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Background: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period. Case presentation: We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc. Conclusion: Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients. [ABSTRACT FROM AUTHOR]

Octreotide acetate, the active pharmaceutical ingredient in the long‐acting release (LAR) drug product Sandostatin®, is a cyclic octapeptide that mimics the naturally occurring somatostatin peptide hormone. Modern NMR can be a robust analytical method to identify and quantify octreotide molecules. Previous 1H chemical shift assignments were mostly performed in organic solvents, and no assignments for heteronuclear 13C, 15N, and aromatic 1H nuclei are available. Here, using state‐of‐the‐art 1D and 2D homo‐ and heteronuclear NMR experiments, octreotide was fully assigned, including water exchangeable amide protons, in aqueous buffer except for 13CO and 15NH of F1, 15NH of C2, and 15NζHζ of K5 that were not observed because of water exchange or conformational exchange. The solution NMR spectra were then directly compared with 1D 1H/13C/15N solid‐state NMR (SSNMR) spectra showing the potential applicability of 13C/15N SSNMR for octreotide drug product characterization. [ABSTRACT FROM AUTHOR]

Octreotide is the first synthetic peptide hormone, consisting of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software have established X-Ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information from biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X'Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable, and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d ~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit cell is reported mainly upon controlled relative humidity variation. In addition, an improvement in the signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, such as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products. [ABSTRACT FROM AUTHOR]

A pancreatic cancer patient presents with functionally disabling chronic refractory diarrhoea that is unresponsive to common antidiarrheal pharmacotherapies, including octreotide. Autonomic enteropathy was thought to be an underlying mechanism of the diarrhoea, given the patient's history of diabetes, coeliac plexus blocks, and pancreaticoduodenectomy. In the non-palliative context, clonidine is increasingly being used to treat diarrhoea of multiple aetiologies, including autonomic enteropathy. Within 1 week of commencing clonidine, the patient's diarrhoea had resolved, without significant adverse events, suggesting a potential role for clonidine in the palliation of refractory diarrhoea. [ABSTRACT FROM AUTHOR]

Background: Following mastectomy, prolonged wound drainage delays adjuvant therapy and also prolongs hospitalization in an otherwise fit patient. This study determined the effect of octreotide on the duration of postmastectomy wound drainage. Methods: Patients scheduled for modified radical mastectomy were randomized into a treatment group that received 100 µg of octreotide and a control group that received 1 mL of sterile water intravenously 8 hourly for 5 days from the first postoperative day. Sociodemographic data, time to drain removal, total drain volume, and incidence of seroma were obtained. The groups were compared for the time to drain removal, total drain output, average drain output per day, and incidence of seroma. Statistical significance was set at P < 0.05. Results: Forty‑one female breast cancer patients were recruited. The mean age was 53.1 ± 13.0 years. The most common histologic variant was invasive carcinoma of no special type (n = 27; 65.9%). Although not statistically significant, patients in the intervention group had a lower median time to drain removal of 11 days (interquartile range [IQR] = 3) compared with 13 days (IQR = 3) in the control group (P = 0.106) and similarly had a lower median total drain output compared with controls (892.0 mL vs. 1182.8 mL; P = 0.095). Both groups were comparable in terms of postoperative complications and these occurred in 13 patients (31.7%), the most common being seroma (n = 11; 50.0%). Conclusion: Octreotide had no statistically significant effect on either the total drain output or the duration of postmastectomy wound drainage among breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Chyle leak is a rare complication following otolaryngologic, thoracic, and trauma surgery wherein the thoracic duct is transected. Case reports and small case series describe octreotide for the medical management of chyle leak, but limited data exist to determine the ideal dose. Objective: To evaluate octreotide dosing in patients with acute chyle leak. Methods: This retrospective, single center, cohort study evaluated adult patients admitted to the otolaryngology, cardiothoracic, and trauma surgery teams over a 9-year period. Patients diagnosed with a chyle leak who received octreotide were eligible for inclusion. Groups were defined as successful medical management or failure requiring definitive surgery. The primary endpoint was daily octreotide dose between groups. Results: Forty-seven patients were included with 29 (61.7%) admitted to the otolaryngology service and 44 (93.6%) with surgical complication as the chyle leak cause. Thirty-two (68.1%) patients had successful medical management while 15 (31.9%) patients failed and required surgical intervention. There was no difference in median daily octreotide dose (250 [IQR, 170-288] µg vs 253 [IQR, 200-282] µg, P =.9). Octreotide weight-based dose, treatment duration, and route of administration were similar between groups. Daily drain output and complete bowel rest were significantly higher in the failure group. Daily drain output was identified as an independent risk factor for failure. Conclusion: Octreotide dose was similar in patients with and without successful medical management of chyle leak. Future studies are needed to determine optimal octreotide dosing and elucidate the relationship between octreotide, drain output, and surgical intervention need. [ABSTRACT FROM AUTHOR]

Background: ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH). Methods: We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations. Results: The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation. Conclusions: Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene. [ABSTRACT FROM AUTHOR]

