Histological Recurrence Research Articles

Tumour budding : an emerging prognostic factor in colorectal carcinoma

Tumour budding, is a morphological feature seen in colorectal carcinoma and known to be associated with a poor outcome. It is thought to be representing the phenomenon of epithelial-mesenchymal transition of colorectal carcinoma. Colorectal malignancies exhibiting budding have shown an association with lymphatic invasion and lymph node metastasis. In addition, tumour budding has proven to be associated with tumour recurrence and is a negative prognostic indicator of overall survival of patients with colorectal carcinoma. Objectives of the study was to assess the prevalence of tumour budding in CRC (higher colorectal carcinoma) specimens and to determine the association between tumour budding and the histological grade, nodal involvement and tumour recurrence. A retrospective study was carried out at the Department of Pathology, Faculty of Medical Sciences, University of Sri Jayewardenepura. The study sample included 58 cases of colorectal carcinoma during the period January 2015 to June 2018. The histological grade, nodal status and tumour recurrence was recorded following review of histology slides. In addition, the slides were examined for the presence or absence of tumour budding, according to the ITBCC (November 2016) recommendations. Study population showed a tumour budding percentage of 32.75%. Tumour budding in colorectal carcinoma showed a statistically significant association with high histological grade, lymph nodal involvement and tumour recurrence (p-value Tumour budding in CRC is strongly predictive of high histological grade, lymph node metastases, and tumour recurrence. The study population included 02 cases of tumour recurrence in the budding group and a single case of cancer-related deaths.

Quantitative Assessment of Bladder Cancer Reflects Grade and Recurrence: Comparing of Three Methods of Positioning Region of Interest for ADC Measurements at Diffusion-weighted MR Imaging

To determine the impact of three different regions of interests (ROIs) positioning methods for apparent diffusion coefficient (ADC) measurements on the assessment of the grade and recurrence and to examine the correlation between ADC value and histopathological grade/ Ki-67 labeling index (LI) in patients with bladder cancer. Sixty-one patients with bladder cancer were retrospectively evaluated. Two observers measured mean ADC values using whole-volume-ROIs, single-section-ROI and three-ROIs methods. Interclass correlation coefficient was analyzed to assess interobserver variability. The grade and recurrence in patients with bladder cancer were assessed by calculating the areas under the receiver operating characteristic curves with Az values. Spearman's correlation was used to analyze the correlations of ADC value with grade and Ki-67 LI. For the mean ADC value, the interclass correlation coefficient were excellent with the whole-volume and the single-section method (0.90 [95% CI: 0.84, 0.94] and 0.89 [95% CI: 0.81, 0.93]) and was good with the three-ROIs method (0.72 [95% CI: 0.53, 0.83]). The Az value for determining histological grade and recurrence of bladder cancer were not significantly different from each positioning method (all p > 0.05). There's significant correlation between histological grade and ADC measuring by whole-volume-ROIs and single-section-ROI methods (r = 0.31, p = 0.02; r = 0.37, p < 0.05). The ADC measured by whole-volume-ROIs, single-section-ROI, and three-ROIs methods were significantly and inversely correlated with the Ki-67 LI (r = -0.3; r = -0.49; r = -0.40, all p < 0.05). There's no significant difference among any of the ROI positioning methods in evaluation of tumor grade and recurrence. There's significant correlation between histological grade and ADC measuring by whole-volume-ROIs and single-section-ROI methods. The ADC value obtained by either of three methods was significantly and inversely correlated with the Ki-67 LI.

Functional and Oncological Outcome After Treatment of Chondroblastoma With Intralesional Curettage.

