Is it Possible to Avoid Liver Biopsy in Living Donors for Liver Transplantation by Using Two-Dimensional Shear Wave Elastography?

PURPOSE: The present study aims to evaluate the correlation of two-dimensional shear wave elastography results with histopathological findings performed simultaneously with liver biopsy (LB) in healthy liver transplant donors. METHODS: A total of 53 living donors, 35 male and 18 female, were included in this prospective, observational, single-center study. Patients with abnormal liver function tests were not included in our study. Hepatosteatosis, fibrosis, and inflammation were evaluated with the Fatty Liver Inhibition of Progression and Steatosis, Activity, and Fibrosis algorithm of donor LB. RESULTS: The mean age of the donors was 33.04 ± 9.07 years and the mean body mass index was 23.41 ± 6.23 kg/m2. The mean elastography kilo pascal (kPA) value of all donors was determined as 6.03 ± 2.32 kPa. The mean LB activity scores of the donors were found to be 1.64 ± 1.18 and ranged from 0 to 5. There was no significant correlation between elastography kPa value and pathologic activity score, steatosis score, balloon degeneration, and inflammation grade fibrosis scores (P > .05). CONCLUSION: Shear wave elastography measurements showed that the predictive power of pathologic findings in donor LB was not sufficient.

Trans-Arterial Chemoembolization with 50 µm Degradable Starch Microspheres Versus 300-500 µm Drug Eluting Beads in Hepatocellular Carcinoma: A Comparative Analysis of Initial Treatment Outcomes.

Background and Aims: Trans-arterial chemoembolization (TACE) has become a widely accepted treatment in unresectable hepatocellular carcinoma (HCC). We aimed at comparing the efficacy of Degradable Starch Microspheres (DSMs)-TACE with 50 ± 7 µm versus 300-500 µm Drug Eluting Beads (DEB)-TACE in terms of initial clinical and radiological treatment response parameters. Material and Methods: A total of 54 patients with unresectable HCC who underwent DEB-TACE (n = 25) or DSMs-TACE (n = 29) were included in this retrospective study. Baseline demographic and clinical characteristics, duration of follow-up, local recurrence and survival status, as well as treatment outcome including treatment response via modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, viable and total tumor diameter and serum alpha-fetoprotein (AFP) levels were analyzed in both study groups. Results: No significant difference was noted between the two groups in terms of local recurrence (31.6 vs. 16.7%) or mortality (73.9 vs. 85.7%) rates after 36-month and 12-month follow-up, respectively. DSMs-TACE vs. DEB-TACE was associated with significantly higher complete response rate (27.6 vs. 0.0%, p = 0.011) and significant decrease in serum AFP levels (p = 0.013). Conclusion: Both DSMs-TACE with 50 ± 7 µm microspheres and 300-500 µm DEB-TACE are effective for local control of unresectable HCC. Our findings revealed superiority of DSMs-TACE over DEB-TACEnin terms of initial clinical and radiological tumor response; though no significant difference was noted between the two patient groups in terms of local recurrence or mortality during follow up.

APOBEC mutagenesis and selection for NFE2L2 contribute to the origin of lung squamous-cell carcinoma.

Lung squamous-cell carcinoma originates as a consequence of oncogenic molecular variants arising from diverse mutagenic processes such as tobacco, defective homologous recombination, aging, and cytidine deamination by APOBEC proteins. Only some of the many variants generated by these processes actually contribute to tumorigenesis. Therefore, molecular investigation of mutagenic processes such as cytidine deamination by APOBEC should also determine whether the mutations produced by these processes contribute substantially to the growth and survival of cancer. Here, we determine the processes that gave rise to mutations of 681 lung squamous-cell carcinomas, and quantify the probability that each mutation was the product of each process. We then calculate the contribution of each mutation to increases in cellular proliferation and survival. We performed in vitro experiments to determine cytidine deamination activity of APOBEC3B against oligonucleotides corresponding with genomic sequences that give rise to variants of high cancer effect size. The largest APOBEC-related cancer effects are attributable to mutations in PIK3CA and NFE2L2. We demonstrate that APOBEC effectively deaminates NFE2L2 at the locations that confer high cancer effect. Overall, we demonstrate that APOBEC activity can lead to mutations in NFE2L2 that have large contributions to cancer cell growth and survival, and that NFE2L2 is an attractive potential target for therapeutic intervention.

Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer.

Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptor-negative/HER2+ tumors is seen in 27-45% of cases. In contrast, estrogen receptor (ER)+/HER2+ tumors demonstrate pathologic complete response in ∼ 8% of cases and is generally limited to weak-to-moderate ER+/HER2+ tumors. It is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2+ tumors. A list of HER2+ patients who received neoadjuvant chemotherapy (with trastuzumab) in the years 2007-2010 was obtained from our hospital database. The 104 HER2+ tumors were classified into three groups based on semiquantitative hormone receptor and HER2 results as follows: ERBB2 (ER-/PR-[H-score ≤10]/HER2+), Luminal B-HER2 Hybrid (LBHH; weak to moderate ER+ [H-score 11-199]/HER2+), and Luminal A-HER2 Hybrid (LAHH; strong ER+[H-score ≥200]/HER2+). Pathologic complete response was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor volume reduction was also calculated based on pretherapy size and detailed evaluation of the resection specimen. In all, 52% (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was significantly higher than the pathologic complete response rate in LBHH (33%; 10 of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%) tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy regimen significantly increases the pathologic complete response rates in all HER2+ tumors. However, the benefit of trastuzumab is highest in ER-negative tumors and progressively decreases with increase in tumor ER expression. This information can be utilized to counsel patients considered for neoadjuvant chemotherapy and the same principle could be applied in the adjuvant setting.

The efficacy of percutaneous transluminal angioplasty for the endovascular management of arteriovenous fistula dysfunction: a retrospective analysis in patients with end-stage renal disease.

BACKGROUND: To evaluate efficacy of percutaneous transluminal angioplasty (PTA) for the endovascular management of arteriovenous fistula (AVF) dysfunction in patients with end-stage renal disease (ESRD). METHODS: A total of 135 consecutive patients with ESRD (mean±SD age: 58.8±9.4 years, 74.8% were males) who underwent endovascular treatment for a dysfunctional native AVF were included in this retrospective single-center study. Data on patient demographics, etiology of ESRD, characteristics of AVF, stenotic segments, PTA parameters and postoperative recurrence and patency rates within the 12 months were recorded. RESULTS: Technical and clinical success rates of PTA were 100.0% and 97.0%, respectively. Dysfunction recurrence rate was 30.4%. In patients with vs. without presence of recurrent AVF dysfunction, there was higher percentage of males (P=0.030), older age (P=0.018), diabetic or hypertensive rather than polycystic etiology (P<0.001), younger AVF (P<0.001), longer-segment stenosis (P=0.019) and lower median number (P=0.038) of stenotic segments. Presence of hypertension (OR 12.23, 95% CI: 4.29 to 34.85, P<0.001) and age of the AVF (OR 1.04, 95% CI: 1.00 to 1.08, P=0.029) were significant determinants of increased risk of recurrent AVF dysfunction. CONCLUSIONS: Our findings emphasize favorable safety and efficacy of PTA in the management of dysfunctional hemodialysis AVFs in terms of high technical and clinical success and low rates of residual stenosis, complications and post-PTA recurrence of AVF dysfunction. Male gender, older patient age, younger AVF and longer-segment stenosis were associated with higher likelihood of AVF failure, whereas hypertension and age of AVF were the two significant determinants of increased risk of post-PTA recurrence of AVF dysfunction.

The Role of Telecytology in the Primary Diagnosis of Thyroid Fine-Needle Aspiration Specimens.

