In patients with well-differentiated neuroendocrine tumours, there is no apparent benefit of somatostatin analogues after disease control by peptide receptor radionuclide therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSAs) are commonly combined as primary treatment for neuroendocrine neoplasms (NEN), and SSAs given as maintenance. We sought to evaluate whether sequential therapy with PRRT followed by SSAs has progression or survival benefits in patients with NEN after disease control by PRRT. METHODS: This prospective, randomised, single-centre study had as principal eligibility criteria: unresectable, locally advanced, or metastatic, histologically confirmed well-differentiated NEN; no symptoms/biochemical diagnosis of carcinoid syndrome; no SSAs or ≤ 3 months of SSAs before PRRT; and stable disease or partial or complete response after PRRT. Altogether, 115 patients were randomised 2:1 to an SSA group (n = 74) given octreotide acetate LAR every 4 weeks, or a control group (n = 41) receiving only best supportive care. Octreotide treatment was to stop upon intolerable toxicity or patient refusal, or, at physician/patient discretion, upon NEN progression. The primary endpoint was progression-free survival (PFS), the secondary endpoint, and overall survival (OS). RESULTS: Median (25th-75th percentile) follow-up from the first PRRT activity to death or latest observation was 6.6 (3.18-10.22) years. During that time, 71/115 patients (62%) progressed, 52/74 (70%) in the SSA group, and 19/41 (46%) in the control group (p = 0.01). Eighty-eight/115 patients (76%) died, 58/74 (78%) in the SSA group, and 30/41 (73%) in the control group (p = 0.52). Median (95% CI) PFS was 4.7 (2.8-7.7) years in the SSA group, and 6.4 (4.1-not reached) years in controls. Overall, median OS was 6.6 years. Neither PFS nor OS differed between groups (p = 0.129, p = 0.985, respectively). CONCLUSIONS: In patients with disease control after PRRT, subsequent SSA treatment appeared not to be associated with better PFS or OS. Whether to continue SSA administration upon progression after PRRT requires evaluation in a prospective, randomised, controlled multicentre study with a relatively homogeneous sample.

Laparoscopic cortical-sparing adrenal surgery in pheochromocytomas associated with hereditary neoplasia syndromes.

INTRODUCTION: Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas. MATERIAL AND METHODS: We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3-1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5-4 years). RESULTS: No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved. CONCLUSIONS: In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.

131-I MIBG therapy of malignant pheochromocytoma and paraganglioma tumours - a single-centre study.

INTRODUCTION: Pheochromocytomas and paragangliomas are rare tumors deriving from chromaffin cells of adrenal medulla or paraganglia. They are usually benign but 10-35% of them present malignant behavior. The aim of the study was to evaluate the efficacy and safety of 131-I MIBG therapy in malignant pheochromocytoma /paraganglioma patients (MPPGL). MATERIAL AND METHODS: 18 patients (7 women and 11 men) were included in this study. Between 2002 and 2016 they underwent 131-I MIBG therapy because of MPPGL and their medical data were analyzed retrospectively. Clinical indications for the treatment included progressive disease or massive tissue involvement independently from disease progression. Tumor response for the first time was assessed 3 months after the last treatment according to Response Evaluation Criteria in Solid Tumors criteria and by 131-I MIBG scans. RESULTS: The mean single dose used was 7.25 GBq (196 mCi) and mean cumulative dose 33.08 GBq ( 894 mCi). In 2 (11%) patients complete tumor response was achieved. In 1 (6%) patient partial response was obtained. In 13 (72%) patients stable disease was observed. In 2 (11%) patients progression was diagnosed three months after treatment discontinuation. In the whole studied group the progression free survival time was 85 months and overall 5-year survival was 87%. CONCLUSIONS: Radionuclide treatment with use of 131-I MIBG may be effective form of palliative treatment for patients with inoperative neoplasm spread, progressive disease or patients requiring alleviation of symptoms. < p > < /p >.

Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma. 2018 Update.

Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines "Diagnostics and Treatment of Thyroid Carcinoma" have been formulated at the "Thyroid Cancer and Other Malignancies of Endocrine Glands" conference held in Wisla in November 2015 [1].

Indoor 222Rn concentration in the exhibition and storage rooms of Polish geological museums.

The radon exhaled from radioactive mineral collections exhibited in five Polish geological museums may influence its total indoor concentration. Radon concentrations measured in the exhibition halls do not pose a risk for visitors or museum staff. However, air exceeding the ICRP (2007) action limit for workers (equal to 300Bq/m3) was noted in the storage rooms of two museums. Significant222Rn activity concentrations equal to more than ~300kBq/m3were measured inside lead containers where radioactive minerals were stored.

Occurrence of phaeochromocytoma tumours in RET mutation carriers - a single-centre study.

