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Hypertrophic osteoarthropathy (HOA: MIM 167100)) is classified into primary and secondary types. Primary HOA, also known as pachydermoperiostosis (PDP), is a rare genetic condition with distinct clinical features including digital clubbing, skin thickening, and periostosis. Secondary HOA often occurs as a paraneoplastic syndrome or is associated with systemic diseases. In this report, we present a 17-year-old male patient who initially presented with significant digital clubbing, enlarged hands and feet, and excessive sweating. Although the initial suspected diagnosis was acromegaly, the patient's plasma level of insulin-like growth factor 1 was normal and growth hormone levels suppressed to <1 ng/dL following oral glucose tolerance test. Whole exome sequencing followed by Sanger sequencing of leukocyte deoxyribonucleic acid revealed a novel splicing variant in the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene (NM_000860.6: c.662 + 5_662 + 8del). Reverse transcription polymerase chain reaction confirmed that this variant led to defective splicing with skipping of exon 6, a frameshift, and truncation at codon 13 of exon 7 downstream. His symptoms did not respond well to nonsteroidal anti-inflammatory drugs but showed excellent response to a trial of lanreotide autogel that has been used for about 1 year. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, numerous treatment options have emerged for patients with locally advanced and metastatic neuroendocrine tumours (NETs). Nevertheless, the optimal timing of treatment interventions remains uncertain, given the highly variable disease course observed in these patients, even when patients have the same tumour stage and grade. The aim of the study was to evaluate the predictive role of standardized uptake values (SUVs) and volumetric parameters obtained from pretreatment [68Ga]Ga-DOTA-TATE for response to SSA therapy in patients with NET. In this retrospective study, we included 42 patients (21 women, 21 men; age range: 46–84 years) with histologically confirmed, metastatic, NET (G1 13, G2 28 cases); median Ki-67 index 5%, range 1–16) who received long acting SSA as a first line treatment and underwent [68Ga]Ga-DOTA-TATE PET/CT before SSA treatment. For all [68Ga]Ga-DOTA-TATE avid lesion SUVmax, SUVmean, somatostatin receptor expression tumour volume (STV), total lesion somatostatin receptor expression (TLD, STV multiplied by SUV mean) and Tmean/Smean (SUVmean of tumours/metastases divided by SUVmean of normal spleen) were measured. Finally, the sum of STV (total STV, TSTV) and TLD (total TLD, TTLD) was calculated for each patient and used in the analysis. Results: During the study period, 14 patients had stable disease (33.3%) and 28 patients experienced progression (66.7%), among whom 12 patients died. The median progression-free survival (PFS) and overall survival (OS) were 26.5 and 46.5 months, respectively. In the univariate and multivariate analysis, in the whole population study, Tmean/Smean ratio (HR 1.88, 95% CI 1.06–3.35, p = 0.03), Ki-67 index (HR 1.14, CI 1.03–1.26, p = 0.01) and pre-treatment chromogranin A serum concentration (HR 1.01, CI 1.0–1.03, p = 0.01) were significantly associated with PFS. Among patients with small intestinal NETs, TSTV (< 125.85 cm3 vs. ≥ 125.85 cm3, p = 0.023) and TTLD (< 4168.95 vs. ≥ 4168.95, p = 0.026) were significantly associated with PFS in the univariate analyses. No significant correlation was found between measured volumetric parameters and OS. Conclusion: Volumetric parameters of pretreatment 68[Ga]Ga-DOTA-TATE PET/CT may be useful in prediction of the response to SSA (used in monotherapy as a first-line therapy) in patients with NET. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients. This article describes the experience and outcomes of managing pregnant women with NEN at a European Neuroendocrine Tumour Society (ENETS) Centre of Excellence. In this retrospective analysis, we evaluated a total of 22 pregnancies in 18 pregnant women with concurrent diagnoses of NENs who were managed at Royal Free Hospital ENETS Centre of Excellence throughout their pregnancy. These were identified from our tumour registry of 3500 NEN patients between 2015 and 2023. Cross‐sectional imaging (computed tomography (CT)/magnetic resonance imaging (MRI)), pre‐ and post‐pregnancy, for each patient was reviewed by an experienced radiologist. Tumour growth rate (TGR) was calculated using the formula: TGR = 100 × [exp (TG) − 1]; TG. [3 × log (D2/D1)]/time (months), where D1 is the tumour size at date 1; D2 is the tumour size at date 2; and time (months) = (Date 2 − Date 1 + 1)/30.44. Tumour growth rate pre‐conception (TGRpc) and tumour growth rate post‐partum (TGRpp) were calculated for each patient. In a sub‐group of patients, positivity for oestrogen and progesterone receptors were analysed on the tumour tissue to evaluate whether the presence of these receptors affected tumour progression during the pregnancy. We also reviewed the pregnancy outcome in patients treated with somatostatin analogues during pregnancy. We analysed the data of a total 22 pregnancy encounters in 18 women: 15 pregnancies (68%) preceded the diagnosis of the NEN, whereas the diagnosis of NEN was made during pregnancy or in the post‐partum period in 5 (23%) and 2 (9%) pregnancies respectively. Eight patients (44%) had a diagnosis of a pancreatic NEN, whereas 5 (28%) were diagnosed with mid‐gut NENs, and a further 5 at other sites. The majority of the patients (n = 12, 67%) had evidence of metastatic disease at the time of diagnosis. Most pregnancies had a successful outcome (n = 19, 86%), whereas 3 patients (14%) had miscarriages in the 1st trimester. Five patients in total of 6 pregnancies were treated with somatostatin analogues as monotherapy during the pregnancy, and all of them had stable disease after pregnancy. All of them delivered healthy babies without any side effects or complications due to therapy. The average TGRpc was −0.8% (n = 5) and the average TGRpp was +0.96% (n = 6); 2 patients who did not have suitable targets for calculation of TGRpc developed new lesions suggesting disease progression. Moreover, 2 of the 4 patients who have had both pre‐conception and post‐pregnancy scans showed an increase in TGRpp compared to TGRpc. The management of NENs during pregnancy should be multidisciplinary with an individualised approach to each patient. Somatostatin analogues appear to be safe during pregnancy, though further robust studies are needed. Pregnancy per se may accelerate tumour progression, and patients should be counselled regarding this possibility. [ABSTRACT FROM AUTHOR]

