Rofecoxib Reduces Polyp Recurrence in Familial Polyposis

The long-term (mean of 16.4±4.2 months) efficacy and safety of rofecoxib (a specific COX-2 inhibitor) in maintaining the colon free of polyps in familial polyposis patients was assessed. Eight patients were treated with rofecoxib 25 mg every day. Sigmoidoscopy/colonoscopy was performed at study entry and every six months. At each endoscopy the number, size, and histological grade of all polyps were assessed, and the polyps were removed. The drug was well tolerated with no significant adverse events throughout the study. A highly significant reduction in the rate of polyp formation (70–100%) was observed in all patients from a mean number of 15.1±11.7 at baseline to 6.0±5.8 at one year and 1.6±1.6 at the end of follow-up (P =0.016 and 0.008, respectively). No patient developed cancer or high-grade adenoma. In conclusion, Long-term use of rofecoxib is well tolerated and effective in inhibiting polyp formation in polyposis patients.     

The Role of Chromoendoscopy in the Surveillance of the Duodenum of Patients with Familial Adenomatous Polyposis

Adenomas of the duodenum have been described in patients with familial adenomatous polyposis (FAP). Patients with FAP are at high risk for the development of periampullary cancer. The aim of our study was to evaluate if endoscopic visualization of small polyps, often overlooked at standard endoscopic examination, was improved by chromoendoscopy. Ten patients with FAP and previous colectomy underwent upper gastrointestinal endoscopy. Two skilled endoscopists were involved for each endoscopy. Evaluation of number and diameter of polyps was made before and after staining. After staining we detected a larger number of duodenal polyps than found at the standard endoscopic examination, the difference being statistically significant. This result seems to suggest that chromoendoscopy may improve diagnostic yield of endoscopy. Further studies are needed to suggest the best surveillance program and the appropriate therapeutic modality for these patients.     

Inflammatory Fibroid Polyp of the Duodenum

Inflammatory fibroid polyp of the gastrointestinal tract is an unusual lesion of apparent submucosal origin but of unknown etiology. The stomach is most commonly involved with typical presentation being a rounded or oval polyp in the gastric antrum. Occurrence in the duodenum is distinctly rare since only three previous cases have been reported. We present a patient with an unusually long inflammatory fibroid polyp arising in the third portion of the duodenum.     

An Anti-adenoma Antibody, Adnab-9, May Reflect the Risk for Neoplastic Progression in Familial Hamartomatous Polyposis Syndromes

Patients with the hamartomatous polyposis Peutz-Jeghers and familial juvenile polyposis syndromes are predisposed to colorectal cancer but lack early genetic alterations found in adenomatous premalignant lesions. We studied hamartomatous polyps for the expression of an early preneoplastic colorectal neoplasia risk marker also found in familial adenomatous polyposis patients. Retrospective, genetic, and hospital archival tissue immunohistochemistry using Adnab-9, a premalignant marker often found in Paneth-like cells (PCs), was performed on sections of polyps from eight patients with Peutz-Jeghers syndrome, eight patients with familial juvenile polyposis, and 36 hyperplastic polyp control sections. Anti-α-defensin 5 (AD5), a universal PC marker, was also used to label a subgroup of sections. Hamartomatous polyposis patients also underwent specific genetic analysis. Eighty-nine percent of Peutz-Jeghers syndrome polyps labeled with Adnab-9 compared with 63% for AD5; 88% of familial juvenile polyposis sections also labeled with Adnab-9. Of the 36 hyperplastic polyp sections, only four (11%) labeled with Adnab-9 and one (3%) with AD5. Adnab-9 labeling of PCs in the epithelial elements of hamartomatous colonic lesions of hereditary hamartomatous syndrome patients reflects the predisposition to colorectal cancer, further justifying early intervention strategies.     

Duodenal Polyposis and Malignancy in a Case of Familial Polyposis Coli

Familial polyposis coli is characterized by progressive adenomatosis with ultimate progression to colon cancer. It is becoming clear that these patients also have a high incidence of upper gastrointestinal adenomatous polyps, with some developing periampullary malignancies similar to those seen in Gardner's syndrome. This has led to recommendations for periodic endoscopic screening of asymptomatic polyposis patients. We report a patient with familial polyposis coli who developed an adenocarcinoma in the distal duodenum. This case points out the importance of screening the upper gastrointestinal tract in patients at risk.     

Germline variants in Hamartomatous Polyposis Syndrome-associated genes from patients with one or few hamartomatous polyps

Objective: A subgroup of patients with hamartomatous polyps in the GI tract has a hereditary Hamartomatous Polyposis Syndrome with an increased risk of cancer. The distinction between patients with one or few polyps and patients with a syndrome can be difficult. A pathogenic germline mutation can be detected in a majority of HPS patients. This study investigates whether patients with one or few hamartomatous polyps could have a syndrome based on genetic screening of relevant genes.

Methods: We designed a gene panel including 26 hamartomatous polyposis-associated genes. Using targeted Next Generation Sequencing, DNA samples from 77 patients with 84 hamartomatous polyps were sequenced. The detected germline variants were classified into pathogenicity classes.

Results: We detected several germline variants, among them three in ENG, two in BMPR1A, one in PTEN, and one in SMAD4. Although some of the detected variants have been reported previously none could be definitely pathogenic or likely pathogenic.

Conclusions: Our study points towards that genetic testing for the Hamartomatous Polyposis Syndromes in patients with one or few polyps does not improve diagnostics, however we illustrate that the clinical significance of genetic variants can be difficult to interpret. A family history of polyps, cancer, or extraintestinal findings or a minimum of 3–5 polyps seems to be relevant information to include before genetic testing.     

Clinical and Genetic Problems in Familial Intestinal Polyposis

The history of a family suffering from familial intestinal polyposis is presented, showing how a delayed onset of symptoms together with a lack of knowledge of affected relatives may obscure the familial nature of the disease. The necessity of examining all accessible relatives, irrespective of their advancing years, is stressed. Further, it is shown that in the absence of any familial incidence the proper diagnosis of an isolated case of polyposis is that the disease is the result of a fresh mutation.

The possibility of a non-familial form of this disease cannot be proved at present and will require a special genetic investigation. It is emphasized that the diagnosis of non-familial polyposis should not be made, as this will lead to a relaxation of the vigil that should be kept on the descendants of all patients with polyposis.

     

Impact of Screening Examinations on Survival in Familial Adenomatous Polyposis

Background: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). Methods: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. Results: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause ofdeath was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. Conclusion: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.     

家族性结肠息肉病合并癌变1例

家族性结肠息肉病(familial polyposis coli,FPC)又名家族性腺瘤性息肉病(familial adenomatous polyposis,FAP),系由位于人类5号染色体长臂5q21区域的腺瘤性结肠息肉病(adenomatous polyposis coli,APC)基因种系突变所致,是一种常染色体显性遗传病。FPC多于青少年期(15岁左右)起     

Intramucosal Gastric Carcinoma in a Patient with Familial Polyposis Coli

Upper gastrointestinal polyps commonly occur in patients with familial polyposis coli; but the occurrence of gastric carcinoma is very rare in this disorder. We report a case of intramucosal gastric carcinoma in a patient with familial polyposis coli and multiple gastrointestinal adenomatous polyps.