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Fine-needle aspiration demonstrated clusters of spindle cells with mild anisonucleosis, elongated nuclei, small nucleoli and haemosiderin granules (Figure A,B). Microscopic examination showed a lymph node with a thin rim of lymphoid tissue (Figure A) and spindle cells arranged in solid sheets exhibiting ovoid to elongated nuclei, small nucleoli and nuclear inclusions. GLO:EW1/01sep19:his13859-fig-0001.jpg PHOTO (COLOR): A, Spindle cells cluster as well as isolated spindle cells (arrows). [Extracted from the article]

Background and purpose Cancer-associated fibroblasts (CAFs) are increasingly recognised as promoters of tumour progression. It is poorly investigated whether cancer management protocols, such as neoadjuvant radio(chemo)therapy, have an impact on CAFs and, by consequence, on tumour progression. This prompted us to study the impact of neoadjuvant radio(chemo)therapy on the α-SMA/epithelial area ratio in rectal cancer, and the impact of this ratio on recurrence-free survival. Material and methods Immunohistochemistry for the CAF marker α-SMA and the proliferation marker Ki67 was performed on sections from 98 rectal cancers of which 62 had undergone neoadjuvant radio(chemo)therapy. Results Computer-assisted quantitative analysis showed that the α-SMA/neoplastic epithelial area ratio was higher after neoadjuvant therapy, and that rectal cancers with high α-SMA/epithelial area ratio had low proliferation rates. Interestingly, the α-SMA/epithelial area ratio was an adverse prognostic factor with regard to recurrence-free survival in univariate analysis. In addition, multivariate analysis showed that an α-SMA/epithelial area ratio above 1 provides an independent prognostic value associated with a poor recurrence-free survival. Conclusion These results suggest that neoadjuvant treatment has an impact on CAFs in rectal cancer. The correlation of CAFs with decreased recurrence-free survival and abundant experimental data in the literature suggest that under certain circumstances, not yet very well understood, CAFs may favour tumour progression. [ABSTRACT FROM AUTHOR]

The article present a case study of a 70‐year‐old White man revealed biological cholestasis with an increased level of γ‐GT. It mentions abdominal tomography showed a mass in the left hepatic lobe, which is four centimetres in diameter and associated with a dilated left bile duct; and also mentions macroscopic examination displayed a four centimetres whitish mass invading the liver parenchyma and exhibiting intraductal growth.

The coronavirus pandemic raging worldwide since December 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which invades human cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Although it has already been identified in many organs, ACE2 expression remains largely unknown in the head and neck (HN) sphere. Thus, this study aims to investigate its protein expression in several sites of the upper aerodigestive tract in order to highlight potential routes of infection. We compared ACE2 immunohistochemical expression between 70 paraffin-embedded specimens with two different antibodies and reported the quantified expression in each histological location. Surprisingly, we obtained different results depending on the antibody, an absence of labeling having been observed with a monoclonal antibody raised against the extracellular domain, whereas the polyclonal, against the cytoplasmic part of the protein, revealed enriched ACE2 expression, particularly in sinuses, vocal cords, salivary glands and oral cavity epithelial cells. The interpretation of these discordant results has brought several exciting lines of reflection. In conclusion, this study provides possible routes of entry for the SARS-CoV-2 in HN region and, above all, has led us to encourage caution when studying the ACE2 expression which is currently at the center of all attention. [ABSTRACT FROM AUTHOR]

We report the case of a 79-year-old woman with a large pelvic mass and postmenopausal bleeding, associated with hyperestrogenism. A pelvic MRI shows the presence of a large mass of 12.6 cm originating from the right ovary without signs of metastasis. A total abdominal hysterectomy with unilateral salpingooophorectomy was performed, knowing the patient underwent a left salpingooophorectomy decades ago. The pathological findings showed an ovarian clear cell carcinoma (pT1A) with associated endometrial intraepithelial neoplasia. There is convincing evidence that the production of estrogen is located in the activated ovarian stroma. This supports the view that functioning stroma of ovarian cancer can lead to hyperestrogenism and eventually endometrial cancer. [ABSTRACT FROM AUTHOR]

