Eosinophilic esophagitis: Does age matter?

OBJECTIVES: Eosinophilic esophagitis (EoE) is often diagnosed in school-age children between 6- and 9-year-old. There is less known about those who are diagnosed with EoE that are younger than 6 years old. The objective of this study is to compare clinical presentation, comorbidities, and outcomes based on age at diagnosis of EoE. METHODS: Single-center retrospective chart review of children (<18 years) diagnosed with EoE between 2005 and 2020. We recorded demographics, clinical presentation, family history, past medical history, treatment, and endoscopic findings. Children in this cohort were classified based on age into three age groups: <2 years, 2-<6 years, and 6-<18 years. RESULTS: We identified 256 children with EoE, the mean age (SD) at the time of diagnosis was 9 (5.2) years and 184 (72%) were male. We had 164 (64%) patients with available follow-up esophagogastroduodenoscopies (EGDs) data (495 EGDs in total) of those 99/164 (60%) reached mucosal remission. In the very young children (<2 years) vomiting was the most common presentation, while poor weight gain was seen more in the 2-<6-year group in comparison to the >6-years. Food impaction and abdominal pain were most likely to present in older children 6-18 years. Combination therapy, as opposed to a single therapy, induced remission at a higher frequency in the <6-year group in comparison to the 6-<18-year group (85% vs. 66%). CONCLUSION: EoE should be considered in younger children presenting with feeding difficulty and poor weight gain. Combination therapy seems to be more effective in younger children with EoE, but further studies with bigger sample size are needed to study the efficacy of the different combination therapies.

WITHDRAWN: Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.

Digital Hepatic Iron Content: An Artificial Intelligence Model for Spatially Resolved Histologic Iron Quantitative Analysis in Liver Samples.

Currently, the precise evaluation of tissue hepatic iron content (HIC) requires laboratory testing using tissue-destructive methods based on colorimetry or spectrophotometry. To maximize the use of routine histologic stains in this context, we developed an artificial intelligence (AI) model for the recognition and spatially resolved measurement of iron in liver samples. Our AI model was developed using a cloud-based, supervised deep learning platform (Aiforia Technologies). Using digitized Pearl Prussian blue iron stain whole slide images representing the full spectrum of changes seen in hepatic iron overload, our training set consisted of 59 cases, and our validation set consisted of 19 cases. The study group consisted of 98 liver samples from 5 different laboratories, for which tissue quantitative analysis using inductively coupled plasma mass spectrometry was available, collected between 2012 and 2022. The correlation between the AI model % iron area and HIC was Rs = 0.93 for needle core biopsy samples (n = 73) and Rs = 0.86 for all samples (n = 98). The digital hepatic iron index (HII) was highly correlated with HII > 1 (area under the curve [AUC] = 0.93) and HII > 1.9 (AUC = 0.94). The percentage area of iron within hepatocytes (vs Kupffer cells and portal tract iron) identified patients with any hereditary hemochromatosis-related mutations (either homozygous or heterozygous) (AUC = 0.65, P = .01) with at least similar accuracy than HIC, HII, and any histologic iron score. The correlation between the Deugnier and Turlin score and the AI model % iron area for all patients was Rs = 0.87 for total score, Rs = 0.82 for hepatocyte iron score, and Rs = 0.84 for Kupffer cell iron score. Iron quantitative analysis using our AI model was highly correlated with both detailed histologic scoring systems and tissue quantitative analysis using inductively coupled plasma mass spectrometry and offers advantages (related to the spatial resolution of iron analysis and the nontissue-destructive nature of the test) over standard quantitative methods.

Adding Inflammatory Markers and Refining National Institute on Alcohol Abuse and Alcoholism Criteria Improve Diagnostic Accuracy for Alcohol-associated Hepatitis.

