ABSTRACT
BACKGROUND: Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the different steps of colorectal tumorigenesis using whole exome sequencing and search for associated splicing events via RNA sequencing at the bulk-tumor and single-cell levels. RESULTS: Our results demonstrate that MSI leads to hundreds of noncoding DNA mutations, notably at polypyrimidine U2AF RNA-binding sites which are endowed with cis-activity in splicing, while higher frequency of exon skipping events are observed in the mRNAs of MSI compared to non-MSI CRC. At the DNA level, these noncoding MSI mutations occur very early prior to cell transformation in the dMMR colonic crypt, accounting for only a fraction of the exon skipping in MSI CRC. At the RNA level, the aberrant exon skipping signature is likely to impair colonic cell differentiation in MSI CRC affecting the expression of alternative exons encoding protein isoforms governing cell fate, while also targeting constitutive exons, making dMMR cells immunogenic in early stage before the onset of coding mutations. This signature is characterized by its similarity to the oncogenic U2AF1-S34F splicing mutation observed in several other non-MSI cancer. CONCLUSIONS: Overall, these findings provide evidence that a very early RNA splicing signature partly driven by MSI impairs cell differentiation and promotes MSI CRC initiation, far before coding mutations which accumulate later during MSI tumorigenesis.
Subject(s)
Alternative Splicing , Colorectal Neoplasms , Microsatellite Instability , Splicing Factor U2AF , Colorectal Neoplasms/genetics , Humans , Splicing Factor U2AF/genetics , Splicing Factor U2AF/metabolism , Mutation , Binding Sites , ExonsABSTRACT
OBJECTIVE: To report the 90-day mortality benefit associated with the implementation of the new regulatory reform on oncological surgical digestive authorizations. SUMMARY BACKGROUND DATA: New thresholds in digestive cancer surgery were applied in 2023, accrediting centers for major interventions. No evidence has been provided to support their justification. METHODS: Any French adult operated for digestive cancer from January 1, 2019 to December 31, 2021 was included from the PMSI. A 90-day mortality logistic regression was performed by adjusting by age, sex, Charlson score, Frailty index, hospital-volume (<5 or ≥5 interventions/year), emergency intervention, specialty. RESULTS: 143,582 patients were identified. Of these, 64,268 underwent surgery of one of the subspecialties subject to the new thresholds (stomach N = 8283, liver N = 18,668, pancreas N = 11,220, esophagus N = 3704, rectum N = 22,393). 4808 (7.5 %) patients underwent surgery in low-volume centers, distributed as follows: stomach 1757/8283 (22.94 %), liver 970/18,668 (5.19 %), pancreas 895/11,220 (7.98 %), esophagus 672/3704 (18.14 %) and rectum 514/22,393 (2.29 %). In univariate analysis, the 90-day mortality rate was significantly lower in high-volume centers, for all subspecialties, gastric: 127/1757 (7.23 %) vs 330/6526 (5.06 %), p = 0.0004, hepatic: 64/970 (6.6 %) vs 824/17,698 (4.66 %), p = 0.006, pancreatic: 74/895 (8, 27 %) vs 608/10,325 (5.89 %), p = 0.004, esophageal: 58/672 (8.63 %) vs 195/3032 (6.43 %), p = 0.04, rectal 26/514 (5.06 %) vs 639/21,879 (2.92 %), p = 0.005. The multivariate analysis, showed a mortality reduction for high-volume centers: OR = 0.78 CI95[0.71-0.87], p < 0.001. CONCLUSION: The recent implementation of regulatory decrees appears to be justified. The enforcement of these hospital volume thresholds is likely to contribute to a reduction in postoperative mortality following digestive cancer surgery.
ABSTRACT
This study explores the conversion coefficients from air kerma to operational quantities for radiation protection, using x-ray spectrometry for the narrow-beam qualities below 300 keV as defined by ISO 4037-1. By employing custom spectral correction algorithms combined with modern cadmium telluride (CdTe) semiconductor detectors, we effectively corrected spectral distortions caused by detection processes, ensuring more reliable measurements. These measurements are crucial for meeting radiation protection standards. The study also analyses the sources of uncertainty associated with the determination of conversion coefficients, thereby providing improved accuracy and reproducibility in photon dosimetry.
