Therapy-Associated Polyposis, Late Presentation of a Childhood-Treated Disease.

Therapy-associated polyposis (TAP), an acquired gastrointestinal polyposis in childhood cancer survivors, poses diagnostic challenges resembling hereditary syndromes. Four TAP patients were studied, revealing upper gastrointestinal lesions after radiotherapy in 2 patients, managed by endoscopic resection. Two underwent total colectomy; 1 had adenocarcinoma from a polyp. Next-generation sequencing on diseased tissue revealed no alteration in mismatch repair genes with stable microsatellite status; however, there was somatic mutation in APC gene altering Wnt signaling pathway in all 3 precancerous lesions. Integrating endoscopic and surgical interventions is crucial, although ongoing studies aim to elucidate pathophysiology for potential targeted therapies in TAP management.

An Electronic Questionnaire to Survey Colorectal Cancer Screening Status and Identify High-Risk Cohorts in Large Health Care Organizations.

Though improved screening practices have reduced the incidence and mortality of colorectal cancer (CRC), screening rates continue to be suboptimal. This is especially true of high-risk individuals, who are difficult for clinicians to identify during a typical health care encounter. The authors developed an electronic patient questionnaire that determined an individual's CRC screening status and identified high-risk individuals. The questionnaire was administered to employees through the Department of Human Resources. The response rate was 44.7%; 81.2% of respondents aged ≥50 years were up-to-date on CRC screening; 878 high-risk individuals were identified, 77.7% of whom were up-to-date on CRC screening. However, among high-risk individuals aged 40 to 49 years, only 45.8% reported up-to-date CRC screening. The questionnaire was effective in measuring CRC screening rates and identifying high-risk individuals. Dissemination by the Department of Human Resources was novel, effective, and was not dependent on a health care encounter to assess screening or high-risk status.

Efficacy and safety of liquid nitrogen cryotherapy for treatment of Barrett's esophagus.

AIM: To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE, with and without dysplasia, or intramucosal adenocarcinoma (IMC). METHODS: This was a retrospective, single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-naïve or who had persistent intestinal metaplasia (IM), dysplasia, or IMC despite prior therapy. Barrett's mucosa was resected via EMR when clinically appropriate, then patients underwent cryotherapy until eradication or until deemed to have failed treatment. Surveillance biopsies were taken at standard intervals. RESULTS: From 2010 through 2014, 33 patients were studied regarding the efficacy of cryotherapy. Overall, 29 patients (88%) responded to cryotherapy, with 84% having complete regression of all dysplasia and cancer. Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy. Following cryotherapy, 15 patients with high-grade dysplasia (HGD) had 30% complete regression, 50% IM, and 7% low-grade dysplasia (LGD); one subject had persistent HGD. Complete eradication of dysplasia occurred in all 5 patients with LGD. In 5 patients with IM, complete regression occurred in 4, and IM persisted in one. In 136 cryotherapy sessions amongst 45 patients, adverse events included chest pain (1%), stricture (4%), and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR. CONCLUSION: Cryotherapy is an efficacious and safe treatment modality for Barrett's esophagus with and without dysplasia or intramucosal adenocarcinoma.