Chondroblastoma is a rare cartilaginous benign bone tumor that commonly arises in long bones of young people. Surgical management is the primary treatment of choice for chondroblastoma and it entails adequate intralesional curettage alone or in combination with adjuvants. This study was performed to describe the epidemiological characteristics and clinical and radiologic results of intralesional curettage of chondroblastoma. This was a retrospective study which included an analysis of 91 patients with chondroblastoma who were treated with intralesional curettage and were followed up between 1994 and 2014 for at least 3 years. Epidemiological data, clinical symptoms, radiologic and histologic investigations, surgery, functional outcomes, complications, and local recurrence rate were analyzed. There were 60 males (65.9%) and 31 females (34.1%) with a mean age of 16.4 years. The most commonly involved bone was the proximal tibia in 24 patients (26.4%), followed by distal femur in 20 patients (22%), proximal humerus in 17 patients (18.7%) and proximal femur in 15 patients (16.6%). All patients underwent intralesional curettage. High-speed burr was used in 66 patients (72.5%). The resultant cavity was filled with autogenous bone graft, bone substitute, bone cement or a combination of bone graft and cement. Four patients (4.4%) had complications. Three patients (3.3%) developed local recurrence. Age, site, history of previous intervention or pathologic fracture had no impact on the rate of recurrence. The mean Musculoskeletal Tumor Society (MSTS) score was 28.88 (range, 24 to 30) points. Thorough curettage using high-speed burr and bone-grafting or bone cement in the treatment of chondroblastoma has good local control, low recurrence rate and excellent functional long-term outcome. Level IV, retrospective case series.

Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer.

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues. Two distinct proliferating cell populations were observed: progesterone-receptor-positive and progesterone-receptor-negative. In the training cohort, tissues with progesterone-receptor-positive proliferating cells were associated with lower grade and better disease-free survival (p = 0.0055 and 0.0026, respectively). These associations were confirmed in the validation cohort from the neoadjuvant endocrine trial JFMC34 (p = 0.033 and 0.0003, respectively). In the validation cohort, patients with progesterone-receptor-positive proliferating cells responded better to endocrine therapy and had a lower Oncotype DX Recurrence Score. In the multivariate analysis, progesterone receptor status of proliferating cells, but not progesterone receptor or Ki67 alone, was an independent predictor of disease-free survival in both cohorts (p = 0.0043 and 0.0026). In conclusion, the progesterone receptor status of proliferating cancer cells was associated with histological grade and Recurrence Score, and a potent prognostic factor in estrogen-receptor-positive breast cancers. Results suggest that different driving systems generate different expression patterns of progesterone receptor in proliferating cancer cells. Further studies are warranted to validate the findings.

C-Reactive Protein Level Predicts Survival Outcomes in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation Therapy.

Systemic inflammatory response, as measured by C-reactive protein (CRP), is associated with prognosis in various types of human malignancies. However, to the best of our knowledge, the clinical significance of CRP in patients with locally advanced rectal cancer that undergo preoperative chemoradiation has not been investigated in detail. This retrospective study validates CRP as a potential predictive marker for survival outcomes in rectal cancer patients. In this study, we enrolled 125 patients that received total mesorectal excision after preoperative chemoradiation for rectal cancer between January 2003 and December 2010. We investigated the association between preoperative CRP and clinicopathological characteristics and assessed the prognostic value of CRP. The median follow-up was 41months. Elevated CRP showed significant correlation with high histological grade (P = 0.009) and cancer recurrence (P = 0.027). The 5-year disease-free survival and cancer-specific survival were significantly lower in the elevated CRP group (P = 0.001). Moreover, CRP was the strongest predictive factor for cancer-specific survival in multivariate analysis (P = 0.001). In the subgroup analysis, elevated CRP was a significant prognostic factor in patients with node-positive disease (P = 0.025) and was associated with poorer tumor regression (TRG4-5; P = 0.011). The results of our study suggest that preoperative CRP level shows prognostic significance in rectal cancer patients that have undergone chemoradiation. Therefore, preoperative CRP may help clinicians to identify patients that need additional therapy to reduce systemic failure.

Knockdown of thrombospondin 2 inhibits metastasis through modulation of PI3K signaling pathway in uveal melanoma cell line M23.