Abstract Background Over the past decade, numerous treatment options have emerged for patients with locally advanced and metastatic neuroendocrine tumours (NETs). Nevertheless, the optimal timing of treatment interventions remains uncertain, given the highly variable disease course observed in these patients, even when patients have the same tumour stage and grade. The aim of the study was to evaluate the predictive role of standardized uptake values (SUVs) and volumetric parameters obtained from pretreatment [68Ga]Ga-DOTA-TATE for response to SSA therapy in patients with NET. In this retrospective study, we included 42 patients (21 women, 21 men; age range: 46–84 years) with histologically confirmed, metastatic, NET (G1 13, G2 28 cases); median Ki-67 index 5%, range 1–16) who received long acting SSA as a first line treatment and underwent [68Ga]Ga-DOTA-TATE PET/CT before SSA treatment. For all [68Ga]Ga-DOTA-TATE avid lesion SUVmax, SUVmean, somatostatin receptor expression tumour volume (STV), total lesion somatostatin receptor expression (TLD, STV multiplied by SUV mean) and Tmean/Smean (SUVmean of tumours/metastases divided by SUVmean of normal spleen) were measured. Finally, the sum of STV (total STV, TSTV) and TLD (total TLD, TTLD) was calculated for each patient and used in the analysis. Results During the study period, 14 patients had stable disease (33.3%) and 28 patients experienced progression (66.7%), among whom 12 patients died. The median progression-free survival (PFS) and overall survival (OS) were 26.5 and 46.5 months, respectively. In the univariate and multivariate analysis, in the whole population study, Tmean/Smean ratio (HR 1.88, 95% CI 1.06–3.35, p = 0.03), Ki-67 index (HR 1.14, CI 1.03–1.26, p = 0.01) and pre-treatment chromogranin A serum concentration (HR 1.01, CI 1.0–1.03, p = 0.01) were significantly associated with PFS. Among patients with small intestinal NETs, TSTV (

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Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5–16.5) compared with standard of care (21.2; 95% CI, 15.7–26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4–18.1; P =.012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3–1.5). Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. ClinicalTrials.gov , NCT02384122. [Display omitted] Octreotide treatment was compared with standard of care in an adequately powered randomized controlled trial, which established that octreotide significantly reduces transfusion requirements and endoscopic procedures in patients with angiodysplasia-related anemia. [ABSTRACT FROM AUTHOR]

Introduction: Somatostatin analogues (SSAs) are commonly used in the treatment of hormone hypersecretion in neuroendocrine tumors (NETs), however the extent to which they inhibit proliferation is much discussed. Objective: We studied the antiproliferative effects of novel SSA lanreotide in bronchopulmonary NETs (BP-NETs). We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide. Methods: BP-NET cell lines NCI-H720 and NCI-H727 were treated with PI3K inhibitor BYL719 (alpelisib), mTOR inhibitor everolimus and SSA lanreotide to determine the effect on NET differentiation markers, cell survival, proliferation and alterations in cancer-associated pathways. NT-3 cells, previously reported to express somatostatin receptors (SSTRs) natively, were used as control for SSTR expression. Results: SSTR2 was upregulated in NCI-H720 and NT-3 cells upon treatment with BYL719. Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner. Production of proteins activating cell death mechanisms was also induced. Notably, a multiplexed gene expression analysis performed on NCI-H720 revealed that BYL719 plus lanreotide had a stronger effect on the downregulation of mitogens than lanreotide alone. Discussion/Conclusion: We report a widespread analysis of changes in BP-NET cell lines at the genetic/protein expression level in response to combination of lanreotide with pretreatment consisting of BYL719 and everolimus. Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in highgrade tumors. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment. Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.

Gwen MC Masclee,1 Ad AM Masclee2,3 1Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, the Netherlands; 2Department of Gastroenterology and Hepatology, Maastricht University Medical Center +, Maastricht, the Netherlands; 3NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the NetherlandsCorrespondence: Gwen MC Masclee, Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, the Netherlands, Tel +3120 4440613, Email g.m.c.masclee@amsterdamumc.nlAbstract: Dumping syndrome is a common complication after esophageal, gastric and bariatric surgery and has a significant negative impact on the quality of life of patients. This narrative review describes the clinical syndrome, pathophysiology, diagnosis and reports on standard and pragmatic therapeutical treatment options in order to improve the clinical outcome of patients with dumping syndrome. Dumping syndrome consists of early and late dumping symptoms and can be diagnosed using clinical parameters with the help of the Sigstad’s score, questionnaires or by provocative testing. The prevalence of dumping syndrome varies depending on the employed definition of dumping syndrome. Overall, dumping syndrome is more frequent nowadays due to increasing numbers of upper gastrointestinal and bariatric surgeries being performed. First treatment step includes dietary adjustment and dietary supplements, which are often sufficient to manage symptoms for the majority of patients. Next step of therapy includes acarbose, which is effective for late dumping symptoms, but the use is limited due to side effects. Somatostatin analogues are indicated after these two steps have failed. Somatostatin analogues are very effective for controlling early and late dumping, also in the long term. Glucagon like peptide-1 receptor agonists, endoscopic and surgical (re)interventions are reported as treatment options for refractory dumping syndrome; however, their use is not recommended in clinical practice due to the limited evidence on and uncertainty of outcomes. These alternatives should be considered only as last resort options in patients with otherwise refractory and invalidating dumping syndrome.Keywords: dumping syndrome, early and late dumping, somatostatin analogues, octreotide, bariatric surgery, upper gastrointestinal surgery

(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.