Background: Lymphorrhea is a minor complication after kidney transplantation but may develop into a lymphocele and prolong hospital stay. Treatment is conservative based on percutaneous drainage until lymphatic leakage cessation. It has been reported that povidone iodine instillation and octreotide has beneficial effects to treat lymphorrhea after renal transplantation. Aims and Objectives: The aim of this study was to compare the povidone iodine instillation and octreotide treatment in lymphorrea after kidney transplantation. To evaluate the efficacy of povidone iodine and octreotide injection in comparison to control group for the treatment of lymphorrhea in renal transplant patient. Materials and Methods: It was comparative analytical study included 60 recipients of both cadaveric and live kidney allografts with posttransplant lymphorrhea including 20 treated with instillation of betadine solution, 20 with octreotide (0.1 mg three times a day subcutaneously), and 20 was control group (no betadine and octreotide was used). We reviewed the daily amount of fluid collection, duration of lymphorrhea, complications, lymphocele formation, rejection episodes, graft outcomes, and hospital stay. Results: The average duration of lymphorrhea was (8.85 ± 0.88) and (11.6 ± 0.94) and (16.15 ± 0.81) days for the betadine groups, the octreotide groups and control groups respectively. (P < 0.05). No lymphoceles occurred among the betadine group, while three lymphoceles were found among patients treated with octreotide and five lymphocele were found among control groups. No differences were observed for wound infection, graft dysfunction episodes or renal function and death between the groups. No octreotide and povidone related adverse events were noted. Conclusion: The mean length of lymphorrhea was lower with povidone iodine instillation as compared to octreotide treatment. There was a shorter hospital stay and minor patient discomfort in betadine groups. In conclusion, lymphatic leakage after kidney transplantation may be successfully managed by betadine instillation as compared to octreotide and control groups. [ABSTRACT FROM AUTHOR]

Hypoglycemia is an important cause of morbidity and mortality in patients with diabetes mellitus. However, hypoglycemia in patients without diabetes warrants extensive clinical and biochemical evaluations. Traditionally, it occurs either in patients with underlying illness or is seemingly healthy. In patients with underlying comorbidities, hypoglycemia is usually straightforward and may be multifactorial in etiology. A particularly vulnerable population is patients with chronic kidney disease (CKD). We hereby describe a case of persistent hypoglycemia in a 73-year-old nondiabetic CKD presenting as a diagnostic enigma and the possible mechanisms behind it. [ABSTRACT FROM AUTHOR]

Summary: There are several options for systemic therapy of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), including somatostatin analogues (SSA), molecular-targeted agents, cytotoxic agents, and peptide receptor radionuclide therapy. However, the effectiveness of each agent varies according to the primary site. Although SSA and everolimus are key drugs used for systemic therapy of neuroendocrine tumors arising from the gastrointestinal tract (GI-NET), the optimal strategy for selecting among these modalities remains unexplored. Japanese experts on GI-NET discussed and determined optimal first-line treatment strategies based on the results of previously reported pivotal trials. The consensus was reached that tumor aggressiveness and prognosis can be predicted using hepatic tumor load and Ki-67 labeling index, which are thought to be clinically important factors when selecting systemic therapy for unresectable GI-NET. SSA therapy is considered appropriate for patients with a low hepatic tumor load and low Ki-67 value and everolimus for those with contraindications to SSA therapy. There was also agreement that the treatment strategy should be determined according to whether the origin is in the midgut, considering the biological differences. Based on this strategy, the experts have tentatively created treatment maps and applied them in representative cases of unresectable GI-NET. Japanese experts proposed tentative maps for optimal first-line treatment in patients with unresectable GI-NET. Further investigation is warranted to validate the usefulness of these maps. [ABSTRACT FROM AUTHOR]

Patients with high output enteroatmospheric fistulae (EAF) present a significant challenge to the healthcare system. EAF is a cause of intestinal failure which may necessitate long-term parenteral nutrition. Chyme reinfusion is an enteral nutrition intervention and a potential alternative to parenteral nutrition. A novel chyme reinfusion device developed by The Insides® Company has demonstrated multiple potential benefits in the management of EAF. The aim of this case study is to describe the first use of The Insides® System at a tertiary hospital in south west Sydney for a patient with high-output EAF. [ABSTRACT FROM AUTHOR]

Aim: To study the efficacy of octreotide to reduce lymphorrhea and prevent lymphocele after pelvic lymph node excision in gynecological malignancies. Methods: Patients with more than 200 mL of lymph drained per day until postoperative day 3 after pelvic lymph node excision were enrolled. Of the 75 patients, 36 were managed by conservative methods without the injection of octreotide, and the other 39 patients were treated with the injection of octreotide. The treated group was injected with 0.1 mg octreotide q8h for 5 days, starting on postoperative day 3. The drainage tube was removed when the amount of drained lymph decreased to 100 mL per day. The age, BMI, operation time, removed lymph nodes, amount of lymph, duration of drain placement, proportion of patients with lymphocele and complications between these two group were compared. Results: The total and mean daily amount of lymph produced per patient was significantly lower in the octreotide‐treated group than in the untreated group. The duration of drain placement was shorter in the octreotide group than in the untreated group. The proportion of patients with lymphocele in the treatment group was lower than that in the untreated group. Conclusions: The injection of octreotide is effective to reduce lymphorrhea and prevent lymphocele after pelvic lymph node excision in gynecological malignancies. [ABSTRACT FROM AUTHOR]

