Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors-Extended Analysis of Potential Acute and Chronic Complications.

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.

Renal injuries in conflict zones: a 6-year study of traumatic cases in Afghanistan.

PURPOSE: During hostilities, gunshot wounds are the most common cause of penetrating injuries. In 8-10% of abdominal injuries kidneys are involved. The treatment method include surgical or conservative treatment (fluids + blood components). METHODS: Of 1266 combat trauma cases treated during 6 to 14 rotation of the Polish Military Contingent in Afghanistan, we extracted a subgroup of 44 kidney injuries. Corelation of trauma mechanism, PATI score, treatment methods, and outcomes was evaluated. RESULTS: Out of the 41 renal injuries, 20 considered left, 18 right, and 3 both kidneys. There were no statistical significancy in injury lateralization (p = 0.669), and no differences regarding side of a trauma and quantity of blood component used for the treatment (p = 0.246). Nephrectomy was performed on 17 patients (13 left vs. 4 right). A significant correlation between PATI score and the need for a nephrectomy (p = 0.027) was confirmed. Penetrating trauma recquired higher number of blood components comparing to blunt trauma (p < 0.001). The renal salvage rate was in study group was 61.36%. The overall survival (OS) rate was 90.25% - 4 patients died due to trauma. CONCLUSIONS: The damage side does not result in a statistically significant increase in the need for blood transfusions or differences in the PATI score. The mechanism of trauma does, however, affect the number of blood components required for treatment, particularly in cases of penetrating trauma. With the introduction of proper treatment, the overall survival rate exceeds 90%, even when opting for conservative treatment.

Utility of non-contrast Dual Energy Computed Tomography in diagnosis of differentiated thyroid cancer - two case study.

BACKGROUND: Dual Energy Computed Tomography (DECT) is a technology that allows for viewing computed tomography spectral images. This method, due to ability of presenting specific elements and substances (like water, calcium and iodine), can be used to locate selected type of tissues. Thyroid tissue due to being rich in endogenous iodine, can be located even without administration of contrast agent. CASE PRESENTATION: In presented cases authors used a feature of accumulating endogenous iodine in thyroid derivative tissue for diagnosis of differentiated thyroid cancer metastases. In Patient One DECT was a decisive parameter qualifying for the surgery. Due to use of DECT in Patient Two it was possible to directly localize thyroid cancer metastases, which was unfeasible using standard techniques (scintigraphy and [18 F]FDG PET/CT). It helped to perform targeted biopsy and confirm diagnosis of thyroid cancer metastases, allowing to introduce treatment with sorafenibe. CONCLUSION: DECT confirmed its utility in locating thyroid tissues, including differentiated thyroid cancer (DTC) metastases. The method could be used in the future, especially in borderline or ambiguous cases with no localization of DTC in ultrasonography, RAI scintigraphy, or [18 F]FDG PET/CT, and among patients having contraindications for contrast-CT.

Analysis of Nephrolithiasis Treatment in Highest Reference Hospital-Occurrence of Acromegaly in the Study Group.

BACKGROUND: Urolithiasis is one of the most common diseases of the urinary system, the incidence of which is assumed to be up to 100,000 cases per million (10% of the population). The cause of it is dysregulation of renal urine excretion. Acromegaly is a very rare endocrine disorder that causes a somatotropic pituitary adenoma producing higher amounts of growth hormone. It occurs approximately in 80 cases per million (about 0.008% of the population). One of the acromegaly complications may be urolithiasis. METHODS: Clinical and laboratory results of 2289 patients hospitalized for nephrolithiasis in the highest reference hospital were retrospectively analyzed, distinguishing a subgroup of patients with acromegaly. Statistical analysis was performed to compare the prevalence of the disease in the analyzed subgroup with the epidemiological results available in up-to-date literature. RESULTS: The distribution of nephrolithiasis treatment was definitely in favor of non-invasive and minimally invasive treatment. The methods used were as follows: ESWL (61.82%), USRL (30.62%), RIRS (4.15%), PCNL (3.1%), and pyelolithotomy (0.31%). Such a distribution limited the potential complications of the procedures while maintaining the high effectiveness of the treatment. Among two thousand two hundred and eighty-nine patients with urolithiasis, two were diagnosed with acromegaly before the nephrological and urological treatment, and seven were diagnosed de novo. Patients with acromegaly required a higher percentage of open surgeries (including nephrectomy) and also had a higher rate of kidney stones recurrence. The concentration of IGF-1 in patients with newly diagnosed acromegaly was similar to those treated with somatostatin analogs (SSA) due to incomplete transsphenoidal pituitary surgery. CONCLUSIONS: In the population of patients with urolithiasis requiring hospitalization and interventional treatment compared to the general population, the prevalence of acromegaly was almost 50-fold higher (p = 0.025). Acromegaly itself increases the risk of urolithiasis.

