RESUMEN
Adenomatous polyposis (AP) diseases, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MUTYH-associated polyposis (MAP), are the second most common hereditary causes of colorectal cancer. A frequent extra-colonic manifestation of AP disease is duodenal polyposis, which may lead to duodenal cancer in up to 18% of AP patients. Endoscopic surveillance is recommended at 0.5- to 5-year intervals depending on the extent of polyp growth and histological progression. Although the Spigelman classification is traditionally used to determine surveillance intervals, it lacks information on the (peri-)ampullary site, where 50% of duodenal carcinomas are located. Hence, information on the papilla has recently been added as a prognostic marker. Patients with duodenal adenoma(s) ≥10 mm and ampullary adenomas of any size are suggested to be referred to an expert center for endoscopic therapy, particularly endoscopic mucosal resection and endoscopic ampullectomy. Nonetheless, despite the logic of this approach, the long-term efficacy of endoscopic therapy is still to be demonstrated.
Asunto(s)
Poliposis Adenomatosa del Colon/patología , Poliposis Adenomatosa del Colon/cirugía , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Duodenoscopía , Poliposis Adenomatosa del Colon/diagnóstico , Neoplasias Duodenales/diagnóstico , Resección Endoscópica de la Mucosa , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cooperación del Paciente , Pronóstico , Factores de TiempoRESUMEN
BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/terapia , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Quimioprevención , Colonoscopía , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Técnica Delphi , Procedimientos Quirúrgicos del Sistema Digestivo , Detección Precoz del Cáncer , Femenino , Tamización de Portadores Genéticos , Pruebas Genéticas , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Femeninos/genética , Humanos , Estilo de Vida , Procedimientos Quirúrgicos ProfilácticosRESUMEN
BACKGROUND: Transanal total mesorectal excision (taTME) is a minimally invasive technique which was developed to overcome the difficulties associated with the "top-down" pelvic dissection by enabling a "bottom-up" dissection in patients with mid- and low rectal cancer. While this technique was primarily designed to manage tumors in the mid- and lower rectum, its spectrum of indications has been broadened to include benign colorectal pathologies. The aim of the present study was to assess our initial experience with taTME in patients undergoing restorative proctocolectomy for familial adenomatous polyposis (FAP). METHODS: All consecutive patients (undergoing prophylactic restorative proctocolectomy with IPAA for FAP using taTME between April and October 2016 at our institution) were included in the study. RESULTS: There were 8 patients (6 females and 2 males). The median age was 19.5 years (range 16-31 years). In all cases, surgery was successfully completed using with taTME. No perioperative complications were recorded. A median of 5 bowel movements (range 4-6 bowel movements) with intermittent anti-diarrheal medication was recorded in all cases. CONCLUSIONS: Our initial experience with 8 consecutive cases suggests taTME is safe and effective in patients undergoing prophylactic restorative proctocolectomy with IPAA for FAP.
Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Neoplasias Colorrectales/prevención & control , Proctocolectomía Restauradora/métodos , Cirugía Endoscópica Transanal/métodos , Adolescente , Adulto , Defecación , Incontinencia Fecal , Femenino , Humanos , Masculino , Proctocolectomía Restauradora/efectos adversos , Procedimientos Quirúrgicos Profilácticos/efectos adversos , Procedimientos Quirúrgicos Profilácticos/métodos , Cirugía Endoscópica Transanal/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Approximately 3-5% of all colorectal cancers are based on a hereditary predisposition, of which Lynch syndrome is by far the most frequent hereditary cancer syndrome. Beside colorectal cancer Lynch-Syndrome is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. Genetically Lynch syndrome is caused by a germline mutation in one of the so-called mismatch-repair-genes. Based on several epidemiological studies, increasingly differences in the penetrance of the different cancers occurring are associated with the affected gene and also gender of the patient have been reported. The lifetime risk of colorectal cancer for males with Lynch syndrome generally is significantly higher and the age of first manifestation significantly earlier compared to females. The difference is especially notable in men with a MSH6-mutation. Moreover, the lifetime risk for gastric, bladder, and urothelial cancer is much higher in males. Women with an MSH6 mutation have a much higher risk for endometrial (and ovarian) cancer than for colorectal cancer. In patients with Muir Torre syndrome again males are predominantly affected and almost all affected have a mutation in MSH2 rather than in any other MMR gene. This review is an update of the literature analyzing gen and gender specific aspects of Lynch syndrome. To date these associations are based on retrospective studies, that require confirmation in a prospective setting with large patient numbers in order to identify validated, individualized gene and gender screening recommendations in the future. Especially in a syndrome with multiple potential cancer targets, an intense yearly program comprising several invasive procedures has a negative effect on patient compliance.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Caracteres Sexuales , Distribución por Edad , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Femenino , Marcadores Genéticos/genética , Humanos , Incidencia , Internacionalidad , Masculino , Salud del Hombre/estadística & datos numéricos , Salud del Hombre/tendencias , Factores de Riesgo , Distribución por Sexo , Salud de la Mujer/estadística & datos numéricos , Salud de la Mujer/tendenciasRESUMEN
Lynch syndrome is the most frequent hereditary cancer syndrome, accounting for approximately 3-5â% of all colorectal cancers. In addition, it is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. In clinical practise Lynch syndrome is frequently not detected and many clinicians admit uncertainties regarding diagnostic procedures. Also, counselling of patients is considered difficult regarding therapeutic - especially prophylactic surgical and chemopreventive options and recommendations. Based on a review of available literature we discuss optimized strategies for improved detection of suspected Lynch syndrome patients. The aim of this review is to establish a clinical algorithm of how to proceed on a diagnostic level and to discuss surgical options at the time of a colorectal cancer. In order to identify patients with Lynch syndrome, family history should be ascertained and evaluated in regards to fulfilment of the Amsterdam-II- and/or the revised Bethesda criteria. Subsequently immunohistochemical staining for the mismatch-repair-genes, BRAF testing for MLH1 loss of expression, as well as testing for microsatellite instability in some, followed by genetic counselling and mutation analysis when indicated, is recommended. Pathological identification of suspected Lynch syndrome is readily feasible and straightforward. However, the need of performing these analyses in the tumor biopsy at the time of (gastroenterological) diagnosis of CRC neoplasia is essential, in order to offer patients the option of a prophylactically extended surgery and - as recommended in the German S3 guidelines - to discuss the option of a merely prophylactical hysterectomy and oophorectomy (if postmenopausal) in women. Close cooperation between gastroenterologists, pathologists and surgeons is warranted, so that patients may benefit from options of extended or prophylactically extended surgery at the time of diagnosis of a colorectal primary. Patients nowadays must be involved in informed decision-making regarding prophylactic or extended prophylactic surgery at the time of a colorectal primary. To date, however, limitations in daily clinical practise, the failure to assess family history and the lack of awareness of this important hereditary syndrome is the major asset leading to severe underdiagnosis and putting to risk the indexpatients themselves and their families to (metachronous) CRC and the associated extracolonic cancers. If at all tumors of patients fulfilling Bethesda criteria will be analysed for MSI in the surgical specimen and therefore Lynch syndrome patients are not given the opportunity to opt for extended surgery. In clinical experience the postoperative MSI-analysis is inconsistently performed - even if the Bethesda criteria are fulfilled - and in case of suspected Lynch syndrome genetically counselling is not consistently recommended. Therefore affected cancer patients are left unaware of their increased genetic risk and in average 3 high-risk gene carriers per family miss the opportunity to actively engage in the recommended screening program.
