing primary ileocecal resection, no association between few intraoperative macroscopic findings and postoperative endoscopic/clinical recurrence was observed.
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BACKGROUND: Treatment of perineal defects after abdominoperineal resection or salvage surgery for either locally advanced rectal cancer or anal carcinoma can be challenging. Myocutaneous flap reconstruction has proven to reduce perineal morbidity and abscess formation in the pelvis; however, it is associated with significant donor-site morbidity. To our knowledge, this is the first report of a laparoscopic oblique rectus abdominis myocutaneous flap harvesting for perineal reconstruction. This technical note aimed to demonstrate the feasibility of the technique. IMPACT OF INNOVATION: Introduction of a laparoscopic technique in harvesting of this flap can potentially further reduce morbidity associated with this flap creation by minimizing abdominal wall trauma and obviating the need for laparotomy for tunneling of the flap intra-abdominally. TECHNOLOGY, MATERIALS, AND METHODS: This report describes a technique using a 6-port laparoscopy, in which the harvesting of the myocutaneous flap was performed after a standardized abdominoperineal resection. The flap itself is passed through the rectus sheath toward the pelvis with the help of a retractor. PRELIMINARY RESULTS: Two patients successfully underwent a laparoscopic oblique rectus abdominis flap reconstruction after abdominoperineal resection. CONCLUSION AND FUTURE DIRECTIONS: This report describes our initial experience with laparoscopic harvesting of an oblique rectus abdominis flap for perineal reconstruction after abdominoperineal resection. We believe the technique is easy and reproducible for laparoscopic surgeons and can reduce donor-site morbidity. However, further studies will be needed to confirm this observation.
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There is ongoing debate whether the type of anastomosis following intestinal resection for Crohn's disease (CD) can impact on complications and postoperative recurrence. The aim of the present study is to describe the outcomes of side-to-side (S-S) vs end-to-end (E-E) anastomosis after ileocecal resection for CD. A retrospective comparative study was conducted in consecutive CD patients who underwent primary ileocecal resection between 2005 and 2013. All patients underwent colonoscopy 6 months postoperatively to assess endoscopic recurrence, defined as Rutgeerts' score (RS) ≥ i2. Surgical recurrence implied reoperation due to CD activity at the anastomotic site. Modified surgical recurrence was defined as the need for reoperation or balloon-dilation. Perioperative factors related to recurrence were evaluated. Of the 127 patients included, 51 (40.2%) received an E-E anastomosis. Median follow-up was longer in the E-E group (8.62 vs 13.68 years). Apart from the microscopic resection margins, patient, disease and surgical characteristics were similar between both groups. Anastomotic complications were comparable (S-S 5.3% vs E-E 5.8%, p = 1.00)0. Postoperatively, biologicals were used in 55.3% and 62.7% (p = 0.47) in S-S and E-E patients, respectively. Endoscopic recurrence did not differ between S-S and E-E patients (78.9 vs 72.9%, p = 0.37), with no significant difference in RS values between both groups (p = 0.87). Throughout follow-up, a higher surgical (p = 0.04) and modified surgical recurrence (p = 0.002) rate was observed in the E-E anastomosis group. Type of anastomosis was an independent risk factor for modified surgical recurrence. The type of anastomosis did not influence endoscopic recurrence and immediate postoperative disease complications. However, the wide diameter and the morphologic characteristic of the stapled S-S anastomosis resulted in a significant reduced risk for surgical and endoscopic reintervention on the long term.