Difficulties in achieving euthyroid status in a patient with differentiated thyroid cancer after sleeve gastrectomy.

Not required for Clinical Vignette.

Radioligand Therapy with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a rare group of tumors with a different clinical course, prognosis and location. Radioligand therapy (RLT) can be used as a first or second line of treatment. It is registered in gastroenteropancreatic NENs (GEP-NENs) as grades G1 and G2. Tumors with an unknown point of origin, diagnosed outside the gastrointestinal tract and pancreas (non-GEP) or at the G3 grade, remain in the "grey area" of treatment. MATERIALS AND METHODS: Analysis of 51 patients with NENs who underwent RLT in a single highest reference center from 2018 to 2023 was performed. Treatment was administrated to the patients with neoplasms of unknown origin, non-GEP-NENs, and ones with G3 grade. In total, 35 patients received 177-Lutetium (7.4 GBq), while 16 received 177-Lutetium and 90-Yttrium with equal activities (1.85 + 1.85 GBq). RESULTS: The progression-free survival (PFS) before RLT qualification was 34.39 ± 35.88 months for the whole study group. In subgroups of patients with an unknown tumor location (n = 25), the median PFS was 19 months (IQR = 23), with "other" locations (n = 21) at 31 months (IQR = 28), and with NEN G3 (n = 7) at 18 months (IQR = 40). After RLT, disease stabilization or regression was observed in 42 (87.5% of) patients. RLT did not cause statistical changes in creatinine or GFR values. Hematological parameters (RBC, WBC, PLT, HGB) as well as chromogranin A concentration decreased significantly. There were no statistical differences between both subgroups regarding the type of radioisotope (177-Lutetium vs. 177-Lutetium and 90-Yttrium). After RLT in long-term observation, the median observation time (OT) was 14 months (IQR = 18 months). In patients with progression (n = 8), the median PFS was 20 months (IQR = 16 months), while in patients with confirmed death (n = 9), the median overall survival (OS) was 8 months (IQR = 14 months). CONCLUSIONS: Our study showed that 87.5% of NEN patients with unknown origin, non-GEP-NENs, and those with GEP-NEN G3 grade had benefited from the radioligand therapy. There were no significantly negative impacts on renal parameters. The decrease of bone marrow parameters was acceptable in relation to beneficial disease course. The decrease of chromogranin concentration was confirmed as a predictive factor for disease stabilization or regression.

Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE-A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center.

Neuroendocrine neoplasms (NENs) are a group of neoplasms arising from neuroendocrine cells. The worldwide incidence and prevalence of the NENs are estimated to be 6/100,000 and 35/100,000, respectively. Those numbers are increasing every decade, requiring higher and higher diagnosis and treatment costs. Radioligand therapy (RLT) using beta-emitting radioisotopes is an efficient and relatively safe method of treatment, typically used as a second-line treatment. RLT tolerability is higher than other available pharmacotherapies (chemotherapy or tyrosine kinase inhibitors). Recent studies show an increase in overall survival among patients treated with RLT. The present study aimed to learn the epidemiology of NENs in Poland and assess the effectiveness of RLT in a high-reference center. A prospective analysis of 167 patients treated with RLT in one of Poland's highest-reference NEN centers was performed. The analysis covered 66 months of observation (1 December 2017-30 May 2023), during which 479 RLT single administrations of radioisotope were given. The standard procedure was to give four courses of [177Lu]Lu-DOTA-TATE alone, or tandem therapy-[177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE. Grading analysis showed that most patients had non-functioning G2 NEN with a mean Ki-67 of 6.05% (SD ± 6.41). The most common primary tumor location was the pancreas. Over two-thirds of patients did undergo surgery due to primary tumors or distant metastases. The majority of patients were using lanreotide as a chronically injected somatostatin analog. Median progression-free survival (PFS) on somatostatin analogs was 21.0 (IQR = 29.0) months. Directly after the last course of RLT, disease stabilization was noted in 69.46% of patients, partial regression was noted in 20.36% of patients, complete regression was noted in 0.60% of patients, and progression was noted in 9.58% of patients. In long-term follow-up, the median observation time among patients who underwent four treatment cycles (n = 108) was 29.8 (IQR = 23.9) months. Stabilization of the disease was observed in 55.56% of the patients and progression was observed in 26.85% of the patients, while 17.59% of patients died. Median PFS was 29.3 (IQR 23.9), and the median OS was 34.0 months (IQR 16.0). The mean age of NEN diagnosis is the sixth decade of life. It takes almost three years from NEN diagnosis to the start of RLT. In long-term observation, RLT leads to disease stabilization in over half of the patients with progressive disease. No differences in PFS or OS depend on the radioisotope used for RLT. In Poland, organized coordination of NEN treatment in high-reference centers ensures the continuity of patient care.

