Early diagnosis of renal pelvis villous adenoma:A case report

BACKGROUND Villous adenoma is a rare tumor in the urinary system that usually occurs in the bladder.It is extremely uncommon in the renal pelvis.Most of the previously reported cases have been diagnosed with severe hydronephrosis associated with renal parenchyma atrophy prior to surgery.Because of its rarity,available information on the pathogenesis,diagnosis,treatment and prognosis of the disease is limited.We reported a case of kidney stones with hydronephrosis.During percutaneous nephroscopic lithotripsy,a renal pelvis tumor was found.Biopsy confirmed that the tumor was a villous adenoma of the renal pelvis.CASE SUMMARY A 68-year-old female was admitted to the hospital due to right kidney stones with right hydronephrosis.After admission,a urinary system plain computed tomography scan was performed,which revealed right kidney stones with right hydronephrosis and right upper ureteral dilatation.Multiple new cauliflower-like papillary masses were then discovered in the renal pelvis and calyces during right percutaneous nephroscopic lithotripsy.Biopsy results indicated villous adenoma with high-grade glandular intraepithelial neoplasia.The patient underwent laparoscopic radical resection of the right kidney and ureter.Based on histopathological and immunohistochemical examination,the patient was diagnosed with villous adenoma without adenocarcinoma.CONCLUSION Villous adenoma is rare in the urinary system.We reported a case of renal pelvis villous adenoma,which may provide useful information for the early diagnosis and treatment of this tumor.

Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients

AIM To quantify the presence of villous atrophy in endoscopic images for improved automation.METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy:(1) Statistical and(2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape.RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished.CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients.

Screening for celiac disease in Down's syndrome patients revealed cases of subtotal villous atrophy without typical for celiac disease HLA-DQ and tissue transglutaminase antibodies

A1M： To investigate the prevalence of celiac disease （CD） as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down＇s syndrome （DS） patients. METHODS： Immunoglobulin A （IgA） and G （IgG） type anti-gliadin antibodies （AGA）, IgA type anti-tissue transglutaminase （tTG） antibodies （anti-tTG） with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies （EHA） by indirect immunofiuoresence test. HLA-DQA1＊0501/DQB1＊0201 （DQ2） was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS： 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % [gA EMA （all positive for anti-tTG with human tTG）. Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1＊0S01/DQB1＊0201 and anti-tTG and EMA i.e. typical for CD markers （this case also fulfilled the ESPGHAN diagnostic criteria）, but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1＊0S01/DQB1＊0201 and IgA anti-tTG （EMA） were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % （95 % of confidence interval [CI]： 0.1-5.9 %）. CONCLUSION： We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD （with atypical immunopathogenesis） or some other immune enteropathy, requires further investigations.

Villous adenoma coexistent with focal well-differentiated adenocarcinoma of female urethral orifice: A case report and review of literature

BACKGROUND Villous adenomas of the urinary tract are uncommon. They are morphologically similar to and difficult to differentiate from their counterpart in the colon. The histogenesis and malignant potential are uncertain.CASE SUMMARY A 63-year-old woman was admitted to our hospital with a mass in the urethral orifice. Gross and microscopic pathological examination was suggestive of urethral villous adenoma with focal well-differentiated adenocarcinoma. The whole urethra and part of the bladder were excised. No further treatment was offered. Carcinoembryonic antigen, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, and p53 protein were positive, and the ratio of Ki-67 was 60%. After follow-up at 11 mo, the patient was cured and had no recurrence.CONCLUSION Immunohistochemistry is important for differential diagnosis of villous adenoma of the urinary system. Complete surgical resection of the urinary tract is curative.

Gallbladder villous adenoma in a patient with acromegaly:A case report

Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecific gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large （4.5 cm）, hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After five years of follo up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range.

