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1.
Am J Gastroenterol ; 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38032076

RESUMEN

INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. METHODS: All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses ( International Classification of Disease, 10th Revision ), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. RESULTS: The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP ( P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25-2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17-1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19-2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20-1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09-2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10-3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24-2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26-2.70, P = 0.002). DISCUSSION: Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased likelihood of needing antidepressants and antipsychotics.

2.
Gastroenterology ; 165(3): 573-581.e3, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37201686

RESUMEN

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. METHODS: All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. RESULTS: The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28-5.17; P < .001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58-8.22; P < .001), pancreatic cancer (HR, 6.45; 95% CI, 2.02-20.64; P = .002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76-119.47; P = .013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53-20.23; P = .20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02-3.50; P = .042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. CONCLUSIONS: Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.


Asunto(s)
Poliposis Adenomatosa del Colon , Neoplasias Colorrectales , Neoplasias Duodenales , Neoplasias Primarias Secundarias , Humanos , Estudios de Cohortes , Neoplasias Primarias Secundarias/complicaciones , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/epidemiología , Poliposis Adenomatosa del Colon/cirugía , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/complicaciones , Neoplasias Duodenales/complicaciones , Dinamarca/epidemiología
3.
Am J Gastroenterol ; 117(2): 343-345, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34913876

RESUMEN

INTRODUCTION: In patients with familial adenomatous polyposis, the Spigelman classification is recommended for staging and risk stratification of duodenal adenomatosis. Although the classification has been used for decades, it has never been formally validated. METHODS: We included consecutive FAP patients undergoing upper gastrointestinal endoscopic surveillance and evaluated the inter- and intrarater reliability of the Spigelman classification. RESULTS: The interrater reliability of the endoscopic parameters and the Spigelman classification was good and excellent, respectively. The intrarater reliability of the endoscopic parameters and the Spigelman classification was moderate and good, respectively. DISCUSSION: The results support continued use of the Spigelman classification as the primary end point for future studies and as key endoscopic performance measure.


Asunto(s)
Poliposis Adenomatosa del Colon/clasificación , Neoplasias Duodenales/clasificación , Duodenoscopía/métodos , Duodeno/patología , Estadificación de Neoplasias/métodos , Poliposis Adenomatosa del Colon/diagnóstico , Adulto , Biopsia , Neoplasias Duodenales/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados
5.
Clin Gastroenterol Hepatol ; 17(11): 2294-2300.e1, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30743005

RESUMEN

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that increases risk for colorectal cancer (CRC). We assessed changes in the incidence and prevalence of CRC, and survival times, of patients with FAP participating in the Danish follow-up study. METHODS: We collected data from the Danish Polyposis Registry, a nationwide, complete registry of patients with FAP that includes clinical information, surgical procedures, follow-up findings, and pathology reports. We compared data between the periods of 1990-1999 and 2000-2017. In 2017, the registry contained 226 families with 721 individuals with FAP. Probands were defined as patients diagnosed based on bowel symptoms, without any knowledge of hereditary bowel disease. Call-up patients were defined as those found to have FAP during screening and due to a diagnosis of FAP in first-degree relatives. RESULTS: Although the mean incidence rate of FAP was stable from 1990-1999 (0.19/100,000/year) to 2000-2017 (0.32/100,000/year) (P = .91), the point prevalence increased from 4.86/100,000 in 1999 to 6.11/100,000 by the end of 2017 (P = .005). During 2000-2017, 25 of 72,218 CRC cases were associated with FAP (0.03%)-this was a significant decrease from 1990-1999 (26/30,005 cases; 0.09%) (P = .001). The risk of CRC was significantly higher for probands (n = 191; 61.6%) than call-up cases (n = 5; 1.9%) (P < .001). All CRCs in call-up patients were detected at the diagnosis of FAP (no cases were identified in the follow-up program). The median life expectancy for call-up patients was 72.0 years (95% CI, 63.3-80.7), compared to 55.0 years for probands (95% CI, 51.2-58.8) (P < .001). Therefore, the tracing and follow-up program increased life expectancy by 17.0 years for first-degree family members. CONCLUSION: The Danish Polyposis Registry enables close monitoring of patients with FAP, reducing risk of CRC and prolonging life.


