SPONTANEOUS RESOLUTION OF A NONFUNCTIONING PITUITARY ADENOMA OVER ONE-MONTH PERIOD: A CASE REPORT.

Spontaneous resolution of nonfunctioning pituitary adenoma after hemorrhagic apoplexy is a rare clinical entity of unknown etiology and is defined as disappearance of a tumor without any specific treatment. Here we present a 54-year-old male patient who presented with acute onset of severe headache, vomiting, photophobia, and sonophobia. He was referred to brain computed tomography, which showed a 16x12x16 mm tumor mass located in the sellar region with signs of hemorrhage. Endocrinologic evaluation was consistent with under-function of pituitary gonadotropic cells. Magnetic resonance imaging (MRI) performed ten days later was consistent with hemorrhagic apoplexy of the pituitary adenoma. The patient's symptoms resolved after conservative treatment with dexamethasone, but he was scheduled for elective pituitary surgery. Preoperative MRI was performed one month after the first one and disclosed normal pituitary gland without any signs of adenoma. Our case is remarkable due to the fact that spontaneous remission of pituitary adenoma occurred within the first month, which is the shortest interval reported to date. Our case highlights the importance of conservative therapy as the first-line treatment for pituitary apoplexy in the absence of neurological impairment, since spontaneous remission may occur in a short time interval.

The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. METHODS: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. RESULTS: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. CONCLUSIONS: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

ISCHEMIC PITUITARY APOPLEXY, HYPOPITUITARISM AND DIABETES INSIPIDUS: A TRIAD UNIQUE TO NECROTIZING HYPOPHYSITIS.

- A rare case of necrotizing hypophysitis (NH) in a 52-year-old man presenting with pituitary apoplexy and sterile meningitis is described. This case indicates that the diagnosis of NH could be made without biopsy, based on concomitant presence of diabetes insipidus, hypopituitarism and radiologic features of ischemic pituitary apoplexy. Conservative management of pituitary apoplexy should be advised in NH. Additionally, this is the first report of a case of sterile meningitis caused by ischemic pituitary apoplexy.

Changes in metabolic hormones after bariatric surgery and their predictive impact on weight loss.

BACKGROUND: Although various metabolic hormones have been implicated in bariatric-related weight loss, their use as predictors of weight loss is unknown. Our study evaluates changes in metabolic hormones after bariatric surgery, and their role as predictors of weight loss. METHODS: This nonrandomized study included 51 patients, 21 underwent laporascopic adjustable gastric banding (LAGB), 15 laparoscopic sleeve gastrectomy (LSG) and 15 Roux-en Y gastric bypass (RYGB). Serum ghrelin, leptin, insulin, growth hormone, HOMA-IR and HOMA-ß was recorded at baseline and 1, 3, 6 and 12 months, and correlated with weight loss. Successful weight loss was defined as excess weight loss >50% at 12 months for all groups. RESULTS: Weight loss pattern was similar in all groups. Ghrelin increased only in the LAGB group (P = 0·016). However, baseline ghrelin concentrations >664·6 pg/mL in the LSG group predicted successful weight loss with 81·8% sensitivity and 100·0% specificity, and ghrelin >969·8 pg/mL in the 1st postoperative month predicted success with 83·3% sensitivity and 83·3% specificity in the LAGB group. Insulin and HOMA-IR decreased significantly in the LSG and RYGB group, HOMA-ß increased in the LAGB and LSG group. Serum leptin decreased and GH increased in all groups (P < 0·001 for all changes). Changes in insulin, leptin and growth hormone were not predictors, but a consequence of weight loss. CONCLUSIONS: LSG is the most effective procedure for improvement of beta-cell function. High baseline ghrelin in the LSG group and an adequate 1st month increase in the LAGB group are associated with greater weight loss. Validation studies are required to confirm the role of ghrelin in predicting weight loss after bariatric surgery, but also in selecting candidates for specific bariatric procedures.

Advanced Age, High ß-CTX Levels, and Impaired Renal Function are Independent Risk Factors for All-Cause One-Year Mortality in Hip Fracture Patients.