Intestinal/enteric heterotopia of the vulva is an extremely rare disease with only 3 cases described in the literature. We report here an unusual case of this disease occurring in a 26-year-old patient in a context of Crohn's disease. To the best of our knowledge, such type of association has not been previously described. The potential origins of these lesions including metaplastic transformation, dysontogenetic changes, or epithelial colonic displacement/implantation are discussed. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary team (MDT) meetings aim to optimize patient management. We evaluated the impact of MDT discussions on the management and diagnosis of focal pancreatic lesions in a single tertiary center. Methods All patients with an initial diagnosis of solid or cystic pancreatic lesion discussed in our institution's MDT meeting on pancreatic diseases between January 1, 2020, and December 31, 2021, were included. The impact of MDT discussion on patient management, defined as a modification of the initially proposed therapeutic plan after MDT discussion, as well as the criteria leading to this modification, were the primary outcomes. Impact on diagnosis was the secondary outcome. Results: A total of 522 patients were included. Of these, 185 (35.4%) and 337 (64.6%) had an initial diagnosis of cystic or solid lesion, respectively. The most common referral query was regarding the management plan (349/522; 66.9%). Endoscopy was the procedure most often proposed before MDT discussion (109/522; 20.9%). Overall, the MDT discussion led to modification of the management plan in 377/522 patients (72.2%), with a statistically significant difference between cystic and solid lesions (63.2% vs. 77.2%; P<0.001). Management modifications were mainly driven by revision of cross-sectional radiological images. MDT discussion led to modification of the diagnosis in 92/522 patients (17.6%), with a significant difference regarding cystic lesions (35.7% vs. 7.7%; P<0.001). Conclusion: MDT discussion impacts the management of patients with cystic and solid pancreatic lesions, leading to a modification of the initially proposed management in two-thirds of them, mainly through revision of cross-sectional imaging. [ABSTRACT FROM AUTHOR]

Highlights • We propose a method to automate glandular epithelium segmentation. • Our approach combines Deep Learning and a new method of data augmentation. • Our algorithm efficiently processes H&E as well as IHC images. • Our algorithm achieves state-of-the-art performances. • Our method enables to automate the compartmentalisation of IHC biomarker analyses. Graphical abstract Abstract In this paper, we propose a method for automatically annotating slide images from colorectal tissue samples. Our objective is to segment glandular epithelium in histological images from tissue slides submitted to different staining techniques, including usual haematoxylin-eosin (H&E) as well as immunohistochemistry (IHC). The proposed method makes use of Deep Learning and is based on a new convolutional network architecture. Our method achieves better performances than the state of the art on the H&E images of the GlaS challenge contest, whereas it uses only the haematoxylin colour channel extracted by colour deconvolution from the RGB images in order to extend its applicability to IHC. The network only needs to be fine-tuned on a small number of additional examples to be accurate on a new IHC dataset. Our approach also includes a new method of data augmentation to achieve good generalisation when working with different experimental conditions and different IHC markers. We show that our methodology enables to automate the compartmentalisation of the IHC biomarker analysis, results concurring highly with manual annotations. [ABSTRACT FROM AUTHOR]

B Video 1 b Use of Texture and Color Enhancement Imaging (TXI) combined with near focus during the dissection step of saline-immersion colorectal endoscopic submucosal dissection offers pristine submucosal visibility: a case of a large traditional serrated adenoma. 4 Texture and Color Enhancement Imaging (TXI) mode during the submucosal dissection step of the procedure was associated with bright and clear visibility of the submucosal fibers and location of vessels as well as the muscular plane. [Extracted from the article]

The article presents a case study of a 50-year-old woman presented with previous contact with hepatitis B virus. The patient was diagnosed with typical characteristics of hepatocellular carcinoma at magnetic resonance imaging and contrast-enhanced computed tomography. The patient underwent segment 5 hepatectomy and histology showed a dense mononuclear infiltrate containing numerous plasma cells.

