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

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

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

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

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

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

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

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

Single-incision laparoscopic surgery (SILS) for the treatment of ileocolonic Crohn's disease: a propensity score-matched analysis.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) aims to minimize the surgical access trauma by reducing the number of abdominal incisions to a single site, potentially offering better cosmetic results and decreased postoperative pain. In this study, we compare the results of SILS ileocolic resection for Crohn's disease (CD) to conventional laparoscopy and open surgery using a propensity score-matched analysis in a retrospective national multicentre study. METHODS: All consecutive patients undergoing elective SILS ileocaecal or redo ileocolic resection for primary and recurrent CD from 1 June 2018 to 31 May 2019 were included. Patients were matched 1:1:1 with laparoscopy and open surgery according to perianal disease, recurrent disease, penetrating phenotype of CD, history of previous abdominal surgery, preoperative medical treatment with steroids and anti-TNF. Postoperative morbidity within 30 days of surgery was the primary endpoint. RESULTS: Fifty-eight patients were included in each group, for a total of 174 patients. The conversion rate for SILS and laparoscopy was 10.3% and 12%, respectively, with no difference in the incidence of postoperative complications (13.8% and 12%, p = 0.77), whilst open surgery demonstrated a worse morbidity profile, with a complication rate of 25.9% (p < 0.0001). Median length of hospital stay following SILS ileocolic resection was 5 days, significantly shorter compared to 7 days for laparoscopy and 9 for open surgery (p < 0.0001). CONCLUSIONS: SILS ileocolonic resection for CD demonstrated a comparable morbidity profile compared to laparoscopy in selected patients, with a reduced length of postoperative hospital stay.

Colonic J-Pouch or Straight Colorectal Reconstruction After Low Anterior Resection For Rectal Cancer: Impact on Quality of Life and Bowel Function: A Multicenter Prospective Randomized Study.

