Necrolytic migratory erythema: an important visual cutaneous clue of glucagonoma

Objective: Glucagonoma is an extremely rare neuroendocrine tumor that arises from pancreatic islet alpha cells. Although glucagonoma is usually accompanied by a variety of characteristic clinical symptoms, early diagnosis is still difficult due to the scarcity of the disease. Methods: In this study, we present the cumulative experiences, clinical characteristics and treatments of seven patients diagnosed with glucagonoma during the past 10 years at the First Affiliated Hospital of Xi’an Jiaotong University. Results: The seven patients in our cohort consisted of six females and one male with an average diagnosis age of 40.1 years (range 23-51). The average time from onset of symptoms to diagnosis of glucagonoma was 14 months (range 2-36 months). All the patients visited dermatology firstly for necrolytic migratory erythema (NME) 7/7 (100%), other presenting symptoms included: diabetes mellitus (DM) 4/7 (57%), stomatitis 2/7 (28%), weight loss 4/7 (57%), anemia 4/7 (57%), diarrhea 1/7 (14%), DVT1/7 (14%). Plasma glucagon levels were increased in all patients (range 216.92–3155 pg/mL), and declined after surgery. Imaging studies revealed that four of seven patients had liver metastasis. Six of seven patients received surgical resection, and all of them received somatostatin analogue therapy. Symptoms improved significantly in 6 out of 7 patients. Three of seven patients died of this disease by the time of follow-up. Conclusion: Our data suggest that if persistent NME is associated with DM and high glucagon levels, timely abdominal imaging should be performed to confirm glucagonoma. Once diagnosed, surgery and somatostatin analogues are effective for symptom relief and tumor control.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=−0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

NON SURGICAL TREATMENT OF CARCINOID LUNGS TUMORS

Typical carcinoid lungs tumors are neuroendocrine bronchopulmonary tumors with a low-grade malignancy, and an atypical carcinoid is an intermediate form of these tumors. Their systemic treatment is greatly influenced by therapeutic evidence derived from the more frequent gastroenteropancreatic neuroendocrine neoplasms. Currently, systemic therapies for lung carcinoids, aiming at controlling tumor growth include long acting somatostatin analogues (SSAs), peptide receptor radionuclide therapy, chemotherapy and molecular-targeted therapy.

Preparation of Long-acting Somatostatin and GnRH Analogues and their Applications in Tumor Therapy

Hormonal drugs are essential treatment options for some hormone-dependent or hormone-sensitive tumors. The common dosage forms of hormonal drugs have a short half-life. Hence, frequent administration is needed, which results in poor patient compliance. Nevertheless, using drug delivery technology, somatostatin analogues (SSAs) and gonadotropin-releasing hormone (GnRH) analogues are prepared into long-acting formulations that can significantly prolong the action time of these drugs, reducing medication frequency and increasing patient compliance. Such drugs are advantageous when treating acromegaly, gastroenteropancreatic neuroendocrine tumors (GEP-NETs), breast cancer, prostate cancer, and other diseases having a relatively long course. SSAs and GnRH analogues are two typical hormonal drugs, the long-acting formulations of which are essential in clinical practice. This review summarized the preparation methods and clinical application of long-acting formulations in cancer. Further, the action mechanism and new research of SSAs and GnRH analogues were discussed, and suggestions related to the development of long-acting SSAs and GnRH analogues were provided.

The effects of somatostatin analogues on liver volume and quality of life in polycystic liver disease: a meta-analysis of randomized controlled trials

A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was − 176 ml (95%CI, − 406, 54; p < 0.133). Heterogeneity was low (I2:0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.

Glycemic Status in Acromegaly Patients Receiving Depot Long-Acting Octreotide

Background: Acromegaly is an uncommon, chronic, debilitating condition characterized by hyperinsulinism, insulin resistance, diabetes and prediabetes. One possibility for managing acromegaly's questionable influence on glucose homeostasis is the somatostatin analogues. Aim: To analyze the frequency and risk factors for impaired glucose homeostasis in acromegaly patients treated with depot long-acting octreotide (octreotide LAR), as well as the relationship between risk and treatment duration. Methods: The study included 52 Iraqi adults with acromegaly receiving octreotide LAR. Demographic, anthropometric, and clinical data were collected, as well as the duration of Octreotide LAR administration. Growth hormone, IGF-1, and adenoma size were reported retrospectively from patient data. The glycemic state was assessed and classified as DM, prediabetes, or normal. Results: The prevalence of DM was 39% and prediabetes was 40%, with the exception of being male, which was substantially related with prediabetes. DM and octreotide LAR use had a non-significant correlation. However, octreotide use altered 13% of patients from normal glycemic to prediabetes, with no correlation to treatment duration. Other than hypertension and a family history of diabetes, no other variables were found to be significant. Conclusion: Acromegaly patients have abnormal glucose metabolism, which is associated with prediabetes owing to octreotide LAR medication. Hypertension and family history of diabetes are risk factors.

