-
World Journal of Gastrointestinal... Mar 2024Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, often diagnosed in an advanced stage when curative treatment is impossible and grueling...
BACKGROUND
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients' quality of life. Cardiovascular complications of GEP-NENs, primarily tricuspid and pulmonary valve disease, and right-sided heart failure, are the leading cause of death, even compared to metastatic disease.
CASE SUMMARY
We present a case of a 35-year-old patient with progressive dyspnea, back pain, polyneuropathic leg pain, and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases. During the initial presentation, serum biomarkers were not evaluated, and the patient received five cycles of doxorubicin, which he did not tolerate well, so he refused further therapy and was lost to follow-up. After 10 years, he presented to the emergency room with signs and symptoms of right-sided heart failure. Panneuroendocrine markers, serum chromogranin A, and urinary 5-hydroxyindoleacetic acid were extremely elevated (900 ng/mL and 2178 µmol/L), and transabdominal ultrasound confirmed hepatic metastases. Computed tomography (CT) showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis. Furthermore, an Octreoscan showed lesions in the heart, thoracic spine, duodenum, and ascendent colon. A standard transthoracic echocardiogram confirmed findings of carcinoid heart disease. The patient was not a candidate for valve replacement. He started octreotide acetate treatment, and the dose escalated to 80 mg IM monthly. Although biochemical response and symptomatic improvement were noted, the patient died.
CONCLUSION
Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors, usually with liver metastases, which manifests as right-sided heart valve dysfunction leading to right-sided heart failure. Carcinoid heart disease and tumor burden are major prognostic factors of poor survival. Therefore, they must be actively sought by available biochemical markers and imaging techniques. Moreover, imaging techniques aiding tumor detection and staging, somatostatin receptor positron emission tomography/CT, and CT or magnetic resonance imaging, should be performed at the time of diagnosis and in 3- to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery. Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered, while any delay can worsen right-sided ventricular failure.
PubMed: 38577438
DOI: 10.4251/wjgo.v16.i3.1076 -
Best Practice & Research. Clinical... Mar 2024Although predictors of response to first-generation somatostatin receptor ligands (fg-SRLs), and to a lesser extent to pasireotide, have been studied in acromegaly for... (Review)
Review
Although predictors of response to first-generation somatostatin receptor ligands (fg-SRLs), and to a lesser extent to pasireotide, have been studied in acromegaly for many years, their use is still not recommended in clinical guidelines. Is there insufficient evidence to use them? Numerous biomarkers including various clinical, functional, radiological and molecular markers have been identified. The first ones are applicable pre-surgery, while the molecular predictors are utilized for patients not cured after surgery. In this regard, factors predicting a good response to fg-SRLs are specifically: low basal GH, a low GH nadir in the acute octreotide test, T2 MRI hypointensity, a densely granulated pattern, high immunohistochemistry staining for somatostatin receptor 2 (SSTR2), and E-cadherin. However, there is still a lack of consensus regarding which of these biomarkers is more useful or how to integrate them into clinical practice. With classical statistical methods, it is complex to define reliable and generalizable cut-off values for a single biomarker. The potential solution to the limitations of traditional methods involves combining systems biology with artificial intelligence, which is currently providing answers to such long-standing questions that may eventually be finally included into the clinical guidelines and make personalized medicine a reality. The aim of this review is to describe the current knowledge of the main fg-SRLs and pasireotide response predictors, discuss their current usefulness, and point to future directions in the research of this field.
PubMed: 38575404
DOI: 10.1016/j.beem.2024.101893 -
European Journal of Nuclear Medicine... Apr 2024
PubMed: 38568449
DOI: 10.1007/s00259-024-06701-1 -
Oman Medical Journal Jan 2024To estimate the incidence of pituitary adenomas (PA) in adult Omani patients and describe its epidemiological, clinical, and radiological characteristics.
OBJECTIVES
To estimate the incidence of pituitary adenomas (PA) in adult Omani patients and describe its epidemiological, clinical, and radiological characteristics.
METHODS
In this longitudinal, descriptive study, we reviewed the records of all PA patients from January 2015 to January 2020 who presented at the endocrinology facilities at Sultan Qaboos University Hospital, Muscat.
RESULTS
The participants comprised of 112 Omani patients with PA. The incidence of PA among all adult patients at Sultan Qaboos University Hospital (inpatient and outpatient) over five years (2015-2020) was 0.23%. The cohort had a mean age of 41.0±15.0 years. Of the 112 patients included in this study, 79 (70.5%) were women. Nearly half (51; 45.5%) of adenomas were prolactinomas while 46 (41.1%) were non-functioning adenomas, and seven (6.3%) were growth hormone-secreting adenomas while six (5.4%) were adrenocorticotropic hormone secreting adenomas. Headache was present in 67 (59.8%) patients, followed by visual field defects (40; 35.7%), galactorrhea (26; 23.2%), and fatigue (19; 17.0%). The majority of women (45/79; 57.0%) presented with menstrual cycle abnormalities. Radiological appearances were nearly equally distributed between micro- and macroadenomas. Most cases (58/112; 52.0%) of PA were treated medically by cabergoline, octreotide, and replacement therapies such as hydrocortisone and thyroxin, 38 (33.9%) were treated surgically (mainly by trans-sphenoidal pituitary resection), and the remaining 10 (8.9%) cases were subjected to radiotherapy. Medical treatment combined with surgery was employed for 15 (13.4%) patients.
