Effect of otilonium bromide on contractile patterns in the human sigmoid colon.

BACKGROUND: The mechanism of action of the spasmolytic compound otilonium bromide (OB) on human colonic motility is not understood. The aim of our study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon. METHODS: Circular sigmoid strips were studied in organ baths. Isolated smooth muscle cells from human sigmoid colon were examined using the calcium imaging technique. KEY RESULTS: Otilonium bromide inhibited by 85% spontaneous non-neural rhythmic phasic contractions (RPCs), (IC(50) = 49.9 nmol L(-1)) and stretch-induced tone (IC(50) = 10.7 nmol L(-1)) with maximum effects at micromolar range. OB also inhibited by 50% both on- (IC(50) = 38.0 nmol L(-1)) and off-contractions induced by electrical stimulation of excitatory motor neurons. In contrast, the inhibitory latency period prior to off-contractions was unaffected by OB. OB inhibited acetylcholine-, substance P-, and neurokinin A-induced contractions. The L-type Ca(2+) channel agonist BayK8644 reversed the effects of OB on RPCs, on- and off-contractions. Hexamethonium, atropine, the NK(2) antagonist, or depletion of intracellular Ca(2+) stores by thapsigargin did not prevent the inhibitory effect of OB on RPCs and electrical contractions. KCl-induced calcium transients in isolated smooth muscle cells were also inhibited by OB (IC(50) = 0.2 micromol L(-1)). CONCLUSIONS & INFERENCES: Otilonium bromide strongly inhibited the main patterns of human sigmoid motility in vitro by blocking calcium influx through L-type calcium channels on smooth muscle cells. This pharmacological profile may mediate the clinically observed effects of the drug in patients with irritable bowel syndrome.

Preoperative radio-chemotherapy (RT-CT) in rectal cancer. Prospective study with postoperative RT-CT control group.

INTRODUCTION: Between 1996 and 2000, the colorectal tumour committee of the Hospital Universitario de Bellvitge and the Institut Català d'Oncologia, Hospitalet, carried out a non-randomised prospective study of pre-op radio-chemotherapy (RT-CT) in locally advanced rectal tumours. We herein present the results. On the other hand, and at the same time, patients operated on for locally advanced rectal cancer were admitted and treated by RT-CT during the postoperative process, according to our standard protocol. Results for both series are compared. MATERIAL AND METHODS: The preoperative RT-CT group included 94 patients. They received radiotherapy (RT), 45 Gy on posterior pelvis, and simultaneously, 5-fluorouracil (5FU) by continuous infusion (300 mg/m2/day, 5 days weekly during RT). Surgical intervention was scheduled 6-8 weeks after preoperative treatment; after surgery they received 5FU (425 mg/m2/day) and leucovorin (20 mg/m2/day) bolus, 5 days weekly; 4 cycles at four-week intervals. 237 patients who had been previously operated on and who had been staged as T3-T4 and/or N+, M0 were admitted to our centre during the same time period and received postoperative RT-CT. RESULTS: The preoperative treatment group showed a complete and global response rate to RT-CT in 17% and 68% of cases, respectively. Anal sphincter was preserved in 38.5% of patients exhibiting low rectal tumours (inferior limit of tumour at 6 cm or less from the anal margin). Overall and disease-free survival at 5 years was distinct, showing statistical significance, according to the response obtained through preop treatment; it was better in responsive patients (overall survival: 87% in complete remissions, 75% in partial remissions, 48% in stable disease, and mean survival was 0.84 years for patients who evolved, p<0.05; disease-free survival was: 93% in complete remission, 76% partial remission, 39% in stable disease, p=0.001). We did not see any difference with regard to overall survival, disease-free survival or local control at the time of comparing either pre- or postoperative groups. There were, however, differences with regard to late toxicity; they showed less toxicity when RT-CT was administered preoperatively; no case of radiation enteritis that required surgery was seen in this group, whereas in the postoperative RT-CT it was 4.2%, p=0.022. CONCLUSIONS: Preoperative treatment of locally advanced rectal cancer is recommended, for it yields a high level of response to treatment; it allows preservation surgery of the anal sphincter in one third of patients showing low rectal tumours. There is also a clear diminution of late toxicity with pre-op treatment. On the other hand, response to pre-op treatment selects patients with a better prognosis.

