ACTA ENDOCRINOLOGICA (BUC)

5% of all cases of primary hyperparathyroidism and it is an exceedingly rare endocrine malignancy first described in 1933. Most experts recommend en bloc excision at initial surgery as the only chance for its cure. Both chemotherapy and radiotherapy have not been demonstrated to be beneficial in parathyroid carcinoma. Some patients have multiple recurrences or metastases. Therefore, new therapies are urgently needed. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. Aim. We analysed the expression of PD-L1 in parathyroid cancer to evaluate its potential as target for immunotherapeutic strategy. Subjects and methods. A cohort of 18 patients were diagnosed with primary or metastatic parathyroid cancer. Immunohistochemistry was performed in 18 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody. A 5% cut-off value was applied for PD-L1 positivity. Results. The anti PD-L1 antibody showed a predominantly membranous staining pattern in parathyroid cancer cells. Programmed Death Receptor Ligand-1 expression was found in 22.2% of all parathyroid carcinoma cases. There was no correlation between the expression of PD-L1 with lymph node metastasis, gender and age (P> 0.05). Conclusion. This expression of PD-L1 in human parathyroid cancer suggests that patients with parathyroid cancer could profit from immunotherapeutic strategies using anti-PDL1 antibodies.

Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient’s health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

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The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

controversial. Aim. This study retrospectively reviews the tumor evolution in patients with NFA macroadenomas treated with surgery and conventional RT, as compared to surgery alone. Methods. Of 107 unselected patients with operated NFA (aged 19 - 77 years), evaluated between 1977 - 2008, 71 patients were follow-up without RT (group A), while 36 patients were submitted to RT (group B). Patients submitted to radiosurgery were not included. Both groups underwent serial imaging studies with computed tomography or magnetic resonance. Tumor evolution was conventionally defined as a change of minimum 25% of diameter. Results. The surgical approach was transfrontal in 47% of patients, transsphenoidal in 43% or both in 10% of patients, similar in both study groups. In group B, 30 patients underwent highvoltage RT (mean total dose 50.5 Gy) and 6 patients low-voltage RT (mean emission dose 16,775 R). Mean follow-up after surgery in group A was 3.4 years (range 6 months - 10 years) and after RT in group B it was 6.8 years (range 2 &#8211; 24 years), p < 0.001. In group A, 16 out of 71 patients had no visible tumor remnants. In this subgroup, 2 patients (12.5%) showed tumor recurrence. Fifty-five out of 71 patients had residual tumors, 21 with extrasellar extension after surgery. In this subgroup, 21 patients (38%) showed tumor re-growth and 7 (13%) showed tumor decrease. In group B (n=36) all patients had tumor remnants after surgery with extrasellar extension in 30 patients. After RT, tumor re-growth occurred in 5 out of 36 patients (14%) as compared to subgroup A with residual tumors (p< 0.05) and tumor decrease in 14 out of 34 (41%), as compared to the same subgroup A (p < 0.01). The 5 year-tumor re-growth free survival rate of 88% in irradiated patients was significantly better than in non-irradiated patients with residual tumors (31%, log-rank test, p < 0.01, Kaplan-Meier analysis), but similar to that in patients without remnants (87.5%). Age, sex, tumor parasellar extension and size of residual tumor were not predictors of recurrency. Conclusion. Postoperative radiotherapy provides a significant improvement of local control in patients with residual NFA compared to surgery alone. It is necessary a long term follow-up due to recurrency noticed up to 8 years postsurgery. In patients without tumor remnants, a wait-and-see policy is indicated after surgery.

Background. Indication, type of surgery and choice of surgical approach for adrenal masses continues to be a subject of debate between surgeons. The aim of this study was to report our data and experience with adrenal surgery. Subjects and Methods. We performed a retrospective study on 297 patients diagnosed with adrenal masses and operated in our center between 2002 and 2011. Gender, age, surgical approach, operating time, hospital stay, histology report and complications were analyzed. Results. From a total of 297 patients who underwent adrenalectomies, 82 were performed by laparoscopic approach and 215 in a classical open approach. The most common indication for surgery was pheochromocytoma (50.2% in unilateral and 50% in bilateral adrenal masses) summing 149 patients for both types of surgery. The risk of malignancy was significantly correlated with tumor size and the cut off value of 5cm had 92.5% specificity and 74.6% sensitivity. Patients in laparoscopic group were younger (mean 44.13 years), had shorter operating times (mean 122.7 min), shorter hospital stays (mean 6.8 days), and less complications (1.7 %) compared to open adrenalectomy. Conversion rate to open procedure was 2.4 %. Conclusion. Although many adrenal masses are now excised by laparoscopic techniques, the number of procedures was still low in our center because of high surgical complexity of our cases and high institutional costs. Moreover, we should consider that the best adrenal surgery approach remains open surgical excision for larger masses and malignant conditions.

Background. This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided tissue acquisition. Methods. A prospective study from 2018-2022 included patients with pancreatic masses undergoing EUS with elastography. Univariate binomial logistic regression followed by multiple logistic regression with significant predictors was employed. A forward selection algorithm identified optimal models based on predictor numbers. Variables encompassed EUS tumor characteristics (e.g., location, size, margins, echogenicity, vascularity on Doppler, main pancreatic duct dilation, elastography appearance, vascular invasion, and hypoechoic rim), alongside demographic and risk factors (smoking, alcohol, diabetes). Results. We evaluated 165 patients (24 PNETs). EUS features significantly linked with PNET diagnosis were well-defined margins (79% vs. 26%, p < 0.001), blue elastography appearance (46% vs. 9.9%, p < 0.001), vascularization (67% vs. 25%, p < 0.001), hypoechoic rim (46% vs. 10%, p < 0.001). The top-performing model, with 89.1% accuracy, included two predictors: a homogeneous lesion (OR, 95% CI) and a hypoechoic rim (OR, 95% CI). Conclusions. EUS appearance can differentiate PNETs from non-PNETs, with the hypoechoic rim being an independent predictor of PNET diagnosis. The most effective predictive model for PNETs combined the homogeneous lesion and presence of the hypoechoic rim.