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst Ablation Protocol.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage followed by infusion of paclitaxel is effective for the treatment of mucinous pancreatic cysts. However, complications arise in 3%-10% of patients, presumably linked to the inflammatory effects of ethanol. We aimed to determine whether alcohol is required for effective pancreatic cyst ablation, if removing alcohol from the ablation process would improve complication rates, and whether a multi-agent chemotherapeutic cocktail could increase the rate of complete cyst resolution compared with findings reported from previous trials using alcohol followed by paclitaxel alone. METHODS: Between November 2011 and December 2016, we conducted a single-center, prospective, double-blind trial of 39 patients with mucinous-type pancreatic cysts. Patients were randomly assigned to 1 of 2 groups that underwent EUS-guided pancreatic cyst lavage with either 80% ethanol (control) or normal saline (alcohol-free group). Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after the procedure, and rates of serious and minor adverse events within 30 days of the procedure. RESULTS: At 12 months, 67% of patients who underwent alcohol-free EUS-guided cyst chemoablation had complete ablation of cysts compared with 61% of patients in the control group. Serious adverse events occurred in 6% of patients in the control group vs none of the patients in the alcohol-free group. Minor adverse events occurred in 22% of patients in the control group and none of the patients in the alcohol-free group. The overall rate of complete ablation was 64%. CONCLUSIONS: In this prospective, randomized, controlled trial, we found that alcohol is not required for effective EUS-guided pancreatic cyst ablation, and when alcohol is removed from the ablation process, there is a significant reduction in associated adverse events. A multi-agent chemotherapeutic ablation admixture did not appear to significantly improve rates of complete ablation compared with the current standard of alcohol lavage followed by paclitaxel alone. ClinicalTrials.gov ID: NCT01475331.

Endoscopic Management of Large (≥2 cm) Non-pedunculated Colorectal Polyps: Impact of Polyp Morphology on Outcomes.

BACKGROUND AND AIMS: Referrals for endoscopic management of large non-pedunculated (NP) colorectal polyps have increased as new techniques have emerged. The outcomes for referred large NP polyps based on the polyp morphology were investigated METHODS: A retrospective review of patients referred for large (≥20 mm) NP polyp management from January 2010 through June 2014 was completed. Polyp morphology was classified as either a NP polyp with depression (M1) or NP polyp with no depression (M0). Differences in treatment, histology, adverse events, outcomes at follow-up including residual disease, and need for surgical treatment were determined by morphology for all NP polyps ≥20 mm in size. RESULTS: One-hundred and sixty-nine M1 and 136 M0 polyps ≥20 mm were removed endoscopically during the review period. Mean size was 31.9 ± 11.0 mm in M1, and 26.8 ± 9.5 mm in M0 group (p < 0.0001). En bloc resection was possible in 18.3 % of M1 and 30.9 % of M0 lesions (p = 0.011) with endoscopic submucosal dissection used in 13 and 2.2 % of polyps, respectively (p < 0.0001). Residual polyp was found in 26.5 % (27/102) of M1 and 13.6 % (12/88) of M0 patients at surveillance colonoscopy (p = 0.029). On multivariate analysis, piecemeal resection and M1 morphology showed significant association with residual polyp (OR 4.23, 95 % CI 1.23-14.59, p = 0.022, and OR 2.15, 95 % CI 1.004-4.62, p = 0.049, respectively). CONCLUSION: Effective endoscopic management of large NP colorectal polyps, especially polyps without depression (M0), can be accomplished in the great majority of patients. Polyp morphology, particularly the presence or absence of depression, is a useful tool which influenced treatment, histology, and outcomes.

Is alcohol required for effective pancreatic cyst ablation? The prospective randomized CHARM trial pilot study.

BACKGROUND AND STUDY AIMS: In this study, we aim to determine the safety and feasibility of an alcohol-free approach to pancreatic cyst ablation using a chemotherapeutic ablation cocktail. PATIENTS AND METHODS: In this prospective, randomized, double-blinded pilot study, 10 patients with known mucinous type pancreatic cysts underwent endoscopic ultrasound (EUS)-guided fine needle aspiration and then lavage with either 80 % ethanol or normal saline. Both groups were then treated with a cocktail of paclitaxel and gemcitabine. Primary outcomes were reduction in cyst volume and rates of complications. RESULTS: At 6 months, patients randomized to the alcohol arm had an 89 % average volume reduction, with a 91 % reduction noted in the alcohol-free arm. Complete ablation was achieved in 67 % of patients in the alcohol-free arm at both 6 and 12 months, whereas the alcohol group recorded complete ablation rates of 50 % and 75 % at 6 and 12 months, respectively. One patient in the alcohol arm developed acute pancreatitis (20 %) with no adverse events in the alcohol-free arm. CONCLUSIONS: This study revealed similar ablation rates between the alcohol ablation group and the alcohol-free arm and demonstrates the safety and feasibility of an alcohol-free ablation protocol. This pilot study suggests that alcohol may not be required for effective cyst ablation.

