Study of colorectal mortality in the Andalusian population.

OBJECTIVES: to provide up-to-date information and to analyze recent changes in colorectal cancer mortality trends in Andalusia during the period of 1980-2008 using joinpoint regression models. PATIENTS AND METHODS: age- and sex-specific colorectal cancer deaths were taken from the official vital statistics published by the Instituto de Estadística de Andalucía for the years 1980 to 2008. We computed age-specific rates for each 5-year age group and calendar year and age-standardized mortality rates per 100,000 men and women. A joinpoint regression analysis was used for trend analysis of standardized rates. Joinpoint regression analysis was used to identify the years when a significant change in the linear slope of the temporal trend occurred. The best fitting points (the "join-points") are chosen where the rate significantly changes. RESULTS: mortality from colorectal cancer in Andalusia during the period studied has increased, from 277 deaths in 1980 to 1,227 in 2008 in men, and from 333 to 805 deaths in women. Adjusted overall colorectal cancer mortality rates increased from 7.7 to 17.0 deaths per 100,000 person-years in men and from 6.6 to 9.0 per 100,000 person-years in women Changes in mortality did not evolve similarly for men and women. Age-specific CRC mortality rates are lower in women than in men, which imply that women reach comparable levels of colorectal cancer mortality at higher ages than men. CONCLUSIONS: sex differences for colorectal cancer mortality have been widening in the last decade in Andalusia. In spite of the decreasing trends in age-adjusted mortality rates in women, incidence rates and the absolute numbers of deaths are still increasing, largely because of the aging of the population. Consequently, colorectal cancer still has a large impact on health care services, and this impact will continue to increase for many more years.

Andalusian Registry for familial adenomatous polyposis. Analysis of patients included.

OBJECTIVE: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. MATERIAL AND METHODS: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. RESULTS: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p < 0.05). CONCLUSIONS: The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic-genotypic correlation with statistical significance.

Registro Andaluz de la Poliposis Adenomatosa Familiar. Análisis de los pacientes incluidos / No disponible

Objetivos: Valorar las características fenotípicas y genotípicas de los pacientes incluidos en el Registro Andaluz de la poliposis adenomatosa familiar, la relación genotipo/fenotipo y el impacto del Registro en la frecuencia de cáncer colorrectal de los familiares registrados. Material y métodos: Estudio descriptivo de 77 pacientes con PAF, pertenecientes a 33 familias, incluidos en una base de datos centralizada a la que tienen acceso los responsables de los hospitales participantes, previa firma de cartas de confidencialidad. Todos los estudios genéticos se realizan en el Servicio de Inmunología de nuestro Hospital. Resultados: 77 pacientes registrados (50,6% varones): 31 probandos, edad media: 32 años (13-51) y 46 familiares afectos, edad media 21,8 años (6-55). Estudio genético informado en 68/77 con resultado positivo en 92,6%. Cáncer colorrectal al diagnóstico en diez probandos (32,2%) y 2 familiares afectos (4,3%), diferencia estadísticamente significativa (p < 0,05). Se observó afectación de tramos altos en 30/61 (49%), tumor desmoides en 7/77 (9,1%) e hipertrofia del epitelio pigmentario de la retina en 23/35 (65,7%). El 86,7% de los pacientes con esta alteración mostraron mutaciones entre los codones 454 y 1.019, relación estadísticamente significativa (p < 0,05). Conclusiones: El Registro Andaluz ha permitido ofrecer el diagnóstico genético en todas las familias afectas independientemente de su provincia de origen, mejorar el cribado, iniciar medidas preventivas precozmente y disminuir la frecuencia de cáncer colorrectal al diagnóstico en los familiares afectos registrados. La relación de la hipertrofia congénita del epitelio pigmentario de la retina con determinadas mutaciones es la única relación feno-genotípica con significación estadística(AU)

Objective: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. Material and methods: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. Results: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p< 0.05). Conclusions: The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic- genotypic correlation with statistical significance(AU)

Malignant colonic adenomas. Therapeutic criteria. Long-term results of therapy in a series of 42 patients in our healthcare area

