Incidence and Management of Appendiceal Neuroendocrine Tumors in Pediatric Population: A Bicentric Experience with 6285 Appendectomies.

BACKGROUND: Neuroendocrine tumors (NETs) are rare tumors that arise from neuroendocrine cells and are the most common tumors of the appendix. NETs of the appendix usually cause no symptoms and often go unnoticed until they cause acute appendicitis or are discovered during an accidental appendectomy. As the trend towards the conservative treatment of acute appendicitis increases in the pediatric population, the question arises as to whether the majority of NETs go undetected and are only discovered at an advanced stage. The purpose of the proposed study is to review the incidence and outcomes of treatment for NETs of the appendix in children and include the data presented in the data pool for further review. METHODS: From 1 January 2009 to 1 November 2023, a total of 6285 appendectomies were performed in two large pediatric centers in Croatia. After a retrospective review of the case records and histopathologic findings, a total of 31 children (0.49%) were diagnosed with NET of the appendix and included in the further analysis. The primary outcome of this study was the incidence and treatment outcome of pediatric patients diagnosed with NET of the appendix. Secondary outcomes included the patients' demographic, clinical, and laboratory data and the histopathologic characteristics of tumor species. RESULTS: The overall incidence of NETs of the appendix was stable over the study years, with minor fluctuations. The median age of patients was 14 (interquartile range-IQR: 12, 16) years, with a female predominance (64.5%). The majority of patients (96.8%) presented with acute abdominal pain and underwent appendectomy because acute appendicitis was suspected. Acute appendicitis was confirmed by histopathology in 18 (58%) cases. NETs of the appendix were not detected preoperatively in any of the patients. Among patients with confirmed acute appendicitis, most (n = 14; 77.8%) were found to have non-perforated acute appendicitis. In most children, the tumor was located at the tip of the appendix (n = 18; 58.1%), and the majority of tumors had a diameter of less than 1 cm (n = 21, 67.7%). The mitotic count (n = 25, 80.6%) and Ki-67 proliferation index (n = 23, 74.2%) were low in most patients, so most tumors were classified as NET G1 (n = 25, 80.6%), while NET G2 and NET G3 were found in four (12.9%) and two (6.5%) patients, respectively. All children were treated with appendectomy only. The median follow-up time was 54 (IQR: 24, 95) months. CONCLUSIONS: The incidence of appendiceal NET among pediatric patients is very low. NET occurs most frequently in adolescents, with a female predominance. Most tumors are less than 1 cm in diameter, located at the tip, and associated with non-perforated appendicitis. Appendectomy is the treatment of choice, and major surgery was not necessary in our cohort.

Prognostic Significance of Lymphocyte Infiltrate Localization in Triple-Negative Breast Cancer.

High infiltration by tumor-infiltrating lymphocytes (TILs) is associated with favorable prognosis in different tumor types, but the clinical significance of their spatial localization within the tumor microenvironment is debated. To address this issue, we evaluated the accumulation of intratumoral TILs (itTILs) and stromal TILs (sTILs) in samples from 97 patients with early triple-negative breast cancer (TNBC) in the center (sTIL central) and periphery (sTIL peripheral) of tumor tissues. Moreover, the presence of primary and secondary lymphoid aggregates (LAs) and the expression levels of the cancer testis antigen (CTA), NY-ESO-1, and PD-L1 were explored. High infiltration by itTILs was observed in 12/97 samples (12.3%), unrelated to age, Ki67 expression, tumor size, histologic type and grade, and LA presence. NY-ESO-1 was expressed in tumor cells in 37 samples (38%), with a trend suggesting a correlation with itTIL infiltration (p = 0.0531). PD-L1 expression was detected in immune cells in 47 samples (49%) and was correlated with histologic grade, sTILs, and LA formation. The presence of primary LAs was significantly correlated with better disease-free survival (DFS) (p = 0.027). Moreover, no tumor progression was observed during >40 months of clinical follow up in the 12 patients with high itTILs or in the 14 patients with secondary LAs. Thus, careful evaluation of lymphoid infiltrate intratumoral localization might provide important prognostic information.

The Effect of Subcutaneous and Intraperitoneal Instillation of Local Anesthetics on Postoperative Pain after Laparoscopic Varicocelectomy: A Randomized Controlled Trial.

