Kaposi's sarcoma with atypical gastrointestinal involvement.

A 31-year-old human immunodeficiency virus (HIV) positive male presented with weight loss, asthenia and anorexia of three weeks evolution. On physical exam, the patient had painless purple-colored papules on the trunk and upper limbs. Laboratory studies showed severe immunosuppression, with an absolute CD4 cell count of 114 cell/ul and HIV1-RNA level of 180,000 copies/ml. Esophagogastroduodenoscopy showed an exophytic lesion in the distal esophagus composed of three polyps and multiple flat and nodular maculopapular erythematous lesions in the gastric body, antrum and duodenum. Colonoscopy was also performed and identified several flat erythematous lesions in the colorectal mucosa. A neoplasm composed of small irregular vascular channel proliferation and spindled endothelial cells with minimal atypia was observed in all the esophageal, gastric, duodenal, colic and skin biopsies.

Development of an Online App to Predict Post-Endoscopic Retrograde Cholangiopancreatography Adverse Events Using a Single-Center Retrospective Cohort.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure with a high risk for adverse events (AEs). AIM: evaluate patient- and procedure-related risk factors for ERCP-related AEs and develop an online app to estimate risk of AEs. METHODS: retrospective study of 1,491 consecutive patients who underwent 1,991 ERCPs between 2012 and 2017 was conducted. AEs definition and severity were classified according to most recent ESGE guidelines. Each variable was tested for association with occurrence of overall AEs, post-ERCP pancreatitis (PEP) and cholangitis. For each outcome, 2 regression models were built, from which an online Shiny-based app was created. RESULTS: Overall AE rate was 15.3%; in 19 procedures, >1 AE occurred. Main post-ERCP AE was PEP (7.5%), followed by cholangitis (4.9%), bleeding (1.3%), perforation (1%), cardiopulmonary events (0.9%), and cholecystitis (0.3%). Seventy-eight percent of AEs were mild/moderate; of severe (n = 55) and fatal (n = 20) AEs, more than half were related to infection, cardiac/pulmonary AEs, and perforation. AE-related mortality rate was 1%. When testing precannulation, procedural covariates, and ERCP findings, AE occurrence was associated with age (odds ratio [OR] 0.991), previous PEP (OR 2.198), ERCP complexity grade III/IV (OR 1.924), standard bile duct cannulation (OR 0.501), sphincterotomy (OR 1.441), metal biliary stent placement (OR 2.014), periprocedural bleeding (OR 3.024), and biliary duct lithiasis (OR 0.673). CONCLUSION: Our app may allow an optimization of the patients' care, by helping in the process of decision-making, not only regarding patient or endoscopist's selection but also definition of an adequate and tailored surveillance plan after the procedure.

Unexpected diagnosis for nodular hepatic lesions.

Uveal melanoma is the most common primary ocular tumor and has a significant predilection for metastasis to the liver. Nevertheless, metastatic uveal melanoma usually occurs in the first years after the initial treatment, and late recurrence is extremely rare.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels.

OBJECTIVE: Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. DESIGN: Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. RESULT: GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. CONCLUSIONS: GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

Infectious proctitis: a necessary differential diagnosis in ulcerative colitis.

INTRODUCTION: In the last years, there was a rising in the incidence of sexually transmitted infections, including proctitis. Infectious proctitis (IP), mainly caused by agents like Neisseria gonorrhea and Chlamydia trachomatis, is an entity that should be considered when patients with suspected inflammatory bowel disease (IBD) are approached, mainly if they have risk factors such as anal intercourse. CLINICAL CASES/DISCUSSION: The symptoms of IP, like rectal blood, mucous discharge, and anorectal pain, may appear in other causes of proctitis, like IBD. Therefore, to establish the diagnosis, it is crucial to take a detailed history and perform a physical examination, with the diagnosis being supported by complementary tests such as rectosigmoidoscopy, histology, serology, and culture. Depending on the etiology, treatment of IP is based in antibiotics or antivirals, which may be empirically initiated. Co-infections, mainly those that are sexually transmitted, and HIV should be tested and sexual partners should be treated, accordingly. In this article, the authors report three cases of IP, referent to three different patients, and review the initial approach required in cases where there is a clinical and/or endoscopic suspicion of this pathology.

Why anal cytology is not enough in a dysplasia screening program.

