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There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI‐NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI‐NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI‐NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra‐abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni‐ and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52–139.48) months in the PTR group and 52 (95% CI: 30.55–73.46) in the non‐PTR group (p = 0.024), but the non‐PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow‐up of 51 months (PTR group 10.9% and non‐PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C‐reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI‐NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non‐PTR approach regarding bowel complications. [ABSTRACT FROM AUTHOR]

Purpose It is assumed that primary hyperparathyroidism (pHPT) in Multiple Endocrine Neoplasia (MEN) and lithium-associated pHPT (LIHPT) are associated with multiple gland disease (MGD), persistence and recurrence. The studies purpose was to determine frequencies, clinical presentation and outcome of sporadic pHPT (spHPT), LIHPT and pHPT in MEN. Additional main outcome measures were the rates of MGD and persistence/recurrence. Methods Retrospective analysis of medical records of 682 patients with pHPT who had attended the University Hospital of Marburg between 01–01–2004 and 30–06–2013. All patients were sent a questionnaire asking about their history of lithium medication. Results Out of 682 patients, 557 underwent primary surgery (532 spHPT, 5 LIHPT, 20 MEN), 38 redo-surgery (31 spHPT, 7 MEN), 55 were in follow-up due to previous surgery (16 spHPT, 1 LIHPT, 38 MEN) and 37 were not operated (33 spHPT, 1 LIHPT, 3 MEN). Primary surgeries were successful in 97.4%, revealed singular adenomas in 92.4%, double adenomas in 2.9% and MGD in 3.4% of the cases. Rates of MGD in MEN1 (82.35%) were significantly higher than in spHPT (3.8%), while there was no significant difference between LIHPT (20%) and spHPT. Rates of persistence/recurrence did not significantly differ due to type of surgery (bilateral/unilateral) or type of HPT (spHPT/LIHPT/MEN). Conclusions History of lithium medication is rare among pHPT patients. While MGD is common in MEN1, rates of MGD, persistence or recurrence in LIHPT were not significantly higher than in spHPT. [ABSTRACT FROM AUTHOR]

Importance: Guidelines advocate subtotal parathyroidectomy (SPTX) or total parathyroidectomy with autotransplantation (TPTX) with bilateral cervical thymectomy for primary hyperparathyroidism (pHPT) associated with multiple endocrine neoplasia type 1 (MEN1). However, both procedures are associated with a significant risk of permanent hypoparathyroidism. Objective: The aim of the current study was to compare long‐term results of either single gland excision (SGE, 1‐2 glands), SPTX and TPTX for the treatment of MEN1‐associated pHPT. Design and setting: Data of genetically confirmed MEN1 patients who underwent surgery for pHPT between 1987 and 2017 were retrieved from a prospective database and were retrospectively analysed. Results: Eighty‐nine MEN1 patients underwent either TPTX (n = 38, 42.7%), SPTX (n = 23, 25.8%) or SGE (n = 28, 31.5%). The rate of disease persistence after initial surgery was 2.6%, 0% and 14.2% in the TPTX, SPTX and SGE groups, respectively. After median follow‐up of 112 (range 7‐411) months, the rate of recurrent pHPT was significantly higher in the SGE group (n = 19, 21.3%) compared with the TPTX (n = 4, 4.4%, P = .001) and the SPTX (n = 9, 10.1%, P = .03) groups. Analysis of the recurrence‐free time among the surgical groups revealed a significant difference (P = .036). The median time to recurrence was significantly shorter after SGE (101, range 3‐301 months) than after SPTX (139, range 28‐278 months, P = .018) and TPTX (204, range 75‐396 months, P = .049). Twelve (32%) patients who underwent TPTX developed permanent hypoparathyroidism compared with only 4 (17%, P = .06) in the SPTX and 0 in the SGE group (P = .001). Conclusion: Given the high rate of postoperative permanent hypoparathyroidism after TPTX and SPTX, SGE is a valid option for the treatment of MEN1‐associated pHPT. [ABSTRACT FROM AUTHOR]

Mucorales can cause cutaneous to deep-seated infections, mainly in the immunocompromised host, resulting in high mortality rates due to late and inefficient treatment. In this study, Galleria mellonella larvae were evaluated as a heterologous invertebrate host to study pathogenicity of clinically relevant mucormycetes (Rhizopus spp. Rhizomucor spp. Lichtheimia spp. Mucor spp.). All tested species were able to infect G. mellonella larvae. Virulence potential was species-specific and correlated to clinical relevance. Survival of infected larvae was dependent on (a) the species (growth speed and spore size), (b) the infection dose, (c) the incubation temperature, (d) oxidative stress tolerance, and (e) iron availability in the growth medium. Moreover, we exploited the G. mellonella system to determine antifungal efficacy of liposomal amphotericin B, posaconazole, isavuconazole, and nystatin-intralipid. Outcome of in vivo treatment was strongly dependent upon the drug applied and the species tested. Nystatin-intralipid exhibited best activity against Mucorales, followed by posaconazole, while limited efficacy was seen for liposomal amphotericin B and isavuconazole. Pharmacokinetic properties of the tested antifungals within this alternative host system partly explain the limited treatment efficacy. In conclusion, G. mellonella represents a useful invertebrate infection model for studying virulence of mucormycetes, while evaluation of treatment response was limited. [ABSTRACT FROM AUTHOR]