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A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy.
Murphy, CF, Stratford, N, Docherty, NG, Moran, B, Elliott, JA, Healy, ML, McMorrow, JP, Ravi, N, Goldstone, AP, Reynolds, JV, et al
The Journal of clinical endocrinology and metabolism. 2021;(1):e204-e216
Abstract
BACKGROUND Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. METHODS This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. RESULTS Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). CONCLUSION The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.
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Prophylactic octreotide does not reduce the incidence of postoperative chylothorax following lobectomy: Results from a retrospective study.
Zhang, C, Zhang, H, Wu, W, Liu, D, Yang, D, Zhang, M, Lu, C
Medicine. 2019;(29):e16599
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Abstract
Chylothorax after lobectomy is common, lacking reliable preventive measures. Octreotide is widely used for treatment of chyle leakage, but its role in preventing chylothorax has not been estimated. The aim of this study was to evaluate whether prophylactic octreotide could reduce the incidence of postoperative chylothorax.Patients who underwent lobectomy for lung cancer from January 2016 to September 2018 were retrospectively reviewed. The cases in prophylactic group received octreotide 1 day before the surgery until removal of chest tubes, while those in the control group did not use it unless the diagnosis of chylothorax.A total of 379 patients were enrolled, with 190 patients in control and 189 cases in prophylactic group. Octreotide was well tolerated in patients who received this agent. No 30-day mortality was indicated. Seven cases in control (3.7%, 7/190) and 3 cases in prophylactic group (1.6%, 3/189) with chylothorax were observed (P = .337). The patients in prophylactic group showed shorter duration of chest drainage ([3.6 ± 1.6] days vs [4.1 ± 2.0] days, P = .006) and reduced drainage volume ([441.8 ± 271.1] mL vs [638.7 ± 463.3] mL, P < .001). In addition, they showed similar stations and numbers of dissected lymph nodes, surgery-related complications, and postoperative hospital stay. Besides, 11 (5.8%, 11/190) patients in control and 6 (3.2%, 6/189) cases in the prophylactic group were readmitted for pleural effusion needing reinsertion of chest tubes (P = .321). Moreover, multivariable logistic analysis showed that induction therapy (odds ratio [OR] =12.03; 95% confidence interval [CI] 3.15-46.03, P < .001) was a risk factor, while high-volume experience of the surgeon (OR = 0.23; 95% CI 0.06-0.97, P = .045) was a preventive factor of surgery-related chylothorax. Additionally, prophylactic octreotide (OR = 0.18; 95% CI 0.11-0.28, P < .001) and perioperative low-fat diet (OR = 0.46; 95% CI 0.29-0.73, P = .001) were negatively associated with the drainage volume of pleural effusion. Furthermore, high-volume experience of the surgeon (OR = 6.03; 95% CI 1.30-27.85, P = .021) and induction therapy (OR = 8.87; 95% CI 2.97-26.48, P < .001) were risk factors of unplanned readmission.Prophylactic octreotide does not reduce the incidence of postoperative chylothorax or unplanned readmission following anatomic lobectomy. The routine application of octreotide should not be recommended. High-quality trials are required to validate these findings.
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Surgical chylothorax in neonates: management and outcomes.
