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1.
Tech Coloproctol ; 22(4): 305-311, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29603042

RESUMEN

Rectovaginal fistulae (RVF) are not uncommonly seen by the colorectal surgeon and gynaecologist, often debilitating for patients and typically managed with multiple operative procedures, achieving control rather than cure. Transvaginal repair is the least common surgical approach but has clear advantages and equivalent healing rates to other approaches. Here, we describe a simple, safe and effective flapless transvaginal technique for the repair of primary and recurrent low- and mid-level RVF of varying aetiology. We report 15 cases of RVF (nine recurrent) treated by this technique at a single UK centre. The healing rate was 67%. There were no major complications. Median follow-up was 48 months.


Asunto(s)
Fístula Rectovaginal/cirugía , Vagina/cirugía , Adulto , Anciano , Cirugía Colorrectal , Femenino , Humanos , Persona de Mediana Edad , Cirujanos , Resultado del Tratamiento , Reino Unido
2.
Tech Coloproctol ; 22(7): 545-551, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30022331

RESUMEN

BACKGROUND: Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection. METHODS: Participants were randomised to receive bilateral (50 + 50 units) or unilateral (100 units) Dysport® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores. RESULTS: Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year. CONCLUSIONS: Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.


Asunto(s)
Inhibidores de la Liberación de Acetilcolina/administración & dosificación , Toxinas Botulínicas Tipo A/administración & dosificación , Fisura Anal/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal , Enfermedad Crónica , Femenino , Humanos , Inyecciones/efectos adversos , Inyecciones/métodos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/etiología , Resultado del Tratamiento , Adulto Joven
3.
Colorectal Dis ; 14(10): 1224-30, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22251617

RESUMEN

AIM: Accurate and reliable imaging of pelvic floor dynamics is important for tailoring treatment in pelvic floor disorders; however, two imaging modalities are available. Barium proctography (BaP) is widely used, but involves a significant radiation dose. Magnetic resonance (MR) proctography allows visualization of all pelvic midline structures but patients are supine. This project investigates whether there are measurable differences between BaP and MR proctography. Patient preference for the tests was also investigated. METHODS: Consecutive patients referred for BaP were invited to participate (National Research Ethics Service approved). Participants underwent BaP in Poole and MR proctography in Dorchester. Proctograms were reported by a consultant radiologist with pelvic floor subspecialization. RESULTS: A total of 71 patients were recruited. Both tests were carried out on 42 patients. Complete rectal emptying was observed in 29% (12/42) on BaP and in 2% (1/42) on MR proctography. Anismus was reported in 29% (12/42) on BaP and 43% (18/42) on MR proctography. MR proctography missed 31% (11/35) of rectal intussusception detected on BaP. In 10 of these cases no rectal evacuation was achieved during MR proctography. The measure of agreement between grade of rectal intussusception was fair (κ=0.260) although MR proctography tended to underestimate the grade. Rectoceles were extremely common but clinically relevant differences in size were evident. Patients reported that they found MR proctography less embarrassing but harder to empty their bowel. CONCLUSIONS: The results demonstrate that MR proctography under-reports pelvic floor abnormalities especially where there has been poor rectal evacuation.


Asunto(s)
Bario , Medios de Contraste , Defecografía/métodos , Imagen por Resonancia Magnética/métodos , Trastornos del Suelo Pélvico/diagnóstico , Recto/diagnóstico por imagen , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Intususcepción/diagnóstico , Intususcepción/etiología , Masculino , Persona de Mediana Edad , Prioridad del Paciente/estadística & datos numéricos , Trastornos del Suelo Pélvico/complicaciones , Enfermedades del Recto/diagnóstico , Enfermedades del Recto/etiología , Rectocele/diagnóstico , Rectocele/etiología , Recto/fisiopatología , Método Simple Ciego , Encuestas y Cuestionarios
5.
J Clin Pathol ; 47(8): 709-10, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7962621