Objective: a) to evaluate the appropriateness of histological criteria as proposed by Morson as indicators for surgery; and b) to compare the adequacy of Morson’s criteria with Haggitt’s levels as indicators for surgery in the case of malignant sessile lesions. Material and methods: we carried out a prospective, protocolized study of 42 patients with polyps with invasive carcinoma (IC) who underwent colonoscopic polypectomy from 1979 through 2008. We applied the histological criteria proposed by Morson to all the patients included in the series. Results: we treated 24 polyps with IC and favorable histological criteria (FC) and 18 polyps showing unfavorable histological criteria (UC). All polyps with FC were treated by means of colonoscopic polypectomy. None of the patients showed signs of disease after a mean follow-up period o f 9.67 yrs. Patients with polyps with UC were recommended to undergo surgery. The presence of unfavorable histological criteria in the polypectomy sample was clearly associated with an unfavorable patient outcome and showed a 100% sensitivity level, a negative prognostic value (NPV) of 100%, and a false negative (FN) percentage of 0% for the prognosis of the disease. We found 12 sessile polyps (Haggitt’s level 4). Colonoscopic polypectomy was the treatment employed in 9 out of 12 cases. All patients are free from disease (mean follow- up 7.3 yrs). If Haggitt’s level criteria had been applied, all 12 patients would have undergone surgery. This means 58% more patients than following Morson’s criteria. Conclusions: Morson’s criteria are considered an adequate diagnostic tool for the indication of surgery in patients with malignant adenomas. Haggitt’s invasion levels do not accurately discriminate the necessity for surgery in case of malignant sessile lesions(AU)

Malignant colonic adenomas. Therapeutic criteria. Long-term results of therapy in a series of 42 patients in our healthcare area.

OBJECTIVE: a) to evaluate the appropriateness of histological criteria as proposed by Morson as indicators for surgery; and b) to compare the adequacy of Morson s criteria with Haggitt s levels as indicators for surgery in the case of malignant sessile lesions. MATERIAL AND METHODS: we carried out a prospective, protocolized study of 42 patients with polyps with invasive carcinoma (IC) who underwent colonoscopic polypectomy from 1979 through 2008. We applied the histological criteria proposed by Morson to all the patients included in the series. RESULTS: we treated 24 polyps with IC and favorable histological criteria (FC) and 18 polyps showing unfavorable histological criteria (UC). All polyps with FC were treated by means of colonoscopic polypectomy. None of the patients showed signs of disease after a mean follow-up period o f 9.67 yrs. Patients with polyps with UC were recommended to undergo surgery. The presence of unfavorable histological criteria in the polypectomy sample was clearly associated with an unfavorable patient outcome and showed a 100% sensitivity level, a negative prognostic value (NPV) of 100%, and a false negative (FN) percentage of 0% for the prognosis of the disease. We found 12 sessile polyps (Haggitt s level 4). Colonoscopic polypectomy was the treatment employed in 9 out of 12 cases. All patients are free from disease (mean follow-up 7.3 yrs). If Haggitt s level criteria had been applied, all 12 patients would have undergone surgery. This means 58% more patients than following Morson s criteria. CONCLUSIONS: Morson s criteria are considered an adequate diagnostic tool for the indication of surgery in patients with malignant adenomas. Haggitt s invasion levels do not accurately discriminate the necessity for surgery in case of malignant sessile lesions.

[Follow-up after surgical treatment of patients with familial adenomatous polyposis: results in a southern Spanish population]. / Seguimiento posquirúrgico de los pacientes con poliposis adenomatosa familiar: resultados en una población del sur de España.

OBJECTIVE: The study was to assess changes in the rectal mucosa and pouch in a series of patients with familial adenomatous polyposis (FAP) who underwent either subtotal colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA), and to evaluate the suitability of the follow-up interval and postoperative treatment employed to prevent the development of cancer. METHOD: This study involved 28 patients with FAP who underwent IRA (n=20) or IPAA (n=8), and were followed endoscopically over a mean period of 7.47 years. The number and both macroscopic and histological features of polyps before and after surgery, the treatment, and complications were all analyzed. The suitability of the follow-up interval was assessed. RESULTS: None of the 26 patients who complied with follow-up developed rectal cancer. Two patients developed rectal cancer at 21 and 36 months after withdrawing from the protocol. Except in two cases in which surgery was indicated, patients who developed adenomas during follow-up were treated by endoscopic polypectomy. CONCLUSIONS: In our series, the failure to comply with follow-up examinations was associated with cancer development.