Non-invasive prediction of persistent villous atrophy in celiac disease

BACKGROUND Celiac disease(CD)is an immune-mediated enteropathy that is primarily treated with a gluten-free diet(GFD).Mucosal healing is the main target of the therapy.Currently,duodenal biopsy is the only way to evaluate mucosal healing,and noninvasive markers are challenging.Persistent elevation of anti-tissue transglutaminase antibodies(aTTG)is not an ideal predictor of persistent villous atrophy(VA).Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies(aDGP)and abdominal ultrasonography are lacking.AIM To evaluate the ability of aTTG,aDGP,small bowel ultrasonography,and clinical and laboratory parameters in predicting persistent VA determined using histology.METHODS Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy,levels of aTTG and aDGP,and underwent small bowel ultrasonography were included in this retrospective cohort study.We evaluated the sensitivity,specificity,and positive and negative predictive values of aTTG,aDGP,small bowel ultrasonography,laboratory and clinical parameters to predict persistent VA.A receiver operating characteristic(ROC)curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction.RESULTS Complete data were available for 82 patients who were followed up over a period of four years(2014-2018).Among patients included in the analysis,women(67,81.7%)were predominant and the mean age at diagnosis was 33.8 years.Followup biopsy revealed persistent VA in 19 patients(23.2%).The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50%and 85.7%,respectively,while the sensitivity and specificity of aDGP(using the diagnostic cutoff value)was 77.8%and 75%,respectively.Calculation of an optimal cutoff value using ROC analysis(13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA)increased the accuracy and reached 72.2%[95%confidence interval(CI):46.5-90.3]sensitivity and 90%(95%CI:79.5-96.2)specificity for aDGP IgA and 66.7%(95%CI:41.0-86.7)sensitivity and 93.7%(95%CI:84.5-98.2)specificity for aTTG IgA.The sensitivity and specificity of small bowel ultrasonography was 64.7%and 73.5%,respectively.A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9%and 98%for aTTG IgA and to 90.0%and 97.8%for aDGP IgA.Laboratory and clinical parameters had poor predictive values.CONCLUSION The sensitivity,specificity,and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values.The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Digesting gluten with oral endopeptidases to improve the management of celiac disease

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals.Although avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa.As villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid complications.Oral administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under investigation.The article is about the utility of one endopeptidase isolated from Aspergillus niger.We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t（8;14）（q24;q32） translocation

Splenic lymphoma with villous lymphocytes （SLVL） or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t（8;14）（q24;q32） translocation has been reported. In this study, we report a case of B- lymphoproliferative disorder with villous lymphocytes harboring t（8;14）（q24;q32） chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis （lymphocytes 〉 200 × 10^9/L）. The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19^＋, CD20^＋, HLA- DR^＋, CD22^＋, CD5^＋, Kappa^＋, CD25^dim, CD71^dim, Lambda, CD7, CD10-, CD23 , CD34, CD33, CD13 , CD14, CDll7, CD64, CD103, and CD11c-. The karyotype showed complex abnormality： 46XX,＋ 3,-10, t（8;14）（q24; q32）lll]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t（8,14） chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t（8;14）（q24;q32） translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

Implementation of a polling protocol for predicting celiac disease in videocapsule analysis

