Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

Konservative versus chirurgische Therapie beim idiopathischen und sekundären Megakolon oder Megarektum im Erwachsenenalter - eine retrospektive multizentrische Kontrollstudie.

BACKGROUND: Idiopathic and secondary megacolon (MC) and megarectum (MR) in adults is associated with persistent bowel dilatation and reduced intestinal motility. Little is known about the optimal treatment of this rare disease. Therefore, we retrospectively analysed long-term data from these patients in 5 community and university hospitals, focusing on conservative versus surgical treatment. METHODS: Patient records from 7/2004 to 9/2021 were screened for colorectal diseases with severe constipation and persistent megacolon ≥ 9.0 cm and/or megarectum ≥ 6.5 cm. Follow up-data was collected through telephone interviews and written surveys. ClinicalTrialsgov NCT04340856. RESULTS: Sixty-seven patients with idiopathic (n=10) and secondary (n=57) MC or MR were identified with only 20 of 67 patients (29.9%) correctly diagnosed. Mean/median age was 64/69 (range 18-93) years. Thirty-two patients were treated with laxative regimens, and 35 underwent surgery (colostomy: n=12, segmental resection, or hemicolectomy: n=10, (sub)total colectomy: n= 13) after conservative treatment attempts in 32/35 (91.4%). The mean/median follow-up was 4.2/2.7 (range 0.1-17.0) years. The readmission rate for MC-associated symptoms was significantly higher after conservative treatment than after surgical therapy at 12 (0.84 vs. 0.36 per patient, p=0.036), 24 (1.00 vs. 0.52, p=0.048) and 36 (1.13 vs. 0.58, p=0.047) months, as was the number of patients with persistent laxative dependence (28/32 (87.5%) vs. 19/33 (57.6%); p = 0.007). Therapy-associated adverse events (Clavien-Dindo classification) were documented more often in surgically treated patients (11/35, 31.4%) (p=0.025). CONCLUSION: Surgical treatment may be considered earlier if idiopathic or secondary MC or MR is correctly diagnosed, and conservative treatment has been attempted.

Impact of concomitant cardiovascular medications on overall survival in patients with liver cirrhosis.

OBJECTIVES OF THE ARTICLE: Liver cirrhosis is the end-stage liver disease associated with poor prognosis and cardiovascular comorbidity could significantly impact mortality of cirrhotic patients. We conducted a large, retrospective study to investigate the survival impact of cardiovascular co-medications in patients with liver cirrhosis. MATERIALS AND METHODS: A study-specific R package was processed on the local databases of partner institutions within the Observational Health Data Sciences and Informatics consortium, namely Columbia University, New York City (NYC), USA and Ajou University School of Medicine (AUSOM), South Korea. Patients with cirrhosis diagnosed between 2000 and 2020 were included. Final analysis of the anonymous survival data was performed at Medical Faculty Mannheim, Heidelberg University. RESULTS: We investigated a total of 32,366 patients with liver cirrhosis. Our data showed that administration of antiarrhythmics amiodarone or digoxin presented as a negative prognostic indicator (p = 0.000 in both cohorts). Improved survival was associated with angiotensin-converting enzyme inhibitor ramipril (p = 0.005 in NYC cohort, p = 0.075 in AUSOM cohort) and angiotensin II receptor blocker losartan (p = 0.000 in NYC cohort, p = 0.005 in AUSOM cohort). Non-selective beta blocker carvedilol was associated with a survival advantage in the NYC (p = 0.000) cohort but not in the AUSOM cohort (p = 0.142). Patients who took platelet inhibitor clopidogrel had a prolonged overall survival compared to those without (p = 0.000 in NYC cohort, p = 0.003 in AUSOM cohort). CONCLUSION: Concomitant cardiovascular medications are associated with distinct survival difference in cirrhotic patients. Multidisciplinary management is needed for a judicious choice of proper cardiovascular co-medications in cirrhotic patients.

Depression and fatigue in active IBD from a microbiome perspective-a Bayesian approach to faecal metagenomics.

BACKGROUND: Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease, potentially due to inflammation-mediated changes in the microbiota-gut-brain axis. The aim of this study was to investigate the associations between structural and functional microbiota characteristics and severity of fatigue and depressive symptoms in patients with active IBD. METHODS: We included clinical data of 62 prospectively enrolled patients with IBD in an active disease state. Patients supplied stool samples and completed the questionnaires regarding depression and fatigue symptoms. Based on taxonomic and functional metagenomic profiles of faecal gut microbiota, we used Bayesian statistics to investigate the associative networks and triangle motifs between bacterial genera, functional modules and symptom severity of self-reported fatigue and depression. RESULTS: Associations with moderate to strong evidence were found for 3 genera (Odoribacter, Anaerotruncus and Alistipes) and 3 functional modules (pectin, glycosaminoglycan and central carbohydrate metabolism) with regard to depression and for 4 genera (Intestinimonas, Anaerotruncus, Eubacterium and Clostridiales g.i.s) and 2 functional modules implicating amino acid and central carbohydrate metabolism with regard to fatigue. CONCLUSIONS: This study provides the first evidence of association triplets between microbiota composition, function and extraintestinal symptoms in active IBD. Depression and fatigue were associated with lower abundances of short-chain fatty acid producers and distinct pathways implicating glycan, carbohydrate and amino acid metabolism. Our results suggest that microbiota-directed therapeutic approaches may reduce fatigue and depression in IBD and should be investigated in future research.

[Budd-Chiari syndrome, review and illustration]. / Budd-Chiari Syndrom, Review und Illustration der Bildgebung.

