Prognostic Value of the Circumferential Resection Margin After Curative Surgery for Rectal Cancer: A Multicenter Propensity Score-Matched Analysis.

BACKGROUND: Recently, positive circumferential resection margin has been found to be an indicator of advanced disease with a high risk of distant recurrence rather than local recurrence. OBJECTIVE: The study aimed to analyze the prognostic impact of the circumferential resection margin on long-term oncological outcomes in patients with rectal cancer. DESIGN: This was a multicenter, propensity score-matched (2:1) analysis comparing the positive and negative circumferential resection margins. SETTINGS: The study was conducted at 5 high-volume centers in Spain. PATIENTS: Patients who underwent total mesorectal excision with curative intent for middle-low rectal cancer between 2006 and 2014 were included. MAIN OUTCOME MEASURES: The main outcomes were local recurrence, distant recurrence, overall survival, and disease-free survival. RESULTS: The unmatched initial cohort consisted of 1599 patients, of whom 4.9% had a positive circumferential resection margin. After matching, 234 patients were included (156 with a negative circumferential margin and 78 with a positive circumferential margin). The median follow-up period was 52.5 (22.0-69.5) months. Local recurrence was significantly higher in patients with a positive circumferential margin (33.3% vs 11.5%; p < 0.001). Distant recurrence was similar in both groups (46.2% vs 42.3%; p = 0.651). There were no statistically significant differences in 5-year overall survival (48.6% vs 43.6%; p = 0.14). Disease-free survival was lower in patients with a positive circumferential margin (36.1% vs 52.3%; p = 0.026). LIMITATIONS: This study was limited by its retrospective design. The different neoadjuvant treatment options were not included in the propensity score. CONCLUSIONS: The positive circumferential resection margin was associated with a higher local recurrence rate and worse disease-free survival in comparison with the negative circumferential resection margin. However, the positive circumferential resection margin was not a prognostic indicator of distant recurrence and overall survival. See Video Abstract at http://links.lww.com/DCR/B950 . VALOR PRONSTICO DEL MARGEN DE RESECCIN CIRCUNFERENCIAL DESPUS DE LA CIRUGA CURATIVA PARA EL CNCER DE RECTO UN ANLISIS MULTICNTRICO EMPAREJADO POR PUNTAJE DE PROPENSIN: ANTECEDENTES:En los últimos años, se ha encontrado que el margen de resección circunferencial positivo es un indicador de enfermedad avanzada con alto riesgo de recurrencia a distancia más que de recurrencia local.OBJETIVO:El objetivo fue analizar el impacto pronóstico del margen de resección circunferencial sobre la recidiva local, a distancia y las tasas de supervivencia en pacientes con cáncer de recto.DISEÑO:Este fue un análisis multicéntrico emparejado por puntaje de propensión 2: 1 que comparó el margen de resección circunferencial positivo y negativo.AJUSTES:El estudio se realizó en 5 centros Españoles de alto volumen.PACIENTES:Se incluyeron pacientes sometidos a escisión total de mesorrecto con intención curativa por cáncer de recto medio-bajo entre 2006-2014. Las características clínicas e histológicas se utilizaron para el emparejamiento.PRINCIPALES MEDIDAS DE RESULTADO:Los resultadoes principales fueron la recurrencia local, la recurrencia a distancia, la supervivencia global y libre de enfermedad.RESULTADOS:La cohorte inicial no emparejada consistió en 1599 pacientes; El 4,9% tuvo un margen de resección circunferencial positivo. Tras el emparejamiento se incluyeron 234 pacientes (156 con margen circunferencial negativo y 78 con margen circunferencial positivo). La mediana del período de seguimiento fue de 52,5 meses (22,0-69,5). La recurrencia local fue significativamente mayor en pacientes con margen circunferencial positivo, 33,3% vs 11,5% [HR 3,2; IC 95%: 1,83-5,43; p < 0,001]. La recidiva a distancia fue similar en ambos grupos (46,2 % frente a 42,3 %) [HR 1,09, IC 95 %: 0,78-1,90; p = 0,651]. No hubo diferencias significativas en la supervivencia global a 5 años (48,6 % frente a 43,6 %) [HR 1,09, IC 95 %: 0,92-1,78; p = 0,14]; La supervivencia libre de enfermedad fue menor en pacientes con margen circunferencial positivo, 36,1% vs 52,3% [HR 1,5; IC 95%: 1,05-2,06; p = 0,026].LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo. Las diferentes opciones de tratamientos neoadyuvantes no se han incluido en la puntuación de propensión.CONCLUSIONES:El margen de resección circunferencial positivo se asocia con una mayor tasa de recurrencia local y peor supervivencia libre de enfermedad en comparación con el margen de resección circunferencial negativo. Sin embargo, el margen de resección circunferencial positivo no fue un indicador pronóstico de recidiva a distancia ni de supervivencia global. Consulte el Video del Resumen en http://links.lww.com/DCR/B950 . (Traducción- Dr. Yesenia Rojas-Khalil ).

