RESUMEN
BACKGROUND: The major manifestation of familial adenomatous polyposis is colorectal adenomas, which, if untreated, lead to colorectal cancer. The impact of IPAA on quality of life in adolescents with familial adenomatous polyposis is favorable. There is a group of children who develop polyps at a younger age requiring earlier colectomy. Little is known about this very young subgroup in relation to bowel function or quality of life. OBJECTIVE: The aim of this study was to investigate the outcome in patients with familial adenomatous polyposis who had colectomy at ≤14 years. DESIGN: A cross-sectional quantitative survey was designed to assess outcome. Standardized validated instruments included bowel/psychosocial functioning and quality of life. RESULTS: Among 1337 patients with familial adenomatous polyposis from 409 kindreds, 4% (n = 59) of patients underwent colectomy at ≤14 years of age. Response rate was 84% (n = 32). The mean age at colectomy was 12 years (SD 2), with a current mean age of 24 years (SD 8.5). Fifty-seven percent of patients reported continence. Of the 43% reporting daytime or nighttime incontinence, the majority are <18 years (86%). Younger participants (currently less than 18 years of age) report more restrictions. Mental health is significantly lower among participants with incontinence. They report higher depression and anxiety symptoms, higher levels of intrusion and avoidance, and inferior mental health. The percentage of those worrying about risk of cancer is significantly higher in the younger group (71% vs 24%). Most patients (n = 24, 75%) have had surveillance endoscopy within the past 2 years. LIMITATIONS: This study is limited by study generalizability, selection bias, and small sample size. CONCLUSIONS: Twelve years after colectomy more than half of the patients have favorable bowel function. The rate of incontinence is high, especially among younger patients who have had a shorter time since surgery. Patients with incontinence reported lower psychosocial functioning, are very concerned about their cancer risk, and experience greater distress. This subgroup would benefit from added psychological interventions to enhance coping with familial adenomatous polyposis and surgery.
Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Colectomía/métodos , Calidad de Vida , Adolescente , Ansiedad/epidemiología , Distribución de Chi-Cuadrado , Niño , Estudios Transversales , Depresión/epidemiología , Incontinencia Fecal/epidemiología , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Recuperación de la Función , Autoimagen , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
AIMS: MYH is a DNA glycosylase in the base excision repair pathway. Germ-line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics. METHODS AND RESULTS: Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status (P = 0.0053). All biallelic cancers were low grade, with high-grade tumours more common in monoallelics and controls (P = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls (P = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups. CONCLUSIONS: Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study.
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Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , ADN Glicosilasas/genética , Poliposis Intestinal/enzimología , Poliposis Intestinal/patología , Adulto , Anciano , Sustitución de Aminoácidos/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Femenino , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Poliposis Intestinal/genética , Masculino , Persona de Mediana EdadRESUMEN
Vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of retinopathy of prematurity (ROP) and inhibition of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP. It is suggested that retinoids exert a highly potent antiangiogenic activity by inhibiting VEGF expression. The aim of this study was to demonstrate the preventive effect of retinoic acid (RA) on the VEGF-induced retinal neovascularization in a rat model of ROP. Wistar albino rats were placed into incubators at birth and exposed to an atmosphere alternating between 50 % and 10 % O(2) every 24 hours. After 14 days, the animals were removed to room air and received either an intraperitoneal injection of RA (5 mg/kg/day) (n=9) or saline (n=4) daily for six days, and sacrificed at 21 days. Other rats (n=4) were raised in room air and served as age-matched controls. The globe of each eye was cut through the cornea and embedded in paraffin. Serial sections were stained with hematoxylin-eosin for quantification of neovascular nuclei. The avidin-biotin peroxidase method was performed for evaluation of VEGF expression. The average number of neovascular nuclei was significantly lower in the control group compared to that in the ROP groups. In addition, it significantly decreased in the RA-treated ROP group compared to that of the saline-administrated ROP group. VEGF immunostaining was overall negative in room air-exposed rats. The VEGF immunostaining score significantly decreased in the RA-treated ROP group compared to that in the saline-administered ROP group. RA treatment might be beneficial in preventing neovascularization resulting from oxygen-induced retinopathy by downregulation of VEGF expression.