RESUMEN

AIMS: To explore the association between duodenal adenoma and carcinoma in patients with familial adenomatous polyposis (FAP). METHODS: A multicentre survey of 1262 patients with FAP yielded 47 cases of duodenal cancer. The association between adenoma and cancer was assessed in these cases. RESULTS: Adenomatous tissue was found within duodenal cancer in 29 of 44 (66%) patients with FAP and in mucosa adjacent to duodenal cancer in 31 of 42 (73%) such patients. Adenomas were found as a component of, or adjacent to, duodenal cancer in 38 of 45 (84%) patients. CONCLUSIONS: These observations support the existence of the adenomacarcinoma sequence in the duodenum of patients with FAP. Factors associated with malignant change included villous histology, moderate or severe dysplasia, and the presence of stage IV duodenal polyposis.


Asunto(s)
Adenoma/patología , Poliposis Adenomatosa del Colon/patología , Carcinoma/patología , Neoplasias Duodenales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
6.
Ann R Coll Surg Engl ; 77(5): 372-6, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7486766

RESUMEN

Attempts at improving outcome from colorectal cancer have recently focused on prevention. This paper describes how both surgical and chemotherapeutic intervention can cause a fall in cell proliferation, polyp regression and a decline in rectal cancer risk in patients with familial adenomatous polyposis. Other patients at high risk of colorectal cancer, or of cancers in other sites, may also have their risks modified by pharmacological intervention.


Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Antiinflamatorios no Esteroideos/uso terapéutico , Neoplasias Colorrectales/prevención & control , Antiinflamatorios no Esteroideos/farmacología , División Celular , Colon/cirugía , Humanos
7.
J R Soc Med ; 87(11): 704-6, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7837198

RESUMEN

Familial adenomatous polyposis (FAP) is characterized by the presence of premalignant adenomas of the large and small bowel. Prophylactic colectomy deals with the risk for colon cancer, leaving duodenal cancer as the leading cause of death. Although most FAP patients have duodenal adenomas, only approximately 5% develop duodenal cancer. This study looks at progression of duodenal polyps with time. The outcome of endoscopic surveillance in the duodenum of 70 patients with familial adenomatous polyposis was determined. A mean of 40 months elapsed between endoscopies. Outcome was measured using video comparison and a staging system that includes histological assessment. Duodenal cancer developed in one patient, and was suspected in two others. The stage of duodenal polyposis worsened in another seven patients. When histology was ignored, comparison of video recordings in 52 patients showed a worsening in 21 (40%). In conclusion, further surveillance appears warranted so that patients at high risk for duodenal cancer might receive early treatment. Should slow progression of duodenal polyposis be shown to be associated with low risk, then most patients can be safely offered less frequent endoscopies than hitherto.


Asunto(s)
Poliposis Adenomatosa del Colon/complicaciones , Neoplasias Duodenales/etiología , Pólipos Adenomatosos/etiología , Pólipos Adenomatosos/patología , Adulto , Anciano , Progresión de la Enfermedad , Neoplasias Duodenales/patología , Duodenoscopía , Femenino , Estudios de Seguimiento , Humanos , Pólipos Intestinales/etiología , Pólipos Intestinales/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Grabación de Cinta de Video
9.
Ann R Coll Surg Engl ; 93(6): 451-9, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21929915

