Reservoritis secundaria a infección por citomegalovirus: reporte de caso y revisión de la literatura / Pouchitis secondary to cytomegalovirus infection: Case report and literature review

Resumen La proctocolectomía total con reservorio ileal es el procedimiento quirúrgico de elección para la colitis ulcerativa refractaria (CUR) al tratamiento médico y la reservoritis es la complicación más frecuente y puede afectar hasta al 50% de los pacientes en los primeros 5 años del procedimiento. Aunque la etiología no está bien establecida, su presentación podría estar relacionada con disbiosis como resultado de la estasis fecal en individuos genéticamente susceptibles y con una respuesta inmunitaria alterada. Los síntomas típicos de reservoritis como diarrea, dolor abdominal, tenesmo, urgencia, incontinencia fecal y, menos frecuentemente, sangrado rectal no son específicos y el diagnóstico debe confirmarse mediante una evaluación endoscópica e histológica. La infección por citomegalovirus es infrecuente como causa de reservoritis; sin embargo, debe considerarse en pacientes con reservoritis refractaria al manejo antibiótico inicial. Las pruebas diagnósticas incluyen pruebas serológicas como la medición de anticuerpos, antigenemia y proteína C-reactiva (PCR) en sangre. El tratamiento de elección es el ganciclovir, medicamento de administración endovenosa que puede inducir complicaciones graves como mielosupresión, neutropenia y trombocitopenia. Se recomienda el seguimiento endoscópico posterior al tratamiento para asegurar la cicatrización mucosa, especialmente cuando hay sospecha de enfermedad de Crohn o compromiso del asa aferente en la endoscopia inicial.

Abstract Total proctocolectomy with ileal pouch is the surgical procedure of choice for ulcerative colitis refractory to medical treatment, and pouchitis is the most frequent complication. It can affect up to 50% of patients in the first five years of the procedure. Although the etiology is not well established, its manifestation could be related to dysbiosis resulting from fecal stasis in genetically susceptible individuals with altered immune responses. Typical symptoms of pouchitis, such as diarrhea, abdominal pain, tenesmus, urgency, fecal incontinence, and, less commonly, rectal bleeding, are nonspecific, and the diagnosis must be confirmed by endoscopic and histologic examination. Cytomegalovirus infection is an infrequent cause of pouchitis; however, it should be considered in patients with pouchitis refractory to initial antibiotic management. Diagnostic tests include serological tests such as the measurement of antibodies, antigenemia, and C-reactive protein (CRP) in blood. The treatment of choice is ganciclovir, an intravenous drug that can induce severe complications such as myelosuppression, neutropenia, and thrombocytopenia. Post-treatment endoscopic follow-up is recommended to ensure mucosal healing, especially when there is suspicion of Crohn's disease or involvement of the afferent loop on initial endoscopy.

Reservoritis, una complicación del tratamiento quirúrgico de la colitis ulcerativa. Diagnóstico y tratamiento. Revisión / Pouchitis, a complication associated with the surgical treatment of ulcerative colitis. Diagnosis and treatment. Review

Resumen Del 20% al 30% de los pacientes con colitis ulcerativa (CU) son sometidos a cirugía, ya sea por intratabilidad, curso fulminante, aparición de displasia o cáncer de colon. La cirugía de elección es la proctocolectomía con reservorio ileoanal. Sin embargo, el 20%-50% de los pacientes presentan reservoritis a 10 años. El diagnóstico se realiza con base en las manifestaciones clínicas, las alteraciones endoscópicas y la histología. Los medicamentos utilizados en el tratamiento de la CU no son tan eficaces en la reservoritis y el tratamiento de primera línea es los antibióticos. Dependiendo de la respuesta inicial y el curso clínico de la entidad, se elegirá el tratamiento posterior. En esta revisión se discuten los aspectos más importantes con respecto a la epidemiología, diagnóstico, patogénesis y tratamiento de la reservoritis.

Abstract Between 20% and 30% of patients with ulcerative colitis (UC) undergo surgery because it is not treatable or because it is associated with a fulminant course, dysplasia, or colon cancer. The surgery of choice is proctocolectomy with ileal-anal pouch. However, 20%-50% of patients present with pouchitis 10 years after surgery. The diagnosis is made based on clinical manifestations, endoscopic alterations, and histology. The drugs used in the treatment of UC are not as effective in pouchitis and the first-line treatment is antibiotics administration. Depending on the initial response and clinical course of the condition, subsequent treatment will be chosen. This review discusses the most important aspects of the epidemiology, diagnosis, pathogenesis, and treatment of pouchitis.