AIM: To investigate the presence of small intestinal villous atrophy in celiac disease patients from quantitative analysis of videocapsule image sequences.METHODS: Nine celiac patient data with biopsy-proven villous atrophy and seven control patient data lacking villous atrophy were used for analysis. Celiacs had biopsy-proven disease with scores of Marsh Ⅱ-Ⅲ C except in the case of one hemophiliac patient. At four small intestinal levels (duodenal bulb, distal duodenum, jejunum, and ileum), video clips of length 200 frames (100 s) were analyzed. Twenty-four measurements were used for image characterization. These measurements were determined by quantitatively processing the videocapsule images via techniques for texture analysis, motility estimation, volumetric reconstruction using shape-from-shading principles, and image transformation. Each automated measurement method, or automaton, was polled as to whether or not villous atrophy was present in the small intestine, indicating celiac disease. Each automaton's vote was determined based upon an optimized parameter threshold level, with the threshold levels being determined from prior data. A prediction of villous atrophy was made if it received the majority of votes (≥ 13), while no prediction was made for tie votes (12-12). Thus each set of images was classified as being from either a celiac disease patient or from a control patient. RESULTS: Separated by intestinal level, the overall sensitivity of automata polling for predicting villous atrophy and hence celiac disease was 83.9%, while the specificity was 92.9%, and the overall accuracy of automata-based polling was 88.1%. The method of image transformation yielded the highest sensitivity at 93.8%, while the method of texture analysis using subbands had the highest specificity at 76.0%. Similar results of prediction were observed at all four small intestinal locations, but there were more tie votes at location 4 (ileum). Incorrect prediction which reduced sensitivity occurred for two celiac patients with Marsh type Ⅱ pattern, which is characterized by crypt hyperplasia, but normal villous architecture. Pooled from all levels, there was a mean of 14.31 ± 3.28 automaton votes for celiac vs 9.67 ± 3.31 automaton votes for control when celiac patient data was analyzed (P<0.001). Pooled from all levels, there was a mean of 9.71 ± 2.8128 automaton votes for celiac vs 14.32 ± 2.7931 automaton votes for control when control patient data was analyzed (P<0.001). CONCLUSION: Automata-based polling may be useful to indicate presence of mucosal atrophy, indicative of celiac disease, across the entire small bowel, though this must be confirmed in a larger patient set. Since the method is quantitative and automated, it can potentially eliminate observer bias and enable the detectionof subtle abnormality in patients lacking a clear diagnosis. Our paradigm was found to be more efficacious at proximal small intestinal locations, which may suggest a greater presence and severity of villous atrophy at proximal as compared with distal locations.

Emerging role of narrow band imaging in duodenum

Endoscopy using magnification narrow band imaging(m NBI) allows detailed assessment of mucosal surface and vascular pattern. This may help in better identification and prediction of the nature of the lesion. The role of this technology in duodenum is still evolving. Studies have shown that m NBI has high accuracy in predicting villous atrophy in the duodenum. Limited data suggests that this technique can provide additional information on duodenal polyps,nodules and ampullary tumour which can help guide their management. In this paper we describe the technique for duodenal assessment using NBI and review the existing literature evaluating its role in diagnosis of various duodenal pathologies.

Synovial lipomatosis: A rare cause of knee pain in an adolescent female

Synovial lipomatosis is a benign proliferative disease of the subsynovial adipose which can lead to a variety of presentations. Cases of synovial lipomatosis in children or adolescents are rare. This case report describes an adolescent patient with a rare bilateral presentation of synovial lipomatosis. She had been treated for years prior to her presentation for juvenile idiopathic arthritis. She presented with chronic bilateral knee pain, swelling, and mechanical symptoms. Bilateral MR imaging demonstrated effusions, hypertrophy of the synovium, and polyp-like projections of tissue with the same signal intensity as fat which is pathognomonic for synovial lipomatosis. Arthroscopic synovectomy and extensive debridement of polyp like fat projections of the right knee was performed. Histopathology was consistent with the synovial lipomatosis diagnosis. Postoperatively, the patient was satisfied with her outcome with improved pain relief and function in her right knee.

Pancreatitis complicating mucin-hypersecreting common bile duct adenoma

Villous adenomas of the bile ducts are extremely uncommon. We describe a 58-year-old man presenting with clinical signs and laboratory findings of acute pancreatitis and obstructive jaundice. Preoperative investigation demonstrated a dilated papillary orifice with mucus exiting （fish-mouth sign） and a filling defect in the distal common bile duct. He underwent a modified Whipple operation and histological examination of the surgical specimen showed villous adenoma with rich secretion of mucus.