Subject(s)
Radiation Protection , Algorithms , Radiometry/methods , Reproducibility of Results , Tellurium/chemistry , Cadmium Compounds/chemistry , Air , Radiation DosageABSTRACT
BACKGROUND: Esophageal cancer posed significant global health challenges, particularly due to poor survival rates, especially in advanced stages. Primary endoscopic resection had emerged as an alternative treatment for early esophageal cancer, aiming to preserve organ function and reduce surgical morbidity. METHODS: This retrospective multicenter cohort study included 334 patients with early esophageal cancer (T1a-b, N0) from 30 French-speaking European centers between 2000 and 2010. Patients underwent either primary endoscopic resection followed by esophagectomy (E group, n = 36) or esophagectomy alone (S group, n = 298). Cox proportional hazards models adjusted for TNM stage and propensity score weighting were used to assess the impact of primary endoscopic resection on recurrence-free survival (RFS), overall survival (OS), and postoperative complications. RESULTS: Primary endoscopic resection did not significantly influence RFS (adjusted HR 0.92, 95% CI 0.31 to 2.68, p = 0.88) or OS (adjusted HR 1.06, 95% CI 0.35 to 3.13, p = 0.92) compared to esophagectomy alone. Initial higher thromboembolic complications in the endoscopic resection group were not significant after adjustment (adjusted OR 4.73, 95% CI 0.34 to 64.27, p = 0.24). CONCLUSIONS: Primary endoscopic resection followed by esophagectomy for early esophageal cancer did not alter oncological outcomes or overall survival in this retrospective cohort. These findings supported the role of primary endoscopic resection as a safe initial treatment strategy, warranting validation in larger prospective studies. REGISTRATION: Our study was registered retrospectively on the Clinicaltrials.com website under the identifier NCT01927016. We acknowledge the importance of prospective registration and regret that this was not done before the commencement of the study.
Subject(s)
Esophageal Neoplasms , Esophagectomy , Propensity Score , Humans , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Esophagectomy/methods , Retrospective Studies , Female , Male , Middle Aged , Aged , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Esophagoscopy/methodsABSTRACT
AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection. METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12 months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected. DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy. TRIAL REGISTRATION: NCT05010850.
Subject(s)
Anastomosis, Surgical , Anastomotic Leak , Colon , Rectal Neoplasms , Rectum , Humans , Anastomosis, Surgical/instrumentation , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Anastomotic Leak/prevention & control , Prospective Studies , Rectal Neoplasms/surgery , Rectum/surgery , Colon/surgery , Female , Male , Treatment Outcome , Ileostomy/instrumentation , Ileostomy/adverse effects , Ileostomy/methods , Middle Aged , Quality of Life , Adult , Aged , Proctectomy/adverse effects , Proctectomy/methods , Proctectomy/instrumentation , Postoperative Complications/prevention & controlABSTRACT
AIM: Some patients with inflammatory bowel disease (IBD) require subtotal colectomy (STC) with ileostomy. The recent literature reports a significant number of patients who do not undergo subsequent surgery and are resigned to living with a definitive stoma. The aim of this work was to analyse the rate of definitive stoma and the cumulative incidence of secondary reconstructive surgery after STC for IBD in a large national cohort study. METHOD: A national retrospective study (2013-2021) was conducted on prospectively collected data from the French Medical Information System Database (PMSI). All patients undergoing STC in France were included. The association between definitive stoma and potential risk factors was studied using univariate and multivariate analyses. RESULTS: A total of 1860 patients were included (age 45 ± 9 years; median follow-up 30 months). Of these, 77% (n = 1442) presented with ulcerative colitis. Mortality and morbidity at 90 days after STC were 5% (n = 100) and 47% (n = 868), respectively. Reconstructive surgery was identified in 1255 patients (67%) at a mean interval of 7 months from STC. Seveny-four per cent (n = 932) underwent a completion proctectomy with ileal pouch anal anastomosis and 26% (n = 323) an ileorectal anastomosis. Six hundred and five (33%) patients with a definitive stoma had an abdominoperineal resection (n = 114; 19%) or did not have any further surgical procedure (n = 491; 81%). Independent risk factors for definitive stoma identified in multivariate analysis were older age, Crohn's disease, colorectal neoplasia, postoperative complication after STC, laparotomy and a low-volume hospital. CONCLUSION: We found that 33% of patients undergoing STC with ileostomy for IBD had definitive stoma. Modifiable risk factors for definitive stoma were laparotomy and a low-volume hospital.