BACKGROUND & AIMS: Although histology is considered the gold standard for diagnosis of alcohol-associated hepatitis (AH), it is not required for entry into therapeutic studies if patients meet National Institute on Alcohol Abuse and Alcoholism (NIAAA) consensus criteria for probable AH. Our aim was to assess the diagnostic accuracy of NIAAA criteria against liver biopsy and to explore new criteria to enhance diagnostic accuracy for AH. METHODS: A total of 268 consecutive patients with alcohol-related liver disease with liver biopsy were prospectively included: 210 and 58 in the derivation and validation cohorts, respectively. NIAAA criteria and histological diagnosis of alcoholic steatohepatitis (ASH) were independently reviewed by clinical investigators and pathologists from Hospital Clínic and Mayo Clinic. Using biopsy-proven ASH as gold standard we determined diagnostic capability of NIAAA criteria and proposed the new improved criteria. RESULTS: In the derivation cohort, diagnostic accuracy of NIAAA for AH was modest (72%) due to low sensitivity (63%). Subjects who did not meet NIAAA with ASH at liver biopsy had lower 1-year survival compared with subjects without ASH (70% vs 90%; P < .001). NIAAAm-CRP criteria, created by adding C-reactive protein and modifying the variables of the original NIAAA, had higher sensitivity (70%), accuracy (78%), and specificity (83%). Accuracy was also higher in a sensitivity analysis in severe AH (74% vs 65%). In the validation cohort, NIAAAm-CRP and NIAAA criteria had a sensitivity of 56% vs 52% and an accuracy of 76% vs 69%, respectively. CONCLUSION: NIAAA criteria are suboptimal for the diagnosis of AH. The proposed NIAAAm-CRP criteria may improve accuracy for noninvasive diagnosis of AH in patients with alcohol-related liver disease.

Performance of an Artificial Intelligence Model for Recognition and Quantitation of Histologic Features of Eosinophilic Esophagitis on Biopsy Samples.

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [rs] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; rs = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (rs = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists.

Artificial intelligence-based reticulin proportionate area - a novel histological outcome predictor in hepatocellular carcinoma.

AIMS: Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour-related outcomes. METHODS AND RESULTS: We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud-based, deep-learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow-up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease-free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. CONCLUSION: Our data indicate that decreased RPA is a strong predictor of various HCC-related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.

Metallothionein immunohistochemistry has high sensitivity and specificity for detection of Wilson disease.

Diagnosis of Wilson disease (WD) can be difficult because of its protean clinical presentations, but early diagnosis is important because effective treatment is available and can prevent disease progression. Similarly, diagnosis of WD on liver biopsy specimens is difficult due to the wide range of histologic appearances. A stain that could help identify WD patients would be of great value. The goal of this study was to use mass spectrometry-based proteomics to identify potential proteins that are differentially expressed in WD compared to controls, and could serve as potential immunohistochemical markers for screening. Several proteins were differentially expressed in WD and immunohistochemical stains for two (metallothionein (MT) and cytochrome C oxidase copper chaperone (COX17)) were tested and compared to other methods of diagnosis in WD including copper staining and quantitative copper assays. We found diffuse metallothionein immunoreactivity in all liver specimens from patients with WD (n = 20); the intensity of the staining was moderate to strong. This staining pattern was distinct from that seen in specimens from the control groups (none of which showed strong, diffuse staining), which included diseases that may be in the clinical or histologic differential of WD (steatohepatitis (n = 51), chronic viral hepatitis (n = 40), autoimmune hepatitis (n = 50), chronic biliary tract disease (n = 42), and normal liver (n = 20)). COX17 immunostain showed no significant difference in expression between the WD and control groups. MT had higher sensitivity than rhodanine for diagnosis of WD. While the quantitative liver copper assays also had high sensitivity, they require more tissue, have a higher cost, longer turnaround time, and are less widely available than an immunohistochemical stain. We conclude that MT IHC is a sensitive immunohistochemical stain for the diagnosis of WD that could be widely deployed as a screening tool for liver biopsies in which WD is in the clinical or histologic differential diagnosis.

Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. METHODS: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. RESULTS: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1-306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. CONCLUSIONS: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.

Diagnostic challenges of focal nodular hyperplasia: interobserver variability, accuracy, and the utility of glutamine synthetase immunohistochemistry.

AIMS: The diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH. METHODS AND RESULTS: The study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non-lesional liver specimens). Pathologists were reasonably accurate (83.1%) in the diagnosis of FNH with haematoxylin and eosin alone. Ductular reaction and nodularity had the highest sensitivity for a diagnosis of FNH (88.1% and 82.2%, respectively), whereas central scar was the most specific feature (90.6%). The presence of two or more of the classic histological features had 89.6% sensitivity and 86.2% specificity for a diagnosis of FNH. Diagnostic accuracy was significantly higher with the addition of a GS stain. A map-like GS staining pattern was highly specific (99.3%) for FNH. However, GS staining was interpreted as non-map-like in 14.4% of reviews of true FNH cases, and overall interobserver agreement for interpretation of the GS staining pattern was only moderate (kappa = 0.42). CONCLUSIONS: Pathologists are reasonably accurate in the diagnosis of FNH on virtual biopsies, and GS staining improves accuracy. However, a subset of FNH cases remain challenging. Steatosis and a pseudo-map-like GS staining pattern were associated with increased difficulty. Therefore, although a map-like GS staining pattern is useful for confirmation of a diagnosis, the lack of a map-like GS staining pattern on needle biopsy does not necessarily exclude a diagnosis of FNH.