Asunto(s)
Poliposis Adenomatosa del Colon/complicaciones , Neoplasias Colorrectales/epidemiología , Tamizaje Masivo , Sistema de Registros , Poliposis Adenomatosa del Colon/diagnóstico , Adolescente , Adulto , Neoplasias Colorrectales/etiología , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto Joven
6.
Pol Przegl Chir ; 88(2): 99-105, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-27213256

RESUMEN

UNLABELLED: Invasion of urinary organs due to advanced colorectal cancer can comprise a surgical challenge in achieving negative resection margins. The aim of the study was to asses the outcome of patients with colorectal cancer invading the lower urinary organs. MATERIAL AND METHODS: This is a cohort study that retrospectively evaluated the surgical and pathological findings after the resection of colorectal cancer with adjacent urological organs due to advanced colorectal cancer. Patients with primary colorectal cancer invading urological organs where primary resection was attempted were included. RESULTS: The study included 31 patients who underwent surgery in our department between 1997 and 2012. Median age was 65 years (range 44-77 years). Seventeen patients underwent partial cystectomy, one had partial prostatectomy performed, eight patients underwent cystoprostatectomy, two had cystectomy performed and three had prostatectomy performed. Overall morbidity rate was 71% (95% Confidence Interval (CI): 55-84%, n=22). The 30-day mortality rate was 10% (95% CI: 0-23%, n=3). Twentyseven of 31 patients had free resection margins. Four of 28 patients developed distant metastasis (14%, 95% CI: 4-29%), 11% developed local recurrence (95% CI: 0-25%, n=3). Median follow-up was 41 months (range 0-150 months). Histopathological examination revealed tumour invasion in 52% (95% CI: 35-69%, n=15) of the resected urological organs. The overall five-year survival rate was 70%. The five-year survival rate in the radical resection group was 74%. CONCLUSIONS: En-bloc resection of colorectal cancer with adjacent urological organs has a high morbidity rate. However it is still possible to achieve negative resection margins in most cases.


Asunto(s)
Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/cirugía , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Urológicas/etiología , Neoplasias Urológicas/cirugía , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Polonia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
7.
Gastrointest Endosc ; 84(1): 115-125.e4, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26769407

RESUMEN

BACKGROUND AND AIMS: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. RESULTS: The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.


Asunto(s)
Poliposis Adenomatosa del Colon/patología , Cirugía Colorrectal , Gastroenterólogos , Neoplasias Primarias Múltiples/patología , Índice de Severidad de la Enfermedad , Poliposis Adenomatosa del Colon/terapia , Colectomía , Colonoscopía , Consenso , Resección Endoscópica de la Mucosa , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Sigmoidoscopía , Sulfasalazina , Grabación en Video
8.
Gut ; 65(2): 286-95, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25792707

RESUMEN

BACKGROUND AND AIM: Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. METHODS: The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. RESULTS: 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). CONCLUSIONS: CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number N01-CN95040.


Asunto(s)
Pólipos Adenomatosos/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Celecoxib/administración & dosificación , Celecoxib/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Eflornitina/administración & dosificación , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/patología , Adolescente , Adulto , Celecoxib/efectos adversos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sigmoidoscopía , Carga Tumoral , Adulto Joven
9.
Ugeskr Laeger ; 175(19): 1335-9, 2013 May 06.
Artículo en Danés | MEDLINE | ID: mdl-23663370

RESUMEN

Familial adenomatous polyposis (FAP) is an autosomally dominant disease characterized by early development of up to thousands of colorectal adenomas and colorectal carcinoma in untreated patients. Extra-colonic manifestations include duodenal adenomatosis and desmoid development. Due to identification of gene carriers by DNA analysis or endoscopy the prognosis is good after early colectomy, but life-long surveillance of the rectum and the duodenum is necessary. The Danish Polyposis Register coordinates prophylactic examination and treatment in the families, and serves as basis for research.


Asunto(s)
Poliposis Adenomatosa del Colon , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/patología , Poliposis Adenomatosa del Colon/cirugía , Colectomía , Diagnóstico Diferencial , Humanos , Clasificación del Tumor , Estadificación de Neoplasias , Sistema de Registros
10.
Dan Med J ; 59(10): A4517, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23158893

RESUMEN

INTRODUCTION: A de-functioning loop ileostomy (LI) reduces the consequences of anastomotic leak following low anterior resection, but its construction as well as its closure can be associated with complications. The aim of the present study was to identify risk factors for postoperative complications and particularly to determine if operation performed by trainees carry a higher risk of complications than operation performed by experienced surgeons. MATERIAL AND METHODS: This was a retrospective single-centre analysis of the medical records of 159 consecutive patients who underwent LI closure following low anterior resection for rectal cancer in the period from January 2002 to December 2008. RESULTS: Postoperative complications developed in 32 patients (20.1%). Surgical complications occurred in 27 patients (17%) including small bowel obstruction in five (3%), anastomotic leak in four (2.5%), wound infection in eight (5%) and incisional hernia in eight (5%). There was no postoperative mortality. Univariate analysis showed that an increased rate of complications was associated with female gender (p = 0.02), small bowel resection at closure (p = 0.009) and a long interval between construction and closure of the loop ileostomy (p = 0.049). CONCLUSION: Closure of an LI is associated with a low mortality, but a relatively high rate of complications. Operation performed by trainees was not associated with an increased complication rate. More complications were seen in patients who underwent small bowel resection and those who had delayed ileostomy closure. FUNDING: not relevant TRIAL REGISTRATION: not relevant.


Asunto(s)
Fuga Anastomótica/epidemiología , Ileostomía , Obstrucción Intestinal/cirugía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/cirugía , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Neoplasias del Recto/complicaciones , Reoperación , Estudios Retrospectivos , Factores de Riesgo
11.
Dan Med J ; 59(9): A4507, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22951201

RESUMEN

INTRODUCTION: Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In patients with unfavourable post-TEM histology, salvage surgery can be performed. The aim of this study was to evaluate the results of early radical surgery after TEM for rectal cancer. MATERIAL AND METHODS: From 1997 to 2010, 86 TEM procedures were performed in 79 patients due to rectal cancer. Early salvage surgery was performed in 25 patients. Data were obtained from the patients' charts and reviewed retrospectively. Perioperative data and oncological outcome were analysed. RESULTS: No patients received preoperative chemotherapy. The median time to salvage surgery was 37 days. Five patients underwent laparoscopic surgery. The median operative time was 165 min (range: 101-341 min, 95% confidence interval (CI): 156-214 min) and the median blood loss 275 ml (range: 0-1,275 ml, 95% CI: 232-530 ml). The 30-day mortality was 8% (95% CI: 1-19%, n = 2). Intraoperative perforation occurred in 20% (95% CI: 3-37%, n = 5). The median number of harvested lymph nodes was 12 (range: 3-25, 95% CI: 9-14) and the median circumferential resection margin (CRM) was 10 mm (range: 0-20 mm, 95% CI: 5-12 mm). Only one patient (4%, 95%CI: 1-12%) had a positive CRM. The median follow-up time was 25 months (range: 3-80 months). There was no local recurrence. Distant metastasis occurred in 4% (95% CI: 1-12%, n = 1). CONCLUSION: Early salvage surgery after TEM seems to be safe despite a high risk of specimen perforation during the operation. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.


Asunto(s)
Adenocarcinoma/cirugía , Adenoma/cirugía , Microcirugia , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Terapia Recuperativa , Adenocarcinoma/secundario , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/cirugía , Fuga Anastomótica/etiología , Endoscopía Gastrointestinal , Femenino , Humanos , Obstrucción Intestinal/etiología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Estudios Retrospectivos , Terapia Recuperativa/efectos adversos , Dehiscencia de la Herida Operatoria/etiología , Factores de Tiempo , Resultado del Tratamiento
12.
Dis Colon Rectum ; 54(10): 1229-34, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21904137

RESUMEN

BACKGROUND: Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice. OBJECTIVES: Our aim was to assess several risk factors for desmoid tumor development in an international cohort of patients with familial adenomatous polyposis and to evaluate the clinical relevance of risk factors. DESIGN: This was a retrospective cohort study. SETTING AND PATIENTS: Polyposis registries in The Netherlands, France, Denmark, Finland, and Italy provided information on familial adenomatous polyposis patients with desmoid tumors. MAIN OUTCOME MEASURES: We used univariate and multivariable analyses of data from registries in The Netherlands, France, Denmark, and Finland to test whether gender, APC mutation site, previous colorectal surgery, colorectal cancer, and family history for desmoid tumors contribute to risk of developing desmoid tumors at any location, or specifically at an intra-abdominal location. The effect of family history was tested with a generalized linear mixed model. RESULTS: : Of 2260 patients with familial adenomatous polyposis from 912 families in The Netherlands, France, Denmark, and Finland, 220 patients (10%) had desmoid tumors (101 men). In 387 patients with desmoid tumors (including 167 patients from the Italian registry), the median age at diagnosis of the first desmoid tumor was 31 years (range, 4 months-74 years). Desmoid locations were intra-abdominal (53%), abdominal wall (24%), extremities (9%), and unknown sites or combinations of sites (14%). Multivariable analysis of risk factors for desmoids at any location showed surgery (OR, 2.58; P = .0004), an APC mutation 3' of codon 1444 (OR, 3.0; P < .0001), and a positive family history (P < .0001) to be independently associated with desmoid development. When only intra-abdominal location was analyzed, APC mutation site was not associated with desmoid development. LIMITATIONS: Selection bias may have occurred. CONCLUSIONS: A positive family history for desmoid tumors, abdominal surgery, and APC mutation site are significant risk factors for development of desmoid tumors. The results may have implications for determining the optimal management of FAP patients and guide future studies.