Subject(s)
Colectomy , Ileostomy , Humans , Middle Aged , Female , Male , France/epidemiology , Colectomy/methods , Colectomy/statistics & numerical data , Colectomy/adverse effects , Ileostomy/statistics & numerical data , Ileostomy/adverse effects , Retrospective Studies , Adult , Risk Factors , Inflammatory Bowel Diseases/surgery , Surgical Stomas/statistics & numerical data , Surgical Stomas/adverse effects , Reoperation/statistics & numerical data , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Colitis, Ulcerative/surgery , Crohn Disease/surgeryABSTRACT
BACKGROUND: Abdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. OBJECTIVES: We aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. METHODS: We retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. RESULTS: Among the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. CONCLUSION: The Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.
Subject(s)
Perineum , Plastic Surgery Procedures , Postoperative Complications , Proctectomy , Rectus Abdominis , Humans , Male , Female , Retrospective Studies , Proctectomy/methods , Proctectomy/adverse effects , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Perineum/surgery , Middle Aged , Aged , Plastic Surgery Procedures/methods , Plastic Surgery Procedures/adverse effects , Rectus Abdominis/transplantation , Rectal Neoplasms/surgery , Adult , Risk Factors , Aged, 80 and over , Myocutaneous Flap/transplantation , Surgical FlapsABSTRACT
BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.
Subject(s)
Gastrointestinal Stromal Tumors , Margins of Excision , Humans , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Female , Male , Middle Aged , Retrospective Studies , Aged , Prognosis , Europe , Adult , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/surgery , Disease-Free Survival , Aged, 80 and over , Neoplasm Recurrence, Local , Proportional Hazards Models , Kaplan-Meier EstimateABSTRACT
BACKGROUND: Although numerous treatments exist for the management of rectovaginal fistula, none has demonstrated its superiority. The role of diverting stoma remains controversial. A few series include Martius flap in the armamentarium. OBJECTIVE: Determine the role of gracilis muscle interposition and Martius flap in the surgical management of rectovaginal fistula. DESIGN: Retrospective cohort study of a pooled prospectively maintained database from 3 centers. PATIENTS: All consecutive eligible patients with rectovaginal fistula undergoing Martius flap and gracilis muscle interposition were included from 2001 to 2022. MAIN OUTCOME MEASURES: Success was defined by the absence of stoma and rectovaginal fistula. RESULTS: Sixty-two patients were included with 55 Martius flap and 24 gracilis muscle interposition performed after failures of 164 initial procedures. Total length of stay was longer for gracilis muscle interposition by 2 days ( p = 0.01) without a significant difference in severe morbidity (20% vs 12%, p = 0.53). Twenty-seven percent of the Martius flap interpositions were performed without a stoma, which did not have an impact on overall morbidity ( p = 0.763). Per patient immediate success rates were not significantly different between groups (35% vs 31%, p > 0.99). The success of gracilis muscle interposition after the failure of the Martius flap was not significantly different from an initial gracilis muscle interposition ( p > 0.99). After simple perineal procedures, the immediate success rate rose to 49.4% (49% vs 50%, p > 0.99). After a median follow-up of 23 months, no significant difference was detected in success rate between the 2 procedures (69% vs 69%, p > 0.99). Smoking was the only negative predictive factor ( p = 0.02). LIMITATIONS: By its retrospective nature, this study is limited in its comparison. CONCLUSIONS: This novel comparison between Martius flap and gracilis muscle interposition suggests that Martius flap presents several advantages, including shorter length of stay, similar morbidity, and similar success rate. Proximal diversion via a stoma for Martius flap does not appear mandatory. Gracilis muscle interposition could be reserved as a salvage procedure after Martius flap failure. See Video Abstract . FSTULA RECTOVAGINAL CUL ES EL ROL DEL COLGAJO DE MARTIUS Y LA INTERPOSICIN DEL MSCULO GRACILIS EN LA ESTRATEGIA