BACKGROUND: Patient-reported outcomes associated with different bowel reconstruction techniques following anterior resection for rectal cancer are still a matter of debate. OBJECTIVE: This study aimed to assess quality of life and bowel function in patients who underwent colonic J-pouch or straight colorectal anastomosis reconstruction after low anterior resection. DESIGN: Bowel function and quality of life were assessed within a multicenter randomized trial. Questionnaires were administered before the surgery (baseline) and at 6, 12, and 24 months after surgery. SETTINGS: Patients were enrolled by 19 centers. The enrollment started in October 2009 and was stopped in February 2016. The study was registered at www.clinicaltrials.gov (Identifier: NCT01110798). PATIENTS: Patients who underwent low anterior resection for primary mid-low rectal cancer and who were randomly assigned in a 1:1 ratio to receive either stapled colonic J-pouch or straight colorectal anastomosis were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and bowel function. RESULTS: Of the 379 patients who were evaluable, 312 (82.3%) completed the baseline, 259 (68.3%) the 6-month, 242 (63.9%) the 12-month, and 199 (52.5%) the 24-month assessment. Bowel functioning and quality of life did not significantly differ between arms for almost all domains. The total bowel function score, the urgency, and the stool fractionation scores significantly worsened after surgery and remained impaired over time in both arms (p < 0.0032), whereas constipation improved after surgery but recovered to baseline levels from 1 year onward (p < 0.0036). All patients showed a significant and continuous improvement in emotional functioning (p < 0.0013) and future perspective (p < 0.0001) from baseline to the end of the study. LIMITATIONS: Limitations of the study include missing data, which increased over time; the possibility that some treatments have slightly changed since the study was conducted; and investigators not blind to treatment allocation. CONCLUSION: The findings of this study do not support the routine use of colonic J-pouch reconstruction in patients with rectal cancer who undergo a low anterior resection. See Video Abstract at http://links.lww.com/DCR/B328. BOLSA J COLÓNICA O RECONSTRUCCIÓN COLORRECTAL RECTA DESPUÉS DE RESECCIÓN ANTERIOR BAJA PARA CÁNCER RECTAL: IMPACTO EN LA CALIDAD DE VIDA Y LA FUNCIÓN INTESTINAL: UN ESTUDIO ALEATORIZADO PROSPECTIVO MULTICÉNTRICO: Los resultados informados por el paciente asociados con diferentes técnicas de reconstrucción intestinal después de la resección anterior para el cáncer de recto aún son tema de debate.Evaluar la calidad de vida y la función intestinal en pacientes que se sometieron a una bolsa en J colónica o reconstrucción de anastomosis colorrectal recta después de una resección anterior baja.La función intestinal y la calidad de vida se evaluaron en un ensayo aleatorizado multicéntrico. Los cuestionarios se administraron antes de la cirugía (basal) y a los 6, 12 y 24 meses después de la cirugía.Los pacientes fueron incluidos en 19 centros. La inscripción comenzó en Octubre de 2009 y se detuvo en Febrero de 2016. El estudio se registró en www.clinicaltrials.gov (Identificador: NCT01110798).Pacientes que se sometieron a resección anterior baja por cáncer rectal primario medio-bajo y que fueron aleatorizados en una proporción de 1: 1 para recibir bolsa J colónica con grapas o anastomosis colorrectal recta.calidad de vida y función intestinal.De los 379 pacientes que fueron evaluables, 312 (82.3%) completaron la evaluación inicial, 259 (68.3%) a los 6 meses, 242 (63.9%) a los 12 meses y 199 (52.5%) a los 24 meses. . El funcionamiento intestinal y la calidad de vida no difirieron significativamente entre los dos grupos en casi todos los dominios. La puntuación total de la función intestinal, la urgencia y las puntuaciones de fraccionamiento de las heces empeoraron significativamente después de la cirugía y continuaron con el tiempo extra en ambos grupos (p <0.0032), mientras que el estreñimiento mejoró después de la cirugía pero se recuperó a los niveles basales a partir de 1 año en adelante (p <0.0036). Todos los pacientes mostraron una mejora significativa y continua en el funcionamiento emocional (p <0.0013) y la perspectiva futura (<0.0001) desde el inicio hasta el final del estudio.Datos faltantes, que aumentaron con el tiempo; la posibilidad de que algunos tratamientos hayan cambiado ligeramente desde que se realizó el estudio; investigadores no cegados a la asignación del tratamiento.Los hallazgos de este estudio no respaldan el uso rutinario de la reconstrucción de la bolsa J colónica en pacientes con cáncer rectal que se someten a una resección anterior baja. Consulte Video Resumen en http://links.lww.com/DCR/B328. (Traducción-Dr. Yesenia Rojas-Khalil).

From high volume to "zero" proctology: Italian experience in the COVID era.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic hit Italy early and strongly, challenging the whole health care system. Proctological patients and surgeons are experiencing a previously unseen change in care with unknown repercussion. Here we discuss the proctological experience of 4 Italian hospitals during the COVID-19 pandemic. METHODS: Following remote brainstorming, the authors summarised their experience in managing proctological patients during the COVID-19 pandemics and put forward some practical observations to further investigate. RESULTS: The 4 hospitals shifted from a high-volume proctological activity to almost "zero" visits and surgery. Every patient accessing the hospital must respect a specific COVID-19 protocol. Proctological patients can be stratified based on presentation and management considerations into (1) neoplastic patients, the only allowed to be surgically treated, (2) the ones requiring urgent care, operated only in highly selected cases and (3) the stable, already known patients, managed remotely. Changes in the clinical management of the proctological disease are presented together with some considerations to be explored. CONCLUSIONS: In the absence of scientific evidence, these practical considerations may be valuable to proctological surgeons starting to face the COVID-19 pandemics. Beside the more clinical considerations, this crisis produced unexpected consequences such as an improvement of the therapeutic alliance and a shift towards telemedicine that may be worth exploring also in the post-COVID-19 era.

Setting up and exploitation of a nano/technological platform for the evaluation of HMGA1b protein in peripheral blood of cancer patients.