CONCLUSIONS
In our investigation, PA was primarily prevalent among Omani female patients, and the most common subtype of pituitary tumors was prolactinomas. The most common presentation symptom was headaches; most female patients had menstrual irregularities. Medical treatment was the primary approach for the applicable types of PAs, while surgery and radiotherapy were found to be secondary and tertiary treatment options, respectively.
PubMed: 38567166
DOI: 10.5001/omj.2024.44 -
ACG Case Reports Journal Apr 2024Chylous ascites is a rare manifestation of decompensated cirrhosis that is associated with increased short-term mortality. Exclusion of other etiologies must be...
Chylous ascites is a rare manifestation of decompensated cirrhosis that is associated with increased short-term mortality. Exclusion of other etiologies must be performed to allow for appropriate management, which itself can be a challenge in the setting of decompensated cirrhosis. We report a case of chylous ascites in a patient with decompensated cirrhosis that was successfully managed with octreotide before liver transplantation.
PubMed: 38560017
DOI: 10.14309/crj.0000000000001322 -
Clinical Nuclear Medicine Jun 2024Diffuse involvement of pancreatic neuroendocrine tumor (PNET) is a rare presentation. Here, we report a case of suspected autoimmune pancreatitis with 18 F-FDG and 18...
Diffuse involvement of pancreatic neuroendocrine tumor (PNET) is a rare presentation. Here, we report a case of suspected autoimmune pancreatitis with 18 F-FDG and 18 F-FAPI-42 PET/CT showing increased tracer uptake in the entire pancreas, which was eventually confirmed by biopsy pathologic analysis as diffuse PNET. 18 F-AlF-NOTA-octreotide PET/CT imaging showed heterogeneous tracer uptake in the entire pancreas.
Topics: Humans; Fluorodeoxyglucose F18; Neuroendocrine Tumors; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography
PubMed: 38557744
DOI: 10.1097/RLU.0000000000005225 -
Pediatric Blood & Cancer Jun 2024
Topics: Child; Female; Humans; Male; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms
PubMed: 38556730
DOI: 10.1002/pbc.30961 -
Nuclear Medicine and Biology 2024DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors...
Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [Cu]Cu-DOTATATE.
DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). In vivo measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity. A peptide called melittin, a main component of honeybee venom, has been shown to disrupt plasma membranes and increase the permeability of biological membranes. In this study, we assessed the feasibility of using melittin to facilitate the passage of [Cu]Cu-DOTATATE through the BBB and its binding to somatostatin receptors in the cortex. Evaluation included in vitro autoradiography on Long Evans rat brains to estimate the binding affinity of [Cu]Cu-DOTATATE to the somatostatin receptors in the cortex and an in vivo evaluation of [Cu]Cu-DOTATATE binding in NMRI mice after injection of melittin. This study found an in vitro B = 89 ± 4 nM and K = 4.5 ± 0.6 nM in the cortex, resulting in a theoretical binding potential (BP) calculated as B/K ≈ 20, which is believed suitable for in vivo brain PET imaging. However, the in vivo results showed no significant difference between the control and melittin injected mice, indicating that the honeybee venom failed to open the BBB. Additional experiments, potentially involving faster injection rates are required to verify that melittin can increase brain uptake of non-BBB permeable PET tracers. Furthermore, an evaluation of whether a venom with a narrow therapeutic range can be used for clinical purposes needs to be considered.
Topics: Animals; Receptors, Somatostatin; Melitten; Rats; Feasibility Studies; Positron-Emission Tomography; Organometallic Compounds; Blood-Brain Barrier; Male; Mice; Copper Radioisotopes; Octreotide
PubMed: 38555651
DOI: 10.1016/j.nucmedbio.2024.108905 -
Frontiers in Immunology 2024Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more...
Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering -emitting Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer,F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.
Topics: Animals; Neoplasms; Octreotide; T-Lymphocytes; Immunotherapy; Radioisotopes
PubMed: 38550578
DOI: 10.3389/fimmu.2024.1355388 -
Journal of Medical Case Reports Mar 2024Pancreaticopleural fistula is a rare complication of pancreatitis and poses diagnostic and therapeutic challenges. This case report sheds light on the unique challenges... (Review)
Review
BACKGROUND
Pancreaticopleural fistula is a rare complication of pancreatitis and poses diagnostic and therapeutic challenges. This case report sheds light on the unique challenges posed by pancreaticopleural fistula as a rare complication of pancreatitis. The aim is to contribute valuable insights to the scientific literature by presenting a case involving a middle-aged man with acute necrotizing pancreatitis and associated pleural effusion.
CASE PRESENTATION
A 41-year-old Asian male with a history of pancreatitis and chronic alcohol use presented with severe dyspnea, chest pain, and left-sided pleural effusion. Elevated serum amylase lipase levels and imaging confirmed acute necrotizing pancreatitis with a computed tomography severity index of 8/10. Magnetic resonance cholangiopancreatography revealed pancreatic necrosis and pseudocyst formation and findings suggestive of pancreaticopleural fistula. The patient was then treated with octreotide therapy.
CONCLUSION
The management of pancreaticopleural fistula demands a comprehensive and individualized approach. Recognition guided by high clinical suspicion coupled with appropriate investigations and a careful balance between medical, endoscopic, and surgical interventions is crucial for achieving favorable outcomes. This case report adds to the scientific literature by providing insights into the complexities of pancreaticopleural fistula and emphasizing the importance of personalized strategies in its management.
Topics: Adult; Humans; Male; Cholangiopancreatography, Endoscopic Retrograde; Pancreatic Fistula; Pancreatitis, Acute Necrotizing; Pleural Diseases; Pleural Effusion; Respiratory Tract Fistula
PubMed: 38549170
DOI: 10.1186/s13256-024-04457-8