Search Results (115)

Somatostatin is a potent endocrine regulator and neurotransmitter, exerting predominantly inhibitory effects in different tissues of the body, via G-protein coupled receptors. Five such specific receptors have been identified, with different effects and tissue distribution. The multifaceted actions and effects of somatostatin make it useful as a potential therapeutical means in various pathologies; however, in clinical practice, somatostatin analogues, namely octreotide, lanreotide and pasireotide, are commonly used instead, due to their increased half-life and increased receptor selectivity, with pasireotide showing a more extensive receptor binding profile and high affinity for somatotastin receptor (SSTR) 5, which may prove effective in cases of resistance to first-generation analogues. Apart from their many uses in neoplastic pathologies, somatostatin analogues represent viable treatment choices in some ocular pathologies, congenital hyperinsulinism, gastrointestinal bleedings and portal hypertension, acute pancreatitis, and dumping syndrome. They have also been used in some cases, with varying degrees of success, in patients with post-surgical gastrointestinal and lymphatic fistulas, refractory chronic diarrhoea and polycystic kidney disease; many applications in paediatric patients have also been documented. The aim of this review is to present the applications of somatostatin and its analogues as alternative or second-line therapies, along with insights into their effectiveness and future potential. Full article

Background: Pancreatic trauma (PT) in children is rare and associated with significant morbidity. The optimal form of management—operative versus non-operative—remains controversial, particularly in the presence of acute post-traumatic peripancreatic fluid collection, which may later evolve into pancreatic pseudocysts. Isolated pancreatic injuries without associated organ damage are uncommon and pose diagnostic and therapeutic challenges. Case Presentation: We report a 5-year-old boy who sustained an isolated grade IB blunt pancreatic head contusion following blunt abdominal trauma after falling onto a wooden fence. He presented with epigastric pain, repeated emesis, and an abdominal wall bruise. Initial ultrasound (US) findings were subtle; however, serial imaging and contrast-enhanced computed tomography (CECT) revealed focal contusion of the pancreatic head/uncinate process with a small peripancreatic fluid collection. Pancreatic enzymes were markedly elevated, with peak serum lipase reaching approximately 6579 U/L. The child remained hemodynamically stable and was managed conservatively with bowel rest, intravenous fluids, octreotide, proton-pump inhibition, pancreatic enzyme replacement therapy (PERT), and antibiotics. Serial US demonstrated the dynamic evolution of an acute peripancreatic fluid collection (APFC) (~2 cm), which remained stable without complications. Clinical and biochemical parameters gradually improved, and no invasive intervention was required. The patient was discharged on hospital day 16 with planned outpatient imaging follow-up. Conclusions: This case demonstrates that isolated pediatric pancreatic contusions complicated by small, evolving peripancreatic fluid collections can be safely managed non-operatively in hemodynamically stable patients. Serial ultrasound plays a key role in monitoring lesion evolution and guiding management decisions. In accordance with current pediatric trauma guidelines, careful observation with structured follow-up may prevent unnecessary invasive interventions while achieving excellent clinical outcomes. Full article

Background. Somatostatin and its synthetic analog octreotide are suppressive hormones that have been used in the treatment of variceal bleeding or bleeding from portal hypertensive gastropathy. They are also used in the treatment of some cancers, including hepatocellular carcinoma (HCC). Experimental evidence reported that they have potentially useful effects on liver inflammation and fibrosis, acting on Kupffer cells (KCs) and hepatic stellate cells (HSCs). However, clinical data is missing. Therefore, the effect of somatostatin and octreotide was studied on several fibrosis mediators in patients with compensated cirrhosis. Patients and Methods. Fifty-eight patients with HCV-related compensated cirrhosis treated with either somatostatin or octreotide for bleeding from portal gastropathy were compared with twenty-nine healthy controls matched for age and sex. Serum levels of three metalloproteases (MMP1, MMP2 and MMP9) and their inhibitors, TIMP1 and TIMP2, were measured. Additional fibrosis and inflammation mediators—such as nitric oxide (NO), TNFα, soluble ICAM-1, and the CC chemokines RANTES (CCL5) and MIP1a (CCL3)—were also measured. Results. Serum levels of MMP1, MMP2, MMP9 and TIMP1 were significantly decreased in cirrhosis (p < 0.01). TIMP2 levels were increased (p < 0.01). RANTES levels were also significantly decreased (p < 0.01), but NO, TNFα, MIP1a and sICAM-1 were significantly increased (p < 0.01). Administration of somatostatin had no effect on MMP2 or MMP9 but significantly decreased all other mediators. Octreotide had similar but milder effects, but it had no effects on MIP1a and sICAM-1 were demonstrated. Conclusions. Somatostatin and octreotide modulate factors implicated in the progression of fibrosis in the short term. Whether they could be used in the long term as treatment for liver diseases with progressive fibrosis or in cases with intense inflammatory reactions, such as alcoholic hepatitis, requires further investigation. Full article

