Gracilis muscle transposition in complex anorectal fistulas of diverse types and etiologies: long-term results of 60 cases.

PURPOSE: Complex fistulas often require several attempts at repair and continue to be a challenging task for the surgeon, but above all, a major burden for the affected patient. This study is aimed at evaluating the potential of gracilis muscle transposition (GMT) as a therapeutic option for complex fistulas of diverse etiologies. METHODS: A retrospective study was conducted over a period of 16 years with a total of 60 patients (mean age 50 years). All were treated for complex fistula with GMT at St. Josef's Hospital in Regensburg, Germany. Follow-up data were collected and analyzed using a prospective database and telephone interview. Success was defined as the absence of fistula. RESULTS: A total of 60 patients (44 women, 16 men; mean age 50 years, range 24-82 years) were reviewed from January 2005 to June 2021. Primary fistula closure after GMT was achieved in 20 patients (33%) and 19 required further interventions for final healing. Overall healing rate was 65%. Fistula type was heterogeneous, with a dominant subgroup of 35 rectovaginal fistulas. Etiologies of the fistulas were irradiation, abscesses, obstetric injury, and iatrogenic/unknown, and 98% of patients had had previous unsuccessful repair attempts (mean 3.6, range 1-15). In 60% of patients with a stoma (all patients had a stoma, 60/60), stoma closure could be performed after successful fistula closure. Mean follow-up after surgery was 35.9 months (range 1-187 months). No severe intraoperative complications occurred. Postoperative complications were observed in 25%: wound healing disorders (n = 6), gracilis necroses (n = 3), incisional hernia (n = 2), scar tissue pain (n = 2), suture granuloma (n = 1), and osteomyelitis (n = 1). In 3 patients, a second gracilis transposition was performed due to fistula recurrence (n = 2) or fecal incontinence (n = 1). CONCLUSION: Based on the authors' experience, GMT is an effective therapeutic option for the treatment of complex fistulas when other therapeutic attempts have failed and should therefore be considered earlier in the treatment process. It should be seen as the main but not the only step, as additional procedures may be required for complete closure in some cases.

Contribution of CD3+CD8- and CD3+CD8+ T Cells to TNF-α Overexpression in Crohn Disease-Associated Perianal Fistulas and Induction of Epithelial-Mesenchymal Transition in HT-29 Cells.

BACKGROUND: Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta, and interleukin (IL)-13 are known to trigger epithelial-mesenchymal transition (EMT), promoting fistula formation. Here, we investigated the role of T-lymphocytes (T cells) in fistula pathogenesis. METHODS: CD3+CD8-, CD3+CD8+, or CD45+CD3- cells from healthy volunteers, patients with CD, and patients with CD with perianal fistula were co-cultured with HT-29 cells. The EMT, cytokine production, and mRNA expression were analyzed. Perianal CD fistula specimens were immunohistochemically stained for cytokines and their receptors. The effect of cytokines on EMT induction was investigated using an EMT spheroid model. RESULTS: Patients with CD with fistula revealed more CD3+CD8- and less CD3+CD8+ T cells in blood than healthy control patients and patients with CD without fistula. In perianal fistula specimens, CD4+ cells-and to a lesser extent CD8+ cells-were highly present around fistula tracts. When co-cultured with HT-29 cells, both cell subsets promoted EMT-related gene expression and TNF-α production in a time-dependent manner. The CD3+CD8- T cells from patients with CD with fistula also produced higher amounts of IL-13 than cells from healthy control patients or patients with CD without a fistula. We found that IL-22 and IL-22Rα1 were highly expressed in perianal CD fistula specimens and that IL-22 cotreatment potentiated TNF-α-induced EMT in HT-29 spheroids. CONCLUSIONS: Our data indicate that both CD3+CD8- and CD3+CD8+ T cells play an important role in the pathogenesis of perianal CD fistulas by the secretion of TNF-α. Our data support clinical evidence indicating that anti-TNF-α therapy is effective in fistula treatment and identify IL-13 and IL-22 as possible novel therapeutic targets for fistula therapy.

Health services research in colorectal cancer: a quasi-experimental interventional pilot study on in- and outpatient oncology.