TERAPUTICA: ANTECEDENTES:Si bien existen numerosos tratamientos para el manejo de la fistula rectovaginal, ninguno ha demostrado su superioridad. El papel del estoma de derivación sigue siendo controvertido. Pocas series incluyen colgajo de Martius en el armamento.OBJETIVO:Determinar el rol de la interposición del músculo gracilis y del colgajo de Martius, en el manejo quirúrgico de la fístula rectovaginal.DISEÑO:Estudio de cohorte retrospectivo de una base de datos mantenida prospectivamente en 3 centros.AJUSTES/PACIENTES:Se incluyeron todos los pacientes elegibles consecutivos con fistula rectovaginal sometidos a colgajo de Martius y la interposición del músculo gracilis desde 2001 hasta 2022.RESULTADOS PRINCIPALES:El éxito se definió por la ausencia de estoma y fistula rectovaginal.RESULTADOS:Se incluyeron 62 pacientes con 55 colgajo de Martius y 24 con interposición del músculo gracilis realizados después de fracasos de 164 procedimientos iniciales. La duración total de la estancia hospitalaria fue dos días más larga para la interposición del músculo gracilis ( p = 0,01) sin una diferencia significativa en la morbilidad grave (20% frente a 12%, p = 0,53). El 27% de los colgajos de Martius se realizaron sin estoma, sin impacto en la morbilidad global ( p = 0,763). Las tasas de éxito inmediato por paciente no fueron significativamente diferentes entre los grupos (35% vs. 31%, p = 1,0). El éxito de la interposición del músculo gracilis después del fracaso del colgajo de Martius no fue significativamente diferente de una interposición del músculo gracilis inicial (p = 1,0). La tasa de éxito inmediato aumentó al 49,4% (49% frente a 50%, p = 1,0) después de procedimientos perineales simples. Después de una mediana de seguimiento de 23 meses, no se detectaron diferencias significativas en la tasa de éxito entre los dos procedimientos (69 % frente a 69 %, p = 1,0). El tabaquismo fue el único factor predictivo negativo ( p = 0,02).LIMITACIONES:Por su naturaleza retrospectiva, este estudio tiene limitaciones en su comparación.CONCLUSIÓN:Esta novedosa comparación entre colgajo de Martius y la interposición del músculo gracilis sugiere que el colgajo de Martius presenta varias ventajas, incluida una estancia prolongada más corta, una morbilidad similar y un éxito. La derivación proximal a través de un estoma para el colgajo de Martius no parece obligatoria. La interposición del músculo gracilis podría reservarse como procedimiento de rescate después de una falla de colgajo de Martius. (Traducción-Dr. Aurian Garcia Gonzalez ).
Subject(s)
Gracilis Muscle , Rectovaginal Fistula , Surgical Flaps , Humans , Gracilis Muscle/transplantation , Female , Retrospective Studies , Middle Aged , Rectovaginal Fistula/surgery , Adult , Superficial Back Muscles/transplantation , Treatment Outcome , Aged , Length of Stay/statistics & numerical data , Plastic Surgery Procedures/methods , Surgical Stomas/adverse effectsABSTRACT
A major advance has been made in the management of rectal cancer, with the emergence in 2021 of total neoadjuvant treatment. The main publications from the RAPIDO and PRODIGE-23 trials reported a significant improvement in progression-free survival and the pathological complete response rate. The aim of this review is to synthesize recent data on neoadjuvant treatment of rectal cancer, to explain the long-term results of the RAPIDO and PRODIGE-23 trials, and to put them into perspective, considering current advances in de-escalation strategies. The update of the 5-year survival data from the RAPIDO trial highlights an increased risk of loco-regional relapse, with 11.7% of relapses in the experimental group and 8.1% in the control group, while the update of the PRODIGE-23 trial confirms the benefits of this treatment regimen, with a significant improvement in overall survival. In addition, the results of the OPRA and PROPSPECT trials confirm the benefit of total neoadjuvant treatment with induction chemotherapy, as well as the possibility of surgical de-escalation in the OPRA trial and radiotherapy in the PROSPECT trial. The challenge for the future is to identify patients who require total neoadjuvant treatment with the aim of curative surgery to obtain a cure without local or distant relapse, and those for whom therapeutic de-escalation can be envisaged.