Abordagem diagnóstica e de manuseio da pouchite em doença inflamatória intestinal / Diagnostic and management approach to pouchitis in inflammatory bowel disease

ABSTRACT In patients with ulcerative colitis refractory to medical therapy, total proctocolectomy and posterior ileal-anal pouch anastomosis is the standard surgical therapy. One of the possible complications is pouchitis. Depending on the duration of the symptoms, it can be classified as acute, recurrent, or chronic. The latter, according to the response to therapy, can be defined as antibiotic-dependent or refractory. The treatment of pouchitis is based on the use of antibiotics and probiotics. Thiopurine and biological therapy have been suggested in patients with refractory pouchitis. Special care should be taken in the endoscopic surveillance of these patients, especially if they present risk factors such as dysplasia or previous colorectal cancer, primary sclerosing cholangitis or ulcerative colitis for more than 10 years.

RESUMO Em pacientes com colite ulcerativa refratária à terapia médica, a proctocolectomia total e anastomose de bolsa ileal-anal posterior é a terapia cirúrgica padrão. Uma das possíveis complicações é a pouchite. Dependendo da duração dos sintomas, pode ser classificado como aguda, recorrente ou crônica. Esta última, de acordo com a resposta à terapia, pode ser definida como dependente de antibióticos ou refratária a eles. O tratamento da pouchite baseia-se no uso de antibióticos e probióticos. A thiopurina e a terapia biológica têm sido sugeridas em pacientes com pouchite refratária. Um cuidado especial deve ser tomado na vigilância endoscópica desses pacientes, especialmente se apresentarem fatores de risco, como displasia ou câncer colorretal anterior, colangite esclerosante primária ou colite ulcerativa por mais de 10 anos.

Reservoritis/pouchitis: fisiopatología y manejo basado en la evidencia / Reservoirs/pouchitis: physiopathology and evidence-based management

Pouchitis is a frequent complication following proctocolectomy with ileal pouch-anal anastomosis, mainly in patients with ulcerative colitis. Though etiology is still unknown, evidence shows that there is a relation with host microbiota. Management of chronic refractory pouchitis is challenging, and current evidence showns that the use of biologic agents may have a favourable response.

La reservoritis es una complicación frecuente en pacientes en quienes se ha practicado una proctocolectomía con reservorio ileal, principalmente en pacientes con colitis ulcerosa. La etiología si bien es desconocida, la evidencia actual apunta a que exista una relación con la microbiota del huésped. La reservoritis refractaria crónica es un desafio en el manejo y actualmente ha surgido evidencia que apunta que el uso de biológicos puede tener una respuesta favorable.

Role of intestinal flora imbalance in pathogenesis of pouchitis

Objective To discuss the role of intestinal flora imbalance in the pathogenesis of pouchitis. Methods The pouchitis rat model was established and the faeces sample and the mucous membrane sample were collected regularly, in which the bacterial nucleic acids were extracted for quantitative analysis of the intestinal flora in the samples through using the real-time quantitative PCR technique and high energy sequencing technology. Results The disorder phenomenon of the intestinal flora appeared at the 7th day of the experiment, and the pouchitis was presented at the 21st day of the experiment. At the 31st day of the experiment, compared to control group and non-pouchitis group, the quantity of Bifidobacterium and the Lactobacillus of the pouchitis model rats in the mucous membrane sample and the faeces sample were significantly decreased (P < 0.05), and the Bacteroidetes, Faecalibacterium prausnitzii and XIV Clostridium leptum subgroup in the mucous membrane of pouchitis were significantly decreased (P < 0.05). The IV Clostridium coccoides group was the main flora in the mucous membrane of pouchitis, the bacterial diversity of non-pouchitis group and control group was significantly higher than that of the pouchitis group (P < 0.05). Conclusions The intestinal flora imbalance is one of the factors that cause the incidence of the pouchitis; this study provides a clue of the pathogenesis and treatment direction of the intestinal inflammatory disease.