Risk factors for increased mortality in hip fracture patients include older age, male sex, fracture type, bone mineral density, and pre-existing co-morbidities. The role of biochemical and other anthropometric parameters on hip fracture mortality remains unclear. The aim of this study was to identify the risk factors for one-year mortality in patients with hip fractures. A total of 236 consecutive patients (59 males) with hip fractures were followed over a one-year period. Patient age, gender, type of fracture, type of treatment, time from admission to surgery, type of anesthesia, body mass index, and electrocardiograms were recorded. Complete blood counts, serum electrolytes, urea, creatinine, d-dimers, calcium, phosphate, osteocalcin, and beta-isomerised C-terminal telopeptide of collagen type I (ß-CTX) were measured at admission and estimated glomerular filtration rate (eGFR) was calculated. Multivariate Cox regression models were used to analyze the association of these parameters with survival. One-year mortality rate was 28.4%. Age was independently associated with mortality (HR 1.117, 95% CI 1.062-1.174, P < 0.001). In a multivariable model, mortality was increased in patients with higher ß-CTX (HR 4.63 95% CI 1.87-11.45, P = 0.001) and lower eGFR (HR 0.972, 95% CI 0.956-0.987, P < 0.001). Patients younger than 84 years, with eGFR < 55.4 ml/min had ten times higher mortality rates (3.2 vs. 24.5%, HR 9.73, 95% CI 2.06-45.93) as well as those with ß-CTX > 0.276 g/L (3.5 vs. 25.7%, HR 9.5, 95% CI 2.11-42.76). Advanced age, high ß-CTX levels, and impaired renal function are independent risk factors of mortality in patients with hip fractures.

Obesity and hypercholesterolemia in patients with prolactinomas: Could DHEA-S and growth hormone be the missing link?

PURPOSE: Increasing evidence exists that hyperprolactinemia alters metabolic profile. The mechanism of this effect is unknown. We aimed to investigate the differences between the metabolic profile of patients with prolactinomas and nonfunctional pituitary adenomas and to evaluate the impact of other pituitary hormones on their metabolic profile. METHODS: Our retrospective study included 86 consecutive patients with prolactinomas and nonfunctional adenomas (29 prolactinomas and 57 adenomas). Body mass index (BMI), blood pressure, serum prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), adrenocorticotropic hormone (ACTH), cortisol, urinary free cortisol, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), testosterone in men, triglycerides, total cholesterol, HDL (high-density lipoprotein) cholesterol, LDL (Low-density lipoprotein) cholesterol, alanine-transaminase, aspartate-transaminase, fasting glucose, and C-reactive protein (CRP) were obtained for all patients. Regression analyses were performed on log-transformed data. RESULTS: After adjustment for age, gender, and tumor size, prolactinomas were associated with higher BMI (OR 5.61, 95%CI 1.70-9.51, p = 0.005), LDL cholesterol (OR 3.60, 95%CI 1.35-5.93, p = 0.015), DHEA-S (OR 1.97, 95%CI 1.23-3.72, p = 0.026), and lower GH levels (OR 0.43, 95%CI 0.03-0.84, p = 0.037). In a linear multivariate regression, the association between DHEA-S, GH, and prolactin remained significant even after adjustment for BMI. GH and IGF-I were associated with BMI and LDL cholesterol, but the association diminished after adjustment for serum prolactin. CONCLUSIONS: Prevalence of obesity is four times higher in patients with prolactinomas than in patients with nonfunctional adenomas. Higher DHEA-S and lower GH levels in patients with prolactinomas may have an important role in prolactin-induced metabolic effects. Further studies are needed.

[CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES]. / HRVATSKE SMJERNICE ZA FARMAKOLOSKO LIJECENJE SECERNE BOLESTI TIPA 2.

INTRODUCTION: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. PARTICIPANTS: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. EVIDENCE: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. CONCLUSIONS: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

Remission of Graves' disease is not related to early restoration of euthyroidism with high-dose methimazole therapy.

UNLABELLED: Introduction and aims: The most recent hypothesis postulated that early restoration of euthyroid state in patients with Graves' disease changes the course of the disease and leads to better disease control. Therefore, we analyzed the efficacy of methimazole therapy and the course of disease in patients with restored euthyroidism and in patients with active disease on first control visit. PATIENTS AND METHODS: We included 63 patients with total T4 level >190 nmol/L or T3 >7 nmol/L and diffuse goiter with no previous episodes of hyperthyroidism. All patients received initially high doses of methimazole (60-80 mg) followed by a rapid dose reduction. RESULTS: Ten percent of patients were excluded from the study due to side effects. Two different groups emerged after 5 weeks of treatment with same dose of methimazole: group 1 with active disease (48%) and group 2 with restored euthyroidism. Further controls on 12th, 24th and 68th weeks of treatment showed no difference in remission rates, number of iatrogenic hypothyroid episodes, and number of exacerbations between the two groups, regardless of methimazole dose. There was no association between age, gender, thyroid hormone levels, and remission and exacerbation rates. CONCLUSIONS: Initially, higher methimazole doses with rapid progressive decrease to maintenance dose result in similar remission rates and are followed by similar incidence of adverse side-effect as fixed low dose therapy. Our results indicate that neither an early restoration of euthyroidism nor the difference in methimazole doses influence the course of Graves' disease.

A first case of endoscopical removal of an eroded adjustable gastric band in Croatia.

