Stem cell markers: A guide to neoadjuvant therapy in breast carcinomas.

Aim: This study aims to investigate potential associations between the stem cell population and the degree of tumor regression in breast carcinomas treated with neoadjuvant therapy. Settings and Design: The study included 92 patients with breast carcinoma who received neoadjuvant therapy. Tumor regression was defined based on Miller and Payne grading system. Patients with grade 1 or 2 regression on a 5-point scale were included in group 1 (n = 37), grade 3 regression in group 2 (n = 32), and grade 4 or 5 regression in group 3 (n = 23). Materials and Methods: Immunohistochemical staining was performed on paraffin block sections of every case using CD44, CD24, CD29, CD133, ID4, and ALDH1 antibodies to detect stem cells. Statistical Analysis Used: IBM Statistical Package for the Social Sciences (SPSS), version 23.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analyses, and a P value less than 0.05 was considered statistically significant. Results: Histologically high-grade tumors are more common in the near-complete/complete response group (P = 0.004). HER2-positive tumors were more common in the complete/near-complete response group (P = 0.054). Tumor cells positive for stem cell markers CD44 and CD24 were more common in the poor response group (P = 0.027 and P = 0.001, respectively). CD29 expression was reduced in the posttreatment residual tumor tissue in the near-complete/complete response group. Conclusion: High CD44 and CD24 expression may be a predictor of poor response/nonresponse to neoadjuvant therapy in breast carcinomas. Background: In recent years, stem cells have been defined as the main cell population responsible for resistance to anticancer therapies.

High-risk Human Papillomavirus (hrHPV) Prevalence and Genotype Distribution among Turkish Women.

Purpose: This study aimed to determine the rates of distribution of high-risk HPV (hrHPV) genotypes according to cervical smear samples and biopsy results in a large sample of Turkish women. Methods: The study was conducted with 4,503 healthy volunteer women aged 19-65 years. Samples of cervical smears were collected during the examination and liquid-based cytology was used for the Pap tests. The Bethesda system was used for reporting the cytology. High-risk HPV genotypes including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were investigated in samples. The study cohort was grouped according to age in decades, with comparisons made according to these age groups, Bethesda class, and cervix biopsy results. Results: Among all cases, 903 (20.1%) participants were positive for 1074 hrHPV-DNA genotypes. HPV-DNA positive cases were most common in the 30-39 age group (28.0%), followed by women under the age of 30 (38.5%). HPV genotypes were determined as, in order of frequency: Other hrHPV (n = 590, 65.3%), HPV16 (n = 127, 14.1%), Other HPV + HPV16 (n = 109, 12.1%), HPV 18 (n = 33, 3.6%), and Other HPV + HPV 18 (n = 32, 3.5%). Cervical smears were reported as ASCUS in 304 (6.8%) samples and high-grade squamous intraepithelial lesion (HSIL) in 12 (0.3%) of the samples. Biopsy demonstrated the presence of HSIL in 110 (12.5%) participants, with 644 (73.3%) negative cases. Conclusion: This showed an increasing incidence of Other HPVs besides the known importance of HPV 16 and 18 genotypes as risk factors for cervical cancer.

Effects of tissue cytomegalovirus quantitative polymerase chain reaction in the management of ulcerative colitis flare-ups: Should we wave aside?