INTRODUCTION: Due to frequent treatment side effects and weight loss, colorectal cancer patients require oncologic care and nutritional counseling both during and after hospitalization. The current study evaluated differences in discharge and side effects management and nutritional behavior between colorectal cancer patients of a control group without systematic counseling and of an intervention group with access to structured in- and outpatient oncology nurse and nutritional counseling. METHODS: The presented explorative, quantitative, single-center, interventional pilot study is a health services research project with a quasi-experimental design. Using a self-designed standardized questionnaire, data were collected from the control group (n = 75) before and from the intervention group (n = 114) after the introduction of in- and outpatient oncology nurse and structured systematic nutritional counseling. The in- and outpatient counseling services were developed and evaluated in the form of a structured nurse-led counseling concept. RESULTS: Intervention group patients profited significantly from inpatient oncology nurse counseling in seven different areas of discharge management. No differences were observed concerning patient-reported general and gastrointestinal side effects except for xerostomia and dysphagia, but of the patients participating in both in- and outpatient oncology nurse counseling, 90.0% were better able to cope with general side effects of treatment. Patients with in- and outpatient structured systematic nutritional counseling more frequently received nutritional information (p = 0.001), were better at gauging food intolerances (p = 0.023), and followed the dietician's advice in cases of gastrointestinal side effects significantly more often (p = 0.003) than control patients. Counselor-reported outcomes concerning gastrointestinal side effects showed improvement in most of the patients taking part in systematic in- and outpatient nutritional counseling, except for weight loss in 4 patients. CONCLUSION: In- and outpatient counseling in discharge and side effects management and nutrition improve the outcomes of colorectal cancer patients. Outpatient counseling should be further developed and evaluated in future studies.

Reducing Patient Burden and Improving Data Quality With the New Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire.

BACKGROUND: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire was developed in response to the need for a new, fast, and comprehensive tool for evaluating quality of life in patients who have colorectal cancer. Available surveys such as the SF-12, SF-36, Functional Assessment of Cancer Therapy-Colorectal, and European Organization for Research and Treatment of Cancer are either too general to be informative or too lengthy to complete. OBJECTIVE: The aim was to validate the Cleveland Clinic Foundation Colorectal Quality of Life Questionnaire. DESIGN: Data were obtained as part of a prospective randomized controlled trial. SETTINGS: This was a worldwide multicenter study with 2 domestic and 5 international locations. PATIENTS: This study randomly assigned 190 patients between the ages of 18 and 80 undergoing surgery for low rectal cancer. Of those randomly assigned, 142 with partially complete surveys were analyzed for selection bias and acceptability, and 95 with complete surveys were analyzed for survey validity. INTERVENTIONS: Patients received either a J-pouch, side-to-end anastomosis, or straight anastomosis. MAIN OUTCOME MEASURE: The study evaluated survey validity measures such as standardized Cronbach α for internal consistency and Spearman correlation coefficients for construct validity, convergent validity, and responsiveness. Univariate analyses were used to assess discriminative validity. RESULTS: Sufficient acceptability, construct, and convergent validity and responsiveness were achieved. All scores showed great internal consistency (Cronbach α >0.8). Superior discriminative ability was demonstrated by significant differences (p < 0.05) in 2 of 7 scores between neoadjuvant treatment groups, and in 6 of 7 scores between complication groups, none of which were detected by the SF-12 or Functional Assessment of Cancer Therapy-Colorectal surveys. LIMITATIONS: Limitations included a small sample size, cultural differences, and failure to assess test-retest ability of the questionnaire. CONCLUSIONS: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire is an efficient and reliable quality-of-life measure that better incorporates factors specific to colorectal cancer surgery. See Video Abstract at http://links.lww.com/DCR/B155. REDUCIENDO LA CARGA AL PACIENTE Y MEJORANDO LA CALIDAD DE DATOS CON EL NUEVO CUESTIONARIO DE CALIDAD DE VIDA EN CÁNCER COLORRECTAL DE CLEVELAND CLINIC (CCF-CAQL): El cuestionario de calidad de vida en cáncer colorrectal de Cleveland Clinic se desarrolló en respuesta a la necesidad de una herramienta nueva, rápida e integral para evaluar la calidad de vida en pacientes con cáncer colorrectal. Los cuestionarios disponibles como SF-12, SF-36, FACT-C y EORTC son demasiado generales para ser informativas o demasiado largas para completar.El objetivo fue validar el cuestionario de calidad de vida colorrectal de la Cleveland Clinic Foundation.Los datos se obtuvieron como parte de un ensayo prospectivo aleatorizado y controlado.Este fue un estudio multicéntrico mundial con dos sedes nacionales y cinco internacionales.Este estudio aleatorizó a 190 pacientes entre las edades de 18 y 80 sometidos a cirugía por cáncer rectal bajo. De aquellos aleatorizados, 142 con encuestas parcialmente completas se analizaron para determinar el sesgo de selección y la aceptabilidad, y 95 con encuestas completas se analizaron para determinar la validez de la encuesta.Los pacientes recibieron un reservorio en J, anastomosis latero-terminal o anastomosis termino-terminal.El estudio evaluó medidas de validez de la encuesta, como el Alfa de Cronbach estandarizado para la consistencia interna y los coeficientes de correlación de Spearman para la validez de construcción, la validez de convergencia y la capacidad de respuesta. Se utilizaron análisis univariados para evaluar la validez discriminativa.Se obtuvo suficiente aceptabilidad, construcción, validez de convergencia, y capacidad de respuesta. Todos los puntajes mostraron una gran consistencia interna (alfa de Cronbach > 0.8). Una capacidad discriminativa superior fue demostrada por diferencias significativas (p < 0.05) en dos de siete puntajes entre grupos de tratamiento neoadyuvante, y en seis de siete puntajes entre grupos de complicaciones, ninguno de los cuales fue detectado por SF-12 o FACT-C.Las limitaciones incluyeron un tamaño de muestra pequeño, diferencias culturales y la falta de evaluación de la confiabilidad test-retest del cuestionario.El Cuestionario de Calidad de Vida en Cáncer Colorrectal de Cleveland Clinic es una medida de calidad de vida eficiente y confiable que incorpora mejor factores específicos asociados a la cirugía de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B155.

