Vitamin B12 deficiency.

No international treatment standard for B12 deficiency exists. Current practice predominantly relies on more than 50 years old data. Consequently, this review investigates that we still recommend five injections with 1 mg B12 over 10 days followed by maintenance therapy with 1 mg oral B12 daily or injections, of which the interval is guided by symptom relief rather than normalization of biomarkers. Clinical studies are highly warranted and should include formulation and administration of B12. Subcutaneous self-injection may prove cost-effective and benefit an individualized treatment strategy.

Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study.

INTRODUCTION: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. METHOD: In this study, we report retrospective data on median overall survival (OS) and median progression-free survival (PFS) for all Danish patients treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate or 90Y-Dotatate over the past 15 years. One standard treatment of PRRT consisted of 4 consecutive cycles with 8-14-week intervals. RESULTS: We included 28 patients; 10 were diagnosed with pheochromocytoma and 18 with paraganglioma. Median age at first PRRT was 47 (IQR 15-76) years. The median follow-up time was 31 (IQR 17-37) months. Eight patients died during follow-up. Median OS was 72 months, and 5-year survival was 65% with no difference between pheochromocytoma and paraganglioma. Patients with germline mutations had better survival than patients without mutations (p = 0.041). Median PFS after the first cycle of PRRT was 30 months. For patients who previously received systemic treatment, the median PFS was 19 months, compared with 32 months for patients with no previous systemic treatment (p = 0.083). CONCLUSIONS: The median OS of around 6 years and median PFS of around 2.5 years found in this study are comparable to those reported in previous studies employing PRRT. Based on historical data, the efficacy of PRRT may be superior to 131I-MIBG therapy, and targeted therapy with sunitinib and PRRT might therefore be considered as first-line treatment in this patient group.

Case of primary low-grade neuroendocrine carcinoma of the skin.

A man presents a 4 mm skin tumour at his general practitioner. The tumour is removed on the suspicion of a dermatofibroma. Important differential diagnoses are sebaceous neoplasms, melanomas, Merkel cell carcinomas and large cell neuroendocrine carcinoma, and metastases of neuroendocrine neoplasms from the gut or lung. Immunohistochemical staining excluded sebaceous neoplasm, melanoma and Merkel cell carcinoma, however, was positive for multiple neuroendocrine markers. Relevant scans showed no signs of a primary tumour anywhere else. The final diagnosis was a primary low-grade neuroendocrine carcinoma of the skin. At 30 months follow-up, there was no sign of recurrence.

Thyroid Disease and Hepatocellular Carcinoma Survival: A Danish Nationwide Cohort Study.

Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide. Recent animal studies suggest that thyroid hormone treatment improves HCC prognosis. The aim of this study was to describe the association between thyroid disease and HCC prognosis in humans. Methods: We performed a nationwide cohort study including all persons with an HCC diagnosis from 2000 to 2018. Patients' age, sex, HCC treatment, and diagnoses of thyrotoxicosis, nontoxic goiter, and myxedema were obtained from Danish national healthcare registries. We used regression models to examine the association between thyroid disease and mortality hazard and restricted mean survival time after HCC diagnosis, adjusting for confounding by sex and age. Results: We included 4,812 patients with HCC and 107 patients with thyroid disease. Median follow-up time was 5 months (total 5,985 person-years). The adjusted mortality hazard ratio was 0.68 (95% CI: 0.47-0.96) for thyrotoxicosis and 0.60 (95% CI: 0.41-0.88) for nontoxic goiter. The restricted mean survival time during the 5 years following HCC diagnosis was 6.8 months (95% CI: 1.1-12.6) longer for HCC patients with thyrotoxicosis than for patients without thyroid disease, and it was 6.9 months (95% CI: 0.9-12.9) longer for HCC patients with nontoxic goiter than for patients without thyroid disease. Conclusions: In this large nationwide cohort study, thyrotoxicosis and nontoxic goiter were associated with prolonged HCC survival.

Cognitive impairment after liver transplantation: residual hepatic encephalopathy or posttransplant encephalopathy?

Liver transplantation (LT) represents the definitive treatment for end-stage liver disease. Cognitive impairment following LT is frequent, referred to as postliver transplant encephalopathy (PLTE). LT removes the underlying chronic liver disease, and until recently hepatic encephalopathy (HE) was assumed to be fully reversible after LT. However, increasing evidence indicates that some degree of cognitive impairment may be present after LT. To which extent PLTE reflects cognitive impairment caused by residual HE (RHE) or the combined effect of other factors affecting brain function before, during, and after LT is not clarified. None of the available psychometric and neurophysiological tests used for detecting HE is shown to be able to distinguish between etiologies. The available, mostly retrospective, clinical studies indicate a high prevalence of abnormal psychometric tests after LT, and not all seem to recover completely. The patients with earlier HE show the most marked improvements, suggesting that the clinical picture of the early PLTE, in fact, represents RHE. Other early post-LT etiologies for PLTE comprise cerebral ischemia, critical illness encephalopathy, and immunosuppressive therapy. Late-onset etiologies comprise diabetes and hypertension, among others. PLTE regardless of etiology is a worrying issue and needs more attention in the form of mechanistic research, development of diagnostic/discriminative tools, and standardized prospective clinical studies.

Update on the Therapeutic Management of Hepatic Encephalopathy.

PURPOSE OF REVIEW: Hepatic encephalopathy (HE) is a common and devastating complication to chronic liver disease. In this paper, we summarize the latest research and evidence of both conventional and up-coming treatments. RECENT FINDINGS: Meta-analyses report beneficial effects of lactulose, branched-chain amino acids, rifaximin, and to some degree L-ornithine L-aspartate on the manifestations of HE in patients with cirrhosis, and generally the numbers needed to treat are low. Recent studies on newer HE treatments including ornithine phenylacetate, spherical carbon, and fecal microbiota transplant also report potentially beneficial effects on HE manifestations. The conventional treatments benefit patients with HE. Newer treatments are under study and more research is needed for their validation.

Survival and Predictors of Death for Patients with Bronchopulmonary Carcinoid at a Danish Tertiary NET Centre.

BACKGROUND/AIM: Bronchopulmonary carcinoids comprise of typical carcioids (TC) and atypical carcinoids (AC). We present characteristics and associated mortality in patients with TC and AC followed-up at a Danish NET Centre between 2000-2014. PATIENTS AND METHODS: Data were obtained from medical records, computed tomographic scans, and pathology reports. Mortality was investigated by Kaplan-Meier survival analysis. RESULTS: We included 68 patients, 55 with TC (81%) and 13 with AC (19%). Median follow-up was 5.6 years (range=1.0-26.3). Fourteen patients died; 13 were smokers, and nine had a Ki67 index >2%. Metastatic disease, smoking and male gender were significantly associated with risk of dying within the first 5 years (log-rank, all p<0.05), while Ki67 index >2% showed a trend for being associated with risk of death (p=0.11). CONCLUSION: Survival is strongly associated with tumor type and current/previous smoking. Metastatic disease at diagnosis and male gender are predictors of death within 5 years.