Purpose: Hepatorenal syndrome (HRS) is renal dysfunction associated with the hemodynamic consequences of advanced liver disease and cirrhosis. HRS is associated with a high mortality, and there remain high failure rates with first-line therapy aimed at improving perfusion. We report the use of droxidopa, an oral norepinephrine precursor, to aid in the management of HRS-AKI refractory to first-line therapy. Summary: A 51-year-old Caucasian male with alcohol-related cirrhosis presented with 1-week history of pre-syncope and falls. He was found to have acute kidney injury meeting diagnostic criteria of HRS based on absence of identifiable contributing factors. After no response to volume expansion, medical management was initiated with midodrine and octreotide and eventually escalated to norepinephrine intravenous infusion. The patient's renal function and urine output improved initially on norepinephrine, but worsened when attempting to wean to a suitable outpatient regimen, becoming dependent upon norepinephrine. On day 13 of hospitalization, droxidopa was initiated at a dose of 100 mg three times daily and titrated to a dose of 400 mg three times daily. Norepinephrine infusion was weaned and discontinued on day 16 of hospitalization. The patient remained hemodynamically stable and was able to be discharged on droxidopa 400 mg three times daily, midodrine 20 mg three times day, and octreotide 200 mcg three times daily. Conclusion: Droxidopa, an oral norepinephrine precursor, presents a novel adjunctive agent for management of HRS refractory to first-line medical management. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapy for nonfunctioning pituitary adenomas (NFPAs) is a significant unmet medical need since these adenomas are frequently invasive, are difficult to resect completely and often recur. NFPAs express high levels of somatostatin receptor 3 (SSTR3), and SSTR3 agonists could be a promising new treatment, but SSTR3 agonists with sufficient characterization to allow clinical testing are not available. We unexpectedly discovered that ITF2984, a molecule originally developed as a pan-SSTR agonist, is a full agonist of SSTR3 in in vitro assays. A similar full agonism was not observed with Pasireotide another pan-SSTR agonist approved for the treatment of Cushing's disease. These unexpected findings prompted us to test ITF2984 in an in vivo model that recapitulates the human disease, where ITF2984 showed significant antitumor activity. ITF2984 has completed phase II clinical trials in acromegaly patients, is well tolerated and can be directly tested in NFPA patients, potentially providing a long-sought-after therapeutic option. Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA. [ABSTRACT FROM AUTHOR]

This document is an editorial discussing a clinical trial of long-acting somatostatin for high-output ostomies and fistulas. Intestinal fistulas are abnormal connections between the intestine and another organ, often caused by surgeries. High output refers to excessive gastrointestinal fluid loss, which can lead to various complications. The trial evaluated the effectiveness of lanreotide, a long-acting somatostatin analogue, as an adjunct to standard care. The results showed that lanreotide significantly reduced output and may be a beneficial treatment option for high-output fistulas and enterostomies. However, the study's design and sample size should be considered when interpreting the results. Further research is needed to confirm these findings. [Extracted from the article]

Background Treatment recommendations for patients with neuroendocrine tumors (NETs) include the use of octreotide long-acting release (LAR) for long-term therapy and immediate-release (IR) as rescue therapy to control the breakthrough symptoms of carcinoid syndrome (CS). High doses of LAR are commonly used in clinical practice. This study aimed to evaluate the real-world utilization of LAR and preceding IR use at the prescription and patient levels. Methods We used an administrative claims database (2009-2018) containing privately insured enrollees. We calculated the normalized LAR dose from pharmacy claims and the initial mean IR daily dose at the prescription level. At the patient level, we conducted a retrospective cohort study that included patients continuously enrolled with ≥1 pharmacy claim of LAR and evaluated the frequency and the clinical reason for dose escalation of LAR. The definition of the above-label maximum dose of LAR was ≥30 mg/4 weeks. Results Nineteen percent of LAR prescriptions had an above-label maximum dose. Only 7% of LAR prescriptions had preceding IR use. There were 386 patients with NETs or CS vs. 570 with an unknown diagnosis. Comparing patients with NETs or CS to those with an unknown diagnosis, 22.3% vs. 11.0 % experienced dose escalations and 29.0% vs. 26.6% had IR use before dose escalation, respectively. LAR dose escalation occurred in 50.9% vs. 39.2% for symptom control, 12.3% vs. 7.1% for tumor progression control, and 16.6% vs. 6.0% for both reasons in NETs/CS and unknown groups, respectively. Conclusion Octreotide LAR dosing above the label-maximum dose is common and IR rescue dosing appears to be underutilized. [ABSTRACT FROM AUTHOR]

Thymic atypical carcinoids are extremely rare tumors and have a poor prognosis owing to their aggressive clinical course. The efficacy of treatments other than complete surgical resection is unclear. We herein report a postoperative recurrent case of thymic atypical carcinoid treated with everolimus and octreotide long‐acting repeatable (LAR). A 75‐year‐old woman was admitted to our department because a nodule was detected in the right lobe of thymus by annual computed tomography. The patient underwent thymothymectomy, and a diagnosis of thymic atypical carcinoid was made. One year and seven months after surgery, she developed multiple metastases in the lung, hilar and mediastinal lymph nodes, liver, and bone. Everolimus 10 mg/day was administered; however, the dose had to be reduced to 5 mg/day due to grade 3 hyperglycemia and grade 3 interstitial lung disease. Metastatic lesions other than liver metastasis markedly responded to everolimus, although the liver metastases gradually progressed. Three years and six months after surgery, she was administered octreotide LAR 30 mg per month in combination with everolimus. She has maintained stable disease for 8 months after the application of this combination therapy. [ABSTRACT FROM AUTHOR]