Thrombospondin 2 (THBS2) expression and its prognostic value have been documented in several types of cancer. Nevertheless, the potential role and clinical significance of THBS2 in uveal melanoma (UM) have never been reported. Thus, in our study, we aimed to explore the clinical significance and prognostic impact of THBS2 in UM. Survival and prognosis analyses were implemented using the Kaplan-Meier method and COX's proportional hazards model based on the clinical data retrieved from The Cancer Genome Atlas (TCGA) database. Colony formation, cell proliferation, invasion and migration assays in M23 cell line were performed to evaluate the effects of THBS2 on UM in vitro. To further reveal whether the dysregulated THBS2 expression regulates the UM metastasis, protein biomarkers including serine-threonine kinase (AKT), p-AKT, phosphoinositide 3-kinase (PI3K), p-PI3K, and p70S6K were measured using Western blotting analysis. THBS2was up-regulated in metastatic UMs. Relationship of THBS2 expression level with the clinicopathological factors demonstrated that the expression level of THBS2 was significantly correlated to histological type, recurrence, and dead. Univariate as well as multivariate COX analyses demonstrated that THBS2 could serve as an independent prognostic factor for overall survival of UM. The knockdown of THBS2 significantly inhibited the proliferation rate of M23 cells, suppressed the colony numbers of M23 cells, lowered the invasive and migratory cell proportion. Importantly, Western blotting results implicated that THBS2 knockdown significantly decreased the expression level of p-AKT, p-PI3K, and p70S6K in M23 cell line. This is the first study to report that THBS2 may play important roles in UM progression and might be a novel prognosis biomarker for UM.

Cytoplasmic CD133 expression correlates with histologic differentiation and is a significant prognostic factor in extrahepatic bile duct cancer and gallbladder cancer.

Prominin-1 (CD133) is one of the most important stem cell markers among various malignant tumor types, but the clinicopathological significance of CD133 expression in intrahepatic cholangiocarcinoma remains controversial. To the best of our knowledge, there have been no reports on extrahepatic bile duct cancer (EHBDCA) and gallbladder cancer (GBCA). The present study examined the clinicopathological significance of CD133 expression in EHBDCA and GBCA. Immunohistochemistry was used to evaluate CD133 expression in resected specimens obtained from 82 patients with EHBDCA and GBCA, and this expression was compared with the clinicopathological parameters and survival data of the patients. Cytoplasmic CD133 expression was identified in 20 patients, and its incidence was significantly associated with histopathological grade (P=0.035), pT factor (P=0.020) and recurrence (P=0.046). Survival analysis revealed that cytoplasmic CD133 expression in patients was significantly associated with a poorer overall survival (OS) and relapse-free survival (RFS) compared with those without cytoplasmic expression (5-year OS rate, 11.6% vs. 39.1%; 3-year RFS rate, 12.5% vs. 42.0%, respectively). Multivariate analysis revealed that cytoplasmic CD133 expression was an independent prognostic factor for OS and RFS (P=0.0036 and P<0.0001, respectively). To the best of our knowledge, this is the first report demonstrating that cytoplasmic CD133 expression was associated with histologic differentiation, cancer progression, recurrence and poor prognosis in EHBDCA and GBCA. CD133 expression may be a useful marker for clinical prognosis in patients with EHBDCA and GBCA.

Expression of interleukin-15 in canine mammary carcinoma: relationships with histologic grades, Bcl-2, recurrence, and overall survival

Spontaneous tumors arising from mammary tissue are considered the most common tumor in female dogs and are of great importance both in veterinary and comparative medicine. Interleukin-15 is a cytokine involved in many physiologic processes such as activation of immune cells, autoimmune diseases, and cancer pathogenesis; however, the role of interleukin-15 in canine mammary cancers has not been well understood. We designed this study to examine the expression of interleukin-15 (IL-15) in canine mammary carcinoma by means of immunohistochemistry and any possible association with histologic malignancy grades, Bcl-2 expression, tumor recurrence, and overall survival. Results revealed that 14 (46.66%) of tumor samples strongly express IL-15, 7 cases (23.33%) moderately, and 9 cases showed weak immunoreactivity (30%). The expression of interleukin-15 is increased in canine mammary tumors in comparison to healthy tissues (p 0.05). Interleukin-15 could have a role mammary carcinogenesis in dogs but more studies are needed to understand its exact roles.