Even if cancer specific biomarkers are present in peripheral blood of cancer patients, it is very difficult to detect them with conventional technology because of their low concentration. A potential cancer biomarker is the HMGA1b protein, whose overexpression is a feature of several human malignant neoplasias. By taking advantage of the surface plasmon resonance (SPR) phenomenon, we realized a specific nano/technology-based assay for cancer detection. More in details, anti-HMGA1b monoclonal antibodies, whose affinity was previously defined by ELISA, were immobilized onto metallic surfaces to develop a direct SPR-based assay. After having analyzed blood samples from colorectal cancer patients and healthy people for the presence of HMGA1b, we observed a 2-fold increase of the HMGA1b levels in the blood of cancer patients with respect to the healthy control people. We conclude that the set-up technology might allow to detect a tumoral mass through the evaluation of HMGA1b protein blood levels.

Evaluation of Quantitative PET/MR Enterography Biomarkers for Discrimination of Inflammatory Strictures from Fibrotic Strictures in Crohn Disease.

PURPOSE: To retrospectively evaluate positron emission tomography (PET)/magnetic resonance (MR) enterography for the differentiation of fibrotic strictures from inflammatory strictures in patients with Crohn disease. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave their written informed consent for study enrollment. PET/MR enterography images were evaluated in 19 patients with Crohn disease who had strictures that underwent surgical resection with pathologic confirmation. Two radiologists and a nuclear medicine physician in consensus evaluated the following bowel wall PET/MR enterography biomarkers: signal intensity (SI) on T2-weighted images, apparent diffusion coefficient (ADC), PET maximum standardized uptake value (SUVmax), SI on T2-weighted images × SUVmax, and ADC × SUVmax values at levels that corresponded to pathologic specimens. MR, PET, and hybrid PET/MR biomarkers were compared, and the performance for differentiation of inflammatory strictures from fibrotic strictures was assessed. Mixed-model regression analysis was used to compare the mean imaging parameters between groups; the P values were corrected for the five comparisons by using the Bonferroni method. RESULTS: Three of the PET/MR enterography biomarkers, SUVmax, SI on T2-weighted images × SUVmax, and ADC × SUVmax, showed significant differences in the fibrosis group compared with the fibrosis with active inflammation group and the active inflammation only group. The best discriminator between fibrosis and active inflammation was the combined PET/MR enterography biomarker ADC × SUVmax cutoff of less than 3000, which was associated with accuracy, sensitivity, and specificity values of 0.71, 0.67, and 0.73, respectively. CONCLUSION: PET/MR enterography offers a potential noninvasive technique for the differentiation of purely fibrotic strictures from mixed or inflammatory strictures. A hybrid biomarker that incorporates both MR and PET information performed better for stricture evaluation than either modality alone.

UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients.

Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. Despite the progresses made in diagnosis and treatment, the identification of tumor markers is still a strong clinical need, because current treatments are efficacious only in a subgroup of patients. UbcH10 represents a potential candidate biomarker, whose expression levels could be employed to predict response or resistance to chemotherapy or targeted agents. UbcH10 mRNA and protein expression levels have been evaluated in a large group of CRC patients and correlated with clinico-pathological characteristics, including KRAS mutations. Moreover, the endogenous levels of UbcH10 and its role on cell growth have been evaluated in CRC cells. Finally, to investigate the impact of UbcH10 protein expression on the response to irinotecan, its active metabolite SN-38 and cetuximab treatment, UbcH10 silencing experiments were carried-out on two colon carcinoma cell lines, Caco-2, and DLD1. Overexpression of UbcH10 mRNA and protein was observed in the vast majority of patients analyzed. UbcH10 suppression decreased CRC cell growth rate (at least in part through deregulation of Cyclin B and ERK1) and sensitized them to pharmacological treatments with irinotecan, SN-38 and cetuximab (at least in part through a down-regulation of AKT). Taken together, these findings indicate that UbcH10 expression regulates CRC growth and could play an important role in the personalization of the therapy of CRC patients.

Effect of Surgery on Health-Related Quality of Life of Patients With Locally Recurrent Rectal Cancer.