Costa, KM, Saxena, AK
World journal of pediatrics : WJP. 2018;(2):110-115
Abstract
BACKGROUND Postoperative chylothorax occurs due to trauma to lymphatic vessels and can occur after any thoracic procedure. This study reviewed recent literature to evaluate the management and outcomes of surgical chylothorax in neonates. METHODS PubMed database was searched for articles in English, Portuguese and Spanish from 2000 to 2016. Data were collected for surgery, chylothorax management, complications, mortality and length of hospital stay (LOS). RESULTS Twenty studies offered 107 neonates: congenital diaphragmatic hernia (CDH) (n = 76, 71%), cardiac malformations (n = 25, 23.4%), esophageal atresia (n = 5, 4.7%) and CDH + extralobar sequestration (n = 1, 0.9%). Medium-chain triglycerides (MCT) was the initial treatment in 52 neonates (48.6%), prednisolone + MCT in one (0.9%), total parenteral nutrition in 51 patients (47.7%), and three patients (2.8%) did not require any treatment. Octreotide and somatostatin were used as second or third line treatment in 25 neonates (23.4%), and 15 neonates (14%) underwent 17 surgeries, including thoracic duct ligation (TDL) (n = 9); pleurodesis (n = 3) (2 patients required TDL); TDL + pleurodesis (n = 2), and TDL + placement of hemostat (n = 1). Complications due to the chylothorax were reported in 27 neonates (25.2%): hypoalbuminemia + hyponatremia (n = 18), hypoalbuminemia (n = 4), hypoalbuminemia with cutaneous flushing as colateral effect of somatostatin (n = 1), loose stool after somatostatin use (n = 1), pneumonia (n = 1), congestive heart failure + hypernatremia (n = 1), and hyponatremia (n = 1). There were 21 deaths (19.6%) and median LOS was 53.4 days (30-93.1 days). CONCLUSIONS Conservative management is appropriate as initial treatment for neonatal postsurgical chylothorax. Octreotide and somatostatin are safe in neonates and surgical approach should be considered in prolonged leaks.
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A Proposed Classification System and Therapeutic Strategy for Chyle Leak After Laparoscopic Living-Donor Nephrectomy: A Single-Center Experience and Review of the Literature.
Ng, ZQ, He, B
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2018;(2):143-149
Abstract
OBJECTIVES Chyle leak or chylous ascites remains a rare complication after laparoscopic living-donor nephrectomy. Its cause and management have not been well elucidated in the literature. Thus, the aim of this study was to review the incidence of chyle leak/chylous ascites after laparoscopic living-donor nephrectomy in our institute and in the literature to propose a classification system with its associated treatment strategy. MATERILAS AND METHODS In this retrospective review of laparoscopic living-donor nephrectomy patients from January 2005 to April 2016, we identified patients with chyle leak/chylous ascites along with the care performed. A proposed classification system based on our experience and literature is described. RESULTS Chylous leak developed in 4 donors (2.25%). Of the 4 donors, 3 were treated nonoperatively with diet modification and subcutaneous octreotide injection. One patient required surgical intervention after not responding to second-line therapy with total parenteral nutrition. CONCLUSIONS Chyle leak/chylous ascites after laparoscopic living-donor nephrectomy is rare, but a delayed diagnosis may lead to morbidity secondary to malnutrition and immunosuppression. Meticulous surgical dissection is essential to seal the lymphatic tubes during laparoscopic living-donor nephrectomy. The proposed classification system provides a practical and tailored guide to management based on the drainage volume of chyle leak and a guide to the earlier identification of refractory cases.
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Octreotide Is Ineffective in Treating Tumor-Induced Osteomalacia: Results of a Short-Term Therapy.
Ovejero, D, El-Maouche, D, Brillante, BA, Khosravi, A, Gafni, RI, Collins, MT
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017;(8):1667-1671
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Abstract
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which unregulated hypersecretion of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMT) causes renal phosphate wasting, hypophosphatemia, and osteomalacia. The resulting mineral homeostasis abnormalities and skeletal manifestations can be reversed with surgical resection of the tumor. Unfortunately, PMTs are often difficult to locate, and medical treatment with oral phosphate and vitamin D analogues is either insufficient to manage the disease or not tolerated. Octreotide has been proposed as a potential treatment for TIO due to the presence of somatostatin receptors (SSTR) on PMTs; however, the role of somatostatin signaling in PMTs and the efficacy of treatment of TIOs with somatostatin analogues is not clear. In an effort to evaluate the efficacy of octreotide therapy in TIO, five subjects with TIO were treated with octreotide for 3 days. Blood intact FGF23, phosphate, and 1,25(OH)2 D3 , and tubular reabsorption of phosphate (TRP) were measured at frequent time points during treatment. Octreotide's effects were assessed by comparing group means of the biochemical parameters at each time-point to mean baseline values. There were no significant changes in blood phosphate, FGF23, 1,25(OH)2 D3 , or TRP during octreotide treatment, consistent with a lack of efficacy of octreotide in treating TIO. © 2017 American Society for Bone and Mineral Research.
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Head-to-Head Comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: A Prospective Study of 59 Patients with Neuroendocrine Tumors.
