Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Case report - Selective internal radiation therapy (SIRT) in a patient with hyperinsulinemic hypoglycemia due to a metastatic insulinoma with late onset of endocrine activity.

Insulinomas are the most common functioning pancreatic neuroendocrine tumors (NET), which can lead to hyperinsulinemic hypoglycemia. In advanced metastatic stages of the disease, the prognosis is poor. Patients with hormonally active insulinomas primarily present with features of neuroglycopenia. Transformation from a nonfunctional to a functional NET is rare. Here, we present a case of a 59-year-old male adult with a metastatic insulinoma and late onset of endocrine activity. Besides medical treatment with Diazoxide and small frequent feedings, continuous intravenous glucose application was eventually required to avoid hypoglycemia. Furthermore, we show that selective internal radiation therapy (SIRT) can be an effective therapeutic approach for symptom reduction in advanced metastatic disease.

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.

A Rare Case of Mixed Adenoneuroendocrine Carcinoma (MANEC) of the Gastroesophageal Junction with HER2/neu Overexpression and Distinct Orbital and Optic Nerve Toxicity after Intravenous Administration of Cisplatin.

BACKGROUND: Mixed adenoneuroendocrine carcinomas (MANECs) are rare malignancies with both neuroendocrine and non-neuroendocrine components. To date, the prognosis of gastroenteropancreatic MANECs remains dismal, and treatment options are mainly based on guidelines for the treatment of pure neuroendocrine carcinomas or small cell lung cancer. Established first-line therapy in the metastatic situation is cisplatin and etoposide. Platinum derivatives are known to cause a variety of side effects also involving the visual system. Severe orbital and optic nerve toxicities have been described mainly after intracarotid infusion of cisplatin. CASE REPORT: Herein we report a rare case of a 60-year-old male patient suffering from MANEC of the gastroesophageal junction with HER2/neu overexpression who developed severe orbital and ocular neurotoxicity (grade 3 according to CTCAE v4.03) after intravenous cisplatin. CONCLUSION: We discuss diagnostic approaches and differential diagnoses in this clinical situation. Before starting treatment with intravenous and topical steroids, it is crucial to rule out meningeal and cerebral spread as well as paraneoplastic and endocrine syndromes.

Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting.

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations.