Local triamcinolone injection and selective add-on oral steroids to prevent post-ESD esophageal stricture: retrospective analysis of a prospective protocol in a Western center.

Background and study aim Extensive esophageal ESDs without preventive measures are at high risk of stricture. Oral steroids and local injection of triamcinolone acetonide have proven to be effective for prevention of esophageal stricture. This study aimed to assess the efficacy of a systematic steroid administration protocol for stricture prevention. Patients and methods A retrospective review of all esophageal ESDs at H.U.B Erasme Hospital (Brussels) between 2016 and 2022 was conducted. Injection of triamcinolone was performed for mucosal defects between 50% and 90% circumference. We added oral corticosteroids for patients with resections of ≥90% circumference . The primary outcome was the incidence of symptomatic stenosis at 3 months. Secondary outcomes were the cumulative stricture rate assessed by endoscopy within 6 months of ESD. Potential risk factors of stricture were evaluated with univariate and multivariate analysis. Results A total of 111 patients underwent 130 esophageal ESDs. Fifty-nine patients received triamcinolone acetonide local injection and 8 patients received local and oral corticosteroids. The primary outcome demonstrated a stricture incidence of 8.4%. The cumulative stricture rate assessed by endoscopy within 6 months of ESD was 10.4%.A mucosal defect of ≥ 6 0 4 0 mm was associated with 15-fold increased risk of stricture. Degree of circumference was also identified as an independent prognostic factor of stricture. Conclusions Our protocol led to a low stricture rate even after extensive resection. As a single session treatment without systemic side effects, triamcinolone injection could provide benefits as a preventive method after large esophageal resection.

The impact of a multidisciplinary team approach on the management of focal pancreatic lesions: a single tertiary center experience.

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.

The current understanding of the immune landscape relative to radiotherapy across tumor types.

Radiotherapy is part of the standard of care treatment for a great majority of cancer patients. As a result of radiation, both tumor cells and the environment around them are affected directly by radiation, which mainly primes but also might limit the immune response. Multiple immune factors play a role in cancer progression and response to radiotherapy, including the immune tumor microenvironment and systemic immunity referred to as the immune landscape. A heterogeneous tumor microenvironment and the varying patient characteristics complicate the dynamic relationship between radiotherapy and this immune landscape. In this review, we will present the current overview of the immunological landscape in relation to radiotherapy in order to provide insight and encourage research to further improve cancer treatment. An investigation into the impact of radiation therapy on the immune landscape showed in several cancers a common pattern of immunological responses after radiation. Radiation leads to an upsurge in infiltrating T lymphocytes and the expression of programmed death ligand 1 (PD-L1) which can hint at a benefit for the patient when combined with immunotherapy. In spite of this, lymphopenia in the tumor microenvironment of 'cold' tumors or caused by radiation is considered to be an important obstacle to the patient's survival. In several cancers, a rise in the immunosuppressive populations is seen after radiation, mainly pro-tumoral M2 macrophages and myeloid-derived suppressor cells (MDSCs). As a final point, we will highlight how the radiation parameters themselves can influence the immune system and, therefore, be exploited to the advantage of the patient.

Mid-gut exploration: video-capsule endoscopy cannot always determine the insertion route of device-assisted enteroscopy.

Video 1Difficult choice between anterograde versus retrograde motorized spiral enteroscopy based on video-capsule endoscopy findings to target a lesion illustrated in a clinical case.

Ovarian Clear Cell Carcinoma with Functioning Stroma and Associated Endometrial Intraepithelial Neoplasia.

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.

Ectopic Fetal Liver Tissue in the Placenta of a Twin Pregnancy: A Case Report and Review of Literature.

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.

Clinical, histological and molecular profiling of different stages of alcohol-related liver disease.

OBJECTIVE: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. DESIGN: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. RESULTS: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. CONCLUSIONS: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

Endoscopic duodenal mucosal resurfacing for nonalcoholic steatohepatitis (NASH): a pilot study.

Background and study aims Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with limited treatment options. Duodenal mucosal resurfacing (DMR) has been associated with improvement in glycaemic parameters and liver function tests (LFTs) in type 2 diabetes. This study aimed to assess the effect of DMR in patients with NASH. Patients and methods This was a single-center, open-label pilot study. Patients with definite, biopsy-proven NASH (nonalcoholic fatty liver disease activity score [NAS] ≥ 4) underwent a single DMR procedure followed by a 2-week postprocedural diet, without lifestyle intervention. The primary outcome was either resolution of NASH with no worsening of fibrosis or improvement in fibrosis (≥ 1 stage) with no worsening of NASH at 12 months. Secondary outcomes were changes in key histological parameters of NASH, surrogate markers of fibrosis, LFTs, and metabolic factors at 12 months. Results From 2017 to 2019, 14 patients underwent successful DMR, of whom 11 were included in the analysis. After 12 months, no resolution of NASH was observed, while three patients (27 %) had marginal improvement in fibrosis with no worsening of NASH. Serious adverse events related to the procedure were reported in two patients out of 14 (14 %). Neither weight loss nor improvement in NAS score, or in the other secondary outcomes, were observed at 12 months. Conclusions In this small and heterogenous study population, we found that DMR, in the absence of lifestyle intervention, did not induce NASH resolution and marginally improved liver fibrosis at 12 months.

