Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS), and 20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD). The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development. White plaque-like deposits on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD. NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers. Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease. In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy. Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis.
Genetic factors play a key role in the pathogenesis of atrial fibrillation (AF). We would like to establish an association between previously described single-nucleotide polymorphisms (SNPs) and AF in haemodialysed patients with end-stage kidney disease (ESKD-HD) as well as to assess the cumulative effect of all genotyped SNPs on AF risk. Sixteen SNPs were genotyped in 113 patients with AF-ESKD-HD and in 157 controls: without AF (NAF) and with ESKD-HD. The distribution of the risk alleles was compared in both groups and between different sub-phenotypes. The multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. Several loci showed a trend toward an association with permanent AF (perm-AF): CAV1, Cx40 and PITX2. However, GRS was significantly higher in the AF and perm-AF groups, as compared to NAF. Three of the tested variables were independently associated with AF: male sex, history of myocardial infarction (MI) and GRS. The GRS, which combined 13 previously described SNPs, showed a significant and independent association with AF in a Polish population of patients with ESKD-HD and concomitant AF. Further studies on larger groups of patients are needed to confirm the associations.
Positron emission tomography (PET/CT) is a non-invasive molecular imaging technique using isotopes with a short half-life usually in combination with chemical compounds. The most commonly used PET/CT tracer is 2-fluoro-2-deoxy-D-glucose labeled with fluorine (18-FDG). It is used mainly in oncological diagnostics as well as myocardial viability, epilepsy and inflammatory diagnostics. The tracer less commonly used in PET/CT could be carbon-labeled methionine (11C-MET). It is mainly used in the diagnosis of focal lesions in the central nervous system. There are also reports of the use of this tracer in diagnostics of the primary, secondary and tertiary hyperparathyroidism as well as multiple myeloma. This tracer may also be used in the diagnosis of lymphoproliferative diseases and solid tumors, although there is no clear evidence of its advantage over 18-FDG. Conclusion: Significant difficulties in the production and transport of this tracer and lack of reimbursement of this type of procedure in Poland limits the use of this tracer for scientific research.
Neuroendocrine neoplasms (NENs) constitute a heterogenous group of tumors originating from neuroendocrine cells scattered throughout the body. Peptide Receptor Radionuclide Therapy (PRRT) is a treatment of choice of unresectable metastasized progressive and well-differentiated NENs. The aim of the study was to assess early bone marrow and kidney injury after administration of Lutetium-177 or Lutetium-177 combined with Yttrium-90. Thirty-one patients received treatment with [177Lu]Lu-DOTATATE with the activity of 7.4 GBq. Eleven patients received tandem treatment with [90Y]Y-DOTATATE with the activity of 1.85 GBq + [177Lu]Lu-DOTATATE with the activity of 1.85 GBq. After PRRT a significant decrease in leukocyte, neutrophil, and lymphocyte counts was noted. Tandem treatment demonstrated a more marked decrease in white blood cell count compared to Lutetium-177 therapy only. Conversely, no significant influence on glomerular filtration was found in this assessment. However, PRRT triggered acute renal tubule dysfunction, regardless of the treatment type. Regarding the acute complications, PRRT appeared to be a safe modality in the treatment of patients with NEN.
Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells spread throughout the body, forming the so-called diffuse endocrine system. The gold standard in treating unresectable or disseminated, progressive, and well-differentiated NENs is therapy with radiolabeled somatostatin analogs (peptide receptor radionuclide therapy -PRRT). PRRT is a method based on peptides combined with beta-emitting radionuclides. The study aimed to assess the early and long-term liver complications after administration of Lutetium-177 or Lutetium-177 combined with Yttrium-90. We enrolled 27 patients treated with [ 177 Lu]Lu-DOTATATE with an activity of 7.4 GBq (200 mCi) and 9 patients received the tandem treatment [ 90 Y]Y-DOTATATE + [ 177 Lu]Lu-DOTATATE with an activity of 3.7 GBq (50 mCi + 50 mCi). In the assessment of early as well as long-term complications, no significant effect of the applied treatment on the parameters of liver injury was found. Regarding liver function PRRT was a safe treatment for patients with highly or moderately differentiated, unresectable, or diffuse NENs.
Background: Neuroendocrine neoplasms are a group of tumors deriving from neural crest. They can be located in every tissue, but most commonly in gastrointestinal tract. Targeted therapy with use of radionuclides is an available and acceptable way of treatment, but its long-term safety is still to be determined, especially with sensitive methods. Methods: Study was performed on a group of 42 patients. They underwent full cycle (4 courses; 8–12 weekly intervals) of radioligand therapy with [177Lu]Lu-DOTATATE alone or tandem therapy with [177Lu]Lu-DOTATATE+[90Y]Y-DOTATATE. Late and long-term marrow and renal complications were assessed. Analysis focused on comparing data before first, fourth, and one year after the last course of RLT. Results: Study showed decreasing of all blood parameters in long-term observation, especially in lymphocytes line. Type of radioisotope, other diseases, primary tumor location, BMI, gender or age did not affect results. The only factor that had influence on hemoglobin and erythrocytes was decreased renal filtration. In long-term observation almost 10% decrease of renal filtration was observed. Type of isotope, gender, age, BMI did not affect these results. Moreover, reduction of urine IL-18, KIM-1, and albumin concentration has been observed. Conclusions: Though low-grade complications of radioligand therapy are possible, it stay a safe method of NEN treatment where benefits outweigh the risk.
Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8–12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.
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