Colorectal cancer screening in high-risk groups is increasing, although current smokers fall behind.

BACKGROUND: There is limited information about colorectal cancer (CRC) screening trends in high-risk groups, including the black, obese, diabetic, and smoking populations. For this study, the authors evaluated national CRC screening trends in these high-risk groups to provide insights into whether screening resources are being appropriately used. METHODS: This was a nationally representative, population-based study using the Behavioral Risk Factor Surveillance System from the Centers for Disease Control. Data analysis was performed using bivariate analyses with weighted logistic regression. RESULTS: In the general population, CRC screening increased significantly from 59% to 65% during the years 2006 to 2010. The screening prevalence in non-Hispanic blacks was 58% in 2006 and 65% in 2010. Among obese individuals, the prevalence of up-to-date CRC screening increased significantly from 59% in 2006 to 66% in 2010. Screening prevalence in individuals with diabetes was 63% in 2006 and 69% in 2010. The CRC screening prevalence in current smokers was 45% in 2006 and 50% in 2010. The odds of CRC screening in the non-Hispanic black population, the obese population, and the diabetic population were higher than in non-Hispanic whites, normal weight individuals, and the population without diabetes, respectively. Current smokers had significantly lower odds of CRC screening than never-smokers in the years studied (2006: odds ratio [OR], 0.71; 95% confidence interval [CI], 0.66-0.76; 2008: OR, 0.67; 95% CI, 0.63-0.71; 2010: OR, 0.69; 95% CI, 0.66-0.73). CONCLUSIONS: The prevalence of CRC screening in high-risk groups is trending upward. Despite this, current smokers have significantly lower odds of CRC screening compared with the general population.

Barrett's Esophagus: Emerging Knowledge and Management Strategies.

The incidence of esophageal adenocarcinoma (EAC) has increased exponentially in the last 3 decades. Barrett's esophagus (BE) is the only known precursor of EAC. Patients with BE have a greater than 40 folds higher risk of EAC compared with the general population. Recent years have witnessed a revolution in the clinical and molecular research related to BE. However, several aspects of this condition remain controversial. Data regarding the true prevalence of BE have varied widely. Recent studies have suggested a lower incidence of EAC in nondysplastic BE (NDBE) than previously reported. There is paucity of prospective data showing a survival benefit of screening or surveillance for BE. Furthermore, the ever-increasing emphasis on healthcare cost containment has called for reexamination of the screening and surveillance strategies for BE. There is a need for identification of reliable clinical predictors or molecular biomarkers to risk-stratify patients who might benefit the most from screening or surveillance for BE. Finally, new therapies have emerged for the management of dysplastic BE. In this paper, we highlight the key areas of controversy and uncertainty surrounding BE. The paper discusses, in detail, the current literature about the molecular pathogenesis, biomarkers, histopathological diagnosis, and management strategies for BE.

Screening for Familial Colorectal Cancer Risk amongst Colonoscopy Patients New to an Open-Access Endoscopy Center.

Purpose. We evaluated a questionnaire to aid in the recognition of CRC risk, as well as patient interest in their risk status within an open-access endoscopy center. Methods. A questionnaire was administered to new patients presenting for colonoscopy from May 2007 to February 2008. 287 patients were enrolled. Family history was evaluated using Amsterdam 1, II, and Revised Bethesda criteria. Recognition of risk and referral for counseling was assessed. Patients' interest to be contacted by a genetic counselor was also assessed. Results. 13.2 % (38/287) of patients met Revised Bethesda criteria. Of these, 18 (47.4 %) were previously told about their increased risk for CRC. Only 1 patient who met Revised Bethesda criteria (2.6 %) was previously referred for genetics, whereas none of the 3 patients who met Amsterdam I or II criteria were referred. 23.7 % of high-risk patients did not want to be contacted if found to be at increased risk for cancer. Conclusion. In our open-access endoscopy system, a significant number of high-risk patients remain unidentified and underreferred for genetic counseling due to numerous barriers. Our findings lend support to taking a public health approach to identifying those at risk for Lynch syndrome by implementing universal screening of all CRC specimens.