In our previous study, we stated that anorectal cytology (ARC) should not be used as the sole method for anal dysplasia screening (ADS). We read with great interest the letter of Revollo et al. and we would like to respond to some points.

Anal cytology, histopathology and anoscopy in an anal dysplasia screening program: is anal cytology enough?

BACKGROUND AND AIM: The human papilloma virus is the leading cause of anal squamous cell carcinoma. Cytological screening may reduce the associated morbidity and mortality. The aim of the study was to estimate the agreement between anal cytological examination, histopathology and anoscopic visual impression. METHODS: A prospective study of patients who underwent anal dysplasia screening between 2011 and 2015, in a proctology clinic of a tertiary referral center. RESULTS: During the study period, 141 patients (91% men, 87% with HIV infection) underwent 175 anal cytology tests. Of these, 33% were negative for intraepithelial lesions or malignancy (NILM), 22% were atypical squamous cells of uncertain significance (ASCUS), 33% were low-grade squamous intraepithelial lesion (LSIL) and 12% were high-grade squamous intraepithelial lesion (HSIL). With regard to anoscopic visual impression, 46% of patients had no lesions and excision/biopsy of the identified lesions was performed in the remaining patients. The weighted kappa-agreement between abnormal cytological results and anoscopic visual impression was moderate (k = 0.48). The weighted kappa-agreement between simultaneous anal cytological examinations and anal histopathologic findings was low (kappa = 0.20). With regard to the histological examination of cases with HSIL or superficially invasive squamous cell carcinoma, 64% of patients had dysplasia of a lower grade according to the cytological analysis (6 ASCUS, 18 LSIL and 4 NILM). CONCLUSION: There was a poor correlation between anal cytology, histopathology and anoscopic visual impression and a high number of histological studies of HGD that were of a lower dysplastic degree according to the cytological examination. Therefore, anal cytology screening should not be used as the sole method of anal dysplasia screening.

Pancreatic cancer screening: Still a delusion?

Pancreatic adenocarcinoma represents the fourth most common cause of cancer mortality and death due to pancreatic cancer (PC) have increased since 2003. Its incidence has also raised about 30% in the past decade and it is expected to become the second cause of cancer mortality by 2020 in the USA. Most PC present with metastatic disease and improvements in treatment outcomes for this group have been disappointing. These observations support the idea that screening to identify patients at an earlier stage might be an important strategy in improving overall PC outcomes. Many protocols have been tested, nevertheless, by now there is no effective screening program. Given the overall low incidence of disease and the current lack of accurate, inexpensive and noninvasive screening tests, the consensus is that widespread population-based screening for PC in the general population or in patients with only one affected first-degree relative is neither practicable nor indicated in most countries. However, a different scenario is screening patients with higher risk for PC, most of them with hereditary conditions predisposing the development of this neoplasia. In fact, some guidelines are now available helping to select these individuals at risk and to screen them, in order to achieve early detection of PC.

Early surgery in Crohn's disease patients with entero-urinary fistulas: does it change the prognosis?

BACKGROUND: Entero-urinary fistulas (EUF) are observed in only 2-8% of Crohn's disease (CD) patients. AIM: To compare the outcome of patients with EUF, after surgical treatment, with those with non-penetrating and non-stenosing, penetrating, and stenosing phenotypes (B1, B2, and B3 phenotypes). METHODS: Case-control study of 21 CD patients with EUF submitted to surgical treatment. Each patient with EUF was compared with six patients, two of each group: B1, B2, and B3 phenotypes. They were randomly selected from inflammatory bowel disease database and had the same extent of disease, smoking status, perianal disease, and age at diagnosis. RESULTS: One hundred and forty-seven patients were included (n = 21 EUF; n = 42 of each group B1, B2, and B3). Comparing B3 group with EUF, the former was more steroid-dependent and resistant (54.8% versus 19.0%, p = 0.037) and needed anti-TNF therapy more frequently (59.5% versus 23.8%, p = 0.004). Moreover, B3 patients had a poorer response to anti-TNF therapy without remission free of steroid therapy in comparison with EUF patients (45.2% versus 95.2%, p < 0.001). EUF patients did not differ from B2 group regarding anti-TNF therapy (p = 0.956) and steroid-dependence or resistance (p = 0.141). Surgery rate after index surgery was inferior in EUF in comparison with B2 and B3 groups. Hospital admission rate of patients with EUF was also lower than the B3 group. CONCLUSION: Early surgery seems to be a good choice for patients with EUF as their response to surgery appears not to differ from B2 patients and had a better prognosis than phenotype B3 patients.