Role of intestinal flora imbalance in pathogenesis of pouchitis

OBJECTIVE@#To discuss the role of intestinal flora imbalance in the pathogenesis of pouchitis.@*METHODS@#The pouchitis rat model was established and the faeces sample and the mucous membrane sample were collected regularly, in which the bacterial nucleic acids were extracted for quantitative analysis of the intestinal flora in the samples through using the real-time quantitative PCR technique and high energy sequencing technology.@*RESULTS@#The disorder phenomenon of the intestinal flora appeared at the 7th day of the experiment, and the pouchitis was presented at the 21st day of the experiment. At the 31st day of the experiment, compared to control group and non-pouchitis group, the quantity of Bifidobacterium and the Lactobacillus of the pouchitis model rats in the mucous membrane sample and the faeces sample were significantly decreased (P < 0.05), and the Bacteroidetes, Faecalibacterium prausnitzii and XIV Clostridium leptum subgroup in the mucous membrane of pouchitis were significantly decreased (P < 0.05). The IV Clostridium coccoides group was the main flora in the mucous membrane of pouchitis, the bacterial diversity of non-pouchitis group and control group was significantly higher than that of the pouchitis group (P < 0.05).@*CONCLUSIONS@#The intestinal flora imbalance is one of the factors that cause the incidence of the pouchitis; this study provides a clue of the pathogenesis and treatment direction of the intestinal inflammatory disease.

Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis

OBJECTIVE: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications. METHODS: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n = 20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n = 14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n = 7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p = 0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p>0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p = 0.05). CONCLUSIONS: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy.

Recovery from Recurrence of Post-operative Pouchitis Due to Ulcerative Colitis through Daitokato / 日本東洋医学雑誌

Pouchitis is the most common complication following ileal pouch-anal anastomosis in patients with ulcerative colitis and is strongly correlated with the risk of pouch failure and malignant mucosal transformation in the pouch. Here we report a case treated successfully with the Kampo decoction, daitokato. A 41-year-old male treated with ileal pouch-anal anastomosis due to severe ulcerative colitis suffered from repeated pouchitis and stenosis of the ileal pouch post-operatively. He complained of general fatigue, chills, continuous lower abdominal pain and discomfort, and severe pain with evacuation. Initial treatment with antibiotics and painkillers was ineffective, so the patient came to our hospital's Kampo clinic, where he was initially prescribed the decoction, shokenchuto. This proved ineffective at resolving his fatigue. Subsequent treatment with ogikenchuto improved physical strength but was ineffective for pouchitis. Antibiotic resistant pouchitis occurred afterwards and we attempted treatment with saikokeishito decoction and the extracts, hochuekkito and juzentaihoto, which similarly improved fatigue but not pouchitis. Following administration of daitokato, instances of pouchitis were reduced with no recurrence 6 months post-treatment. This case illustrates the therapeutic efficacy of daitokato in improving ileal pouch disorders resistant to treatment with Western medicine.

Processo inflamatório em mucosa de reservatórios ileais de doentes assintomáticos / Inflammatory activity of pelvic ileal pouches mucosa in asymptomatic patients

A inflamação inespecífica do reservatório ileal (RI) após retocolectomia total é a complicação pós-operatória mais comum nos doentes operados por retocolite ulcerativa inespecífica (RCUI). Os mecanismos imunológicos envolvidos na etiologia não são totalmente conhecidos. OBJETIVO: Avaliar a ativação de STAT-1 e a expressão da citocina INF-gama em mucosa de RI endoscópica e histologicamente normal, de doentes operados por RCUI e PAF, assintomáticos. CASUISTICA E MÉTODOS: Estudou-se 18 doentes submetidos à retocolectomia total com RI em (J), sendo nove com RCUI e nove com polipose adenomatosa familiar (PAF). Realizou-se biópsias da mucosa dos RI e de íleo terminal. As expressões de INF-gama e a ativação de STAT-1 foram avaliadas por meio de imunoblot de extrato protéico total. RESULTADOS: A ativação de STAT-1 foi maior em mucosa de RI de doentes operados por RCUI, quando comparada aos grupos PAF e Controle (p menor que 0.05). A expressão de INF-gama foi maior no grupo RCUI quando comparada ao grupo Controle (p menor que 0.05), mas não em relação ao grupo PAF (p maior que 0.05). CONCLUSÃO: Estes achados podem justificar a maior susceptibilidade dos doentes com RCUI à inflamação inespecífica do RI quando comparados aos portadores de PAF, sendo a principal via inflamatória similar à verificada na RCUI.

Pouchitis after total retocolectomy is the most common complication in ulcerative colitis (UC). The immunological mechanisms involved in the genesis of pouchitis are unclear. PURPOSE: To evaluate STAT-1 activation and IFN-gama expression in normal ileal pouch mucosa. METHODS: Eighteen asymptomatic patients submitted to total retocolectomy and J pouch, were evaluated, being nine with UC and nine with FAP. The activation of STAT-1 and expressions of the cytokine were determined by immunoblot of total protein extracts from pouch mucosal biopsies. RESULTS: STAT-1 activation was increased in UC, when compared to FAP and controls. Higher levels of IFN-gama expression were observed in UC when compared to control group, but was similar to FAP. CONCLUSIONS: These findings could explain a higher susceptibility to this inflammatory complication in UC when compared to FAP, which may be similar to UC disease.