BACKGROUND AND STUDY AIMS: The role of cytomegalovirus (CMV) infection for disease reactivation in ulcerative colitis (UC) patients remains controversial and diagnostic tests are yet to be standardized. We aimed to define the clinical relevance of CMV detection by mucosal polymerase chain reaction (PCR) in UC patients by comparing the clinical course of UC in CMV-treated and CMV-untreated groups in tissue CMV-PCR positive cases. PATIENTS AND METHODS: In this retrospective study, 141 patients diagnosed with moderate-to-severe UC admitted to our clinic with disease flare, colonic tissue CMV PCR was assessed. RESULTS: The median age of the study population was 39 years, and 99 (70.2%) patients were male. Eighty-eight (62.4%) patients were CMV-PCR (+) and 53 (37.6%) were CMV PCR (-). The CMV-PCR (+) and CMV PCR (-) groups showed no significant difference concerning age, sex, disease duration, site of involvement and disease activity and administered treatments. The median tissue CMV-PCR was 41,098 IU/mL (IQR:2,344.25-136,192). Thirty-four of 88 CMV-PCR (+) patients received antiviral therapy. The tissue CMV-PCR level of patients who received antiviral therapy was 124,381 IU/mL (IQR: 19,309-412,335), and it was 6,292 IU/mL (IQR: 997-71,154) in patients who did not receive antiviral therapy; (p < 0.001). Sixteen (47.1%) of 34 patients who received antiviral therapy achieved remission. Two of the non-responders underwent colectomy (one because of dysplasia and one who did not respond subsequent biologic agent either). Remaing 16 achieved remission by escalating the immunsuppresive/biologic agent therapy. CONCLUSION: CMV infection is responsible for only a minority of cases of UC flares and all are steroid-resistant cases. Most of the patients non-responsive to antiviral treatment respond to increased anti-inflammatory treatment. Hesitancy in the decision of escalating immunsuppresive treatment rather than CMV disease may be responsible for worsening disease course and increased colectomy rate in a significant number of the patients who are tissue CMV-PCR (+).

Rat Model Investigation on the Role of Biomarkers in Hepatic Ischemia-Reperfusion Injury.

OBJECTIVES: Liver function is affected by ischemiareperfusion. Ischemia-reperfusion injury to the liver often follows hepatobiliary surgery. Here, we investigated biomarkers of liver ischemia-reperfusion injury using an animal model. MATERIALS AND METHODS: For this study, 24 male Sprague Dawley rats (146-188 g) were divided into 4 groups: group A was the control group, group B was the partial hepatic ischemia-reperfusion group, group C was the total hepatic ischemia-reperfusion group, and group D was the intermittent total hepatic ischemiareperfusion group. Laboratory liver function levels were measured before ischemia, after ischemia, and after reperfusion. We used liver and renal biopsies for histopathological examination at the end of the study. RESULTS: After clamping and reperfusion, alanine aminotransferase and cystatin C levels in groups B, C, and D were significantly higher than levels in group A. In group B, after clamping, neutrophil gelatinaseassociated lipocalin levels were higher than in groups A and D, with significantly higher level than in group D after reperfusion. Neutrophil gelatinase-associated lipocalin levels decreased significantly in groups B, C, and D after reperfusion. There was significantly greater hepatic damage in groups B, C, and D compared with group A but no significant differences in renal injury scores among the groups. There was a significant positive correlation between hepatic damage and renal injury. With regard to histopathological examination versus laboratory results, a statistically significant positive correlation was shown between grade of hepatic damage and serum alanine aminotransferase and cystatin C levels. Similarly, there was a positive correlation between renal damage score and alanine aminotransferase level. CONCLUSIONS: In our animal model, alanine amino - transferase and cystatin C levels tended to increase with ischemia-reperfusion injury levels but neutrophil gelatinase-associated lipocalin decreased during reperfusion. In liver ischemia, we suggest that neutrophil gelatinase-associated lipocalin may be an important biomarker for distinguishing the reperfusion phase.

Effects of Orally Consumed Rosa damascena Mill. Hydrosol on Hematology, Clinical Chemistry, Lens Enzymatic Activity, and Lens Pathology in Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus is a multisystemic metabolic disorder that may affect the eyes, kidneys, vessels, and heart. Chronic hyperglycemia causes non-enzymatic glycation of proteins and elevation of the polyol pathway resulting in oxidative stress that damages organs. The current study aimed to investigate the dose-dependent effects of orally consumed Rosa damascena Mill. hydrosol on hematology, clinical biochemistry, lens enzymatic activity, and lens pathology in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male Sprague-Dawley rats by intraperitoneal administration of STZ (40 mg/kg body weight). Rose hydrosols containing 1515 mg/L and 500 mg/L total volatiles (expressed as citronellol) were introduced to rats orally for 45 days. Consumption of 1515 mg/L volatile containing rose hydrosol successfully ameliorated hematologic, hepatic, and renal functions. Hydrosols also attenuated hyperglycemia and decreased the advanced glycation end-product formation in a dose-dependent manner. Rose hydrosol components significantly increased the lens enzymatic activities of glutathione peroxidase and decreased the activity of aldose reductase to prevent cataractogenesis. Histopathological examinations of rat lenses also indicated that increasing the dose of rose hydrosol had a protective effect on lenses in diabetic conditions. Additionally, in silico modeling of aldose reductase inhibition with rose hydrosol volatiles was carried out for extrapolating the current study to humans. The present results suggest that rose hydrosol exerts significant protective properties in diabetes mellitus and has no toxic effect on all studied systems in healthy test groups.