Subject(s)
Adenocarcinoma , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/mortality , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Neoplasm Recurrence, Local/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Induction Chemotherapy , Progression-Free Survival , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Capecitabine/administration & dosage , Randomized Controlled Trials as Topic , Leucovorin/administration & dosage , Leucovorin/therapeutic use , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/therapeutic useABSTRACT
AIM: Digestive stoma are frequently performed. The last French guidelines have been published twenty years ago. Our aim was to update French clinical practice guidelines for the perioperative management of digestive stoma and stoma-related complications. METHODS: A systematic literature review of French and English articles published between January 2000 and May 2022 was performed. Only digestive stoma for fecal evacuation in adults were considered. Stoma in children, urinary stoma, digestive stoma for enteral nutrition, and rare stoma (Koch, perineal) were not included. RESULTS: Guidelines include the surgical landmarks to create digestive stoma (ideal location, mucocutaneous anastomosis, utility of support rods, use of prophylactic mesh), the perioperative clinical practice guidelines (patient education, preoperative ostomy site marking, postoperative equipment, prescriptions, and follow-up), the management of early stoma-related complications (difficulties for nursing, high output, stoma necrosis, retraction, abscess and peristomal skin complications), and the management of late stoma-related complications (stoma prolapse, parastomal hernia, stoma stenosis, late stoma retraction). A level of evidence was assigned to each statement. CONCLUSION: These guidelines will be very useful in clinical practice, and allow to delete some outdated dogma.
Subject(s)
Postoperative Complications , Surgical Stomas , Humans , France , Surgical Stomas/adverse effects , Adult , Postoperative Complications/prevention & control , Practice Guidelines as Topic , ColostomyABSTRACT
BACKGROUND: The aim of our study was to evaluate the external validity of the MIRO randomized controlled trial findings in a similar nationwide setting "real life" population, especially the benefit of a hybrid approach in esophageal resection for pulmonary complication. The external validity of randomized controlled trial findings to the general population with the same condition remains problematic because of the inherent selection bias and rigid inclusion criteria. METHODS: This study was a cohort study from a National Health Database (Programme de Medicalisation des Systemes d'Informations) between 2010 and 2022. All adult patients operated on using Ivor Lewis resection for esophageal cancer were included. We first validated the detection algorithm of postoperative complications in the health database. Then, we assessed the primary outcome, which was the comparison of postoperative severe pulmonary complications, leak rate, and 30-day mortality between the 2 surgical approaches (hybrid versus open) over a decade. RESULTS: Between 2010 and 2012, 162 of 205 patients in the MIRO trial were anonymously identified in the health care database. No difference between randomized controlled trials and healthcare database measurements was found within severe respiratory complications (24% vs 22%, respectively) nor within leak rate (10% vs 9%, respectively). After application of selection criteria according to the MIRO trial, 3,852 patients were included between 2013 and 2022. The hybrid approach was a protective factor against respiratory complications after adjustment for confounding variables (odds ratio = 0.83; 95% confidence interval = 0.71-0.98, P = .025). No significant difference in the 30-day mortality rate or 30-day leakage rate between the types of approach was reported. CONCLUSION: This national cohort study demonstrates the external validity of the MIRO randomized controlled trial findings in a real-life population within France.
Subject(s)
Esophageal Neoplasms , Esophagectomy , Adult , Humans , Esophagectomy/methods , Cohort Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Esophageal Neoplasms/surgery , Randomized Controlled Trials as TopicABSTRACT
INTRODUCTION: Contradictions remain on the impact of interhospital competition on the quality of care, mainly the mortality. The aim of the study is to evaluate the impact of interhospital competition on postoperative mortality after surgery for colorectal cancer in France. METHODS: We conducted a retrospective cross-sectional study from 2015 to 2019. Data were collected from a National Health Database. Patients operated on for colorectal cancer in a hospital in mainland France were included. Competition was measured using number of competitors by distance-based approach. A mixed-effect model was carried out to test the link between competition and mortality. RESULTS: Ninety-five percent (n = 152,235) of the 160,909 people operated on for colorectal cancer were included in our study. The mean age of patients was 70.4 ±12.2 years old, and female were more represented (55%). A total of 726 hospitals met the criteria for inclusion in our study. Mortality at 30 days was 3.6% and we found that the mortality decreases with increasing of the hospital activity. Using the number of competitors per distance method, our study showed that a "highly competitive" and "moderately competitive" markets decreased mortality by 31% [OR: 0.69 (0.59, 0.80); p<0.001] and by 12% respectively [OR: 0.88 (0.79, 0.99); p<0.03], compared to the "non-competitive" market. High hospital volume (100> per year) was also associated to lower mortality rate [OR: 0.74 (0.63, 0.86); p<0.001]. CONCLUSIONS: The results of our studies show that increasing hospital competition independently decreases the 30-day mortality rate after colorectal cancer surgery. Hospital caseload, patients' characteristics and age also impact the post-operative mortality.