Resultados funcionales a largo plazo luego de la coloproctectomía con reservorio ileal en pacientes con y sin complicaciones postoperatorias / Long term functional outcomes after ileoanal pouch in patients with and without postoperative complications

Introducción: La coloproctectomía con reservorio ileal es la opción quirúrgica de elección en pacientes con colitis ulcerosa (CU). Las complicaciones postoperatorias on frecuentes pero los resultados definitivos son considerados, en general, buenos. Objetivo: nuestro objetivo fue evaluar los resultados funcionales a largo plazo de una serie consecutiva de pacientes con pouch ileal (PI) y establecer su relación con las complicaciones postoperatorias. Pacientes y métodos: incluimos 144 pacientes categorizados en 2 grupos: I- pacientes sin complicaciones postoperatorias (n: 71); y II- pacientes con complicaciones postoperatorias (n: 73). Los pacientes fueron seguidos por un tiempo medio de 3,8 años (rango 1-15 años). Evaluamos: número de deposiciones, capacidad de discriminación entre gases y materiafecal, inhibición voluntaria de la defecación, requerimiento de medicación antidiarreica y grado de incontinencia. Resultados: los resultados funcionales fueron similares entre los dos grupos con respecto al número de deposiciones, a la necesidad de tomar antidiarreicos, a la discriminación anal y a la inhibición voluntaria de la defecación por más de 5 hs. Se observó una mayor tendencia a presentar escapes en los pacientes con complicaciones (34%) respecto de aquellos sin ellas (20%; p<0.08 NS). Comparado con el grupo II, los escapes en el grupo I estaban significativamente relacionados con el incumplimiento de la dieta (p<0.01). La infección pélvica fue la complicación más frecuente en los pacientes con incontinencia (56%). Conclusiones: nuestro estudio demostró que la mayoría de los parámetros funcionales a largo plazo no son influenciados por la ocurrencia de complicaciones postoperatorias, con excepción de una tendencia a la incontinencia, más frecuentemente asociada con la infección pélvica.

Background: the proctocolectomy with ileal pouch (IP) has become the gold standard for surgical treatment for ulcerative colitis (UC). The postoperative complications are frequent but the definitive outcome is acceptable. Aim: our aim was to evaluate the long term functional outcome in a series of consecutive patients with IP and o establish its relation with postoperative complications. Patients and methods: we included 144 patients categorized in two groups: I- patients without postoperative complications (n: 71); II- patients with postoperative complications (n: 73). Patients were followed for a median time of 3.8 years (range 1-15). We evaluated: stool frequency, anal discrimination between gas and stool, voluntary evacuation inhibition, requirement of antidiarrheal medications and presence of incontinence. Results: the functional outcome was similar between the two groups in terms of stool frequency, medication use, anal discrimination and the voluntary inhibition of evacuation for more than 5 hours. A trend to present seepage was seen in patients with complications (34%) more than in those without them (20%; p<0.08 NS). Compared with group II, seepage in group I was significantly related with dietary lapses (p<0.01). The most frequent complication in incontinent patients was pelvic sepsis (56%). Conclusions: our study showed that most of long-term functional parameters are not influenced by the presence of postoperative complications. However, a trend for incontinence seems to be related to postoperative complications, more frequently with pelvic sepsis.

Analysis of Pouchitis after Restorative Proctocolectomy / 대한소화기학회지

BACKGROUND/AIMS: Pouchitis is one of the most common and debilitating complications of a restorative proctocolectomy. We aimed to analyze the features of pouchitis after restorative proctocolecomy and to determine the risk factors related to its development. METHODS: A study was undertaken in 169 patients who underwent total proctocolectomy with ileal pouch-anal anastomosis between July 1989 and December 2003. Pouchitis was defined as change of bowel habit, change in stool consistency, hematochezia or abdominal pain, febrile sensation and/or low-grade fever improved by metronidazole or ciprofloxacin without evidence of infectious disease and sphincter damage. RESULTS: Among the 169 patients, patients with ulcerative colitis were 64, familial and attenuated adenomatous polyposis 44, Crohn's disease 2, and synchronous or hereditary non-polyposis colorectal cancer were 59 cases. Overall, pouchitis occurred in 15.9% of the patients. The incidence was 37.5% in ulcerative colitis, 1% in non-ulcerative colitis, and 50% in Crohn's disease. In ulcerative colitis group, most of the pouchitis (60.9%) occurred within 6 months after the operation and the remainder experienced the first attack within 1 year after operation. Three patients progressed to chronic pouchitis. There was no association between pouchitis rate and sex, history of smoking, steroid use, temporary ileostomy construction, involvement of appendix or proximal colon, and evidence of indeterminate colitis. Only age was significantly related to the occurrence of pouchitis. CONCLUSIONS: Pouchitis developed exclusively in ulcerative colitis than other disease groups. Pouchitis occurred most frequently within 6 months after the operation, therefore, it is important to investigate carefully during one year after the operation in patients with ulcerative colitis.

