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.

[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.

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.

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.

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.

[Options in the surgical treatment of diffuse cavernous hemangioma of the rectum]. / Opciones en el tratamiento quirúrgico del hemangioma cavernoso difuso de recto.

Cavernous haemangioma of the rectum is an unusual hamartomatous malformation. Patients usually present with painless massive rectal bleeding that generally begins at an early age and frequently surgery is necessary. To avoid abdominoperineal resection of the rectum in these patients, a procedure of colo-anal sleeve anastomosis, that includes a large rectal mucosectomy, has been described. However, in our opinion, if affectation of other pelvic organs can been excluded by MRI, it is easier to do a conservative proctectomy with colo-anal anastomosis. We present a case in a seventeen years old patient.

Antineutrophil cytoplasmic antibodies in sera from colectomised ulcerative colitis patients and its relation to the presence of pouchitis.

BACKGROUND: Few studies have evaluated the influence of colectomy on antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis (UC). In small series of patients it has been suggested that ANCA positivity in UC might be predictive for development of pouchitis after colectomy. AIMS: To assess the prevalence of ANCA in UC patients treated by colectomy and a Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA), and the relation between the presence of ANCA, the type of surgery, and the presence of pouchitis. SUBJECTS: 63 UC patients treated by colectomy (32 with UC-BI and 31 with UC-IPAA), 54 UC, and 24 controls. METHODS: Samples were obtained at least two years after colectomy. ANCA were detected by indirect immunofluorescent assay. RESULTS: There were no differences between patients with (36.3%) or without pouchitis (35.0%) and between patients with UC (55%), UC-BI (40.6%), and UC-IPAA (35.4%). However, ANCA prevalence significantly decreases in the whole group of operated patients (38.0%) compared with non-operated UC (p = 0.044). CONCLUSIONS: The prevalence of ANCA in operated patients was significantly lower than in non-operated UC, suggesting that it might be related either to the presence of inflamed or diseased tissue. ANCA persistence is not related to the surgical procedure and it should not be used as a marker for predicting the development of pouchitis.

Multicentre study of a continent colostomy plug.

A multicentre clinical study was carried out to assess the performance of a new disposable device, the Conseal 1-Piece, for colostomy control and continence. Forty-three patients were studied; none had any complication at the stoma. The time elapsed since surgery and the condition of the stoma and surrounding skin were recorded. The new product was compared with the patients' usual colostomy bag, studying the following parameters: ease of application, reliability, leakage, confidence, ease of removal, adhesion and comfort. Thirty-seven patients completed the study. No complications arose, and complete faecal continence was obtained with 71.1 per cent of applications. The plug was kept in position for a mean of 11.5 h and a normal stoma bag was used for the remainder of the day. Of the 37 patients who completed the trial, 26 preferred the Conseal 1-Piece to a colostomy bag. In this preliminary study the device was easy to apply, involved no major complications and provided a high degree of continence. This product deserves further study because of its simplicity of use. However, research to improve the level of continence should continue.