Re-treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE of patients with progressive neuroendocrine neoplasm.

BACKGROUND: Neuroendocrine neoplasms (NENs) are heterogeneous groups of tumours derived from neuroendocrine cells of the ectoderm or endoderm. They are considered rare, with an estimated incidence and prevalence of 6/100,000 and 35/100,000 respectively, and a noticeable upward trend. Radioligand therapy (RLT) using beta-radiation-emitters combined with somatostatin analogues is an effective and relatively safe treatment method. It is usually used as a second-line therapy in case of progressive disease. MATERIAL AND METHODS: In retrospective analysis covering eight years of observation (2015-2023) of patients treated in a single highest-reference NEN centre, a subgroup of 13 who received RLT re-treatment (¹77Lu or ¹77Lu/9°Y-mixture) was identified. Epidemiological aspects, renal, hepatic, haematological parameters and chromogranin A serum concentration were analysed. RESULTS: The median PFS after the first cycle of RLT was 53.8 months (IQR = 19.3). Directly after the second cycle of RLT disease stabilization and progression was observed in 11/13 (84.6%) and 2/13 (15.4%) patients respectively. After the second cycle of RLT median observation time for the study group was 16.2 months. Eight out of 13 patients were reachable for long-term observation and stabilization was confirmed in 62.5 % (5/8), progression in 12.5% (1/8) and death in 25% (2/8) patients. Median survival time in patients with confirmed death was 7 months. During observation, an increase in creatinine concentration with a decrease in glomerular filtration rate (GFR) was noticed, however, the values were at a statistical trend level (p = 0.056; p = 0.071). The increase of liver parameters was statistically, but not clinically significant. The decrease in albumin concentration and fasting glucose concentration were not significant. An increase in chromogranin A concentration correlated, although not statistically, with the progression of the disease. A statistically significant decrease in the number of all bone marrow cell lines was observed. The first RLT cycle caused a higher decrease in blood parameters than the second. There were no differences in PFS or laboratory parameters depending on the radioligand ([¹77Lu]Lu-DOTA-TATE vs. [¹77Lu]Lu-DOTA-TATE/[9°Y]Y-DOTA-TATE). CONCLUSIONS: In follow-up after RLT re-treatment stabilization was observed in 62.5%, progression in 12.5% and death in 25% of patients. Decrease of glomerular filtration, and bone marrow parameters resulted from the cumulative adverse effect of RLT, the natural ageing process, and the progression of the disease. Side effects were mainly caused by the first treatment cycle. There was no significant influence on the measured parameters, depending on the radioisotope used. Re-treatment of RLT seems to be a reliable and relatively safe method, thus should be considered in patients who underwent one cycle of RLT and responded to the treatment.

Usefulness of PET/CT with Carbon-11-Labeled Methionine in the Diagnosis of Tertiary Hyperparathyroidism.

Introduction: Tertiary hyperparathyroidism (tHP) may develop in patients treated with hemodialysis or peritoneal dialysis. Parathyroidectomy may result in a significant reduction in the severity of symptoms. For the effective surgical treatment of hyperparathyroidism, proper localization of the parathyroid glands prior to surgery is essential. The sensitivity of scintigraphy in the diagnosis of tHP is lower than in the diagnosis of primary hyperparathyroidism. In recent years, positron emission tomography (PET/CT) has been gaining importance, usually as a complementary technique. Aim: The aim of this study was to determine the usefulness of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tertiary hyperparathyroidism caused by chronic kidney disease, in whom first-line diagnostic methods did not allow the localization of pathologically parathyroid glands. Material and methods: The study was conducted in a group of 19 adult patients with severe tHP who were resistant or intolerant to non-invasive treatment, with negative results of scintigraphy and ultrasonography of the neck. The study protocol included measurement of the concentration of calcium, phosphorus, and PTH in the blood serum and performing PET/CT with [11C]MET. Results: A positive result of PET/CT was obtained in 89.5% of the patients (17/19). Parathyroidectomy was performed in 52.9% of the patients (9/17) with positive results of PET/CT with [11C]MET, which were fully consistent with the results of the histopathological examinations of the removed parathyroid glands. On this basis, the sensitivity of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tHP was found to be 100%. Multiple lesions were visualized in 57.9% of the patients (11/19). Ectopic lesions were visualized in 21.1% of the patients (4/19). Conclusions: PET/CT with [11C]MET is a sensitive technique for the second-line preoperative imaging of parathyroid glands in patients with tertiary hyperparathyroidism in whom first-line examinations, such as ultrasound and scintigraphy, has failed.

Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms.

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.