Experiencias clinicoquirúrgicas con 51 bolsas ileales / Clinical and surgical experiences with 51 ileal bags

Antecedentes. La proctocolectomía total con reconstrucción con bolsa ileal (BI) se ha convertido en la cirugía para pacientes con colitis ulcerativa (CU) y las diferentes formas de síndromes polipósicos (SP). Propósito. Informar los resultados de ocho años de experiencia con la proctocolectomía total por enfermedad inflamatoria intestinal y SP y la reconstrucción con bolsa ileal. Métodos. Se evaluaron en forma prospectiva 51 pacientes sometidos a BI desde 1994 al 2002. El diagnóstico histopatológico preoperatorio fue CU (n=39), síndromes de poliposis múltiple (n=10), dos enfermos con Crohn y una resección masiva de colon por cáncer. Se obtuvo información referente a los aspectos demográficos, tipo y duración de la enfermedad, cirugías previas e indicación de la cirugía. Se registraron las complicaciones tempranas (30 días después de la cirugía) y las tardías. El seguimiento incluye la funcionalidad de la bolsa al año, el examen físico, y las biopsias de la bolsa y la zona de transición cuando ésta estaba indicada. Resultados. Los 51 pacientes (24 mujeres) tuvieron un seguimiento promedio de 44,5 meses (rango de 12 a 108 meses), el diagnóstico histopatológico se cambió en dos pacientes de CU a EC. La tasa de mortalidad global fue de 2% (un paciente), relacionada con sepsis perianal 45 meses después de realizarle la BI. La morbilidad global es de 65% (73 complicaciones en 33 pacientes; tempranas 39% y tardías en 49%), la estancia promedio fue de 8,9 días (rango de 6 a 25 días). Las complicaciones más frecuentes fueron las obstructivas en 36% (20% tempranas), sépticas en 22% (18% tempranas) y las reintervenciones en 26% (15% tempranas). La complicación tardía, más frecuente fue la "pouchitis" en 29,4%. La bolsa ileal se retiró en un paciente (2%) y en todos los demás es funcional. El índice de satisfacción fue de bueno-excelente en 82%, regular en 16% y malo en 2%. Conclusiones. La proctocolectomía total con reconstrucción con bolsa ileal es un procedimiento seguro, con baja mortalidad pero con una alta morbilidad. Aunque la morbilidad total es apreciable, los resultados funcionales son buenos y la satisfacción del paciente es aceptable.

Background: Restorative proctocolectomy and ileal pouch (IP) has become an established surgery for patients with chronic ulcerative colitis and poliposis syndromes. Purpose: The authors report the results of 8-year experience of restorative proctocolectomy and IP. Methods: Chart review was performed for 51 patients undergoing IP from 1994 through 2002. Preoperative histopathologic diagnoses were ulcerative colitis (n=39), poliposis syndromes (n=10), 2 Crohn disease and 1 patient with colorectal cancer and extended resection. Information was obtained regarding patient demographics, type and duration of diseases, previous operations, and indications for surgery. Early (within 30 days after surgery) and late complications were noted. Follow-up included an annual function, physical examination, and biopsies of the pouch and anal transitional zone when were indicated. Results: Of the 51 patients (24 women) with mean follow-up time of 44,5 months (range 12-108 months), histopathologic diagnoses of ulcerative colitis were changed for Crohn’s disease in 2 patients. The overall mortality rate was 2% (1 patient), one death was related to perineal sepsis 45 months after ileal pouch. The overall morbidity rate was 65% (73 complications in 33 patients; early 39%; late 49%) the mean hospitalary stancy was 8,9 days (range 6-25 days). Small bowel obstruction, septic complication and reoperation rates were 36%, 22% and 26%, respectively. The most frecuent late complication was "pouchitis" (31,8%). The ileal pouch was removed in 1 patient, and it is functional in 50 (98%). There was a satisfactory index with 82% with excelent-good results, and 16% and 2% with regular and bad results. Conclusions: Restorative proctocolectomy with an IP is a safe procedure, with low mortality and major morbidity rates. Although total morbidity rate is appreciable, functional results generally are good and patient satisfaction is acceptable.