Genetic variants in RNA-induced silencing complex genes and prostate cancer.

PURPOSE: The purpose of this study is to evaluate the potential association between genetic variants in genes encoding the components of RNA-induced silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for this study are rs3742330 in DICER1, rs4961280 in AGO2, rs784567 in TARBP2, rs7813 in GEMIN4 and rs197414 in GEMIN3. METHODS: The study involved 355 PCa patients, 360 patients with benign prostatic hyperplasia and 318 healthy controls. For individuals diagnosed with PCa, clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping was performed using high-resolution melting analysis, PCR-RFLP, TaqMan SNP Genotyping Assay and real-time PCR-based genotyping assay using specific probes. Allelic and genotypic associations were evaluated by unconditional linear and logistic regression methods. RESULTS: The study provided no evidence of association between the analyzed genetic variants and PCa risk. Nevertheless, allele A of rs784567 was found to confer the reduced risk of higher serum PSA level at diagnosis (P = 0.046; Difference = -66.64, 95 % CI -131.93 to 1.35, for log-additive model). Furthermore, rs4961280, as well as rs3742330, were shown to be associated with GS. These variants, together with rs7813, were found to be associated with the lower clinical stage of PCa. Also, rs3742330 minor allele G was found to be associated with lower PCa aggressiveness (P = 0.036; OR 0.14, 95 % CI 0.023-1.22, for recessive model). CONCLUSIONS: According to our data, rs3742330, rs4961280 and rs7813 qualify for potentially protective genetic variants against PCa progression. These variants were not shown to be associated with PCa risk.

Assessment of association between genetic variants in microRNA genes hsa-miR-499, hsa-miR-196a2 and hsa-miR-27a and prostate cancer risk in Serbian population.

Due to their potentially functional significance, genetic variants within microRNA genes have been recognized as candidates for cancer-related genetic biomarkers. Among the most extensively studied so far are rs3746444, rs11614913 and rs895819. Nevertheless, only few previous studies in Asian population analyzed the association of rs3746444 and rs11614913 with prostate cancer (PCa) risk, while rs895819 was not evaluated in relation to this issue. The aim of this study was to assess the possible association between these genetic variants and PCa risk and progression in Serbian population. 355 samples of peripheral blood were obtained from the patients with PCa and 353 samples from patients with benign prostatic hyperplasia (BPH). 312 volunteers derived from general population who gave samples of buccal swabs were included in the control group. Genotyping of rs3746444, rs11614913 and rs895819 was performed by using PCR-RFLP method, HRM analysis and allele-specific PCR, respectively. Allelic and genotypic associations were evaluated by unconditional linear (for serum PSA level in PCa patients) and logistic regression method with adjustment for age. Minor allele C of rs895819 was found to be associated with the increased risk of developing PCa under dominant (P=0.035; OR=1.38, 95%CI 1.02-1.86) and overdominant (P=0.04; OR=1.37, 95%CI 1.01-1.85) genetic model. Same genetic variant was found to be associated with the clinical stage of localized PCa, as well as with the presence of distant metastases. Allele G of rs3746444 was also shown to be associated with the decreased risk of PCa progression. According to our data, rs3746444 qualifies for a genetic variant potentially associated with PCa aggressiveness in Serbian population. Furthermore, our study provided the first evidence of association between rs895819 and PCa risk, as well as for its genetic association with the presence of distant metastases among PCa patients.

Prolene hernia system, ultrapro hernia system and 3D patch devices in the treatment of inguinal, femoral, umbilical and small incisional hernias in outpatient surgery.