INTRODUCTION: The Acibadem Health Group (AHG) has been using telepathology/digital pathology stations since 2006. In 2013, the system was changed from videoconferencing to digital pathology (whole-slide imaging) utilizing 3DHISTECH scanners and software. In 2017, digital cytology started to be used for routine cytopathologic diagnosis for thyroid fine-needle aspiration (FNA) cases. MATERIAL AND METHODS: Two hundred and twenty-seven thyroid cases were received for analysis using telecytology (TC) during the period from November 2017 to May 2018. Rapid on-site evaluation was performed at the Atakent Hospital of the AHG by a cytotechnologist and scanned on the same day. For every case, there were Diff-Quik- and Papanicolaou-stained FNA smears. Each glass slide was digitized with a 3DHISTECH whole-slide scanner in 1 focal Z-plane at ×40 magnification. RESULTS: Two hundred and twenty-seven thyroid FNA specimens were retrieved, of which 25 had histologic follow-up. Samples were classified as nondiagnostic in 3%, benign in 74%, atypia of undetermined significance/follicular lesion of undetermined significance in 13%, suspicious for follicular neoplasia/follicular neoplasia in 3%, suspicious for malignancy in 4%, and malignant in 3%. When only the "suspicious for malignancy" and "malignancy" categories were considered positive tests, cytology sensitivity and specificity using TC for diagnosis was 100%. CONCLUSIONS: Our data demonstrate that TC is suitable to provide a primary diagnosis in daily routine cytology practice. Despite the promising results, there were some challenges stemming from the novelty of using TC for the primary diagnosis. The study also addresses both advantages and disadvantages of TC in daily practice to increase the efficiency of the technique in primary diagnosis.

The Efficacy of Paclitaxel Drug-Eluting Balloon Angioplasty Versus Standard Balloon Angioplasty in Stenosis of Native Hemodialysis Arteriovenous Fistulas: An Analysis of Clinical Success, Primary Patency and Risk Factors for Recurrent Dysfunction.

PURPOSE: To investigate the efficacy of paclitaxel drug-eluting balloons (PEB) versus standard balloon angioplasty (BA) in stenosis of native hemodialysis arteriovenous fistulas (AVFs). MATERIALS AND METHODS: A total of 96 patients with ESRD (mean ± SD age 57.0 ± 9.1 years, 63.5% were males) who underwent endovascular treatment with PEB angioplasty (n = 32) and BA (n = 64) for a dysfunctional native AVF were included. Clinical success, complications, primary patency and postoperative recurrence parameters were recorded in each group. RESULTS: Primary patency rate at 6 months was significantly higher in PEB than in BA group (96.9 vs. 20.3%, p < 0.001), while the two groups had similar primary patency rates at 9 months (66.8 vs. 50.0%) and 12 months (6.3% for each). No significant difference was noted between PEB and BA groups in terms of the rate (21.9% and. 31.3%), time (median 220 vs. 152.5 days) and reasons (reocclusion in 18.8 vs. 28.1%) for dysfunction recurrence as well as the number of recurrent treatments. AVF dysfunction recurrence was more likely in younger age AVF (median 4 vs. 23 months, p < 0.001 in PEB, and 8.5 vs. 20.5 months p = 0.001 in SBA) and in AVF ≤ 6 months in both SBA and PEB groups (71.4 vs. 12.0%, p = 0.005 in PEB, 40.0 vs. 2.3%, p < 0.001). CONCLUSION: In conclusion, our findings emphasize favorable safety and efficacy of PEB and BA in the management of dysfunctional hemodialysis AVFs with similar rates of post-PTA recurrence of AVF dysfunction. Nonetheless, there was a nonsignificant tendency for lower rate and a delay for recurrent dysfunction in patients treated with PEB and a significant association younger AVF age with an increased risk of post-PTA recurrence of AVF dysfunction. LEVEL OF EVIDENCE: 3, Retrospective cohort study.

Liver Transplant in Patients With Portal Vein Thrombosis: The Experience of 55 Patients.