BACKGROUND: Local recurrences of rectal cancer are best treated with surgical resection. Health-related quality of life is an important outcome measure in rectal cancer, but it has been poorly investigated in local recurrences. OBJECTIVE: The purpose of this study was to assess quality of life in patients receiving or not receiving surgery for locally recurrent rectal cancer. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at a single tertiary care institution. PATIENTS: Patients presenting with local recurrent rectal cancer between December 2002 and December 2011 were included. A control group of patients with nonrecurrent rectal cancer was prospectively enrolled (planned ratio, 1:2). MAIN OUTCOME MEASURES: All of the patients received the core Quality of Life Questionnaire C30 of the European Organisation for Research and Treatment of Cancer preoperatively or at diagnosis and then 1 and 3 years later. We compared results according to oncologic clearance (R0 vs R1 vs R2 vs no surgery). Confounding variables were tested with a multivariate logistic regression. RESULTS: Forty-five patients (27 men), median age 62 years (range, 34-80 years), with recurrence were observed. Twelve (26.7%) were not fit for surgery. Twenty one (63.6%), 7 (21.2%), and 5 (15.2%) received R0, R1, and R2 resections. Data for 30 (90.9%) and 25 operated patients (75.75%) were available at 1- and 3-year follow-ups. Irrespective of type of surgery and multimodal treatments, patients receiving R0/R1 resections had improvement in quality of life in all of the domains compared with the R2 and no-surgery groups. Outcomes were inferior compared with nonrecurrent control subjects (N = 71). At 3 years, R0 patients reported scores equal to those of control subjects, with superior emotional functioning. R1 patients had worse symptoms and quality of life at 3-year follow-up. Surgery impaired survival and quality of life of R2 patients compared with those who were not operated on. LIMITATIONS: The study was limited because it involved a single center with a single senior surgeon. CONCLUSIONS: Quality of life of patients with locally recurrent rectal cancer is improved by R0 and ameliorated with R1 resection, irrespective of surgical extent. Full recovery, similar to that of nonrecurrent cancer survivors, can be expected in R0 patients but requires longer follow-up times. Surgery with macroscopic involvement of resection margins accelerates quality of life decline and shortens survival.

CTR2 identifies a population of cancer cells with stem cell-like features in patients with clear cell renal cell carcinoma.

PURPOSE: In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells. MATERIALS AND METHODS: CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized. Colony forming efficiency and self-renewal ability were tested by limiting dilution. Tumorigenic properties were evaluated in vitro by soft agar assay. The angiogenic response was evaluated in vivo by the chorioallantoic membrane angiogenic assay. Microarray analysis was performed on 6 tubular adult renal progenitor cell and 6 renal cell carcinoma derived cell clones. Membrane protein expression was evaluated by flow cytometry and immunofluorescence staining. RESULTS: CD133+/CD24+ cells were isolated from normal and tumor kidney tissue. Fluorescence activated cell sorting revealed that renal cell carcinoma derived cells did not express mesenchymal stem cell markers. CD133+/CD24+ tumor cells were more undifferentiated than tubular adult renal progenitor cells. Renal cell carcinoma derived cells were clonigenic and could differentiate into adipocytes, epithelial and osteogenic cells. They could also regenerate tumor cells in vitro and induce angiogenesis in vivo. Gene expression profile identified CTR2 as a membrane marker for this neoplastic population. CTR2 was involved in renal cell carcinoma derived cell cisplatin resistance. CONCLUSIONS: Our results indicate the presence of a CD133+/CD24+/CTR2+ cancer cell population in clear cell renal cell carcinoma. These cells have some stem cell-like features, including in vitro self-maintenance and differentiating capabilities, and they can induce an angiogenic response in vivo.

Impact of donor-recipient gender on kidney graft and patient survival: short- and long-term outcomes.

PURPOSE: Donor and recipient gender influence on post-transplant kidney and patient survival is still controversial, and the literature data do not present unanimous conclusions. The aim of this study was to evaluate the effect of gender disparities between donor and recipient in 963 kidney transplants performed at our center from January 2000 to December 2010. METHODS: The patients were subdivided into four groups according to recipient and donor gender: male donor-to-male recipient (MDMR; n = 305), male donor-to-female recipient (MDFR; n = 203), female donor-to-female recipient (FDFR; n = 206), and female donor-to-male recipient (FDMR; n = 249). Independent sample's t test and one-way ANOVA were used for statistical analyses. Graft and patient survival were calculated by the Kaplan-Meier method and compared using the log rank test. RESULTS: There were no statistically significant differences between the groups with regard to age, cold ischemia time, delayed graft function, primary non-function, and episodes of acute and chronic rejection. Moreover, no difference in either graft (p = 0.92) or patient (p = 0.41) survival at 1, 3, and 5 years was observed. However, female recipients had significantly lower serum creatinine values and higher estimated GFR, particularly if they received a male donor kidney, and these findings were stable up to 3-year post-transplantation. CONCLUSIONS: No impact of gender on short- or long-term graft and patient survival was observed in deceased kidney transplantation. However, we report a lower creatinine level in the male donors to female recipients group as compared with other recipient-donor gender combinations, although this difference loses statistical significance after the third-year post-transplantation.