Right Colectomy with Intracorporeal Anastomosis: A European Multicenter Propensity Score Matching Retrospective Study of Robotic Versus Laparoscopic Procedures.

BACKGROUND: This study aimed to compare the short- and long-term outcomes of robotic (RRC-IA) versus laparoscopic (LRC-IA) right colectomy with intracorporeal anastomosis using a propensity score matching (PSM) analysis based on a large European multicentric cohort of patients with nonmetastatic right colon cancer. METHODS: Elective curative-intent RRC-IA and LRC-IA performed between 2014 and 2020 were selected from the MERCY Study Group database. The two PSM-groups were compared for operative and postoperative outcomes, and survival rates. RESULTS: Initially, 596 patients were selected, including 194 RRC-IA and 402 LRC-IA patients. After PSM, 298 patients (149 per group) were compared. There was no statistically significant difference between RRC-IA and LRC-IA in terms of operative time, intraoperative complication rate, conversion to open surgery, postoperative morbidity (19.5% in RRC-IA vs. 26.8% in LRC-IA; p = 0.17), or 5-yr survival (80.5% for RRC-IA and 74.7% for LRC-IA; p = 0.94). R0 resection was obtained in all patients, and > 12 lymph nodes were harvested in 92.3% of patients, without group-related differences. RRC-IA procedures were associated with a significantly higher use of indocyanine green fluorescence than LRC-IA (36.9% vs. 14.1%; OR: 3.56; 95%CI 2.02-6.29; p < 0.0001). CONCLUSION: Within the limitation of the present analyses, there is no statistically significant difference between RRC-IA and LRC-IA performed for right colon cancer in terms of short- and long-term outcomes.

Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn's Disease.

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn's disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.

Extended right colectomy, left colectomy, or segmental left colectomy for splenic flexure carcinomas: a European multicenter propensity score matching analysis.

BACKGROUND: The surgical resection of the splenic flexure carcinoma (SFC) is challenging and the optimal surgical procedure for SFCs remains a matter of debate. The present study aimed to compare in a multicenter European sample of patients the short- and long-term outcomes of extended right (ERC) vs. left (LC) vs. segmental left colectomy (SLC) for SFCs. METHODS: This retrospective multicenter study analyzed the surgical and oncological outcomes of SFC patients undergoing elective curative intent surgery between 2000 and 2018. Descriptive and exploratory analyses were first conducted on the whole sample. Outcomes of the different procedures (ERC vs. LC vs. SLC) were then compared using propensity score matching for multilevel treatment. Overall (OS) and disease-free survival (DFS) were evaluated by Kaplan-Meier method. RESULTS: From a total of 399 SFC patients, 143 (35.8%) underwent ERC, 131 (32.8%) underwent LC, and 125 (31.4%) underwent SLC. Overall, 297 (74.4%) were laparoscopic procedures. An increase in operative time, time to flatus, time to regular diet, and hospital stay was observed with the progressive extension of SFC resection. ERC was associated with significantly increased risk of postoperative ileus compared to both LC and SLC. A significantly greater number of lymph nodes were retrieved by ERC, but the objective of at least 12 retrieved lymph nodes was achieved in 85% of patients, without procedure-related differences. No differences were observed in OS or DFS between ERC, LC, and SLC. CONCLUSION: The present study supports the resection of SFCs by colon-sparing surgical techniques, such as SLC.

