Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms in Northern Italy: A Single-Center Cohort Study.

INTRODUCTION: The most typical presentation of COVID-19 is an acute respiratory syndrome whose most common symptoms include fever, cough, and dyspnea. However, gastrointestinal symptoms, such as diarrhea and nausea/vomiting, are increasingly reported in patients affected by COVID-19. This study aimed to describe the prevalence and time of onset of gastrointestinal symptoms in patients affected by COVID-19 and to find potential associations between gastrointestinal symptoms and clinical outcomes. METHODS: We performed a prospective single-center cohort study, enrolling patients who received diagnosis of COVID-19 at our institution between March 23, 2020, and April 5, 2020. We collected patient demographics and medical history, laboratory data, and clinical outcomes. Furthermore, we used a specifically designed questionnaire, administered to patients at time of diagnosis, to obtain data on the presence and time of onset of fever, typical respiratory symptoms, gastrointestinal symptoms, and other symptoms (fatigue, headache, myalgia/arthralgia, anosmia, ageusia/dysgeusia, sore throat, and ocular symptoms). RESULTS: In our cohort, 138 (69%) of 190 patients showed at least 1 gastrointestinal symptom at diagnosis; if excluding hyporexia/anorexia, 93 patients (48.9%) showed at least 1 gastrointestinal symptom. Gastrointestinal symptoms, in particular diarrhea, were associated with a lower mortality. At multivariate analysis, diarrhea was confirmed as independent predictive factor of lower mortality. DISCUSSION: Gastrointestinal symptoms are very frequent in patients with COVID-19 and may be associated with a better prognosis. These data suggest that, in some patients, the gastrointestinal tract may be more involved than the respiratory system in severe acute respiratory syndrome coronavirus 2 infection, and this could account for the less severe course of disease.

Efficacy of a novel self-assembling peptide hemostatic gel as rescue therapy for refractory acute gastrointestinal bleeding.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) results in significant morbidity and mortality. Topical hemostatic products have been developed for endoscopic use to help in the management of difficult bleeding. Our aim was to demonstrate the ease of use, safety, and efficacy of PuraStat, a novel hemostat, to control AGIB. METHODS: We describe 77 patients (41 men) who were treated for acute upper and lower AGIB in a 2-year period. In 50 patients, bleeding occurred as a complication of a previous endoscopic procedure, predominantly endoscopic mucosal resection (EMR) and endoscopic retrograde cholangiopancreatography (ERCP); however, in the other 27 patients, it derived from peptic ulcers, angiodysplasia, cancers, and surgical anastomoses. Bleeding was spurting in 13 of the 77 patients and oozing in 64. PuraStat was used after the failure of at least two conventional hemostatic methods. RESULTS: A mean of 2.6 conventional hemostatic methods had been attempted prior to the application of PuraStat. PuraStat achieved successful hemostasis in 90.9 % of patients. In 41 patients, once hemostasis was obtained with PuraStat, endoscopists further stabilized hemostasis by using at least one additional method. Recurrence of bleeding was observed in eight patients (10.4 %). In 16 patients with intraprocedural bleeding, it was possible to complete the procedures (14 EMR, 2 ERCP) after PuraStat hemostasis. No adverse events related to PuraStat were recorded. CONCLUSIONS: PuraStat is feasible, safe, and effective in controlling different types of gastrointestinal hemorrhage after failure of conventional hemostatic methods. Its application also does not hinder continuing endotherapy.

Full-spectrum (FUSE) versus standard forward-viewing colonoscopy in an organised colorectal cancer screening programme.