Preoperative radio-chemotherapy (RT-CT) in rectal cancer. Prospective study with postoperative RT-CT control group

INTRODUCTION: Between 1996 and 2000, the colorectal tumour committee of the Hospital Universitario de Bellvitge and the Institut Català d'Oncologia, Hospitalet, carried out a non-randomised prospective study of pre-op radio-chemotherapy (RT-CT) in locally advanced rectal tumours. We herein present the results. On the other hand, and at the same time, patients operated on for locally advanced rectal cancer were admitted and treated by RT-CT during the postoperative process, according to our standard protocol. Results for both series are compared. MATERIAL AND METHODS: The preoperative RT-CT group included 94 patients. They received radiotherapy (RT), 45 Gy on posterior pelvis, and simultaneously, 5-fluorouracil (5FU) by continuous infusion (300 mg/m2/day, 5 days weekly during RT). Surgical intervention was scheduled 6-8 weeks after preoperative treatment; after surgery they received 5FU (425 mg/m2/day) and leucovorin (20 mg/m2/day) bolus, 5 days weekly; 4 cycles at four-week intervals. 237 patients who had been previously operated on and who had been staged as T3-T4 and/or N+, M0 were admitted to our centre during the same time period and received postoperative RT-CT. RESULTS: The preoperative treatment group showed a complete and global response rate to RT-CT in 17% and 68% of cases, respectively. Anal sphincter was preserved in 38.5% of patients exhibiting low rectal tumours (inferior limit of tumour at 6 cm or less from the anal margin). Overall and disease-free survival at 5 years was distinct, showing statistical significance, according to the response obtained through preop treatment; it was better in responsive patients (overall survival: 87% in complete remissions, 75% in partial remissions, 48% in stable disease, and mean survival was 0.84 years for patients who evolved, p<0.05; disease-free survival was: 93% in complete remission, 76% partial remission, 39% in stable disease, p=0.001). We did not see any difference with regard to overall survival, disease-free survival or local control at the time of comparing either pre- or postoperative groups. There were, however, differences with regard to late toxicity; they showed less toxicity when RT-CT was administered preoperatively; no case of radiation enteritis that required surgery was seen in this group, whereas in the postoperative RT-CT it was 4.2%, p=0.022. CONCLUSIONS: Preoperative treatment of locally advanced rectal cancer is recommended, for it yields a high level of response to treatment; it allows preservation surgery of the anal sphincter in one third of patients showing low rectal tumours. There is also a clear diminution of late toxicity with pre-op treatment. On the other hand, response to pre-op treatment selects patients with a better prognosis (AU)

[Current status of follow-up of the upper digestive tract in familial adenomatous polyposis]. / Estado actual del seguimiento del área gastroduodenal en la poliposis adenomatosa familiar.

Familiar adenomatous polyposis (FAP) is a hereditary disease characterized by the development of multiple adenomatous polyps in the gastrointestinal tract and colorectal cancer in practically all patients who do not receive appropriate treatment. Although the most commonly involved region in this disease is the colorectal area, it is well known that adenomas can also develop in the upper gastrointestinal tract, mainly in the periampullary area of the duodenum. Because of the possibility of malignant transformation of these polyps, adequate monitoring is required, even though the optimal follow-up schedule has not yet been defined. In the present article, we report a case of a gastric adenocarcinoma detected during the follow-up of a patient diagnosed with FAP, as well as a review of the literature on this subject. We stress the need for early detection and appropriate management of this disease. Sufficient information is available to support the use of upper gastrointestinal endoscopy with lateral vision and serial biopsies of the periampullary region in these patients. The first endoscopy in patients with FAP should be performed at the age of 20 years or at diagnosis. Subsequently, a follow-up schedule should be designed, according to the number and histological characteristics of the polyps observed.

Estado actual del seguimiento del área gastroduodenal en la poliposis adenomatosa familiar / Current status of follow-up of the upper digestive tract in familial adenomatous polyposis