INTRODUCTION: The employment of a diversity of prosthetic materials and several types of mesh different in construction is opening a new chapter in hernia surgery and tension-free techniques are becoming a "golden standard" for repairing abdominal wall defects, whereas the conventional methods, i.e., the tension techniques are performed on young patients having small direct, indirect, or femoral hernias. AIM: The aim of this retrospective study is to present the results of using Prolene Hernia System (PHS), Ultrapro Hernia System (UHS) and 3D Patch (3DP) devices in the treatment of inguinal, femoral, umbilical and small incisional hernias in outpatient surgery. MATERIAL AND METHODS: From January 2006 to January 2009, 70 patients were operated on for abdominal wall hernias (54 inguinal, 4 femoral, 8 umbilical and 4 small incisional hernias) using PHS, UHS and 3DP devices. All the patients underwent surgery under local infiltrative anaesthesia. All the surgical operations were performed by a single surgeon, 19 of them in the General Hospital and 51 in a private polyclinic. RESULTS: The mean size of the hernia defect in the inguinal, femoral and umbilical hernias was 2.5 cm (1-4 cm), while in the incisional hernias it was 4.5 cm (3-6 cm). The mean operating time was 2.4 hrs (2-6 hrs). There were no requirement for urinary drains. The mean follow-up was 18 months (0-36 months). The incidence of infection, chronic pain and recurrence was 0%. Three of the patients had complications: seroma in one patient with an incisional hernia and hematoma in two patients after inguinal hernia repair. CONCLUSION: The employment of PHS, UHS and 3DP devices, which have not yet been widely accepted in our hospitals, has had outstanding results in outpatient surgery. In addition, the type of anaesthesia and the 3D mesh construction prepare the way for a short hospital stay, smooth recovery and a swift return to normal activity.

Fine needle aspiration cytology in the diagnosis of head and neck masses: accuracy and diagnostic problems.

PURPOSE: Fine needle aspiration (FNA) cytology is an established technique associated with minimal complications compared with more invasive techniques such as wide core needle biopsy or open biopsy, and as such, very suitable for obtaining material in the delicate region of head and neck (H&N). The aim of this study was to assess the diagnostic accuracy of FNA cytology H&N masses. METHODS: Aspirations were performed by cytologists using 25 or 27G needles with 20 ml syringes attached, and smears were stained with May-Grunwald-Giemsa. Four hundred and ninety-four patients with palpable H&N masses underwent FNA during the study period of 2 years. RESULTS: Based on cytology alone, the most common findings were reactive lymphoid hyperplasia (28.5%), metastatic carcinoma (22.7%) and lymphoma (13.4%). Sixty-four (12.6%) FNA specimens were inadequate for diagnosis. Histological correlation was available in 164 (33.2%) patients who went on to have surgical excision of the mass. Nondiagnostic aspirate was in 16 (9.75%) patients, so the final group for cyto- histological correlation included 148 patients. The overall accuracy rate of FNA cytology, whether malignant or benign, was 91.89%, while the diagnostic accuracy for the exact type of tumor was 87.16%. There were 3 (2%) false-positive (FP) and 9 (6.1%) false-negative (FN) cytological diagnoses. The sensitivity and specificity of FNA cytology in determining a malignant diagnosis were 91.5% and 92.85%, respectively. Positive (PPV) and negative predictive value (NPV) were 97 and 81.25%, respectively. CONCLUSION: Our results showed that FNA cytology is a simple, safe, and cost-effective diagnostic method, suitable as a first-line investigation in palpable H&N masses. The main causes of the wrong diagnoses were sampling errors, inexperience and misinterpretation.

The role of partial cystectomy in treatment of muscle invasive bladder cancer.

Muscle invasive bladder cancer is usually treated by radical cystectomy, but in some selected cases with solitary tumor with appropriate localization partial cystectomy can be the treatment of choice achieving long term results with bladder preservation. We reviewed records of 11 patients which were treated in 5 year period from June 2002 to June 2007. by partial cystectomy according to the size of the tumor, localization, histology, multifocality, pathological and clinical stage, sex, and age. Male:female ratio was 6:5, mean age of the patients being 64.9 years. All patients bur one had solitary lesions located in the bladder dome in 4, on lateral sides in 5,2 patients had a tumor in diverticulum. TCC gr II was diagnosed 6 pts, TCC gr III in 5. One patient died in a year from disease progression, one from other reason, while all other patients are alive and disease free, the longest disease free interval being 3 years. Bladder capacity is adequate in all patients resulting in good quality of life . Our results suggest that in selected patients cancer control can be achieved with partial cystectomy.

