Assessment of fistulectomy combined with sphincteroplasty in the treatment of complicated anal fistula / Avaliação de fistulectomia combinada com esfincteroplastia no tratamento de fístula anal complicada

Abstract Introduction The ideal method of treating the complex anal fistula is to eradicate the sepsis and preserve the anal sphincter; since there is no definite consensus on the surgical method of treating it. Recent studies show that fistulectomy and immediate sphincteroplasy are a safe and appropriate way to treat the fistula-in-ano. The aim of this study was to evaluate the long term outcomes of fistulectmy and sphincteroplasty in the treatment of complex perianal fistula. Methods In this prospective study, we have analyzed the data of 80 patients who underwent fistulectomy and sphincteroplasty from May 2013 to May 2016. Preoperative information included physical examination, preoperative fecal incontinence evaluation and taking a complete history about underlying diseases and past related surgeries were collected. Results Of all 80 patients with complex fistula, 57.5% (46 patients) were male. 70-Patients were presented with high transsphincteric fistula (87.5%) and anterior fistula was diagnosed in 10 of them (12.5%). 9 patients (11.3%) suffered from hypertension and 43 patients (53.75%) had recurrent fistula after previous surgeries. During the follow-up period, the overall success rate was 98.8% (98.8%) and fistulectomy and sphincteroplasty failed in only one patient (failure rate: 1.3%). preoperative and post-operative scoring showed mild fecal incontinence in 8 patients (10%). We have found no significant relation between the age, gender, hypertension, previous surgery and post-operative recurrence. Conclusion Fistulectomy and sphincteroplasty is a safe surgical procedure in the treatment of anterior anal fistula in females and high transsphincteric fistulas.

Resumo Introdução o método ideal para tratar a fístula anal complexa consiste em erradicar a sepse e preservar o esfíncter anal, uma vez que não existe consenso definitivo com relação ao método cirúrgico para tratamento desse problema. Estudos recentes demonstram que a fistulectomia, seguida imediatamente pela esfincteroplastia, é procedimento seguro e apropriado no tratamento da fístula perianal. O objetivo deste estudo foi avaliar os resultados em longo prazo da fistulectomia e da esfincteroplastia no tratamento da fístula perianal complexa. Métodos Neste estudo prospectivo analisamos os dados de 80 pacientes tratados por fistulectomia e esfíncteroplastia no período de maio de 2013 até maio de 2016. Foram coletadas as seguintes informações pré-operatórias: exame físico, avaliação pré-operatória de incontinência fecal e história completa sobre doenças subjacentes e cirurgias prévias afins. Resultados De todos os 80 pacientes com fístula complexa, 57,5% (46 pacientes) pertenciam ao gênero masculino. Setenta pacientes se apresentaram com fístula trans-esfinctérica alta (87,5%); em 10 desses pacientes (12,5%), foi diagnosticada fístula anterior. Nove pacientes (11,3%) sofriam de hipertensão (HT), tendo sido observada recorrência de fístula após cirurgias prévias em 43 pacientes (53,75%). Durante o período de seguimento, o percentual de sucesso global foi de 98,8%, e em apenas um paciente os procedimentos de fistulectomia e esfincteroplastia não obtiveram sucesso (percentual de falha: 1,3%). Os escores pré-operatórios e pós-operatórios revelaram incontinência fecal leve em 8 pacientes (10%). Não observamos nenhuma relação significativa entre idade, gênero, HT, cirurgia prévia e recorrência pós-operatória. Conclusão Fistulectomia e esfincteroplastia constituem procedimento cirúrgico seguro no tratamento de fístulas anais anteriores em mulheres e de fístulas trans-esfinctéricas altas.