BACKGROUND: The main goal of the present randomized clinical trial was to investigate the effects of subcutaneous administration of two different local anesthetics at trocar incision sites at the abdominal wall in combination with intraoperative intraperitoneal instillation of local anesthetics, on the character of postoperative pain, in adolescents who underwent laparoscopic varicocelectomy. METHODS: A total of 60 patients with a median age of 16 years, who received laparoscopic varicocele repair, were included in this randomized clinical trial. The patients were randomly assigned to three study groups receiving 2% lidocaine, 0.5% levobupivacaine, or the control group. The Visual Analogue Scale (VAS) was used by a blinded nurse at four different time points (2, 6, 12 and 24 h after the surgery) to measure pain intensity. RESULTS: The significant effect of time on the pain intensity (p = 0.001) was found. Additionally, the interaction between time and different local analgesics (p < 0.001) was observed. In patients in whom 0.5% levobupivacaine has been used, significantly lower VAS pain scores were recorded at each time point assessed, in comparison with the patients who received 2% lidocaine or the patients from the control group in whom no local anesthetic was applied (p < 0.001). Furthermore, in patients in whom 2% lidocaine was administrated, significantly lower pain levels according to VAS were reported than in those from the control group, except for the time point at 24 h after surgery when pain levels were comparable. Concerning the postoperative pain control, the number of patients who requested oral analgesics postoperatively was significantly lower in the group of patients in whom local anesthetic was administrated intraoperatively (2% lidocaine-n = 4, 20%; 0.5% levobupivacaine-n = 1, 5%) compared to the patients who did not receive any local anesthetic during the surgery (n = 13; 65%) (p < 0.001). CONCLUSION: A significant reduction in postoperative pain intensity and analgesics consumption in patients undergoing laparoscopic varicocelectomy who received intraoperative local anesthetic was observed. The best effect on postoperative pain intensity, according to the VAS score, was achieved by 0.5% levobupivacaine.

Comparison of new versus reused Harmonic scalpel performance in laparoscopic appendectomy in patients with acute appendicitis-a randomized clinical trial.

BACKGROUND: The aim of this study was to compare lateral thermal damage of the appendix and clinical outcomes after laparoscopic appendectomy using new versus reused Harmonic scalpels. METHODS: A total of 100 consecutive patients with acute appendicitis who underwent laparoscopic appendectomy were enrolled in the two-center, randomized clinical trial. Using a computer random number generator, patients were allocated to new or reused group. Histopathological measurement of lateral thermal damage of the appendiceal base and mesoappendix, speed of transection of the appendiceal base, duration of surgery, subjective rating of device functionality, length of hospital stay, and complications were compared within groups. RESULTS: The median lateral thermal damage on the appendiceal base in the new group (N = 49) was 0.2 mm (IQR 0.1-0.2) and 0.1 mm (IQR 0.1-0.3) in the reused group (N = 51) (P = 0.644), while on the mesoappendix for both groups, thermal damage was 0.1 mm (IQR 0.1-0.2) (P = 0.418). The median time required for base transection in both groups was 8 s (IQR 7-9) (P = 0.776). The median duration of surgery was also comparable between the groups (22 min, IQR 20-30 vs 25 min, IQR 21-35; P = 0.233). Two postoperative complications in the new group and one in the reused group were recorded (4% vs 2%; P = 0.536). Surgeons' subjective assessment of the instrument did not reveal significant difference between the groups in all of the investigated categories. CONCLUSIONS: The results of our study support the reuse of Harmonic scalpels especially in the settings where economic constraints might hamper access to minimally invasive surgery to a larger number of patients. The results obtained on laparoscopic appendectomy might not be reproducible to other more demanding surgical procedures. TRIAL REGISTRATION: ClinicalTrials.gov registry under identifier NCT04226482.

Factors Associated With Ovarian Preservation in Children and Adolescents With Primary Tumors of Ovary.