Seguimiento posquirúrgico de los pacientes con poliposis adenomatosa familiar: resultados en una población del sur de España / Follow-up after surgical treatment of patients with familial adenomtous polyposis: Results in a Southern Spanish population

Objetivo: analizar la evolución de la mucosa rectal y del reservorioasí como idoneidad de los intervalos de seguimiento y deltratamiento realizado para evitar la aparición del cáncer, en unaserie de pacientes con poliposis adenomatosa familiar (PAF), intervenidos.Método: estudio prospectivo de 28 pacientes con PAF intervenidosmediante anastomosis íleo-rectal (20 pacientes) y anastomosisíleo-anal con reservorio (8 pacientes). A todos se les habíarealizado un control endoscópico dos veces al año y análisis delnúmero y características macroscópicas e histológicas de los póliposantes y después de la cirugía así como del tratamiento realizado,de sus complicaciones y de la adecuación del intervalo de seguimiento.El seguimiento medio fue de 6,47 años (DE = 4,59;rango = 0,72-16,75 años).Resultados: ninguno de los 26 pacientes que cumplimentaroncorrectamente el protocolo de seguimiento desarrolló cáncer.Sólo dos pacientes lo desarrollaron al 1,75 y los 3 años, respectivamentedel abandono del protocolo. Los pacientes que desarrollaronadenomas durante el seguimiento fueron tratados con éxitomediante polipectomía endoscópica, salvo en dos casos que se indicócirugía.Conclusiones: en nuestra serie, el incumplimiento de las revisionesha sido el factor que ha condicionado la aparición de cáncer

Objective: the study was to assess changes in the rectal mucosaand pouch in a series of patients with familial adenomatouspolyposis (FAP) who underwent either subtotal colectomy and ileorectalanastomosis (IRA) or proctocolectomy and ileal pouchanalanastomosis (IPAA), and to evaluate the suitability of the follow-up interval and postoperative treatment employed to preventthe development of cancer.Method: this study involved 28 patients with FAP who underwentIRA (n=20) or IPAA (n=8), and were followed endoscopicallyover a mean period of 7.47 years. The number and bothmacroscopic and histological features of polyps before and aftersurgery, the treatment, and complications were all analyzed. Thesuitability of the follow-up interval was assessed.Results: none of the 26 patients who complied with follow-updeveloped rectal cancer. Two patients developed rectal cancer at21 and 36 months after withdrawing from the protocol. Except intwo cases in which surgery was indicated, patients who developedadenomas during follow-up were treated by endoscopic polypectomy.Conclusions: in our series, the failure to comply with followupexaminations was associated with cancer development

Clinical and ethical implications of genetic counselling in familial adenomatous polyposis.

The association of specific genetic disturbances with the development of hereditary cancer helps us to understand the risk of suffering from it, the possibility of an earlier diagnosis, and the treatment and prevention of this disease. Familial adenomatous polyposis (FAP) is a pre-neoplastic syndrome characterized by the presence of hundreds of adenomatous polyps in the colon, which develop into a carcinoma. FAP can be diagnosed using sequencing techniques to detect mutations in the germinal line of the APC (adenomatous polyposis coli) gene. The genetic diagnostic approach in families with FAP, previously followed up in the Gastrointestinal Clinic, has both advantages and disadvantages, and places us nearer the disease and patient. Disclosing the results of this genetic test entails relevant problems in clinical practice, which affect the health field and raise legal and ethical issues, along with the familial, occupational, and social implications that knowing the genetic status can have on the patient. Genetic analysis is rare in normal clinical practice, which involves errors in the interpretation of the results obtained, and during the process of genetic counselling. Specialized multidisciplinary units are necessary for the management of patients with FAP undergoing analysis and appropriate genetic counselling, thus providing an individualized service. The creation of FAP registers and protocols for this healthcare process should optimize the management of these patients and their families.

Implicaciones clínicas y éticas del consejo genético en la poliposis adenomatosa familiar / Clinical and ethical implications of genetic counselling in familial adenomatous polyposis