Asunto(s)
Neovascularización Retiniana/prevención & control , Retinopatía de la Prematuridad/tratamiento farmacológico , Tretinoina/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Humanos , Recién Nacido , Ratas , Ratas Wistar , Retina/efectos de los fármacos , Retina/patología , Retina/fisiopatología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Retinopatía de la Prematuridad/metabolismo , Retinopatía de la Prematuridad/patologíaRESUMEN
A 67 year old man with a clinical diagnosis of attenuated familial adenomatous polyposis (AFAP) and a past history of synchronous colon cancers in the transverse colon was also found to have an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. In addition, several foci of heterotopic gastric oxyntic mucosa were noted in the duodenum, interspersed with flat and polypoid adenomas. The duodenal adenomas showed low grade dysplasia, loss of adenomatous polyposis coli (APC) protein expression, but retention of beta catenin staining, localised to the nucleus and cytoplasm. The IPMN in the pancreas showed an identical immunohistochemical profile to the duodenal adenomas. The heterotopic gastric foci in the duodenum were negative for the APC protein, and beta catenin staining was membranous in location. Although the patient did not show germline truncating APC mutations or mutations in the MYH gene, the past history, clinical features, and immunohistochemical profile of the various lesions suggest strongly that the IPMN is part of the spectrum of lesions encountered in AFAP. Whether the heterotopic oxyntic gastric mucosa in the duodenum is also related is unclear, but it may represent a forme fruste of fundic gland polyps.
Asunto(s)
Poliposis Adenomatosa del Colon/patología , Cistoadenoma Mucinoso/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Pancreáticas/patología , Poliposis Adenomatosa del Colon/metabolismo , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Anciano , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Cistoadenoma Mucinoso/metabolismo , Proteínas del Citoesqueleto/metabolismo , Neoplasias Duodenales/patología , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Pancreáticas/metabolismo , Transactivadores/metabolismo , beta CateninaRESUMEN
BACKGROUND: 50 % of pregnancies are unwanted. For several reasons including difficulty in obtaining contraceptives, no or ineffective contraception is used to prevent these unwanted pregnancies. The Lactational Amenorrhoea Method(LAM) however is a contraceptive method available and accessible for many women. OBJECTIVES: To assess in fully breastfeeding women, staying amenorrheic, the efficacy of the Lactational Amenorrhoea Method as a contraceptive method. The efficacy of LAM, as defined in 1988 in Bellagio, was compared with alternative definitions of LAM; the outcomes were measured using pregnancy and menstruation life tables. DATA SOURCES: MEDLINE searches from 1966 until 2002 and EMBASE from 1988 until 2002; reference lists of studies and review articles; books related to LAM; published abstracts from breastfeeding, reproductive health, contraceptive conferences; and e-mail communication with coordinators of such studies. SELECTION CRITERIA: From 454 potentially relevant studies 154 investigated the risk of pregnancy during LAM or lactational amenorrhea. Two reviewers applied the following inclusion criteria: prospective study, cases and -if available- controls had to be sexually active, pregnancy had to be confirmed by physical examination or a pregnancy test. Life table menstruation rates and life table pregnancy rates were taken as endpoints. Thirteen publications, reporting on 9 intervention groups and 2 control groups, met the inclusion criteria and were included in this systematic review. Their quality was assessed. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, disagreements were resolved through discussion. Because of the heterogeneity of the included studies, the studies were analyzed using narrative methods. MAIN RESULTS: For the outcome two controlled studies of LAM users reported life table pregnancy rates at 6 months of 0.45 and 2.45 percent and 5 uncontrolled studies of LAM users reported 0-7.5 percent. Life table pregnancy rates of women fully breastfeeding and amenorrheic but not using any contraceptive method were 0.88 in one study and 0.9-1.2 percent (95% CI 0. 0-2.4 ) in a second study, depending on the definition of menstruation used. The life table menstruation rate at 6 months in all studies varied between 11.1-39.4 percent. REVIEWER'S CONCLUSIONS: No clear difference in life table pregnancy rates was found between women using LAM and supported in doing so, and fully breastfeeding, amenorroic women not using any method. Because the length of lactation amenorrhoea of women using LAM is too different between populations studied, and population specific, it is uncertain whether LAM extends lactational amenorrhoea.