Grade 1–2 pancreatic neuroendocrine tumors exhibit considerable biological and clinical diversity, which translates into a broad range of available therapeutic approaches. Given the absence of a universally accepted treatment sequence, treatment selection requires a practical framework based on tumor biology and clinical presentation. Clinical management should be individualized by integrating the histologic grade, disease extent, symptom burden, and somatostatin receptor (SSTR) expression. For patients with low-volume, SSTR-positive, and clinically indolent disease (Ki-67 < 10%), long-acting somatostatin analogues, including octreotide and lanreotide, are commonly used as initial therapies to control hormonal symptoms and delay tumor progression. In patients with radiologic progression requiring systemic disease control, targeted agents such as everolimus and sunitinib represent established subsequent options, particularly when disease stabilization is the primary therapeutic goal. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE has demonstrated meaningful antitumor activity and is generally considered in patients with SSTR-positive tumors with progressive disease (Ki-67 ≥ 10%) or increasing tumor burdens, especially when tumor reduction is desirable. Combination cytotoxic chemotherapy, most notably the capecitabine–temozolomide (CAPTEM) regimen, remains an important consideration for patients with higher tumor burdens or more aggressive tumor biology. This review summarizes current evidence and provides a practical overview of treatment selection and sequencing for the systemic management of Grade 1–2 pancreatic neuroendocrine tumors, while also highlighting emerging therapeutic strategies, including targeted alpha therapy and SSTR2 antagonist-based approaches. Full article

Background: Lyotropic liquid crystal (LLC) systems provide sustained release and convenient administration for peptide delivery. Octreotide, a first-line somatostatin analogue, has previously been formulated into LLC systems mainly using the hydrochloride salt. Here, we investigated the acetate salt, which is widely used in marketed products, but presents unique challenges in LLC formulation due to poor stability. Methods: We demonstrate that pH adjustment is a critical determinant for successfully incorporating octreotide acetate into a stable LLC system. By employing 3M HCl–EtOH to adjust pH to approximately 5.7, we obtained a formulation that maintained >90% drug content after 3 months at 40 °C and >98% after 12 months at 4 °C. Results: Structural analyses confirmed the coexistence of cubic and hexagonal mesophases, supporting controlled release. In vivo pharmacokinetic studies in rats further demonstrated sustained-release behavior, as evidenced by prolonged systemic exposure and an extended half-life. Pharmacokinetic profiles were comparable to those of an octreotide hydrochloride LLC. Conclusions: These findings highlight pH modulation as an essential strategy for stabilizing octreotide acetate in LLC systems, providing a foundation for extending LLC technology to clinically relevant salt forms of peptide therapeutics. Full article