The revised Bethesda guidelines: extent of utilization in a university hospital medical center with a cancer genetics program.

BACKGROUND: In 1996, the National Cancer Institute hosted an international workshop to develop criteria to identify patients with colorectal cancer who should be offered microsatellite instability (MSI) testing due to an increased risk for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). These criteria were further modified in 2004 and became known as the revised Bethesda Guidelines. Our study aimed to retrospectively evaluate the percentage of patients diagnosed with HNPCC tumors in 2004 who met revised Bethesda criteria for MSI testing, who were referred for genetic counseling within our institution. METHODS: All HNPCC tumors diagnosed in 2004 were identified by accessing CoPath, an internal database. Both the Tumor Registry and patients' electronic medical records were accessed to collect all relevant family history information. The list of patients who met at least one of the revised Bethesda criteria, who were candidates for MSI testing, was then cross-referenced with the database of patients referred for genetic counseling within our institution. RESULTS: A total of 380 HNPCC-associated tumors were diagnosed at our institution during 2004 of which 41 (10.7%) met at least one of the revised Bethesda criteria. Eight (19.5%) of these patients were referred for cancer genetic counseling of which 2 (25%) were seen by a genetics professional. Ultimately, only 4.9% of patients eligible for MSI testing in 2004 were seen for genetic counseling. CONCLUSION: This retrospective study identified a number of barriers, both internal and external, which hindered the identification of individuals with HNPCC, thus limiting the ability to appropriately manage these high risk families.

Less common colorectal cancer predisposition syndromes.

A variety of syndromes confer increased risk for intestinal polyp development, outside the more commonly occurring syndromes. Each of these uncommon syndromes predispose to pathognomonic histologies that are uncommonly observed. Accurate diagnosis of these syndromes is contingent on higher-level pathology review, evaluation of signs and symptoms beyond sole consideration of the polyps, and collection of a detailed family history. When a genetic mutation can be identified in the proband, the management of intestinal and extra-intestinal cancer screening can be more appropriately tailored.

Psychosocial impact of Peutz-Jeghers Syndrome.

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant inherited cancer predisposition syndrome and gastrointestinal hamartomatous polyposis syndrome characterized by the presence of distinct perioral freckling. To date, we have not found any tool that specifically assesses the psychosocial impact of PJS on patients. We developed a PJS quality of life questionnaire using expert opinions of 3 cancer genetic counselors and a survey of patients with PJS through recruitment of participants involved in a support group over the internet. We measured and compared our questionnaire results to the widely used Center for Epidemiologic Studies and Depression Scale (CES-D) and the Short Form 36 (SF-36). We recruited 38 patients for our study. Volunteers were mailed a consent form, the self-administered CES-D, SF-36 and our developed PJS questionnaire and were instructed to return the completed questionnaires by mail. Results showed that PJS patients suffer from mild depression even though physically they did not feel impacted by their condition compared to the general population. However, having PJS caused them to alter many important life decisions. The PJS Questionnaire correlated with data obtained from analysis of CES-D, as well as the SF-36. More uniquely, it provided specific information regarding the burden of disease and quality of life in patients affected with Peutz-Jeghers syndrome. Its ability to do so for other polyposis syndrome populations remains to be studied. These results are important in developing plan of care for these patients regarding genetic counseling and surveillance strategies for PJS patients.