Background: Chylothorax following congenital heart surgery is a potentially serious complication that requires early diagnosis and treatment. The aim of this study is to review our experience with the treatment of chylothorax occurring in the early period after congenital heart surgery. Materials and Methods: The records of patients who developed postoperative chylothorax among 1215 patients who underwent surgery for congenital heart disease in our hospital between March 2017 and February 2023 were retrospectively reviewed. Results: Seventeen patients, 11 of whom were male, who developed postoperative chylothorax were included in the study. The median age was 7.5 months, and the median body weight was 6.4 kilograms. Surgical procedures were aortic coarctation repair (five), Glenn operation (four), Tetralogy of Fallot repair (two), Fontan operation (one), atrioventricular canal defect repair (one), ventricular septal defect closure (one), vascular ring repair (one), patent ductus arteriosus ligation (one), and right modified Blalock-Taussig shunt in one patient. The median amount of lymphatic drainage was 4.6 ml/kg/day (2.3 to 8.1 ml/kg/day) and the median lymphatic drainage time was 16.5 days (5 to 38 days). After the chylous fluid drained, total parenteral nutrition and enteral medium-chain triglyceride diet were given. Octreotide was used additionally in 82.4% of the patients. After the chylous fluid drainage stopped, the patients were given a medium chain triglyceride diet for 6 weeks. One patient died due to sepsis. Conclusions: Chylothorax is a complication that causes morbidity after cardiac surgery. Morbidity can be reduced if a correct algorithm determined by the clinic is followed. [ABSTRACT FROM AUTHOR]

Context: Cabergoline (CAB) is an off-label medical therapy for acromegaly, overshadowed by first-generation somatostatin receptor ligands, eg, octreotide (OCT). Objective: This was a head-to-head comparison between OCT and CAB in inhibiting growth hormone (GH) secretion in primary cultures of GH and GH/prolactin (PRL)-secreting tumors; we also investigated the role of somatostatin (SST) and dopamine type 2 (D2R) receptor expression. Methods: We evaluated the antisecretory effect of OCT and CAB, together with receptor mRNA expression, in 23 tumor cultures obtained from acromegaly patients referred to the Erasmus Medical Center (Rotterdam, The Netherlands). GH concentrations in cell culture media were determined after 72-hour OCT and CAB treatment (10 nM). Results: OCT showed a slightly higher efficacy compared with CAB (GH decrease −39.5% vs −32.5%, P=0.079). The effect of the 2 drugs was superimposable in GH/PRL co-secreting tumors (−42.1% vs −44.8%), where SST1 and D2R had a higher expression compared with the pure GH secreting tumors (P=0.020 and P=0.026). OCT was more effective than CAB in 8/23 cultures, while CAB was more effective than OCT in 3/23 (CAB+ group). In CAB+ tumors, SST1 expression was higher compared with the other groups (P=0.034). At receiver operating characteristic (ROC) curve analysis, SST1 and D2R discriminated between GH and GH/PRL co-secretion (AUC 0.856, P=0.013; AUC 0.822, P=0.024). SST1 was the best predictor of CAB response (≥50% GH reduction, AUC 0.913, P=0.006; 80% sensitivity, 94% specificity). Conclusion: OCT is 5% to 10% more effective than CAB in vitro. SST1 mRNA expression can represent a reliable marker of GH/PRL co-secreting tumors showing a preferential response to CAB treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is an efficient treatment for patients suffering from metastasized neuroendocrine tumours. Nevertheless, suboptimal effects have been observed in the majority of patients. Hence, strategies to improve 177Lu-DOTATATE efficacy are desirable. Lu-177 induces oxidative stress, eventually leading to tumour cell death. Inhibition of the antioxidant defence mechanisms, using buthionine sulfoximine (BSO), represents an attractive strategy to increase 177Lu-DOTATATE efficacy. In cells and an animal model, the combination of 177Lu-DOTATATE and BSO was more effective than 177Lu-DOTATATE alone. In addition, it did not result in additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE. Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the radiosensitizing potential and the safety of depleting glutathione (GSH) levels using buthionine sulfoximine (BSO) during 177Lu-DOTATATE therapy were assessed in vitro and in vivo using a xenograft mouse model. In vitro, the combination resulted in a synergistic effect in cell lines exhibiting a BSO-mediated GSH decrease. In vivo, BSO neither influenced 177Lu-DOTATATE biodistribution nor induced liver, kidney or bone marrow toxicity. In terms of efficacy, the combination resulted in reduced tumour growth and metabolic activity. Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased 177Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE. [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]