Introduction: Somatostatin analogues (SSAs) are commonly used in the treatment of hormone hypersecretion in neuroendocrine tumors (NETs), however the extent to which they inhibit proliferation is much discussed.Objective: We studied the antiproliferative effects of novel SSA lanreotide in bronchopulmonary NETs (BP-NETs). We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide.Methods: BP-NET cell lines NCI-H720 and NCI-H727 were treated with PI3K inhibitor BYL719 (alpelisib), mTOR inhibitor everolimus and SSA lanreotide to determine the effect on NET differentiation markers, cell survival, proliferation and alterations in cancer-associated pathways. NT-3 cells, previously reported to express somatostatin receptors (SSTRs) natively, were used as control for SSTR expression.Results: SSTR2 was upregulated in NCI-H720 and NT-3 cells upon treatment with BYL719. Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner. Production of proteins activating cell death mechanisms was also induced. Notably, a multiplexed gene expression analysis performed on NCI-H720 revealed that BYL719 plus lanreotide had a stronger effect on the downregulation of mitogens than lanreotide alone.Discussion/Conclusion: We report a widespread analysis of changes in BP-NET cell lines at the genetic/protein expression level in response to combination of lanreotide with pretreatment consisting of BYL719 and everolimus. Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in high-grade tumors.

Simple Summary: Clinically relevant postoperative pancreatic fistula (CR-POPF) continues to be the leading cause of morbidity and mortality after pancreatic surgery. Attempts to prevent the complication have recently expanded to involve non-surgical interventions to supplement surgical solutions and minimise the associated post-pancreatectomy acute pancreatitis. The following narrative review identified ten strategies reported in the literature, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, combination strategies, nutrition, and fluids. As the reported efficacy of these strategies varied, further higher-powered studies are needed to determine if any of the preventative approaches can be recommended for routine CR-POPF prophylaxis. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor. Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the solution to preventing CR-POPF may lie instead in non-surgical, mainly pharmacological interventions. Five databases were searched, identifying eight pharmacological preventative strategies, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, and combination strategies. Two further non-surgical interventions studied were nutrition and fluids. New potential interventions were also identified from related surgical and experimental contexts. Given the varied efficacy reported for these interventions, numerous opportunities for clarifying this heterogeneity remain. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor. [ABSTRACT FROM AUTHOR]

Thyrotroph adenoma is a rare clinical subtype of pituitary adenoma. This article reports a case of a patient presenting with thyrotoxic periodic paralysis (TPP) as the initial clinical manifestation. The examination revealed hypokalemia, significantly elevated thyroid hormone levels with unsuppressed thyroid stimulating hormone (TSH) levels, and MRI suggesting a pituitary adenoma. The diagnosis was confirmed as a thyrotroph adenoma. Preoperative preparation was conducted using a somatostatin analogue, octreotide, followed by neuroendoscopic surgery. The patient's thyroid function returned to normal levels after surgery, and there was no residual tumor or recurrence observed on MRI. [ABSTRACT FROM AUTHOR]

Acromegaly is a severe neuroendocrine disease characterized by hypersecretion of growth hormone (GH) caused in 95% of cases by pituitary adenoma, which leads to the development of pathology of various organs and systems. The severity of the condition is due not only to the direct effect of somatotropic hormone on the body and the effect of the adenoma on the surrounding structures, but also to the age of the patient and complications associated with the disease. Improvement in treatment methods allows for a personalized approach to patient management, taking into account various aspects of the clinical case. It is important for a specialist to take into account comorbidity in acromegaly, both in terms of pathological disorders and the impact on the patient’s psycho-emotional state. We present a clinical case of successful treatment with somatostatin analogues (ASS) in a patient who is afraid of surgery and has cardiovascular complications of acromegaly. Since the onset of acromegaly, confirmed by an elevated level of insulin-like growth factor-1 (IGF-1) and an endosellar pituitary macroadenoma measuring 11x9.5x8 mm, ASS therapy was initiated in the patient. The choice in favor of conservative treatment was due to a burdened cardiovascular history and the patient’s fear of surgery. Within three years from the start of drug therapy, there was a significant improvement in overall well-being, a tendency to reduce the size of the pituitary adenoma, and biochemical remission was achieved. The clinical case described by us confirms the possibility of successful primary treatment of ASS in a patient with acromegaly, taking into account all individual characteristics.