OBJECTIVES: Portal vein thrombosis is no longer a contraindication for liver transplantation. However, varied outcomes are still reported with regard to patients with complete portal vein thrombosis. MATERIALS AND METHODS: We analyzed data of 505 patients who underwent liver transplant between January 2014 and June 2017. Of 505 patients, 55 (10.9%) had portal vein thrombosis, which included 37 patients (67%) who had living-donor and 18 patients (33%) who had deceased-donor liver transplant. According to Yerdel classification, 5 (9%), 28 (51%), 12 (22%), and 10 patients (18%) had grade I, II, III, and IV portal vein thrombosis, respectively. RESULTS: Thrombectomy was successful in 46 patients (84%). Forty-three patients had patent portal inflow (93.5%), but 3 patients (6.5%) required a second thrombectomy on day 1 posttransplant. Of 10 patients with grade IV portal vein thrombosis, 9 (16%) underwent extra-anatomic portal vein anastomosis. Of these 9 patients, 7 (77.7%) showed patent portal inflow during the early postoperative period. Median follow-up time was 15.5 ± 13.1 months. During this time, portal vein stenosis was detected in 5 patients. Risk of repeat thrombosis was not significantly different between patients with deceased-donor and patients with living-donor liver transplant. Overall patient survival rates for patients with and without portal vein thrombosis were 73% (40/55) and 84% (376/450), respectively, which showed significant difference (P = .05). CONCLUSIONS: In contrast to early-grade portal vein thrombosis, complete portal vein thrombosis still provides a treatment challenge with high risk of morbidity and poor early outcomes in liver transplant recipients.

[Detection and typing of human papilloma virus by polymerase chain reaction and hybridization assay in cervical samples with cytological abnormalities]. / Sitolojik atipi izlenen servikal örneklerde insan papilloma virusunun polimeraz zincir reaksiyonu ve hibridizasyon yöntemleriyle saptanmasi ve tiplendirilmesi.

Certain mucosa-tropic human papillomavirus (HPV) types are associated with carcinoma of the uterine cervix or its precursor lesions. In addition to cytological screening, early diagnosis and treatment of cervical carcinoma rely on sensitive detection and typing of HPV isolates. In this study, HPV detection and typing were performed in the cervical samples of patients with abnormal cytological evaluation. Forty randomly-selected cervical samples that comprise 18 ASC-US (Aypical Squamous Cells of Undetermined Significance), four AG-US (Aypical Glandular cells of Undetermined Significance), one ASC-H (Atypical Squamous Cells-can not exclude HSIL), one HSIL (High-grade Intraepithelial Lesion), 14 LSIL (Low-grade Intraepithelial Lesion), one adenocarcinoma and one squamous cell carcinoma, obtained by a commercial liquid-based cytology system (ThinPrep Pap Smear Method, Cytyc, USA), were included to the study. HPV-DNA detection were accomplished by L1 in-house polymerase chain reaction (PCR) performed using MY09/11 and GP5/6 primers along with a commercial real-time PCR (HeliosisTM HPV LC PCR Kit; Metis Biotechnology, Turkey) that detects HPV infections and HPV-16 via melting curve analysis. A commercial PCR-array hybridization test (Rapid HPV Genotyping MacroArray; HybriBio Inc, Hong Kong) that can identify 21 low and high risk HPV types was employed for typing. Viral DNA was detected in 35% (14/40) and 57.5% (23/40) of the samples by MY09/11 and GP5/6 primers, respectively. All in-house PCR positive samples were also positive in the real-time PCR assay. PCR-array hybridization assay provided typing results in 95.6% (22/23) of the PCR positive samples while one LSIL sample could not be typed by any of the methods used. High risk HPV types 16, 18, 31, 45, 52, 56, 58, 59,68 (65.8%); probable high risk type 53 (13.2%), low risk types 6, 42 and 81 (21%) were identified out of a total of 38 HPV isolates. Multiple infections with more than one HPV type were identified in 45.5% (10/22) of positive samples. High/probable high risk types were detected in all single infections and all low risk isolates were present in multiple infections. HPV-16 was identified in 31.8% (7/22) by real-time PCR and in 45.5% (10/23) of positive samples by PCR-array hybridization assay. HPV-16 was observed to be the most frequently detected type (10/22, 45.5%), followed by types 53 and 81 (5/22, 22.7%); 68 (4/22, 18.2%); type 58 (3/22; 13.6%); types 31, 42 and 59 (2/22; 9.1%) and others (1/22, 4.5%). As a result our data have indicated the abundance of high risk HPV isolates and infections with multiple HPV types in that specific area.