Improvement in quality of life measures in patients with refractory hepatitis C, responding to re-treatment with Pegylated interferon alpha -2b and ribavirin.

BACKGROUND: In this paper, we report the health related quality of life (HRQOL) data from patients with hepatitis C viral infection (HCV) who were refractory to prior therapy and had re-treatment with a combination of Pegylated interferon alpha-2b and ribavirin. We hypothesized that the HRQOL will improve in those patients who attain sustained viral response similar to naïve patients undergoing treatment for HCV. METHODS: HRQOL data was obtained from 152 patients enrolled into a randomized study for re-treatment of HCV refractory to prior therapy with interferon alpha-2b in combination with ribavirin. The treatment protocol was for 48 weeks and had a high and low dose arm. The HRQOL data was collected at baseline, weeks 24 and 48 of treatment, and at 24 week follow-up after treatment. A repeated measures statistical model was used for comparing the HRQOL domain scores between the responders and non-responders and the treatment groups. The responders and non-responders were also compared to the age and sex adjusted national mean scores. RESULTS: Twenty-five of the 152 (17%) patients achieved a sustained viral response. At baseline, HRQOL is lower in HCV patients compared to national norms. The norm based HRQOL domain scores for the different domains of the SF-36 instrument were as follows: physical functioning = 47.13, role-physical = 46.87, bodily pain = 48.00, general health = 44.01, vitality = 45.39, social functioning = 47.05, role-emotional = 48.88, mental health = 48.76, physical component score 43.26 and mental component score = 46.17. The scores decreased during therapy in those who would be responders and non-responders, but the pattern of change was different. During the treatment, the HRQOL domain scores of responders decrease notably in the domain of vitality. At week 48 vitality scores were worst in responders. 5 of the 8 domain scores were lower compared to baseline in non-responders. At 24 weeks post treatment follow up, HRQOL in those refractory patients who respond to re-treatment tended to be better than the national average in the domains of vitality (p = .06), social functioning (p = .06) and role-emotional (p = .03) while the non-responders improved their scores in domains of physical function and bodily pain. CONCLUSION: We conclude that patients who are to be responders and non-responders behave differently in terms of the HRQOL domain scores when re-treated with a combination of interferon alpha 2b and ribavirin. The responders sustained a significant decrease in the domain score of vitality while 5 of the 8 domain scores decrease in non-responders at the end of treatment. At the end of follow up, in responders, the HRQOL score tended to be better than the national average notably in the domains of role-emotional, vitality and social functioning. On the other hand, in non-responders, the domain scores of physical function improve, while that of role-emotional worsened.

Disparities Between Blacks and Whites in Stage at Diagnosis, Incidence, and Anatomic Subsite of Colorectal Cancer.

Background A disparity in colorectal cancer (CRC) incidence and mortality has been reported for black men and women in the United States. Objective To determine the magnitude and direction of temporal change in black/white disparity, by anatomic subsites of the colon and rectum. Design Population-based, epidemiologic study. Setting Pennsylvania, 1997-2002. Measurements Black/white ratios of the percentage of cases diagnosed at late stage and of age-adjusted incidence rates, by anatomic subsite, for four 3-year time periods. Results In 2000-2002, 54.6% of CRC cases among blacks were diagnosed at late stage, compared with 51.3% among whites. The percentage of cases in the cecum, transverse colon, splenic flexure, descending colon, sigmoid colon, rectum, and recto-sigmoid diagnosed at a late stage was larger among blacks than among whites. The disparity in the percentage of cases diagnosed at a late stage in the colon and rectum, transverse colon, and descending colon increased during the study period (P<.05). In 2000-2002, incidence was greater among blacks (64.1/100,000) than among whites (59.8/100,000). Incidence for segments of the proximal colon tended to be higher among blacks than among whites. The disparity in the incidence in the transverse colon increased during the study period (P=.021), while the increase in the disparity in the appendix approached statistical significance (P=.051). Limitations The effect of race may have been confounded by unavailable data, including socioeconomic position. Conclusions The black/white disparity in the percentage of cases diagnosed at late stage increased during the study period. The disparity in the percentage of cases diagnosed at a late stage and incidence for the transverse colon also increased. Efforts to increase screening for CRC, especially among blacks, should be enhanced.