Simple Summary: Radioiodine therapy is the main treatment option for metastatic differentiated thyroid cancer (DTC). However, only half of these patients achieve (partial or complete) remission or have stable disease during long-term follow-up. In the remaining ones, disease progresses mainly as they become radioiodine-refractory. The diagnostics of radioiodine-refractory disease are extensively debated. The introduction of novel tracers besides radioiodine isotopes (131I, 123I, and 124I) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) opens new options for the diagnostics and therapy of this subgroup of DTC patients. Prostate-specific membrane antigen (PSMA) ligands, fibroblast activation protein inhibitors (FAPI), and somatostatin receptor-targeted radiopharmaceuticals appear to be new potential theranostics tracers. In this review, we will elaborate on the role of these radiopharmaceuticals in the management of radioiodine-refractory disease. Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [18F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC. [ABSTRACT FROM AUTHOR]

Background: An increased prevalence of depression has been reported in patients with acromegaly. However, most studies included a relatively small sample size owing to the rarity of acromegaly. We aimed to investigate the risk of depression in patients with acromegaly using the Korean National Health Information Database (NHID). Methods: The data of patients with acromegaly in 2006-2016 were collected from the rare incurable disease registry of the NHID. Patients with acromegaly were matched with control participants without acromegaly for age and sex in a 1:5 ratio. Results: Patients who did not receive treatment for acromegaly had a significantly increased risk of depression (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.12-1.82). However, the risk of depression did not increase in patients who received treatment for acromegaly. The multiple Cox regression analysis showed that the risk of depression was significantly higher in the untreated group than in the control group during the first 3 years of observation (HR: 1.829, 95% CI: 1.305-2.563). However, after a time lag of over 3 years, the risk of depression decreased in the untreated group, which is similar to that in the control group. Conclusion: Our nationwide study suggests that patients who did not receive treatment for acromegaly have a higher risk of depression compared with controls. The untreated acromegaly patients should be monitored for the development of depression, especially in the early years after diagnosis. These results could serve as a basis for developing screening strategies to mitigate depression in acromegaly patients. [ABSTRACT FROM AUTHOR]

(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years. [ABSTRACT FROM AUTHOR]

Abstract Pituitary neuroendocrine tumours (PitNETs) are neoplasms of the pituitary that overproduce hormones or cause unspecific symptoms due to mass effect. Growth hormone overproducing GH-producing PitNETs cause acromegaly leading to connective tissue, metabolic or oncologic disorders. The medical treatment of acromegaly is somatostatin analogues (SSA) in specific cases combined with dopamine agonists (DA), but almost half of patients display partial or full SSA resistance and potential causes of this are unknown. In this study we investigated transcriptomic landscape of GH-producing PitNETs on several levels and functional models—tumour tissue of patients with and without SSA preoperative treatment, tumour derived pituispheres and GH3 cell line incubated with SSA to study effect of medication on gene expression. MGI sequencing platform was used to sequence total RNA from PitNET tissue, pituispheres, mesenchymal stromal stem-like cells (MSC), and GH3 cell cultures, and data were analysed with Salmon—DeSeq2 pipeline. We observed that the GH-producing PitNETs have distinct changes in growth hormone related pathways related to its functional status alongside inner cell signalling, ion transport, cell adhesion and extracellular matrix characteristic patterns. In pituispheres model, treatment regimens (octreotide and cabergoline) affect specific cell proliferation (MKI67) and core functionality pathways (RYR2, COL8A2, HLA-G, ARFGAP1, TGFBR2). In GH3 cells we observed that medication did not have transcriptomic effects similar to preoperative treatment in PitNET tissue or pituisphere model. This study highlights the importance of correct model system selection for cell transcriptomic profiling and data interpretation that could be achieved in future by incorporating NGS methods and detailed cell omics profiling in PitNET model research.

Patients with advanced hepatocellular carcinoma (HCC) have a very limited survival rate even after the recent inclusion of kinase inhibitors or immune checkpoint inhibitors in the therapeutic armamentarium. A significant problem with the current proposed therapies is the considerable cost of treatment that may be a serious obstacle in low- and middle-income countries. Implementation of somatostatin analogues (SSAs) has the potential to overcome this obstacle, but due to some negative studies their extensive evaluation came to a halt. However, experimental evidence, both in vitro and in vivo, has revealed various mechanisms of the anti-tumor effects of these analogues, including inhibition of cancer cell proliferation and angiogenesis and induction of apoptosis. Favorable indirect effects such as inhibition of liver inflammation and fibrosis and influence on macrophage-mediated innate immunity have also been noted and are presented in this review. Furthermore, the clinical application of SSAs is both presented and compared with clinical trials of kinase and immune checkpoint inhibitors (ICIs). No direct trials have been performed to compare survival in the same cohort of patients, but the cost of treatment with SSAs is a fraction compared to the other modalities and with significantly less serious side effects. As in immunotherapy, patients with viral HCC (excluding alcoholics), as well as Barcelona stage B or C and Child A patients, are the best candidates, since they usually have a survival prospect of at least 6 months, necessary for optimum results. Reasons for treatment failures are also discussed and further research is proposed.