Pigmented hepatocellular adenoma with ß-catenin activation: case report and literature review.

 Hepatocellular adenomas (HCAs) are benign liver tumors recently characterized into 4 different types according to genetic, pathological and clinical features. The prognosis is not well established yet and malignant transformation has been recently associated with ß-catenin activation. We aimed to describe a case of a pigmented HCA with ß-catenin nuclear expression and inflammatory features and to review the cases of pigmented HCAs in the literature. We report a case of a young female patient without contraceptive use, with a liver tumor diagnosis. Liver biopsy revealed diffuse expression of ß-catenin and a partial hepatic resection was performed. The histologic analysis revealed a hepatocellular tumor composed of uniform trabeculae of hepatocytes and solid areas, the later with a significant amount of black pigment highlighted by Masson-Fontana stain. Immunohistochemistry showed co-expression of C-reactive protein and serum amyloid A in the tumor. Literature review revealed that pigmented HCAs, previously reported as dark adenomas, are rare tumors. In HCAs, the presence of ß-catenin activation should be searched for due to the higher risk of malignant transformation in hepatocarcinoma. We describe a pigmented HCA with ß-catenin nuclear expression and inflammatory features being the fifth case reported so far.

Pseudomelanosis duodeni: is there a common denominator?

A 76-year-old female patient with a past medical history of diabetes mellitus, stage 3 chronic renal failure and iron deficiency anemia was referred for esophagogastroduodenoscopy (EGD) for evaluation of solid food dysphagia. She had been on oral therapy with ferrous sulfate for several years. Besides a Schatzki's ring the EGD revealed a duodenal mucosa with black-speckled pigmentation. Biopsies were performed and disclosed the deposition of brown (hemosiderin) pigment within macrophages in the lamina propria of normal villi. This endoscopic appearance is called pseudomelanosis duodeni (PD).

Increased viability but decreased culturability of Mycobacterium avium subsp. paratuberculosis in macrophages from inflammatory bowel disease patients under Infliximab treatment.

Mycobacterium avium subsp. paratuberculosis (MAP) has long been implicated as a triggering agent in Crohn's disease (CD). In this study, we investigated the growth/persistence of both M. avium subsp. hominissuis (MAH) and MAP, in macrophages from healthy controls (HC), CD and ulcerative colitis patients. For viability assessment, both CFU counts and a pre16SrRNA RNA/DNA ratio assay (for MAP) were used. Phagolysosome fusion was evaluated by immunofluorescence, through analysis of LAMP-1 colocalization with MAP. IBD macrophages were more permissive to MAP survival than HC macrophages (a finding not evident with MAH), but did not support MAP active growth. The lower MAP CFU counts in macrophage cultures associated with Infliximab treatment were not due to increased killing, but possibly to elevation in the proportion of intracellular dormant non-culturable MAP forms, as MAP showed higher viability in those macrophages. Increased MAP viability was not related to lack of phagolysosome maturation. The predominant induction of MAP dormant forms by Infliximab treatment may explain the lack of MAP reactivation during anti-TNF therapy of CD but does not exclude the possibility of MAP recrudescence after termination of therapy.

Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease.

Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.

Ionizing radiation exposure is still increasing in Crohn's disease: Who should be blamed?

BACKGROUND AND AIM: Crohn's disease (CD) patients undergo many radiological studies employing ionizing radiation for diagnosis and management purposes. Our aim was to assess the total radiation exposure of our patients over the years, to estimate the risk factors for exposure to high doses, and to correlate radiation exposure to immunosuppression. METHODS: The cumulative effective dose of radiation (CEDR) was calculated multiplying the number of imaging studies by the effective dose of each examination. RESULTS: A total of 451 patients with CD (226 female) were followed during 11.0 years (interquartile range [IQR]: 6.0-16.0), with 52.1% of the patients being classified with penetrating (B3) and 38.6% being steroid-dependent. About 16% were exposed to high-radiation dose levels (CEDR >50 mSv) and 4% were exposed to CEDR >100 mSv. The mean CEDR between age 26 and 35 years was 12.539 mSv and a significant dose of radiation (over 50 mSv) was achieved at a median age of 40 (IQR: 29.0-47.0). Abdominal-pelvic computed tomography scan was the examination that contributed the most for CEDR. Patients with B3 phenotype, previous surgery, azathioprine, and anti-tumor necrosis factor (TNF)-α therapy were exposed earlier on the course of the disease to CEDR >50 mSv (p < 0.001). The value of CEDR in the patients under immunosuppression mainly increased in the first year of immunosuppression. CONCLUSION: Penetrating phenotype, abdominal surgery, steroid resistance or steroid dependence, and treatment with anti-TNF-α and azathioprine were predictive factors for high CEDR. It was also demonstrated that immunosuppression and anti-TNF-α treatment were followed by a sustained increment of radiation exposure and that a significant dose of radiation was achieved <40 years of age.