Asymptomatic pancreatic body herniation complicated with periauricular squamous cell carcinoma.

Hiatus hernia is defined as herniation of the abdominal elements through the esophageal hiatus into the madiastinum. Type IV hiatal herniation is the rarest of all paraoesaphagial hernias. Herniation of pancreas is extremely rare. A 63-year-old male was admitted to the department of oncology with a periauricular squamous cell carcinoma (SCC). Abdominal CT was performed for organ metastasis. No metastasis was found, but hiatal herniation of the stomach along with the body of the pancreas into the thorax was observed. To our knowledge, this is the first case of herniated pancreatic body complicated with a carcinoma in the literature.

Efficiency of immunohistochemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature.

Diagnosing and grading cervical cancer precursors is challenging. This study investigates the presence of HPV infection, the expression of p16, and any correlation between these two findings. H&E-stained slides of cervical loop excision materials diagnosed as LSIL and HSIL were reviewed. An immunohistochemical panel consisting of p16 as well as of all HPV types and HR-HPV types was applied. Staining of p16 was evaluated according to distribution extent and degree of intensity. All HSIL cases and 80% of LSIL cases were positive for p16. In HSIL cases, the staining distribution was as follows: 50% full thickness, 45% basal, and 5% rare. The staining intensity for the same cases was strong in 70%, variable in 20%, and weak in 10% accordingly. In LSIL cases, staining distribution was basal in 58.3% and rare in 41.7%. None of the LSIL cases showed full thickness of p16 positivity. The staining intensity of the same cases was strong in 25%, variable in 16.7%, and weak in 58.3%. Of all cases, 48.6% were positive for screening kit (all HPV types), and 31.4% of all cases were positive for HR-HPV. The distribution of this positivity was 35% for HSIL and 26.6% for LSIL cases. The total HPV-type positivity rate was 48.6%, the distribution being 50% for HSIL and 46.6% for LSIL cases. p16 is a highly sensitive marker for cervical epithelial dysplasia. Strong and full thickness staining of p16 in the cervix epithelium is highly supportive of HSIL, while weak and basal/rare staining favors LSIL. All HPV-positive cases were also p16-positive, but no statistically significant relationship between HPV infection positivity and the intensity and distribution of p16 was found. HPV is not helpful in the grading of SIL, as an unignorable rate of HR-HPV positivity (26.6%) was detected in LSIL group.

Intrathoracic xanthoma mimicking lung cancer in a patient with familial hypercholesterolemia type II: a case report.

Xanthomas are benign soft-tissue lesions commonly occurring on the skin, subcutis, or tendon sheaths of patients. The lung and thoracic cavity is a rare location for xanthomas. We present a 39-year-old woman who was admitted to our hospital with complaints of dyspnea, cough, and chest pain. She had a prior diagnosis of type II familial hypercholesterolemia. Chest x-ray film and computed tomography scans revealed a large tumor-like mass in the right hemithorax. Thoracal mass and narrowed tracheal segments were removed using cardiopulmonary bypass. Histopathologic findings were consistent with xanthoma.

RET finger protein expression in invasive breast carcinoma: relationship between RFP and ErbB2 expression.