Autologous Adipose Tissue-Derived Mesenchymal Stem Cells Introduced by Biliary Stents or Local Immersion in Porcine Bile Duct Anastomoses.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal versus extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. Pigs were divided into 3 groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, reanastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded Vicryl mesh. Group 2 received stents wrapped in MSC-seeded mesh. Group 3 received unwrapped stents with the anastomosis immersed in an MSC suspension. Animals were killed 1 month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin-eosin and trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and for a marker of neoangiogenesis (CD31). There were no intraoperative complications. One pig died on postoperative day 3 due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in group 3 based on trichrome stain. CD31 staining of group 3 was more pronounced, supporting enhanced neoangiogenesis. In conclusion, adipose-derived MSCs were safely applied to biliary anastomoses. MSCs were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.

Nonaqueous electrophoresis on microchips: A review.

The use of organic solvents as electrolytic medium in electrophoresis has become an important alternative for the analysis of compounds that exhibit low or no solubility in water. In recent years, nonaqueous electrophoresis has been extensively explored in conventional capillary systems for different applications. On the other hand, this separation strategy is still not as popular as free solution electrophoresis on chip-based platforms due to the effects of solvent in the background electrolyte on the sample injection, detection performance, and microfluidic platform compatibility. In this way, this review summarizes the main achievements on nonaqueous microchip electrophoresis (NAME). To the best of our knowledge, this is the first review dedicated to discuss exclusively nonaqueous electrophoresis on chip-based systems. For this purpose, some important theoretical aspects involved when separations are performed in organic medium, such as equilibrium, interactions and electrophoretic considerations, are included in the review. In addition, the main challenges, advantages and influences of nonaqueous media on the sample injection, detection as well as the choice of the substrate to fabricate chip-based electrophoresis devices are highlighted. Last, examples showing the feasibility of nonaqueous microchip electrophoresis for applications exploiting different methodologies, operational, and instrumental conditions are summarized and discussed. We hope this review can be useful to spread the huge potential of nonaqueous electrophoresis on microfluidic platforms.

Rapid separation of post-blast explosive residues on glass electrophoresis microchips.

This study describes the development of an analytical methodology based on the use of microchip electrophoresis (ME) devices integrated with capacitively coupled contactless conductivity detection (C4 D) for the separation and detection of inorganic anions in post-blast explosive residues. The best separation condition was achieved using a running buffer composed of 35 mmol/L lactic acid, 10 mmol/L histidine and 0.070 mmol/L cetyl(trimethyl ammonium) bromide. For C4 D measurements, the highest sensitivity was obtained applying a 700 kHz sinusoidal wave with excitation voltage of 20 Vpp . The separation of Cl- , NO3- , NO2- , SO42- , ClO4- and ClO3- was performed within ca. 150 s with baseline resolution and efficiencies between 4.4 × 104 and 1.7 × 105 plates/m. The found limits of detection ranged between 2.5 and 9.5 µmol/L. Last, real samples of post-blast explosive residues were analyzed on the ME-C4 D devices obtaining successfully the determination of Cl- , NO3- and SO42- . The achieved concentration values varied between 12.8-72.5 mg/L for Cl- , 1.7-293.1 mg/L for NO3- and 1.3-201.3 mg/L for SO42- . The data obtained using ME-C4 D devices were in good agreement with the concentrations found by ion chromatography. The approach reported herein has provided short analysis time, instrumental simplicity, good analytical performance and low cost. Furthermore, the ME-C4 D devices emerge as a powerful and portable analytical platform for on-site analysis demonstrating to be a promising tool for the crime scene investigation.

Screening of seized cocaine samples using electrophoresis microchips with integrated contactless conductivity detection.

This study describes the development of a new analytical method for the separation and detection of cocaine (COC) and its adulterants, or cutting agents, using microchip electrophoresis (ME) devices coupled with capacitively coupled contactless conductivity detection (C4 D). All the experiments were carried out using a glass commercial ME device containing two pairs of integrated sensing electrodes. The running buffer composed of 20 mmol/L amino-2-(hydroxymethyl) propane-1,3-diol and 10 mmol/L 3,4-dimethoxycinnamic acid provided the best separation conditions for COC and its adulterants with baseline resolution (R > 1.6), separation efficiencies ranging from (2.9 ± 0.1) to (3.2 ± 0.2) × 105 plates/m, and estimated LOD values between 40 and 150 µmol/L. The quantification of COC was successfully performed in four samples seized by the Brazilian Federal Police Department and all predicted values agree with values estimated by the reference method. Some other interfering species were detected in the seized samples during the screening procedure on ME-C4 D devices. While lidocaine was detected in sample 3, the presence of levamisole was observed in samples 2 and 4. However, their concentrations were estimated to be below the LOQ. ME-C4 D devices have proved to be quite efficient for the identification and quantification of COC with errors lower than 10% when compared to the data obtained by a reference method. The approach herein reported offers great potential to be used for on-site COC screening in seized samples.

