Pregnancy and ABCB4 gene mutation: risk of recurrent cholelithiasis.

Cholelithiasis is a common problem in the Western world. Recurrent gallstones after cholecystectomy, however, are rare. We describe a case of a young woman with recurrent gallstones after a laparoscopic cholecystectomy leading to cholangitis during pregnancy. Additional testing revealed an ATP-binding cassette B4 (ABCB4) gene mutation. ABCB4 gene mutations leading to a multidrug resistance (MDR)3-P-glycoprotein deficiency are related to, among other diseases, recurrent cholelithiasis. Medical treatment consists of administering oral ursodeoxycholic acid. If untreated, MDR3 deficiency can lead to progressive liver failure requiring liver transplantation.

Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial.

BACKGROUND: Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. METHODS: Patients with FAP received celecoxib (400 mg twice daily) and UDCA (1000-2000 mg daily, ~20-30 mg/kg/day, n=19) or celecoxib and placebo (n=18) orally for 6 months. Primary outcome was drug efficacy, assessed by comparing duodenal polyp density at pre- and post-intervention by blinded review of endoscopic recordings. As secondary outcomes, cell proliferation, apoptosis, and COX-2 levels in normal duodenal mucosa were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. RESULTS: In intention-to-treat analysis, deceased polyp density was observed after celecoxib/placebo treatment (p=0.029), whereas increased polyp density was observed after celecoxib/UDCA treatment (p=0.014). The difference in change in duodenal polyp density was statistically significant between the groups (p=0.011). No changes in secondary outcomes were observed. Thirty patients (81%) reported one or more adverse events, 16 patients (84%, Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade 1-3) treated with celecoxib/UDCA and 14 patients (78%, CTCAE grade 1-2) treated with celecoxib/placebo. Nine patients (24%) discontinued intervention prematurely, 5 patients (26%) treated with celecoxib/UDCA and 4 patients (22%) treated with celecoxib/placebo. CONCLUSIONS: Celecoxib reduces duodenal polyp density in patients with FAP, and unexpectedly, high dose UDCA co-treatment counteracts this effect. The benefit of long term use of celecoxib for duodenal cancer prevention needs to be weighed against the (risk of) adverse events. TRIAL REGISTRATION: http://ClinicalTrials.gov, identifier NCT00808743.

Differences in proximal serrated polyp detection among endoscopists are associated with variability in withdrawal time.

BACKGROUND: Insufficient detection of proximal serrated polyps (PSP) might explain the occurrence of a proportion of interval carcinomas in colonoscopy surveillance programs. OBJECTIVE: To compare PSP detection among endoscopists and to identify patient-related and endoscopist-related factors associated with PSP detection. DESIGN: Prospective study in unselected patients. SETTING: Colonoscopy screening program for colorectal cancer at two academic medical centers. PATIENTS: Asymptomatic consecutive screening participants (aged 50-75 years). INTERVENTION: Colonoscopies were performed by 5 experienced endoscopists. All detected polyps were removed. Multiple colonoscopy quality indicators were prospectively recorded. MAIN OUTCOME MEASUREMENTS: We compared PSP detection among endoscopists by calculating odds ratios (OR) with logistic regression analysis. Logistic regression also was used to identify patient features and colonoscopy factors associated with PSP detection. RESULTS: A total of 1354 patients underwent a complete screening colonoscopy: 1635 polyps were detected, of which 707 (43%) were adenomas and 685 (42%) were serrated polyps, including 215 PSPs. In 167 patients (12%) 1 or more PSPs were detected. The PSP detection rate differed significantly among endoscopists, ranging from 6% to 22% (P < .001). Longer withdrawal time (OR 1.12; 95% confidence interval, 1.10-1.16) was significantly associated with better PSP detection, whereas patient age, sex, and quality of bowel preparation were not. LIMITATIONS: Limited number of highly experienced endoscopists. CONCLUSION: The PSP detection rate differs among endoscopists. Longer withdrawal times are associated with better PSP detection, but patient features are not. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR1888.).