INTRODUCTION: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant genetic syndrome caused by germline mutation in RET proto-oncogene. The most common mutations are in a cysteine rich domain. Phaeochromocytoma will develop in approximately 50% of RET proto-oncogene carriers. MATERIAL AND METHODS: The studied population consisted of 228 RET proto-oncogene mutation carriers. Monitoring for the diagnosis of phaeochromocytoma was carried out in all patients with established genetic status. Mean time of follow up was 138 months. Surveillance consisted of periodically performed clinical evaluation, 24-hour urinary determinations of total metanephrines complementary with imaging (CT, MR, MIBG scintigraphy). RESULTS: Phaeochromocytoma developed in 41 patients (18% of all RET proto-oncogene mutations carriers). The mean age of diagnosis for the whole cohort was 43 years. In eight cases phaeochromocytoma was the first manifestation of the MEN 2 syndrome. Only eight (20%) patients were symptomatic at diagnosis of phaeochromocytoma. The mean size of the tumour was 4.3 cm. There was no extra-adrenal localisation. We observed one case of malignant phaeochromocytoma. CONCLUSIONS: In patients with MEN 2 syndrome phaeochromocytomas are usually benign adrenal tumours with high risk of bilateral development. Taking to account the latter risk and non-specific clinical manifestation of the neoplasm it is mandatory to screen all RET proto-oncogene mutations carriers for phaeochromocytoma.

Recombinant human thyrotropin preparation for adjuvant radioiodine treatment in children and adolescents with differentiated thyroid cancer.

AIM: Although recombinant human thyrotropin (rhTSH) is widely used in treating differentiated thyroid cancer (DTC), almost all clinical investigation has been in adults. The aim of our retrospective study was to evaluate outcomes of adjuvant, rhTSH-aided radioiodine treatment in children/adolescents with DTC and to compare them to (131)I therapy during l-thyroxin withdrawal (THW). METHODS: Patients with the diagnosis of DTC who were ≤18 years of age and had no signs of persistent disease at the time of (131)I treatment were included; 48 patients were treated after rhTSH (rhTSH group) and 82 after THW group. The median time of follow-up after therapy was 67 months and was longer in the THW group (99 vs 43 months, P<0.05). RESULTS: On the day of (131)I administration, all but one patient had TSH levels above 25 µIU/ml. Peak TSH concentration was significantly higher in the rhTSH group (152 µIU/ml vs 91 µIU/ml). Similarly, the thyroglobulin concentration was higher in the rhTSH group (9.7 ng/ml vs 1.8 ng/ml). No side effects requiring medical intervention were recorded after rhTSH administration. The evaluation of disease outcomes during TSH stimulation (6-18 months after (131)I treatment) revealed equal rates of thyroid ablation (71%) in both groups. During subsequent follow-up, five patients showed recurrence (P>0.05). CONCLUSIONS: In children/adolescents, rhTSH-aided adjuvant radioiodine treatment is associated with rates of remnant ablation and short-term recurrence similar to THW. As this preparation has several advantages over THW, rhTSH may become the preferred method of TSH stimulation once studies of long-term outcomes show non-inferiority to THW in this age group.

Radioactive iodine (RAI) treatment of hyperthyroidism is safe in patients with Graves' orbitopathy--a prospective study.

INTRODUCTION: Radioactive iodine (RAI) therapy may induce or worsen orbitopathy (GO) in Graves' disease (GD). The aim of this study was a prospective assessment of the risk of GO exacerbation in a GD patients cohort submitted to RAI therapy for hyperthyroidism. MATERIAL AND METHODS: 208 consecutive GD patients treated with 131I in 2007 were enrolled. The analysis was performed on 156 patients strictly monitored for one year. Glucocorticosteroid (GCS) prophylaxis was administered if GO symptoms or GO history were present, and in cases of tobacco smokers even without GO symptoms. Clinical and biochemical evaluation at one, three, six, and 12 months after therapy was performed in the whole group, then at 24 months in 138 patients. RESULTS: There was no severe GO progression in patients without GO symptoms at the time of RAI treatment. The risk of severe GO worsening for preexisting GO patients (demanding systemic GCS administration) during the 12-month follow-up after RAI therapy was 10%. 12 and 24 months after 131I administration, stable improvement compared to the initial GO status had been achieved in most (98-96%) patients. CONCLUSIONS: 1. In patients with mild GO, the risk of severe GO worsening after RAI therapy is acceptable, as long as RAI therapy is applied with GCS cover. 2. In patients without GO symptoms at the time of RAI therapy but with a history of GO and with subclinical GO diagnosed by MRI only, the risk of severe progression is minimal. 3. Distant outcomes of RAI treatment confirmed its safety in GO patients.

Assessment of the safety and efficiency of sunitinib malate in metastatic neuroendocrine tumours of the pancreas (NEN G1/G2) depending on the number and type of earlier therapeutic lines - initial report.

INTRODUCTION: The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy. MATERIAL AND METHODS: Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-67 < 20%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0. RESULTS: Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) - including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) - occurred in one patient after three lines and in one patient after two lines; anaemia (25%) - in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2-3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months. CONCLUSIONS: Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied.