The hamartomatous polyposis syndromes: a clinical and molecular review.

Inherited forms of gastrointestinal cancer have been a major focus of study and advancement over the past decade. Familial adenomatous polyposis and hereditary nonpolyposis colon cancer are the two most common heritable colon cancer syndromes. Inherited polyposis syndromes are characterized by the dominant type of polyp (whether adenomatous or hamartomatous) present and by the polyp's location within the gastrointestinal tract. The hamartomatous polyposis syndromes are characterized by an overgrowth of cells native to the area in which they normally occur. They represent a small but appreciable number of the gastrointestinal inherited cancer predisposition syndromes; it is now known that many of these syndromes carry a substantial risk for developing colon cancer as well as other gastrointestinal and pancreatic cancers. Patients afflicted with these syndromes are also at significant risk for extraintestinal malignancies. Seven inherited hamartomatous polyposis syndromes have been described: familial juvenile polyposis syndrome, Cowden's syndrome, Bannayan-Ruvalcaba-Riley syndrome, Peutz-Jeghers syndrome, basal cell nevus syndrome, neurofibromatosis 1, and multiple endocrine neoplasia syndrome 2B. Hereditary mixed polyposis syndrome is a variant of juvenile polyposis characterized by both hamartomatous and adenomatous polyps. The hamartomatous syndromes occur at approximately 1/10th the frequency of the adenomatous syndromes and account for <1% of colorectal cancer in Northern America. While the diagnosis of these inherited syndromes is primarily clinical, genetic testing is now available for all six syndromes. However, there are a significant number of spontaneous mutations seen in each of the syndromes. The management of these patients necessitates a coordinated multidisciplinary approach. The purpose of this review is to characterize the clinical and pathological features of these syndromes and to review the targets of cancer surveillance. The molecular alterations responsible for the inherited hamartomatous polyposis syndromes will also be discussed.

Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome.

Germline mutations of the LKB1 gene lead to Peutz-Jeghers syndrome (PJS), which is associated with a predisposition to gastrointestinal polyposis and cancer. In this study we tested for germline mutations of LKB1 in 11 patients with PJS from nine families and analyzed the expression patterns of the LKB1 and cyclo-oxygenase-2 (COX-2) proteins in 28 Peutz-Jeghers polyps (PJPs) and five carcinomas from these patients by immunohistochemical (IHC) analysis. In eight of those families we identified seven different mutations, which consisted of two splice site mutations, two nonsense mutations, one small in-frame deletion, one frame-shift mutation, and one silent mutation. Immunostaining revealed nuclear and cytoplasmic expression of LKB1 protein in 23 PJPs and five carcinomas, nuclear expression alone in one PJP, and loss of LKB1 protein expression in four PJPs, indicating a heterogeneous LKB1 expression pattern in PJPs. Overexpression of COX-2 was detected in 23 (82%) of 28 PJPs and in all carcinomas. Despite heterogeneity in staining of LKB1 among individuals and even among samples from the same individual, we found statistically significant correlations in staining of LKB1 relative to COX-2. These results suggest that COX-2 plays a role in tumorigenesis in PJS and may therefore be considered as a potential target for PJS chemoprevention.

GI polyposis and glycogenic acanthosis of the esophagus associated with PTEN mutation positive Cowden syndrome in the absence of cutaneous manifestations.

