To Örebro University

BACKGROUND/AIMS: Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL).

METHODS: Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis' validation.

RESULTS: We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p = 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n = 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08-1] vs 0.83[0.4-1], respectively; p = 0.929). Among patients with WD-ANEN impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group.

CONCLUSIONS: WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs <20 mm is challenged.

Background/aims: We assessed the levels of autophagy and mitophagy, that are linked to cancer development and drug resistance, in well differentiated pancreatic neuroendocrine neoplasms (PanNENs) and correlated them with clinico-pathological parameters.

Methods: Fluorescent immunostaining for the autophagy markers LC3 Beta and p62/or LAMP1 was performed on 22 PanNENs and 11 controls of normal pancreatic tissues and validated through Western blotting. Autophagy quantitative scoring was generated for LC3B-positive puncta and analysed in relation to clinico-pathological parameters. TOMM20/LC3B qualitative assessment of mitophagy levels was undertaken by fluorescent immunostaining. The presence of autophagy/mitophagy was validated by transmission electron microscopy.

Results: Autophagy levels (LC3B-positive puncta/cell) were discriminative for normal vs. NEN pancreatic tissue (p = 0.007). A significant association was observed between autophagy levels and tumour grade (Ki67 < 3% vs. Ki67 >= 3%; p = 0.021), but not functionality (p = 0.266) size (cut-off of 20 mm; p = 0.808), local invasion (p = 0.481), lymph node- (p = 0.849) and distant metastases (p = 0.699). Qualitative assessment of TOMM20/LC3B demonstrated strong mitophagy levels in PanNENs by fluorescent immunostaining as compared with normal tissue. Transmission electron microscopy revealed enhanced autophagy and mitophagy in PanNEN tissue. Response to molecular targeted therapies in metastatic cases (n = 4) did not reveal any patterns of association to autophagy levels.

Conclusions: Increased autophagy levels are present in primary tumours of patients with PanNENs and are partially attributed to upregulated mitophagy. Grade was the only clinico-pathological parameter associated with autophagy scores.

BACKGROUND: Riedel´s thyroiditis (RT) is a rare inflammatory disease of the thyroid gland, causing compression and fibrosis of adjacent tissues. Typically the goiter is hard and firm. Hoarseness, dyspnea, and dysphagia may be present.

METHODS: We retrospectively reviewed all patients known by us with RT in addition to all patients with appropriate ICD-10 codes evaluated at the Karolinska University Hospital 2003-2015. Clinical, biochemical, and histological data of patients with RT were recorded in detail. Histological preparations were re-examined when available.

RESULTS: RT was diagnosed in six patients. Five were females and the median age at first presentation was 50 years (25-81 years). Median follow-up time was 3.75 years (1-22 years). At diagnosis five had hypothyroidism. Four had extrathyroidal manifestations, and one of these had also distant fibrosis. One patient had a clear IgG4/IgG ratio over 40%. One patient was treated with tracheostomy, one with isthmectomy and one with total thyroidectomy. Four had been treated with glucocorticoids, four with tamoxifen, and two with both drugs. One had also been treated with mycophenolate mofetil combined with Rituximab. At the end of follow-up four was doing fine, one had recurrent episodes of inflammation and one had died of possible complications to RT.

CONCLUSION: It is important to recognize RT and give adequate treatment. Steroids are still the mainstay of therapy but other medications against fibrosclerosis can be considered. Wakefulness of other fibrosing manifestations is essential. Immunohistochemistry can show whether IgG-4 plasma cells are increased which could lead to fibrosis in other organs.

Purpose: Several observational studies have shown an association between vitamin D deficiency and non-skeletal major health issues including impaired cardiorespiratory fitness and adiposity. Only a few studies have examined the impact of vitamin D supplementation on these conditions and the results are ambiguous. The aim of this study was to examine the effect of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight/obese men with vitamin D deficiency.

Methods: This study was a prospective, placebo controlled, double blinded, randomized trial with a study period of 6 months. Forty overweight/obese men (BMI > 25 kg/m²) with vitamin D deficiency (25(OH)D ≤ 55 nmol/L) were randomized to receive either 2000 IU Cholecalciferol drops or the equivalent amount of drops of placebo. At baseline and follow up body composition and cardiorespiratory fitness were measured and blood samples were obtained. Body composition was measured using bioelectrical impedance analysis (BIA) and cardiorespiratory fitness using cardiopulmonary exercise test (CPET). The primary outcomes were changes in percentage body fat and in maximum oxygen uptake (VO_2max).

Results: No statistically significant difference between the placebo and the intervention group regarding changes in percentage body fat (p = 0.54) and VO_2max (p = 0.90) was observed. Moreover, there was no statistically significant difference between the groups concerning changes in BMI (p = 0.26), maximum load (p = 0.89) and oxygen uptake at anaerobic threshold (AT) (p = 0.14).

Conclusions: We conclude that treatment with 2000 IU/d vitamin D for 6 months does not impact body composition or maximum oxygen uptake in overweight/obese men with vitamin D deficiency.

Purpose: Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.

Methods: Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.

Results: Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.

Conclusion: Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.