Zenon Pogorelić

Expression of androgen receptors in triple negative breast carcinomas.

Triple negative breast cancer (TNBC) consists of a group of tumors with poor prognosis, owing to aggressive tumor biology and lack of targeted therapy. The aim of this study was to assess the immunostaining for androgen receptors (ARs) in the group of TNBC, in addition to basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors and to demonstrate its prognostic relevance in this group of tumors. The study included 83 patients. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER2, CK5/6, CK14, EGFR, Ki-67 and AR. Of the 83 TNBC samples, 32.5% showed positive immunostaining for AR, 66.3% had BL immunophenotype, and 48.2% had BL morphology. Positive AR immunostaining was inversely correlated with higher clinical stage, higher mitotic score, higher histological grade and higher proliferation index measured by Ki-67. Significantly more AR negative tumors were observed among the tumors with BL immunophenotype and BL morphology. There was no significant association between positive AR immunostaining and disease free survival or overall survival. More than one third of TNBC were AR-positive, and this represents a potential opportunity for novel targeted treatment in the group of breast tumors for which therapeutic options are currently limited.

ManageMent of ceMent vertebroplasty in the treatMent of vertebral heMangioMa

Background: The vertebral hemangiomas are benign vascular lesions occurring in spine. Although uncommon, symptomatic vertebral hemangiomas can be painful and can limit daily activities. A number of methods have been used in the treatment of symptomatic and aggressive vertebral hemangioma, but none of them is optimal. Treatment with cement vertebroplasty showed very good results. This study aims to illustrate the validity of the treatment with cement vertebroplasty in patients with painful vertebral hemangiomas. Patients and Methods: From January 2000 to January 2007, 24 patients were treated by percutaneous vertebroplasty because of hemangioma: 16 thoracic, 8 lumbar. There were 11 males and 13 females. The average age at the time of surgery was 48 years. All the patients complained of a pain syndrome resistant to continuing medication. All patients underwent X-ray examination, CT-scan and MR of the involved level preoperatively. A unipedicular approach under fluoroscopic guidance has been performed in all patients. All procedures have been carried out under the local anesthesia. The mean follow-up was 5.8 years. Results: In all the patients a successful outcome has been observed with a complete resolution of pain symptom. Extravertebral vascular cement leakage has been observed in 3 patients, without any clinical radicular syndrome onset due to the epidural diffusion. Clinical and radiological follow-up showed stability of the treatment and absence of pain in all patients. Conclusion: Percutaneous treatment with vertebroplasty for symptomatic vertebral hemangiomas is a valuable, less-invasive, and a quick method that allows a complete and enduring resolution of the painful vertebral symptoms without findings of the vertebral bodys fracture.

Prospective validation of Alvarado score and Pediatric Appendicitis Score for the diagnosis of acute appendicitis in children.

Objectives The purpose of this study was to compare the results of the Alvarado and Pediatric Appendicitis Score (PAS) scoring systems and to establish which one is more reliable in setting the diagnosis of acute appendicitis in children. Methods All children operated on because of acute appendicitis from October 2011 to May 2013 were enrolled in this prospective study. Both clinical scoring systems have been compared over the same patients, and cutoff values were determined by the receiver operating characteristic curve analysis. Results A total of 311 patients were included in the study, and 265 (85.2%) of them had acute appendicitis. Mean Alvarado score for patients with appendicitis was 8.2 and 6.7 for those without (P < 0.001). Mean PAS for patients with appendicitis was of 7.8 and 6.6 for those without (P < 0.001). Based on the ROC curve analysis, a cutoff value for both scoring systems was 7. In patients with acute appendicitis and Alvarado score of 7 or higher, the correct diagnosis would have been set in 236 patients (sensitivity, 89%; specificity, 59%; positive predictive value, 93.1%), whereas in patients with acute appendicitis and a PAS of 7 or higher, the correct diagnosis would have been set in 228 patients (sensitivity, 86%; specificity, 50%; positive predictive value, 90.1%). No significant difference was found in sensitivity and specificity between the observed scoring systems. Conclusions Both scoring systems can be of assistance in setting the diagnosis of acute appendicitis, but none has adequate predictive values in assessing acute appendicitis and none can be used as an exclusive standard in setting the diagnosis of acute appendicitis in children. The final decision still remaines on the opinion of an expert pediatric surgeon.

Elastic Stable Intramedullary Nailing for Pediatric Long Bone Fractures: Experience with 175 Fractures

Purpose: To demonstrate the effectiveness of intramedullary fixation of displaced long bones shaft fractures in skeletally immature children using the elastic stable intramedullary nails. Patients and methods: The case records of 173 children who underwent fixation with titanium intramedulary nails because of long bones fractures were reviewed. The average age of the patients was 11.7 years, and mean follow-up was 41.3 months. There were 55 humeral, 42 forearm, 42 femoral and 36 tibial fractures. Subjective satisfaction was assessed. Results: All patients achieved complete healing at a mean of 7.5 weeks. Complications were recorded in 11 (6.3%) patients and included: one neuropraxia, six entry site skin irritations, two protrusions of the wires through the skin and two skin infections at the entry site. In a subjective measure of outcome at follow-up, 89% of patients were very satisfied and 11% satisfied; no patients reported their outcome as not satisfied. The implants were removed at a median time of six months from the index operation. Conclusion: Elastic Stable Intra-medullary Nailing is the method of choice for the pediatrics patients, because it is minimaly invasive and shows very good functional and cosmetic results. It allows an early functional and cast-free follow-up with a quick pain reduction.

Management of blunt pancreatic trauma in children

PurposeBlunt abdominal trauma is the major cause of abdominal injury in children. Because of the retroperitoneal location, insidious signs and symptoms and the lack of sensitivity with common imaging modalities often lead to difficulties in making an accurate diagnosis. The most common complication is the formation of a pancreatic fistula, pancreatitis and a pancreatic pseudocyst, which usually manifests within 3 or 4 weeks after injury.MethodsThe case records of seven children (4 male, 3 female) treated for blunt pancreatic injury in the department of pediatric surgery, University Hospital, Split were reviewed.ResultsThe treatment modalities were selected according to the grade of the pancreatic injury, hemodynamic status and associated injuries. Because all of the patients were classified as grade I or II according to the American Association for the Surgery of Trauma (AAST) classification, a conservative treatment was selected for all seven patients. In four patients the conservative treatment resulted in the total regression of the clinical, biochemical and radiological signs within four weeks (AAST grade I). In the other three patients, pancreatic pseudocysts arose within 3 or 4 weeks after the injury (AAST grade II).ConclusionsThe status of the main pancreatic duct and the location of the pancreatic injury constitute the basis of the AAST scoring system. This scale should be used as a guide to selecting a surgical or conservative strategy. Based on these data, two factors appear to be the most important determinants of the treatment strategy for children with pancreatic injury: the grade of the pancreatic injury, which is determined according to the status of the main pancreatic duct and the clinical status of the patient.

Beneficial Effect of Nifedipine on Testicular Torsion-detorsion Injury in Rats

OBJECTIVE To investigate the effect of nifedipine on testicular torsion-detorsion injury. MATERIALS AND METHODS Twenty-four adult male Sprague-Dawley rats were randomly divided into 3 groups, each containing 8 rats. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion (T/D) group, the left testis was twisted at 720° for 3 hours. After 3 hours of reperfusion, at the end of the experiment, the testes were removed. Rats in the treatment group received the same surgical procedure as the T/D group, but nifedipine was administered intraperitoneally (100 μg/kg) 30 minutes before the time of detorsion. RESULTS Unilateral testicular torsion-detorsion caused a significant increase in the malondialdehyde level and apoptosis and caused significant decreases in superoxide dismutase and glutathione peroxidase activities in ipsilateral testes. The rats treated with nifedipine had a significant decrease in malondialdehyde level and apoptosis and had significant increases in superoxide dismutase and glutathione peroxidase activities in ipsilateral testes compared with those of the T/D group. CONCLUSION These results suggest that biochemical and histological torsion-detorsion injury occurs in the ipsilateral testes after a 3-hour torsion and 3-hour detorsion and that administration of nifedipine before detorsion prevents ischemia/reperfusion cellular damage in the testicular tissue.

The significance of immunohistochemical expression of merlin, Ki-67, and p53 in meningiomas.

Meningiomas are one of the most common CNS tumors whose appearance is closely linked to NF2 gene product merlin. Tumor markers Ki-67 and p53 play established role in tumor progression which should be analyzed in close association with merlin expression. The aim of this study was to investigate the immunohistochemical expression of merlin in meningiomas, correlation with Ki-67 and p53, and to determine the association of these results with histologic grade and subtype. The histologic sections of 170 patients with totally resected meningiomas, between January 2000 and December 2010, were classified according to WHO, immunohistochemically stained for Ki-67, p53, and merlin, and analyzed using light microscope. Ki-67 median was 5.6 times higher in group of patients with negative merlin than in those with positive merlin (P=0.05). Statistically significant correlation of merlin with p53 was found (P<0.001). Merlin expression between 2 combined groups (meningothelial/secretory and fibroblastic/transitional) was statistically significant (P=0.002). By comparing merlin expression and p53 levels, statistically significant difference was found (P=0.017). In the group with positive merlin and negative p53 as well as positive merlin and low p53, meningothelial/secretory subtypes of meningiomas were more common. In combination of negative merlin and negative p53 as well as negative merlin and high p53, there were more meningiomas of fibroblastic/transitional subtype. There was no statistically significant correlation between merlin and tumor grade (P=0.420). There is undeniable influence of merlin on the development and the proliferative ability of meningioma subtypes. Significant role of p53 pathway was confirmed.