La poliposis adenomatosa familiar (PAF) es una enfermedad hereditaria que se caracteriza por el desarrollo de numerosos pólipos adenomatosos gastrointestinales y de cáncer colorrectal en prácticamente el 100% de los pacientes que no reciben un tratamiento adecuado. A pesar de que esta enfermedad tiene como órgano diana fundamental el área colorrectal, es bien conocida la frecuente aparición de adenomas en el tracto digestivo superior, fundamentalmente en el área duodenal periampular. La posibilidad de malignización de estos pólipos hace imperativa la planificación de pautas de seguimiento y tratamiento adecuadas, aunque todavía hoy no se conoce cuál debería ser el calendario de seguimiento. En este trabajo presentamos un caso de adenocarcinoma gástrico en el seguimiento de una paciente afectada de PAF, se revisa la literatura médica y se hace hincapié en la necesidad de detectar y planificar el tratamiento de esta enfermedad. Existe suficiente información para considerar que el seguimiento debería realizarse mediante endoscopia digestiva alta con visión lateral, incluidas biopsias seriadas del área periampular. La primera endoscopia en pacientes con PAF debería realizarse a la edad de 20 años o al inicio de la enfermedad, y programar posteriormente un calendario de seguimiento en función del número y las características histológicas de las lesiones detectadas

Familiar adenomatous polyposis (FAP) is a hereditary disease characterized by the development of multiple adenomatous polyps in the gastrointestinal tract and colorectal cancer in practically all patients who do not receive appropriate treatment. Although the most commonly involved region in this disease is the colorectal area, it is well known that adenomas can also develop in the upper gastrointestinal tract, mainly in the periampullary area of the duodenum. Because of the possibility of malignant transformation of these polyps, adequate monitoring is required, even though the optimal follow-up schedule has not yet been defined. In the present article, we report a case of a gastric adenocarcinoma detected during the follow-up of a patient diagnosed with FAP, as well as a review of the literature on this subject. We stress the need for early detection and appropriate management of this disease. Sufficient information is available to support the use of upper gastrointestinal endoscopy with lateral vision and serial biopsies of the periampullary region in these patients. The first endoscopy in patients with FAP should be performed at the age of 20 years or at diagnosis. Subsequently, a follow-up schedule should be designed, according to the number and histological characteristics of the polyps observed

Estado actual del seguimiento del área gastroduodenal en la poliposis adenomatosa familiar / Current status of follow-up of the upper digestive tract in familial adenomatous polyposis

La poliposis adenomatosa familiar (PAF) es una enfermedad hereditaria que se caracteriza por el desarrollo de numerosos pólipos adenomatosos gastrointestinales y de cáncer colorrectal en prácticamente el 100% de los pacientes que no reciben un tratamiento adecuado. A pesar de que esta enfermedad tiene como órgano diana fundamental el área colorrectal, es bien conocida la frecuente aparición de adenomas en el tracto digestivo superior, fundamentalmente en el área duodenal periampular. La posibilidad de malignización de estos pólipos hace imperativa la planificación de pautas de seguimiento y tratamiento adecuadas, aunque todavía hoy no se conoce cuál debería ser el calendario de seguimiento. En este trabajo presentamos un caso de adenocarcinoma gástrico en el seguimiento de una paciente afectada de PAF, se revisa la literatura médica y se hace hincapié en la necesidad de detectar y planificar el tratamiento de esta enfermedad. Existe suficiente información para considerar que el seguimiento debería realizarse mediante endoscopia digestiva alta con visión lateral, incluidas biopsias seriadas del área periampular. La primera endoscopia en pacientes con PAF debería realizarse a la edad de 20 años o al inicio de la enfermedad, y programar posteriormente un calendario de seguimiento en función del número y las características histológicas de las lesiones detectadas

Familiar adenomatous polyposis (FAP) is a hereditary disease characterized by the development of multiple adenomatous polyps in the gastrointestinal tract and colorectal cancer in practically all patients who do not receive appropriate treatment. Although the most commonly involved region in this disease is the colorectal area, it is well known that adenomas can also develop in the upper gastrointestinal tract, mainly in the periampullary area of the duodenum. Because of the possibility of malignant transformation of these polyps, adequate monitoring is required, even though the optimal follow-up schedule has not yet been defined. In the present article, we report a case of a gastric adenocarcinoma detected during the follow-up of a patient diagnosed with FAP, as well as a review of the literature on this subject. We stress the need for early detection and appropriate management of this disease. Sufficient information is available to support the use of upper gastrointestinal endoscopy with lateral vision and serial biopsies of the periampullary region in these patients. The first endoscopy in patients with FAP should be performed at the age of 20 years or at diagnosis. Subsequently, a follow-up schedule should be designed, according to the number and histological characteristics of the polyps observed

Response to neoadjuvant therapy for rectal cancer: influence on long-term results.