Urinary iodine in patients with differentiated thyroid cancer (DTC) during L-thyroxine treatment.

INTRODUCTION: Urinary iodine concentrations were analyzed in the morning urine samples of patients with differentiated thyroid cancer (DTC). MATERIAL AND METHODS: The analyzed group included 572 DTC patients who were treated with radioiodine or hospitalized for evaluation of radioiodine treatment effects in 2009 at the Institute of Oncology in Gliwice. Ioduria was analyzed by PAMM (Program Against Micronutrient Malnutrition) method before rhTSH administration. A total of 545 tests were performed during L-thyroxine treatment and 27 after L-thyroxine withdrawal. RESULTS: Median L-thyroxine dose was 150 µg/day. Median ioduria was 127.5 µg/L during L-thyroxine therapy and 134 µg/L after the L-thyroxine withdrawal. No distinct relation between ioduria and L-thyroxine dose was observed. Ioduria < 200 µg/L was observed in over 90% of patients and this cut-off was chosen for the reference range. Only 1.2% of patients showed a distinct stable iodine contamination (ioduria ≥ 300 µg/L). CONCLUSIONS: Urinary iodine concentrations in differentiated thyroid cancer patients treated with L-thyroxine vary in a wide range and do not show a clear relation with L-thyroxine dose.

Has differentiated thyroid cancer (DTC) staging changed with in the last ten years in the Silesia region of Poland?

INTRODUCTION: The aim of the study was to compare the advancement of thyroid cancer at diagnosis in Polish patients from the Silesian district in the years 1999 and 2008. MATERIAL AND METHODS: The analyzed group consisted of Silesian district patients with thyroid cancer, who were registered by the Department of Tumour Epidemiology of the Institute of Oncology in Gliwice in the years 1999 and 2008. From a group of 186 patients who entered on record in 1999, 167 were qualified for this analysis. Similarly, from 238 patients registered in 2008, finally 226 were added. We analyzed: sex, age at diagnosis, histotype of thyroid cancer, and DTC staging according to TNM (UICC 2002). In 1999 there were 137 females (82.04 %) and 30 males (17.93%) with thyroid cancer diagnosed at ages 5-81 years. In 2008 there were 183 females (80.97%) and 43 males (19.03%) diagnosed at ages 14-80 years. In both groups, in 1999 and 2008, the median age was the same (51 years). RESULTS: In the year 1999, 119 (71%) and in 2008, 197 (87%) patients were diagnosed with papillary thyroid cancer (p = 0.0003). Relations between age and sex were similar in these years. There was some increase in frequency of patients diagnosed with papillary microcancer (pT1a), which was on the border of statistical significance (p = 0.05). A statistically significant increase of pT1 (p = 0.02) and decrease of pT4 (p = 0.001) and of pTx (p = 0.002) was observed in the year 2008 in the whole cohort of DTC patients. CONCLUSIONS: 1. In 2008 the contribution of papillary histotype to all thyroid cancer patients (87%) was significantly higher than in 1999. 2. The percentage of DTC patients diagnosed with pT1 disease was significantly higher in 2008.

[131I-MIBG therapy in the treatment of pheochromocytoma in children--own experiences]. / Terapia 131I-MIBG w leczeniu guzów chromochlonnych u dzieci--doswiadczenia wlasne.

Three cases of pheochromocytoma in children/adolescents or young adults treated by 131I-MIBG are presented in this study. In one patient 131I-MIBG was administrated after ineffective surgical treatment and chemotherapy of a benign retroperitoneal tumor, whereas in two other patients 131I-MIBG therapy was carried out because of malignant pheochromocytoma dissemination. In a child with retroperitoneal paraganglioma decrease of tumor size and its fibrosis after 131I-MIBG therapy allowed radical surgery and complete recovery. In two other cases partial remission was achieved. All patients showed a good subjective response with improvement of the general condition and better blood pressure control. In two children adverse reactions such as leucopenia, hypothyroidism or hypogonadism were observed. The presented data confirm effectiveness and acceptable tolerance of 131I-MIBG treatment in pheochromocytoma, what is very important in pediatric patients.

Selection of tomato plants resistant to a local Polish isolate of tomato spotted wilt virus (TSWV).

We found that the Sw-5 gene confers resistance to one of the Polish isolates of tomato spotted wilt virus (TSWV). A series of tomato breeding accessions was analysed along with standards of resistance and susceptibility to TSWV. The presence of the Sw-5 gene was determined using the available PCR marker. Subsequently plants from these accessions were grown in the presence of the TSWV isolate from Poland. Some of them developed severe symptoms of the TSWV disease. Expression of the virus proteins was also assayed in tissues of the investigated plants. We found general agreement between either lack or presence of the disease symptoms, virus proteins and resistance gene. Some observed discrepancies of these data are also discussed. Our results indicate that marker-assisted selection can be used for breeding of the TSWV-resistant tomato in Poland.