Asunto(s)
Poliposis Adenomatosa del Colon/complicaciones , Fibromatosis Abdominal/complicaciones , Fibromatosis Abdominal/genética , Genes APC , Mutación/genética , Abdomen/cirugía , Poliposis Adenomatosa del Colon/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Europa (Continente) , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
13.
Ugeskr Laeger ; 173(22): 1563-7, 2011 May 30.
Artículo en Danés | MEDLINE | ID: mdl-21627899

RESUMEN

A protective loop ileostomy is used to reduce the incidence and consequences of anastomotic failure following colorectal resection. Closure of a loop ileostomy is associated with low mortality but many studies have demonstrated high morbidity rates. The aim of this review is to examine the existing evidence on the morbidity following closure of loop ileostomies and to investigate possible risk factors for complications. There is no consensus in the literature about the risk factors for complications. Counseling of the patient about the risks for complications is emphasized.


Asunto(s)
Ileostomía/métodos , Anastomosis Quirúrgica/efectos adversos , Colon/cirugía , Medicina Basada en la Evidencia , Humanos , Ileostomía/efectos adversos , Educación del Paciente como Asunto , Complicaciones Posoperatorias/etiología , Recto/cirugía , Factores de Riesgo , Resultado del Tratamiento
14.
Cancer Prev Res (Phila) ; 4(5): 655-65, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21543343

RESUMEN

Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin--mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas.


Asunto(s)
Poliposis Adenomatosa del Colon/prevención & control , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Almidón/uso terapéutico , Adolescente , Adulto , Niño , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Agencias Internacionales , Masculino , Pronóstico , Recto/efectos de los fármacos , Adulto Joven
15.
Fam Cancer ; 10(2): 303-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21359561

RESUMEN

Familial adenomatous polyposis (FAP) is a rare genetic disease. Without treatment, FAP patients have a 100% lifetime risk of developing colorectal cancer. This study was conducted to evaluate the effect of celecoxib treatment in prolonging the time to FAP-related events and to document the safety profile of the long-term use of celecoxib (≥6 months) in FAP patients. FAP patients receiving celecoxib in routine clinical practice were individually matched with historical/concurrent FAP patients not receiving celecoxib. The study population included patients aged 12 years or older registered in national and regional FAP registries in Denmark, the United States, Spain, and Canada. Descriptive statistics were used to summarize dose and duration among celecoxib treated patients. The primary study endpoints, time-to-next-FAP events, were examined with Kaplan-Meier method. Fifty four celecoxib-treated patients were recruited and a matched control was identified for 13 of these patients. The Kaplan-Meier estimated probability of not having a polypectomy 12 and 60 months post- ileorectal anastomosis in the celecoxib-treated patients (n = 33) was 60.6% and 42.2%, respectively. The estimated probability of not having a polypectomy 6-60 months post-ileal pouch-anal anastomosis the celecoxib-treated patients (n = 24) was 100%. The median total daily dose of celecoxib was 698.9 mg with the majority treated more than 24 months. Five celecoxib-treated patients experienced 6 serious adverse events with one of these events (rash) considered related to celecoxib. Long term celecoxib treatment appeared to be well tolerated in FAP patients with or without FAP-related surgeries.


Asunto(s)
Poliposis Adenomatosa del Colon/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Anciano , Celecoxib , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pirazoles/efectos adversos , Sulfonamidas/efectos adversos , Resultado del Tratamiento
17.
Ugeskr Laeger ; 171(35): 2453-8, 2009 Aug 24.
Artículo en Danés | MEDLINE | ID: mdl-19732529

RESUMEN

Colorectal carcinoma is one of the most prevalent malignancies in Western countries. Lymph node status is a significant prognosticator. The chance of identifying node-positivity is positively correlated with the number of lymph nodes (LN) identified. The present paper discusses various variables that may influence the detection of LNs, including patient- as well as surgeon- and pathologist-related issues. The pathologist-related variable most probably shapes the yield the most. Introduction of guidelines focusing on the most appropriate technique may secure better and more consistent results, and the pathologist's commitment is crucial in this respect.