OBJECTIVE: Pre-operative treatment with chemoradiotherapy (CRT) seems to improve local control and overall survival in patients with rectal cancer. The aims of the study were to analyse the impact on overall, disease free and cancer related survival of tumour response to pre-operative CRT and to analyse the influence of the degree of response on long-terms results. PATIENTS AND METHODS: Patients with a locally advanced rectal cancer, treated by pre-operative CRT were studied. A radical resection of the rectal tumour with mesorectal excision was performed within 6-8 weeks. Judged on the final TNM classification patients were considered responders when the tumour showed histologically a complete response, microscopic residual disease or a partial response. Non-responders were those in whom the extent of disease remained stable or progressed. Results Radical excision was performed in 103 patients, and a palliative resection in five. Forty-three patients underwent abdominoperineal resection and 65 anterior resection of the rectum. Seventy-one (65.7%) patients showed a response to CRT, while 37 (34.3%) did not. The overall local and distant recurrence rates were 6.8% and 21.3%. Tumour recurrence (P < 0.008) and disease free survival (P < 0.007) were significantly different in responders and nonresponders. Of the 71 responders, 16 had a pathological complete response, 27 had persisting microscopic disease and 28 had macroscopic residual disease. No differences in cancer specific outcome were observed in these groups. CONCLUSION: Pathological response to pre-operative CRT is associated with improved tumour recurrence and disease-free survival rates. Any response to pre-operative CRT appears to improve outcomes as much as a complete response.

Long-term urinary dysfunction after rectal cancer surgery.

OBJECTIVE: Urinary dysfunction is a well-known complication of rectal surgery, secondary to injury to the autonomic nervous plexus. The object of this study was to evaluate the incidence, prevalence and type of micturition disorders following rectal cancer surgery and their reversibility during long-term follow-up. PATIENTS AND METHODS: A prospective study of 45 patients who underwent surgery for rectal cancer between 1993 and 1998 was undertaken. Those with pre-operative urinary dysfunction were excluded after sequential uroflowmetry and clinical interview. Ten of the surgical interventions were high anterior resections, 18 low anterior resections, and 17 abdominoperineal amputations. Pre-operative radiotherapy was performed in 47.9% of patients. All patients underwent sequential uroflowmetry and a clinical interview 3 and 12 months after the intervention. Subjects who presented micturition disorders underwent urodynamic examination The follow up period was three years. RESULTS: Three months after surgery alterations were found in 14 (31.3%) patients; the most frequent were stress incontinence, urinary tenesmus and the urge to urinate. At the 12-month assessment only 6 (13.3%) patients had urinary symptomatology or uroflowmetry abnormalities. After three years, micturition disorders persisted in 3 (6.6%) patients. CONCLUSION: Urinary dysfunction after rectal cancer excision is associated with a high degree of reversibility. Seventy-eight percent of the alterations detected after three months and 50% of those that persisted after a year disappeared during follow up.

Immunodulation with tacrolimus (FK506): results of a prospective, open-label, non-controlled trial in patients with inflammatory bowel disease.

UNLABELLED: Tacrolimus (FK506) is widely used in the organ transplant setting, but not in the treatment of IBD. OBJECTIVE: the aim of this study was to analyse the effectiveness of tacrolimus in specific clinical presentations of inflammatory bowel disease (IBD) in which recurrence is likely. PATIENTS AND METHODS: inclusion criteria were: perianal Crohn's disease (PCD), CD in rectal stump, pouchitis and cuffitis with severely impaired function of the ileoanal pouch (IPAA), and proven refractoriness to other therapies. Clinical assessment: Hughes' classification (PCD); Oresland index (OI) in IPAA, endoscopy-biopsy and Quality of life (QoL) using the Spanish version of the IBDQ. Response was determined as complete (CP), partial (PR) or non-existent (NR). Tacrolimus was administered orally at a dose of 0.1 mg/kg/day (levels 5-15 .g/L). RESULTS: nineteen patients entered the study. Mean duration of treatment was 9.6 +/- 6.3 months. In PCD, CR was reported in 66% of cases and PR in 33%, with disappearance of inflammation, stenosis and ulcers. In patients with pouchitis and cuffitis,77% presented either CR or PR. The OI scores and QoL improved significantly after treatment (p<0.006 and p<0.002, respectively). Adverse effects were minor and controlled by regulating the dose. CONCLUSION: oral administration of tacrolimus is easy to per-form and has few adverse effects when used to treat IBD in certain clinical presentations with a high likelihood of recurrence.