Resumen: Introducción: El 50% de las hemorragias del intestino delgado son causadas por angiectasias del intestino delgado (AID) y la tasa de recurrencia es del 80%. Su tratamiento endoscópico es difícil. Algunos estudios han informado efectos beneficiosos del octreótido en angiectasias del tubo digestivo, pero ninguno ha evaluado su eficacia en las AID. Objetivo: Investigar la efectividad del octreótido en la prevención de la recurrencia hemorrágica de las AID. Material y métodos: Dieciséis pacientes con sangrado por AID fueron asignados a un tratamiento con octreótido 100 μg/24 h SC por al menos 6 meses. Esta cohorte se comparó con un grupo de 36 pacientes no tratados. El desenlace primario fue la tasa de recurrencia hemorrágica y los secundarios fueron el número de reingresos hospitalarios, muerte relacionada con el sangrado, y efectos adversos. Resultados: Se administró octreótido durante 10.5 ± 8.4 meses. El seguimiento fue de 12.9 ± 17.3 y 15.3 ± 17.7 meses en pacientes tratados y no tratados (p = 0.09). Al final del seguimiento, el sangrado recurrente se produjo en 4 (25%) pacientes del grupo tratado y en 26 (72.2%) del grupo no tratado (p = 0.002). La probabilidad acumulada de permanecer libre de hemorragia recurrente al año fue del 79% vs. 44.2% y a los 2 años, del 79% vs. 34.6% en el grupo tratado y no tratado, respectivamente (p = 0.05). De acuerdo con el análisis de regresión logística múltiple, el tratamiento fue variable protectora. Los eventos adversos ocurrieron en 6 pacientes. En uno de ellos fueron eventos mayores (6.25%). Conclusiones: Estos resultados sugieren que el tratamiento con octreótido podría ser eficaz para prevenir las hemorragias recurrentes por AID. Abstract: Introduction: Fifty percent of small bowel bleeding is caused by angioectasia and the rebleeding rate due to small bowel angioectasia (SBA) is 80%. Its endoscopic treatment is difficult. Beneficial effects of octreotide on gastrointestinal angioectasia have been described, but no studies have reported its efficacy in SBA. Aim: Our aim was to investigate the effectiveness of octreotide in the prevention of rebleeding due to SBA. Material and methods: Sixteen patients with bleeding caused by SBA were assigned to treatment with octreotide 100 μg/24 h SC, for at least 6 months, and compared with a non-treatment group of 36 patients. The primary outcome was the rebleeding rate, and the secondary outcomes were the number of hospital readmissions, bleeding-related death, and adverse effects. Results: Octreotide was administered for 10.5 ± 8.4 months. Follow-up was 12.9 ± 17.3 months and 15.3 ± 17.7 months, in the treatment and non-treatment groups, respectively (p = 0.09). At the end of follow-up, 4 (25%) treatment group patients and 26 (72.2%) non-treatment group patients presented with rebleeding (p = 0.002). In the treatment group and non-treatment group, the cumulative probability of remaining rebleeding-free at one year was 79% vs 44.2%, and 79% vs 34.6% at 2 years, respectively (p = 0.05). Through the multiple logistic regression analysis, treatment was the protective variable. Six patients presented with adverse events. One of those patients (6.25%) had a major adverse event. Conclusions: Our results suggest that treatment with octreotide could be efficacious in the prevention of rebleeding due to SBA.

Targeted treatment with somatostatin analogues (SA) in acromegaly and neuroendocrine neoplasms may have some benefits compared to curative treatments, because these agents decrease excessive hormone secretion and exert a tumor-suppressive effect. Monotherapy and combination therapy with SA is well tolerated and bears no risk of debilitating iatrogenic complications. In acromegaly caused by somatotropin producing pituitary tumor, first generation SA are treatment of choice after non-radical adenomectomy, as well as in the cases when patients reject surgery. Treatment efficacy depends on the pathomorphological types of somatotropic tumors, which are different in their receptor phenotype, clinical scenario and proliferative activity. The first generation SA are successfully used for medical treatment of other pituitary tumors (thyrotropic, corticotropic, gonadotropic, lactotropic with resistance to dopamine agonists), as well as for adjuvant therapy of neuroendocrine and non-endocrine neoplasms and elimination of various gastrointestinal disorders. The anti-secretory and anti-tumor effects of SA have been proven for gastroenteropancreatic tumors (carcinoid syndrome, vipomas, gastrinomas, insulinomas, glucagonomas, somatostatinomas). Targeted selection of patients for treatment with first generation SA based on the receptor phenotypes of malignant cells would facilitate more rapid achievement of biochemical remission, improvement of quality of life and survival.

With the global increase in life expectancy, there is an increase in gastrointestinal presentations in the elderly. Small bowel bleeding (SBB) is a cause of significant morbidity in the elderly requiring multiple hospital visits, investigations, and potentially expensive therapy. In this review, we will outline the different modalities which are used for the diagnosis and management of SBB. We will also discuss the common causes of SBB in the elderly. SBB in elderly has a significant impact on the quality of life of the elderly. Larger randomized studies in the elderly are urgently required to help guide clinicians on the best and most cost-effective treatment algorithm in this challenging cohort. [ABSTRACT FROM AUTHOR]

Purpose: According to IAEA/EANM/SNMMI guidelines, long-acting somatostatin analogues (LA-SSAs) should be discontinued 4–6 weeks prior to peptide receptor radionuclide therapy (PRRT) to prevent somatostatin receptor saturation. The aim of this study was to determine the effect of continued use of long-acting SSAs during PRRT on the uptake of [177Lu]Lu-HA-DOTATATE on SPECT/CT. Methods: Consecutive patients with neuroendocrine tumours who were treated with PRRT receiving 7.4 GBq of [177Lu]Lu-HA-DOTATATE were included. Patients were divided into 3 groups: (1) control (LA-SSA stopped > 6 weeks prior to PRRT), or continued treatment with (2) long-acting octreotide < 6 weeks prior to PRRT, or (3) long-acting lanreotide < 6 weeks prior to PRRT. The uptake of [177Lu]Lu-HA-DOTATATE was quantified in healthy tissues (spleen, liver, kidneys, bone marrow) and tumour lesions on SPECT/CT performed 24 h after PRRT. A Mann–Whitney U test was used to determine differences in uptake between the long-acting octreotide and long-acting lanreotide groups compared to the control group. Results: Forty-two patients with 135 cycles of PRRT were included: 28 with lanreotide, 50 with octreotide, and 57 cycles without LA-SSAs. Uptake of [177Lu]Lu-HA-DOTATATE was significantly decreased in liver parenchyma in patients with lanreotide (p < 0.001) and in the spleen in patients with either octreotide or lanreotide (both p < 0.001). No differences were observed for uptake in kidneys, bone marrow, and blood pool. Uptake of [177Lu]Lu-HA-DOTATATE in tumours was the same in patients with lanreotide compared to the control (p = 0.862) and in patients with octreotide compared to the control (p = 0.201), independent of tumour location. Conclusion: Long-acting octreotide and lanreotide do not interfere with the uptake of [177Lu]Lu-HA-DOTATATE in tumour lesions 24 h post-injection. Uptake in healthy liver parenchyma significantly decreases after lanreotide administration prior to PRRT, while uptake in healthy spleen tissue significantly decreases with both octreotide and lanreotide administration. [ABSTRACT FROM AUTHOR]

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly.