RESUMEN

INTRODUCTION: Conventional abdominoperineal excision for low rectal cancer has a higher local recurrence and reduced survival compared to anterior resection. An extralevator abdominoperineal excision (ELAPE) may improve outcome through removal of increased tissue in the distal rectum. Experience with ELAPE is limited and no studies have reported on quality of life (QOL) following this procedure. We describe a minimally invasive approach to ELAPE within an enhanced recovery programme, and present short-term results and QOL analyses. METHODS: All laparoscopic ELAPEs were included in a prospective database. Demographics, intra-operative and post-operative outcomes were evaluated. Postoperative QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-CR29. RESULTS: Thirteen laparoscopic ELAPEs were performed over a two-year period. All were enrolled in an enhanced recovery programme. The median age was 76. The median tumour height was 20 mm (range: 0-50 mm) from the dentate line and all patients received neoadjuvant treatment. The median duration of surgery was 300 minutes (range: 120-488 minutes), the mean blood loss was 150 ml and one procedure was converted to open surgery. There was no circumferential resection margin involvement or tumour perforation. The median duration of use of intravenous fluid, patient controlled analgesia and urinary catheterisation was 2, 2 and 2.5 days respectively and the median length of hospital stay was 7.5 days. Two patients developed perineal wound dehiscence. QOL analysis revealed high global health status (90.8), physical (91.3), emotional (98.3) and social functioning (100) scores, which compared favourably with EORTC reference values and published QOL scores following conventional abdominoperineal excision. CONCLUSIONS: Laparoscopic ELAPE within an enhanced recovery setting is a feasible and safe approach with acceptable short-term outcomes and post-operative quality of life.


Asunto(s)
Pared Abdominal/cirugía , Adenocarcinoma/cirugía , Laparoscopía/métodos , Perineo/cirugía , Calidad de Vida , Neoplasias del Recto/cirugía , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Disección/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
10.
Dis Colon Rectum ; 45(1): 121-2, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11786776

RESUMEN

PURPOSE: This article describes the use of intrarectal formalin to treat intractable rectal bleeding from pelvic malignancy. METHODS: Case reports of two patients with intractable rectal bleeding from pelvic malignancy are described. RESULTS: In both cases, treatment with intrarectal formalin stopped the rectal bleeding. CONCLUSION: Formalin instillation into the rectum is an invaluable technique when one is faced with rectal hemorrhage from inoperable pelvic tumors.


Asunto(s)
Desinfectantes/administración & dosificación , Formaldehído/administración & dosificación , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Neoplasias Pélvicas/complicaciones , Enfermedades del Recto/tratamiento farmacológico , Enfermedades del Recto/etiología , Administración Rectal , Anciano , Desinfectantes/uso terapéutico , Formaldehído/uso terapéutico , Humanos , Instilación de Medicamentos , Masculino
11.
Br J Surg ; 79(11): 1204-6, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1334761

RESUMEN

The risk of rectal cancer in 224 patients with familial adenomatous polyposis with an ileorectal anastomosis has been estimated by life-table analysis. Until the age of 50 years the cumulative risk is reasonably low at 10 per cent (95 per cent confidence interval 4.5-16 per cent), increasing sharply to 29 per cent (95 per cent confidence interval 18-40 per cent) by the age of 60 years. This means that surveillance of the retained rectum in older patients must either be improved or they should undergo restorative proctocolectomy in earlier middle age.


Asunto(s)
Poliposis Adenomatosa del Colon/complicaciones , Íleon/cirugía , Neoplasias del Recto/etiología , Recto/cirugía , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Factores de Edad , Anciano , Anastomosis Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proctocolectomía Restauradora , Factores de Riesgo
12.
Dis Colon Rectum ; 36(11): 1059-62, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8223060

RESUMEN

PURPOSE: Despite the introduction of screening, surveillance, and prophylactic colectomy surgery, patients with familial adenomatous polyposis (FAP) are at risk of dying from other malignancies. METHODS: In order to quantify this risk and identify the causes of mortality, a retrospective life table analysis was performed on 222 patients with familial adenomatous polyposis who had undergone a total colectomy and ileorectal anastomosis between 1948 and 1990. These FAP patients were compared with an age- and sex-matched group of the general population and a relative risk of dying was calculated. RESULTS: Of 222 patients, 53 have died. In a matched group of the general population the expected number of deaths would be 15.8. The relative risk of dying is therefore 3.35. There has been no significant improvement with time and the relative risk is greatest for female patients. CONCLUSION: The three main causes of mortality are upper gastrointestinal malignancy, desmoid disease, and perioperative complications. Further research should therefore be aimed at prevention and improved treatment of these in order to improve survival.