Better Function With a Colonic J-Pouch or a Side-to-end Anastomosis?: A Randomized Controlled Trial to Compare the Complications, Functional Outcome, and Quality of Life in Patients With Low Rectal Cancer After a J-Pouch or a Side-to-end Anastomosis.

BACKGROUND INFORMATION: We aimed to compare prospectively the complications and functional outcome of patients undergoing a J-Pouch (JP) or a side-to-end anastomosis (SE) for treatment of low rectal cancer at a 2-year time point after resection for rectal cancer. METHODS: A multicenter study was conducted on patients with low rectal cancer who were randomized to receive either a JP or SE and were followed for 24 months utilizing SF-12 and FACT-C surveys to evaluate the quality of life (QOL). Fecal incontinence was evaluated using the Fecal Incontinence Severity Index (FISI). Bowel function, complications, and their treatments were recorded. RESULTS: Two hundred thirty-eight patients (165 males) were randomized with 167 final eligible patients, 80 in the JP group and 87 in the SE group for evaluation. The mean age at surgery was 61 (range 29 to 82) years. The overall mean recurrence rate was 12 of 238, 5% and similar in both groups. COMPLICATIONS: Overall, 37 of 190 (19%) patients reported complications, 14 of these were Clavien Dindo Grade 3b and 2 were 3a: leak 3 (2 JP,1 SE), fistula 4 (1 JP, 3 SE), small bowel obstruction 4 (3JP, 1 SE), stricture 4 (3 SE, 1 SA), pouch necrosis 2 (JP), and wound infection 5 (2 JP, 3 SE). QOL scores using either instrument between the 2 groups at 12 and 24 months were similar (P > 0.05). Bowel movements, clustering, and FISI scores were similar. CONCLUSION: At time points of 1 and 2 years after a JP or a SE for low rectal cancer, QOL, functional outcome, and complications are comparable between the groups. Although choosing a particular procedure may depend on surgeon/patient choice or anatomical considerations at the time of surgery, SE functions similar to JP and may be chosen due to the ease of construction.

A randomized trial of laparoscopic versus open surgery for rectal cancer.

BACKGROUND: Laparoscopic resection of colorectal cancer is widely used. However, robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking. A trial was designed to compare 3-year rates of cancer recurrence in the pelvic or perineal area (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer. METHODS: In this international trial conducted in 30 hospitals, we randomly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not invading adjacent tissues, and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio. The primary end point was locoregional recurrence 3 years after the index surgery. Secondary end points included disease-free and overall survival. RESULTS: A total of 1044 patients were included (699 in the laparoscopic-surgery group and 345 in the open-surgery group). At 3 years, the locoregional recurrence rate was 5.0% in the two groups (difference, 0 percentage points; 90% confidence interval [CI], -2.6 to 2.6). Disease-free survival rates were 74.8% in the laparoscopic-surgery group and 70.8% in the open-surgery group (difference, 4.0 percentage points; 95% CI, -1.9 to 9.9). Overall survival rates were 86.7% in the laparoscopic-surgery group and 83.6% in the open-surgery group (difference, 3.1 percentage points; 95% CI, -1.6 to 7.8). CONCLUSIONS: Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery. (Funded by Ethicon Endo-Surgery Europe and others; COLOR II ClinicalTrials.gov number, NCT00297791.).