PO-382 Differentially methylated sites in histologically negative surgical margins of oral squamous cell carcinoma patients

Introduction Oral squamous cell carcinoma (OSCC) is the most common malignant tumour of the head and neck. The presence of microscopic tumour in surgical margins contributes to increased local recurrence rates and decreased overall survival. However, from 10% to 30% of patients with negative histological margins present locoregional recurrences. Many studies have suggested the presence of epigenetic changes prior to the onset cancer phenotype in the mucosa adjacent to the primary tumour. Thus, the aim of this study was to evaluate the hypermethylation profile of negative surgical margins from patients with OSCC as a prognostic factor for tumour recurrence. Material and methods The methylation profile of 32 cryopreserved histologically negative surgical margins samples was performed using the Illumina Infinium MethylationEPIC BeadChip platform. The patients were divided into the following two groups: a) 16 who developed local recurrence and b) 16 who did not developed local recurrence. The generated data were analysed with RStudio software using the ChAMP (Chip Analysis Methylation Pipeline) package. Results and discussions The majority of patients were male (68.8%), had initial disease (71.9%) and were tobacco users (71%). All samples presented less than 1% of failed probes, so they were all included in the subsequent analyses. Probes that anneal at more than one site in the genome, probes with Single Nucleotide Polymorphisms (SNPs) and/or failed in more than one sample were excluded, leaving 7 80 437 probes for comparison. In the comparative analysis between the groups, 908 CpG sites differentially methylated were identified using p Conclusion Our results demonstrated that patients with negative histological margins have a differentially methylated signature, which is important for the identification of individuals at high risk of developing local recurrence of OSCC, decreasing morbidity and improving survival rates.

Invasive Hemodynamics and Rejection Rates in Patients With Cardiac Sarcoidosis After Heart Transplantation

BackgroundOrthotopic heart transplant (OHT) is increasingly used for end-stage heart failure due to cardiac sarcoidosis (CS). However, concern regarding long-term outcomes in patients with CS after OHT persists because of multiorgan involvement. MethodsBaseline demographics and invasive hemodynamics were measured in 12 patients with CS and 28 patients with nonischemic cardiomyopathy requiring OHT at the time of transplantation, 1 week after OHT, and in routine follow-up. Primary endpoints included changes in pulmonary artery pressure, right ventricular stroke work index, and pulmonary compliance. Secondary endpoints included degree of allograft rejection and death. ResultsDuring a mean follow-up of 73.8 months, no differences in pulmonary artery pressures, right ventricular stroke work index, or cardiac index were observed in patient with CS (n = 12) compared with those without CS (n = 28) between 1 week after OHT and the most recent follow-up. Long-term follow-up showed that pulmonary hemodynamics remained normal in the CS group. International Society for Heart and Lung Transplantation (ISHLT) 1990 grade ≥ 1a rejection occurred less frequently in the CS group (17% vs 68%, P = 0.006), and 0 of 12 patients in the CS group experienced histologic or clinical recurrence of sarcoidosis or ≥2 rejection. Patients with CS had excellent survival after OHT, with 0 deaths or significant rejection. ConclusionsPatients with CS have similar post-transplant hemodynamics as patients without CS, without evidence of right ventricular dysfunction or pulmonary hypertension. Neither significant rejection nor recurrence of sarcoid in the allograft was observed in this cohort of patients with CS. Survival is similar between patients with CS and those without CS. Heart transplant is a viable strategy in selected patients with CS with excellent outcomes.

Overexpression and clinical significance of IBP in epithelial ovarian carcinoma.

Interferon regulatory factor-4 binding protein (IBP) is as a type of ρ GTPase suggested to serve an important role in tumor occurrence and development through the effects of cytoskeletal remodeling, and cell conduction mechanism. IBP is widely expressed in the immune system and expressed in several types of tumors. However, its expression and prognostic value in epithelial ovarian carcinoma (EOC) remain unclear. The present study aimed to investigate the expression of IBP in EOC, and its effect on clinicopathological variables and prognosis. A total of 107 and 30 cases of epithelial ovarian carcinoma and benign ovarian disease tissue sections, respectively, were examined using immunohistochemistry. The results indicated that the IBP expression status was negative or markedly weak in normal tissues, but highly expressed in EOC tissues. A significant association was observed between IBP overexpression and various clinicopathological factors, including advanced International Federation of Gynecology and Obstetrics stage (P<0.001), poor histologic grade (P=0.002), peritoneal carcinomatosis (P<0.001), lymph-node metastasis (P=0.023) and recurrence (P<0.001). Multivariate Cox regression analysis additionally suggested that IBP overexpression was an independent factor affecting recurrence-free survival [hazard ratio (HR)=4.099; 95% confidence interval (CI), 2.209-7.606; P<0.001) and overall survival (HR=2.317; 95% CI, 1.484-3.617; P<0.001) in patients with EOC. The results of the present study demonstrated that IBP overexpression may be associated with tumor development and progression in EOC, and therefore may serve as a novel target for treating this disease.