OBJECTIVE: To determine management of pediatric ovarian masses and identify the factors associated with ovarian preservation. METHODS: From January, 2002 to January, 2019 the case records of 72 patients (median age 14 y), who underwent surgery for ovarian tumors were retrospectively reviewed. RESULTS: Tumors were most common in the age group 14-17 yrs (58.3%) and most (91.7%) were benign. The most common presenting symptom was abdominal pain (80.5%) followed by vomiting, elevated body temperature, nausea and palpable abdominal mass. 25 (34.7%) patients had an ovarian torsion. Six out of 72 (8.3%) patients had malignant tumors. Of the patients with malignant tumors, 75% had abnormal alpha-fetoprotein and 50% had abnormal b-human chorionic gonadotropin levels (P<0.001). Ovarian-preserving surgery was successfully performed in 74.3% of the benign lesions and two patients (25%) with malignant tumors (P=0.004). CONCLUSION: Factors associated with ovarian-preserving surgery are benign tumor, normal tumor markers levels, and smaller size of tumor.

Prognostic value of IMP3 immunohistochemical expression in triple negative breast cancer.

Triple negative breast cancer (TNBC) account for 12% to 17% of all breast cancers. It is a heterogeneous group of tumors associated with aggressive clinical course. Insulin-like growth factor II mRNA binding protein 3 (IMP3) belongs to a family of insulin-like growth factor type II (IGF2), which plays a key role in the transmission and stabilization of mRNA, cell growth, and migration during embryogenesis. Increased expression of IMP3 is associated with aggressive behavior of different tumor types, advanced clinical stage, distant metastasis, and shorter overall survival (OS).The study included 118 patients with breast carcinoma diagnosed as TNBC and immunohistochemical staining for estrogen receptors (ER), progesterone receptors (PR), epidermal growth factor receptor 2 (HER2/neu), Ki-67, and IMP3 was performed. Correlations between categorical variables were studied using the chi-square and the Mann-Whitney U test. For survival analysis, the Kaplan-Meier method, log-rank test and the Cox proportional hazard regression model were used.Positive expression of IMP3 protein was present in 35.6% of TNBC. The presence of basal morphology was observed in 46.6% of TNBC. Positive IMP3 expression was connected with larger size of tumor, higher clinical stage, and basal morphology (P = .039, P = .034, P < .001). Disease-free survival and OS were significantly shorter in IMP3 positive TNBC.According to results of our study IMP3 expression can be used as negative prognostic factor for triple negative breast carcinomas. Targeting IMP3 molecule could be an effective approach to the management of a triple negative breast cancer with new immunological therapies, which does not yet exist for this group of tumors.

Inter-laboratory comparison of Ki-67 proliferating index detected by visual assessment and automated digital image analysis.

BACKGROUND: Proliferation rate is a major determinant of the biologic behavior of the tumor and provides information that can be used to guide treatment decisions. METHODS: This ring study included 27 pathologists from 14 Institutions, in order to assess inter-observer concordance between pathologists in Croatia. We analyzed Ki-67 proliferative index on ten randomly selected breast cancer samples comparing consistency between visual assessment using light microscopy compared to digital image analyses results from one central laboratory as a referral value. RESULTS: When we analyzed Ki-67 as numeric value high concordance rate was found between Ki-67 score visually assessed in all participating Institutions compared to referral value assessed by digital image analysis (ICC 0.76, 95% CI 0.58-0.91), and Krippendorff's alpha was 0.79 (95% CI 0.58-1.00). Concordance was better in slides with higher Ki-67 values. When we categorized Ki-67 values according to generally accepted 20% cut-off value we noticed the lower concordance rate among participants in our study. CONCLUSION: Proliferation remains one of the most important parameters for tumor characterization helpful in making clinical decisions, but it should be used with great caution. Standardization of the Ki-67 assessment is essential and proliferating index should be expressed as exact numeric value. For patients with proliferative index near the cut-off value, other factors must be considered in making clinical decisions.

Prognostic value of vitamin D receptor and insulin-like growth factor receptor 1 expression in triple-negative breast cancer.

AIM: Triple-negative breast cancer (TNBC) is characterised by shorter overall survival and an early peak of distant recurrences with still no specific targeted treatment available. Vitamin D receptor (VDR) and insulin-like growth factor receptor 1 (IGFR) have recently been described as potential new targets for anticancer therapy, yet their roles in TNBCs are still to be explored. In this study we investigated VDR and IGFR expression in patients with TNBC and compared them with clinical and pathological parameters and survival to possibly demonstrate their prognostic and therapeutic relevance. METHODS: The study included 96 patients with TNBC. Clinical and pathological parameters were compared with the immunohistochemical expression of VDR and IGFR. RESULTS: Positive VDR immunostaining was present in 27% of tumours and inversely correlated with higher mitotic score, histological grade and higher proliferation index measured by Ki-67 and related to the increased overall survival (OS). Out of 96 patients with TNBC, 35.5% of tumours were IGFR positive and correlated with higher mitotic score and Ki-67, and strongly correlated with shorter disease-free survival (DFS). Patients with VDR-negative and IGF-positive tumours had significantly lower DFS and OS. CONCLUSION: Approximately one third of TNBCs express VDR and/or IGFR. Their expression is linked with the recurrence of the disease and survival, which make them possible targets for treatment and a prognostic tool for dividing TNBCs into more homogeneous subgroups.