Crohn's Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat.

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn's disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn's disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms' tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn's disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen-DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn's disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn's disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn's disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

Systematic review of functional outcomes and quality of life after transanal endoscopic microsurgery and transanal minimally invasive surgery: a word of caution.

PURPOSE: The introduction of transanal endoscopic or minimally invasive surgery has allowed organ preservation for rectal tumors with good oncological results. Data on functional and quality-of-life (QoL) outcomes are scarce and controversial. This systematic review sought to synthesize fecal continence, QoL, and manometric outcomes after transanal endoscopic microsurgery (TEM) or transanal minimally invasive surgery (TAMIS). METHODS: A systematic review of the literature including Medline, Embase, and the Cochrane Library databases was conducted searching for articles reporting on functional outcomes after TEM or TAMIS between January 1995 and June 2018. The evaluated outcome parameters were pre- and postoperative fecal continence (primary endpoint), QoL, and manometric results. Data were extracted using the same scales and measurement units as from the original study. RESULTS: A total of 29 studies comprising 1297 patients were included. Fecal continence outcomes were evaluated in 23 (79%) studies with a wide variety of assessment tools and divergent results. Ten studies (34%) analyzed QoL changes, and manometric variables were assessed in 15 studies (51%). Most studies reported some deterioration in manometric scores without major QoL impairment. Due to the heterogeneity of the data, it was not possible to perform any pooled analysis or meta-analysis. CONCLUSIONS: These techniques do not seem to affect continence by themselves except in minor cases. The possibility of worsened function after TEM and TAMIS should not be underestimated. There is a need to homogenize or standardize functional and manometric outcomes assessment after TEM or TAMIS.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on pouchitis in ulcerative colitis. Part 2: Treatment. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la reservoritis en la colitis ulcerosa. Parte 2: Tratamiento.

Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment.

Development and validation of the QUECOMIICAT questionnaire: a tool to assess disease-related knowledge in patients with inflammatory bowel disease.

INTRODUCTION: adequate knowledge of inflammatory bowel disease (IBD) is essential for a successful patient-centered management of IBD. OBJECTIVE: due to the scarcity of up-to-date tools for measuring IBD literacy, this single-center, prospective study aimed to develop and validate a new questionnaire to assess IBD-related knowledge. MATERIAL AND METHODS: the study included patients followed up at the Crohn-Colitis Care Unit (UACC) at the Hospital Vall d'Hebron (Barcelona, Spain). Patients admitted to the UACC for the first time were subsequently enrolled into a standard IBD educational program. A pilot questionnaire was developed and validated in 92 IBD patients by determining the internal consistency reliability (Cronbach's α test), feasibility, construct validity (correlation with the Crohn's and Colitis Knowledge [CCKNOW] questionnaire and a knowledge visual analog scale [VAS]) and sensitivity (score change before and after a standard IBD educational program). The questionnaire, named "Qüestionari Coneixements Malaltia Inflamatòria Intestinal Catalunya" (IBD-knowledge questionnaire Catalonia) (QUECOMIICAT) was written in Spanish and had 25 items addressing six dimensions: general concepts, clinic, treatment, surgery, habits and social context. RESULTS: the median (interquartile range) completion time was 15 (10-20) minutes and the floor and ceiling effects were 1.1% and 2.1%, respectively. The Cronbach's α coefficient was α = 0.75. QUECOMIICAT significantly correlated with the VAS (rho = 0.34, p < 0.01) and CCKNOW questionnaires (rho = 0.74, p < 0.01). Patient knowledge significantly increased 24 hours after attending a standard IBD educational program and remained statistically significant one month later (Pearson's test-retest correlation coefficient r = 0.81, p < 0.001). CONCLUSION: in conclusion, the QUECOMIICAT questionnaire is a new up-to-date tool to assess IBD-related knowledge with good feasibility and validation results for use in the routine clinical practice.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on pouchitis in ulcerative colitis. Part 1: Epidemiology, diagnosis and prognosis. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la reservoritis en la colitis ulcerosa. Parte 1: epidemiología, diagnóstico y pronóstico.