Preliminary results on efficacy in closure of transsphincteric and rectovaginal fistulas associated with Crohn's disease using new biomaterials.

BACKGROUND AND AIMS: It was the aim of this prospective study to analyze the efficacy of the Surgisis AFP anal fistula plug and the Surgisis mesh for the closure of complex fistulas in Crohn's disease. METHODS: All patients with perianal Crohn's disease suffering from transsphincteric and rectovaginal fistulas who underwent surgery using the Surgisis anal fistula plug or the Surgisis mesh were prospectively enrolled in this study. Inclusion criteria included transsphincteric single-tract fistulas and rectovaginal fistulas. Surgery was performed using a standardized technique, including irrigation of the fistula tract, placement and internal fixation of the Surgisis anal fistula plug, and combined transanal/transvaginal excision of rectovaginal fistula with transvaginal placement of the mesh. Success was defined as closure of both internal and external (perianal or vaginal) openings, absence of drainage without further intervention, and absence of abscess formation. Follow-up information was obtained from clinical examination 3, 6, 9, and 12 months postoperatively. RESULTS: Within the observation period, a total of 16 procedures were performed. After a mean follow-up of 9 months and 1 patient lost to follow-up, the overall success rate was 75%. For transsphincteric fistulas, the success rate was 77%, whereas it was 66% in rectovaginal fistulas associated with Crohn's disease. All 4 patients with failure had reoperation. Rate of stoma reversal in those patients who had fecal diversion was 66%. No deterioration of continence was documented. CONCLUSION: The short-term success rates are promising. Further analysis is needed to explain the definite role of this technique in comparison with traditional surgical techniques.

Outcome of laparoscopic surgery for rectal cancer in 101 patients.

PURPOSE: This study was conducted to investigate the feasibility of laparoscopic resection of rectal cancer and to compare early outcome data with the results of the conventional technique. METHODS: From January 1996 to March 2002, 435 patients with primary rectal cancer were operated on at our institution. Low-risk, small rectal tumors treatable by local excision, rectal cancer recurrences, and emergency cases were excluded from the analysis. Three hundred thirty-four patients were operated on by the conventional open approach. One hundred one selected patients underwent surgery by the laparoscopic technique. RESULTS: Because of the selection process, significantly more patients with early tumor stages were operated on by laparoscopy. There were no differences in mean operation time, morbidity, mortality, or the anastomotic leakage rate; however, the need for intraoperative transfusion, mean stay in the intensive care unit, and length of hospital stay were reduced significantly. CONCLUSIONS: In terms of the intraoperative and early postoperative course, the laparoscopic resection of rectal cancer in a selected cohort of patients compares favorably with the open technique. Because follow-up time is limited to date, only very preliminary information can be given on tumor-related outcome data. However, these preliminary data appear to suggest that rectal cancer resection can be performed by laparoscopy in accordance with established principles of cancer therapy and that port-site metastases are not a relevant clinical problem. Prospective, randomized trials are required to determine whether the laparoscopic approach will play a significant role in the treatment of rectal cancer in the future.

Metabolic classification of human rectal adenocarcinomas: a novel guideline for clinical oncologists?

PURPOSE: Based on previous findings in SCC of the human uterine cervix and of the head and neck, metastasis- and survival-related metabolic classification was performed in human rectal adenocarcinomas. Such a characterization is suggested as basis of a novel clinical guideline for an appropriate therapy of epithelium-derived malignancies. METHODS: Tissue concentrations of ATP, glucose, and lactate in viable tumor regions of 33 pretherapeutically taken cryobiopsies from 24 patients were measured at a microscopic level using the technique of imaging bioluminescence. RESULTS: In metastatic carcinomas, lactate levels were significantly higher (mean+/-SD: 13.4+/-3.8 vs 6.9+/-2.5 micro mol/g, P = 0.0046) and glucose levels significantly lower (0.3+/-0.2 vs 1.0+/-0.4 micro mol/g, P = 0.0020) than in non-metastatic carcinomas. No patients had distant metastasis with tumor lactate levels below the population median of 8.0 micro mol/g or glucose levels above 0.9 micro mol/g. CONCLUSIONS: These results support the hypothesis that lactate and glucose levels measured in human primary carcinomas may serve as an early prognostic tool in the clinic with regard to formation of metastasis and patient survival. The present data encourage further studies on possible strategies for a metabolic classification of tumors as a prognostic tool.