Background: Despite the increased incidence of cancer, more effective cancer drugs are being developed and cancer patient survival expectancy has been prolonged. Here, we discuss the contribution of primary healthcare clinics to managing the side effects of cytotoxic chemotherapy and provide a compilation of what is currently being used in this field. Current Concepts: Loperamide is recommended for active use when diarrhea occurs. In severe cases, octreotide can help control diarrhea by reducing small bowel fluid secretion. Mouthwash mixed with salt and sodium bicarbonate is helpful for controlling mucositis, and transdermal fentanyl patches can be used for severe pain. Limited evidence suggests that pilocarpine may be helpful for xerostomia. Neurokinin-1 receptor antagonists, serotonin receptor antagonists, glucocorticoids, metoclopramide, and olanzapine are used for nausea and vomiting. Opioid-related constipation can be relieved without counteracting the analgesic effect of opioids via peripherally acting μ-opioid receptor antagonists. Granulocyte colony-stimulating factor is recommended to treat neutropenic fever. In cases with neutropenia but no fever, the decision to use it should be based on the patient's condition. Minoxidil can be used for hair loss, and scalp cooling can also be considered, but its practical applications are limited. Topical steroid ointments are used to treat hand-foot syndrome. Selective serotonin re uptake inhibitors are recommended for depression in cancer patients because they have little interaction with other drugs and are well tolerated. Discussion and Conclusion: Due to an increased cancer patient management burden and limited medical resources, primary healthcare practitioners should know these management strategies for cancer patients receiving cytotoxic chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to elucidate the role of quantitative tumor burden based on PET/CT of somatostatin receptors in well-differentiated neuroendocrine tumors (NETs). Methods: This study enrolled patients with [68 Ga]Ga-DOTA-NOC PET/CT-positive advanced NETs who did not receive medical treatment prior to PET/CT. Tumor burden was calculated using methods based on the background threshold and relative fixed threshold values (30%, 40%, and 50%). The prognostic value of the measured tumor burden in reference to overall survival (OS) and progression-free survival (PFS) on treatment with octreotide long-acting repeatable (LAR) was assessed using Cox regression analysis, Harrell's C-index, and survival analysis. A classification and regression tree (CART) was used to determine the optimal threshold for tumor burden. Results: A total of 204 patients were included. Somatostatin receptor-expressing tumor volume (SRETV) and liver SRETV derived from a relative fixed threshold of 30% (SRETV30 and liver SRETV30) were statistically significantly associated with OS (C-index: 0.802 [95% confidence interval (CI), 0.658–0.946] and 0.806 [95% CI, 0.664–0.948], respectively). Extrahepatic tumor burden was not correlated with OS (hazard ratio: 0.617, 95% CI: 0.241–1.574, P = 0.312). Among 155 patients with non-functional NETs with a ki-67 index of ≤ 10%, those with a high SRETV30 (P = 0.016) or high liver SRETV30 (P = 0.014) showed statistically significantly worse PFS on treatment with octreotide LAR. Patients receiving a higher dose of octreotide LAR normalized by SRETV30 or liver SRETV30 (a normalized dose or a liver normalized dose) showed prolonged PFS on treatment with octreotide LAR and a prolonged OS. Conclusion: Quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT was correlated with OS and PFS in patients with non-functional NETs with a ki-67 index of ≤ 10% who received octreotide LAR. Calculating normalized and liver normalized doses may help in selecting the starting dose of octreotide LAR. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present work we investigated the clinical utility of Al[18F]F-NOTA-Octreotide (Al[18F]F-OC) in comparison to [68Ga]Ga-DOTA-TATE in patients diagnosed with neuroendocrine tumours. Our aim was to verify the recently published, promising results for Al[18F]F-NOTA-Octreotide in the Latin-American population. Al[18F]F-NOTA-Octreotide provided excellent image quality, detected NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE. PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine Tumors are rare cancers with limited therapeutic options. Functioning NETs could produce bioactive peptides leading to a specific syndrome that impacts on patients' quality of life and also on survival—F-NETs patients who are refractory to SSA respond to 177LU-PRRT with a benefit in terms of prognosis. Introduction: Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome. Patients and Methods: A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed. Results: Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2–63.2) median PFS was 33.0 months (95%CI: 27.1–48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1–94.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2–98.0) vs. 40.0% (95%CI: 6.6–73.4), respectively. A total of 233 adverse events were recorded. Grade 1–2 hematological toxicity was the most frequent. Conclusion: The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long-term durability of therapeutic response. Design: The study design is an OLE of a double-blind placebo-controlled (DPC) trial. Methods: Patients completing the 36-week DPC period on the study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/day OOC dose, with the option to titrate to 40 or 80 mg/ day. The OLE is ongoing; week 48 results are reported. Results: Forty patients were enrolled in the OLE, 20 each having received OOC or placebo, with 14 and 5 patients completing the DPC period as responders, respectively. Ninety percent of patients completing the DPC period on OOC and 70% of those completing on placebo completed 48 weeks of the OLE. Maintenance of response in the OLE (i.e. insulin-like growth factor I (IGF1) ≤ 1.0 x upper limit of normal (ULN)) was achieved by 92.6% of patients who responded to OOC during the DPC period. Mean IGF1 levels were maintained between the end of the DPC period (0.91 x ULN; 95% CI: 0.784, 1.045) and week 48 of the OLE (0.90 x ULN; 95% CI: 0.750, 1.044) for those completing the DPC period on OOC. OOC safety was consistent with previous findings, with no increased adverse events (AEs) associated with the higher dose and improved gastrointestinal tolerability observed over time. Conclusions: Patients with acromegaly maintained long-term biochemical response while receiving OOC, with no new AEs observed with prolonged OOC exposure. [ABSTRACT FROM AUTHOR]

Individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) have elevated plasma lipids as well as glucagon, although glucagon suppresses hepatic VLDL-triglyceride (TG) secretion. We hypothesize that the sensitivity to glucagon in hepatic lipid metabolism is impaired in MAFLD. We recruited 11 subjects with severe MAFLD (MAFLD+), 10 with mild MAFLD (MAFLD-), and 7 overweight control (CON) subjects. We performed a pancreatic clamp with a somatostatin analog (octreotide) to suppress endogenous hormone production, combined with infusion of low-dose glucagon (0.65 ng/kg/min, t = 0-270 min, LowGlucagon), followed by high-dose glucagon (1.5 ng/kg/min, t = 270-450 min, HighGlucagon). VLDL-TG and glucose tracers were used to evaluate VLDL-TG kinetics and endogenous glucose production (EGP). HighGlucagon suppressed VLDL-TG secretion compared with LowGlucagon. This suppression was markedly attenuated in MAFLD subjects compared with CON subjects (MAFLD+: 13% ± [SEM] 5%; MAFLD-: 10% ± 3%; CON: 36% ± 7%, P < 0.01), with no difference between MAFLD groups. VLDL-TG concentration and VLDL-TG oxidation rate increased between LowGlucagon and HighGlucagon in MAFLD+ subjects compared with CON subjects. EGP transiently increased during HighGlucagon without any difference between the three groups. Individuals with MAFLD have a reduced sensitivity to glucagon in the hepatic TG metabolism, which could contribute to the dyslipidemia seen in MAFLD patients. ClinicalTrials.gov: NCT04042142. [ABSTRACT FROM AUTHOR]