New Treatment Strategy Targeting Galectin-1 against Thyroid Cancer.

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 ß-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.

Efficacy and safety of bismuth-based quadruple therapy for Helicobacter pylori eradication in children.

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 13 C-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 in 35/36 patients (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.

Undifferentiated Pancreatic Carcinoma With Osteoclast-Like Giant Cells: What Do We Know So Far?

Undifferentiated carcinoma of the pancreas is an aggressive but rare tumor for which several other terms have been used to describe its histological appearance. In addition, as osteoclast-like giant cells may accompany undifferentiated carcinoma of the pancreas, the WHO Classification distinguishes undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) from plain undifferentiated carcinoma since there are a few histopathological and clinical differences. UC-OGC was initially thought to be associated with worse prognosis compared to invasive ductal pancreatic adenocarcinoma, since it is often unresectable at diagnosis and tends to recur rapidly even if completely resected. When true UC-OGGs are carefully dissected out from other anaplastic carcinomas, it becomes, however, clear that UC-OGCs do have more indolent behavior, especially the pure UC-OGCs. This mini-review summarizes the current knowledge on UC-OGC.

Myeloid tumor necrosis factor and heme oxygenase-1 regulate the progression of colorectal liver metastases during hepatic ischemia-reperfusion.

The liver ischemia-reperfusion (IR) injury that occurs consequently to hepatic resection performed in patients with metastases can lead to tumor relapse for not fully understood reasons. We assessed the effects of liver IR on tumor growth and the innate immune response in a mouse model of colorectal (CR) liver metastasis. Mice subjected to liver ischemia 2 days after intrasplenic injection of CR carcinoma cells displayed a higher metastatic load in the liver, correlating with Kupffer cells (KC) death through the activation of receptor-interating protein 3 kinase (RIPK3) and caspase-1 and a recruitment of monocytes. Interestingly, the immunoregulatory mediators, tumor necrosis factor-α (TNF-α) and heme oxygenase-1 (HO-1) were strongly upregulated in recruited monocytes and were also expressed in the surviving KC following IR. Using TNFflox/flox LysMcre/wt mice, we showed that TNF deficiency in macrophages and monocytes favors tumor progression after IR. The antitumor effect of myeloid cell-derived TNF involved direct tumor cell apoptosis and a reduced expression of immunosuppressive molecules such as transforming growth factor-ß, interleukin (IL)-10, inducible nitric oxyde synthase (iNOS), IL-33 and HO-1. Conversely, a monocyte/macrophage-specific deficiency in HO-1 (HO-1flox/flox LysMcre/wt ) or the blockade of HO-1 function led to the control of tumor progression post-liver IR. Importantly, host cell RIPK3 deficiency maintains the KC number upon IR, inhibits the IR-induced innate cell recruitment, increases the TNF level, decreases the HO-1 level and suppresses the tumor outgrowth. In conclusion, tumor recurrence in host undergoing liver IR is associated with the death of antitumoral KC and the recruitment of monocytes endowed with immunosuppressive properties. In both of which HO-1 inhibition would reinforce their antitumoral activity.

ACE2 Protein Landscape in the Head and Neck Region: The Conundrum of SARS-CoV-2 Infection.

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.

Vulval Intestinal/Enteric Heterotopia in a Patient with Crohn's Disease.

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.

Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey's discriminant function <32.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LAY SUMMARY: 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.

[Comparison of the mismatch repair deficiency of colorectal cancers between African and European cohorts]. / Comparaison du « deficit mismatch repair ¼ des cancers colorectaux entre des cohortes africaines et européennes.

INTRODUCTION: According to European and American series, up to 20% of colorectal cancers are characterised by instability at microsatellites sites. MMR deficient colorectal cancers are predominantly found in the right colon. Although an increasing rate of colorectal cancer has been observed in many low-income countries including in West-Africa, data on epidemiology and biology of colorectal cancer in native Africans from this region are scarce. MATERIALS AND METHODS: We aimed to study the incidence of MMR deficiency in Côte d'Ivoire and to compare the data with those from a tertiary center in Belgium. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 was performed on paraffin-embedded tissue samples from 83 colorectal cancers (46% males) operated in Abidjan and from 343 colorectal cancers (53% males) from Brussels. RESULTS: Colorectal cancer was occuring at a younger age in Côte d'Ivoire compared to Belgium (median age: 53 versus 66). MMR deficiency was detected in 11,7% of Belgian cases and in 13,3% of Ivorian cases. Whereas MMR deficient cancers in Brussels were mainly found in women (24/40 i.e. 60%), in Abidjan only 3/11 (27%) were female. Moreover, the predominant location of MMR deficient tumours was different between both series: in Brussels, mainly located in the right colon (24/40 i.e. 60%) whereas in Abidjan predominantly (10/11 i.e. 91%) in the left colon. In Brussels we observed in the majority of cases (67,5%) loss of expression of MLH1 and PMS2, in Abidjan loss of expression of MSH2 and MSH6 (54,5%). CONCLUSIONS: Our pilot study reveals differences in presentation of MMR deficient colorectal cancer between the two geographic regions suggesting differences in epidemiology and biology of colorectal cancer in native Africans.