Pouchitis is a common complication in ulcerative colitis patients after total proctocolectomy. This is an unspecific inflammation of the ileo-anal pouch, the aetiology of which is not fully known. This inflammation induces the onset of symptoms such as urgency, diarrhoea, rectal bleeding and abdominal pain. Many patients suffering from pouchitis have a lower quality of life. In addition to symptoms, an endoscopy with biopsies is mandatory in order to establish a definite diagnosis. The recommended index to assess its activity is the Pouchitis Disease Activity Index (PDAI), but its modified version (PDAIm) can be used in clinical practice. In accordance with the duration of symptoms, pouchitis can be classified as acute (<4 weeks) or chronic (>4 weeks), and, regarding its course, pouchitis can be infrequent (<4 episodes per year), recurrent (>4 episodes per year) or continuous.

Pathologic response grade after long-course neoadjuvant chemoradiation does not influence morbidity in locally advanced mid-low rectal cancer resected by laparoscopy.

PURPOSE: Patients with locally advanced rectal cancer and pathologic complete response to neoadjuvant chemoradiation therapy have lower rates of recurrence compared to those who do not. However, the influences of the pathologic response on surgical complications and survival remain unclear. This study aimed to investigate the influence of neoadjuvant therapy for rectal cancer on postoperative morbidity and long-term survival. METHODS: This was a comparative study of consecutive patients who underwent laparoscopic total mesorectal excision for rectal cancer in two European tertiary hospitals between 2004 and 2014. Patients with and without pathologic complete responses were compared in terms of postoperative morbidity, mortality, and survival. RESULTS: Fifty patients with complete response (ypT0N0) were compared with 141 patients who exhibited non-complete response. No group differences were observed in the postoperative mortality or morbidity rates. The median follow-up time was 57 months (range 1-121). Over this period, 11 (5.8 %) patients, all of whom were in the non-complete response group, exhibited local recurrence. The 5-year overall survival and disease-free survival were significantly better in the complete response group, 92.5 vs. 75.3 % (p = 0.004) and 89 vs. 73.4 % (p = 0.002), respectively. CONCLUSIONS: Postoperative complication rate after laparoscopic total mesorectal excision is not associated with the pathologic response grade to neoadjuvant chemoradiation therapy.

Multicentre propensity score-matched analysis of laparoscopic versus open surgery for T4 rectal cancer.

BACKGROUND: The use of laparoscopy for advanced-stage rectal cancer remains controversial. This study aimed to compare the operative and oncologic outcomes of laparoscopic (LAR) versus open anterior rectal resection (OAR) for patients with pT4 rectal cancer. METHODS: This is a multicenter propensity score matching (PSM) study of patients undergoing elective curative-intent LAR or OAR for pT4 rectal cancer (TNM stage II/III/IV) between 2005 and 2015. RESULTS: In total, 137 patients were included in the analysis. After PSM, demographic, clinical and tumor characteristics were similar between the 52 LAR and the 52 OAR patients. Overall, 52 tumors were located in the high rectum, 25 in the mid-rectum and 27 in the low rectum. Multivisceral resection was performed in 26.9% of LAR and 30.8% of OAR patients (p = 0.829). Conversion was required in 11 LAR patients (21.2%). The LAR group showed significantly shorter time to flatus (3.13 vs. 4.97 days, p = 0.001), time to regular diet (3.59 vs. 6.36 days, p < 0.0001) and hospital stay (15.49 vs. 17.96 days, p = 0.002) compared to the OAR group. The 90-day morbidity and mortality were not different between groups. In the majority of patients (85.6%), R0 resection was achieved. A complete mesorectal excision was obtained in 82.7% of LAR and 78.8% of OAR patients (p = 0.855). The 1-, 2- and 3-year overall survival rates were, respectively, 95.6, 73.8 and 66.7% for the LAR group and 86.7, 66.9 and 64.1% for the OAR group (p = 0.219). The presence of synchronous metastases (hazard ratio 2.26), R1 resection (HR 2.71) and lymph node involvement (HR 2.24) were significant predictors of overall survival. CONCLUSION: The present study suggests that LAR for pT4 rectal cancer can achieve good pathologic and oncologic outcomes similar to open surgery despite the risk of conversion. Moreover, laparoscopy offers the benefits of a faster recovery and a shorter hospital stay.