Carcinoid tumors are neuroendocrine tumors (NET) that secrete hormones and other substances into the circulation, causing shifts in hemodynamics and other unpleasant symptoms. This case report describes a case in which the patient had a midgut NET that metastasized to the liver, causing carcinoid syndrome. The patient underwent general anesthesia for an exploratory laparotomy, small bowel resection with anastomosis, mesenteric mass resection, and a right liver lobectomy. The patient had carcinoid syndrome and developed carcinoid crisis during the surgery. Octreotide and phenylephrine infusions and phenylephrine boluses were used during the procedure to stabilize hemodynamics. The pathophysiology of carcinoid tumors, carcinoid syndrome, carcinoid crisis, and carcinoid heart disease are reviewed and octreotide application in the setting of carcinoid syndrome and carcinoid crisis is also reviewed. Octreotide is a first-generation somatostatin analog that binds to somatostatin receptor 2 with high affinity, somatostatin receptor 3 and somatostatin receptor 5 with lower affinity, and suppresses the secretion of serotonin. Anesthesia recommendations are given for patients undergoing surgery with carcinoid syndrome. [ABSTRACT FROM AUTHOR]

Objective: Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).Data Sources: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception.Study Selection and Data Extraction: Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.Data Synthesis: We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty).Conclusions: Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS. [ABSTRACT FROM AUTHOR]

Chylothorax is the accumulation of lymphatic fluid in pleural space following traumatic injury to lymphatic vessels, systemic venous obstruction, dysfunction of the right ventricle, thrombosis of the duct, superior vena cava or subclavian vein, or postoperatively. A 2 ½-year-old male child operated for transposition of great arteries (TGA), tricuspid atresia (TA), and hypoplastic right ventricle 15 days ago developed chylothorax and left internal jugular vein thrombus. The child was initially managed conservatively with nutritional management, anticoagulation, and octreotide followed by interventional radiological management with lipoidol injection. Early suspicion and diagnosis are crucial. The management was difficult owing to a lack of proper guidelines. Further research is warranted. [ABSTRACT FROM AUTHOR]

Octreotide is a synthetic cyclic octapeptide analogue of somatostatin-14. It is mainly administered for the treatment of acromegaly, severe diarrhea, and neuroendocrine neoplasias. In this work, a hydrophilic interaction liquid chromatography (HILIC) method with fluorescence (FL) detection was developed and validated for the quantitation of octreotide in solutions for injection. Chromatographic separation was performed on an XBridge®-HILIC analytical column under isocratic elution with a short chromatographic run time of less than 10 min. The mobile phase consisted of ammonium bicarbonate 8.6 mM (pH 8.1)/acetonitrile 35/65 (v/v). The high sensitivity and selectivity of the fluorescence detection, with the excitation wavelength (λexcitation) set at 280 nm and the emission wavelength set at (λemission) 330 nm, enabled a simple sample preparation procedure that included only dilution steps. The calibration curve showed good linearity with a correlation coefficient greater than 0.998. The method was successfully applied to the analysis of commercially available octreotide injection forms.

PURPOSE Somatostatin analogs octreotide long-acting release (octLAR) and lanreotide are equally acceptable in National Comprehensive Cancer Network guidelines for neuroendocrine tumors (NETs). Lanreotide is more expensive and given by deep subcutaneous injection, whereas octLAR is given intramuscularly. We evaluated patient preference between these agents in terms of injection site pain. MATERIALS AND METHODS Randomized, single-blinded study. Patients with NETs received injections every 4 weeks. Arm 1: octLAR x 3, then lanreotide x 3; arm 2: reverse order. Self-reported injection site pain scores (range, 0-10) were obtained after each of the first three injections. Primary end point was comparison of mean pain scores over the first three injections. Secondary end points included patient-reported preference. RESULTS Fifty-one patients enrolled (26 in arm 1 and 25 arm 2), all evaluable for primary end point. No significant difference was identified in the mean pain score over the first three injections (2.4 ± 1.9 v 1.9 ± 1.5, P = .5). Thirty-four of 51 (67%) patients (15 in arm 1 and 19 in arm 2) completed post-therapy questionnaires and were evaluable for secondary end points. Seven patients (47%) in arm 1 and eight patients (42%) in arm 2 indicated no drug preference at the end of treatment. In the other 19 patients, more patients indicated mild or strong preference for octLAR over lanreotide. CONCLUSION We found minimal pain with octLAR and lanreotide and no significant pain score differences between the two. Patients indicating a drug preference trended toward favoring octLAR. [ABSTRACT FROM AUTHOR]