BRAF V600E mutation and BRAF VE1 immunoexpression profiles in different types of glioblastoma.

Abnormalities in proto-oncogene B-Raf (BRAF) are typical in several subgroups of gliomas, including pilocytic astrocytomas, optic nerve gliomas, pleomorphic xanthoastrocytomas (PXA), anaplastic PXAs and gangliogliomas. However, they are rarely reported in adult gliomas. BRAF alterations are frequent in a distinct variant of glioblastomas (GBMs) known as epithelioid GBMs (E-GBMs). There are limited studies on whether immunohistochemistry (IHC) can be used to determine the presence of BRAF VE1 mutations in these tumors. The aim of the current study was to examine BRAF V600E mutations in 20 GBMs, including GBMs with epithelioid features, giant cell GBMs and conventional GBMs. V600 mutations were detected using the Cobas 4800 BRAF V600 Mutation Test, and IHC analysis was also performed. Of the 6 cases of GBM with epithelioid features, 1 exhibited a BRAF V600E mutation, while the other cases did not. IHC staining was positive in 3 out of the 8 conventional GBMs. Vemurafenib is a targeted therapy that has mainly been used for the treatment of melanoma patients for several years, and as a possible alternative treatment for cases of GBM harboring BRAF mutations, its existence may make testing for BRAF status important.

Rare Entities of Histopathological Findings in 755 Sleeve Gastrectomy Cases: a Synopsis of Preoperative Endoscopy Findings and Histological Evaluation of the Specimen.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most preferred technique in morbidly obese patients for weight loss. There is a controversy about the routine preoperative evaluation of the stomach and the routine microscopic examination of all LSG specimens. Our aim is to analyze the results of both preoperative upper gastrointestinal endoscopy and endoscopic biopsies and also the results of histopathological examination of LSG specimens. MATERIALS AND METHODS: The data of patients who underwent LSG from January 2011 to November 2016 were analyzed retrospectively from a prospectively collected database. Seven hundred fifty five of 819 patients who met the inclusion criteria were included in this study. Data on patients' demographic variables [age, gender, BMI (kg/m2)], preoperative upper GI endoscopy and biopsy results, postoperative histopathological results of the specimens, and the process of the patients with malignant histopathological investigation in the follow-up period were collected. RESULTS: This study involves 755 patients with a mean age of 39.6 ± 11.7 years and has 496 (65.6%) to 259 (34.4%) female to male ratio. None of the patients harbored macroscopic or microscopic malignant pathological finding in the preoperative assessment. Hiatal hernia was detected in 78 (10.2%) patients and gastric/duodenal ulcers were detected in 52 (6.8%) patients in endoscopy. Incidental malignant and/or premalignant histopathological findings-intestinal metaplasia (1.4%) and malignant lesions (0.5%)-were rarely found in the evaluation of the surgical specimens. CONCLUSIONS: Both preoperative endoscopic assessment and postoperative histopathological examination of the specimen are mandatory in LSG patients.

Utilization of Wilms' tumor 1 antigen in a panel for differential diagnosis of ovarian carcinomas.