Authenticity screening of seized whiskey samples using electrophoresis microchips coupled with contactless conductivity detection.

This report describes for the first time the use of microchip electrophoresis (ME) devices integrated with capacitively coupled contactless conductivity detection (C4 D) to investigate the authenticity of seized whiskey samples, which were probably adulterated by simple dilution with tap water. The proposed microfluidic platform was explored for the monitoring of anionic species (Cl- and F- ) in both original and tampered samples. The best separations were achieved within 70 s using a running buffer composed of lactic acid and histidine (pH = 5.9). ME-C4 D devices were used to analyze samples from three different brands (five samples each). Based on the presence of inorganic anions like Cl- , F- , SO42- and NO2- in different amounts, the authenticity of seized whiskeys was compared to original samples. According to the reported data, the proposed microfluidic platform can be useful to help regulatory authorities in the investigation and monitoring of authenticity of commercialized whiskey beverages.

A case report of sevelamer-associated recto-sigmoid ulcers.

BACKGROUND: Optimal phosphorous control is an important aspect of the care of patients with end-stage renal disease, and phosphate binders are usually needed. CASE PRESENTATION: A 74-year-old woman with end-stage renal disease on maintenance hemodialysis presented to the emergency room with abdominal discomfort, rectal pain, and blood-tinged stools. Initial concern was for a rectal carcinoma, based on the symptoms and imaging in initial computerized tomography of the abdomen showing rectal wall thickening, and her clinical presentation. She had been treated with the phosphate binder sevelamer for two months. In this case report, we explore the unique features of sevelamer-associated recto-sigmoid ulcers which led to her symptoms. CONCLUSION: Sevelamer is widely used in chronic kidney disease and end-stage renal disease patients with hyperphosphatemia. It is a crosslinked polymeric amine that binds phosphates and bile acids; it is not systemically absorbed. To the authors' knowledge, this is the first reported case of recto-sigmoid ulcers associated with use of this phosphate binder. Nephrologists, pathologists, and gastroenterology sub-specialists should be aware of this recently-reported entity in patients on sevelamer with suggestive symptoms, as this medication is widely used in renal patients.

Eugenia dysenterica DC. (Myrtaceae) exerts chemopreventive effects against hexavalent chromium-induced damage in vitro and in vivo.

CONTEXT: Eugenia dysenterica DC. (Myrtaceae) has been widely used in the folk medicine and it presents phytochemicals constituents associated to antioxidant properties. OBJECTIVE: The objective of this study was to investigate the protective effects of E. dysenterica leaf hydroalcoholic extract (EDE) in vitro and in vivo using AMJ2-C11 cells and Swiss mice exposed to hexavalent chromium [Cr(VI)], respectively. MATERIALS AND METHODS: AMJ2-C11 cells were pretreated with EDE and exposed to Cr(VI) to evaluate cytotoxicity and the pathways involved in the chemopreventive effects of the extract. Mice were daily pretreated with EDE and then exposed to Cr(VI). Survival analysis, histopathological examination and determination of Cr levels in biological tissues were carried out. RESULTS: In vitro studies showed that pretreatment of the AMJ2-C11 cells with EDE protected against the cytotoxicity and oxidative stress induced by Cr(VI). Consequently, the pretreatment with EDE reduced reactive oxygen species and apoptosis triggered by Cr(VI), probably by a marked antioxidant and chelating activities demonstrated by EDE. Regarding in vivo studies, pretreatment for 10 days with EDE increased survival of the mice exposed to Cr(VI). In addition, EDE prevented liver and kidney pathological damages, in parallel with reduction in chromium levels found in these organs and plasma. EDE also showed a marked antioxidant potential associated with the presence of polyphenols, especially flavonoids and tannins, as confirmed by HPLC-PDA. CONCLUSION: The study showed that EDE protects against Cr(VI)-induced damage in vitro and in vivo supporting further studies for the development of therapeutic products applied to prevent the damage induced by toxic metals, especially Cr(VI).

Bile salt export pump: a sensitive and specific immunohistochemical marker of hepatocellular carcinoma.