The predictive value of PSA in diagnosis of prostate cancer in non screened population.

INTRODUCTION: [corrected] PSA is the most important tumor marker in all solid tumor, indispensable in the management of prostate cancer. Screening for prostate cancer is still not recomended, although performed in many countries, which introduced questions about the usefulnes of PSA in detection of prostate cancer. The PSA treshold has also been changed, the value of PSA derivatives revised. Whether such changes are applicable in non scrrened population is questionable. Aim of this study was to evaluate the predictive value of PSA, free/ total PSA and PSA density in our non screened population. PATIENTS AND METHODS: TRUS guided prostate biopsy was performed in 579 patients. The number of cores was 6-12. Mean age of the patients was 67.5 years (30-90). PSA was ranging from 0.41 to 2250 (mean 38.6 ng/ml, median: 11.95, SD 140,45). Digitorectal examination was considered positive in 351 patients. Free PSA was measured in 352 patients with the index ranging from 0.02 to 0.88 (mean free/total PSA: 0.14, median: 0.13). The volume of the prostate was measured in all patients according the prostate ellipsoid model, and PSA density calculated according to the formula PSA/PV. Patients were stratified in 6 groups according to PSA value (I: PSA ng/ml, II: PSA 2.5-4, III: PSA 4-10, IV: PSA 10-20, V: PSA: 20 to 50, Group 6: PSA 50). RESULTS: Non homogenicity of the patients can be seen through the wide range of PSA which was from 0.4 to 2025). Prostate cancer was diagnosed in 233 pts (40.2%). As expected, the probability of detecting cancer was raised with PSA (p), and was extremely rare in pts with PSA below 4 ng/ml. PSA, free/total PSA, volume of the prostate and PSA density were significantly different according to the presence of cancer. Most of our patients had PSA between 4 and 20 ng/ml. Predictive value of PSA was 20.6% for pts with PSA from 4 to 10 and 32.7% for those with PSA from 10 to 20 ng/ml. Sensitivity, specificity, positive and negative predictive values for different cut off's of PSA (4, 10 and 20) was performed. The best results were obtained for PSA cut off of 10 ng/ml. In the group of patient with PSA, PSA density more reliable than free/total PSA index. CONCLUSION: PSA is still valuable marker for detection of prostate cancer in our non screened population. According to our results PSA treshold should not be lowered below 4 ng/ml. PSA density is a reliable PSA derivative, free/total PSA index having less importance in pts with PSA below 20 ng/ml.

Diagnosis of prostate cancer in Serbia.

PURPOSE: A rising incidence of prostate cancer is noticed in USA and Europe, which might be due to better diagnostic procedures and screening programs started in some countries. We still lack epidemiological studies confirming the same trend in our country, but the rising number of patients in whom radical prostatectomy is performed is an indirect proof of bigger recruitment of patients with prostate cancer. The purpose of this study was to establish the most appropriate diagnostic protocol for detection of prostate cancer in our unscreened population. MATERIALS AND METHODS: Transrectal ultrasound (TRUS) -guided biopsies of the prostate were performed in 229 patients. Biplanar transrectal probe with needle channel was used. Six to 10 tissue cores were obtained from each patient. RESULTS: The mean patients' age was 67.12 years (range 42-88). All patients had serum prostatic specific antigen (PSA) estimation before biopsy, which ranged from 0.41 to 1550 ng/ml (mean 50.83), with 146 (63.8%) patients having PSA level greater than 10 ng/ml. Free (F) PSA was performed in 120 (52.4%) patients; the range of F to total (T) PSA ratio was 0.02 to 0.74 (mean > 0.13). Digital rectal examination (DRE) was positive in 65% of the patients. The mean prostate volume was 40.5 ml (range 11-140). Cancer was diagnosed in 99 (43.2%) patients, prostate cancer in situ (PIN) alone was diagnosed in 37 (16.2%), chronic prostatitis in 73 (31.9%), while benign prostatic hyperplasia (BPH) was found in 20 (8.7%) patients. CONCLUSION: The cancer detection rate in our patients was high. In a lot of patients the biopsy was needed only for histological proof, not as a staging tool, the intention of which is the selection of patients with localized prostate cancer amenable to curative treatment. There is still reluctance to use PSA as a sole indication for biopsy, positive DRE still being mandatory. With such a policy we are missing a lot of curable prostate cancer cases, thus increasing the cost of treatment. A national policy including screening should be considered.