Molecular Imaging of Vulnerable Coronary Plaque with Radiolabeled Somatostatin Receptors (SSTR)

Atherosclerosis is responsible for the majority of heart attacks and is characterized by several modifications of the arterial wall including an inflammatory reaction. The silent course of atherosclerosis has made it necessary to develop predictors of disease complications before symptomatic lesions occur. Vulnerable to rupture atherosclerotic plaques are the target for molecular imaging. To this aim, different radiopharmaceuticals for PET/CT have emerged for the identification of high-risk plaques, with high specificity for the identification of the cellular components and pathophysiological status of plaques. By targeting specific receptors on activated macrophages in high-risk plaques, radiolabelled somatostatin analogues such as 68Ga-DOTA-TOC, TATE,0 or NOC have shown high relevance to detect vulnerable, atherosclerotic plaques. This PET radiopharmaceutical has been tested in several pre-clinical and clinical studies, as reviewed here, showing an important correlation with other risk factors.

Self-Administration of Long-Acting Somatostatin Analogues in NET Patients—Does It Affect the Clinical Outcome?

Background and Objectives: Long-acting somatostatin analogues (SSA) (octreotide LAR and lanreotide Autogel) are recommended as first line treatment of locally advanced or metastatic well-differentiated neuroendocrine tumors (NETs) with a good expression of somatostatin receptor (SSTR). Both of these SSAs are usually administered via injections repeated every 4 weeks. The purpose of the study was to compare the route of SSA administration (injection performed by professional medical staff and self-administration of the drug) with progression-free survival. Materials and methods: 88 patients in 2019 and 96 patients in 2020 with locally advanced or metastatic well-differentiated NETs were included in the study. All patients had a good expression of SSTR type 2 and had been treated for at least 3 months with a stable dose of long-acting somatostatin analogue every 4 weeks. All of them had received training on drug self-injections from professional NET nurses at the beginning of the COVID-19 epidemic. Results: The rate of NET progression in the study group in 2020 was higher than in 2019 29.1% vs. 18.1% (28 vs. 16 cases), p = 0.081. Conclusions: The method of administration of long-acting SSA injection performed by professional medical staff vs. self-injection of the drug may significantly affect the risk of NET progression. The unequivocal confirmation of such a relationship requires further observation.

Practical kidney dosimetry in peptide receptor radionuclide therapy using [177Lu]Lu-DOTATOC and [177Lu]Lu-DOTATATE with focus on uncertainty estimates

Background Kidney dosimetry after peptide receptor radionuclide therapy using 177Lu-labelled somatostatin analogues is a procedure with multiple steps. We present the SPECT/CT-based implementation at Aarhus University Hospital and evaluate the uncertainty of the various steps in order to estimate the total uncertainty and to identify the major sources of uncertainty. Absorbed dose data from 115 treatment fractions are reported. Results The total absorbed dose with uncertainty is presented for 59 treatments with [177Lu]Lu-DOTATOC and 56 treatments with [177Lu]Lu-DOTATATE. For [177Lu]Lu-DOTATOC the mean and median specific absorbed dose (dose per injected activity) is 0.37 Gy/GBq and 0.38 Gy/GBq, respectively, while for [177Lu]Lu-DOTATATE the median and mean are 0.47 Gy/GBq and 0.46 Gy/GBq, respectively. The uncertainty of the procedure is estimated to be about 13% for a single treatment fraction, where the absorbed dose calculation is based on three SPECT/CT scans 1, 4 and 7 days post-injection, while it increases to about 19% if only a single SPECT/CT scan is performed 1 day post-injection. Conclusions The specific absorbed dose values obtained with the described procedure are comparable to those from other treatment sites for both [177Lu]Lu-DOTATOC and [177Lu]Lu-DOTATATE, but towards the lower end of the range of reported values. The estimated uncertainty is also comparable to that from other reports and judged acceptable for clinical and research use, thus proving the kidney dosimetry procedure a useful tool. The greatest reduction in uncertainty can be obtained by improved activity determination, partial volume correction and additional SPECT/CT scans.