Asunto(s)
Poliposis Adenomatosa del Colon/mortalidad , Colectomía/mortalidad , Esperanza de Vida , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Factores de Edad , Anciano , Anastomosis Quirúrgica/mortalidad , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Humanos , Íleon/cirugía , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Tasa de Supervivencia
13.
Dis Colon Rectum ; 39(6): 659-62, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8646953

RESUMEN

BACKGROUND: Recent work has demonstrated a correlation between frequency of aspirin ingestion and colorectal cancer prevention. Sulindac, another nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause polyp regression and a fall in cell proliferation in patients with familial adenomatous polyposis, who are destined to develop colorectal cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determined, although a prostaglandin-mediated mechanism seems likely. METHODS: Rectal or duodenal biopsies from 20 patients with familial adenomatous polyposis, who had been randomized to sulindac or placebo, were analyzed for prostaglandin (PG) E2 and F2 alpha levels before and after treatment. RESULTS: A significant fall in prostaglandin E2 and F2 alpha levels was seen in patients who were on sulindac; this correlated with a visual improvement in number and size of polyps in the same patients (P = 0.0096; PGE2, P = 0.036; PGF2 alpha, Spearman's rank correlation). CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may prevent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neovascularization, or via a mutagenic effect.


Asunto(s)
Poliposis Adenomatosa del Colon/tratamiento farmacológico , Poliposis Adenomatosa del Colon/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Dinoprost/metabolismo , Dinoprostona/metabolismo , Sulindac/uso terapéutico , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/inmunología , Biopsia , Dinoprost/inmunología , Dinoprostona/inmunología , Humanos , Inducción de Remisión
14.
Gut ; 35(12): 1718-20, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7829008

RESUMEN

Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby protect against colorectal cancer. Cell turnover is increased in ulcerative proctocolitis, which might therefore respond to vitamin D3 metabolites. This study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis. Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M). After 15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest, and CCPR was determined by linear regression analysis of accumulated metaphases. Compared with values in 17 controls with incidental anal conditions, median rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80 (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22) cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition.


Asunto(s)
Calcitriol/análogos & derivados , Colitis Ulcerosa/tratamiento farmacológico , Neoplasias Colorrectales/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Calcitriol/uso terapéutico , División Celular/efectos de los fármacos , Depresión Química , Epitelio/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Cultivo de Órganos
15.
Gut ; 34(9): 1269-70, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8406166

RESUMEN

The first case of a patient with familial adenomatous polyposis (FAP) who developed pancreatitis after routine screening and biopsy of the ampulla of Vater is described.


Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Ampolla Hepatopancreática/cirugía , Biopsia/efectos adversos , Enfermedad Iatrogénica , Pancreatitis/etiología , Enfermedad Aguda , Anciano , Duodenoscopía , Femenino , Humanos , Instrumentos Quirúrgicos
16.
Dis Colon Rectum ; 42(12): 1569-74, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10613475

RESUMEN

BACKGROUND: Patients with stomas face many difficulties both physical and psychological. Little is known about the long-term problems and the impact on patient lifestyle of a permanent stoma. This study was designed to address the problems faced by patients with stomas. METHODS: Patients were identified from the Stoma Care Department records for the years 1985 to 1992 and were contacted by mail. A questionnaire was designed to assess postoperative care, quality of life issues, and equipment problems. Responses were recorded on either a visual analog scale, a choice of yes-or-no alternatives, or by selection from a list of responses. RESULTS: A total of 542 eligible patients were contacted, and 391 replies were received. Major stomal problems included rashes (51 percent), leakage (36 percent), and ballooning (90 percent of patients with ileostomy). The majority of patients experienced some change in lifestyle (80 percent), and more than 40 percent of patients had problems with their sex lives. CONCLUSION: Many patients cope extremely well with a stoma; however, some patients experience considerable difficulty and distress. Improved preoperative assessment and counseling with longer follow-up by the stoma department would be helpful in the management of these patients and probably would contribute to improvement in the quality of their lives.


Asunto(s)
Colostomía/psicología , Ileostomía/psicología , Calidad de Vida , Adaptación Psicológica , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/efectos adversos , Actitud Frente a la Salud , Colostomía/efectos adversos , Colostomía/instrumentación , Consejo , Exantema/etiología , Femenino , Estudios de Seguimiento , Humanos , Ileostomía/efectos adversos , Ileostomía/instrumentación , Estilo de Vida , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Conducta Sexual , Encuestas y Cuestionarios
17.
Cancer Detect Prev ; 18(4): 253-8, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7982235

RESUMEN

Patients with familial adenomatous polyposis (FAP) are at high risk for duodenal tumors, the distribution of which suggests that bile is important in their development. Studies of the bile of FAP patients suggest that it contains an excess of active carcinogens. Defective hepatic metabolism of carcinogens might account for these findings. The isozyme glutathione S-transferase mu (GST-mu) plays a major role in the hepatic metabolism of carcinogens. Peripheral blood GST-mu status reflects hepatic GST-mu status. The concentration of GST-mu was therefore measured by enzyme-linked immunosorbent assay of heparinized peripheral blood samples taken from 31 unrelated patients with FAP and from 38 unrelated control patients. FAP and control patients were matched for age, sex, diet, and smoking status. The median GST-mu concentration (micrograms per milliliter) was 0.5 (interquartile range, 0 to 11.6) in the FAP group and 8.85 (0.9 to 29.4, p = 0.0013) in the control group. Of the 31 FAP patients, ten had no detectable GST-mu activity compared with only one of the 38 controls (p = 0.002), while 71% of FAP patients had GST-mu concentrations less than a supplied positive control, compared with 50% of control patients (p = 0.064). Abnormal hepatic metabolism of carcinogens by GST-mu might contribute to the development of intestinal tumors in patients with FAP.


Asunto(s)
Poliposis Adenomatosa del Colon/enzimología , Glutatión Transferasa/análisis , Isoenzimas/análisis , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo
18.
Gastroenterology ; 105(3): 698-700, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8395444

RESUMEN

BACKGROUND: Solitary juvenile polyps are considered benign. In contrast, juvenile polyposis is associated with malignancy and poor long-term outcome. Recent reports suggest that solitary juvenile polyps may also undergo both adenomatous and malignant change. The long-term outcome of patients with solitary juvenile polyps is unknown. Patients are treated conservatively and discharged from follow-up. The present study was designed to examine the incidence of cancer and mortality of these patients, comparing their life expectancy with that of the general population. METHODS: The outcome of 82 patients with a solitary juvenile polyp between 1958 and 1982 was examined by life table analysis. Patients were traced through the Office of Population Censuses and Surveys for death and cancer registration. Patients were compared with an age- and sex-matched group of the general population. RESULTS: The relative risk of dying for patients who have previously had a solitary juvenile polyp in comparison with the general population was found to be 0.66 (95% confidence interval, 0.34-1.14). There was only one case of colorectal cancer. CONCLUSIONS: Patients with a solitary juvenile polyp are not at increased risk of dying of or developing colorectal cancer and do not require further follow-up or investigations.