The histological diagnosis of dysplastic and neoplastic lesions in inflammatory bowel disease: a pathological perspective.

Patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), are at an increased risk for developing colorectal carcinoma (CRC). The accurate diagnosis of dysplasia in biopsies taken during periodic surveillance of long-standing IBD patients is most important in prevention of UC and CD related cancer. Distinction of low from high grade IBD-related dysplasia and differential diagnosis between IBD-related dysplasia and dysplasia in sporadic adenoma as well as distinction from pseudodysplastic lesions in inflammatory pseudopolyps or reparative lesions is often very subtle and difficult and demands expertise of second experienced gastrointestinal pathologist. Although surveillance colonoscopy with multiple biopsies does not reduce the cancer mortality, it offers a reasonable chance of detecting precancer and performed prophylactic colectomy. Novel methods of detecting dysplasia are continuously being evaluated, including chromoscopy and molecular biology markers. In the future, one may expect, from these new markers to detect the dysplasia in IBD patients before development of histological evidence of neoplastic changes.

[Papillary carcinoma of the thyroid in intrathoracic goiter]. / Papilarni tireoidni karcinom u intratoraksnoj strumi.

Intrathoracic goiter (more than 80% of tissue in the thoracic cavity) represents very rare clinical entity (less than 1% of total number of thyroid gland surgical procedures). Cancer incidence in these goiter is 0-5%. The aim of this article is to present a case report of intrathoracic thyroid papillary carcinoma with multiple compressive syndrome and review of compressive intrathoracic syndrome of thyroid etiology. In our patient we have found: tracheal and oesophageal deviation and compression, superior vena cava syndrome, downhill varices, chylothorax, pericardial effusion, compress of the left a. subclavia, unilateral lesion of recurrent and phrenic nerve, and brachial plexopathy. This was a unique case with multiple compressive syndrome between 3000 patients surgically treated for all kinds of thyroid diseases. Intrathoracic goiter can cause all the known symptoms and syndromes of intrathoracic compression with possibility of rapid deterioration and fatal end.

[Papillary microcarcinoma of the thyroid and secondary hyperparathyroidism in a patient on hemodialysis]. / Papilarni mikrokarcinom stitaste zlezde i sekundarni hiperparatireoidizam kod bolesnika na hemodijalizi.

Association between non-medullary thyroid carcinoma and secondary hyperparathyroidism have been rarely reported in patients with renal failure. A few cases of micropapillary thyroid carcinoma have been reported in patients before and after renal transplantation. We present a case of incidental detection of thyroid carcinoma at the time of parathyroidectomy in patient on dialysis after cadaver renal transplantation.

[Early complications in surgical treatment of thyroid diseases: analysis of 2100 patients]. / Rane komplikacije operativnog lecenja oboljenja stitaste zlezde: analiza 2100 bolesnika.

