Srbislav Ilic

[Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer].

BACKGROUND/AIM Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC) neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC). METHODS A clinical trial included 158 patients (74% males and 26% females), with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion) or chemotherapy only in stage III (with pleural effusion) and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. RESULTS A total of 53 patients (34%) had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively). Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.50/0), 34 (21.5%) and 33 (20.1%) patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (< 0.001); a two-year survival time noted in 30% of the patients (p = 0.000). One year follow-up survival time was longer in the patients with neuron specific enolase and chromogranin A expression lung cancer (p < 0.001). Synapthophysin expression was not statisticaly significant for survival (p > 0.05). CONCLUSION The results of this study suggest that almost the third of the advanced NSCLC has neuroendocrine differentiation. The median survival time of the treated patients is longer when the tumor is associated with neuron specific enolase and chromogranin A expression.

[Influence of metal-ceramic fixed dental restorations on the occurrence of discoloration of gingiva].

BACKGROUND Adverse effects of dental cast alloys on the health of patients are the problem in clinical practice. The aim of this paper was to describe the case of a patient with discolorated gingivae in the presence of fixed dental restorations and used diagnostic and therapeutic procedures. CASE REPORT A 30-year old pacient, presented with the complaints about unsatisfactory esthetic of his fixed dental restorations. He complained about the greyish discoloration of gingivae, inappropriate color of the crowns, and a larger space between the central incisors. Both discolorated and normal gingivae around the fixed dental restorations were taken by excision and the samples of gingivae were examined histopathologically, and by using the Atomic Absorption Spectrophotometry test (AAS). Histopathological examination of the discolorated gingivae showed the presence of non-specific inflammation with a foreign body. AAS revealed the presence of various metals in the samples and the higher metal contents in the samples of discolorated gingivae as compared with the samples of normal gingivae. New metal-ceramic crowns were made for the patient. CONCLUSION A main cause of greyish discoloration of gingivae was presence of a metal in gingival tissue. After the excision of discolorated gingivae old metal-ceramic crowns should be replaced with new crowns.

[Influence of chemiotherapeutic protocol and neuroendocrine differentiation on metastatic non-small cell lung cancer treatment results].

BACKGROUND/AIM In 40-50% of patients with non-small cell lung cancer (NSCLC) at the time of making a diagnosis, the disease is yet at IIIb and IV stage. Standard in the treatment of these patient is the application of systemic chemiotherapy based on CIS/Carboplatin preparations. The aim of this study was to determine the influence of two different chemiotherapeutic protocols and neuroendocrine differentiation on treatment response and survival in patients with metastatic NSCLC. METHODS We examined 85 patients with metastatic NSCLC, of which 51 with stage IIIb, and 34 with stage IV of the disease. The histologic diagnosis of NSCLC was determined by tissue assays using hematoxylin eosin method. Neuroendocrine differentiation was determined by immunohistochemical analysis of neuron-specific enolase (NSE), chromogranin A, and synapthophysin expression using monoclonal mouse anti-human bodies (DAKO, Denmark). According to chemiotherapeutic protocol, the patients were randomly assigned into combined Taxol + Cisplatin group (Tax + Cis, n = 35), and Cyclophosphamide + Etoposide + Carboplatin group (CEP, n = 50). The treatment was conducted within 4-6 chemiotherapeutic cycles. The efficacy was assessed after the therapy regimen and median survival time was assessed after the randomization. RESULTS A total of 31 (36.47%) patients had a favourable therapeutic response, both partial and complete response (54.2% in the Tax + Cis group and 24% in CEP group of patients, respectively, p < 0.001). The median survival time in both groups was 13.1 months (15.3 months in the Tax + Cis group and 10.6 months in the CEP group, respectively, p < 0.001). A one-year follow-up survival period was confirmed in 40% of patients (60% only in the Tax + Cis group). A total of 23 (27.05%) patients with metastatic NSCLC had neuroendocrine differentiation. The disease progression or stable disease was noted only in patient with NSCLC without neuroendocrine differentiation (n = 42, 67.7%, p < 0.001). The median survival time in patients with NSCLC and neuroendocrine differentiation was 14.8 months, without neuroendocrine differentiation 10.7 months (p < 0.001). The patients with NSCLC and neuroendocrine differentiation in the CEP group had a longer one-year follow-up survival period than patients in Tax + Cis group (p < 0.001). In Tax-Cis group of patients, there was no significant difference in one-year follow-up survival period with neuroendocrine differentiation. CONCLUSION Better therapeutic response and longer median survival time in metastatic NSCLC was obtained using Tax + Cis as compared to CEP protocol. Similar effect was noted using CEP protocol in patients with NSCLC and neuroendocrine differentiation.

Brown tumor of the maxilla in patient with secondary hyperparathyroidism

Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH-1 050 ng/l). The level of calcium in blood was normal (Ca 2.34 mEq/L). The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions.

Advanced prostatic carcinomas with low serum levels of prostate-specific antigen

The serum levels of prostate-specific antigen (PSA) represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC). The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistological studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage In serum samples from PC patients 27 (73.7%) normal (≤ 4.0 ng/ml), and 10 (27.3%) intermediate (4.1-10 ng/ml) PSA levels were found Immunohistochemistry, in 36 PC (97.3%) had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.

Fungus‐like hyphochytrids associated with human disease

We report two cases, with liver and brain abscess, respectively, where fungus‐like organisms belonging to the Hyphochytriomycota were found at the site of inflammation together with Peptococcus in the first and Cysticercus cellulosae in the second case. This is the first time these groups of organisms have been reported in human material. The role of hyphochytrids in human pathology remained uncertain as they were found together with already known human pathogens.