Asunto(s)
Adenocarcinoma/epidemiología , Poliposis Adenomatosa del Colon/diagnóstico , Neoplasias Colorrectales/epidemiología , Pólipos Intestinales/epidemiología , Adenocarcinoma/etiología , Adenocarcinoma/patología , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/patología , Adolescente , Adulto , Anciano , Transformación Celular Neoplásica/patología , Niño , Preescolar , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/patología , Femenino , Humanos , Incidencia , Pólipos Intestinales/etiología , Pólipos Intestinales/patología , Tablas de Vida , Masculino , Persona de Mediana Edad , Factores de Riesgo
19.
Carcinogenesis ; 14(6): 1107-10, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8389670

RESUMEN

Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal adenomas and carcinomas. The distribution of these neoplasms resembles mucosal exposure to bile, suggesting that bile may play a role in adenoma development. Our previous results, using DNA adducts detected by 32P-postlabelling as an index of genotoxicity, have supported this hypothesis. We found significantly higher adduct labelling in the duodenum of FAP patients than in the duodenum of control patients and significantly higher labelling in the small bowel of rats gavaged with FAP bile than in rats given control bile. We have now investigated the ability of human bile to form adducts with DNA in vitro. Bile obtained from the gallbladder of 18 FAP patients immediately before colectomy, and from 18 control patients, was incubated with salmon sperm DNA in solution at 37 degrees C for 1 h, after which the purified DNA was analysed for DNA adducts, using the nuclease P1 method of 32P-postlabelling. Relative adduct labelling values (RAL, adducts per 10(9) nucleotides) produced by FAP bile samples were significantly higher than RAL values produced by control bile samples (medians 197 versus 86, P = 0.0016, Mann-Whitney test). We found a consistent pattern of adduct labelling, varying in intensity between samples. Adduct spots were eluted from TLC plates and analyzed by reverse-phase HPLC. Each major spot gave several peaks that were consistent between bile samples from different patients and were similar in FAP and control bile. These results indicate that bile from FAP and control patients contains similar, directly acting genotoxic compounds but that levels are higher in FAP than in control patients. This suggests that bile from FAP patients is more genotoxic than bile from control patients. Incubation of bile with free-radical scavengers and deconjugating enzymes failed to influence adduct labelling in this system.


Asunto(s)
Poliposis Adenomatosa del Colon/genética , Bilis/metabolismo , ADN/metabolismo , Autorradiografía , Cromatografía Líquida de Alta Presión , Vesícula Biliar/metabolismo , Humanos , Técnicas In Vitro , Radioisótopos de Fósforo
20.
Br J Surg ; 80(12): 1618-9, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8298943

RESUMEN

Twenty-four patients with familial adenomatous polyposis who had previously undergone prophylactic colectomy and had advanced duodenal polyposis were entered into a randomized trial to assess the effect of the non-steroidal anti-inflammatory drug sulindac on duodenal and rectal polyps. Polyp size and number were assessed by videotaped duodenoscopy (and rectoscopy in 14 patients) at entry and after 6 months of treatment; the tapes were compared by two assessors who were unaware of the randomization and the shuffled chronological order of the recordings. Mucosal cell proliferation was measured by in vitro incorporation of 5-bromo-2'-deoxyuridine. Sulindac therapy was associated with a reduction in epithelial cell proliferation in the duodenum (median labelling index (LI) 15.8 versus 14.4 per cent, P = 0.003) and a trend towards duodenal polyp regression (P = 0.12). In the rectum, cell proliferation showed a marked reduction (median LI 8.5 versus 7.4 per cent, P = 0.018), and significant (P = 0.01) polyp regression was seen. Rectal polyposis was less severe than that in the duodenum and responded more dramatically. Sulindac is a possible treatment for patients in whom rectal polyps have failed to show significant regression after ileorectal anastomosis and who are unsuitable for pouch surgery; it may be useful in early duodenal polyposis or as an adjunct after duodenal clearance.


Asunto(s)
Poliposis Adenomatosa del Colon/tratamiento farmacológico , Neoplasias Duodenales/tratamiento farmacológico , Pólipos Intestinales/tratamiento farmacológico , Sulindac/uso terapéutico , Poliposis Adenomatosa del Colon/patología , Adulto , Anciano , División Celular/efectos de los fármacos , Método Doble Ciego , Duodeno/patología , Femenino , Humanos , Mucosa Intestinal/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/tratamiento farmacológico , Recto/patología
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