Thyroid gland surgery today is not saddled with high incidence of main complications. Miscellaneous surgical institutions with different surgical approach, operative technique and radicality have published reports with great discrepancy in incidence of complications, analyzing them with different methods of diagnosis and result evaluation. In the same way it is well known that higher latitude of operative procedure gave better control of thyroid diseases, but it can be accompanied with more complications. All of that motivate us to analyze complications of operative treatment in our patients under well known criteria, with hypothesis that higher radicality of operative procedure do not increase incidence of complications, and that this incidence is in correlations with results published in world literature. Aim of this nonrandomized study was to analyze results of operative treatment for huge number of consecutively operated patients in our teaching hospital, to analyze and compare results according to group of diseases and operative procedures, and to compare final results with results published in the world literature. Complications of operative treatment were analyzed retrospectively for period 1988-1997 (Group I) and prospectively in period 1998-2002 (Group II). Operations were performed by 20 surgeons and 20 young surgeons during their education. We have analyzed only complications during first 30 days after operation. In Group I there was 1425 patients with 1451 operations (192 thyroid malignancies, 247 hyperthyreosis, 98 reoperations, 13% thyroidectomies and 14.8% lobectomies), with complication rate of 14.3%. Most common complication was recurrent laryngeal nerve injury in 9.3% patients or 6.3% according to number of exposed nerves (nerve at risk), then postoperative hypocalcemia with rate of 4.7% (persistent in 1.3%). In Group II in 675 patients there was 687 operations (96 thyroid malignancies, 111 hyperthyreosis, 35 reoperations, 36.6% thyreoidectomies and 25% lobectomies), with complication rate of 10.7%. Most common postoperative complication was hypocalcemia with 5% rate (persistent in 0.7%), then recurrent laryngeal nerve injury in 4.4% patients or 2.9% according to number of exposed nerves. Incidence of recurrent laryngeal nerve injury in Group II is less frequent than in Group I, highly statistically significant (p < 0.01), while for other complications there is no statistically significant difference. Totally for both groups there was 0.7% tracheotomies, postoperative bleeding in 1.1% of patients, wound hemathoma in 0.5%. wound infections in 0.9%, pneumonia in 0.5%, mortality 0.5% and most common cause of death (8/11) was problem with respiration, Airway obstruction. In Group II complications were less frequent in total thyroidectomies in relation to lobectomy with contra lateral subtotal lobectomy. In both groups and totally incidence of complications was higher in reoperations, in patients with more extensive operative procedure, in malignant diseases and hyperthyreosis. In thyroid gland surgery more extensive operative treatment with improved operative technique (micro dissection, recurrent laryngeal nerve visualization and parathyroid gland preservation), in our teaching hospital, do not have influence on incidence of postoperative complications, even recurrent laryngeal nerve injury was significantly less frequent. This results are in correlation with published results of similar hospitals around the world.

[Cystic mesothelioma of the greater omentum]. / Cisticni mezoteliom velikog omentuma.

Peritoneal cystic mesothelioma is very rare clinical entity, and only a few cases situated on the greater omentum are described. The authors here presented two cases of the greater omentum cystic mesothelioma that were diagnosed in 260,000 adult patients hospitalized for the first time, during the fifteen year period. Cystic tumor of 30 cm in diameter was found in a 78 years old male patient, and the second one was 35 cm in diameter in female patient 56 years old. Symptomatology was not characteristic. Peritoneal pseudocyst or parasitic, lymphogen, urogenital, enteric or dermoid cyst origin was preoperatively excluded, and correct diagnosis was established upon the operative findings and immuno-histochemical investigations. In both cases keratin and vimentin were clearly positive in tumor cells, but other markers were negative (EMA, Actin, S-100, NSE, chromogranin and sinoptophysin). Cystic mesothelioma was not infiltrative and surgical treatment was simple and successful.

[Adhesive ileus caused by a peritoneal reaction to starch]. / Adhezivnih ileus izazvan reakcijom peritoneuma na skrob.

Peritoneal reaction caused by glove powder is not so rare in surgical practice. We have presented a case report of a patient who was operated on due to the adhesive bowel obstruction, two years after the total gastrectomy for gastric cancer. Changes found on the peritoneal surface were similar to carcinomatous dissemination, but intraoperative frozen section analysis showed granulomatous lesions caused by foreign bodies. Nature of these changes was confirmed by PAS smear and polarization microscopy. Clarification of the peritoneal changes during relaparotomy is possible only with careful microscopic analysis of these granulomas.

[Mesothelial cyst and cystic mesothelioma of the greater omentum:case report and literature review]. / Mezotelna cista i cisticni mezoteliom velikog omentuma: prikaz slucaja i pregled literature.