AIMS: Bile salt export pump (BSEP) is a transporter expressed exclusively at hepatic canaliculi and drives bile-salt efflux. Minimal data exist about BSEP expression in tumours. We hypothesized that BSEP immunohistochemistry would be specific for hepatocellular carcinoma (HCC). METHODS AND RESULTS: Tissue microarrays, including 48 HCC, 41 cholangiocarcinomas and 24 metastatic tumours in liver, were immunostained for BSEP. Expression was compared with common markers of hepatocytic differentiation including CD10, hepatocyte paraffin-1 antigen (HepPar-1), carcinoembryonic antigen, arginase-1 (ARG) and glypican-3 (GPC-3). BSEP expression was assessed in normal tissues. Special attention was given to adrenal gland (normal and neoplasia). BSEP was easy to interpret and showed no background staining. Canalicular expression was seen in all normal livers, but not in other normal tissue. BSEP was 90% sensitive and 100% specific for HCC (canalicular in 33 of 43 positive cases). The sensitivity of ARG was slightly higher, but specificity was slightly lower (94% for both). HepPar-1 was 90% sensitive and 97% specific. CD10, polyclonal carcinoembryonic antigen (pCEA) and GPC-3 all had lower sensitivity (74, 81 and 54%, respectively). CONCLUSIONS: In malignant tumours in the liver, BSEP marking was 100% specific and 90% sensitive for HCC. The specificity of BSEP for HCC obviates the need to identify a 'canalicular' pattern, which can limit the utility of other canalicular markers.

Esophagitis Dissecans Superficialis: Clinical, Endoscopic, and Histologic Features.

BACKGROUND: Esophagitis dissecans superficialis (EDS) is a desquamative disorder of the esophagus, but there is a paucity of the literature regarding this condition. AIM: We examined our institution's experience to further characterize clinical outcomes, and endoscopic and histopathologic features. METHODS: Endoscopy and pathology databases were retrospectively reviewed from 2000 to 2013 at Mayo Clinic Rochester to identify potential cases of EDS. Medical records and endoscopic images were reviewed to identify cases, and original pathologic specimens were also reviewed. Clinical, endoscopic, and histologic characteristics of EDS were defined. RESULTS: Forty-one subjects were identified with a median age at diagnosis of 65.0 years (IQR 52.8-76.1) and a female preponderance (63.4 %). Many patients were taking a psychoactive agent (73.1 %) or acid-suppressive therapy (58.5 %) preceding the index endoscopy. Strips of sloughed membranes had a predilection for the distal and/or middle esophagus and resolved in 85.7 % of subjects at endoscopic follow-up. Parakeratosis and intraepithelial splitting were histologic features seen in all patients, while splitting of the connective tissue and intraepithelial bullae were seen in 46.2 and 11.1 %, respectively. There were no disease-related complications at a median follow-up of 10.4 months (IQR 1.2-17.2). CONCLUSIONS: EDS is likely under-recognized. A distinct endoscopic feature of EDS is "sloughing" strips of mucosa with parakeratosis and intraepithelial splitting being sine qua non histologic findings. The use of psychoactive agents (particularly a SSRI or SNRI) was prevalent at endoscopic diagnosis, although the clinical relevance of this is uncertain. EDS appears to be a benign, incidental finding without complications.

Clinical, radiographic, and histological analyses of calcium phosphate cement as filling material in maxillary sinus lift surgery.

BACKGROUND: The installation of dental implants in the posterior maxilla is often faced with resorbed alveolar processes, resulting from a combination of pneumatization of the maxillary sinus, the effects of periodontal disease, and physiological bone resorption. The sinus lift surgery has been practiced since 1980 with the aim to increase bone height in this region for an implant supported prosthetic rehabilitation, and various filling materials have been used for such. OBJECTIVES: This study aimed to clinically, radiographically, and histologically evaluate a preparation of calcium phosphate cement (Bone Source(®), BS) used as filling material in maxillary sinus elevation surgery. METHODS: Ten patients were operated requiring maxillary sinus graft for future placement of osseointegrated implants. After a period ranging from 9 to 16 months, a clinical evaluation and biopsy of the grafted area in the region adjacent to the axis of the implant to be inserted were performed. RESULTS: Clinically and radiographically, no evidence of resorption/substitution of BS was noticed. Although no patients have had postoperative complications and the material presented fully biocompatible characteristics with woven bone in intimate contact with BS, it was not possible to place any implants due to minimal bone formation and friability of the material. CONCLUSION: It was concluded that despite the osteoconductive capacity of BS, this conventional calcium phosphate preparation does not support sufficient amount of new bone formation that could allow its use as filling material for maxillary sinus floor lift and subsequent dental implant placement.