Asunto(s)
Amenorrea , Conducta Anticonceptiva , Anticoncepción/métodos , Periodo Posparto , Lactancia Materna , Servicios de Planificación Familiar , Femenino , Humanos , Lactancia , EmbarazoRESUMEN
BACKGROUND: The lifetime risk of developing duodenal cancer in familial adenomatous polyposis (FAP) is about 5 per cent. When and to what extent surgical intervention should be undertaken to prevent death from invasive carcinoma is controversial. The aim of this study was to determine the effectiveness of various surgical treatments for cancer and severe duodenal adenomatosis. METHODS: A questionnaire was mailed to the members of the Leeds Castle Polyposis Group to obtain data on patients with FAP, treated for duodenal cancer or severe duodenal adenomatosis after 1990. RESULTS: Sixty-nine patients were included. The indication for surgery was invasive cancer in 13 patients, of whom six died from metastatic disease. Fifty-six patients were initially treated for severe duodenal adenomatosis, five (9 per cent) of whom died from metastatic disease (P = 0.002). In surviving patients, adenomas recurred after ampullectomy (six of eight, at mean follow-up of 11 months), after duodenotomy with polypectomy (17 of 21, at mean 29 months) and after pancreatoduodenectomy (six of 25, at mean 47 months). None of six patients who underwent a pancreas-sparing duodenectomy had recurrence of adenoma (mean follow-up 11 months). CONCLUSION: Surgery for duodenal adenomatosis should take place before endoscopic biopsy reveals invasive cancer. Even after extensive surgical procedures, small bowel adenomas may occur, emphasizing the need for chemoprevention.
Asunto(s)
Adenoma/cirugía , Poliposis Adenomatosa del Colon/complicaciones , Neoplasias Duodenales/cirugía , Adenoma/etiología , Adulto , Anciano , Colectomía/métodos , Neoplasias Duodenales/etiología , Salud Global , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Encuestas y CuestionariosAsunto(s)
Genes APC , Mutación/genética , Sitios de Empalme de ARN/genética , Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon/genética , Adolescente , Adulto , Edad de Inicio , Empalme Alternativo/genética , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Estudios RetrospectivosRESUMEN
Amelogenesis imperfecta (AI) is a diverse group of hereditary disorders that are characterized by a defect in the formation of the tooth enamel and a high degree of clinical diversity. X-linked, autosomal dominant and recessive inheritance have been demonstrated. Growth hormone (GH) has an effect on bone and soft tissue development. Dental and facial abnormalities associated with pituitary dwarfism have been reported, but GH deficiency with AI is very rare. We describe a 12 year-old pre-pubertal boy who was referred to our hospital with teeth deformities and growth retardation. His teeth had brown-yellow pigmented surfaces, and dental examination showed extensive enamel deficiency in his permanent teeth. He also had severe growth retardation; height SDS was -3.6. Laboratory examinations showed reduced GH levels, and he was diagnosed as having idiopathic isolated GH deficiency and AI.
Asunto(s)
Amelogénesis Imperfecta/complicaciones , Amelogénesis Imperfecta/diagnóstico , Hormona de Crecimiento Humana/deficiencia , Amelogénesis Imperfecta/genética , Niño , Trastornos del Crecimiento/etiología , Humanos , Masculino , LinajeRESUMEN
BACKGROUND: Cytotoxic chemotherapy can achieve a good initial response in inoperable desmoid tumors that have caused progressive obstruction of the gastrointestinal and urinary tracts and have caused unrelenting pain. METHODS: We have reviewed 8 patients (3 male) with desmoid tumors and familial adenomatous polyposis who underwent cytotoxic chemotherapy for inoperable gastrointestinal obstruction and/or uncontrolled pain. They were treated with doxorubicin and dacarbazine followed by carboplatin and dacarbazine. RESULTS: Follow-up after cytotoxic chemotherapy in the 7 patients for whom it was available was a mean of 42 (range 24-54) months. Two patients achieved complete remission after therapy. Four patients achieved a partial remission after completing all or some of the chemotherapy regimen; of these, three remained in stable remission, whereas the other was lost to follow-up. There were two recurrences that required further therapy; one of these patients was treated with further chemotherapy, which induced a second remission, and the other was treated with pelvic exenteration and has subsequently died. CONCLUSIONS: Most patients had a substantial response to cytotoxic chemotherapy; however, two patients required additional therapy 24 and 30 months after cytotoxic chemotherapy, respectively. Cytotoxic chemotherapy is effective in producing short-term and long-term remission in these difficult patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fibromatosis Abdominal/tratamiento farmacológico , Poliposis Adenomatosa del Colon , Adulto , Carboplatino/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fibromatosis Abdominal/patología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: In this prospective cross-sectional observational study, the distribution of organic pathologies in patients initially presenting with strabismus was evaluated. METHODS: Thirty-one of 243 patients examined between May 1997 and May 1998 had strabismus due to organic causes and 28 patients had posterior segment abnormalities. RESULTS: Toxoplasma chorioretinitis, morning glory anomaly, toxocara retinopathy, retinopathy of prematurity and Coats' disease were the most common diagnoses. Eighteen patients (58%) had esotropia and 13 (42%) had exotropia. The mean age of onset of deviation was significantly lower in the esotropic patients. There was no correlation between the degree of visual impairment and direction of deviation. CONCLUSIONS: Our study strongly underlines the importance of fundus examination in each strabismic patient.