OBJECTIVE: Ovarian metasteses are often mistaken for primary adenocarcinoma. Studies conducted in recent years have focused on a search for an immunohistochemical marker to aid the differential diagnosis primary and metastatic ovarian carcinoma. Our study objective was to study the usefulness of Wilms tumor 1 (WT 1) antigen in this context. MATERIALS AND METHODS: The study was conducted at the pathology clinic of Lütfi Kirdar Training and Research Hospital. Deparaffinated blocks of 40 epithelial ovarian tumors, 40 colon adenocarcinomas, and 35 cases of omentum metastases were studied. Cytokeratin 7 (CK 7), cytokeratin 20 (CK 20), and WT 1 were applied to all specimens. RESULTS: All ovarian adenocarcinomas were stained with CK 7 (100%). Colorectal adenocarcinomas were stained positive with CK 20 in 87.5% of cases. Primary ovarian adenocarcinomas stained positive with WT 1 in 82.5% of the cases and none of the colorectal adenocarcinomas showed staining with WT 1 (0%). CONCLUSION: WT 1 can be used in conjuction with CK 7 in the differential diagnosis of ovarian carcinomas.

In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).

OBJECTIVE: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). MATERIAL AND METHOD: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. RESULTS: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. CONCLUSION: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.

Effect of local bleomycin sulfate application on seroma formation in a rat mastectomy and axillary lymph node dissection model.

Seroma formation is one of the most common complications following breast cancer surgery. It may lead to delay of adjuvant therapies and increasement of therapy costs. Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. It is locally used in the treatment of pleural effusion. The present study aimed to investigate seroma-reducing effect of local bleomycin application after mastectomy. Sixteen female Wistar Albino rats were used in this study. The rats were divided into two equal groups. Under general anesthesia all rats underwent unilateral mastectomy as definition by Harada. Serum physiologic was applied to animals in Group 1 (control group) and bleomycin to Group 2. Mastectomized localization was explored on the 10th day postoperatively. Seroma and tissue samples were obtained from axilla and thoracic wall for histopathological examination. The amount of seroma was significantly lower in the bleomycin group as compared to the control group (P=0.002). Fibrosis, PNL infiltration and the number of fibroblasts were significantly higher in the bleomycin group. No difference was identified between the groups in terms of angiogenesis, edema, congestion, and monocyte, lymphocyte and macrophage infiltration. Local bleomycin sulfate application might be a therapeutic option in patients with seroma formation, as well as in the patients with malignant pleural effusion. Nonetheless, further studies that compare the efficacy and adverse effects (benefit-to-harm ratio) of bleomycin sulfate are needed.

Toxic Anterior Segment Syndrome following Phacoemulsification Secondary to Overdose of Intracameral Gentamicin.

Objective. To report a case of toxic anterior segment syndrome (TASS) that was caused by inadvertent anterior chamber and cornea stromal injection with high dose gentamicin following cataract surgery. Methods. Case report. Results. We report a 72-year-old female patient who developed TASS that was caused by high dose gentamicin (20 mg/0.5 mL), which was inadvertently used during the formation of the anterior chamber and hydration of the corneal incision. Unlike previous cases, hyphema and hemorrhagic fibrinous reaction were seen in the anterior chamber. Despite treatment, bullous keratopathy developed and penetrating keratoplasty was performed. The excised corneal button was sent for histopathological examination. Conclusions. Subconjunctival gentamicin is highly toxic to the corneal endothelium and anterior chamber structures. Including it on the surgical table carries a potentially serious risk for contamination of the anterior chamber.

Association between human papillomavirus and endometrial adenocarcinoma.

Several studies have suggested a possible role of human papillomavirus (HPV) in the pathogenesis of endometrial carcinoma. The aim of the study was to investigate the presence of HPV DNA in endometrium cancers and nonneoplastic endometrium. Sixty endometrial adenocarcinomas with and without squamous differentiation and the nonneoplastic endometrium tissue of fifty-six of the same patients were analyzed for the presence of family 16 and family 6 HPV DNA by using chromogenic in situ hybridization technique on formalin-fixed and paraffin-embedded archival samples, and the results were confirmed by polymerase chain reaction method. HPV DNA was not detected either in the endometrial adenocarcinoma with or without squamous differentiation, or in the nonneoplastic endometrium tissue. It appears that HPV does not play any role in the pathogenesis of endometrial carcinoma, since endometrium may not to be a suitable host for HPV replication.

A prospective comparative study to assess the contribution of radioisotope tracer method to dye-only method in the detection of sentinel lymph node in breast cancer.