Asunto(s)
Neoplasias Colorrectales/patología , Ganglios Linfáticos/patología , Neoplasias Colorrectales/cirugía , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática/patología , Variaciones Dependientes del Observador , Patología Quirúrgica , Pautas de la Práctica en Medicina , Pronóstico , Fijación del Tejido/métodos
18.
Ugeskr Laeger ; 171(35): 2458-62, 2009 Aug 24.
Artículo en Danés | MEDLINE | ID: mdl-19732530

RESUMEN

INTRODUCTION: The number of identified lymph nodes (LNs) is an essential element in the pathologist's rapport on colorectal resection specimens with carcinoma (CRSC). A considerable number of papers discuss the acceptable minimum number of identified LNs to secure a correct LN status (LNS). Details as to the most appropriate grossing technique for LN detection are, however, largely lacking. In this paper the influence of the time invested by the pathologist in the pursuit of LN is investigated. MATERIAL AND METHODS: The material comprised 150 CRSCs. The usual gross examination was extended by 15 minutes in an effort to identify additional LNs. Provided this careful analysis failed to produce 12 LNs and all detected LNs were benign (pNx), the specimen was re-sampled for an additional 15-minute period. Data were correlated with a baseline material comprising 100 CRSCs. RESULTS: The intensified search for LNs increased the average number of LNs pr. specimen from 9.1 to 14.9. The number of cases with pNx was reduced from 54% to 18%. Re-sampling performed on 25 specimens resulted in the detection of another 61 LNs in 21 cases, ranging from 1 to 8 LN pr. specimen (median 2), whereby pNx was converted to pN0 in eight cases. In another four cases, additional LNs were not detected. Re-sampling did not uncover metastatic disease. CONCLUSION: This intensified effort in the Department of Pathology resulted in a more reliable LNS.


Asunto(s)
Neoplasias Colorrectales/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias Colorrectales/cirugía , Humanos , Escisión del Ganglio Linfático/métodos , Estadificación de Neoplasias , Estudios Prospectivos , Manejo de Especímenes , Factores de Tiempo
19.
Ugeskr Laeger ; 171(35): 2476-81, 2009 Aug 24.
Artículo en Danés | MEDLINE | ID: mdl-19732535

RESUMEN

INTRODUCTION: The treatment of rectum cancer depends on the tumour stage, and until 2005 treatment included preoperative radiation therapy for the T3 and T4 cancer stages. An exact preoperative assessment of the cancer stage is therefore essential. In Denmark rectal Magnetic Resonance Imaging (MRI) is used as a standard procedure in preoperative evaluation, sometimes supplemented by transrectal ultrasound (TRUS). The purpose of this study was to determine the accuracy of preoperative MRI in tumour stage evaluation in order to correctly select the patients who will benefit from preoperative radiation therapy. MATERIAL AND METHODS: The MRI reports from 173 patients (98 male, 75 female, mean age 71 years) who underwent surgery for rectum cancer at Hvidovre Hospital, Copenhagen during the 2002-2005-period were evaluated. The T-stage of the MRI report was compared to the histological T-stage of the resected tumour. RESULTS: The overall accuracy of T-staging was 58% (n = 100) of which 41% T2 tumours (n = 18), 78% T3 tumours (n = 78) and 33% T4 tumours (n = 4) were correctly staged. In all, 29% of cancers were overstaged (n = 50) (100% of T1 tumours, 59% of T2 tumours, 7% of T3 tumours). A total of 13% of the cancers were understaged (15% of T3 tumours, 67% of T4 tumours). The selection of patients for preoperative radiation therapy had a sensitivity and specificity of 83% and 48%, respectively. CONCLUSION: The overall accuracy of 58% indicates that MR imaging in the early learning phases was not an optimal method for the preoperative T-staging of rectal cancer. In particular, the low specificity of MRI in selecting the patients who will benefit from preoperative radiation can result in overtreatment and increased morbidity.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Radioterapia Adyuvante , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Sensibilidad y Especificidad
20.
Ugeskr Laeger ; 171(38): 2735-8, 2009 Sep 14.
Artículo en Danés | MEDLINE | ID: mdl-19771662

RESUMEN

Danish rectal cancer patients previously had an inferior prognosis compared with the other Scandinavian countries. An analysis of overall and relative survival in 1994-2006 was based on the Danish Colorectal Cancer Group's national colorectal cancer databases and the Central Population Registry. The 5-year overall survival in 10,632 operated patients increased from 37% to 51% and the 5-year relative survival rose from 46% to 62%. In conclusion, the prognosis improved considerably mainly due to implementation of total mesorectal excision, improved preoperative staging and centralised surgical treatment.


Asunto(s)
Neoplasias del Recto/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Dinamarca/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/cirugía , Sistema de Registros , Análisis de Supervivencia , Tasa de Supervivencia , Adulto Joven
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