The article presents a case study of a 68-year-old male who presented to the hospital for follow-up of the resection of melanoma. It says that oncocytic lesion without any argument for melanoma metastasis was shown by the biopsy of the liver mass diagnosed in the patient. Moreover, biliary adenoma with oncocytic features was the final diagnosis to the patient.

Ectopic liver tissue represents a rare entity and is mostly attributed to events occurring during embryogenesis. Previous case reports documented the presence of fetal liver parenchyma within temporarily developed organs during pregnancy, such as the placenta or the umbilical cord. Moreover, the terminology of these benign findings varies from "ectopic liver" to "hepatocellular adenoma-like neoplasm" or "hepatocellular adenoma". Ancillary tests performed on these lesions have shown positive immunohistochemical staining for hepatocellular origin marker HepPar-1. Only one recent case report comprising molecular analysis showed no beta-catenin gain-of-function mutation. We report a case of ectopic liver in one placenta of a twin pregnancy, with an updated review of literature. [ABSTRACT FROM AUTHOR]

Peritoneal metastasis is life threatening and is the result of an extensive communication between disseminated cancer cells, mesothelial cells and cancer-associated fibroblasts (CAF). CAFs secrete extracellular matrix (ECM) proteins creating a receptive environment for peritoneal implantation. Considering cancer as an ecosystem may provide opportunities to exploit CAFs to create biomimetic traps to deceive and redirect cancer cells. We have designed microparticles (MP) containing a CAF-derived ECM-surface that is intended to compete with natural niches. CAFs were encapsulated in alginate/gelatine beads (500–750 μm in diameter) functionalised with a polyelectrolyte coating (MP[CAF]). The encapsulated CAFs remain viable and metabolically active (≥35 days), when permanently encapsulated. CAF-derived ECM proteins are retained by the non-biodegradable coating. Adhesion experiments mimicking the environment of the peritoneal cavity show the selective capture of floating cancer cells from different tumor origins by MP[CAF] compared to control MP. MP[CAF] are distributed throughout the abdominal cavity without attachment to intestinal organs and without signs of inflammatory reaction. Intraperitoneal delivery of MP[CAF] and sequential removal redirects cancer cell adhesion from the surgical wound to the MP[CAF], delays peritoneal metastasis formation and prolongs animal survival. Our experiments suggest the use of a biomimetic trap based on tumor–environment interactions to delay peritoneal metastasis. [ABSTRACT FROM AUTHOR]

Endoscopic evaluation 1 month after radiotherapy, administered with curative intent (40 Gy), suggested a non-responding lesion (Fig. Lesion delineation was obtained using narrow-band imaging (NBI) and texture and color enhancement imaging. 3 Endoscopic image showing subepithelial antral lesion 1 month after completion of radiotherapy (20 × 2 Gy). [Extracted from the article]

Objectives: To evaluate the efficacy and safety of a 10‐day quadruple therapy containing colloidal bismuth sub‐citrate (CBS), esomeprazole (ESO), amoxicillin (AMO), and metronidazole (MET) for Helicobacter pylori (H. pylori) eradication in children. Methods: Monocentric, open‐label, prospective, single‐arm clinical trial in children aged 6–17 years with H. pylori infection. The study was carried out on consecutive patients with upper gastrointestinal symptoms and H. pylori infection confirmed by histology and culture of gastric biopsies. The outcome was evaluated using a 13C‐urea breath test 8–10 weeks post‐therapy. Adverse events and compliance were evaluated by daily journal and pill counting. Results: A total of 36 children fulfilling the inclusion criteria were enrolled. Eight (22.2%) of them had a prior H. pylori eradication treatment. Thirteen (36.1%) patients were infected by a strain resistant to MET and 8 (22.2%) by a strain resistant to both MET and Clarithromycin (CLA). In the intention‐to‐treat population (ITT), eradication was achieved in35/36patients (95%CI: 85%−99%). Twenty‐three children reported at least one adverse event (63.8%), mostly mild (nausea, vomiting, abdominal pain, diarrhea, dark stool, metallic taste, headache, and rash). The compliance rate was high, with 30 (83.3%) patients taking >90% of the treatment. Conclusion: 10‐day quadruple therapy containing CBS, ESO, AMO, and MET for H. pylori eradication in children is a safe and very effective solution, especially for previously treated patients and those infected with double resistant strains. [ABSTRACT FROM AUTHOR]