OBJECTIVE: Miss rate of polyps has been shown to be substantially lower with full-spectrum endoscopy (FUSE) compared with standard forward-viewing (SFV) colonoscopy in a tandem study at per polyp analysis. However, there is uncertainty on whether FUSE is also associated with a higher detection rate of colorectal neoplasia, especially advanced lesions, in per patient analysis. METHODS: Consecutive subjects undergoing colonoscopy following a positive faecal immunochemical test (FIT) by experienced endoscopists and performed in the context of a regional colorectal cancer population-screening programme were randomised between colonoscopy with either FUSE or SFV colonoscopy in seven Italian centres. Randomisation was stratified by gender, age group and screening history. Primary outcomes included detection rates of advanced adenomas (A-ADR), adenomas (ADR) and sessile-serrated polyps (SSPDR). RESULTS: Of 741 eligible subjects, 658 were randomised to either FUSE (n=328) or SFV (n=330) colonoscopy and included in the analysis. Overall, 293/658 and 143/658 subjects had at least one adenoma (ADR 44.5%) and advanced adenoma (A-ADR 21.7%), respectively, while SSP was the most advanced lesion in 18 cases (SSPDR 2.7%). ADR and A-ADR were 43.6% and 19.5% in the FUSE arm, and 45.5% and 23.9% in the SFV arm, with no difference for both ADR (OR for FUSE: 0.96, 95% CI 0.81 to 1.14) and A-ADR (OR for FUSE: 0.82, 95% CI 0.61 to 1.09). No difference in SSPDR or multiplicity was detected between the two arms. In the per polyp analysis, the mean number of adenomas and proximal adenomas per patient was 0.81±1.25 and 0.47±0.93 in the FUSE arm, and 0.85±1.33 and 0.48±0.96 in the SFV colonoscopy arm (p=NS for both comparisons). CONCLUSIONS: No statistically significant difference in ADR and A-ADR between FUSE and SFV colonoscopy was detected in a per patient analysis in FIT-positive patients. TRIAL REGISTRATION NUMBER: ISRCTN10357435.

Management and prognosis of hepatocellular carcinoma in the elderly: Results of an in-field multicenter cohort study.

AIMS: This multicentre cohort study evaluated the role of ageing on clinical characteristics, treatment allocation and outcome of new hepatocellular carcinomas (HCCs), in clinical practice. MATERIAL & METHODS: From September 2008, 541 patients >70 years old (elderly group), and 527 ≤70 years old (non-elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group. Survival differences were measured by unadjusted and adjusted (by inverse probability weight) survival analysis. RESULTS: Elderly patients were mainly females, hepatitis C virus infected and with better conserved liver function (P<.001). At presentation, HCC median size was similar in both groups while, in youngers, HCC was more frequently multinodular (P=.001), and associated with neoplastic thrombosis (P=.009). Adjusted survival analysis showed that age did not predict short-mid-term survival (within 24 months), while it was a significant independent predictor of long-term survival. Moreover, age had a significant long-term survival impact mainly on early HCC stages (Barcelona Clinic for Liver Cancer [BCLC] 0-A), its impact on BCLC B stage was lower, while it was negligible for advanced-terminal stages. CONCLUSIONS: Age per se does not impact on short-mid-term prognosis (≤24 months) of HCC patients, and should not represent a limitation to its management.

Aspecific ileitis: Crohn's disease or not Crohn's disease? A prospective study.

PURPOSE: It is not clear whether aspecific ileitis may represent an early manifestation or a milder variant of Crohn's disease or not. The aim of this study was to evaluate the clinical outcomes of aspecific ileitis. METHODS: Subjects with at least one of the following signs at retrograde ileoscopy: erythema, nodularity, aftae, erosions, and ulcers were considered. They should not have had defined gastrointestinal disease, biochemical signs of inflammation, use of drugs, celiac disease, and intestinal infectious disease. RESULTS: We enrolled 51 subjects (22 men), mean age (± SD) at colonoscopy of 41.1 ± 13.1 years. Indications to colonoscopy were overt or occult intestinal bleeding (18), diarrhoea (15), systemic signs (10), IBS-like symptoms (5), other (3). Ileal lesions were ulcers (9), erosions (26), aftae (10), nodularity (3), and erythema (3). At histological evaluation aspecific findings were observed. Forty-four out of 51 (86.3%) subjects underwent further investigations of small bowel. Second colonoscopy was performed in 31 (60.8%) persisting symptomatic subjects: ileitis was confirmed in 14 (46.6%). Ten out of 51 (19.6%) were eventually diagnosed as affected by Crohn's disease. CONCLUSIONS: A substantial proportion of subjects with endoscopic and histological findings of aspecific ileitis is eventually diagnosed as affected by Crohn's disease. In these subjects, a strict follow-up is strongly recommended.