Preventing Parastomal Hernia Using a Modified Sugarbaker Technique With Composite Mesh During Laparoscopic Abdominoperineal Resection: A Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to assess the reduction in the incidence of parastomal hernia (PH) after placement of prophylactic synthetic mesh using a modified Sugarbaker technique when a permanent end-colostomy is needed. SUMMARY OF BACKGROUND DATA: Prevention of PH formation is crucial given the high prevalence of PH and difficulties in the surgical repair of PH. METHODS: A randomized, prospective, double-blind, and controlled trial. Rectal cancer patients undergoing laparoscopic abdominoperineal resection with permanent colostomy were randomized (1 : 1) to the mesh and nonmesh arms. In the mesh group, a large-pore lightweight composite mesh was placed in the intraperitoneal/onlay fashion using a modified Sugarbaker technique. PH was detected by computed tomography (CT) after a minimum follow-up of 12 months. Analysis was per-protocol. RESULTS: The mesh group included 24 patients and the control group 28. Preoperative data, surgical time, and postoperative morbidity were similar. The median follow-up was 26 months. After CT examination, 6 of 24 PHs (25%) were observed in the mesh group compared with 18 of 28 (64.3%) in the nonmesh group (odds ratio 0.39, 95% confidence interval 0.18-0.82; P = 0.005). The Kaplan-Meier curves showed significant differences in favor of the mesh group (long-rank = 4.21, P = 0.04). The number needed to treat was 2.5, which confirmed the effectiveness of the intervention. CONCLUSIONS: Placement of a prosthetic mesh by the laparoscopic approach following the modified Sugarbaker technique is safe and effective in the prevention of PH, reducing significantly the incidence of PH.

Hospital variability in postoperative mortality after rectal cancer surgery in the Spanish Association of Surgeons project: The impact of hospital volume.

OBJECTIVE: This multicentre observational study examines variation between hospitals in postoperative mortality after elective surgery in the Rectal Cancer Project of the Spanish Society of Surgeons and explores whether hospital volume and patient characteristics contribute to any variation between hospitals. METHODS: Hospital variation was quantified using a multilevel approach on prospective data derived from the multicentre database of all rectal adenocarcinomas operated by an anterior resection or an abdominoperineal excision at 84 surgical departments from 2006 to 2013. The following variables were included in the analysis; demographics, American Society of Anaesthesiologists classification, tumour location and stage, administration of neoadjuvant treatment, and annual volume of surgical procedures. RESULTS: A total of 9809 consecutive patients were included. The rate of 30-day postoperative mortality was 1.8% Stratified by annual surgical volume hospitals varied from 1.4 to 2.0 in 30-day mortality. In the multilevel regression analysis, male gender (OR 1.623 [1.143; 2.348]; P<.008), increased age (OR: 5.811 [3.479; 10.087]; P<.001), and ASA score (OR 10.046 [3.390; 43.185]; P<.001) were associated with 30-day mortality. However, annual surgical volume was not associated with mortality (OR 1.309 [0.483; 4.238]; P=.619). Besides, there was a statistically significant variation in mortality between all departments (MOR 1.588 [1.293; 2.015]; P<.001). CONCLUSION: Postoperative mortality varies significantly among hospitals included in the project and this difference cannot be attributed to the annual surgical volume.