Lateral thermal damage of mesoappendix and appendiceal base during laparoscopic appendectomy in children: comparison of the harmonic scalpel (Ultracision), bipolar coagulation (LigaSure), and thermal fusion technology (MiSeal).

BACKGROUND: The aim of this study was to compare lateral thermal damage of mesoappendix and appendiceal base using three different instruments for sealing and cutting of mesoappendix. MATERIALS AND METHODS: A total number of 99 patients (54 males and 45 females) who underwent laparoscopic appendectomy because of suspected appendicitis between December 2013 and May 2015 were enrolled in the study. The patients were divided in three groups based on instrument used for sealing of mesoappendix: group 1 (Ultracision; n = 36), group 2 (LigaSure; n = 32), and group 3 (MiSeal; n = 31). Lateral thermal damage, intraoperative and postoperative complications, duration of surgery, hospital stay, and economic value were compared within groups. RESULTS: The median age of patients was 14 y (range 3-17). A histopathologic analysis revealed a positive diagnosis of appendicitis in 84 patients (85%). The median lateral thermal damage on appendiceal base using Ultracision, LigaSure, and MiSeal was 0.10 mm, 0.16 mm, and 0.10 mm respectively, and on mesoappendix, 0.08 mm, 0.13 mm, and 0.08 mm, respectively. Significantly higher thermal damage was found on mesoappendix (P = 0.015) and appendiceal base (P = 0.012) in patients treated with LigaSure than in patients from other groups. There were no statistical differences among the groups regarding intraoperative and postoperative complications (P = 0.098). No significant difference in thermal damage between appendicitis and nonappendicitis group was found (P = 0.266). CONCLUSIONS: Using of Ultracision, LigaSure, and MiSeal for sealing of mesoappendix in laparoscopic appendectomy in children is safe and useful. LigaSure produces significantly greater lateral thermal damage compared with other instruments.

A Comparison of Endoloop Ligatures and Nonabsorbable Polymeric Clips for the Closure of the Appendicular Stump During Laparoscopic Appendectomy in Children.

BACKGROUND: The aim of this prospective trial was to evaluate the clinical outcomes of nonabsorbable polymeric clips in laparoscopic appendix stump closure in children by comparing the endoloop ligature. PATIENTS AND METHODS: From June 2011 to June 2016, 277 children who underwent laparoscopic appendectomy were included in the study. The patients were divided into two groups based on the technique used for appendiceal stump closure: there were 101 patients in the polymeric clips group and 176 in the endoloop group. The risk of intraoperative and postoperative complications was investigated for two different techniques to close the appendiceal stump. RESULTS: Among the 277 patients who underwent laparoscopic appendectomy, no intraoperative complications and 17 (6.1%) postoperative complications were recorded. There were no significant differences between the groups with respect to the postoperative complications (P = .546). The median length of the operation was 10 minutes shorter when the polymeric clips were used (P < .001). The median hospital stay was also shorter in the polymeric clips group (P = .008). Costs of polymeric clip were significantly lower (€ 17.64) compared to endoloop (€ 34.16). CONCLUSIONS: Closure of the appendix stump with polymeric nonabsorbable clips in laparoscopic appendectomy reduces operative time and may be a cost-effective and simpler alternative to widely used endoloops.

Bilateral Simultaneous Testicular Torsion in a Newborn: Report of a Case.