Johnbeck, CB, Knigge, U, Loft, A, Berthelsen, AK, Mortensen, J, Oturai, P, Langer, SW, Elema, DR, Kjaer, A
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017;(3):451-457
Abstract
Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up, and treatment planning of neuroendocrine tumor (NET). PET-based tracers using 68Ga as the radioisotope have in most centers replaced SPECT-based tracers as the gold standard. 64Cu-DOTATATE is a new PET tracer that has been shown to be far superior to the SPECT tracer 111In-diethylenetriaminepentaacetic acid-octreotide. Because of the advantages of 64Cu over 68Ga, we hypothesized that the tracer has a higher sensitivity than 68Ga-based tracers. To test this hypothesis, we compared on a head-to-head basis the diagnostic performance of 64Cu-DOTATATE with that of 68Ga-DOTATOC in NET patients. Methods: Fifty-nine NET patients were scanned with both 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT and compared on a head-to-head basis. Discordant lesions were verified during at least 30 mo of follow-up. Results: A total of 701 lesions were concordantly detected on both 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT scans, whereas an additional 68 lesions were found by only one of the scans. 64Cu-DOTATATE showed 42 lesions not found on 68Ga-DOTATOC, of which 33 were found to be true-positive on follow-up. 68Ga-DOTATOC showed 26 lesions not found on 64Cu-DOTATATE, of which 7 were found to be true-positive on follow-up. False-positives were mainly lymph node lesions. Accordingly, 83% of the additional true lesions found on only one of the scans were found by 64Cu-DOTATATE. On a patient-basis, additional true lesions were found by 64Cu-DOTATATE and 68Ga-DOTATOC in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusion:64Cu-DOTATATE has advantages over 68Ga-DOTATOC in the detection of lesions in NET patients. Although patient-based sensitivity was the same for 64Cu-DOTATATE and 68Ga-DOTATOC in this cohort, significantly more lesions were detected by 64Cu-DOTATATE. Furthermore, the shelf life of more than 24 h and the scanning window of at least 3 h make 64Cu-DOTATATE favorable and easy to use in the clinical setting.
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Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly.
Strasburger, CJ, Karavitaki, N, Störmann, S, Trainer, PJ, Kreitschmann-Andermahr, I, Droste, M, Korbonits, M, Feldmann, B, Zopf, K, Sanderson, VF, et al
European journal of endocrinology. 2016;(3):355-62
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BACKGROUND Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. METHODS The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. RESULTS In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be 'avoiding injections' and 'better symptom control'. CONCLUSION Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.
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Multicentre, open-label, randomised, parallel-group, superiority study to compare the efficacy of octreotide therapy 40 mg monthly versus standard of care in patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias: a protocol of the OCEAN trial.
Grooteman, KV, van Geenen, EJ, Drenth, JP
BMJ open. 2016;(9):e011442
Abstract
INTRODUCTION Gastrointestinal angiodysplasias are an important cause of difficult-to-manage bleeding, especially in older patients. Endoscopic coagulation of angiodysplasias is the mainstay of treatment, but may be difficult for small bowel angiodysplasias because of the inability to reach them for endoscopic intervention. Some patients are red blood cell (RBC) transfusion dependent due to frequent rebleeding despite endoscopic treatment. In small cohort studies, octreotide appears to decrease the number of bleeding episodes in patients with RBC transfusion dependency due to gastrointestinal angiodysplasias. This trial will assess the efficacy of octreotide in decreasing the need for RBC transfusions and parenteral iron in patients with anaemia due to gastrointestinal bleeding of small bowel angiodysplasias despite endoscopic intervention. STUDY DESIGN Randomised controlled, superiority, open-label multicentre trial. PARTICIPANTS 62 patients will be included with refractory anaemia due to small bowel angiodysplasias, who are RBC transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation. INTERVENTION Patients will be randomly assigned (1:1) to standard care or 40 mg long-acting octreotide once every 4 weeks for 52 weeks, in addition to standard care. The follow-up period is 8 weeks. MAIN OUTCOME MEASURES The primary outcome is the difference in the number of blood and iron infusions between the year prior to inclusion and the treatment period of 1 year. Important secondary outcomes are the per cent change in the number of rebleeds from baseline to end point, adverse events and quality of life. ETHICS AND DISSEMINATION The trial received ethical approval from the Central Committee on Research Involving Human Subjects and from the local accredited Medical Research Ethics Committee of the region Arnhem-Nijmegen, the Netherlands (reference number: 2014-1433). Results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER NCT02384122; Pre-results.