[Hospital variation in anastomotic leakage after rectal cancer surgery in the Spanish Association of Surgeons project: The contribution of hospital volume]. / Variabilidad interhospitalaria de la dehiscencia anastomótica en el Proyecto del Cáncer de Recto de la Asociación Española de Cirujanos: La influencia del volumen quirúrgico.

OBJECTIVE: This multicentre observational study aimed to determine the anastomotic leak rate in the hospitals included in the Rectal Cancer Project of the Spanish Society of Surgeons and examine whether hospital volume may contribute to any variation between hospitals. METHODS: Hospital variation was quantified using a multilevel approach on prospective data derived from the multicentre database of all adenocarcinomas of the rectum operated by an anterior resection at 84 surgical departments from 2006 to 2013. The following variables were included in the analysis; demographics, American Society of Anaesthesiologists classification, use of defunctioning stoma, tumour location and stage, administration of neoadjuvant treatment, and annual volume of elective surgical procedures. RESULTS: A total of 7231 consecutive patients were included. The rate of anastomotic leak was 10.0%. Stratified by annual surgical volume hospitals varied from 9.9 to 11.3%. In multilevel regression analysis, the risk of anastomotic leak increased in male patients, in patients with tumours located below 12 cm from the anal verge, and advanced tumour stages. However, a defunctioning stoma seemed to prevent this complication. Hospital surgical volume was not associated with anastomotic leak (OR: 0.852, [0.487-1.518]; P=.577). Furthermore, there was a statistically significant variation in anastomotic leak between all departments (MOR: 1.475; [1.321-1.681]; P<0.001). CONCLUSION: Anastomotic leak varies significantly among hospitals included in the project and this difference cannot be attributed to the annual surgical volume.

Effect of hospital caseload on long-term outcome after standardization of rectal cancer surgery in the Spanish Rectal Cancer Project. / Influencia del volumen quirúrgico en los resultados oncológicos después de estandarizar la cirugía en el Proyecto Español del Cáncer de Recto.

UNLABELLED: INTRODUCCIóN: The purpose of this prospective multicentre multilevel study was to investigate the influence of hospital caseload on long-term outcomes following standardization of rectal cancer surgery in the Rectal Cancer Project of the Spanish Society of Surgeons. METHODS: Data relating to 2910 consecutive patients with rectal cancer treated for cure between March 2006 and March 2010 were recorded in a prospective database. Hospitals were classified according to number of patients treated per year as low-volume, intermediate-volume, or high volume hospitals (12-23, 24-35, or ≥36 procedures per year). RESULTS: After a median follow-up of 5 years, cumulative rates of local recurrence, metastatic recurrence and overall survival were 6.6 (CI95% 5.6-7.6), 20.3 (CI95% 18.8-21.9) and 73.0 (CI95% 74.7 - 71.3) respectively. In the multilevel regression analysis overall survival was higher for patients treated at hospitals with an annual caseload of 36 or more patients (HR 0,727 [CI95% 0,556-0,951]; P=.02). The risk of local recurrence and metastases were not related to the caseload. Moreover, there was a statistically significant variation in overall survival (median hazard ratio [MHR] 1.184 [CI95% 1.071-1,333]), local recurrence (MHR 1.308 [CI95% 1.010-1.668]) and metastases (MHR 1.300 [CI95% 1.181; 1.476]) between all hospitals. CONCLUSIONS: Overall survival was higher for patients treated at hospitals with an annual caseload of 36 or more patients. However, local recurrence was not influenced by caseload.

Brush border myosin Ia has tumor suppressor activity in the intestine.