BACKGROUND: Metastasis in the axillary lymph nodes is the most important known prognostic factor for breast cancer. We aimed to investigate the contribution of the radioisotope tracer method to the dye-only method by performing sentinel lymph node biopsy on the same patient group during a single surgical session. METHODS: Forty-two patients who underwent operations in our clinic from February 2010 to October 2011 and with masses of <5 cm and clinically and radiologicallly negative axilla (T1-2 N0) were prospectively included in this study. After paraffin examination results were obtained, the numbers and metastatic states of the lymph nodes that were unidentifiable during surgery (although they were stained) but were detected by a gamma probe, lymph nodes that were only stained, lymph nodes that were only radioactive (hot), and lymph nodes that were both stained and radioactive (stained-hot) were determined in all patients. In patients who underwent axillary lymph node dissection, the total numbers of lymph nodes removed and their metastatic states were determined separately. RESULTS: At least one blue-stained sentinel lymph node was identified in all patients during the blue-stained lymph node detection stage. The average number of sentinel nodes removed at this stage was 2.1 ± 1.1. In the second surgical stage (the stage in which nodes with axillary counts were investigated with the gamma probe) in these 41 patients, at least one additional hot node was removed, or at least one of the nodes that was removed because it was blue was also hot. In addition to the lymph nodes removed in the dye stage, 34 hot lymph nodes were excised from 21 patients. Overall, the average number of hot lymph nodes removed was 2.9 ± 1.5. In all patients, subsequent frozen sections and histopathological examinations were 100% concordant with the sentinel lymph nodes that were removed; the stained sentinel lymph nodes that were removed first did not affect the decision to perform axillary dissection. CONCLUSION: The results of our study indicate that performing sentinel lymph node biopsy with dye only is sufficient and as effective as the combined method.

Effects of local phenytoin on seroma formation after mastectomy and axillary lymph node dissection: an experimental study on mice.

BACKGROUND: Seroma formation is the most common complication after breast cancer surgery. It is an important complication since it prolongs therapy duration, increases cost, and negatively affects patient psychology. Currently, there is no widely accepted method that prevents seroma formation. We tried to investigate impact of local phenytoin application on seroma formation following an experimental mastectomy model created in rats. METHODS: Two groups including eight rats in each were randomized. Saline injection was applied in the first group, whereas 1% phenytoin was locally used in the second group. Ten days after the surgery, seroma formation and wound-healing processes were evaluated using histopathological and biochemical examinations. RESULTS: Phenytoin significantly decreased seroma formation. Fibrosis was significantly increased and angiogenesis was significantly reduced in the phenytoin group (P < 0.05). Increased levels of macrophage and lymphocyte infiltration was detected in the control group (P < 0.05). No difference was detected between the groups in terms of necrosis, edema, congestion, and PNL (Polymorphonuclear leucocyte) and fibroblast infiltration. CONCLUSIONS: Seroma formation-reducing effect of phenytoin might have occurred over its anti-inflammatory, anti-angiogenetic, and fibrosis augmenting effects.

Low-grade endometrial stromal sarcoma with retroperitoneal metastases: an unusual case report.

BACKGROUND: Endometrial stromal sarcoma (ESS) is an uncommon malign neoplasm, and its occurrence outside the uterus is extremely rare in the absence of metastasis or extension of a primary uterine neoplasm. When arising in the pelvis or abdominal cavity, ESS is associated with uterine adnexa or serosal surface of various organs. CASE: We present the case of a 46-year-old woman with lower abdominal pain and regular menstruation who underwent laparotomy after a diagnosis of pelvic mass mimicking a right adnexial tumor. Exploration of the pelvis revealed a retroperitoneal mass of 15 cm in diameter in the right illiac fossa without accompanying pelvic or paraaortic lymphadenopathy. Uterus and ovaries were bilaterally normal in size. The pathology showed low-grade ESS of the uterus with direct spread to retroperitoneum without serosal metastases. CONCLUSION: This case shows that despite its well-known good prognostic nature, low-grade ESS may behave as an aggressive malignancy.