Patients with alcoholic hepatitis and a modified Maddrey's discriminant function (mDF) <32 have a low risk of short-term mortality. However, few data exist concerning long-term outcomes. The aims of this study were to evaluate 5-year survival rates and to identify predictive factors for long-term prognosis in this patient population. We studied patients from 2 centers who were admitted for hepatic decompensation (ascites, hepatic encephalopathy, or jaundice) and who had histological findings of steatohepatitis and an mDF <32. Clinical and biological parameters were recorded at the time of liver biopsy and alcohol consumption was recorded during follow-up. We performed Cox proportional hazard survival analysis to identify factors associated with 5-year survival. One hundred and twenty-one patients were included (male: 64%, mean age: 51.5 ± 10.3 years, presence of cirrhosis: 84%). The median model for end-stage liver disease and mDF scores were 14 (IQR 11.7–16.1) and 19 (IQR 11.1–24), respectively. During follow-up, 30% of the patients remained abstinent. Survival rates at 1, 6, 12, 24, and 60 months were 96.7 ± 1.6%, 90.1 ± 2.7%, 80.8 ± 3.6%, 69.9 ± 4.3%, and 50.7 ± 4.9%, respectively. The majority of deaths (80%) were liver related. In multivariable analysis, encephalopathy at baseline and alcohol abstinence were predictive of 5-year survival. The 5-year survival rates of patients without and with encephalopathy at baseline were 60.5 ± 5.8% and 29.7 ± 8.0%, respectively, and the 5-year survival rates of abstinent and non-abstinent patients were 74.0 ± 8.0% and 40.9 ± 5.8%, respectively. The mortality rate of patients with alcoholic hepatitis and an mDF <32 is around 50% at 5 years. Hepatic encephalopathy at baseline and lack of alcohol abstinence impair long-term prognosis. New treatment strategies, including measures to ensure abstinence, are required. Patients with alcoholic hepatitis that is of intermediate severity have a low risk of short-term mortality but not much is known regarding long-term outcomes for these patients. This study clearly indicates that patients with intermediate disease characteristics have poor long-term outcomes. The presence of hepatic encephalopathy at the time of diagnosis and the absence of alcohol abstinence during follow-up are factors that predict poor long-term mortality. • Patients with non-severe alcoholic hepatitis have a low risk of short-term mortality. • The 5-year mortality of decompensated patients with alcoholic steatohepatitis and an mDF <32 is about 50%. • Hepatic encephalopathy and lack of alcohol abstinence impair long-term prognosis. [ABSTRACT FROM AUTHOR]

Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to D-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression. [ABSTRACT FROM AUTHOR]

Keywords: papillary immature squamous metaplasia; anal canal EN papillary immature squamous metaplasia anal canal 886 887 2 10/18/21 20211101 NES 211101 Case summary A 63-year-old man presented with a condylomatous hemicirconferential exophytic lesion of the anal canal. Cervical dysplasia is another precancerous lesion mediated by HPV (nearly 100%), and also involves the maturation of a squamous mucosa. Papillary immature metaplasia of the anal canal: a low-grade lesion that can mimic a high-grade lesion. [Extracted from the article]

Background & Aims: Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD. Methods: Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D. Results: Severe deficiency in 25(OH)D (<10ng/ml) was significantly associated with higher aspartate aminotransferase levels (p =1.00×10−3), increased hepatic venous pressure gradient (p =5.80×10−6), MELD (p =2.50×10−4), and Child-Pugh scores (p =8.50×10−7). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18–3.84, p =0.013) and mortality (HR=4.33, 95% CI=1.47–12.78, p =7.94×10−3) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p =3.00×10−3), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p =0.04). Conclusions: Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD. [ABSTRACT FROM AUTHOR]