A 62-yr-old man was referred for management of GI polyposis. Large bowel polyps were initially diagnosed >25 yr ago, and the patient had undergone multiple colonoscopies and polypectomies. Personal and family history were notable for thyroid goiter and hypothyroidism. Physical examination was notable for lingular papillomatosis. No cutaneous lesions were seen. Upper endoscopy revealed esophageal glycogen acanthosis. There were multiple polyps throughout the stomach and the small and large intestines. Histology of these polyps showed multiple cell types including juvenile polyps, inflammatory polyps with fibromuscular proliferation and lamina propria ganglion cells, and focal adenomatous change. A clinical diagnosis of Cowden syndrome was made. Mutation analysis revealed a variant in exon 8 of the PTEN gene. Direct sequencing revealed a germline heterozygous C.892-895InsA, which is predicted to result in a truncated PTEN protein. Cowden syndrome is an underdiagnosed, underrecognized, autosomal dominant, inherited syndrome. For the gastroenterologist, esophageal acanthosis and multiple hamartomatous polyps should suggest the diagnosis. Sensitive molecular diagnostic tests looking for mutations in the appropriate genes are clinically available. Together with genetic counseling, molecular diagnostic testing will allow more accurate risk assessment and surveillance for cancer for both the patient and family members.

Overexpression of cyclooxygenase 2 in hamartomatous polyps of Peutz-Jeghers syndrome.

OBJECTIVE: Peutz-Jeghers syndrome (PJS) is an autosomal-dominant hamartomatous polyposis syndrome. Affected individuals are at risk for intestinal and extraintestinal malignancies. Prostaglandins and polyamines are small molecules believed to be important in tumor formation and growth. Cyclooxygenase (COX) and ornithine decarboxylase (ODC) are key enzymes in the prostaglandin and polyamine biosynthetic pathways, respectively. The aim of this study was to measure and compare COX-1 and COX-2 expression in normal and hamartomatous tissue of PJS patients. METHODS: We measured COX-1 and COX-2 protein expression in normal and hamartomatous GI tissues from affected PJS individuals and compared it with that in normal controls. COX-2 RNA in these tissues was also measured and compared by reverse transcription polymerase chain reaction (PCR). In addition, COX-2 expression was detected in tissue slides by immunostaining. ODC activity was measured between normal and hamartomatous tissues of PJS compared with control tissues. RESULTS: COX-1 expression was similar in normal and control GI tissues. In contrast, COX-2 overexpression was noted in hamartomatous polyp tissue from PJS patients compared with normal control and PJS tissue. COX-2 expression by reverse transcription PCR was 10-fold greater in a hamartoma compared with other tissues. COX-2 expression was noted in the epithelial cells of hamartomatous polyps, and also coursing throughout the stromal tissue of the lamina propria, including muscle cells. ODC activity was similar in the tissues studied. CONCLUSIONS: Selective COX-2 overexpression was noted in hamartomatous polyp tissue from PJS individuals. The results of the study provide an avenue for possible effective chemoprevention of polyp formation and growth in PJS.

Synchronous proximal polyps and cancer in patients with polyps detected at sigmoidoscopy: results of a single, rural-based sigmoidoscopy clinic.

The prevalence of polyps and cancer in the proximal colon among patients who have polyps detected on sigmoidoscopy was determined in a large rural referral hospital in north central Pennsylvania. Eleven thousand one hundred sixty patients underwent sigmoidoscopy between 1991 and 1997. Polyps were detected in 709 patients. Five hundred twenty-three patients who had a polyp at sigmoidoscopy and full colonoscopy completed within one year were included in this study. 120 patients (23%) had a proximal polyp detected at colonoscopy. The prevalence of proximal polyps and histologically advanced polyps was related to the size, number, and histology of the distal index polyp found at sigmoidoscopy. However, the absolute difference in prevalence of proximal polyps stratified by dings at sigmoidoscopy was small. A total of 5 adenocarcinomas were detected in the proximal colon. All proximal cancers detected at colonoscopy occurred in patients with a distal polyp less than 10 mm. Our data emphasize the importance of colonoscopy in all patients with a polyp detected at sigmoidoscopy independent of its size and histology.