How to Handle Lymphadenectomy Specimens to Identify Metastasis More Accurately in Gynecologic Pathology.

AIM: To identify the value of processing multiple sections to detect metastasis in lymph nodes (LNs) dissected during gynecologic cancer surgery, and to evaluate the sizes of metastatic LNs in each region to compare with the largest one. MATERIALS AND METHODS: This retrospective study included 362 patients who had gynecologic cancer with at least one metastatic LN. Slides of 627 metastatic LN specimens were categorized according to the processing technique into single and more than one section (MOS) groups. In the MOS group, the LNs were cut into 2 or 3 parallel slices because their greatest dimensions exceeded 0.5 cm. Sizes of LN metastatic foci (MF) were measured and defined as follows: MF ⩽2 mm as micrometastasis and MF >2 mm as macrometastasis. The largest LN diameters among the metastatic LNs and the largest LNs in those regions were measured. Groups were compared using the Kruskal-Wallis test. RESULTS: Sixty-five (10.3%) of the metastatic LNs included in this study had micrometastases and 40 (6.3%) of them had MF ⩽1 mm. The rate of micrometastasis was higher in the MOS group than in the single-section group (11.8% vs 8.5%, respectively). Twenty-eight percent (n = 175) of metastatic LNs were not the largest, and 55.5% of those were less than 1 cm in diameter. CONCLUSION: Methods of LN processing and macroscopic evaluation are not standardized, and processing single sections from LNs may overlook micrometastases. The detection rate of micrometastases can be improved by processing multiple sections from LNs.

Thyroid FNAC containing hürthle cells and hürthle-like cells: A study of 128 cases.

AIM: It is a diagnostic challenge to differentiate benign and malignant cytology in the presence of Hürthle cells. In our previous study, it was determined that in fine needle aspirations (FNA), the malignancy outcome of the Hürthle cells containing group tend to be papillary thyroid carcinoma (PTC) in a higher percentage. The most common misinterpretation is caused by PTC cells with large cytoplasm-like Hürthle cells. The aim of this study is to predict histologic outcome of the nodules, which have Hürthle cells in FNA according to cytological, clinical features, and BRAFV600E mutation status. MATERIALS AND METHODS: Detailed cytological features of 128 cases were compared with histopathological diagnosis. The analysis of BRAFV600E mutation of the PTC cases were performed by real-time polymerase chain reaction. RESULTS: The neoplastic outcome was increased statistically significantly with younger age (P = 0.020), increase in cellular dyshesion (P = 0.016), presence of nuclear budding (P = 0.046), and granular chromatin (P = 0.003). Nuclear budding (P = 0.014), granular chromatin (P = 0.012), and hypoechoic nodules in ultrasonography (P = 0.011) were significant independent factors for the increase in the malignancy risk. Increased lymphocytes (P= 0.015) and colloid were related to non-neoplastic outcome. According to the surgical outcome, more than half of the malign cases were PTC (74%). BRAFV600E mutation was detected in 27.8% of the PTC cases. CONCLUSION: PTC cases containing Hürthle cell-like cells may lead to diagnostic errors. Nuclear budding and granular chromatin of Hürthle cells are significant, remarkable findings to predict the outcome of neoplasm and malignancy.

Serous versus high-grade endometrioid endometrial carcinoma: immunohistochemistry of RFP is not useful for differentiation.

We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve,  statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The  values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.

In Vivo Healing Effects of Ankaferd Blood Stopper on the Residual Pancreatic Tissue in a Swine Model of Distal Pancreatectomy.

The aim of this study was to determine whether intraoperative Ankaferd blood stopper (ABS) application into the pancreatic channel and to the pancreatic remnant surface following distal pancreatectomy can or cannot prevent postoperative pancreatic fistula formation. Three pigs underwent distal pancreatectomy under general anesthesia. In two of the pigs, 0.5 ml of ABS was applied to the stump surface area after adding 0.5 ml of ABS into the pancreatic channel. The remaining one animal served as the control. The pigs were sacrificed on the seventh postoperative day for autopsy. The pancreatic remnants from the animals were then taken for histopathological analyses. It was observed that the oral intake had been broken and abdominal distention had developed in the control pig following on the third postoperative day. However, no significant clinical changes were observed in the ABS-applied pigs. In the autopsy, it was found that the control pig had generalized peritonitis with pancreatic necrosis. On the other hand, the ABS-applied pigs had either macroscopically and microscopically normal pancreatic tissue architecture with an occluded Wirsung duct at the pancreatic stump. It was concluded that application of ABS on the transected surface and into the pancreatic channel could prevent pancreatic fistula formation and improve wound healing in the residual pancreatic tissue following distal pancreatectomy.

Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy.

PURPOSE: Excision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy. MATERIALS AND METHODS: Thirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival. RESULTS: Pathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012-0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2-11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤ 60 years) (HR 3.4, 95% CI 1.2-9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014-0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9-19.9, P = 0.002) were significantly associated with OS. CONCLUSIONS: Our results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.

The efficacy of silver-embedded polypropylene-grafted polyethylene glycol-coated ventricular catheters on prevention of shunt catheter infection in rats.