Randomized clinical study of Gastrografin administration in patients with adhesive small bowel obstruction.

BACKGROUND: Oral Gastrografin has been used to differentiate partial from complete small bowel obstruction (SBO). It may have a therapeutic effect and predict the need for early surgery in adhesive SBO. The aim of this study was to determine whether contrast examination in the management of SBO allows an early oral intake and reduces hospital stay. METHODS: Eighty-three patients admitted between February 2000 and November 2001 with 90 episodes of symptoms and signs suggestive of postoperative adhesive SBO were randomized into two groups, a control group and Gastrografin group. Patients in the control group were treated conservatively. If symptoms of strangulation developed or the obstruction did not resolve spontaneously after 4-5 days, a laparotomy was performed. Patients in the Gastrografin group received 100 ml Gastrografin. Those in whom the contrast medium reached the colon in 24 h were considered to have partial SBO, and were fed orally. If Gastrografin failed to reach the colon and the patient did not improve in the following 24 h a laparotomy was performed. RESULTS: Conservative treatment was successful in 77 episodes (85.6 per cent) and 13 (14.4 per cent) required operation. Among patients treated conservatively, hospital stay was shorter in the Gastrografin group (P < 0.001). All patients in whom contrast medium reached the colon tolerated an early oral diet. Gastrografin did not reduce the need for operation (P = 1.000). No patient died in either group. CONCLUSION: Oral Gastrografin helps in the management of patients with adhesive SBO and allows a shorter hospital stay.

Acute colonic diverticulitis in patients under 50 years of age.

BACKGROUND: There is ongoing controversy concerning the virulence and management of diverticulitis in young patients. This study reports on the management of acute diverticulitis with reference to the virulence and outcome of the disease with respect to age. METHODS: Between January 1994 and June 1999, 327 patients were treated for acute left colonic diverticulitis. Patients were divided in two groups: those aged 50 years or less (group 1, 72 patients) and those older than 50 years (group 2, 255 patients). The diagnosis was confirmed histologically or radiologically in all patients. RESULTS: There were differences in gender distribution related to age (P < 0.001). During the first hospital stay, 226 patients (69.1 per cent) had successful conservative treatment, 78 (23.9 per cent) needed emergency surgery and 23 (7.0 per cent) had a semielective operation (P = 0.47). The recurrence rate was 25.5 per cent in group 1 and 22.3 per cent in group 2 (P = 0.93). The type of surgical procedure and grade of peritonitis in emergency patients were similar in the two groups. Overall the mortality rate in patients who underwent an operation was 16.3 per cent. The mortality rate was zero in group 1 and 2.2 per cent in group 2 after elective or semielective operation (P = 1.0), and zero in group 1 and 34.9 per cent in group 2 after emergency operation (P < 0.001). CONCLUSION: Diverticulitis in young patients does not have a particularly aggressive course and the risk of recurrence is similar to that of older patients.

Cáncer colorrectal. ¿Qué factores pueden ser determinantes en su curación o recidiva? / Colorectal cancer. Which factors determine cure or relapse?

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Resección de metástasis hepáticas de carcinoma colorrectal. Índice de resecabilidad y supervivencia a largo plazo / Resection of colorectal liver metastases. Resectability rate and long term survival

