Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry.

BACKGROUND: Lynch syndrome (LS) is the most frequent inherited colorectal cancer syndrome. AIM: To assess the burden of adenoma in LS patients under 50 years-old followed in the PRED-IdF network. METHODS: From January 2010 to January 2019, all patients under 50 years of age with a confirmed LS germline mutation were included. The main objective was the description of adenomas characteristics according to path_MMR. RESULTS: We analyzed data from 708 patients (mean age 34.8 ± 8.6), of which 41.8 % were male. Among these patients, 37.6% had path_MLH1, 45.4% path_MSH2, 13.9% path_MSH6, 2.9% path_PMS2, and 1.2% path_EpCAM. The analysis included 1721 (70.9%) follow-up colonoscopies. A total of 682 adenomas were detected, including 140 (20.5%) advanced adenomas. The adenoma detection rates during the first and follow-up colonoscopies were 19.2% and 20.5%, respectively. Most adenomas were <10 mm (57.9%), located in the proximal colon (334, 48.9%), and presented as non-polypoid lesions (493, 72.3%). The median growth time for adenomas was 23 months (range 9-114) irrespective of the path_MMR mutation (p = 0.62). CONCLUSION: LS patients under 50 years of age have a high burden of adenomas, particularly small non-polypoid adenomas located in the proximal colon. These results highlight the need for intensive screening, with a particular focus on the proximal colon.

Back-to-Back Comparison of Colonoscopy With Virtual Chromoendoscopy Using a Third-Generation Narrow-Band Imaging System to Chromoendoscopy With Indigo Carmine in Patients With Lynch Syndrome.

INTRODUCTION: Colonoscopic screening with indigo carmine chromoendoscopy (ICC) in patients with Lynch syndrome (LS) improves the adenoma detection rate but is time consuming and poorly used in clinical practice. Narrow-band imaging (NBI), a virtual chromoendoscopy technique, highlights superficial mucosal vessels and improves adenoma characterization. We conducted a prospective multicenter trial in a back-to-back fashion to compare the third-generation NBI with ICC for detecting colonic adenomas in patients with LS. METHODS: In a multicenter, prospective, noninferiority trial, 138 patients underwent a double colonoscopy, first with NBI, followed by ICC, in a back-to-back design. The primary noninferiority outcome measure was the number of patients with at least one adenoma after NBI compared with the number of patients with at least one adenoma after NBI and ICC. RESULTS: The 138 analyzable patients were all proven mismatch repair mutation carriers for LS (MLH1 = 33%, MSH2 = 47%, MSH6 = 15%, PMS2 = 4%, and EPCAM = 1%). The mean age (SD) was 40.5 (14.7) years, and 64 (46.4%) were men. The median withdrawal time for an NBI procedure was 8 minutes (interquartile range 6-11) compared with 13 minutes (interquartile range 8-17) for ICC. At least one adenoma was detected during the initial NBI pass in 28 patients (20.3%), and 42 patients (30.4%) had at least one adenoma detected after both NBI and ICC (difference, 10.1%; 95% confidence interval, -0.1%-20.3%); this represents an increase of 50.0% of the adenoma detection rate. ICC detected additional adenomas in 25 patients (18.1%). DISCUSSION: Colonoscopy combining NBI and ICC detects more adenomas than third-generation NBI alone in patients with LS, respectively, 30.4% vs 20.3% (difference, 10.1%; 95% confidence interval, -0.1 to 20.3), thus failing the noninferiority assumption of NBI compared with combined NBI and ICC. Although less time consuming, colonoscopy using the third-generation NBI cannot be recommended to replace ICC in patients with LS.

Clinical implications of CTNNA1 germline mutations in asymptomatic carriers.

In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.

Catastrophic antiphospholipid syndrome (CAPS)-induced ischemic pancreatic ducts injury mimicking intraductal papillary mucinous neoplasm (IPMN).

OBJECTIVES: Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening disease characterized by multiple small-vessel occlusions of rapid onset. Ischemic pancreatic duct lesions secondary to CAPS have never been reported. METHODS: We describe 4 patients who presented lesions suspected to be intraductal papillary mucinous neoplasm (IPMN) of the pancreas following a CAPS. RESULTS: All patients had a history of CAPS months or years before the IPMN diagnosis. They had abdominal pain or abnormal liver test results and had undergone radiography. In a 36-year-old man, endoscopic ultrasonography and magnetic resonance cholangiopancreatography demonstrated parietal thickening, stenoses and dilatations of the main pancreatic duct, which suggested IPMN. A pancreatic resection was performed because of presumed risk of malignancy. Histology revealed pancreatitis and thrombosis of small pancreatic vessels but no IPMN. The 3 other cases had lesions consistent with IPMN disclosed on MRI. From the first case experience, regular radiography surveillance was decided for the 3 other patients. After more than 4 years of follow-up, lesions remained unchanged. CONCLUSION: Physicians must be aware that these lesions may be encountered in CAPS and may closely mimic IPMN, with subsequent risk of performing unnecessary pancreatectomy.

Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified?