PURPOSE: Catheter-related infection is a major complication of ventriculoperitoneal shunt in children. The aim of this study is to determine inflammatory response and the efficacy of polypropylene-grafted polyethylene glycol (PP-g-PEG) copolymer and silver nanoparticle-embedded PP-g-PEG (Ag-PP-g-PEG) polymer-coated ventricular catheters on the prevention of catheter-related infections on a new experimental model of ventriculoperitoneal shunt in rats. METHODS: Thirty six Wistar albino rats were divided into six groups: group 1, unprocessed sterile silicone catheter-embedded group; group 2, sterile PP-g-PEG-coated catheter group; group 3, sterile Ag-PP-g-PEG-coated catheter group; group 4, infected unprocessed catheter group; group 5, infected PP-g-PEG-coated catheter group; and group 6, infected Ag-PP-g-PEG-coated catheter group, respectively. In all groups, 1-cm piece of designated catheters were placed into the cisterna magna. In groups 4, 5, and 6, all rats were infected with 0.2 mL of 10 × 10(6) colony forming units (CFU)/mL Staphylococcus epidermidis colonies before the catheters were placed. Thirty days after implantation, bacterial colonization in cerebrospinal fluid and on catheter pieces with inflammatory reaction in the brain parenchyma was analyzed quantitatively. RESULTS: Sterile and infected Ag-PP-g-PEG-covered groups revealed significantly lower bacteria colony count on the catheter surface (ANOVA, 0 ± 0, p < 0.001; 1.08 ± 0.18, p < 0.05, respectively). There was moderate inflammatory response in the parenchyma in group 4, but in groups 5 and 6, it was similar to that of the sterile group (ANOVA, 16.33 ± 3.02, p < 0.001; 4.00 ± 0.68, p < 0.001, respectively). CONCLUSIONS: The PP-g-PEG, especially Ag-PP-g-PEG polymer-coated ventricular catheters are more effective in preventing the catheter-related infection and created the least inflammatory reaction in the periventricular parenchyma.

Effects of thyroid hormone supplementation on anastomotic healing after segmental colonic resection.

BACKGROUND: Alterations of thyroid hormones in colorectal surgery were previously studied. The aim of the present study was to determine the effects of triiodothyronine (T3) supplementation on anastomotic healing after segmental colectomy. MATERIAL AND METHODS: Thirty male Wistar albino rats were divided into sham (n = 6), control (n = 12), and experimental (n = 12) groups. Sham group rats were immediately sacrificed after segmental colonic resection. Control and experimental group rats underwent resection and anastomosis. Experimental group rats received a single dose of T3 (400 µg/100 g) in postoperative day 1. Half of both control and experimental group rats were sacrificed on postoperative d 3 and the remaining half were sacrificed on postoperative d 7. Hydroxiproline (HP), myeloperoxidase (MPO), thyroid stimulating hormone (TSH), free T3 (FT3), and free thyroxine (FT4) levels, bursting pressure, and histologic analyses of the anastomotic segments were compared. RESULTS: FT3 levels significantly decreased in control groups rats compared with the sham group (P < 0.01). However, T3 hormone given rats had no decline in FT3 levels. Anastomotic bursting pressure was significantly higher in the experimental group rats on postoperative d 7 (P = 0.015). Histopathologic analyses of the anastomotic segments determined significantly more severe edema and necrosis in control group rats (P < 0.05). Collagen deposition in the anastomotic tissue was significantly higher in experimental group rats on postoperative d 7 (P = 0.015). CONCLUSION: Anastomosis after colon resection is associated with decreased FT3 level. T3 supplementation ameliorates the reduction in FT3 and seems to provide constructive therapeutic effects on anastomotic healing.

Effects of dexamethasone on ischemia reperfusion injury following pringle maneuver.

BACKGROUND/AIMS: Hepatic ischemia reperfusion injury induced by Pringle maneuver leads to bacterial translocation, endotoxemia and apoptosis. Our aim was to compare the effects of low and high dose dexamethasone pretreatment on antioxidant enzyme activities, bacterial translocation, endotoxemia and apoptosis, following Pringle maneuver. METHODOLOGY: Thirty-two rats were randomized into four groups; sham, control and two treatment groups; low dose dexamethasone (0.1 mg/kg) and high dose dexamethasone (1 mg/kg). In the treatment groups dexamethasone was administered intraperitoneally one hour before Pringle maneuver. Twenty-four hours after closing rats' abdomen, re-laparotomy was performed and tissue samples were taken from the mesenteric lymph nodes, liver, ileum and spleen and 1 mL of blood was drawn from the aorta. Bacterial translocation, endotoxemia, apoptosis and enzyme activities of G6PD, 6-PGD, GR, GST, GPx and CAT were evaluated. RESULTS: Low dose dexamethasone significantly decreased bacterial translocation to mesenteric lymph nodes, and reduced liver and enterocyte apoptosis, whereas high dose dexamethasone caused only a significant reduction in enterocyte apoptosis (p<0.05). Dexamethasone both in low and high doses significantly reduced the decrease in antioxidant enzyme levels (p<0.05). CONCLUSIONS: Low dose dexamethasone pretreatment caused constructive therapeutic effects after Pringle maneuver, whereas these effects were seen partially with a high dose.