Asunto(s)
Algoritmos , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/cirugía , Conducta Cooperativa , Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Reparación de la Incompatibilidad de ADN/genética , Análisis Mutacional de ADN , Asesoramiento Genético , Adhesión a Directriz , Humanos , Comunicación Interdisciplinaria , Inestabilidad de Microsatélites , Homólogo 1 de la Proteína MutL , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas B-raf/genética , Transcriptoma/genéticaRESUMEN
BACKGROUND AND AIM: Lynch syndrome is a frequent autosomal dominant cancer predisposition leading to an estimated incidence of 3000-4000 new cancer diagnoses of colorectal and endometrial cancer in Germany per year. The underlying hereditary condition is largely underestimated and underrecognized by physicians. The usually young at-risk population, feeling insecure about their personal risk assessment, seeks information online. The aim of this study was to evaluate whether this online risk assessment tool for identification of increased risk for hereditary cancer predisposition reaches the target population and whether it succeeds in positively influencing intensified screening compliance. METHODS: The underlying algorithm for the test is based on the Bethesda and Amsterdam criteria and recent literature on polyposis syndromes. In the context of interrogating family and personal history, a total of five risk categories were defined. In addition to the cancers as defined in the above mentioned criteria, precursor lesions (polyps) were integrated into the risk estimate. Prior to launching, the algorithm was validated in family pedigrees of 102 mutation carriers with identified MLH-1 or MSH-2 mutations. RESULTS: During the time interval analysed, which was between October 2008 and April 2011 a total of 656 participants were included. Among these 19.1â% (125/656) belonged to the target population at increased familial or hereditary risk. 72.8â% (91/125) were yet healthy with known cancer-affected relatives. Merely 34.4â% (11/32) of the high-risk population were currently participating in a risk adjusted screening program. After completion of the online test 62.5â% (20/32) felt motivated to reconsider and adjust accordingly with increased surveillance. The test received an overall "good" evaluation (83â%) based on handling, performance and information content. CONCLUSION: This online risk-assessment tool was mainly completed by healthy (not cancer-affected) individuals with an increased risk for familial or hereditary colorectal cancer predisposition. The family pedigrees were comparable to these of known mutation carriers. The at-risk population was positively motivated to intensify screening strategies and the test received an overall positive evaluation.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/prevención & control , Colonoscopía , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/prevención & control , Diagnóstico por Computador , Detección Precoz del Cáncer , Cooperación del Paciente , Medición de Riesgo , Proteínas Adaptadoras Transductoras de Señales/genética , Poliposis Adenomatosa del Colon/diagnóstico , Algoritmos , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Diagnóstico Precoz , Femenino , Tamización de Portadores Genéticos , Pruebas Genéticas , Alemania , Humanos , Masculino , Homólogo 1 de la Proteína MutL , Proteínas MutL , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Aceptación de la Atención de Salud , Linaje , Encuestas y CuestionariosRESUMEN
Lynch syndrome is characterised by a familial predisposition of colorectal and endometrial carcinomas in association with a variety of other cancers. The underlying autosomal dominant inheritance has a penetrance of 85-90%. The molecular genetic underlying mechanism is a mutation in one of the mismatch-repair genes. The identification of the molecular genetic basis of Lynch syndrome enabled the implementation of predictive testing in families with a proven mutation. A prerequisite to detect patients with Lynch syndrome is a knowledge of the clinical and histopathological features of this disease. Typical for Lynch syndrome associated carcinomas is the early age of onset of about 45 years as well as the characteristic localisation within the right hemicolon. However, in order to increase the rate of identification of this underestimated syndrome, the awareness of the clinician must extend beyond this classical phenotype. For this purpose close interdisciplinary cooperation is warranted! The cancers are mostly low-differentiated with solid areas without a tubular structure. Crohn's-like lesions as well as peritumoural and tumour-infiltrating lymphocytes may frequently be found in the periphery of the malignant formation. Within the framework of the clinical evaluation of any index patient, an extended family history must be ascertained and matched with the Amsterdam-I and -II criteria as well as with the revised Bethesda criteria. If a patient fulfills these criteria, testing for microsatellite instability and if positive after genetic counselling mutation analysis should be recommended. Patients with a proven mutation and high risk individuals from families with an unidentified underlying mutation are encouraged to participate in an intensified screening programme. Due to the incomplete penetrance there is no recommendation towards prophylactic surgery in high-risk individuals without tumour manifestation. Nevertheless, the effect on quality of life of prophylactic, extended surgery in addition to the obligatory oncologic resection with or without prophylactic hysterectomy needs to be established in prospective controlled trials.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/terapia , Pruebas Genéticas/métodos , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Humanos , PrevalenciaRESUMEN
Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.