Subject(s)
Colorectal Neoplasms , Hospitals , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Cross-Sectional Studies , Retrospective Studies , Patients , Colorectal Neoplasms/surgery , Hospital MortalityABSTRACT
The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)KMT2C = 2.54, 95%CI = [1.25,5.17], P value = .010; HRPIK3CA = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials.
Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , Proctectomy , Humans , Anus Neoplasms/genetics , Anus Neoplasms/pathology , Anus Neoplasms/surgery , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Class I Phosphatidylinositol 3-Kinases/genetics , Mutation , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Phosphatidylinositol 3-Kinases/genetics , PrognosisABSTRACT
BACKGROUND: Postoperative complications occur in up to 43% of patients after surgery, resulting in increased morbidity and economic burden. Prehabilitation has the potential to increase patients' preoperative health status and thereby improve postoperative outcomes. However, reported results of prehabilitation are contradictory. The objective of this systematic review is to evaluate the effects of prehabilitation on postoperative outcomes (postoperative complications, hospital length of stay, pain at postoperative day 1) in patients undergoing elective surgery. METHODS: The authors performed a systematic review and meta-analysis of RCTs published between January 2006 and June 2023 comparing prehabilitation programmes lasting ≥14 days to 'standard of care' (SOC) and reporting postoperative complications according to the Clavien-Dindo classification. Database searches were conducted in PubMed, CINAHL, EMBASE, PsycINFO. The primary outcome examined was the effect of uni- or multimodal prehabilitation on 30-day complications. Secondary outcomes were length of ICU and hospital stay (LOS) and reported pain scores. RESULTS: Twenty-five studies (including 2090 patients randomized in a 1:1 ratio) met the inclusion criteria. Average methodological study quality was moderate. There was no difference between prehabilitation and SOC groups in regard to occurrence of postoperative complications (OR = 1.02, 95% c.i. 0.93 to 1.13; P = 0.10; I2 = 34%), total hospital LOS (-0.13 days; 95% c.i. -0.56 to 0.28; P = 0.53; I2 = 21%) or reported postoperative pain. The ICU LOS was significantly shorter in the prehabilitation group (-0.57 days; 95% c.i. -1.10 to -0.04; P = 0.03; I2 = 46%). Separate comparison of uni- and multimodal prehabilitation showed no difference for either intervention. CONCLUSION: Prehabilitation reduces ICU LOS compared with SOC in elective surgery patients but has no effect on overall complication rates or total LOS, regardless of modality. Prehabilitation programs need standardization and specific targeting of those patients most likely to benefit.
Subject(s)
Pain, Postoperative , Preoperative Exercise , Humans , Databases, Factual , Morbidity , Postoperative Complications/prevention & control , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND AND AIMS: Postoperative recurrence is a major concern in Crohn's disease. The Kono-S anastomosis has been described to reduce the rate of recurrence. However, the level of evidence for its effectiveness remains low. The KoCoRICCO study aimed to compare outcomes between Kono-S anastomosis and conventional anastomosis in two nationwide prospective cohorts. METHODS: Adult patients with Crohn's disease who underwent ileocolonic resection with Kono-S anastomosis were prospectively included in seven referral centers between 2020 and 2022. Patients with conventional side-to-side anastomosis were enrolled from a previously published cohort. A propensity score analysis was performed to compare recurrence at first endoscopy in a matched 1:2 ratio population. RESULTS: A total of 433 patients with ileocolonic anastomosis were enrolled, of whom 155 had a Kono-S anastomosis. Before matching, both groups were unbalanced for preoperative, intraoperative, and postoperative characteristics. After matching patients with available endoscopic follow-up, endoscopic recurrence ≥i2 was found in 47.5% of the Kono-S group and 44.3% of the conventional side-to-side group (p=0.6745). CONCLUSIONS: The KoCoRICCO study suggests that Kono-S anastomosis does not reduce the risk of endoscopic recurrence in Crohn's disease compared to conventional side-to-side anastomosis. Further research with a longer follow-up is necessary to determine whether there is a potential benefit on surgical recurrence.