Background & Aims: A recent genome-wide association study identified genetic polymorphism (rs738409 C>G) in the PNPLA3/adiponutrin gene associated with liver steatosis. This variant has also been linked to increased risk of alcoholic liver disease (ALD) and cirrhosis in Mestizo Mexicans with excessive alcohol intake. Our aim was to study the influence of this polymorphism on European Caucasian patients with histologically suggestive ALD. Methods: Three-hundred-and-twenty-eight healthy controls and 330 ALD patients, among whom 265 had cirrhosis, were genotyped for the rs738409 polymorphism. We studied the impact of rs738409 on clinical and biological parameters, together with histological staging of steatosis and fibrosis. PNPLA3 messenger RNA (mRNA) levels were measured by quantitative real-time PCR according to the patient’s phenotype. Results: The G-allele was significantly more frequent in ALD patients than in controls (odds ratio [OR]=1.54, 95% confidence interval [CI]=1.12–2.11 p =0.008) and was, among ALD patients, significantly associated with steatosis (p =0.048), fibrosis (p =0.001), and greater risk of cirrhosis (p =0.001). In multivariate analysis, rs738409 remained the strongest independent factor associated with risk of cirrhosis (OR=2.08; 95% CI=1.15–3.77; p =0.02). Furthermore, the PNPLA3 mRNA liver expression level was significantly lower in patients with more advanced fibrosis (p =0.03) and negatively correlated with the hepatic venous pressure gradient (r =−0.41, p =0.006). Conclusions: In European Caucasians, the rs738409 variant is associated with increased risk of ALD, liver damage, and cirrhosis. Further prospective studies are required to confirm these results and to evaluate the potential of PNPLA3 as both a predictor and a therapeutic target in ALD. [Copyright &y& Elsevier]

Background & Aims: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test. Methods: Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0–F1 at baseline were included. Patients were classified as progressors if they showed an increase ⩾2 fibrosis stages at the second histological evaluation after a follow-up ⩾5years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex® 200TM and computer analysis. Results: In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p =0.050 in Brussels; p =0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p =0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (odds-ratio=2.23, 95%CI 1.21–4.11 p =0.01). Conclusions: Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC. [ABSTRACT FROM AUTHOR]

Although the overall survival rate of papillary or follicular thyroid cancers is good, anaplastic carcinomas and radio iodine refractory cancers remain a significant therapeutic challenge. Galectin-1 (Gal-1) is overexpressed in tumor cells and tumor-associated endothelial cells, and is broadly implicated in angiogenesis, cancer cell motility and invasion, and immune system escape. Our team has previously demonstrated a higher serum level of Gal-1 in patients with differentiated thyroid cancers versus healthy patients, and explored, by a knockdown strategy, the effect of Gal-1 silencing on cell proliferation and invasion in vitro, and on tumor and metastasis development in vivo. OTX008 is a calixarene derivative designed to bind the Gal-1 amphipathic β-sheet conformation and has previously demonstrated anti-proliferative and anti-invasive properties in several cancer cell lines including colon, breast, head and neck, and prostate cancer lines. In the current work, the impacts of OTX008 were evaluated in six thyroid cancer cell lines, and significant inhibitions of proliferation, migration, and invasion were observed in all lines expressing high Gal-1 levels. In addition, the signaling pathways affected by this drug were examined using RPPA (reverse phase protein array) and phosphoprotein expression assays, and opposite regulation of eNos, PYK2, and HSP27 by OTX008 was detected by comparing the two anaplastic lines 8505c and CAL 62. Finally, the sensitive 8505c line was xenografted in nude mice, and 3 weeks of OTX008 treatment (5 mg/kg/day) demonstrated a significant reduction in tumor and lung metastasize sizes without side effects. Overall, OXT008 showed significant anti-cancer effects both in vitro and in vivo in thyroid cancer lines expressing Gal-1, supporting further investigation of the molecular mechanisms of the drug and future clinical trials in patients with anaplastic thyroid cancer. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 9-year-old girl with progressive dysphagia, thoracic pain and weight loss. Topics discussed include biopsy of the oesophageal mass revealing fibrous tissue with numerous plasmocytes; Barium swallow confirmed the circumferential narrowing of the oesophagus; and treatment of Immunoglobulin (IgG4)-related disease with corticosteroids and immunomodulators.