Methotrexate induced sprue-like syndrome

A 52 year-old male patient diagnosed of ankylosing spon-dylitis presented with an iron deficiency anemia after a ten-month treatment of methotrexate. He did not respond to treatment with oral iron not a proton pump inhibitor and an upper endoscopy was performed. The histological study of the duodenal biopsies showed villus atrophy. After removing the methotrexate, administrating intra-muscular iron and undertaking a gluten-free diet, the histological and analytical alterations progressively resolved.

Understanding celiac disease monitoring patterns and outcomes after diagnosis:A multinational,retrospective chart review study

BACKGROUND Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease.AIM To understand patterns of follow-up and management of patients with celiac disease,and to characterize symptoms and villous atrophy after diagnosis.METHODS A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease.Three gastroenterology referral centers,with substantial expertise in celiac disease,participated in the United Kingdom,United States,and Norway.Demographic and clinical data were collected from medical charts.Descriptive analyses were conducted on patients with biopsyconfirmed celiac disease,diagnosed between 2008 and 2012,with at least one follow-up visit before December 31,2017.Patient demographic and clinical characteristics,biopsy/serology tests and results,symptoms,and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period(i.e.,before the study end date of December 31,2017).RESULTS A total of 300 patients were included in this study[72%female;mean age at diagnosis:38.9 years,standard deviation(SD)17.2].Patients were followed-up for a mean of 29.9 mo(SD 22.1)and there were,on average,three follow-up visits per patient during the study period.Over two-thirds(68.4%)of patients were recorded as having ongoing gastrointestinal symptoms and 11.0%had ongoing symptoms and enteropathy during follow-up.Approximately 80%of patients were referred to a dietician at least once during the follow-up period.Half(50.0%)of the patients underwent at least one follow-up duodenal biopsy and 36.6%had continued villous atrophy.Patterns of monitoring varied between sites.Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration.CONCLUSION This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

Quantitative Evaluation of Nucleolar Organizer Region-associated Proteins in Colon Tumors

By using silver colloid staining technique,nucleolar organizer region-associated proteins(AgNORs)were studied quantatively in paraffin sections of 12 casesof polypoid adenomas,10 cases of villous adenomas,22 cases of colonadenocarcinomas,and 10 cases of normal colonic mucosa as control.The resultsshowed that the mean number of AgNORs per nucleus in the villous adcnoma was similarto that of adenocaranoma,which significantly exceeded those of the normal mucosa andthe polypoid adenoma.The granules of AgNORs in adcnocarcinoma were much largerand more irregular in sizc and shape.It is suggested that benign villous adenoma is akind of lesion between polypoid adenoma and adenocarcinoma,and AgNOR techniquemay be very helpful in differential diagnosis of colon tumors.

Serologic diagnosis of celiac disease: May it be suitable for adults?

The diagnosis of coeliac disease(CD)in adult patients requires the simultaneous assessment of clinical presentation,serology,and typical histological picture of villous atrophy.However,several years ago,the European Society of Pediatric Gastroenterology,Hepatology,and Nutrition guidelines approved new criteria for the diagnosis in children:Biopsy could be avoided when antitransglutaminase antibody(TGA)values exceed the cut-off of×10 upper limit of normal(ULN)and anti-endomysium antibodies are positive,independently from value.This“no biopsy”approach is a decisive need for pediatric population,allowing to avoid stressful endoscopic procedures in children,if unnecessary.This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh’s classification.Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels.Therefore,we aim to perform a narrative review on the topic in adults.Despite that some studies confirmed that the×10 ULN threshold value has a very good diagnostic performance,several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture.In conclusion,the heterogeneity of study reports as well as some conditions,which may hamper the serological diagnosis of CD(such as seronegative CD and non-celiac villous atrophy)and are much more common in adults than in children,could represent a limitation for the“no biopsy”approach to CD diagnosis in patients outside the pediatric age.