Asunto(s)
Enfermedades de la Retina/complicaciones , Estrabismo/etiología , Estrabismo/patología , Edad de Inicio , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Pronóstico , Estudios Prospectivos , Enfermedades de la Retina/patología , Estrabismo/epidemiología , Agudeza VisualAsunto(s)
Antibacterianos/uso terapéutico , Clostridioides difficile , Colitis/terapia , Diarrea/microbiología , Diarrea/terapia , Levadura Seca/uso terapéutico , Clostridioides difficile/aislamiento & purificación , Colitis/microbiología , Diarrea/diagnóstico , Femenino , Humanos , Metronidazol/uso terapéutico , Persona de Mediana Edad , Recurrencia , Saccharomyces cerevisiae , Vancomicina/uso terapéuticoRESUMEN
Hereditary colorectal cancer results from specific genetic alterations. The causative genes for familial adenomatous polyposis, juvenile polyposis, Peutz-Jeghers syndrome, and hereditary nonpolyposis colorectal cancer have been cloned and characterized within the past decade. Genetic testing has therefore become more widely used to confirm the clinical diagnosis of each of those syndromes, to provide adequate surveillance, to allow screening of at-risk family members, and to help the surgeon in surgical decision making. The aim of this review is to analyze the importance of genetic testing in view of the clinical and surgical management of those gene-carriers individuals, and to discuss how should the surgeon integrate genetic testing in the evaluation of such patients.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/cirugía , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Humanos , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/cirugía , Pólipos/genética , Pólipos/cirugíaRESUMEN
Desmoid tumors arise sporadically or as part of the extraintestinal manifestations of familial adenomatous polyposis (FAP). In FAP, two distinct clinical presentations of the desmoid phenotype are seen: 1) one or a few desmoid tumors present predominantly in the abdominal wall or the abdomen; 2) a florid proliferation of tumors early in life, mostly near the axial skeleton or extremities. These different phenotypes have been associated with different sites of germline mutations in the adenomatous polyposis coli gene (APC gene). We present a large, French-Canadian kindred with a florid desmoid tumor phenotype caused by a germline mutation at codon 2643-2644 of the APC gene. The phenotype was characterized by the early onset of multiple tumors, arising near the axial skeleton and in proximal extremities. The penetrance of desmoid tumors was near 100% in this kindred. However, the expression of the disease was variable amongst the different affected relatives. Many gene carriers had cutaneous cysts. Polyposis of the colon was rarely observed in the affected individuals and we did not document upper gastro-intestinal polyps. The mutant APC allele did not express a stable truncated protein in vivo. Molecular analysis of the proband's tumor DNA revealed a somatic inactivating mutation of the wild-type allele. Immunohistochemistry on the tumor also demonstrated elevated levels of beta-catenin. The present study demonstrates that this extreme 3' APC mutation is associated with a severely penetrant desmoid phenotype and attenuated polyposis coli. It also suggests the involvement of the beta-catenin pathway in the development of desmoid tumors in FAP. The natural history of the disease is variable between individuals, and surgical interventions have to be timed appropriately due to the frequent recurrences.