Edoxaban and/or colchicine in outpatients with COVID-19: rationale and design of the CONVINCE trial.

BACKGROUND: An excessive inflammatory response and a hypercoagulable state are not infrequent in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse clinical outcomes. However, the optimal treatment strategy for COVID-19 patients managed in the out-of-hospital setting is still uncertain. DESIGN: The CONVINCE (NCT04516941) is an investigator-initiated, open-label, blinded-endpoint, 2 × 2 factorial design randomized trial aimed at assessing two independently tested hypotheses (anticoagulation and anti-inflammatory ones) in COVID-19 patients. Adult symptomatic patients (≥18 years of age) within 7 days from reverse transcription-PCR (RT-PCR) diagnosis of SARS-CoV-2 infection managed at home or in nursery settings were considered for eligibility. Eligible patients fulfilling all inclusion and no exclusion criteria were randomized to edoxaban versus no treatment (anticoagulation hypothesis) and colchicine versus no treatment (anti-inflammatory hypothesis) in a 1 : 1:1 : 1 ratio. The study had two co-primary endpoints (one for each randomization), including the composite of major vascular thrombotic events at 25 ±â€Š3 days for the anticoagulation hypothesis and the composite of SARS-CoV-2 detection rates at 14 ±â€Š3 days by RT-PCR or freedom from death or hospitalizations (anti-inflammatory hypothesis). Study endpoints will be adjudicated by a blinded Clinical Events Committee. With a final sample size of 420 patients, this study projects an 80% power for each of the two primary endpoints appraised separately. CONCLUSION: The CONVINCE trial aims at determining whether targeting anticoagulation and/or anti-inflammatory pathways may confer benefit in COVID-19 patients managed in the out-of-hospital setting. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04516941.

Inflammatory bowel disease in a colorectal cancer screening population: Diagnosis and follow-up.

BACKGROUND: Inflammatory bowel disease (IBD) is usually diagnosed in subjects with gastrointestinal symptoms, but may also be asymptomatic and diagnosed incidentally. AIMS: to determine the prevalence of IBD in asymptomatic adults. METHODS: we identified subjects who underwent colonoscopy between 1 September 2013 and 31 August 2019 in a regional colorectal cancer screening program with endoscopic findings suggestive of IBD, and retrieved their clinical, histological and therapeutic information. RESULTS: 5116 subjects underwent colonoscopy, and 4640 persons were considered assessable. Of these, 54 (1.16%) had endoscopic findings suggestive of IBD, including 40 of Crohn's disease (CD) and 14 of ulcerative colitis (UC). A definite diagnosis of IBD was made in 19 patients, for an overall IBD prevalence of 0.41%, with 13 cases of CD (0.28%) and 6 of UC (0.13%). The mean follow-up was 26.8 months after the first colonoscopy. Therapy was started in 5 of 13 CD patients and all UC patients. CONCLUSION: Endoscopic findings suggestive of IBD are not infrequent in an asymptomatic colorectal cancer screening population. Visualization of the terminal ileum is recommended in this setting. A definite diagnosis of IBD was made in about 1 out of 3 subjects with endoscopic lesions. Most IBD patients had a mild form of disease, but some needed biologic therapy.

Algorithm for Individual Prediction of COVID-19-Related Hospitalization Based on Symptoms: Development and Implementation Study.