INTRODUCTION: Testicular torsion is a urological emergency. If not recognized in time, this condition may result in ischaemic injury and loss of testis. Simultaneous bilateral neonatal testicular torsion is extremely rare and is usually misdiagnosed. CASE REPORT: We report a case of a male newborn, who presented with bilateral scrotal swelling and redness of the scrotum. Doppler ultrasound supported the diagnosis of bilateral testicular torsion, with an absent blood flow signal on the right side and a weak signal on the left side. Testicular exploration through scrotal incision was performed and bilateral testicular torsion was found. Right testis was grossly gangrenous, and right orchiectomy was performed. Left testicle was dark but showed recovery after detorsion with some bleeding from incised tunica albugenia. Fixation of the left testicle was performed. At six month follow-up, the left testis showed signs of atrophy and hormonal assay showed very low testosterone and elevated LH and FSH, suggesting hypogonadism. CONCLUSIONS: Management of neonatal testicular torsion is a matter of controversy. Testicular torsion results into acute ischemia and urgent surgical exploration is the key point of management. Although the possibility of salvaging the involved testicles is usually very low it is hard to justify a passive approach to a bilateral torsion resulting in such a devastating condition as anorchia.

The Value of Injury Severity Score and Abbreviated Injury Scale in the Management of Traumatic Injuries of Parenchymal Abdominal Organs.

The aim of this study was to investigate the influence of etiology, types of injury, levels of consciousness and the Injury Severity Score (ISS) and Abbreviated Injury Scale (AIS) values on the selection of treatment modality and survival in patients with injuries of parenchymal abdominal organs. Case records of 224 patients treated for traumatic injury of parenchymal abdominal organs from January 2003 until December 2015 were reviewed. Th e values of ISS and AIS of injury severity were calculated and compared to the values obtained according to the etiology, state of consciousness and survival. Of the 224 patients, 172 (76.8%) were treated by surgical approach and 52 (23.2%) were treated conservatively. Th e mean patient age was 40.1}18.3 years. Th ere were 97 (43.3%) polytrauma cases. Of the 224 injured patients, 143 (63.8%) were treated with transfusions of blood products. Two hundred and six (92%) patients survived. Th e mean AIS and ISS values were significantly lower in patients that survived (AIS=3; ISS=28) than in those that died (AIS=5; ISS=34) (p< 0.001). There was a statistically significant difference in AIS and ISS values between conscious (AIS=2.7; ISS=25.9) and unconscious (AIS=3.2; ISS=33) patients (p< 0.001). Of the 224 patients that did not survive, 18 (8%) were hemodynamically unstable. Survival depended on hemodynamic stability at admission; the ISS and AIS values were associated with the injuries and state of consciousness at admission. Hemodynamic stability, state of consciousness, and ISS and AIS values were the quality predictors of survival after abdominal traumatic injury.

Management of acute scrotum in children: a 25-year single center experience on 558 pediatric patients.

INTRODUCTION: The aim of this study was to analyze management and outcomes of treatment in patients with acute scrotum. MATERIAL AND METHODS: From January 1990 until January 2015 case records of 558 patients who underwent surgery for acute scrotum were retrospectively reviewed. Mean age was 12 years old. Each patient was analyzed for following parameters: history data, localization of pain, physical examination, operating results and the results of follow up, age, etiology, and the time from initial symptoms to surgery. RESULTS: Scrotal explorations revealed 142 cases (25%) of spermatic cord torsion, 344 (62%) torsion of the testicular appendage, 54 (10%) epididymitis, 10 (2%) testicular trauma and 8 cases (1%) of other conditions. Two peaks of incidence of spermatic cord torsion were found, the first during first year of life and the second between 13 and 15 years of life. In patients with spermatic cord torsion, median duration of symptoms in the group of salvaged testes was 6 hours; while in the group of patients who underwent orchiectomy was 46 hours. Of the total number of patients with spermatic cord torsion 40 patients (28%) underwent orchiectomy while 102 testicles (72%) were saved. There were no major complications. Acute scrotum is significantly more common in the winter. Torsion of the testis has the highest incidence in January and August. CONCLUSION: Early scrotal exploration based on careful physical examination decreases the risk of misdiagnosis of spermatic cord torsion. It is of great importance that the patient seeks immediate medical attention. If the patient arrived within 6 hours the testicle can be saved.

Unusual cause of acute abdomen in a child--torsion of greater omentum: report of two cases.