Pediatric tibial eminence fractures: arthroscopic treatment using K-wire.

Background: Fractures of the tibial intercondylar eminence are observed mostly in children and adolescents, often after minimal trauma. The purpose of this paper is to evaluate the use of K-wire fixation for the arthroscopic treatment of tibial eminence fractures in children. Patients and Methods: From January 2002 through January 2009 ten patients were treated arthroscopically because of the intercondylar eminence fracture in a Department of pediatric surgery, University Hospital Split. Arthroscopically controlled reposition was done, and using mobile X-ray two crossed K-wires were introduced percutaneously from the proximal part of the tibia to the fractured intercondylar eminence. Subjective outcome was obtained using IKDC subjective questionnaire. Results: Average hospitalization time was 11 days. Average duration of treatment was 12.5 weeks. Average follow-up was 42 months. Follow-up radiographs showed union in all cases. The mean IKDC subjective score was 96/100. Clinically, all patients exhibited a solid endpoint on the Lachman test. The global IKDC objective score was normal in eight knees and nearly normal in two knees. Conclusion: Arthroscopic reduction and fixation by Kirschner wires or a small fragment screw is the best way for treatment intercondylar tibial eminence fractures, in the pediatric population, because is not crossing the epiphyseal plate.

Titanium intramedullary nailing for treatment of simple bone cysts of the long bones in children.

Background Simple or unicameral bone cysts are common benign fluid-filled lesions usually located in the long bones of children before skeletal maturity. Pathological fracture is common, and is often the presenting feature. Aim The objective of the present study was to evaluate the results of titanium intramedullary nailing for the treatment of unicameral bone cysts with or without a pathological fracture. Methods During the period 2001 to 2007, flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in 18 children. Four of these patients presented with a pathological fracture. The cyst was located in the humerus in 14 patients, in the femur in three, and in the tibia in one. The diagnosis was based on typical radiographs and computed tomography. The mean age of the patients at the time of surgery was 9.4 years, and the mean duration of follow-up was 53 months. Radiographic evaluation was performed, and the cyst was classified as completely healed, healed with residual radiolucency, recurred, or having no response. Results Mean hospital stay was 24 hours. At one to four weeks postoperatively, all patients were pain free and had full range of motion of adjacent joints. Radiographic signs of cyst healing were present at three months in all patients, and all cysts healed ompletely. All of the cysts responded to treatment, with no cyst recurrence. No major complications were observed. Conclusion Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to normal activities

Expression of topoisomerase II-α in triple negative breast cancer.

Triple negative breast cancer (TNBC)—defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity is a group with poor prognosis, due to aggressive tumor biology and lack of targeted therapy. Topoisomerase II-&agr; (topoII&agr;) protein is one of the intracellular targets for anthracycline-based therapy, and high levels of topoII&agr; expression are recently observed in TNBC. The study included 83 patients who underwent surgery between January 2003 and December 2009. Paraffin blocks were stained immunohistochemically with CK5/6, CK14, EGFR, Ki-67, and topoII&agr;. Basal-like (BL) immunophenotype was defined by positivity for ≥1 basal cell markers: CK5/6, CK14, or EGFR. Of 83 TNBC, 66.26% were of the BL immunophenotype, which was significantly associated with higher mitotic count (P=0.023), BL morphology (P=0.005), higher histologic grade (P=0.022), and higher proliferation rate assessed by Ki-67 (P<0.001). TopoII&agr; expression was significantly correlated with invasive ductal carcinoma NOS (P=0.010), higher mitotic count (P=0.001), higher histologic grade (P=0.007), and higher Ki-67 (P<0.001). In conclusion, due to lack of expression of ER, PR, and human epidermal growth factor receptor 2 receptor in TNBC, specific targeted therapies are not effective, and chemotherapy is currently the only modality of available systemic therapy. Due to expression of topoII&agr;, anthracyclines may be effective in treatment of TNBC.