Growth factors play a significant role in the immunopathogenesis of liver diseases, especially liver cirrhosis and hepatocellular carcinoma (HCC). The somatostatin analog octreotide has been used as treatment in advanced HCC, based on its anti-neoplastic effects in vitro. Therefore, the effect of somatostatin and octreotide was studied on several growth factors in patients with HCC. Nineteen patients with advanced HCC were treated with octreotide and compared with thirty-seven patients with viral cirrhosis (19 decompensated) treated with intravenous somatostatin for severe bleeding from portal gastropathy. Five growth factors, namely Gastrin, Insulin-like growth factor 1 (IGF 1), Hepatocyte growth factor (HGF), Stem cell factor (SCF) and Vascular endothelial growth factor (VEGF) were measured in serum before and after treatment with specific commercially available ELISAs. Seventeen healthy individuals and nineteen patients with chronic viral hepatitis C (CAH) were used as pre-treatment controls. Eighteen patients with advanced Primary Biliary Cholangitis (stage III and IV) before and after Ursodeoxycholic acid (UDCA) treatment were also studied. Pre-treatment levels of Gastrin were significantly increased in HCC, cirrhosis and PBC but not in CAH. Levels were significantly reduced by octreotide or somatostatin but also by UDCA in PBC. By contrast, IGF1 showed a mirror image being significantly reduced in HCC, cirrhosis and PBC, but not in CAH. Post-treatment levels were reduced in all groups, but not in PBC. Levels of HGF were significantly increased in HCC and cirrhosis but not in CAH and PBC. They were further increased in HCC after treatment. SCF increased only in HCC and was reduced after octreotide but not after somatostatin treatment. VEGF was reduced in cirrhosis and CAH but not in PBC. It was not significantly increased in HCC, but it was reduced by octreotide and was increased after UDCA. In this retrospective observational study, somatostatin and its analog octreotide have a significant effect on several growth factors involved in HCC pathogenesis. Full article

Background: In ectopic adrenocorticotropic hormone (ACTH) syndrome, locating the responsible lesion is often challenging. Case Presentation: A 68-year-old woman was transferred to Nara Medical University hospital for a detailed investigation of her ACTH-dependent Cushing’s syndrome. Because of hypercortisolism-induced immunosuppression, she subsequently developed severe Nocardia pneumonia and was forced to temporarily depend on noninvasive positive pressure ventilation (NIPPV). Intravenous antifungal agents and antibiotics were administered, resulting in significant symptomatic improvement. Metyrapone was administered to suppress excessive cortisol. Contrast-enhanced magnetic resonance imaging of the pituitary revealed a 4 mm sized poorly enhanced area, and microadenoma was suspected. Although cavernous venous sampling was indispensable prior to trans-spheroidal surgery (TSS), this examination could not be performed because of the presence of deep vein thrombosis. TSS was performed for both diagnostic and therapeutic purposes, but hypercortisolism did not improve. Moreover, immunohistochemical findings of the specimen revealed nonfunctional pituitary tumor. Methods: We re-evaluated the responsible lesion causing ACTH-dependent Cushing’s syndrome. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed weak and abnormal FDG uptake in the right pericardium, but the possibility of nonspecific uptake could not be ruled out. However, gallium-68 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic-acid-D-Phe¹-Tyr³-octreotide (⁶⁸Ga-DOTATOC)-PET demonstrated the same degree of abnormal uptake; therefore, a functional pulmonary tumor was strongly suspected. Results: Video-Assisted Thoracic Surgery (VATS) was performed, and histopathological findings of the specimen revealed a neuroendocrine tumor with positive ACTH staining. After VATS, ACTH and cortisol levels were normalized. Conclusions: Here, we report a case of ACTH-dependent Cushing’s syndrome caused by a lung neuroendocrine tumor, in which ⁶⁸Ga-DOTATOC PET was helpful in detecting the functional tumors. Full article