Simple Summary: Neuroendocrine tumours, recently reclassified as neuroendocrine neoplasms (NENs), are a heterogeneous group of tumours with variability in their disease course and outcome. Complex mechanisms involving spatial and temporal changes in tumour biology affect their treatment response and survival. Treatment strategies are often based on information regarding tumour stage and grade. Tumour heterogeneity, however, is a common phenomenon in NENs, and it is not uncommon for these neoplasms to show intra- and inter-tumour heterogeneity that may lead to incomplete understanding of their tumour biology and behaviour. This review summarises the available evidence on gastroenteropancreatic NEN heterogeneity and its impact on diagnosis and clinical management. Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumours (NETs) represent a heterogenous group of tumours, with diversity in their primary tumour sites, functional status (ie hormone secreting or non-functional) and degrees of aggressiveness (ranging from well-differentiated, grade 1 neuroendocrine tumours to poorly differentiated grade 3, neuroendocrine carcinomas). The most common sites are the lung, small bowel, pancreas and appendix. Clinical presentation is variable, ranging from incidental lesions detected on cross-sectional imaging, small bowel obstruction, carcinoid syndrome or other syndromic presentations (eg hypoglycaemia resulting from insulinoma) through to florid carcinoid heart disease. Diagnosis relies on biochemical markers, computed tomography (CT), magnetic resonance imaging (MRI) and somatostatin-receptor based functional imaging. Treatment comprises surgery where curative resection is possible through to approaches where disease stabilisation is the key, involving somatostatin analogues, peptide receptor radionuclide therapy (PRRT), everolimus, sunitinib, liver-directed therapies and sometimes chemotherapy. Although local and systemic complications can occur, they are associated with reasonable 5- and 10-year survival rates, respectively. [ABSTRACT FROM AUTHOR]

Small intestinal neuroendocrine tumours (Si-NET) are often studied as a uniform group. Proliferation index Ki-67 influences prognosis and determines tumour grade. We hypothesized that Si-NET grade 2 (G2) tumours, which have a higher Ki-67 than G1 tumours, might benefit less from established treatments for metastatic disease. We conducted a retrospective cohort study of 212 patients with metastatic Si-NET G2 treated in two Swedish hospitals during 20 years (2000-2019). Median cancer-specific survival on first-line somatostatin analogues (SSA) was 77 months. Median progression-free survival (PFS) was 12.4 months when SSA was given as monotherapy and 19 months for all patients receiving first-line SSA. PFS after SSA dose es calation was 6 months in patients with radiological progression. Treatment efficacies of SSA and peptide receptor radionuclide treatment (PRRT) were studied separately in patients with Ki-67 of 3-5%, 5-10% and 10-20%. For SSA, PFS was significantly shorter at high er Ki-67 levels (31, 18 and 10 months, respectively), while there was only a minor diffe rence in PFS for PRRT (29, 25 and 25 months). Median PFS for sequential treatment with interferon-alpha (IFNα), everolimus and chemotherapy was 6, 5 and 9 months. IFNα seemed to be effective in tumours with low somatostatin-receptor expression. In conclusion, established treatments appeared effective in Si-NET G2, despite their higher proliferation index compared to G1 tumours. However, efficacy of SSA but not PRRT was reduced at higher Ki-67 levels. SSA dose escalation provided limited disease stabilization. [ABSTRACT FROM AUTHOR]

Angiogenic factors (AF) promote vascular formation and may thus support neuroendocrine tumour (NET) development. This study aimed to assess AF serum level changes in NET patients treated with prolonged-acting somatostatin analogues (SSAs). The study enrolled 49 healthy volunteers (Group A) and 56 NET patients: treatment naïve (Group B) and after-SSA treatment in various periods (months): under 12 (Group C), 13–24 (Group D), 25–36 (Group E), 37–60 (Group F), and over 60 months (Group G). The serum vascular endothelial growth factor receptors 2, 3 (VEGF-R2, VEGF-R3), and vascular cell adhesion molecule-1 (VCAM-1) concentrations were tested using the ELISA. We noted significant differences in the concentrations of VEGF-R2, VEGF-R3, and VCAM-1 depending on the SSA treatment duration (p < 0.001). In the studied AFs, the highest decreasing levels of VEGF-R2 were observed after two years of therapy. However, monitoring VEGF-R2, VEGF-R3, and VCAM-1 during SSA treatment did not allow for the identification of good responders for this kind of therapy. Therefore, these biomarker measurements were not helpful in assessing SSA treatment effectiveness in NET patients. [ABSTRACT FROM AUTHOR]