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Congenital Chylothorax: A Unique Presentation of Nonimmune Hydrops Fetalis in a Preterm Infant.
Brock, WW, Bradshaw, WT
Advances in neonatal care : official journal of the National Association of Neonatal Nurses. 2016;(2):114-23
Abstract
BACKGROUND Nonimmune hydrops fetalis secondary to congenital chylothorax (CC) is a rare disease process associated with high morbidity and mortality related to abnormal formation of the lymphatic system and disrupted management of fetal fluid. Hydrops fetalis is typically diagnosed prenatally by the presence of pleural effusions or other fluid collection on ultrasonography. Congenital chylothorax is diagnosed when the analysis of pleural fluid is deemed chylous. Neonatal presentation is often respiratory distress secondary to lung compression or pulmonary hypoplasia. Management ranges from supportive medical management such as high-frequency ventilation, chest drainage, and nutrition support, to controversial therapies such as octreotide administration and chemical pleurodesis, to surgical interventions such as thoracic duct ligation and mechanical pleurodesis. PURPOSE To discuss a range of management techniques and supportive therapies for hydrops fetalis and CC. METHODS/SEARCH STRATEGY PubMed and CINAHL were searched using the terms "hydrops fetalis," "congenital," "chylothorax," "neonate," and "preterm." Twenty-two English language articles published within the last five years were identified and included to determine the current body of evidence surrounding treatment options for hydrops fetalis and CC. CASE FINDINGS In this case, a preterm male infant presented at birth with prenatally known bilateral pleural effusions and ascites, later diagnosed as nonimmune hydrops fetalis secondary to CC. A combination of supportive medical management, octreotide therapy, and surgical intervention effectively resolved this infant's chylothorax and hydrops. IMPLICATIONS FOR PRACTICE Antenatal intervention may be appropriate for some infants, otherwise supportive medical management including respiratory and nutrition therapies should be prioritized for infants born with hydrops fetalis and CC. IMPLICATIONS FOR RESEARCH Nonimmune hydrops fetalis secondary to CC presents a complex challenge for neonatal providers, as no definitive treatment strategy currently exists. Further research is needed to determine the safety and efficacy of controversial therapies including octreotide.
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Chyle Fistula After Neck Dissection: An 8-Year, Single-Center, Prospective Study of Incidence, Clinical Features, and Treatment.
Ahn, D, Sohn, JH, Jeong, JY
Annals of surgical oncology. 2015;:S1000-6
Abstract
BACKGROUND Chyle fistula is a relatively rare complication of neck dissection, and there is a lack of consensus regarding its incidence, risk factors, and management. METHODS Between 2007 and 2014, a total of 472 cases of neck dissection involving the level IV compartment were included in the study. The incidence, risk factors, and clinical course of chyle fistula were investigated, as well as the outcomes of conventional management and the use of octreotide injection in high-output chyle fistula. RESULTS The overall incidence of chyle fistula was 4.7 % (22/472), with an incidence of 3.0 % and 6.2 % after right and left neck dissection, respectively. The presence of a metastatic lesion around the junction of the internal jugular vein and subclavian vein was the only factor significantly associated with the development of chyle fistula (approximately fourfold higher risk) in univariate and multivariate analyses. In 22 cases of chyle fistula, the mean total drainage volume was 3226 mL during a mean 15.4 days of drain placement. Total parental nutrition for the management of chyle fistula was required in 16 cases. Nine (40.9 %) of 22 cases experienced additional complications related to chyle fistula. Of the six high-output cases, four were managed with conservative methods plus octreotide injection, and three did not require surgery. CONCLUSIONS The incidence of chyle fistula after neck dissection was higher than expected, especially on the right side. Surgeons should pay greater attention to chyle fistula from preoperative evaluation to postoperative management.