Asunto(s)
Proteínas del Citoesqueleto/biosíntesis , Fibromatosis Agresiva/metabolismo , Genes APC , Mutación de Línea Germinal , Transactivadores , Regiones no Traducidas 3' , Adolescente , Adulto , Anciano , Alelos , Secuencia de Bases , Western Blotting , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Fibromatosis Agresiva/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fenotipo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , beta CateninaRESUMEN
PURPOSE: The aim of this retrospective study was to review the clinical features, and surgical and medical management of patients with familial adenomatous polyposis-associated desmoid tumors. METHODS: From 1980 to 1997, 97 of 780 patients with familial adenomatous polyposis developed desmoid disease. Clinical and demographic data; operative notes; and histologic, radiologic, and follow-up reports were retrieved from patients' medical records. Risk factors for desmoid disease, such as prior surgery, age at desmoid tumor diagnosis, pregnancy, and family history were sought. The outcome after noncytotoxic and cytotoxic therapy was evaluated with respect to improvement of symptoms. RESULTS: There were 38 males with a mean age of 32.1 years and 59 females with a mean age of 29.1 years. A family history of desmoid tumors was found in 41 patients (42 percent), and a history of pregnancy was documented in 33 females (56 percent). The most common clinical presentation was small-bowel obstruction (58 percent). One-half of the desmoids were located in the mesentery, and 32 percent were located in the mesentery and the abdominal wall. Desmoids developed after colectomy in 77 cases (80 percent), after a mean time of 4.6 years. Partial resection of desmoid tumor was performed in 46 patients (47 percent), resection of extra-abdominal desmoid tumors was performed in 17 cases (17 percent), and biopsy only was performed in 34 patients (35 percent). Postoperative morbidity was 23 percent after desmoid tumor resection. Eight patients (8 percent) died of their intra-abdominal desmoid. Mean follow-up time was 5.3 years. Sulindac, tamoxifen, or toremifene therapy was able to alleviate symptoms in only 4 of 31 patients. Symptomatic improvement was noted after chemotherapy in six of ten patients with extremely complex desmoids. CONCLUSION: Desmoid disease was found in 12.4 percent of our patients with familial adenomatous polyposis. In view of the high rate of morbidity, indication for surgery should be limited mainly to acute or chronic small-bowel obstruction, because resection triggers a high recurrence rate. Noncytotoxic therapy was not effective for progressive desmoid tumors, whereas chemotherapy was effective in aggressive cases of intra-abdominal desmoid tumors.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Fibromatosis Abdominal/genética , Poliposis Adenomatosa del Colon/tratamiento farmacológico , Poliposis Adenomatosa del Colon/mortalidad , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Fibromatosis Abdominal/tratamiento farmacológico , Fibromatosis Abdominal/mortalidad , Fibromatosis Abdominal/cirugía , Estudios de Seguimiento , Humanos , Obstrucción Intestinal/tratamiento farmacológico , Obstrucción Intestinal/genética , Obstrucción Intestinal/mortalidad , Obstrucción Intestinal/cirugía , Masculino , Persona de Mediana Edad , Embarazo , Pronóstico , Tasa de SupervivenciaRESUMEN
Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers. We conducted a detailed investigation of germline STK11 alterations by protein truncation test and genomic DNA sequence analysis in ten unrelated PJS families. We identified a novel truncating deletion spanning STK11 exons 2-7 in a single patient and several known polymorphisms. Loss of heterozygosity studies in PJS polyps of four of these patients identified an allelic deletion of D19S886 in another patient. Our results suggest that STK11 mutations account for only a proportion of PJS cases.