BACKGROUND: The COVID-19 pandemic has placed a huge strain on the health care system globally. The metropolitan area of Milan, Italy, was one of the regions most impacted by the COVID-19 pandemic worldwide. Risk prediction models developed by combining administrative databases and basic clinical data are needed to stratify individual patient risk for public health purposes. OBJECTIVE: This study aims to develop a stratification tool aimed at improving COVID-19 patient management and health care organization. METHODS: A predictive algorithm was developed and applied to 36,834 patients with COVID-19 in Italy between March 8 and the October 9, 2020, in order to foresee their risk of hospitalization. Exposures considered were age, sex, comorbidities, and symptoms associated with COVID-19 (eg, vomiting, cough, fever, diarrhea, myalgia, asthenia, headache, anosmia, ageusia, and dyspnea). The outcome was hospitalizations and emergency department admissions for COVID-19. Discrimination and calibration of the model were also assessed. RESULTS: The predictive model showed a good fit for predicting COVID-19 hospitalization (C-index 0.79) and a good overall prediction accuracy (Brier score 0.14). The model was well calibrated (intercept -0.0028, slope 0.9970). Based on these results, 118,804 patients diagnosed with COVID-19 from October 25 to December 11, 2020, were stratified into low, medium, and high risk for COVID-19 severity. Among the overall study population, 67,030 (56.42%) were classified as low-risk patients; 43,886 (36.94%), as medium-risk patients; and 7888 (6.64%), as high-risk patients. In all, 89.37% (106,179/118,804) of the overall study population was being assisted at home, 9% (10,695/118,804) was hospitalized, and 1.62% (1930/118,804) died. Among those assisted at home, most people (63,983/106,179, 60.26%) were classified as low risk, whereas only 3.63% (3858/106,179) were classified at high risk. According to ordinal logistic regression, the odds ratio (OR) of being hospitalized or dead was 5.0 (95% CI 4.6-5.4) among high-risk patients and 2.7 (95% CI 2.6-2.9) among medium-risk patients, as compared to low-risk patients. CONCLUSIONS: A simple monitoring system, based on primary care data sets linked to COVID-19 testing results, hospital admissions data, and death records may assist in the proper planning and allocation of patients and resources during the ongoing COVID-19 pandemic.

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Endoscopic ultrasound-guided gallbladder drainage in pancreatic cancer and cholangitis: A case report.

BACKGROUND: Head pancreatic cancers often present with clinical challenges requiring biliary drainage for chemotherapy or palliative scope. If usual endoscopic modalities fail or if percutaneous approach is not feasible, endoscopic ultrasound (EUS) guided biliary drainage can be considered. Here we describe and discuss an interesting clinical case in which EUS-guided gallbladder drainage (EUS-GBD) was chosen to treat acute severe cholangitis in a patient with advanced pancreatic cancer. CASE SUMMARY: An 84-year-old female with a previous EUS-biopsy proven diagnosis of head pancreatic cancer presented with clinical signs of acute cholangitis. In September 2018 she had positioned a biliary and duodenal stent to relieve jaundice and an initial duodenal substenosis. In the emergency ward, an abdominal computed tomography scan showed proximal biliary stent occlusion due to neoplastic progression, but endoscopic retrograde cholangiopancreatography was impossible because of worsening duodenal stenosis and the absence of a chance to reach the Vater's papilla area. EUS-guided choledocoduodenostomy was not technically feasible but because the cystic duct was free of neoplastic infiltration, an EUS-GBD using an Axios™ stent was successfully performed. The patient started to feed after 48 h and was discharged 1 wk later. No other hospitalizations due to cholangitis or symptoms of Axios™ stent occlusion/dysfunction were observed up until her death 6 mo later due to underlying disease. CONCLUSION: This case demonstrated how different EUS therapeutic approaches could have a key role to treat critical and seemingly unsolvable situations and that they could play a more fundamental role in the next future.

Tolerability of Bowel Preparation and Colonoscopy in IBD Patients: Results From a Prospective, Single-Center, Case-Control Study.