Is it possible to change phenotype progression in Crohn's disease in the era of immunomodulators? Predictive factors of phenotype progression.

OBJECTIVES: Crohn's disease (CD) induces cumulative structural damage, initially characterized by a non-stenosing non-penetrating behavior (B1) with progression over time to a fibro-stenosing (B2) and/or penetrating phenotype (B3). Our aim was to assess the long-term evolution of disease behavior of CD and determine what factors predict phenotype progression. METHODS: This was a study based on prospectively collected data from a CD database in an inflammatory bowel disease outpatient clinic. B1 corresponds to a non-stenosing non-penetrating disease, B2 to a stenosing behavior, and B3 to a penetrating one. RESULTS: Seven hundred and thirty-six patients with CD (368 female) were followed up for 12.3 years (± 8.4), with 87.0% of them exhibiting B1 phenotype at diagnosis. Of these patients, 28.5% progressed to B2 phenotype and 23.5% to B3. Fifty percent of the patients started azathioprine treatment before phenotype change and 13.9% started anti-tumor necrosis factor-α (anti-TNFα) treatment before phenotype change. Monotherapy with azathioprine before phenotype change as well as combination therapy with azathioprine/anti-TNFα before phenotype change delayed disease progression (B1-B2 or B3) in comparison with patients who did not receive treatment (P<0.001). The hazard ratio (HR) for disease progression was lower for both monotherapy with azathioprine (HR: 0.15, P<0.001) or combination therapy with anti-TNFα (HR: 0.33, P<0.001). Upper gastrointestinal tract involvement, male gender, and steroid use were associated with an early progression of phenotype from B1 to B2 or B3 (P<0.001). The HR for disease progression was higher in patients who used steroids without criteria of dependence or resistance (HR: 2.67, P<0.001) and was even higher in patients with criteria of dependence or resistance (HR: 6.44, P<0.001). Longer delays between CD diagnosis and beginning of therapy with azathioprine and/or anti-TNFα were associated with disease progression. The longer the duration of treatment, the less likely the disease progression. CONCLUSIONS: Monotherapy with azathioprine before behavior change as well as combination therapy with azathioprine and anti-TNFα before behavior change delays phenotype progression of CD, whereas upper gastrointestinal tract involvement, male gender, and steroid use with or without criteria of steroid dependence are associated with a higher risk for disease progression.

Gastroenterology healthcare in LGBTQ+ individuals.

Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare that physicians must consider in clinical practice. Particularly, gastroenterologists are nowadays facing different issues in several fields regarding LGBTQ+ healthcare, such as endoscopy, inflammatory bowel disease, hepatology, and proctology. In this study, the authors provide a practice-oriented and up-to-date review reinforcing the importance of some of the most prevalent pathologies associated with sexuality that gastroenterologists may encounter in their clinical practice. In terms of endoscopy, authors describe the endoscopic findings related to human papillomavirus (HPV) infection: the esophageal squamous papilloma and cell carcinoma; also highlight the importance of retroflexion maneuver during a routine colonoscopy that allows detection of anal intraepithelial neoplasia lesions that can be anal cancer precursors. Regarding inflammatory bowel disease, some considerations are made about the differential diagnosis with infectious proctitis, and the topic of the risk of anal cancer due to HPV infection, in this specific population, is also addressed. Considering hepatology, the authors review the most important issues related to hepatotropic sexually transmitted infections. The authors also make some comments regarding the possibility of drug-induced liver injury in gender-affirming hormone therapy and pre-exposure prophylaxis for HIV prevention. Finally, considering the proctology field, an up-to-date review is performed regarding anal cancer screening, HPV infection and related diseases, and infectious proctitis management.