Long-term results of ligation of intersphincteric fistula tract (LIFT) for management of anal fistula / Resultados em longo prazo da ligadura interesfincteriana do trato fistuloso (LIFT) para o tratamento de fístula anal

ABSTRACT Background: Ligation of intersphincteric fistula tract technique is a new sphincter saving method with good results in management of anal fistula, but few studies report long-term follow-up data. Material and methods: This study investigated the use of ligation of intersphincteric fistula tract as a sphincter saving method based on long term results. This was a retrospective review of prospectively collected data. The study was conducted at two tertiary care university medical centers. 36 patients with complex fistula from January 2010 to January 2014 treated with classic ligation of intersphincteric fistula tract were retrospectively followed. Demographic data, previous repair attempts, the type of the fistula and score of fecal continence were collected. The procedure was performed by colorectal surgeons. Primary healing rate, failures and fecal incontinence score of patients were followed for 6-48 months. Results: A total of 36 patients underwent ligation of intersphincteric fistula tract during 24 months. The mean age of the patients was 35 years and 50% had two previous attempts at surgery. A total of 25 patients (69/5%) had high transsphincteric fistula. The mean follow up was 27 months. Successful fistula closure was achieved in 63/8% of the patients (23 of 36). The mean time of recurrence was 4.5 weeks. Only one (2/77%) patient reported gas incontinence (score: 3) after the procedure. Conclusion: The recurrence rate and fecal incontinence were measured. The ligation of intersphincteric fistula is a promising sphincter-preserving procedure that is simple and safe. Our study demonstrates favorable long-term results of ligation of intersphincteric fistula tract for management of complex anal fistulas.

RESUMO Introdução: A técnica LIFT (Ligation of Intersphincteric Fistula Tract; ligadura interesfincteriana do trato fistuloso) é um novo método de preservação esfinctérica com bons resultados no tratamento da fístula anal, mas são poucos os estudos que relatam dados de seguimento em longo prazo. Material e métodos: Esse estudo investigou o uso de LIFT como método de preservação esfinctérica, com base em resultados em longo prazo. Essa foi uma revisão retrospectiva de dados prospectivamente coletados. O estudo foi realizado em dois centros médicos terciários universitários. Trinta e seis pacientes com fístula complexa tratados com LIFT cássica de janeiro de 2010 até janeiro de 2014 foram retrospectivamente seguidos. Foram coletados dados demográficos, tentativas precedentes de reparo, tipo de fístula, e escore de continência fecal. O procedimento foi realizado por cirurgiões colorretais. Percentual de cicatrização primária, insucessos, e escore de incontinência fecal dos pacientes foram monitorados durante 6 a 48 meses. Resultados: No total, 36 pacientes foram submetidos a LIFT em um período de 24 meses. A média de idade dos pacientes era de 35 anos e 50% já tinham sido previamente submetidos a duas tentativas de cirurgia. Vinte e cinco pacientes apresentavam fístula trans-esfinctérica alta. A média do seguimento foi de 27 meses. Foi obtido fechamento bem-sucedido da fístula em 63,8% dos pacientes (23 de 36). O tempo médio até a recorrência foi de 4,5 semanas. Apenas um (2,77%) paciente informou incontinência gasosa (escore = 3) após o procedimento. Conclusão: O percentual de recorrência e a incontinência fecal foram mensurados. A ligadura de fístula intersfinctérica é um procedimento promissor de preservação esfinctérica, de simples execução e seguro. Nosso estudo demonstra resultados favoráveis com o uso de LIFT em longo prazo para o tratamento de fístulas anais complexas.

The Effects of Isoproterenol and Propranolol on Cytokine Profile Secretion by Cultured Tumor-infiltrating Lymphocytes Derived from Colorectal Cancer Patients.

OBJECTIVE: Anti-tumor immunity and cytokine profiles have important roles in the development of cancer. Norepinephrine (NE) release due to sympathetic activation leads to a Th2 deviation via the beta-2 adrenergic receptor Beta-2 adrenergic receptor (ß-2AR) and could increase cancer progression. This study intends to determine the effects of isoproterenol (ISO; beta-agonist) and propranolol (PRO; beta-antagonist) on the production of IFN-γ, IL-4, and IL-17. Cytokine levels have been examined in tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) of patients with colorectal cancer (CRC). The ß-2AR expression on lymphocyte subsets was also assessed. MATERIALS AND METHODS: In this experimental study, TILs were isolated from fresh CRC tissue and patient PBMCs were obtained just prior to surgery. The cells were cultured in medium for 72 hours. Concomitantly, cells were stimulated with 10 µg/ml phytohemagglutinin (PHA) alone or in the presence of either 1 µmol/L of PRO or 1 µmol/L ISO. The concentration of cytokines in the supernatants was measured by ELISA. Three-color flow cytometry was used to determine the expression of ß-2AR on the lymphocyte subsets. Statistical analyses were performed via paired or independent t-test. RESULTS: Levels of IFN-γ, IL-4 and IL-17 were elevated after PHA-stimulation of PBMCs and TILs. However, the elevation of IFN-γ and IL-17 production by TILs in response to PHA was significantly lower than PBMCs. In the presence of ISO, the IFN-γ/IL-4 ratio reduced in all groups, but this reduction was very low in TILs. Interestingly, the effects of PRO on cytokine production were, at least partially, comparable to those of ISO. Depressed levels of ß-2AR expression were demonstrated on CD4+IFN-γ+ and CD4+IL-17+ lymphocytes in patients' PBMCs and TILs. CONCLUSION: This study has demonstrated the effects of ISO and PRO on cytokine production by TILs and determined ß-2AR expression on these cells. ISO failed to induce a shift toward the expected Th2 cytokine profile in CRC patients' TILs, which might be due to the downregulation of ß-2AR expression on TILs. Additionally, in this study, PRO induced a shift to a Th2 profile in PBMCs.