Background: Endoscopy plays a fundamental role in the management of patients with inflammatory bowel disease (IBD). The aim of this study was to prospectively evaluate the tolerability and efficacy of bowel preparation and colonoscopy in ulcerative colitis (UC) and Crohn's disease (CD) patients compared to subjects participating in a colorectal cancer population screening program. Methods: Consecutive enrolment of CD and UC patients and screening subjects (SS) undergoing colonoscopy. Bowel preparation was done by split dose of 2 L PEG-ELS + simethicone. We recorded endoscopic, clinical, and demographic features; cleanliness rating using the Boston Bowel Preparation Scale (BBPS); and sedation doses. Bowel-preparation tolerability, discomfort, and pain during colonoscopy were assessed using a Visual Analogue Scale from 0 to 100 mm. Results: Sixty-three UC (mean age 49.9 ± 14.9 years), 63 CD (mean age 44.0 ± 14.0 years), and 63 SS (mean age 59.9 ± 6.3 years) patients were enrolled. Bowel preparation was similarly tolerated in UC, CD, and SS (P = 0.397). A complete colonoscopy was similarly performed in UC (59/63, 93.7%), CD (58/63, 92.1%), and SS (60/63, 95.2%) (P = 0.364). The BBPS did not show significant differences between UC (6.2 ± 1.6), CD (6.1 ± 1.3), and SS (6.2 ± 1.4) (P = 0.824). The need to increase sedation doses was significantly higher in CD (24/63, 38.1%) and UC (16/63, 25.4%) than in SS (4/63, 6.3%) (P < 0.0001). Conclusions: Bowel preparation is equally tolerated and efficacious in IBD patients and in healthy SS. In IBD, higher sedation doses are needed to guarantee an equally tolerated colonoscopy.

Comparison of asymmetric (low morning-dose) and standard split-dose regimen of PEG plus bisacodyl for bowel preparation: A randomized controlled trial.

BACKGROUND: Reducing the morning dose of PEG solution may be a reliable strategy to improve the patient compliance of split-dose regimens without affecting efficacy of bowel cleansing. AIMS: to compare the efficacy for bowel cleansing of an asymmetric split-dose regimen (25% of the dose on the day of colonoscopy and 75% on the day before) with the standard split-dose regimen. METHODS: Outpatients were enrolled in a randomized, single-blind, non-inferiority clinical trial. All subjects received a split-dose preparation with a 2L PEG-citrate-simethicone plus Bisacodyl. Patients were randomly assigned to: group A, asymmetric split-dose regimen; group B, symmetric split-dose regimen. Primary endpoint was the proportion of adequate bowel cleansing. RESULTS: Split-dose was taken by 81 and 80 patients in group A and B. Adequate bowel cleansing was achieved in 92.6% and 92.5% patients in group A and B (p = 1.000). No differences were observed regarding Boston Bowel Preparation Scale total score, adenoma detection rate and scores of each colon segment. CONCLUSIONS: The reduction of morning dose of PEG in a split-dose regimen is not inferior to the standard split-dose regimen in achieving an adequate bowel cleansing. However, further studies are needed to evaluate whether asymmetric preparation is associated to a higher tolerability compared to symmetric split-dose regimen. (NCT03146052).

Efficacy of withdrawal time monitoring in adenoma detection with or without the aid of a full-spectrum scope.