Background/Objectives: For completely resected well differentiated (WD) gastroenteropancreatic (GEP) NET, guidelines differ in recommendations for utilization of SSTR-based functional imaging in post-operative surveillance. While ¹¹¹In-Octreotide has previously been the standard of care, imaging with ⁶⁸Ga-labelled peptides has expanded in recent years due to increased sensitivity to detect smaller volume diseases and reduced costs. Though many centres have widely adopted imaging with ⁶⁸Ga-labelled peptides, its role in surveillance of resected GEP NET has not been well defined. We sought to characterize current utilization of imaging with ⁶⁸Ga-DOTATATE PET CT (⁶⁸Ga-DOTA) for post-operative surveillance of WD GEP NET and assess the impact on clinical management. Methods: We conducted a retrospective review of all ⁶⁸Ga-DOTA scans performed from April 2019 to August 2024. Inclusion criteria were age ≥ 18 years with WD grade 1 and 2 GEP NET that had undergone curative-intent surgery, had Stage I-III disease at diagnosis, and had ⁶⁸Ga-DOTA post-operatively. Results: Forty-six scans met the inclusion criteria. We identified four indications for ⁶⁸Ga-DOTA: (1) post-operative assessment (n = 12); (2) routine surveillance (n = 18); (3) recurrence suspected based on cross-sectional imaging (n = 10); and (4) recurrence suspected based on biochemical monitoring (n = 6). Avidity for each indication was observed in 45%, 8%, 50%, and 80%, respectively. Initiation of long-acting somatostatin analogue was the most common management following avidity. Conclusions: ⁶⁸Ga-DOTA best informed clinical decision making when there was clinical suspicion for residual or metastatic disease post-operatively or based on cross-sectional imaging or biochemistry. The utility of this modality for routine surveillance appears limited. Full article

Background: Pancreatic neuroendocrine tumor (pNET) is a rare and complex disease that requires careful management and treatment. Currently, a range of treatments, including surgery, somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy, exist for pNETs. However, determining the optimal treatment strategies remains challenging. Aim: To evaluate the efficacy and safety of non-surgical therapies, such as somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy in treating pNETs. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science databases for relevant studies published from inception until August 2025. Randomized clinical trials (RCTs), non-randomized clinical trials, and prospective studies were included in this meta-analysis if they evaluated the efficacy and safety of any treatment of interest in patients with pNETs. Results: Thirty-three studies involving 2374 pNET patients were analyzed. Targeted therapies showed modest objective response rates (ORRs) but high disease control rates (DCRs): everolimus (ORR 7%, 95% CI: 3–10%; DCR 81%, 95% CI: 75–87%), sunitinib (ORR 12%, 95% CI: 5–19%; DCR 79%, 95% CI: 70–88%), surufatinib (ORR 19%, 95% CI: 12–27%; DCR 81%, 95% CI: 73–89%). Cytotoxic chemotherapy demonstrated higher ORRs: dacarbazine-based (32%, 95% CI: 21–43%), streptozocin-based (40%, 95% CI: 25–54%), temozolomide-based (42%, 95% CI: 29–55%). PRRT showed varying efficacy: ¹⁷⁷Lu-DOTATATE (ORR 36%, 95% CI: 27–44%; DCR 84%, 95% CI: 76–92%), ⁹⁰Y-DOTATOC (ORR 27%, 95% CI: 18–36%; DCR 73%, 95% CI: 63–83%). SSAs had low ORRs but high DCRs: lanreotide (ORR 0%, DCR 67%, 95% CI: 57–77%), octreotide (ORR 23%, 95% CI: 15–31%; DCR 75%, 95% CI: 66–84%). Immunotherapy with pembrolizumab showed limited efficacy (ORR 7%, 95% CI: 0–14%). Treatment-related adverse events were common across therapies, with specific toxicity profiles for each modality. Conclusions: Cytotoxic chemotherapy offers better response rates than other treatment modalities. However, toxicity management is crucial. PRRT also shows robust antitumor activity and disease control, while SSAs and targeted therapies are effective treatment options for disease stabilization. Immunotherapy demonstrated limited antitumor activity, and further research is needed to establish its role in pNET treatment. Full article

Acromegaly is associated with a higher risk of certain malignancies, but not hematological neoplasia, although multiple myeloma (MM) was found in very limited cases. We aim to present such a case, adding a particular presentation with co-occurrence of a plasmocytoma. A 52-year-old male with acromegaly confirmed at 46 (MRI: pituitary macroadenoma of 12 × 11 × 10 mm) underwent hypophysectomy followed by 3 years of octreotide LAR then lanreotide depot. After another 6 months, he experienced a rapidly growing, painful lump in the right lateral thoracic area confirmed by CT as a 9-cm osteolytic lesion at the third rib. Core biopsy revealed plasmocytoma of the bone and medullary biopsy confirmed MM. Plasmacytoma was managed with 10 radiotherapy sessions, with favorable outcome and mass resorption; MM was managed with a VRD regimen, followed by autologous hematopoietic stem-cell transplantation. Six months after sFLC normalization and plasmacytoma resorption, complete remission was reported. In the meantime, lanreotide was continued, with complete acromegaly control. To conclude, what started as a rather typical scenario for an otherwise rare condition, as is acromegaly in the general population (but not so rare for endocrinologists), turned into an unexpected and more severe outcome. Noting this exceptional association, we pinpoint that further research is needed for understanding the dual acromegaly–MM relationship. Full article