Development and validation of a practical score to predict pain after excisional hemorrhoidectomy.

PURPOSE: Excisional hemorrhoidectomy (EH) can be complicated by high early (EP) and prolonged pain (PP). This study aimed to determine predictors of high postoperative pain and to develop a risk score suitable to identify patient candidates to a more active analgesic treatment. METHODS: We collected data of patients undergoing EH between January 2005 and September 2012 (development group). Patient-, disease-, surgery-, and surgeon-related characteristics were gathered. Anxiety was evaluated by means of STAI-Y. EP was assessed at 1-day, while PP at 15-day follow-up by means of a 10-cm VAS (cutoff, EP ≥ 5; PP ≥ 3 cm). On the basis of the odds ratio from a logistic regression, independent risk factors were assigned a weighted integer. The sum comprised the risk score, which was validated on a prospective cohort of patients undergoing EH between September 2012 and January 2014. RESULTS: Five hundred fourteen patients were included in development group. Incidence of EP was 18.3 %, with 40.4 % developing PP. Younger age, male gender, advanced education, constipation, external component, anxious state and trait, and high anal resting tone were independent predictors of EP. Previous pain exerted a protective effect. Incomplete postoperative evacuation, advanced education level, high anal resting tone, and anxious trait were predictors of PP. In the development group, the risk of EP ranged between 1 % (low risk) and 21 % (high risk). Receiver operating curve (ROC) analysis of validation group (n = 130) confirmed the discriminatory power of this model (area under the ROC = 0.69). CONCLUSION: The score can stratify the risk of EP following EH, identifying high-risk patient candidates to active analgesic administration or alternative surgical procedures.

Surgical treatment of perianal fistulizing Crohn's disease: from lay-open to cell-based therapy--an overview.

BACKGROUND: Perianal Crohn's disease (CD) can be challenging. Despite the high incidence of fistulizing CD, literature lacks clear guidelines. Several medical, surgical, and combined treatment modalities have been proposed, but evidences are scarce. METHODS: We searched the literature to assess the facets of perianal CD, with particular focus on complex fistulae. Disease epidemiology, classification, diagnosis, activity scoring systems, and medical-surgical treatments were assessed. RESULTS: Perianal fistulizing CD is common, frequently associated with upper gastrointestinal and colorectal CD. Complex fistulas often require repeated treatments. Continence is a major concern when dealing with repeated procedures. A prudent pathway is to resolve active sepsis and to limit damages, delaying a definitive treatment to the time when acute phase has been controlled. The improved diagnostic techniques allow better preoperative planning and are useful in monitoring the response to treatment. Besides newer devices, cell-based treatments are promising tools which have recently enriched the treatment portfolio. However, the need for proctectomy is still disturbingly high in CD patients with complex perianal fistulae. CONCLUSIONS: Perianal CD can impair quality of life and lead to need for proctectomy. A staged approach is reasonable. Treatment success can be improved by multimodal treatment and collaborative management by experienced gastroenterologists and surgeons.

Effects of a new pocket device for negative pressure wound therapy on surgical wounds of patients affected with Crohn's disease: a pilot trial.