ABSTRACT
BACKGROUND: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. METHODS: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). RESULTS: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). CONCLUSION: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.
Subject(s)
Anastomotic Leak , Rectal Neoplasms , Humans , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Cohort Studies , Anastomosis, Surgical/methods , Rectum/surgery , Rectal Neoplasms/surgery , Rectal Neoplasms/complications , Retrospective StudiesABSTRACT
AIM: A complete or subcomplete tumour response (CTR) is observed in 10%-25% of patients with mid/low rectal cancer after neoadjuvant chemoradiotherapy (CRT). The aim of our study was to report a multicentric French experience in local excision (LE) after CRT. METHOD: All patients who underwent LE for mid/low rectal cancer with suspected CTR after CRT, from 2006 to 2019 in seven GRECCAR centres were included. LE was considered adequate if the specimen showed a ypT0/Tis/T1R0 tumour, otherwise, a completion total mesorectal excision (TME) was discussed. Morbi-mortality, functional results and oncological outcomes were studied. RESULTS: A total of 257 patients were included. LE specimens showed 36% ypT0, 4% ypTis and 19% ypT1. Thus, 108 patients (42%) had theoretical indication of completion TME, which was performed in only 42 patients. Overall, 30-day morbidity after LE was 11%, including 2% Clavien-Dindo grade III or IV complications. After completion TME, 47% described major low anterior resection syndrome versus 5% after LE alone (p < 0.001). After a mean follow-up of 4 years (range 2-6 years), the recurrence rate was 11% after LE, 32% after completion TME and 20% in patients for whom completion TME was indicated but not performed (p = 0.021). CONCLUSION: TME remains the gold standard for mid/low rectal cancer after CRT. LE in selected patients is safe for operative and functional, but also oncological, results. However, completion TME was indicated in 42% of patients after LE, highlighting the difficulty of the preoperative diagnosis of CTR after CRT.
Subject(s)
Digestive System Surgical Procedures , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Neoadjuvant Therapy , Postoperative Complications/pathology , Neoplasm Staging , Chemoradiotherapy , Treatment Outcome , Neoplasm Recurrence, Local/pathologyABSTRACT
AIM: Intersphincteric resection (ISR) is an oncologically complex operation for very low-lying rectal cancers. Yet, definition, anatomical description, operative indications and operative approaches to ISR are not standardized. The aim of this study was to standardize the definition of ISR by reaching international consensus from the experts in the field. This standardization will allow meaningful comparison in the literature in the future. METHOD: A modified Delphi approach with three rounds of questionnaire was adopted. A total of 29 international experts from 11 countries were recruited for this study. Six domains with a total of 37 statements were examined, including anatomical definition; definition of intersphincteric dissection, intersphincteric resection (ISR) and ultra-low anterior resection (uLAR); indication for ISR; surgical technique of ISR; specimen description of ISR; and functional outcome assessment protocol. RESULTS: Three rounds of questionnaire were performed (response rate 100%, 89.6%, 89.6%). Agreement (≥80%) reached standardization on 36 statements. CONCLUSION: This study provides an international expert consensus-based definition and standardization of ISR. This is the first study standardizing terminology and definition of deep pelvis/anal canal anatomy from a surgical point of view. Intersphincteric dissection, ISR and uLAR were specifically defined for precise surgical description. Indication for ISR was determined by the rectal tumour's maximal radial infiltration (T stage) below the levator ani. A new surgical definition of T3isp was reached by consensus to define T3 low rectal tumours infiltrating the intersphincteric plane. A practical flowchart for surgical indication for uLAR/ISR/abdominoperineal resection was developed. A standardized ISR surgical technique and functional outcome assessment protocol was defined.