Introducción. Para obtener los mejores resultados posibles, el tratamiento de las metástasis hepáticas de carcinoma colorrectal debe ser multidisciplinario. Sin embargo, las posibilidades de curación o supervivencia a largo plazo se basan en la resección completa de toda la enfermedad tumoral detectable en el estudio de extensión, que debe ser lo más preciso posible para evitar laparotomías innecesarias. Objetivos. Establecer la eficacia de nuestro estudio de extensión a través del índice de resecabilidad y conocer cuáles son nuestros resultados en cuanto a supervivencia a largo plazo. Pacientes y métodos. Desde enero de 1991 hasta diciembre de 2000 practicamos 273 hepatectomías por metástasis de carcinoma colorrectal en 250 pacientes. Ni el número, ni el tamaño de las metástasis, ni la invasión locorregional fueron considerados criterios de exclusión. El único criterio utilizado para indicar la intervención fue la presunción preoperatoria de que la exéresis sería completa y macroscópicamente curativa. Resultados. El índice de resecabilidad fue del 91,3 por ciento (273 de 299 casos) y la mortalidad postoperatoria del 3,3 por ciento. En 37 casos se practicó cirugía simultánea del tumor primario, en 23 se llevó a cabo una segunda resección hepática y en 18 pacientes se realizó una resección pulmonar por metástasis pulmonares. En 106 pacientes (55 por ciento) se instauró quimioterapia adyuvante. La supervivencia actuarial a los 1, 3 y 5 años fue del 87, 57 y 36 por ciento, respectivamente. En el análisis multivariante, la presencia de cuatro o más metástasis y el margen de resección invadido fueron los únicos factores predictivos de mala evolución. La quimioterapia adyuvante mejoró significativamente la supervivencia. Conclusiones. La resección de las metástasis hepáticas puede realizarse con una baja mortalidad operatoria y obtiene buenos resultados en cuanto a supervivencia. Con el método de estudio preoperatorio que aplicamos, es posible obtener un alto índice de resecabilidad. La indicación quirúrgica agresiva, el seguimiento sistemático, el rescate quirúrgico con intención curativa de recidivas y la quimioterapia adyuvante comportan una supervivencia a largo plazo del 36 por ciento (AU)

Resección y anastomosis primaria en pacientes con peritonitis por enfermedad del colon izquierdo / Resection and primary anastomosis in patients with peritonitis secondary to left-sided colonic disease

Introducción. Clásicamente, la presencia de un cuadro de peritonitis aguda localizada y sobre todo difusa se consideró una contraindicación para la anastomosis primaria en cirugía de colon urgente. El objetivo de este trabajo es definir qué lugar ocupa la cirugía en un tiempo (resección y anastomosis primaria tras lavado intraoperatorio de colon) en casos de peritonitis aguda localizada y difusa por enfermedad del colon izquierdo. Pacientes y método. Desde enero de 1994 hasta junio de 1999 fueron intervenidos de forma urgente 139 pacientes con peritonitis aguda por enfermedad del colon izquierdo. De éstos, 66 (47,5 por ciento) (41 con peritonitis localizada y 25 con peritonitis difusa) fueron tratados con resección, lavado intraoperatorio de colon y anastomosis primaria. Se analizaron los resultados con esta técnica, así como las diferencias entre los grupos con peritonitis localizada y difusa. Resultados. La incidencia de dehiscencia anastomótica fue del 3 por ciento (2 pacientes) y la morbilidad global fue del 42,4 por ciento, siendo la infección de herida quirúrgica la complicación más frecuente. La mortalidad fue del 3,1 por ciento (2 pacientes). No hubo diferencias estadísticamente significativas entre los resultados de los enfermos con peritonitis localizada y difusa. Conclusiones. La cirugía en un tiempo constituye un tratamiento seguro y eficaz en la terapia de pacientes con peritonitis purulenta localizada y difusa por enfermedad del colon izquierdo si se realiza una buena selección de los casos (AU)

Role of resection and primary anastomosis of the left colon in the presence of peritonitis.

BACKGROUND: Classically a primary colonic anastomosis is not performed in the presence of left colonic peritonitis. Recently there has been a trend towards resection and anastomosis in selected patients, but no prospective study concerning the safety of this approach has been published. The objective of this study was to define the role of intraoperative colonic lavage with resection and primary anastomosis (RPA) in left colonic peritonitis, and to evaluate the differences in outcome in patients with diffuse or localized peritonitis. METHODS: Between January 1994 and December 1998, 127 patients underwent emergency operation for a distal large bowel perforation. RPA was the operation of choice and was performed in 61 patients, 38 with localized and 23 with diffuse peritonitis. Septic shock, faecal peritonitis, immunocompromised status and American society of Anesthesiologists grade IV were contraindications to the one-stage procedure. Alternative operations used in high-risk patients were Hartmann's procedure in 55 patients, subtotal colectomy in eight and colostomy in three. RESULTS: There were two deaths (3 per cent) among 61 patients treated by RPA and one (2 per cent) case of clinical anastomotic dehiscence. Overall morbidity was 39 per cent and the overall mean(s.d.) hospital stay was 18(15) days. No statistical differences were observed between patients with localized and diffuse peritonitis treated by RPA. CONCLUSION: RPA may be the operation of choice in selected patients with left colonic diffuse peritonitis.

Standardized approach for microsatellite instability detection in colorectal carcinomas.