Mesothelial cysts and cystic mesotheliomas of the greater omentum are very rare clinical entities. About 30 cases of mesothelial cysts and only 4 cases of cystic mesotheliomas were described in the world literature so far. Over 13 years period (1987-2000), between 15,000 laparotomised adult patients, we have diagnosed one case of mesothelial cyst and one of cystic mesothelioma only. Mesothelial cyst, 7 cm in diameter, covered by regular mesothelial cells, was found accidently during gaster cancer surgery. In a 78 years old man, 30 cm in diameter cystic mesothelioma was diagnosed with immunohistochemical studies, necessarily for differentiation between cystic mesothelioma and other peritoneal cysts. Due to possible aggressive course at the diseases and tendency to recurrency, a complete surgical excision and log term follow-up are necessary.

[Primary liposarcoma of bone]. / Primarni liposarkom kosti.

A case of 75-year-old man with extremely rare primary liposarcoma of the bone was presented. Stains for lipid, Sudan III, Sudan IV, and Oil Red "O", demonstrated the presence of intracellular lipid in the lipoblasts. Similarly, the S-100 immunoreactivity and electron microscopic findings of tumor cells confirmed the diagnosis of liposarcoma. Histochemical stains for PAS, Alcian-blue, mucikarmin, Toluidin-blue and Coloidal Iron were negative.

[Lipedema complicated with lymphedema and chyloderma]. / Lipedem komplikovan limfedemom i hilodermijom.

Lipedema never reveals clinical picture of extreme lymphedema-elephantiasis, and skin signs and complications have not been observed. Aim of this paper is to present a case of lipedema with the initial lymphedema in which, after one episode of lymphangiitis and cellulitis, came to the rapid development of lymphedema followed by chyloderma. During the local treatment of extreme chyloderma with excessive exudation, semiocclusive synthetic dressings have been used for moist wound healing. The treatment was completed after 20 weeks with total epithelizsation, without maceration and irritation, without additional spreading of the chyloderma field, without wound infections, with fast and full relief of the pain. Lipedem with extreme lymphedema can be followed by skin complications of lymphedema like chylodermia.

[Surgical treatment of rare anatomic variations and anomalies of the thyroid gland]. / Hirursko lecenje retkih anatomskih varijacija i anomalija stitaste zlezde.

Choristoma and thyroid gland malpositions are embryonal disorders. The aim of this article is ten years analysis of their diagnostic and operative treatment. In 1425 thyroidectomies we have found: one lingual, intratracheal, intracardial thyroid and ovarial struma; six separated intrathoracic goitre and 10 mostly intrathoracaly (80%) situated goitre; 1.4% out of all. Correct preoperative diagnosis we have in lingual thyroid, two intrathoracal thyroid and in all mostly intrathoracal thyroids, and in others after histopathological examination. Operative approach was: collar incision with medial sternotomy in nine, collar incision with lateral thoracotomy in three, right thoracotomy in two, and only collar incision in one. There were two operative complications, one recurrent nerve lesion and one mediastinal haematoma. There was no hypocalcaemia and mortality. Thyroid gland anomalies are very rare and associated with lot of problems in diagnostic and treatment. In specialised institutions frequency of operative complications is the same like in routine thyroid gland surgery.

[Lipedema of the leg associated with dermatomyositis]. / Lipedem nogu udruzen sa dermatomiozitisom.

Lipedema represents a form of lipodistrophy, which consists of abnormal accumulation of fat in subcutaneous tissue of the lower limbs with consecutive development of lymphostasis and lymphedema. The aim of this article was to review one clear case of lower limbs lipedema, of unusual occurrence and appearance, which was associated with dermatomyositis. A moderately manifested lipedema in 8 years old little girl was reported with its expressive segmental distribution to upper and lower legs, without significant increase in its size during last 10 years and without signs of lymphostasis. The hereditary influence was not confirmed. Histological examination of lipedematous tissue revealed significant presentation of immune component of the disease. According to the available literature, association between lipedema and dermatomyositis, lower limbs lipedema with segmental distribution as noticed above and its appearance as a consequence of corticosteroid therapy have not yet been published.