Expression of costimulatory molecule CD80 in colonic dysplasia in ulcerative colitis: an immunosurveillance mechanism against colorectal cancer?

BACKGROUND AND AIMS: Ulcerative colitis is an established risk factor for colorectal cancer but dysplasia reports are much more frequent than invasive neoplasm diagnosis. The effective activation of T lymphocytes that provide antitumor surveillance requires the presence of costimulation molecules such as CD80 and CD86 on the surface of antigen-presenting cells. The aim of our study was to verify the presence of an in vivo immunosurveillance mechanism in the early stages of colon tumorigenesis. PATIENTS AND METHODS: Expression of CD80, CD86, and IFN-gamma in the colonic mucosa of 21 consecutive ulcerative colitis (UC) patients was quantified using reverse transcription polymerase chain reaction. After a 7-year follow-up period, we reviewed the histology of all surveillance colonoscopy specimens for colonic dysplasia. Correlation, frequency, and survival analyses were performed. RESULTS: CD80 was detectable in seven patients while expression of CD86 and IFN-gamma was evident in all patients. Histology confirmed the presence of dysplasia in eight patients. Patients who had dysplasia showed higher CD80 levels compared to those without dysplasia (p=0.02). Survival analysis demonstrated that cumulative dysplasia rates of CD80-positive patients were significantly higher than those of CD80-negative patients (p=0.04). CONCLUSION: Even if partially limited by a relatively small sample size, our study seems to show an association between CD80 expression and colonic dysplasia in UC patients that may suggest a role for CD80 in the immunosurveillance against colorectal cancer in this early stage of tumorigenesis. On the contrary, CD86 seems to be involved in the inflammatory pathogenesis of UC.

The role of costimulatory molecules CD80 and CD86 and IFNgamma in the pathogenesis of ulcerative colitis.

Several studies showed that costimulatory signals on antigen presenting cells are up-regulated in inflammatory bowel disease. We quantified the expression of CD80, CD86, and IFNgamma in colonic mucosa of patients affected by ulcerative colitis and correlated it with clinical and biochemical parameters to identify the context of this up regulation. We enrolled 21 patients affected by ulcerative colitis and 6 healthy subjects. We evaluated for each patient gender, age, duration of disease, clinical, endoscopic and histologic disease activity index, medical therapy, ESR, serum CRP, WBC, and serum al-acid glycoprotein. CD80, CD86, and IFNgamma expression in the colonic mucosa was quantified using reverse transcription polymerase chain reaction. Statistical analysis was performed using Mann-Whitney U test and Spearman's rank correlation test. Significance was set at P < 0.05. CD80 was detectable in seven patients, while CD86 and IFNgamma expression was evident in all UC patients. CD80 and CD86 were not detectable in control specimens. Colonic CD80 expression was correlated to the age of the patients. CD86 expression showed an inverse correlation with duration of disease and a direct correlation with serum CRP levels and histologic grade of disease activity. IFNgamma was not correlated with any of the examined parameter. Our study confirms a major role in ulcerative colitis pathogenesis for CD86 which correlates with histologic grade of disease and with serum CRP levels, and its upregulation seems to be higher at the beginning of the disease. In "in vivo" conditions IFNgamma may not be the only factor responsible for CD86 up-regulation in the ulcerative colitis colonic mucosa.