Background and study aims Withdrawal time (WT) monitoring and full-spectrum endoscopy (FUSE) have been suggested to increase adenoma detection rate (ADR) due to more accurate evaluation of the hidden areas of the colon. We aimed to evaluate the efficacy of WT monitoring and FUSE on ADR. Patients and methods This was a prospective observational study involving consecutive outpatients, aged 18 to 85 years, undergoing colonoscopy with unselected indications. In phase 1, endoscopists performed 660 colonoscopies either with standard forward-viewing endoscope (SFVE) (n = 330) or with FUSE (n = 330). In this phase, WTs were measured without endoscopist awareness of being monitored. In phase 2, endoscopists were informed of being monitored and performed additional 660 colonoscopies either with SFVE (n = 330) or with FUSE (n = 330). Results WT was lower in phase 1 compared to phase 2 (SFVE: 269 ±â€Š83 vs. 386 ±â€Š60 sec, P  < 0.001; FUSE: 289 ±â€Š97 vs. 403 ±â€Š65 sec, P  < 0.001). Use of FUSE increased ADR both in phase 1 (33.0 % vs. 27.3 %, P  = 0.127) and in phase 2 (41.8 % vs. 33.6 %, P  = 0.037). When endoscopists were aware of being monitored, ADR was higher in SFVE (33.6 % vs. 27.3 %; P  = 0.090) and FUSE arms (41.8 % vs. 33.0 %; P  = 0.024). Improvement in detection of proximal adenomas was associated with WT monitoring [OR 1.577 (95 % C. I. 1.158 - 2.148); P  = 0.004], whereas detection of distal adenomas was associated with use of FUSE [OR 1.320 (95 % C. I. 1.022 - 1.705); P  = 0.037]. Conclusions Unmonitored endoscopists have suboptimal WT, which increases when they are monitored. WT monitoring and use of FUSE are two reliable and alternative strategies to increase ADR.

First clinical experiences with a novel endoscopic over-the-scope clip system.

We describe our experience with a new over-the-scope clip (OTSC) system (Padlock Clip?) in the treatment of 14 patients. Eight of the 14 patients were treated for closure of gastrointestinal fistulas (n?=?4), iatrogenic gastrointestinal perforations (n?=?2), or hemostasis of post-polypectomy bleeding (n?=?2). The site of clipping was the lower gastrointestinal tract in five patients and the upper gastrointestinal tract in three patients. The clip was successfully delivered in seven out of the eight patients and clinical success was achieved in all patients. Endoscopic full thickness resection (EFTR) was performed to treat six patients: four with recurrent adenoma (n?=?4), one with ulcerated nodules at ileorectal anastomosis, and one with a neuro-endocrine tumor of the rectum. A complete intestinal wall resection was achieved in three of the six patients (50?%) and an R0 resection in five of the six patients (83.3?%). No complications related to the procedure and no recurrence at endoscopic follow-up were observed in any patient. The novel Padlock Clip seems to be an effective and safe tool to treat gastrointestinal fistulas, perforations or post-polypectomy bleeding, and to perform EFTR.

Immunophenotype of sporadic and familial adenomatous polyposis associated fundic gland polyps: a mucin and MIB1 study.

BACKGROUND: Fundic Gland Polyps (FGPs) are small sessile (2-5 mm) usually multiple polyps arising in the gastric, acid-secreting mucosa, described both in a sporadic form, prevalently in middle aged females, and associated with familial adenomatosis coli (FAP)-Gardner's syndrome and their attenuated variants (syndromic form). AIMS: We performed an immunohistochemical study on 5 syndromic (4 cases without and 1 case with dysplasia) and 28 sporadic FGPs, using monoclonal antibodies (MoAbs) against normal epitopes of fundic mucosa (Ck20, the surface gastric mucin M1, EMA, ChA), H. pylori and HLA-DR(Ia) antigens, CEA and mucin epitopes, and the Ki67 (MIB1) proliferation antigen, in order to establish the immunophenotype of FGPs; find any possible differences between sporadic and syndromic polyps. RESULTS: Ck20 and M1 were positive on surface and foveolar epithelium of controls, whereas sporadic and syndromic FGPs showed an enhanced deep positivity below foveolar necks ("foveolar metaplasia"); EMA was strongly positive on parietal cells, highlighting intracytoplasmic canaliculi. Chromogranin-positive cells in FGPs were alike controls, except for a sporadic case with micronodular hyperplasia. Ck7, as expected, was negative in controls, whereas the 5 syndromic FGPs and 25 of 28 sporadic FGPs showed a diffuse superficial and deep expression. H. pylori anti-serum gave negative results on all cases, and only 3 sporadic FGPs showed epithelial expression of HLA-DR(Ia). Syndromic FGPs were CEA negative, whereas 32% of sporadic FGPs expressed it. FGPs showed a neoexpression of the mucin oncofetal epitopes syalil-Tn (3/5 syndromic, 82% sporadic) CA19.9 and CA50 (4/5 syndromic, 14% sporadic). MIB1-labelling index of surface (30.5%) and deep (37.1%) compartments of the 4 syndromic FGPs without dysplasia was enhanced, with high statistical significance (p < 0.0001) both in comparison to controls (16.9% superficial stain only) and sporadic FGPs (15.8% surface, 19.5% deep labeling indexes). Moreover, the MIB1 labeling-index of the syndromic case with dysplasia (60.8% surface, 56.6% deep labeling indexes) was further enhanced in comparison with the other 2 syndromic cases. CONCLUSIONS: Sporadic and syndromic FGPs showed a neoexpression of Ck7, CEA, and mucin epitopes. As these markers are normal antigens of fetal stomach, FGPs showed a fetal, "immature" immunophenotype. The only difference we found between syndromic and sporadic polyps was a statistically significant enhanced MIB1-labelling index expression by syndromic FGPs, further enhanced in the syndromic FGP with dysplasia.