RET finger protein (RFP), which belongs to the large B-box RING finger protein family, has been reported to be expressed in breast carcinoma cell lines. We conducted this study to evaluate the expression level of RFP in breast carcinomas. Tissue microarrays were constructed from 133 cases of invasive breast carcinoma. Sections obtained from tissue arrays and whole sections from 10 non-neoplastic breast tissues were stained for ER, PR, ErbB2, and RFP using immunohistochemistry, and ErbB2 gene status was evaluated by FISH. The correlation between various immunohistochemical markers was determined. We found nuclear RFP expression in 41.4% of invasive carcinomas and in none of the non-neoplastic breast tissues. We also stained whole sections of 29 cases of invasive breast carcinoma, which included the TMA study, and 10 cases of ductal carcinoma in situ (DCIS) by RFP. We observed that four (40%) of the DCIS cases were positive with RFP. In statistical analysis, there was a significant, positive association between RFP and ErbB2 status at the protein level (p=0.002) and the gene level (p=0.049). There was no statistically significant association between the expression of RFP and tumor size, LN status, ER, PR, and grade (p>0.05). However, we found a significant association between age and RFP expression. RFP expression was stronger in patients 50 years or older (p=0.048). In our study, the expression of RFP correlated strongly with ErbB2 status. Our study is the first in the literature to show expression of RFP in patients with breast carcinoma. However, the possible role of RFP in breast carcinogenesis needs to be investigated in more detailed clinical and experimental studies.

Utility of a dual immunostain cocktail comprising of p53 and CK20 to aid in the diagnosis of non-neoplastic and neoplastic bladder biopsies.

BACKGROUND: Distinction between non-neoplastic and neoplastic bladder lesions is therapeutically and prognostically important. Our objective is to describe the use of double immunohistochemistry (DIHC) for p53+CK20 as a tool for diagnosing neoplasia in bladder biopsies. METHODS: p53+CK20 DIHC were examined in 38 reactive atypia, 10 dysplasia, 9 carcinoma in situ (CIS) and 7 invasive carcinoma (IC) cases. CK20 was evaluated according to distribution extent and degree of intensity whereas percentage of positive cells together with staining intensity was taken into account in the evaluation of p53. RESULTS: 92% of reactive cases were either CK20(-) or (+) only in the upper 1/3 urothelium. In dysplastic cases CK20 staining distribution was as follows: 60% in 2/3 of the urothelium, 30% full thickness, 10% in the upper 1/3 urothelium. Among CIS cases, 89% had full thickness CK20 positivity, of which 62% were p53(+). 71% of IC cases exhibited strong and full thickness dual staining. CONCLUSION: This is the first study in the literature to use DIHC of p53+CK20 in distinction of non-neoplastic and neoplastic bladder lesions. Dual staining by p53+CK20 cocktail allows for histologic correlation and diminishes the risk of losing the area of interest in limited biopsy specimens.

The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1.

Rsf-1 interacts with human sucrose nonfermenting protein 2 homologue (hSNF2H) to form a chromatin remodeling complex that participates in several biological processes. We have previously shown that Rsf-1 gene amplification was associated with the most aggressive type of ovarian cancer and cancer cells with Rsf-1 overexpression depended on Rsf-1 to survive. In this report, we determine if formation of the Rsf-1/hSNF2H complex could be one of the mechanisms contributing to tumor cell survival and growth in ovarian carcinomas. Based on immunohistochemistry, we found that Rsf-1 and hSNF2H were co-upregulated in ovarian cancer tissues. Ectopic expression of Rsf-1 in SKOV3 ovarian cancer cells with undetectable endogenous Rsf-1 expression enhanced hSNF2H protein levels and promoted SKOV3 tumor growth in a mouse xenograft model. Our studies also indicated that induction of Rsf-1 expression affected the molecular partnership of hSNF2H and translocated hSNF2H into nuclei where it colocalized with Rsf-1. Furthermore, analysis of Rsf-1 deletion mutants showed that the Rsf-D4 fragment contained the hSNF2H binding site based on coimmunoprecipitation and in vitro competition assays. As compared with other truncated mutants, expression of Rsf-D4 resulted in remarkable growth inhibition in ovarian cancer cells with Rsf-1 gene amplification and overexpression, but not in those without detectable Rsf-1 expression. The above findings suggest that interaction between Rsf-1 and hSNF2H may define a survival signal in those tumors overexpressing Rsf-1.