The hyperinsulinemic–euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and central venous access surgical procedures for blood collection are provided. Personnel functions are described for execution of the clamp protocol. A total of 24 hyperinsulinemic–euglycemic clamp studies were performed over 6 weeks. Infusaports remained functional for 1454 blood samples. There were three CSII catheter occlusions during bolus administration, and the swine showed no signs of infection or disease. IM telazol at 1.0 mg/kg, administered 1–2 h prior (mean of 3.26 mL ± 1.59) was effective in keeping animals comfortable. SpO₂ and heart rate remained within normal ranges. Means ± SD total infused volumes for octreotide, 10% dextrose, and saline were 9.7 ± 0.93 mL, 2328.0 ± 672.8 mL, and 690.3 ± 206.8 mL. Mean blood glucose was maintained between 75.7 and 87.8 mg/dL (CV 3.17%) for the 24 experiments. The GIR infusion rate peaked between 15 and 60 min after insulin bolusing, with insulin C_max of 108.5 pmol/L and t_max at 10 min. All aspects of the protocol were effectively carried out. The animals remained in good health, and the implanted infusion ports remained patent for over 700 blood draws per animal. This method could potentially reduce the number of animals used and the costs of other similar experiments. Full article

Dumping Syndrome (DS) is a significant complication following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). This condition is characterised by gastrointestinal and vasomotor symptoms resulting from altered anatomy and hormonal dysregulation, notably accelerated gastric emptying and an exaggerated release of gut peptides. Based on the timing of symptom onset after food ingestion, DS is classified as early (EDS) or late (LDS). The critical roles of peptides such as GLP-1, GIP, insulin, and YY peptide are highlighted, along with the involvement of neuroendocrine pathways in symptom manifestation. Diagnosis relies on a combination of clinical evaluation and dynamic testing, with the oral glucose tolerance test (OGTT) often considered a key reference standard for diagnosis. Initial management involves dietary modifications, emphasising the glycaemic index of foods and meal distribution. In cases where nutritional interventions are insufficient, pharmacotherapy with agents such as acarbose, somatostatin analogues (octreotide and pasireotide), GLP-1 receptor agonists (liraglutide), calcium channel blockers (verapamil), and emerging therapies, including herbal medicine, may be considered. For refractory cases, surgical options like bypass reversal or partial pancreatectomy are reserved, although their efficacy can be variable. Despite advancements in understanding and treating DS, further large-scale, randomised controlled trials are essential to validate novel strategies and optimise long-term management. This review provides an updated and comprehensive overview of the aetiology, pathophysiological mechanisms, diagnostic approaches, and current management strategies for DS. Full article

Neuroendocrine tumors of unknown primary (CUP-NET) present a diagnostic challenge when conventional imaging fails to localize the primary tumor. This study aimed to evaluate the diagnostic value of concurrent [⁶⁸Ga]Ga-DOTA-TOC and [¹⁸F]FDG PET/CT imaging in localizing primary tumors in patients with histologically confirmed CUP-NET. Thirty-four patients underwent both imaging modalities as part of a prospective imaging protocol after negative conventional imaging or [¹¹¹In]In-octreotide scintigraphy. Primary tumor detection rates were assessed, and imaging characteristics compared between the two modalities. The overall localization rate was 58.9% (20/34). Of these, 90% (18/20) of primary tumors were identified solely by [⁶⁸Ga]Ga-DOTA-TOC PET/CT, with the remaining two visualized by both modalities. [¹⁸F]FDG PET/CT did not independently localize any primary tumors. Identified primaries were limited to grade 1 (60%) or grade 2 (40%) tumors, predominantly in the small intestine (95%). Among localized cases, 45% (9/20) underwent surgical resection and 15% (3/20) became eligible for peptide receptor radionuclide therapy. [⁶⁸Ga]Ga-DOTA-TOC PET/CT demonstrated superior detection of metastatic lesions compared to [¹⁸F]FDG PET/CT (97.1% vs. 70.6%, p = 0.006). No significant survival differences were observed between patients with localized versus non-localized primaries. These findings support the value of [⁶⁸Ga]Ga-DOTA-TOC PET/CT for identifying primary tumors in CUP-NET. Further research is warranted to explore the role of [¹⁸F]FDG PET/CT in high-grade NETs. Full article