The morphological and immunohistochemical spectrum of gastric biopsies of patients with absorptive hypercalciuria.

OBJECTIVE: Idiopathic hypercalciuria is characterised by renal stone formation and vertebral osteoporosis. The syndrome displays high clinical variability with patients almost equally distributed between fasting or renal type (prevalent calcium loss) and absorptive type (prevalent increase of intestinal absorption). Absorptive hypercalciuria (AH) is characterised by hypersensitivity of calcium-sensing receptors of antral G cells with normal fasting gastrinaemia and meal hypergastrinaemia. To the best of our knowledge, no study has been published about the morphological aspects of gastric biopsies of patients with AH and the immunohistochemical findings of gastrin-producing G cells. So we studied morphologically and immunohistochemically a group of 38 patients with AH, describing their gastric findings and associated lesion. DESIGN: All 38 patients had a clinical-laboratory diagnosis of AH with normal fasting hypergastrinaemia and an abnormal rise of gastrinaemia after a standardised meal test. Their 38 antral and 27 body-fundus biopsies, and 5 normal antral and body controls, were stained with H&E, Giemsa stain, polyclonal antiserum anti-Gastrin and a monoclonal antibody anti-Chromogranin A. RESULTS: Antral biopsies of all 38 patients showed a simple (15) or linear (23) hyperplasia of G cells, whereas only 2 of 27 body biopsies showed a nodular hyperplasia of endocrine cells. In five patients with AH, we found an association with fundic gland polyps (FGPs). CONCLUSIONS: We found in all of the patients with AH a correlation between meal hypergastrinaemia and morphological antral G-cell hyperplasia. Moreover, in five patients, AH was associated with FGPs. We know from literature data that FGPs' development in Zollinger-Ellison syndrome is statistically associated with hypergastrinaemia. From our present data, we suggest that even in AH the stimulated hypergastrinaemia may have a role in polyp development.

Irreversible alopecia universalis during treatment with pegylated interferon-ribavirin for chronic hepatitis C virus infection: Case report and published work review.

Hair disorders that have been described in association with pegylated interferon-ribavirin combination treatment include canities, hypertrichosis, telogen effluvium, and the most common cutaneous side-effect by far, alopecia. Alopecia is a heterogeneous disease characterized by hair loss on the scalp or any hair-bearing surface with a wide range of clinical presentations, from a single patch of hair loss to complete loss of hair on the entire body (alopecia universalis). Although some cases of reversible alopecia universalis associated with pegylated interferon-ribavirin combination therapy have been reported in the published work, irreversible alopecia universalis has not yet been reported in relation to pegylated interferon and ribavirin combination treatment. For the first time, we report a case of irreversible alopecia universalis during pegylated interferon-ribavirin combination therapy in a man infected with hepatitis C virus in the absence of clinical or biochemical evidence of immunological disorders or thyroid dysfunction at any time before, during or after antiviral therapy.