Asunto(s)
Síndrome de Peutz-Jeghers/diagnóstico , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Niño , Preescolar , Endoscopía Gastrointestinal , Medicina Basada en la Evidencia/métodos , Femenino , Neoplasias Gastrointestinales/diagnóstico , Neoplasias de los Genitales Femeninos/diagnóstico , Genotipo , Humanos , Cuidados a Largo Plazo/métodos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/terapia , Fenotipo , Vigilancia de la Población/métodos , Adulto JovenRESUMEN
INTRODUCTION: Guajac based fecal occult blood tests have proven to reduce mortality of colorectal cancer - despite their unsatisfactory statistical values. The potential of newer tests is yet inconclusive. We compared two guajac based, four immunochemical and the M2-PK test with colonoscopic and histological results as a reference. METHODS: In 1128 stool samples of patients undergoing (screening) colonoscopy the mentioned tests were performed. RESULTS: Positivity rate was 1.9 to 4.1 % for guajac based and immunochemical tests, M2-PK reached 11.6 %. In case of advanced neoplasias, no significant differences in sensitivity (7.3 - 20 %), specifity (96.6 - 98.4 %), positive predictive value (16.7 - 30.6 %) or accuracy (92.9 - 94.0 %) between guajac based and immunochemical tests were encountered. The slightly higher sensitivity of M2-PK (27.3 %) did not reach statistical significance - however the comparatively low specifity (89.2 %) and accuracy (86.2 %) were clearly lower compared to all other tests. Regarding all neoplasia, immunochemical tests performed better than conventional hemoccult, but the difference did not reach statistical significance. In this group, the sensitivity of M2-PK is clearly better, but specifity is clearly inferior to all other tests. DISCUSSION: Low sensitivity and low predictive values are explained by the study design with single test and low prevalence of neoplasia. Due to small numbers, there is only a trend, but no significant difference between the performance of conventional hemoccult compared with immunochemical and high senstitive guajac tests. Because of its low specificity, M2-PK is not an appropriate screening test for colorectal neoplasia.
Asunto(s)
Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Tamizaje Masivo/métodos , Sangre Oculta , Interpretación Estadística de Datos , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIM: The study aimed to describe genetical and clinical features of attenuated familial adenomatous polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance. METHOD: A questionnaire study was carried out of polyposis registries with data on patients with presumed AFAP, defined as having ≤ 100 colorectal adenomas at age ≥ 25. RESULTS: One hundred and ninety-six patients were included. The median number of adenomas was 25 (0-100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty-two patients had a colectomy and an ileorectal anastomosis and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5' end, exon 9 and 3' end). CONCLUSIONS: A subset of FAP patients with a milder phenotype does exist and treatment and surveillance had to be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following clinical diagnostic criteria for AFAP: a dominant mode of inheritance of colorectal adenomatosis and <100 colorectal adenomas at age 25 or older. Colonoscopy had to be preferred to sigmoidoscopy and surveillance had to be life-long. In the majority of patients, prophylactic colectomy and ileorectal anastomosis are recommended at the age of 20-25 years.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/patología , Sistema de Registros , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Colectomía , Análisis Mutacional de ADN , Femenino , Genes APC , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Estadísticas no Paramétricas , Adulto JovenRESUMEN
Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2-4% of all cases. Surveillance of individuals at high risk for CRC prevents the development of advanced CRC. About 1 million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires were distributed amongst members of a European collaborative group of experts that aims to improve the prognosis of families with hereditary CRC. The survey showed that in all countries obtaining a family history followed by referral to clinical genetics centres of suspected cases was the main strategy to identify familial and hereditary CRC. In five out of seven countries with a (regional or national) CRC population screening program, attention was paid in the program to the detection of familial CRC. In only one country were special campaigns organized to increase the awareness of familial CRC among the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Reparación de la Incompatibilidad de ADN , Europa (Continente)/epidemiología , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Directrices para la Planificación en Salud , Humanos , Anamnesis , Proteína 2 Homóloga a MutS/genética , Mutación , Linaje , Factores de RiesgoRESUMEN
One of the main challenges in the clinical management of familial colorectal cancer (CRC) remains the overlap of syndromes with different underlying genetic causes and the differentiated risk management of colorectal and associated malignancies. The Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is characterized by the development of colorectal, endometrial, gastric and other cancers and is caused by a mutation in one of the mismatch repair (MMR) genes. Microsatellite instability (MSI) and/or immunohistochemistry (IHC) are important prognostic factors and may predict the response to chemotherapy. Familial adenomatous polyposis (FAP) may be seen as a counterpart to Lynch syndrome, responsible for <1% of all CRC cases. Recently the MUTYH gene has been identified as a further polyposis gene. The associated disorder has been termed MYH-associated polyposis (MAP) and displays an autosomal recessive pattern of inheritance. For clinical management, distinguishing between Lynch syndrome, attenuated FAP and MAP is important for risk assessment, surveillance recommendations and indication for prophylactic surgery.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/cirugía , Colectomía , Colonoscopía , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Análisis Mutacional de ADN , Diagnóstico Precoz , Medicina Basada en la Evidencia , Pruebas Genéticas , Genotipo , Laparoscopía , Fenotipo , Recto/cirugíaRESUMEN
In 75 to 90 % of patients with rectal cancer, a sphincter-preserving resection can be performed without violating oncological principles. However, almost 50 % of the patients suffer from an anterior resection syndrome after total or subtotal rectal resection with a straight colorectal or coloanal anastomosis. This syndrome describes the characteristic complaints of minor or major incontinence. The anastomosis with the colonic pouch has been proved to result in better continence in the short- and long-terms compared to the straight anastomosis. Based on grade 1 evidence, the colonic pouch should be recommended as a standard procedure after low anterior resection with total mesorectal excision (TME). Both the colonic J pouch of 6-cm length and the coloplasty have been shown to be of equal value in respect to function and morbidity. With regard to the complicated procedure and the poorer functional outcome, the ileocecal pouch should only be applied in cases without the option of an alternative pouch design. The temporary loss of the rectoanal inhibitory reflex, the sphincter lesion caused by the instrumental dilatation in stapling or peranal hand-sutured anastomosis and the disturbed function of the internal sphincter due to the autonomous nerve damage additionally contribute to the anterior resection syndrome. In the intersphincteric resection, the loss of the transitional zone and the hemorrhoidal cushion as well as the removal of the upper part of the internal sphincter aggravate the incontinence. For better continence, two operative procedures should be recommended: By applying the inverse double stapling technique in anastomizing the colonic J pouch, the sphincter lesion as a consequence of the dilatation can be avoided. The nerve-sparing mesorectal excision helps to preserve the function of the internal sphincter.
Asunto(s)
Canal Anal/cirugía , Colon/cirugía , Reservorios Cólicos , Incontinencia Fecal/prevención & control , Complicaciones Posoperatorias/prevención & control , Neoplasias del Recto/cirugía , Recto/cirugía , Anastomosis Quirúrgica , Incontinencia Fecal/etiología , Estudios de Seguimiento , Humanos , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome , Factores de TiempoRESUMEN
BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.