Purpose: Neuroendocrine tumors (NETs) negatively impact patients' quality of life. Octreotide long-acting release (LAR) and lanreotide depot are somatostatin analogs (SSAs) approved to treat NETs. The study objective was to explore SSA treatment experiences and preferences of patients with NETs.Methods: Qualitative interviews were conducted in US adults (≥ 21 years) with NETs who had ≥ 6 months' treatment with each SSA and transitioned from octreotide LAR to lanreotide depot within the previous year. Participants were asked open-ended questions about their experiences with octreotide LAR and lanreotide depot, treatment preferences, and SSA treatment attributes.Results: Twenty participants (mean age: 58 years; 90% female; 85% white) completed interviews. The most common reasons for treatment transition were doctor recommendation (70%), treatment not working as expected (55%), and injection type preference (45%). Participants reported 34 unique favorable attributes of SSA treatment and 82 unique unfavorable attributes. Symptom control was the most frequently reported favorable attribute (associated with octreotide LAR by 60% of participants and lanreotide depot by 65%). Painful injection (65%) was most frequently cited unfavorable attribute for octreotide LAR and injection experience dependent on administrator (35%) for lanreotide depot. The three SSA treatment attributes rated as most important were side effects, symptom control, and ability to stabilize tumor.Conclusion: Our qualitative data provide valuable insight into the treatment attributes that patients with NETs consider important when making SSA treatment decisions. Factors related to injection administration, side effects, and symptom control are important to patients and should be included in patient-provider communications in clinical contexts. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication for patients with neuroendocrine tumors (NET). Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting the use of perioperative octreotide to prevent CC. The aim of our meta-analysis was to evaluate the existing evidence characterizing CC and the efficacy of prophylactic octreotide. We found that CC occurs frequently in patients having midgut NETs surgery, specifically those with NET liver metastasis, and is associated with worse postoperative outcomes. Our findings did not show a decreased risk in CC with prophylactic octreotide and questioned the advantage of routine prophylactic octreotide. Background: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide. Methods: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000–2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models. Results: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06–0.36]). Liver metastasis (odds ratio 2.85 [1.49–5.47]) and gender (male 0.58 [0.34–0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03–4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32–1.66]). Notably, there was no standard prophylactic octreotide strategy used. Conclusions: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC. [ABSTRACT FROM AUTHOR]

The article describes the case of a 14-year-old previously healthy male with acute hematemesis from varices. Topics discussed include hematemesis as the presenting symptom of a wandering spleen (WS), development of varices from sinistral portal hypertension, and variceal hemorrhage that required emergent resuscitation and splenectomy.

Background: Octreotide has been used to control bleeding episodes with variceal origin in the pediatric population. To date, there is no clear evidence of octreotide use for non-variceal bleeding in clinical trials. Objectives: We aimed to assess the octreotide efficacy as an add-on therapy to the conventional regimen of proton pump inhibitors for controlling upper non-variceal gastrointestinal (GI) bleeding in the pediatric population. Methods: This prospective randomized controlled clinical trial was performed on pediatric patients aged 1 -15 years and diagnosed with acute non-variceal upper GI bleeding. The participants were allocated to receive octreotide or placebo and pantoprazole con-comitantly. The study was conducted in Mofid Children's Hospital, Tehran, Iran, during February 2019- December 2019. Patients with hepatic failure, liver stigma, and coagulopathy due to thrombocytopenia were excluded. Demographic, clinical, and preclinical data were recorded in prepared sheets. All the patients were followed until therapy discontinuation. P-value < 0.05 was considered significant. Results: Forty-three patients with a mean age of 4.98 ± 3.79 years and confirmed non-variceal upper GI bleeding were included in the present study. Most patients had no specific etiology for their bleeding episodes. Patients in the intervention and control groups received pantoprazole in comparable doses. No differences were observed between the two groups in terms of baseline hemoglobin values (P = 0.08), while final hemoglobin values were significantly higher in the intervention group (P = 0.014). The bleeding duration was not significantly different between the two groups (P = 0.99). Moreover, none of the cases showed adverse drug reactions due to octreotide infusion. Conclusions: Our study demonstrated that octreotide did not alter bleeding duration or need for blood transfusion. However, positive results were observed for hemoglobin, affecting blood loss volume. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aim to evaluate the efficacy and safety of 225AC-DOTATATE targeted alpha therapy in advanced-stage paragangliomas (PGLs). Methods: Nine (6 males and 3 females) consecutive patients with histologically proven PGLs were treated with 225Ac-DOTATATE targeted alpha therapy (TAT) and concomitant radiosensitizer, capecitabine, at 8-weekly intervals up to a cumulative activity of ~ 74 MBq. The primary endpoint included evaluating therapy response and disease control rate (DCR) using the RECIST 1.1 criteria. Additional secondary endpoints comprised clinical response assessment using EORTC QLQ-H&N35 questionnaire, Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group performance status (ECOG), analgesic score (AS), dose alterations of anti-hypertensive drugs (anti-HTN), and the safety and side-effect profile evaluation as per CTCAE criteria version 5.0. Results: Following 225Ac-DOTATATE treatment, morphological response revealed partial response in 50%, stable disease in 37.5%, and disease progression in 12.5%, with a DCR of 87.5%. Similarly, the symptomatic response was remarkable, and anti-HTN drugs were stopped in 25% and reduced in 37.5%. Another significant finding in our study revealed a morphologic DCR of 66.6% (2/3) in patients who failed previous lutetium-177 peptide receptor radionuclide therapy (177Lu-PRRT). Regarding the KPS, ECOG, and AS performance scores, a notable improvement was observed post-225Ac-DOTATATE treatment. The QLQ-H&N35 symptom scores evaluated in seven H&N PGL patients showed significant improvement in all aspects. No improvement in sexual function was noted (P = 0.3559). Despite the significant reduction in the analgesic score post-treatment (P = 0.0031), the QLQ-H&N35 revealed only marginal significance concerning the intake of pain killers (P = 0.1723). No grade III/IV hematological, renal, and hepatological toxicities were noted. Conclusion: The evidence from this study suggests 225Ac-DOTATATE therapy is effective and safe in the treatment of advanced-stage PGLs and also reports a clear benefit even in patient's refractory to the previous 177Lu-PRRT. [ABSTRACT FROM AUTHOR]