BACKGROUND: Duodenal polyposis is a manifestation of adenomatous polyposis that predisposes to duodenal or ampullary adenocarcinoma. Duodenal polyposis is monitored by upper GI endoscopies and may require iterative resections and prophylactic radical surgical treatment when malignancy is threatening. OBJECTIVE: The purpose of this study was to evaluate severity scoring for surveillance and treatment in a large series of duodenal polyposis. DESIGN: From 1982 to 2014, every patient surveyed by upper GI endoscopies for duodenal polyposis was included. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: We performed 1912 upper GI endoscopies in 437 patients (median = 3; interquartile range, 2-6 endoscopies). MAIN OUTCOME MEASURES: Conservative treatment was performed in 103 patients (159 endoscopic and 17 surgical resections), whereas radical surgical treatment (Whipple procedure or duodenectomy) was required in 52 (median age, 47.5 y; range, 43.0-57.3 y) because of high-grade dysplasia or unresectable lesions. RESULTS: Genes involved were APC (n = 274; 62.7%) and MUTYH (n = 21; 4.8%). First upper GI endoscopies (median age, 32 y; range, 21-44 y) revealed duodenal polyposis in 190 (43.5%). Rates of low-grade dysplasia, high-grade dysplasia, and duodenal or ampulary adenocarcinoma at 5 years were 65% (range, 61.7%-66.9%), 12.1% (range, 10.3%-13.9%), and 2.4% (range, 1.5%-3.3%), whereas 10-year rates were 75.8% (range, 73.1%-78.5%), 20.8% (range, 18.2%-23.4%), and 5.4% (range, 3.8%-7.0%). The rate of ampullary abnormalities rose during surveillance from 18.3% at the first upper GI endoscopies to 47.4% at the fourth. Predictive factors for high-grade dysplasia were age at first upper GI endoscopy, type and age of colorectal surgery, Spigelman score, presence of an ampullary abnormality, and number of endoscopic treatments. In multivariate analysis, only age at first upper GI endoscopy and presence of an ampullary abnormality were independent predictive factors. Histologic analysis after radical surgical treatment showed high-grade dysplasia in 30 patients and duodenal or ampulary adenocarcinoma in 11 (4 patients had lymph node involvement). LIMITATIONS: The study was limited by its retrospective analysis of a prospective database. CONCLUSIONS: More than 20% of patients developed high-grade dysplasia with duodenal polyposis after 10 years. Iterative endoscopic resections allowed extended control, but surgery remained necessary in 12% of the patients and happened too late in many cases; 20% of those operated had developed duodenal or ampulary adenocarcinoma, whereas 8% exhibited malignancy with lymph node involvement. The trigger for prophylactic surgery required a more accurate predictive score leading to closer endoscopic surveillance. Modifying the Spigelman score by accounting for ampullary abnormalities should be considered as a means to increase compliance with closer endoscopic follow-up in high-risk patients. See Video Abstract at http://links.lww.com/DCR/A430.

Primary intestinal lymphangiectasia (Waldmann's disease).

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool alpha1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur.

Irritable bowel syndrome in France: a common, debilitating and costly disorder.

OBJECTIVE: This epidemiological investigation aims to measure the prevalence of irritable bowel syndrome (IBS) in the general population using the Rome II criteria and to evaluate the medical management including treatments and the impact of IBS on patient life. METHODS: A nationally representative sample of 20,000 French subjects, aged 18 years and over, were interviewed by SOFRES (French Public Opinion Poll Institute) in May 2001. In a second phase (June/July 2001), a 48-question self-administered questionnaire was given to the subjects who have been selected during the first phase as suffering from IBS (Rome II criteria). RESULTS: The prevalence of IBS was 4.7% (confidence interval, 4.36-5.04% with 5% risk) with a predominance in women (5.7% versus 3.7%, P < 0.01). The abdominal pain was often longstanding (> 5 years, 50%), intense (43%) and nocturnal (35%). During the most recent painful episode the levels of associated transit problems were almost equally divided between diarrhoea (36%), constipation (29%) and alternate episodes of both (31%). Apart from pain, bloating was given as the most frequent (73%) and most troublesome (24%) symptom. Since the onset, 80% of subjects with IBS had consulted a doctor (90% consulted a general physician, 57% a gastroenterologist, 50% both) and of these, 80% consulted within the previous 12 months. Sixty-seven per cent of subjects underwent additional investigations since the start of their illness (average of 3.4 examinations per patient examined: colonoscopy, 34.1%; laboratory tests, 34%; and abdominal ultrasound, 27.7%). Over the previous 12 months, 8% of the subjects had been admitted to hospital (average length of stay, 6.6 days), 11% of employed subjects had to take time off, 93% of subjects had taken prescribed medication (87%), but 43% of people thought it was ineffective. The effect on daily life was considerable (score, 6.2/10; close to the score for flu, 7/10). Two-thirds of the individuals changed their diet; 54% said it affected their social life and 29% their professional life. Seventy-four per cent of patients trusted their doctor, with a satisfaction index of 63%, but 45% of patients would like to have more information on IBS. CONCLUSION: This study confirmed that the Rome II criteria detected IBS with a prevalence of 4.7%. The recruited subjects had severe symptoms (frequency, intensity and duration) that had a considerable effect on their daily life. The high level of referrals and initial consultations in all categories and the patient's attitudes towards the illness and its treatment emphasize the relative ineffectiveness of care for patients suffering from IBS.