Laparoscopic gastric banding (LAGB) is one of the most common surgical procedures in the treatment of morbid obesity since it provides good long-term outcomes in weight loss and decrease of comorbidities associated with obesity. Although the procedure has low morbidity and almost none-existing mortality, certain complications can occur. Erosion of the band into the gastric wall is one of the rare complications in LAGB. The reported incidence varies from 1 to 11%, however the largest study reported an incidence of 1.6%. This is in accordance with the incidence in our Centre for obesity, where only one case of erosion occurred among 112 operative procedures. The aim of this paper is to present a patient with gastric band erosion and it's removal by using the endoscopic techniques as a minimally invasive management method.

Dexketoprofen Trometamol and Tramadol Hydrochloride Fixed-Dose Combination in Moderate to Severe Acute Low Back Pain: A Phase IV, Randomized, Parallel Group, Placebo, Active-Controlled Study (DANTE).

INTRODUCTION: Dexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE). METHODS: A total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61). RESULTS: The proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score < 4 or pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose, was higher in the DKP/TRAM arm than in the placebo group, but the difference was not statistically significant (46.1% vs. 42.6%, respectively; hazard ratio 1.11; 95% confidence interval 0.775, 1.595; p = 0.566). DKP/TRAM achieved superiority over TRAM in total pain relief at 4, 6, and 8 h (p < 0.05). Conversely, in relation to the secondary endpoints, a significantly greater reduction in NRS-PI score was seen with DKP/TRAM versus placebo starting from 1 h, and this reduction remained numerically lower throughout 8 h. Summed pain intensity difference values were also significantly lower at 4, 6, and 8 h with DKP/TRAM compared to TRAM (p < 0.05). Overall, DKP/TRAM was well tolerated. CONCLUSION: Although the primary endpoint was not met, secondary efficacy analyses suggest the superiority of DKP/TRAM over placebo and TRAM alone in terms of total pain relief. DKP/TRAM can be considered to be an effective and safe option for the treatment of moderate to severe acute LBP. DANTE STUDY REGISTRATION: EudraCT number: 2019-003656-37; ClinicalTrials.gov Identifier: NCT05170841.

The role of the NY-ESO-1 in the prognosis of gastric cancer.

Gastric cancer is one of the most common malignancies worldwide and the fourth leading cause of cancer-related deaths. Gastric cancer is a multifactorial disease influenced by both environmental and genetic factors. Its most critical features include invasiveness and high metastatic potential. Metastasis is a complex process, and our understanding of the mechanisms involved remains incomplete. Growing evidence suggests that cancer-testis antigens (CTAs) play a crucial role in the metastatic potential of various tumors. Several studies have linked CTA expression with lower tumor differentiation, higher metastatic potential, and poor chemotherapy response. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen, part of the CTA group, is expressed in tumor tissues, while its expression in normal tissues is restricted to spermatogonia. This study aimed to determine the expression of NY-ESO-1 in primary adenocarcinoma of the stomach, both with and without metastasis in regional lymph nodes, and to compare it with TNM stage, age, gender, and survival. We analyzed gastric cancer tissue from 53 node-negative and 55 node-positive primary gastric carcinoma patients for NY-ESO-1 expression using immunohistochemical assay. The results were correlated with clinicopathological parameters and survival. Patients with positive NY-ESO-1 expression in primary tumors had a median survival of 19.0 months (range 14.1 - 24.0), in contrast to those with negative expression, who had a median survival of 52.0 months (range 0.0 - 133.3) (chi-square 7.99, P = 0.005). T status, N status, and NY-ESO-1 expression were all independently associated with shorter survival. No significant difference in NY-ESO-1 expression in primary tumors was observed concerning lymph node metastasis status. In summary, our findings suggest that increased expression of NY-ESO-1 could potentially serve as a prognostic biomarker for gastric cancer.

Corrigendum to: Post-treatment neutrophil to lymphocyte ratio as a prognostic tool in patients treated with tocilizumab for severe COVID-19 pneumonia - a single center experience.

[This corrects the article DOI: 10.11613/BM.2023.020704.].

Endocrinological outcomes of pure endoscopic transsphenoidal surgery: a Croatian Referral Pituitary Center experience.

AIM: To analyze early remission, complications, and pituitary function recovery after pure endoscopic endonasal transsphenoidal surgery (PEETS), a novel method in pituitary adenoma treatment. METHODS: Testing of all basal hormone values and magnetic resonance imaging (MRI) were performed preoperatively and postoperatively (postoperative MRI only in nonfunctioning adenomas) in 117 consecutive patients who underwent PEETS in the period between 2007 and 2010. The series consisted of 21 somatotroph adenomas, 61 prolactinomas, and 4 corticotroph and 31 nonfunctioning adenomas. Sixty-three were macroadenomas and 54 were microadenomas. Remission was defined as hormonal excess normalization on the seventh postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas. The presence of hypogonadism, growth hormone deficiency, and hypothyroidism was assessed on the seventh postoperative day. Hypocortisolism was assessed through necessity for replacement therapy within 18 months postoperatively. RESULTS: Remission was achieved in 84% of patients: in 100% of microadenoma and 70% of macroadenoma patients (P<0.001, odds ratio [OR], 28.16, 95% confidence interval [CI], 1.61-491.36), respectively. Endocrinological complications occurred in 17.1% of patients: in 9% of microadenoma and 24% of macroadenoma patients (P=0.049, OR, 3.06; 95% CI, 1.03-9.08). Duration of empirical hydrocortisone replacement therapy was significantly shorter in microadenoma patients (P<0.001). Thirty-five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery. CONCLUSION: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma treatment.