Soft tissue response to the presence of polypropylene-G-poly(ethylene glycol) comb-type graft copolymers containing gold nanoparticles.

The aim of this study is to evaluate the soft tissue response of the pure and Au-embedded PPg-PEG. PP-g-PEG2000, PP-g-PEG4000, Au-PP-g-PEG2000, and AuPP-g-PEG4000 were obtained via chlorination of polypropylene and polyethylene glycol in the presence of a base with a "grafting onto" technique. Solvent cast films of these four copolymers with PP as a control group were embedded into five different rats. After 30 days of implantation, microscopic evaluation of inflammation and SEM analysis were done. PP had the most intense inflammatory reaction among the other polymers. PP-PEG block copolymers with high molecular weight and gold-nanoparticles-embedded ones revealed mild inflammatory reaction independently. SEM assessment revealed punched hole-like defects on the surface of all polymer samples except for PP. Graft copolymers with PEG, especially Au-attached ones, have favorable soft tissue response, and inflammatory reaction becomes milder as the number of PEG side chains increases.

The relationship between mean platelet volume levels and the inflammation in Helicobacter pylori gastritis.

Helicobacter pylori is a cause of chronic gastritis. Mean platelet volume (MPV) has been started to be used as a simple inflammatory indicator in some diseases. We have aimed especially to investigate the usability of MPV as a simple indicator that may reflect severity of inflammation in gastric mucosa. Included in the study were a total of 114 patients who visited the outpatient clinic of gastroenterology with complaint of dyspepsia. Blood MPV levels in hemogram results were evaluated. Esophagogastroduodenoscopy was performed on patients included in the study, and histological analysis was performed by obtaining 2 specimens from each of antrum, corpus, and incisura angularis. All specimens were evaluated according to the updated Sydney System. No statistically significant result was found among blood MPV levels, the intensity of H pylori, and the severity of inflammation of gastric mucosa. However, it is interesting that mean MPV levels in cases with lymphoid follicle were lower. We suggest that MPV level cannot be used as a simple marker to reflect H pylori intensity and severity of inflammation in gastric endoscopic biopsies.

Relationship of the intensity of Helicobacter pylori and severity of inflammation with beta-2 microglobulin levels in serum according to the updated Sydney System.

OBJECTIVE: Helicobacter pylori (HP) is a cause of chronic gastritis. Beta-2 microglobulin has been used as a simple inflammatory indicator in some diseases. We investigate the usability of beta-2 microglobulin as a simple marker that may reflect the severity of inflammation and intensity of HP in gastric mucosa. MATERIALS AND METHODS: A total of 114 patients was included in the study, who applied to an outpatient gastroenterology clinic with complaint of dyspepsia. Serum beta-2 microglobulin levels were evaluated in 109 patients. Esophagogastroduodenoscopy was performed on patients included in the study, and histological analysis was performed by obtaining two specimens from each of antrum, corpus, and incisura angularis. All specimens were evaluated according to the updated Sydney System. RESULTS: No statistically significant result was found between serum beta-2 microglobulin levels and the intensity of HP and the severity of inflammation of gastric mucosa. However, it was observed that the serum beta-2 microglobulin level in specimens taken from corpus was found to be higher in patients with moderate-severe HP intensities compared to those with lower HP intensities. CONCLUSIONS: Although HP is the cause of the chronic active gastritis characterized with the infiltration of lymphocytes, plasma cells, and neutrophils, it is accompanied by local involvement apart from diseases with a course of systemic involvement. We suggest that the serum beta-2 microglobulin level cannot be used as a simple marker of HP intensity and severity of inflammation in gastric endoscopic biopsies.

Study of FHIT and WWOX expression in mucoepidermoid carcinoma and adenoid cystic carcinoma of salivary gland.

Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms with divergent morphological features and clinical behavior. ACC is a basaloid tumor whereas MEC is a glandular epithelial neoplasm. FHIT and WWOX are tumor suppressor genes that encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. In previous studies, we have shown concordant loss of Fhit and Wwox expression in breast cancer, with significantly more frequent loss in cancers of basal-like phenotype. To determine if there is a similar association in salivary gland neoplasms, we designed a study of MEC and ACC of salivary gland on tissue microarrays (TMA). TMAs were constructed from 25 MEC and 19 ACC of salivary gland. Fhit and Wwox protein expression was assessed by immunohistochemical staining of cores on TMAs. Correlations among immunohistochemical markers and histological type were determined by statistical analyses. Significantly reduced Fhit and Wwox expression was observed in ACC (p=0.002 and p<0.001, respectively). The results suggest that, as for breast cancer, loss of Fhit and Wwox expression might have a role in the pathogenesis of basaloid differentiation in salivary gland neoplasms; alternatively, differences in chromatin structure at chromosome fragile regions might make fragile genes more accessible to DNA damage and rearrangement early during preneoplastic stages of basaloid cancers. Studies of basaloid tumors of other organ systems may show similar results and these findings may have implications for treatment modalities designed for basal-like tumors.