Surgical management for advanced duodenal adenomatosis and duodenal cancer in Dutch patients with familial adenomatous polyposis: a nationwide retrospective cohort study.

BACKGROUND: Duodenal cancer is a major cause of mortality in patients with familial adenomatous polyposis (FAP). The clinical challenge is to perform duodenectomy before cancer develops; however, procedures are associated with complications. Our aim was to gain insight into the pros and cons of prophylactic duodenectomy. METHODS: Patients with FAP from the nationwide Dutch polyposis registry who underwent prophylactic duodenectomy or were diagnosed with duodenal cancer were identified and classified as having benign disease or cancer at preoperative endoscopy. Surveillance, clinical presentation, surgical management, outcome, survival, and recurrence were compared. RESULTS: Of 1,066 patients with FAP in the registry, 52 (5%; 25 males) were included: 36 with benign adenomatosis (median: 48 years old; including two (6%) cancer cases diagnosed after operation), and 16 with cancer (median: 53 years old). Cancer cases had been diagnosed with colorectal cancer more often (6% vs 44%; P < .01). Forty-three patients underwent duodenectomy (35 benign/eight cancer): 30-day mortality was 4.7% (n = 2), and in-hospital morbidity occurred in 21 patients (49%), without differences between patients with benign adenomatosis and cancer. Adenomas recurred in reconstructed proximal small bowel in 14 of 28 patients (50%, median time to recurrence: 75 months), and one patient developed cancer. Median survival of all 18 cancer cases in the registry (1.7%; 12 ampullary/six duodenal) was 11 months. CONCLUSION: Prognosis of duodenal cancer in patients with FAP is poor, which justifies an aggressive approach to advanced benign adenomatosis. Strict adherence to recommended surveillance intervals is essential for a well-timed intervention. Given the substantial morbidity and mortality of duodenectomy, patients' individual characteristics are to be critically evaluated preoperatively. As adenomas recur, postoperative endoscopic surveillance is mandatory.

Adenoma detection with cap-assisted colonoscopy versus regular colonoscopy: a randomised controlled trial.

OBJECTIVE: Conventional colonoscopy (CC) is considered the reference standard for detection of colorectal neoplasia, but it can still miss a substantial number of adenomas. The use of a transparent plastic cap may improve colonic visualisation. Cap-assisted colonoscopy (CAC) was compared with CC for adenoma detection. Secondary outcomes were caecal intubation time, caecal intubation rate and the degree of discomfort of colonoscopy. DESIGN: This is a parallel, randomised, controlled trial at two centres. Asymptomatic participants (aged 50-75 years) in a primary colonoscopy screening programme were consecutively invited. Consenting subjects were 1:1 randomised to either CAC or CC. All colonoscopies were performed by experienced endoscopists (≥ 1000 colonoscopies) who were trained in CAC. Colonoscopy quality indicators were prospectively recorded. RESULTS: A total of 1380 participants were randomly allocated to CC (N=694) or CAC (N=686). Caecal intubation rate was comparable in the two groups (98% vs 99%; p=0.29). Caecal intubation time was significantly lower in the CAC group: 7.7 ± 5.0 min with CAC vs 8.9 ± 6.2 min with CC (p<0.001) (values mean ± SD). Adenoma detection rates of all endoscopists were ≥ 20%. The proportion of subjects with at least one adenoma was similar in the two groups (28% vs 28%; RR 0.98; 95% CI 0.82 to 1.16), as well as the mean number of adenomas per subject (0.49 ± 1.05 vs 0.50 ± 1.03; p=0.91). Detection of small size, flat and proximally located adenomas was comparable. CAC participants had lower Gloucester Comfort Scores during colonoscopy (2.2 ± 1.0 vs 2.0 ± 1.0; p=0.03). CONCLUSION: CAC does not improve adenoma detection, but does reduce caecal intubation time by more than 1 min and does lessen the degree of discomfort during colonoscopy.

Small bowel Crohn's disease: MR enteroclysis and capsule endoscopy compared to balloon-assisted enteroscopy.