INTRODUCTION: Torsion of the omentum is twisting along its long axis and a rare cause of acute abdomen. Depending on associated conditions, it is classified as primary and secondary. It may mimic different pathologies presenting as acute abdomen, most common of them being acute appendicitis. Current choice for management of omental torsion is laparoscopic surgery. CASE PRESENTATION: We present two cases of omental torsion of two boys who presented with abdominal pain, nausea and vomiting and underwent emergency laparoscopy. CONCLUSION: Omental torsion is very rare, and its diagnosis is usually made only after surgery. At laparoscopy, omental torsion is suspected when the appendix is normal and the symptoms and findings of torsion are present. Laparoscopy is a safe and effective approach for the diagnosis and management of omental torsion, with the advantages of reduced postoperative pain and hospital stay.

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.

Pneumoperitoneum in in-vitro Conceived Quadruplet Neonate: Rare Manifestation of Hirschsprung's Disease--Report of a Case.

INTRODUCTION: Hirschsprung's disease is a congenital colonic aganglionosis, usually presented as inability or difficulty in passing of meconium, chronic and persistent obstipation, maleficent feeding, vomiting, distension and lethargy. CASE PRESENTATION: We presented a case of an in-vitro conceived quadruplet premature neonate who presented with pneumoperitoneum caused by transverse colon spontaneous perforation and microcolon appearance of distal bowel, treated by resection and temporary colostomy turns to be a rare manifestation of Hirschsprung's disease. CONCLUSION: Assisted reproductive technologies increases chances for multiple pregnancies and may increase chance for major congenital anomalies. Rare manifestation of Hirschsprung's disease is spontaneous pneumoperitoneum which remains a surgical emergency. Delay in recognizing and treatment can significantly worsen prognosis. In neonate with intestinal perforation one should consider Hirschsprung's disease.

Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas.

Triple negative breast cancers (TNBC) are characterized by aggressive tumor biology, lack of targeted treatments and poor prognosis. Anthracyclins were shown to induce immunogenic death in target cells, potentially leading to "endogenous" vaccination. We comparatively assessed expression of cancer testis antigens (CTA) and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors. The study included 83 patients undergoing surgery between January 2003 and December 2009. Tissue sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10, NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL immunophenotype and 48.2% had BL morphology. MAGE-A1 specific staining was most frequently detectable (69.2%), followed by multi-MAGE-A (58%), NY-ESO (27.1%) and MAGE-A10 (16%) specific staining. MAGE-A10 expression significantly correlated with tumor size (p=0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A specific stainings significantly correlated with advanced clinical stage (p=0.024, p=0.041, p=0.031, respectively). We found no significant association between CTA expression and disease free (DFS) or overall survival (OS). Most interestingly, a significant correlation was observed between expression of MAGE-A10 and NY-ESO and expression of TOPO2A (p=0.005, p=0.013). Expression of defined CTA and TOPO2A are significantly correlated in TNBC. Considering the limited therapeutic options for TNBC, these findings might suggest novel forms of combination therapies that should be further explored.

Improved staging using intraoperative ultrasound for mediastinal lymphadenectomy in non-small lung cancer surgery.

BACKGROUND: Extent of lymph node involvement in patients with non-small cell lung cancer (NSCLC) is the cornerstone of staging and influences both multimodality treatment and final outcome. The aim of this study was to investigate accuracy and characteristics of intraoperative ultrasound guided systematic mediastinal nodal dissection in patients with resected NSCLC. METHODS: From January 2008 to June 2013, 244 patients undergoing intraoperative surgical staging after radical surgery for NSCLC were included in prospective study. The patients were divided in two groups according to systematic mediastinal nodal dissection: 124 patients in intraoperative ultrasound nodal dissection guided group and 120 in standard nodal dissection group. The lymph nodes were mapped by their number and station and histopathologic evaluation was performed. RESULTS: Operating time was prolonged for 10 min in patients with ultrasound guided mediastinal nodal dissection, but number and stations of evaluated lymph nodes were significantly higher (p < 0.001) in the same group. Skip nodal metastases were found in 24% of patients without N1 nodal involvement. Twelve (10%) patients were upstaged using US guided mediastinal lymphadenectomy. In US guided group 5-year survival rate was 59% and in the group of standard systematic mediastinal lymphadenectomy 43% (p = 0.001) Standard staging system seemed to be improved in ultrasound guided mediastinal lymphadenectomy patients. Complication rate showed no difference between analyzed groups. CONCLUSION: Higher number and location of analyzed mediastinal nodal stations in patients with resected NSCLC using ultrasound is suggested to be of great oncological significance. Our results indicate that intraoperative ultrasound may have important staging implications.

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.