BACKGROUND: Ubiquitous mutations in microsatellite DNA sequences define a specific type of genetic instability, termed microsatellite instability (MSI). Various approaches have been used to identify the presence and degree of MSI. To define standard diagnostic criteria for MSI, we developed and tested a mathematical model. METHODS: We designed an algorithm for the efficient characterization of MSI and used it to analyze data on six microsatellite markers in colorectal carcinoma and normal tissues from 415 patients. Theoretical models considering one, two, or three populations were tested against the data collected. RESULTS: The observed frequencies of MSI in our series of samples best fit a two-population model, stable and unstable, defined by instability in two or more of four to six markers analyzed. MSI was observed in 7.5% of the tumors. The misclassification rate was less than 5% when any four loci were analyzed and less than 1% when the six markers were used. A stepwise strategy, consisting first of a bulk screening of two loci and then a second screening of two to four additional markers, provided excellent sensitivity (>/=97%) and specificity (100%). Tumors with MSI had distinctive genetic and clinicopathologic features, including better patient survival. CONCLUSION: To assess the presence of MSI in colorectal cancer, we have developed a simple, sensitive, and specific approach based on the apparent good fit of the data to a two-population model. Its application to a prospective series of patients with colorectal carcinomas demonstrates that the presence of MSI characterizes a subset of less aggressive tumors.

Factors related to the presence of IgA class antineutrophil cytoplasmic antibodies in ulcerative colitis.

OBJECTIVES: Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. METHODS: Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. RESULTS: The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. CONCLUSIONS: A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa.

Plasma and mucosal fatty acid pattern in colectomized ulcerative colitis patients.

Patients with inflammatory bowel disease (IBD) have increased plasma n3 polyunsaturated fatty acids (PUFAs), which in ulcerative colitis (UC) patients persists six months after colectomy, suggesting a primary abnormality in fatty acid (FA) metabolism in IBD. This finding needed to be confirmed in a larger series of UC long-term colectomized patients. We aimed to assess the plasma FA pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA) and the mucosal FA pattern in the ileal reservoir of the UC-IPAA patients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30 controls. In 26 UC-IPAA (8 with pouchitis and 18 without pouchitis) and in 13 healthy controls gut mucosal FAs were also investigated. FAs were detected by capillary column gas-liquid chromatography. Increased levels of saturated fatty acids (SFAs) and decreased percentages of monounsaturated fatty acids (MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. The mucosal FA pattern of the ileal reservoir consisted of increased long-chain PUFAs, specially n6 PUFA, and a decrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were also seen. The plasma FA profile previously described in IBD is not observed long-term after colectomy in UC, suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAs and decreased percentages of MUFAs might represent early events in disturbed FA metabolism in IBD. The changes in FAs of the ileal reservoir, which closely resemble those found in human and experimental IBD, probably represent a common pattern of intestinal inflammation.

Double-barreled wet colostomy: a safe and simple method after pelvic exenteration.

UNLABELLED: The clinical and functional outcome of ureteric division to the distal segment of a loop colostomy: the double-barrelled wet colostomy have been analysed. METHODS: 13 patients (8 female and 5 male, age 37 to 72 years) underwent pelvic exenteration with double-barrelled wet colostomy. The primary tumour included endometrial (n = 6), rectal (n = 1), anal (n = 1), cervical (n = 2), prostatic (n = 1) and bladder (n = 2). Indications for pelvic exenteration were locally advanced disease, recurrence and severe radiation or surgical damage. Six patients had pre-existing colostomy, and three had a Bricker ureteroileal diversion. The double-barrelled-wet colostomy technique consisted in anastomosing both ureters to a colon segment 25 cm distal to the loop colostomy. There was no operative mortality. Complications included one urinary leak which closed with conservative management and one case of recurrent episodes of pyelonephritis which finally required nephrectomy. Intravenous urography in the remaining patients showed good flow through the ureters to the conduit with no reflux. Postoperative plasma electrolytes, urea and creatinine were normal from day seven onwards. Urodynamic studies in four patients showed efficient contraction of the colon conduit with pressure levels similar to those in the colon proximal to the colostomy. In five cases biopsies of the conduit were taken at 3 and 16 months; no dysplasias were found. Four patients died due to disease progression. The overall mean survival was 41.2 months. The remainder are currently disease-free, maximum followup period being 19 months. Double-barrelled wet colostomy is a safe and simple technique with low morbidity. The patient needs to carry only one stoma and functional results are good.