Asunto(s)
Mutación de Línea Germinal , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adolescente , Adulto , Niño , Cromosomas Humanos Par 19/genética , Femenino , Eliminación de Gen , Marcadores Genéticos , Humanos , Intrones , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Polimorfismo Genético , Análisis de Secuencia de ADNRESUMEN
PURPOSE: The aim of this study was to evaluate the surgical complications and long-term outcome and assess the functional results and quality of life after ileorectal anastomosis and ileal pouch-anal anastomosis in patients with familial adenomatous polyposis. METHODS: From 1980 to 1997, 131 patients with familial adenomatous polyposis were operated on or were followed up or both at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital. Demographic and operative data were prospectively collected in the ileal pouch-anal anastomosis group, and retrospectively in the ileorectal anastomosis group. A questionnaire or telephone interview or both were undertaken to evaluate functional outcome and quality of life. RESULTS: The ileorectal anastomosis group consisted of 60 patients (mean age, 31 years; mean follow-up, 7.7 years). In the ileal pouch-anal anastomosis group there were 50 patients (mean age, 35 years; mean follow-up, 6 years). There were no statistically significant differences with respect to anastomotic leak rate in ileal pouch-anal anastomosis vs. ileorectal anastomosis (12 vs. 3 percent; P = 0.21), risk of small-bowel obstruction (24 vs. 15 percent; P = 0.58), and risk of intra-abdominal sepsis (3 vs. 2 percent; P = 0.86). Reoperation rate was similar in the two groups (14 vs. 16 percent; P = 0.94). Twenty-one patients (37 percent) with ileorectal anastomosis were converted to ileal pouch-anal anastomosis (12 patients) or proctocolectomy (9 patients), because of rectal cancer (5 patients), dysplasia (1 patient), or uncontrollable rectal polyps (15 patients). Two pelvic pouches were excised, and another one was defunctioned. Information regarding functional results and quality of life was obtained in 40 patients (66.6 percent) in the ileorectal anastomosis group and in 43 patients (86 percent) in the ileal pouch-anal anastomosis group. Patients with ileorectal anastomosis had a significantly better functional outcome with regard to nighttime continence and perineal skin irritation. But otherwise, functional results and quality of life were similar. CONCLUSIONS: Although ileorectal anastomosis has a better functional outcome, ileal pouch-anal anastomosis may be preferable because of the lower long-term failure rate. Ileorectal anastomosis is still an option in patients with familial adenomatous polyposis with rectal polyp sparing and good compliance for follow-up.
Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Canal Anal/cirugía , Íleon/cirugía , Proctocolectomía Restauradora , Adolescente , Adulto , Anciano , Anastomosis Quirúrgica/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios RetrospectivosRESUMEN
PURPOSE: The aim of this study was to review the functional outcome in 20 patients with familial adenomatous polyposis and ulcerative colitis who were converted from ileorectal anastomosis to ileal pouch-anal anastomosis. METHODS: From 1985 to 1997, 12 patients with familial adenomatous polyposis (5 males; mean age, 39.1 years) and 8 patients with ulcerative colitis (5 males; mean age, 36.7 years) underwent conversion from ileorectal anastomosis to ileal pouch-anal anastomosis. Clinical and operative data were analyzed retrospectively. Functional results were obtained by telephone interview in 16 patients (94 percent) after pouch construction. Four patients were not interviewed (2 were deceased, 1 was lost to follow-up, and 1 was not reachable). RESULTS: Indications for conversion were uncontrollable rectal polyps (10 patients) and colonic cancer found in the pathology specimen after ileorectal anastomosis in patients with familial adenomatous polyposis (2 patients), intractable proctitis (5 patients), colonic cancer found in the pathology specimen of patients with ulcerative colitis after ileorectal anastomosis (2 patients), and rectal dysplasia (1 patients). Mean follow-up time was 5 (range, 1-11) years. Ileal pouch-anal anastomosis was handsewn in 14 patients, and the remaining cases were double-stapled in 4 patients with ulcerative colitis. No intraoperative difficulties were reported in 13 cases; technical problems were related to adhesions (3 cases), difficult rectal dissection (2 cases), and stapler-related difficulties (2 cases). Postoperative complications after ileal pouch-anal anastomosis included small-bowel obstruction (4 patients) and ileal pouch-anal anastomosis leak (1 patient). Patients with ileorectal anastomosis vs. those with ileal pouch-anal anastomosis had a better functional outcome with regard to nighttime continence (14 (88 percent) vs. 6 (38 percent) patients) and average bowel movements (<6/day; 12 (75 percent) vs. 4 (25 percent) patients). Complete daytime continence, 15 (94 percent) vs. 10 (62 percent) patients, was similar in the two groups. Physical and emotional well-being were similarly rated as very good to excellent. CONCLUSIONS: In patients with familial adenomatous polyposis and ulcerative colitis with ileorectal anastomosis, conversion to ileal pouch-anal anastomosis may be required. In view of the risk of rectal cancer or intractable proctitis, patients seem to accept the conversion in spite of poorer bowel function.
Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Colitis Ulcerosa/cirugía , Íleon/cirugía , Proctocolectomía Restauradora , Recto/cirugía , Adolescente , Adulto , Anastomosis Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: The goal of genetic testing is to define individual risk, which in turn may guide clinical management. METHODS: Thirty-two international familial adenomatous polyposis registries were surveyed regarding their approach to a specific clinical management question. There were 30 respondents. Respondents declared their clinical policy for an at-risk, first-degree relative who undergoes direct mutation analysis and does not have an APC gene mutation known to be present in his or her family. RESULTS: Nineteen of 30 (63.3 percent) registries would discharge this negative APC mutation case from clinical screening. Eleven of 30 (37 percent) registries would maintain clinical screening. Reasons offered for maintaining surveillance included the need for additional confirmation of the APC mutation in two affected relatives, the possibility of sampling error or two different mutations in an affected family, limited prospective data, and patient anxiety. CONCLUSIONS: The discrepancy in response to the survey suggests that some clinicians are as yet reluctant to accept fully that predictive genetic analysis is a definitive guide to clinical management in familial adenomatous polyposis. Nevertheless, we believe that use of a predictive gene test for familial adenomatous polyposis should alter management, decrease cost, and reduce psychological trauma for the tested individual. Although the benefit of APC analysis is accepted for the positive gene carrier, the challenge remains to reclassify the negative gene carriers who are no longer at risk for familial adenomatous polyposis.
Asunto(s)
Poliposis Adenomatosa del Colon/diagnóstico , Genes APC , Pruebas Genéticas , Poliposis Adenomatosa del Colon/genética , Análisis Mutacional de ADN , Heterocigoto , Humanos , Pautas de la Práctica en Medicina , Sistema de RegistrosRESUMEN
Recent characterization of the molecular genetic basis of hereditary nonpolyposis colorectal cancer provides an important opportunity for identification of individuals and their families with germline mutations in mismatch repair genes. Cancer family history criteria that accurately define hereditary colorectal cancer are necessary for cost-effective testing for germline mutations in mismatch repair genes. The present report describes the results of analysis of 33 colorectal cancer cases/families that satisfy our modified family history criteria (Mount Sinai criteria) for colorectal cancer. Fourteen of these families met the more stringent Amsterdam criteria. Germline MSH2 and MLH1 mutations were identified by the reverse transcription-polymerase chain reaction and the protein truncation test, and confirmed by sequencing. Microsatellite instability analysis was performed on available tumors from affected patients. MSH2 or MLH1 mutations were detected in 8 of 14 Amsterdam criteria families and in 5 of the remaining 19 cases/families that only satisfied the Mount Sinai criteria. Three of the latter families had features of the Muir-Torre syndrome. A high level of microsatellite instability (MSI-H) was detected in almost all (16/18) colorectal cancers from individuals with MSH2 and MLH1 mutations, and infrequently (1/21) in colorectal cancer specimens from cases without detectable mutations. Families with germline MSH2 and MLH1 mutations tended to have individuals affected at younger ages and with multiple tumors. The Amsterdam criteria are useful, but not sufficient, for detecting hereditary colorectal cancer families with germline MSH2 and MLH1 mutations, since a proportion of cases and families with mutations in mismatch repair genes will be missed. Further development of cancer family history criteria are needed, using unbiased prospectively collected cases, to define more accurately those who will benefit from MSH2 and MLH1 mutation analysis.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , ADN de Neoplasias , Proteínas de Unión al ADN , Mutación de Línea Germinal , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Adaptadoras Transductoras de Señales , Disparidad de Par Base , Proteínas Portadoras , Reparación del ADN , Femenino , Humanos , Masculino , Repeticiones de Microsatélite , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS , Proteínas Nucleares , LinajeRESUMEN
BACKGROUND: Mutations of the APC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome. AIMS: To conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer. METHODS: All direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model. RESULTS: The baseline analysis predicted that screening a prototype FAP family would cost $4975/ pound3109 by molecular testing and $8031/ pound5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if the APC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/ pound4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives. CONCLUSIONS: In FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be non-carriers.