Pituitary neuroendocrine tumours (PitNETs) are neoplasms of the pituitary that overproduce hormones or cause unspecific symptoms due to mass effect. Growth hormone overproducing GH-producing PitNETs cause acromegaly leading to connective tissue, metabolic or oncologic disorders. The medical treatment of acromegaly is somatostatin analogues (SSA) in specific cases combined with dopamine agonists (DA), but almost half of patients display partial or full SSA resistance and potential causes of this are unknown. In this study we investigated transcriptomic landscape of GH-producing PitNETs on several levels and functional models—tumour tissue of patients with and without SSA preoperative treatment, tumour derived pituispheres and GH3 cell line incubated with SSA to study effect of medication on gene expression. MGI sequencing platform was used to sequence total RNA from PitNET tissue, pituispheres, mesenchymal stromal stem-like cells (MSC), and GH3 cell cultures, and data were analysed with Salmon—DeSeq2 pipeline. We observed that the GH-producing PitNETs have distinct changes in growth hormone related pathways related to its functional status alongside inner cell signalling, ion transport, cell adhesion and extracellular matrix characteristic patterns. In pituispheres model, treatment regimens (octreotide and cabergoline) affect specific cell proliferation (MKI67) and core functionality pathways (RYR2, COL8A2, HLA-G, ARFGAP1, TGFBR2). In GH3 cells we observed that medication did not have transcriptomic effects similar to preoperative treatment in PitNET tissue or pituisphere model. This study highlights the importance of correct model system selection for cell transcriptomic profiling and data interpretation that could be achieved in future by incorporating NGS methods and detailed cell omics profiling in PitNET model research. [ABSTRACT FROM AUTHOR]

Background: Somatostatin analogues (SSAs) are the cornerstone of treatment for carcinoid syndrome (CS)-related symptoms. The aim of this systematic review and meta-analysis is to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of long-acting SSAs in patients with CS. Methods: A systematic electronic literature search was conducted in PubMed, Cochrane, and Scopus to identify eligible studies. Any clinical trials reporting data on the efficacy of SSAs to alleviate symptoms in adult patients were considered as potentially eligible. Results: A total of 17 studies reported extractable outcomes (PR/CR) for quantitative synthesis. The pooled percentage of patients with PR/CR for diarrhea was estimated to be 0.67 (95% confidence interval (CI): 0.52–0.79, I2 = 83%). Subgroup analyses of specific drugs provided no evidence of a differential response. With regards to flushing, the pooled percentage of patients with PR/CR was estimated to be 0.68 (95% CI: 0.52–0.81, I2 = 86%). Similarly, no evidence of a significant differential response in flushing control was documented. Conclusions: We estimate there is a 67–68% overall reduction in symptoms of CS associated with SSA treatment. However, significant heterogeneity was detected, possibly revealing differences in the disease course, in management and in outcome definition. [ABSTRACT FROM AUTHOR]

Purpose: Somatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [18F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT. Methods: 77 patients were examined with standardised [18F]SiTATE-PET/CT within clinical routine: 40 patients with long-acting SSAs up to 28 days prior to PET/CT examination and 37 patients without pre-treatment with SSAs. Maximum and mean standardized uptake values (SUVmax and SUVmean) of tumours and metastases (liver, lymphnode, mesenteric/peritoneal and bones) as well as representative background tissues (liver, spleen, adrenal gland, blood pool, small intestine, lung, bone) were measured, SUV ratios (SUVR) were calculated between tumours/metastases and liver, likewise between tumours/metastases and corresponding specific background, and compared between the two groups. Results: SUVmean of liver (5.4 ± 1.5 vs. 6.8 ± 1.8) and spleen (17.5 ± 6.8 vs. 36.7 ± 10.3) were significantly lower (p < 0.001) and SUVmean of blood pool (1.7 ± 0.6 vs. 1.3 ± 0.3) was significantly higher (p < 0.001) in patients with SSA pre-treatment compared to patients without. No significant differences between tumour-to-liver and specific tumour-to-background SUVRs were observed between both groups (all p > 0.05). Conclusion: In patients previously treated with SSAs, a significantly lower SSR expression ([18F]SiTATE uptake) in normal liver and spleen tissue was observed, as previously reported for 68Ga-labelled SSAs, without significant reduction of tumour-to-background contrast. Therefore, there is no evidence that SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT. [ABSTRACT FROM AUTHOR]

Objective: Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review is to analyse and appraise the current evidence for the generalized use of preoperative medications and the various surgical approaches as described in the literature. Design: A thorough search from MEDLINE via PubMed, EMBASE, and Cochrane Library has been performed which identified a total of 37 papers. Conclusion: The preoperative use of somatostatin receptor agonists (SAs) in acromegaly is a controversial topic with current guidelines suggesting against their generalized routine use. Most authors noticed an insignificant long‐term remission of acromegaly when given SAs compared with nil preoperative therapy, except for invasive macroadenomas as SAs have been found to reduce the tumour volume and aid towards the total resection of the adenoma. Furthermore, according to the evidence available, endoscopic transsphenoidal surgery is the optimum method for hypophysectomy in terms of its remission and safety profile. [ABSTRACT FROM AUTHOR]

PurposeSomatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [18F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.Methods77 patients were examined with standardised [18F]SiTATE-PET/CT within clinical routine: 40 patients with long-acting SSAs up to 28 days prior to PET/CT examination and 37 patients without pre-treatment with SSAs. Maximum and mean standardized uptake values (SUVmax and SUVmean) of tumours and metastases (liver, lymphnode, mesenteric/peritoneal and bones) as well as representative background tissues (liver, spleen, adrenal gland, blood pool, small intestine, lung, bone) were measured, SUV ratios (SUVR) were calculated between tumours/metastases and liver, likewise between tumours/metastases and corresponding specific background, and compared between the two groups.ResultsSUVmean of liver (5.4 ± 1.5 vs. 6.8 ± 1.8) and spleen (17.5 ± 6.8 vs. 36.7 ± 10.3) were significantly lower (p < 0.001) and SUVmean of blood pool (1.7 ± 0.6 vs. 1.3 ± 0.3) was significantly higher (p < 0.001) in patients with SSA pre-treatment compared to patients without. No significant differences between tumour-to-liver and specific tumour-to-background SUVRs were observed between both groups (all p > 0.05).ConclusionIn patients previously treated with SSAs, a significantly lower SSR expression ([18F]SiTATE uptake) in normal liver and spleen tissue was observed, as previously reported for 68Ga-labelled SSAs, without significant reduction of tumour-to-background contrast. Therefore, there is no evidence that SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.