Background: Lutetium-177-labeled somatostatin analogue, [177Lu]Lu-DOTA-TATE is most commonly used across the world for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs). The primary objective of this study was to estimate the absorbed doses in organs and tumor lesions in NET patients treated with indigenously produced "direct-route" [177Lu]Lu-labeled DOTA-TATE and impact of multiple treatment cycles on absorbed doses, and compare with those treated with no-carrier-added [177Lu]Lu-labeled DOTA-TATE. Materials and Methods: Sixty patients of NET were enrolled in this prospective study. These patients received up to 6 cycles of PRRT with [177Lu]Lu-DOTA-TATE (total 232 cycles) at 10- to 12-week intervals between the two successive therapy cycles. The patients were administered 5.55-7.4 GBq (150-200 mCi) of [177Lu]Lu-DOTA-TATE in 100 mL of normal saline over a period of 30 min. Postadministration whole-body planar scintigraphy were acquired at five time points 0.5 (prevoid), 2, 12, 24, and 72 h (postvoid) and one SPECT scan at 24 h (postvoid). Number of disintegrations was determined from time-activity curves generated by drawing regions of interests (ROIs) on the images. Tumor masses were derived from computed tomography (CT) data. The absorbed doses for normal organs and tumor lesions were calculated using OLINDA 2.1.1 software. The same were also estimated in a group of 22 patients who were treated with no-carrier-added [177Lu]Lu-labeled DOTA-TATE. Results: The mean absorbed organ doses (mean ± SD) in Gy/GBq received by normal organs were as follows: kidneys 0.64 ± 0.21, liver 0.10 ± 0.05, spleen 0.88 ± 0.35, bone marrow 0.04 ± 0.02, urinary bladder 0.26 ± 0.06, heart wall 0.04 ± 0.02, and whole-body 0.06 ± 0.02. Tumor dosimetry was performed in a total of 410 tumor lesions, the mean absorbed dose to the tumor lesions was 4.79 ± 4.23 Gy/GBq. Large variations were observed in absorbed doses received by these lesions (range: 0.15-21.26 Gy/GBq). With no-carrier-added [177Lu]Lu-DOTA-TATE, the mean absorbed organ doses (mean ± SD) in Gy/GBq received by normal organs were as follows: kidneys 0.76 ± 0.16, liver 0.10 ± 0.05, spleen 1.14 ± 0.31, bone marrow 0.05 ± 0.02, urinary bladder 0.27 ± 0.05, heart wall 0.06 ± 0.02, whole-body 0.07 ± 0.02, and tumor dose 5.87 ± 5.74. Conclusions: There was no statistically significant difference in the dosimetry data of patients treated with no-carrier-added (indirect route) [177Lu]Lu-labeled DOTA-TATE and the dosimetry data of patients treated with [177Lu]Lu-labeled with DOTA-TATE formulated using 177Lu produced through "Direct-route" and were comparable with the data reported. [ABSTRACT FROM AUTHOR]

Objective: We used network meta‐analysis (NMA) to characterize the relative effectiveness and harms of acute treatment options for cluster headache. Background: There are few evidence‐based acute treatments available for cluster headache. As most treatments were compared only against placebos in clinical trials, few head‐to‐head comparisons of treatments are available. Methods: An a priori registered scoping review was performed to identify randomized controlled trials evaluating treatments in adult patients (>18 years old) with cluster headache per accepted diagnostic criteria. Bayesian NMAs were performed to compare treatments in terms of headache relief at 15 or 30 min, and also the occurrence of adverse events. We report odds ratios (ORs) of relative treatment effects along with corresponding 95% credible intervals (CrIs), as well as measures of treatment ranking. Results: A total of 13 randomized controlled trials informed NMAs. We found high flow oxygen to be the most effective therapy for headache response at 15 and 30 min (OR 9.0, 95% CrI 5.3 to 15.9 vs. placebo), with injectable sumatriptan demonstrating the next highest effect (OR 6.4, 95% CrI 3.75 to 11.1 vs. placebo). High flow oxygen was also more effective than low flow oxygen (OR 2.55, 95% CrI 1.13 to 5.8), nasal spray zolmitriptan (OR 3.75, 95% CrI 1.72 to 8.4), octreotide (OR 4.5, 95% CrI 1.64 to 12.5), and non‐invasive vagal nerve stimulation (nVNS; OR 5.2, 95% CrI 2.29 to 11.9). Sumatriptan injectable was also effective for headache relief and was found to be better than nasal spray zolmitriptan (OR 2.67, 95% CrI 1.21 to 5.9), octreotide (OR 3.20, 95% CrI 1.17 to 8.8), and nVNS (OR 3.69, 95% CrI 1.63 to 8.4). Octreotide (OR 4.1, 95% CrI 1.71 to 10.5) and sumatriptan (OR 2.40, 95% CrI 1.39 to 4.2) were associated with greater risk of adverse events compared to placebo, while other treatments did not demonstrate increased risk. When focusing on patients with episodic cluster headache, nVNS was significantly better than placebo (OR 4.9, 95% CrI 1.89 to 14.1). Conclusions: Our findings suggest that high flow oxygen is more efficacious when compared to low flow oxygen for headache relief. When low flow oxygen fails in patients who can tolerate oxygen, increased flow rates should be tried. Additionally, high flow oxygen is likely more effective than zolmitriptan nasal spray, nVNS, and octreotide. Sumatriptan injectable is more likely to be effective when compared to zolmitriptan nasal spray, octreotide, and nVNS. [ABSTRACT FROM AUTHOR]