Background/Objectives: Portal hypertension (PH) is a common complication in children with chronic liver diseases. Primary and secondary prophylaxis of variceal bleeding in these patients remains controversial. Our study aims to evaluate the management of gastrointestinal (GI) varices in children with PH in Italy. Methods: A questionnaire was sent to 21 major pediatric hepatology centers. It included 34 questions referring to the medical, endoscopic, radiological, and surgical management of GI varices. Results: Out of 21 centers, 16 returned a completed questionnaire (survey response rate 76%) with a high level of completeness. A total of 1206 children with PH were under follow-up. Splenomegaly associated with hypersplenism was the main indication for endoscopic surveillance in all centers (100%). Primary prophylaxis was performed with endoscopy plus non-selective beta-blockers (NSBBs) in 50%, endoscopy alone in 38%, and NSBBs alone in 12%. All centers managed acute variceal bleeding with endoscopy within 24 h, acid suppression, and octreotide infusion. Secondary prophylaxis of variceal bleeding was conducted using endoscopy (100%) and NSBBs (87%). Transjugular intrahepatic portosystemic shunt (TIPS) was considered a good option when endoscopic treatment failed in 94% of centers. Conclusions: In Italy, there is broad consensus among centers regarding the management of gastrointestinal varices in children with portal hypertension. All participating centers endorsed the use of endoscopic screening for children presenting with clinical signs of portal hypertension. Nonetheless, further research is essential to establish evidence-based guidelines and to improve overall quality of care. Full article

Background and Aims: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common cause of hospitalizations, with proton pump inhibitors (PPIs) being the mainstay treatment. However, there is a lack of high-level evidence to show if adjunctive medical therapy (somatostatin and its analogs) can improve outcomes. This systematic review and meta-analysis aim to evaluate the outcomes of PPIs with adjunctive therapy versus PPI monotherapy in treating NVUGIB in an in-patient setting. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, major databases were systematically searched to retrieve English-only, original studies, published from 1 January 2000 to 31 December 2023, investigating NVUGIB only. The primary outcomes included the mortality rate within 7 days of therapy, rebleeding rate within 7 days of therapy, and length of hospital stay. Results: Seven studies with 789 patients had a pooled mortality rate of 2.0% (95% CI, 0–4.0%), and the pooled risk ratio was 1.11 (95% CI, 0.50–2.48; p = 0.79) between PPI monotherapy and PPIs with adjunctive medical therapy. The pooled rebleeding rate was 13% (95% CI, 6–20%) and the risk ratio was 1.04 (95% CI, 0.73–1.48; p = 0.83). The pooled average length of stay in the hospital was 5.47 days (95% CI, 3.72–7.21 days), with insignificant weighted differences between the two groups. No statistically significant differences were noted in surgical management risk ratios or amount of blood transfusion. Conclusions: Among patients with NVUGIB, adjunctive medical therapy offered no clinical benefits given the statistically insignificant differences in the primary outcomes. However, this conclusion is limited by the considerable variability in treatment protocols, weak control of confounding variables, and missing clinical information in the original studies. Therefore, better-quality, large-scale randomized controlled trials are needed, ideally using standardized somatostatin dosing, timing, delivery routes, and clearly defined inclusion criteria to more accurately evaluate the role of somatostatin in NVUGIB management. Full article