Asunto(s)
Poliposis Adenomatosa del Colon/terapia , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/genética , Edad de Inicio , Antiinflamatorios no Esteroideos/uso terapéutico , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/terapia , Femenino , Fibromatosis Agresiva/diagnóstico , Fibromatosis Agresiva/terapia , Genes APC , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Humanos , Masculino , Factores de RiesgoRESUMEN
Diagnostic and treatment of rectal cancer need a continuous quality assessment. Indicators of quality were compiled as indicator profile for a summarizing evaluation. The indicators selected should potentially show an appreciable variation of the quality target and in addition should be decisive for the outcome. For the evaluation of the clinical diagnostic the frequency of the determination of the pretherapeutic T, N and M categories and the proportion of pT 1-tumors were chosen, for the pathological diagnostic the number of histologically examined lymph nodes and the proportion of lymphnode positive patients. Process quality of treatment was defined by the following indicators: proportion of tumor excision, of definite therapy by local tumor removal, of neo-adjuvant long-term radiochemotherapy, of adjuvant treatment in patients not selected for neoadjuvant therapy, of total / partial mesorectal excision, of abdomino-perineal resection, postoperative mortality, frequency of clinically apparent anastomotic leakage, and of neurogenic bladder dysfunction at hospital discharge. The indicators for the quality of the performance of treatment were differentiated between surrogate indicators that can be determined immediately after accomplishment of primary surgical therapy giving strong clues for the further course of disease at an early date, and definite indicators. Important surrogate indicators comprise the occurrence of intraoperative local tumor cell dissemination, R 1 / 2-resection, pathohistologically CRM-positive tumor resection, and the quality of mesorectal excision (proportion of incomplete mesorectal excision). The definite indicators include the 5-year local recurrence rate and the 5-year overall survival rate. The corresponding quantifying parameters for the individual indicators are specified in this paper with precise figures.
Asunto(s)
Indicadores de Calidad de la Atención de Salud , Neoplasias del Recto/cirugía , Terapia Combinada , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Invasividad Neoplásica , Siembra Neoplásica , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Recto/patología , Recto/cirugía , Tasa de SupervivenciaRESUMEN
The task force "workflow rectal cancer II" defined operative techniques in lower rectal cancer, especially the total mesorectal excision and an improved technique of abdominalperineal resection. New aspects for treatment of rectal cancer with primary distant metastases are described. Due to newer publications a concept of bidirectional procedure with surgery and radiochemotherapy is recommended, where the operation must not be inevitably the first step. In anastomoses below 6 cm of the anocutaneous verge a reservoir should be performed on principle due to better functional results. The colon-j-pouch with a maximal loop length of 6 cm is best investigated under these conditions, the other procedures should be further evaluated.
Asunto(s)
Neoplasias del Recto/cirugía , Algoritmos , Reservorios Cólicos , Humanos , Estadificación de Neoplasias , Neoplasias del Recto/patología , Recto/patología , Recto/cirugíaRESUMEN
Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/terapia , Guías de Práctica Clínica como Asunto , Colon/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Endometriales/epidemiología , Europa (Continente)/epidemiología , Femenino , Pruebas Genéticas , HumanosRESUMEN
BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by germline STK11 mutations and characterised by gastrointestinal polyposis. Although small bowel intussusception is a recognised complication of PJS, risk varies between patients. OBJECTIVE: To analyse the time to onset of intussusception in a large series of PJS probands. METHODS: STK11 mutation status was evaluated in 225 PJS probands and medical histories of the patients reviewed. RESULTS: 135 (60%) of the probands possessed a germline STK11 mutation; 109 (48%) probands had a history of intussusception at a median age of 15.0 years but with wide variability (range 3.7 to 45.4 years). Median time to onset of intussusception was not significantly different between those with identified mutations and those with no mutation detected, at 14.7 years and 16.4 years, respectively (log-rank test of difference, chi(2) = 0.58, with 1df; p = 0.45). Similarly no differences were observed between patient groups on the basis of the type or site of STK11 mutation. CONCLUSIONS: The risk of intussusception in PJS is not influenced by STK11 mutation status.
Asunto(s)
Intususcepción/genética , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The most frequent hereditary colorectal cancer predisposition is Lynch syndrome, or hereditary non-polyposis colorectal cancer. The option of prophylactic surgery relies on the penetrance of the genetic defect and the heterogeneity of the condition. Since 20% of all mutation carriers never move on to develop cancer, the purely prophylactic setting is not indicated. However, when colorectal cancer is diagnosed, the question arises if the patient may benefit from extended surgery -- total colectomy or (restorative) proctocolectomy. These patients should be entered into the ongoing prospective-randomized study by German Cancer Aid (http://www.hnpcc-studie.de). Due to substantially increased cancer risk and poor surveillance options, the endometrium and stomach are also subject to the question of prophylactic intervention.