INTRODUCTION: Surgical site infections (SSIs) affect costs of care and prolong length of stay. Crohn's disease (CD) represents an independent risk factor for SSI. The risk can be further increased by concomitant administration of immunosuppressive drugs and poor performance status at the time of surgery. Patients suffering from CD often need more than one surgical intervention during life, sometimes requiring fashioning of a stoma. The aim of this pilot study was to compare a portable device for negative pressure wound therapy (PICO, Smith & Nephew, London, UK) to conventional gauze dressings in patients undergoing surgery for stricturing CD. METHODS: Between January 2010 and November 2011, this controlled trial enrolled 30 patients, who were assigned to treatment with either PICO (n = 13) or conventional dressings (n = 17). Each patient completed a 3-month follow-up. RESULTS: Patients receiving PICO experienced significantly less postoperative wound complications (P = .001) and SSI (P = .017) compared with those who received conventional dressings. This resulted in shorter hospital stay (P = .0007). No significant differences in cosmetic results were found. CONCLUSION: These data suggest that PICO allows faster and safe discharge by reducing the incidence of SSI and wound-related complications in selected patients undergoing surgical intervention for stricturing CD. This could be particularly useful in patients receiving steroids.

New advances in negative pressure wound therapy (NPWT) for surgical wounds of patients affected with Crohn's disease.

Surgical site complications (SSC) negatively affect costs of care and prolong length of stay. Crohn's disease (CD) is a risk factor for SSC. CD patients often need surgery, sometimes requiring stoma. Our primary aim was to compare the effects on SSC of a portable device for NPWT (PICO, Smith & Nephew, London, UK) with gauze dressings after elective surgery for CD. Secondary aims were manageability and safety of PICO and its feasibility as home therapy. Between 2010 and 2012, 50 patients were assigned to treatment with either PICO (n = 25) or conventional dressings (n = 25). Each patient completed 12-month follow-up. Parameters of interests for primary aim were SSC, surgical complications, and readmission rates. Data on difficulties in managing PICO and device-related complications were also collected. Patients receiving PICO had less SSC, resulting in shorter hospital stay. At last follow-up, readmission rates were lower with PICO. No differences were observed in surgical complications between groups. No patients reported difficulties in managing the device. Among patients discharged with PICO, none needed to come back to the hospital for device malfunctioning or inability to manage it. PICO reduces SSC and length of stay in selected CD patients compared with conventional dressings. The device is safe and user friendly.

Predictive value of resistive index in graft survival after kidney transplant.

INTRODUCTION: The intrarenal resistance index (RI) is a calculated parameter for the assessment of the status of the graft during the follow-up ultrasound of the transplanted kidney. Currently it is still unclear the predictive value of RI, also in function of the time. MATERIALS AND METHODS: We retrospectively investigated the correlation between the RI and the graft survival (GS) and the overall survival (OS) after transplantation. We evaluated 268 patients transplanted between 2003 and 2011, the mean followup was 73 months (12-136). The RI was evaluated at 8 days, 6 months, 1 year and 3 years. The ROC analysis was used to calculate the predictive value of RI and the Kaplan Mayer curves was used to evaluated the OS and PS. RESULTS: The ROC analysis, correlated to the GS, identified a value of RI equal to 0.75 as a cut-off. All patients was stratified according to the RI at 8 days (RI ≤ 0,75: 212 vs RI > 0.75: 56), at 6 months (RI ≤ 0.75: 237 vs RI > 0.75: 31), at 1 year (RI ≤ 0.75: 229 vs RI > 0.75: 39) and at 3 years (RI ≤ 0.75: 224 vs RI > 0.75: 44). The RI showed statistically significant differences between the two groups in favor of those who had an RI ≤ 0.75 only at 8 days and at 6 moths (p = 0.0078 and p = 0.02 to 8 days to 6 months) on the GS. On the contrary, we observed that the RI estimated at 1 year and 3 years has not correlated with the GS. The same RI cut-off was correlate with PS after transplantation. We observed that there are no correlations between the RI and OS. CONCLUSIONS: The RI proved to be a good prognostic factor on survival organ when it was evaluated in the first months of follow- up after transplantation. This parameter does not appear, however, correlate with OS of the transplanted subject.

Capillary hemangioma of the scrotum mimicking an epididymal tumor: case report.

We report a case of capillary hemangioma of the scrotum. A 52-year-old male presented with a left scrotum swelling that had arisen suddenly two months before. Scrotal ultrasound revealed a dishomogeneous mass in the left scrotum. The mass demonstrated blood flow in the color Doppler mode. Scrotal mass excision was performed. Pathological evaluation revealed a capillary hemangioma.