Intrathyroid parathyroid carcinoma with intrathyroidal metastasis to the contralateral lobe: source of diagnostic and treatment pitfalls.

Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.

Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma.

Gastric cancer is related to high mortality rates and advanced disease stage at the time of diagnosis. Its carcinogenesis is extensively studied and is associated with genetic and epigenetic changes, changed the interaction between tumor and adjacent stromal cells, and changes in the microenvironment molecule status. Neural precursor cell-expressed developmentally down-regulated 9 (NEDD9) affects different signaling proteins and pathways, apoptosis, adhesion, cell migration, and invasiveness. Connexin-43 (Cx43) also assists in intercellular communications and has several channel-independent functions. Aberrant expression of those two gap junction proteins plays an essential role in metastatic processes. Our scope was to detect the expression of Cx43 and NEDD9 in epithelial and stromal gastric cancer compartments and its relation to tumor progression and lymph node metastases. Cancer tissue from 53 cases of node-negative and 55 cases of node-positive primary gastric carcinoma patients was analyzed for Cx43 and NEDD9 expression by immunohistochemical assay, and the results were correlated with the remaining clinical and pathological findings and survival. In our cohort of patients with lymph node metastases, we detected higher expression of epithelial Cx43 in the primary tumor and stromal Cx43 expression correlated with both epithelial NEDD9 (rho = 0.453) and stromal NEDD9 (rho = 0.484). Higher epithelial Cx43 and NEDD9 expression were associated with higher mortality (HR 1.54, 95% CI 1.01-2.37, p = 0.048). Epithelial Cx43 expression, both epithelial and stromal NEDD9 expression, T and N status were all independently associated with shorter survival. In summary, our findings suggest that increased expression of both epithelial and stromal NEDD9 and epithelial Cx43 could potentially be used as prognostic gastric cancer biomarkers.

Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer.

Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case-control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience.

BACKGROUND: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Oncologist Burnout Syndrome in Eastern Europe: Results of the Multinational Survey.

PURPOSE: Burnout is defined as a three-dimensional syndrome-emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA)-caused by chronic occupational stress. The aim of the current study was to investigate the prevalence of burnout among oncologists in Eastern Europe and to identify the contributing factors. METHODS: The study was conducted as an online survey between October 2017 and March 2018. Oncologists (including medical, radiation, clinical, and surgical oncologists) from 19 countries were invited to participate. The survey consisted of 30 questions, including the standardized burnout instrument, Maslach Burnout Inventory, and eight demographic questions. Burnout risk was scored according to the scoring manual for health care workers. RESULTS: The study included 637 oncologists. Overall, 28% were at low or intermediate risk and 72% were at high risk for burnout. Forty-four percent of participants were at high risk for EE, 28.7% for DP, and 47.3% for PA. EE risk was associated with female sex. DP risk was highest among clinical and radiation oncologists, whereas PA risk was positively correlated with years of service, percentage of cancer deaths, and availability of the number of oncologists. In multivariate logistic regression analysis, burnout was significantly associated with standardized cancer mortality and fewer years of practice. CONCLUSION: Burnout among oncologists in Eastern Europe is high, and younger oncologists are the most vulnerable group. Preventive measures should be taken to address this issue, which negatively affects optimal care delivery and poses a threat to oncologists' health and well-being.

Remission of Recurrent Cochlear Hydrops Associated With Bromocriptine Treatment for Macroprolactinoma.

Objective Current recommendations for cochlear hydrops treatment include systemic glucocorticoids and diuretics. Cochlear cells express dopamine receptors, although their role is unknown in the pathophysiology of cochlear hydrops. Case Description We report the case of remission of recurrent right-sided cochlear hydrops in a young male patient treated with bromocriptine due to pituitary macroprolactinoma. Transient improvement was observed after oral steroid and diuretic treatment, but cochlear hydrops recurred until the dose of bromocriptine was increased to 10 mg daily. Conclusion Bromocriptine may stimulate dopamine receptors in cochlear cells with potential therapeutic role in patients with cochlear hydrops. There are no widely accepted and effective treatments for endolymphatic hydrops, and identifying potential new and efficacious therapeutics is of high relevance.