La asociación de determinadas alteraciones genéticas con laaparición de cáncer hereditario, nos permite conocer el riesgo depadecerlo, posibilitando el diagnóstico precoz, el tratamiento y laprevención de la enfermedad. La poliposis adenomatosa familiar(PAF) es un síndrome preneoplásico que se caracteriza por la presenciade cientos de pólipos adenomatosos en colon, que evolucionaránhacia carcinoma. La PAF puede ser diagnosticada mediantetécnicas de secuenciación que detectan mutaciones en lalínea germinal del gen APC (adenomatous poliposis coli).El abordaje del diagnóstico genético en familias con PAF seguidaspreviamente en la consulta de digestivo, ha permitido ponerde manifiesto tanto las ventajas como los inconvenientes de estaforma de acercarnos a la enfermedad y a los pacientes. La revelaciónde los resultados de la prueba genética comporta importantesproblemas en la práctica clínica, que afectan tanto al ámbito sanitario,como al ético y legal, además de las implicaciones familiares,laborales y sociales que el conocimiento del status genéticopuede tener para el paciente.El análisis genético es poco frecuente en la práctica clínica habitual,lo que conlleva errores tanto en la interpretación de los resultadosobtenidos como durante el proceso del consejo genético.Son necesarias unidades multidisciplinares especializadas en elmanejo de pacientes con PAF, en las cuales se realice un análisis yun consejo genético adecuado, permitiendo así una atención personalizada.La creación de registros de PAF y la protocolizaciónde este proceso sanitario debería optimizar el manejo de estos pacientesy sus familias

The association of specific genetic disturbances with the developmentof hereditary cancer helps us to understand the risk of sufferingfrom it, the possibility of an earlier diagnosis, and the treatmentand prevention of this disease. Familial adenomatouspolyposis (FAP) is a pre-neoplastic syndrome characterized by thepresence of hundreds of adenomatous polyps in the colon, whichdevelop into a carcinoma. FAP can be diagnosed using sequencingtechniques to detect mutations in the germinal line of the APC(adenomatous polyposis coli) gene.The genetic diagnostic approach in families with FAP, previouslyfollowed up in the Gastrointestinal Clinic, has both advantagesand disadvantages, and places us nearer the disease and patient.Disclosing the results of this genetic test entails relevantproblems in clinical practice, which affect the health field and raiselegal and ethical issues, along with the familial, occupational, andsocial implications that knowing the genetic status can have onthe patient.Genetic analysis is rare in normal clinical practice, which involveserrors in the interpretation of the results obtained, and duringthe process of genetic counselling. Specialized multidisciplinaryunits are necessary for the management of patients with FAPundergoing analysis and appropriate genetic counselling, thusproviding an individualized service. The creation of FAP registersand protocols for this healthcare process should optimize themanagement of these patients and their families

Whipple's disease: report of cases diagnosed in our hospital.

We present here a retrospective study of nine patients diagnosed with Whipple's disease (WD) in our hospital. This report em-phasises clinical presentation, diagnostic methods, treatment and response to treatment. In our study, the disease was more frequent in males, and the most frequent presenting symptoms were arthralgia, diarrhoea and weight loss. Since the intestine is almost always affected, oral endoscopy is a useful technique for the diagnosis of WD because it shows the typical miliary pattern and aids in obtaining biopsies to show the presence of PAS-positive macrophages (a suggestive though not diagnostic finding), to show bacilli using electron microscopy, or to detect genetic material using PCR. Our patients responded well to treatment. The most frequently used antibiotic was oral trimethoprim-sulfamethoxazole for at least one year. Treatment with penicillin G and IM streptomycin for 14 days was reserved for severe cases or cases that responded poorly to treatment.

Enfermedad de Whipple: presentación de los casos diagnosticados en nuestro hospital / Whipple's disease: report of cases diagnoses in our hospital

Presentamos un estudio retrospectivo de nueve pacientes diagnosticados de enfermedad de Whipple (EW) en nuestro hospital, haciendo hincapié en las formas de presentación clínica, métodos diagnósticos, pautas de tratamiento y respuesta al mismo. En nuestra serie la enfermedad fue más frecuente en el varón, siendo los síntomas más frecuentes las artralgias, diarrea y pérdida de peso. Al ser la afectación intestinal casi constante, la endoscopia oral es una técnica útil para el diagnóstico de EW ya que además de mostrar el típico patrón miliar permite la toma de biopsias demostrando la presencia de macrófagos PAS + (hallazgo sugestivo pero no diagnóstico) y la demostración de los bacilos mediante microscopía electrónica o material genético de los mismos mediante técnicas de PCR. La respuesta al tratamiento fue favorable en nuestros pacientes, siendo el fármaco más utilizado el trimetropim-sulfametoxazol vía oral durante al menos un año, reservando el tratamiento intramuscular durante 14 días con penicilina G y estreptomicina en los casos más graves o con escasa respuesta al tratamiento. (AU)