The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progression of genetically and carcinogen-initiated intestinal tumors was significantly accelerated in Myo1a knockout mice compared with Myo1a wild-type animals. Moreover, MYO1A tumor expression was found to be an independent prognostic factor for colorectal cancer patients. Patients with low MYO1A tumor protein levels had significantly shorter disease-free and overall survival compared with patients with high tumoral MYO1A (logrank test P = 0.004 and P = 0.009, respectively). The median time-to-disease recurrence in patients with low MYO1A was 1 y, compared with >9 y in the group of patients with high MYO1A. These results identify MYO1A as a unique tumor-suppressor gene in colorectal cancer and demonstrate that the loss of structural brush border proteins involved in cell polarity are important for tumor development.

Outpatient versus hospitalization management for uncomplicated diverticulitis: a prospective, multicenter randomized clinical trial (DIVER Trial).

OBJECTIVE: We compare the results of 2 different strategies for the management of patients with uncomplicated left colonic diverticulitis and to analyze differences in quality of life and economic costs. BACKGROUND: The most frequent standard management of acute uncomplicated diverticulitis still is hospital admission both in Europe and United States. METHODS: This multicenter, randomized controlled trial included patients older than 18 years with acute uncomplicated diverticulitis. All the patients underwent abdominal computed tomography. There were 2 strategies of management: hospitalization (group 1) and outpatient (group 2). The first dose of antibiotic was given intravenously to all patients in the emergency department and then group 1 patients were hospitalized whereas patients in group 2 were discharged. The primary end point was the treatment failure rate of the outpatient protocol and need for hospital admission. The secondary end points included quality-of-life assessment and evaluation of costs. RESULTS: A total of 132 patients were randomized: 4 patients in group 1 and 3 patients in group 2 presented treatment failure without differences between the groups (P=0.619). The overall health care cost per episode was 3 times lower in group 2, with savings of €1124.70 per patient. No differences were observed between the groups in terms of quality of life. CONCLUSIONS: Outpatient treatment is safe and effective in selected patients with uncomplicated acute diverticulitis. Outpatient treatment allows important costs saving to the health systems without negative influence on the quality of life of patients with uncomplicated diverticulitis. Trial registration ID: EudraCT number 2008-008452-17.

International validation of the low anterior resection syndrome score.

OBJECTIVE: The aims of this study were to investigate the convergent and discriminative validity and reliability of the low anterior resection syndrome (LARS) score in an international setting. BACKGROUND: The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal cancer surgery. The score is intended to be commonly used in international research and clinical practice in the future. Therefore, a thorough validation in an international setting is of utmost importance. METHODS: The LARS score was translated using methods in keeping with current international recommendations. A total of 801 patients operated for rectal cancer in Sweden, Spain, Germany, and Denmark completed the LARS score questionnaire, including an anchor question assessing the impact of bowel function on quality of life. A subgroup of 218 patients completed the LARS score twice. Data were analyzed per country. RESULTS: The LARS score has demonstrated a high convergent validity in terms of a high correlation between LARS score and quality of life (P < 0.001). Sensitivity ranged from 67.7% to 88.3% and specificity from 58.1% to 86.3%. The LARS score was able to discriminate between groups of patients differing with regard to radiotherapy, surgery, and age (P < 0.05). The score also demonstrated high reliability at test-retest with narrow limits of agreement and no statistically significant difference between scores at the first and second test. CONCLUSIONS: The Swedish, Spanish, German, and Danish versions of the LARS score have proven to be valid and reliable tools for measuring LARS in European rectal cancer patients.

Low anterior resection syndrome and quality of life: an international multicenter study.

BACKGROUND: An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to 90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome. OBJECTIVE: The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer. DESIGN: The study was designed as an international cross-sectional study involving 5 centers in 4 European countries. PATIENTS: All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery. INTERVENTIONS: The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30. MAIN OUTCOME MEASURES: Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea. RESULTS: A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation. LIMITATIONS: The cross-sectional design prevents an evaluation of causality. CONCLUSIONS: The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.