Neuroendocrine tumors (NETs) occur in various regions of the body and present with complex clinical and biochemical phenotypes. The molecular underpinnings that give rise to such varied manifestations have not been completely deciphered. The management of neuroendocrine tumors (NETs) involves surgery, locoregional therapy, and/or systemic therapy. Several forms of systemic therapy, including platinum-based chemotherapy, temozolomide/capecitabine, tyrosine kinase inhibitors, mTOR inhibitors, and peptide receptor radionuclide therapy have been extensively studied and implemented in the treatment of NETs. However, the potential of immune checkpoint inhibitor (ICI) therapy as an option in the management of NETs has only recently garnered attention. Till date, it is not clear whether ICI therapy holds any distinctive advantage in terms of efficacy or safety when compared to other available systemic therapies for NETs. Identifying the characteristics of NETs that would make them (better) respond to ICIs has been challenging. This review provides a summary of the current evidence on the value of ICI therapy in the management of ICIs and discusses the potential areas for future research. [ABSTRACT FROM AUTHOR]

Summary: Neuroendocrine neoplasms of the gastroenteropancreatic system (GEP-NENs) have historically been graded into well-differentiated neuroendocrine tumors (NETs) G 1 and 2 and undifferentiated neuroendocrine carcinomas (NEC) G3 according to the proliferative index Ki-67, with the latter being larger than 20% for G3 NENs. However, clinical and pathological findings have suggested G3 NENs to be heterogeneous, and the most recent World Health Organization (WHO) classification has further subdivided G3 NENs into NET G3 with differentiated features and a usually lower Ki-67 (20–55%) as opposed to undifferentiated NECs. Currently, however, no standard approach to patients with NET G3 has been defined. As opposed to NET G1/G2, application of somatostatin analogues is not recommended, and the response to platinum-based chemotherapy is inferior when compared to NEC. The objective of this short review is to summarize pathological characteristics as well as therapeutic data obtained in patients with NET G3. [ABSTRACT FROM AUTHOR]

Patients with advanced hepatocellular carcinoma (HCC) have a very limited survival rate even after the recent inclusion of kinase inhibitors or immune checkpoint inhibitors in the therapeutic armamentarium. A significant problem with the current proposed therapies is the considerable cost of treatment that may be a serious obstacle in low- and middle-income countries. Implementation of somatostatin analogues (SSAs) has the potential to overcome this obstacle, but due to some negative studies their extensive evaluation came to a halt. However, experimental evidence, both in vitro and in vivo, has revealed various mechanisms of the anti-tumor effects of these analogues, including inhibition of cancer cell proliferation and angiogenesis and induction of apoptosis. Favorable indirect effects such as inhibition of liver inflammation and fibrosis and influence on macrophage-mediated innate immunity have also been noted and are presented in this review. Furthermore, the clinical application of SSAs is both presented and compared with clinical trials of kinase and immune checkpoint inhibitors (ICIs). No direct trials have been performed to compare survival in the same cohort of patients, but the cost of treatment with SSAs is a fraction compared to the other modalities and with significantly less serious side effects. As in immunotherapy, patients with viral HCC (excluding alcoholics), as well as Barcelona stage B or C and Child A patients, are the best candidates, since they usually have a survival prospect of at least 6 months, necessary for optimum results. Reasons for treatment failures are also discussed and further research is proposed. [ABSTRACT FROM AUTHOR]

Somatostatin (SST), cortistatin (CORT), and their receptors (SSTR1-5/sst5TMD4-TMD5) comprise a multifactorial hormonal system involved in the regulation of numerous pathophysiological processes. Certain components of this system are dysregulated and play critical roles in the development/progression of different endocrine-related cancers. However, the presence and therapeutic role of this regulatory system in prostate cancer (PCa) remain poorly explored. Accordingly, we performed functional (proliferation/migration/colonies-formation) and mechanistic (Western-blot/qPCR/microfluidic-based qPCR-array) assays in response to SST and CORT treatments and CORT-silencing (using specific siRNA) in different PCa cell models [androgen-dependent (AD): LNCaP; androgen-independent (AI)/castration-resistant PCa (CRPC): 22Rv1 and PC-3], and/or in the normal-like prostate cell-line RWPE-1. Moreover, the expression of SST/CORT system components was analyzed in PCa samples from two different patient cohorts [internal (n = 69); external (Grasso, n = 88)]. SST and CORT treatment inhibited key functional/aggressiveness parameters only in AI-PCa cells. Mechanistically, antitumor capacity of SST/CORT was associated with the modulation of oncogenic signaling pathways (AKT/JNK), and with the significant down-regulation of critical genes involved in proliferation/migration and PCa-aggressiveness (e.g., MKI67/MMP9/EGF). Interestingly, CORT was highly expressed, while SST was not detected, in all prostate cell-lines analyzed. Consistently, endogenous CORT was overexpressed in PCa samples (compared with benign-prostatic-hyperplasia) and correlated with key clinical (i.e., metastasis) and molecular (i.e., SSTR2/SSTR5 expression) parameters. Remarkably, CORT-silencing drastically enhanced proliferation rate and blunted the antitumor activity of SST-analogues (octreotide/pasireotide) in AI-PCa cells. Altogether, we provide evidence that SST/CORT system and SST-analogues could represent a potential therapeutic option for PCa, especially for CRPC, and that endogenous CORT could act as an autocrine/paracrine regulator of PCa progression. [ABSTRACT FROM AUTHOR]