Budd-Chiari syndrome is a rare vascular disorder characterized by obstruction of the hepatic venous outflow. Various diseases causing coagulopathy play a role in aetiology, such as myeloproliferative disorders. Acute vascular occlusion may lead to acute phlebitis with fever. The classic triad of acute liver failure may be present with ascites, hepatomegaly, and abdominal pain. However, subacute courses of disease were also observed. Because of the variable symptoms and severity extent, depending on the acuity of the course and the extent of the affected vessels, diagnosis is often difficult. Sonography, as a ubiquitously available and cost-effective diagnostic tool, plays a leading role. Doppler ultrasonography can be used to visualize hemodynamics in particular. In acute thrombotic occlusion, the affected hepatic veins usually cannot or only partially be visualized. In non-occluding thrombi, turbulent flow patterns may develop in the area of venous outflow obstruction, and flow velocity is then increased in the area of stenosis. Contrast enhanced ultrasound offers even better specificity of diagnosis. Computed tomography and magnetic resonance imaging can directly visualize thrombi and the cause of obstruction. Once the diagnosis is confirmed, anticoagulation must be initiated, but therapy of the underlying disease must also be started. If symptom-controlling measures are not sufficient, angioplasty/stenting to reopen short-segment stenoses or implantation of a TIPSS device may be considered. Liver transplantation remains ultima ratio. As studies on the precision of diagnostic methods are controversial, the characteristics of imaging for BCS are therefore summarized in this review on the basis of several illustrating case reports.

Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. Paired related homeobox 1 (PRRX1) is a transcription factor that regulates cell growth and differentiation, but its importance in HCC is unclear. METHODS: We examined the expression pattern of PRRX1 in nine microarray datasets of human HCC tumour samples (n > 1100) and analyzed its function in HCC cell lines. In addition, we performed gene set enrichment, Kaplan-Meier overall survival analysis, metabolomics and functional assays. RESULTS: PRRX1 is frequently upregulated in human HCC. Pathway enrichment analysis predicted a direct correlation between PRRX1 and focal adhesion and epithelial-mesenchymal transition. High expression of PRRX1 and low ZEB1 or high ZEB2 significantly predicted better overall survival in HCC patients. In contrast, metabolic processes correlated inversely and transcriptional analyses revealed that glycolysis, TCA cycle and amino acid metabolism were affected. These findings were confirmed by metabolomics analysis. At the phenotypic level, PRRX1 knockdown accelerated proliferation and clonogenicity in HCC cell lines. CONCLUSIONS: Our results suggest that PRRX1 controls metabolism, has a tumour suppressive role, and may function in cooperation with ZEB1/2. These findings have functional relevance in HCC, including in understanding transcriptional control of distinct cancer hallmarks.

Co-Medication and Nutrition in Hepatocellular Carcinoma: Potentially Preventative Strategies in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, with about 841,000 new cases and 782,000 deaths annually. Given the clearly defined population at risk, mostly patients with liver cirrhosis, prevention of HCC could be highly effective. SUMMARY: Besides regular ultrasound surveillance, numerous publications have suggested protective effects of diverse drugs and nutrients. However, none of those preventive options has made it into clinical routine or practice guidelines. We therefore summarize the current status of preventive effects of drugs such as statins, acetylsalicylic acid (ASA), and metformin, but also dietary aspects and nutrients such as coffee, tea, and vitamin D supplementation. A successful implementation of some of these strategies may potentially lead to improved prevention of HCC development in patients with liver cirrhosis. Key Messages: Accumulating data suggest that particularly ASA, antidiabetic therapies, and statins may substantially decrease HCC incidence in patients at risk.

[Prevention of gastrointestinal cancer]. / Prävention gastrointestinaler Tumore.

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.

[Current standard of antibiotic prophylaxis in esophageal varices bleeding in Germany]. / Aktueller Stand der Antibiotikaprophylaxe bei Ösophagusvarizenblutungen in Deutschland.

OBJECTIVES: Antibiotic prophylaxis in patients with liver cirrhosis and upper gastrointestinal bleeding significantly reduces the risk of concomitant bacterial infections and early mortality. The goal of our study was to determine the current status of antibiotic prophylaxis in departments of gastroenterology in Germany. METHODS: Representatives of gastroenterology departments were asked to provide data about indication for, and duration of, antibiotic prophylaxis and choice of antibiotic in esophageal varices bleeding in patients with liver cirrhosis. RESULTS: 326 of 779 contacted departments of gastroenterology participated in the study. Whereas antibiotic prophylaxis is used in 98.5 % (n = 321/326) of cases, it is used only in 7.1 % (n = 23/322) depending on the Child-Pugh-Score. In 19.4 % (n = 62/320), a prophylaxis is given even to patients with an elective banding of esophageal varices without bleeding. Third generation cephalosporins are used most frequently (66.5 %; n = 248/373) followed by fluoroquinolones (19.9 %; n = 74/373). The duration of prophylaxis was 3 days in most cases (32.3 %; n = 104/322), 1 day in 9.3 % (n = 30/322) and 7 days as recommended by German treatment guidelines in 24.8 % (n = 80/322). A standard of procedure (SOP) for antibiotic prophylaxis in esophageal varices bleeding is available in 45.1 % (n = 147/326). CONCLUSION: Our study shows that the applied standards for antibiotic prophylaxis in esophageal varices bleeding varies greatly in Germany. Future studies about the necessary duration of prophylaxis and its dependency from the Child-Pugh-Score are needed so that unnecessary antibiotic prescriptions can be avoided. The avoidance of antibiotic prophylaxis in elective banding of non-bleeding esophageal varices, which is not recommended by guidelines and was used by about 20 % of participants in our study, can already reduce antibiotic use.

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn's disease - a regional multi-center pilot study.

BACKGROUND AND AIM: The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16. METHODS: Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration. RESULTS: Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001). CONCLUSION: Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.