New modalities are available to visualize the small bowel in patients with Crohn's disease (CD). The aim of this study was to compare the diagnostic yield of magnetic resonance enteroclysis (MRE) and capsule endoscopy (CE) to balloon-assisted enteroscopy (BAE) in patients with suspected or established CD of the small bowel. Consecutive, consenting patients first underwent MRE followed by CE and BAE. Patients with high-grade stenosis at MRE did not undergo CE. Reference standard for small bowel CD activity was a combination of BAE and an expert panel consensus diagnosis. Analysis included 38 patients, 27 (71%) females, mean age 36 (20-74) years, with suspected (n = 20) or established (n = 18) small bowel CD: 16 (42%) were diagnosed with active CD, and 13 (34%) by MRE with suspected high-grade stenosis, who consequently did not undergo CE. The reference standard defined high-grade stenosis in 10 (26%) patients. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value of MRE and CE for small bowel CD activity were 73 and 57%, 90 and 89%, 88 and 67%, and 78 and 84%, respectively. CE was complicated by capsule retention in one patient. MRE has a higher sensitivity and PPV than CE in small bowel CD. The use of CE is considerably limited by the high prevalence of stenotic lesions in these patients.

Reproductive wish represents an important factor influencing therapeutic strategy in inflammatory bowel diseases.

OBJECTIVE: Inflammatory bowel disease (IBD) affects patients in reproductive age but little is known about the peri-conceptional use of medication for IBD. The aim of this study was to assess the type of medication used by IBD patients with the desire to reproduce and changes in medication in the peri-conceptional period. MATERIAL AND METHODS: IBD patients with active conception plans and pregnant patients were prospectively recruited from the outpatient clinic of a single academic medical center. IBD-related medication and changes in this medication for reasons of a desire to conceive or pregnancy were analyzed. RESULTS: In total, 61 patients (51 females; 40 with Crohn's disease, 21 with ulcerative colitis) were included. Thirteen patients (21%) used no medication, 44 (72%) used monotherapy and four (7%) used combination treatment. Of patients on monotherapy, 11 (19%) used 5-aminosalicylates, five (9%) used steroids, 11 (19%) used thiopurines, five (9%) used methotrexate and 11 (19%) used anti-tumor necrosis factor agents. Thirty-seven patients (61%) consulted a physician prior to conception. About one-third of these patients required a change in their medication due to their conception plans. CONCLUSIONS: In a referral center, the majority of IBD patients with conception plans require medication for which limited information on the safety of peri-conceptional use is available. In addition, the desire to reproduce leads to medication changes in about one-third of these patients.

Risk of developing adenomas and carcinomas in the ileal pouch in patients with familial adenomatous polyposis.

BACKGROUND & AIMS: At present, more than half of patients with familial adenomatous polyposis (FAP) are treated with a proctocolectomy and an ileal pouch-anal anastomosis (IPAA). Originally it was thought that this procedure would eliminate the risk of developing rectal cancer. However, an increasing number of studies reported development of adenoma and carcinoma in the pouch. The aim of this study was to evaluate the long-term risk of developing adenomas and carcinomas in the pouch in a large cohort of Dutch FAP patients. METHODS: A total of 254 patients with FAP who underwent an IPAA were selected from the Dutch Polyposis Registry. The results of the surveillance examinations and the pathology reports were analyzed. Surveillance with chromoendoscopy was offered to a subgroup of patients. RESULTS: Full information on follow-up was available in 212 (84%) patients. These patients (56% male) underwent a total of 761 endoscopies. The mean follow-up was 7.9 years (range, 0.4-20.3 years). The cumulative risk of developing an adenoma in the pouch at 10-year follow-up was 45%. Twenty-five patients (11.8%) developed an adenoma with advanced pathology, and 4 (1.9%) developed a carcinoma. The cumulative risk of developing a pouch carcinoma at 10-year follow-up was 1%. A very high prevalence (75.7%) of adenomas was found in a subgroup of patients who were examined with chromoendoscopy. CONCLUSIONS: This study demonstrated that although the risk of developing adenomas in the pouch after an IPAA is high, the risk of malignant degeneration appears to be low. The use of chromoendoscopy improves the detection of small adenomas.

Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis.

BACKGROUND & AIMS: Desmoid tumors are a severe extracolonic manifestation in familial adenomatous polyposis (FAP). Identification of risk factors might be helpful in the management of FAP patients with such tumors. The aim of this study was to assess potential risk factors for the development of desmoids in a cohort of Dutch FAP patients. METHODS: The medical records of 735 FAP patients were analyzed for the occurrence of desmoids. Relative risks and survival times were calculated to assess the influence of potential risk factors (female sex, family history, mutation site, abdominal surgery, and pregnancy) on desmoid development. RESULTS: Desmoid tumors were identified in 66 of the 735 patients (9%). The cumulative risk of developing desmoids was 14%. No correlation was found between specific adenomatous polyposis coli mutation sites and desmoid development. Patients with a positive family history for desmoids had a significant increased risk to develop this tumor (30% vs 6.7%, P < .001). No association was found between female sex or pregnancy and desmoid development. Most desmoid patients (95%) had undergone previous abdominal surgery. In a substantial proportion of patients with an ileorectal anastomosis, it was impossible to convert the ileorectal anastomosis to an ileal pouch-anal anastomosis as a result of desmoid development. CONCLUSIONS: A positive family history of desmoids is an evident risk factor for developing desmoids. Most desmoids develop after colectomy. No correlation was found between desmoids and the adenomatous polyposis coli gene mutation site, female sex, and pregnancy. Ileal pouch-anal anastomosis is the appropriate type of surgery in FAP patients with a positive family history for desmoids.

Argon plasma coagulation for radiation proctitis.

BACKGROUND: Rectal blood loss is a common late sequel of radiation proctitis. Teleangiectasias appear in the mucosa in 2-5% of patients after radiotherapy of the pelvis. Since pharmacotherapy is usually not beneficial, local treatment modalities with formalin irrigation, Nd:YAG laser and argon plasma coagulation (APC) have been advocated, but experience is still limited. METHODS: Between January 1997 and August 2001, 50 consecutive patients with rectal bleeding due to radiation proctitis were included for treatment with APC. Thirteen patients suffered from anaemia, six of whom required blood transfusion. Nine patients were receiving anticoagulant therapy and 10 patients used low-dose aspirin. APC was performed, applying the no-touch spotting technique at an electrical power of 50 Watt and an argon gas flow of 2.0 l/min. Pulse duration was less than 0.5 s. Treatment sessions were carried out at intervals of 3 weeks. RESULTS: In 47 out of 48 patients (98%) in whom the effect could be assessed, APC led to persistent clinical and endoscopic remission of rectal bleeding after a median of three sessions. One patient developed recurrent blood loss after resuming anticoagulant therapy for his aortic valve prosthesis. No adverse effects were encountered after initial treatment. One serious complication occurred in a patient with recurrent blood loss when he was prescribed aspirin for a transient ischaemic attack 2 years after the initial APC. Re-treatment resulted in a major rectal bleeding from a small ulcer with a visible vessel. CONCLUSIONS: APC is a safe, effective and well-tolerated treatment for blood loss due to radiation proctitis. The use of anticoagulants and aspirin seems to be a co-factors that induces bleeding.

A solitary tuberculous ulcer in the oesophagus.

A 48-year-old woman born in Pakistan was evaluated for dysphagia. Endoscopy showed a solitary ulcerative oesophageal lesion. Cultures were positive for mycobacterium tuberculosis. Additional imaging showed no other manifestations of tuberculosis. Oesophageal tuberculosis is a rare entity, especially as a primary manifestation defined as involvement of the oesophagus without signs of disseminated disease. Therefore, this case was classified as primary oesophageal tuberculosis.

Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of Chlamydia trachomatis serovar l2 proctitis in The Netherlands among men who have sex with men.

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) and is rare in the Western world. Recently, 3 men who have sex with men presented with LGV proctitis at the Erasmus Medical Center, Rotterdam, The Netherlands. We investigated a possible outbreak in a sexual network of men who have sex with men (MSM). METHODS: After active case finding, a total of 15 men presented and were investigated. Serum antibody titers to Chlamydia trachomatis were determined. Urine and rectum specimens were analyzed by polymerase chain reaction (PCR) for the presence of C. trachomatis. C. trachomatis-positive specimens were genotyped to detect the specific C. trachomatis serovars. All subjects underwent routine STD screening. Sociodemographic, clinical, and endoscopic characteristics were evaluated. RESULTS: Thirteen subjects had high immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis. All urine specimens were negative. Genotyping revealed serovars L(2) (n=8) and L(1) (n=1). An ulcerative proctitis was found in all subjects obtaining sigmoidoscopy (n=9). Eleven of 13 subjects with an LGV diagnosis were seropositive for human immunodeficiency virus (HIV), 6 had another concomitant STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual contacts were reported from The Netherlands, Germany, Belgium, the United Kingdom, and France. CONCLUSIONS: We revealed an outbreak of LGV proctitis among MSM in The Netherlands. The ulcerous character favors transmission of HIV, other STDs, and blood-borne diseases. From a public health perspective, it seems important to increase the awareness of possible LGV in MSM with symptomatic proctitis.

Ingestion of acid and alkaline agents: outcome and prognostic value of early upper endoscopy.

BACKGROUND: Ingestion of caustic substances often leads to severe morbidity and, frequently, death. This study compared complications and survival for patients who ingested an acidic substance, mainly glacial acetic acid, or an alkaline agent. METHODS: Records for 179 patients hospitalized for ingestion of a caustic agent (85 acid [75 glacial acetic acid], 94 alkali) were reviewed. Mucosal injury, systemic and GI complications, and survival were scored. RESULTS: Outcome was less favorable for patients who ingested acid compared with those who ingested alkali with respect to mucosal injury (median: grade 2 vs. grade 1; p=0.013), hospital stay (mean: 9.9 vs. 7.2 days; p=0.01), admittance to the intensive care unit (44% vs. 22%; p=0.002), systemic complications (24% vs. 3%; p < 0.001), perforation (6% vs. 0%; p=0.017), and mortality (14% vs. 2%; p=0.003). There was no difference in the development of strictures (acid, 15% vs. alkali, 17%). The grade of mucosal injury at endoscopy was the strongest predictive factor for the occurrence of systemic and GI complications and mortality (relative risk 9: 95% CI[3, 30]). Ten of 29 (34%) patients with strictures were treated by endoscopic dilation alone, whereas the others primarily (n=7) or secondarily (n=11) underwent surgery. One patient with an esophageal stricture died from systemic complications. CONCLUSIONS: Acid ingestion, particularly glacial acetic acid, is associated with a higher frequency of complications and mortality rate than alkali ingestion. Early endoscopy probably is safe and provides important prognostic information. Endoscopic treatment of caustic-induced strictures is only moderately successful.

Hypertension is frequently present in patients with reflux esophagitis or Barrett's esophagus but not in those with non-ulcer dyspepsia.

BACKGROUND: Elevated mortality due to cardiovascular disease has been reported for patients with Barrett's esophagus (BE). We compared the prevalence of risk factors for cardiovascular disease in patients with BE, reflux esophagitis (RE), and non-ulcer dyspepsia (NUD) with that of the general population. METHODS: Patients with upper gastrointestinal complaints and BE, RE, or NUD were compared with a matched cohort from the general population using a questionnaire and blood pressure and cholesterol measurements. RESULTS: Hypertension occurred more frequently in patients with BE (odds ratio 5.1, P<0.0001) and RE (odds ratio 3.8, P<0.001), but not in those with NUD. Serum total cholesterol was higher in BE (P=0.02) and borderline in RE (P=0.06) but not in NUD. Mean HDL cholesterol levels, body mass index, and smoking did not differ. CONCLUSIONS: This study suggests that BE and RE found at diagnostic endoscopy are associated with an increased prevalence of hypertension and a higher total cholesterol level than in the general population. If so, this would explain the increased mortality during the follow-up of BE patients, and it should be taken into account when designing or evaluating follow-up studies of BE.