Aggressive Surgical Approach for Treatment of Primary and Recurrent Retroperitoneal Soft Tissue Sarcoma

To analyze treatment and survival in a series of resected patients with primary or recurrent retroperitoneal sarcoma (RPS) treated and prospectively followed at a single institution. Between July 1994 and December 2015, 89 patients (36 M, 53 F; mean age 60years, range 25-79) were evaluated. For the purpose of analysis, complete resection was defined as removal of gross tumor with histologically confirmed clear resection margins. Eighty-three out of the 89 patients (93%), 46 of whom affected by primary RPS, and 37 by recurrent RPS, underwent surgical exploration. Sixty-two had a grossly and microscopically complete resection. Fifty-three out of 83 patients (64%) underwent removal of contiguous intra-abdominal organs. Preoperative mortality was nil and significant preoperative complications occurred in six cases only (7%). High-grade tumor pointed out to be a significant variable for a worse survival in all 83 patients amenable to undergo surgical resection (57% 5years survival for low grade vs 14% for high grade; P = 0.0004). Among completely resected patients, only histologic grade clearly affected disease-free survival (72% 5years survival for low grade vs 50% for high grade; P = 0.04), while the role of preoperative blood transfusions (67% 5years survival for non-transfused patients vs 29% for transfused patients; P = 0.05) has to be evaluated in connection to patient complexity. Histological grade and recurrence are the most valuable prognostic predictors; in this clinical subset, an aggressive surgical approach in both primary and recurrent RPS is associated with a best long-term survival and disease-free survival.

Endoscopic submucosal dissection versus endoscopic mucosal resection for type 0-II superficial gastric lesions larger than 20 mm.

Background:Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are increasingly used for the treatment of superficial gastrointestinal neoplasia. However, the limits and the indications for each technique are still debated. Our retrospective study aimed to compare these techniques in patients with gastric flat lesions larger than 20 mm without the non-lifting sign.Methods:Between January 2013 and July 2016, a total of 36 patients with early gastric flat lesions larger than 20 mm and without the non-lifting sign were resected by ESD and were followed up by endoscopy. As a control group, 40 EMR cases from our database were matched. En bloc and curative resection were compared between the two groups according to histological assessment, tumor size, recurrence, complication rate, and procedure time. A Kaplan-Meier comparison was performed for both groups with a log-rank test to compare the survival curves; the chi-square test was employed for other parameters.Results:En bloc resection rate and curative resection rate were significantly higher in the ESD group than in the EMR group. Procedure time was significantly longer in the ESD group. No significant differences were found in the recurrence and complication rates, although the former were higher in the EMR group and the latter in the ESD group. Survival curves were similar for both groups.Conclusions:Our retrospective analysis seems to confirm a clear advantage for ESD over EMR in removing early superficial gastric neoplasm. Although ESD has expanded the endoscopic resectability of endoscopic gastric lesions, EMR may still be considered one of the therapeutic options for flat gastric lesions without the non-lifting sign.

Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study.

BackgroundEnd-stage liver disease (ESLD) is the most common cause of secondary immunoglobulin A nephropathy (IgAN). Multiple mechanisms have been proposed to explain the association between liver disease and IgAN. Although some mechanisms are expected to reverse in patients after liver transplant, the long-term renal prognosis is unclear for these patients.MethodsThis observational retrospective cohort study examined the renal outcomes of 14 patients who had IgAN with end-stage liver disease and subsequently underwent either liver transplant alone or combined liver and kidney transplant at a single tertiary care center.ResultsOf the 7 patients who underwent liver transplant alone, hematuria persisted in 2, 4 had progressive loss of kidney function with worsening proteinuria in 3 but only 1 reached end-stage renal disease 5 years posttransplant. Among 7 combined liver and kidney transplant recipients, 1 had histologic and 1 had histologic and clinical recurrence of IgAN without kidney allograft loss.ConclusionsIgAN in patients with advanced liver disease does not necessarily resolve after liver transplant but has overall favorable renal outcomes.

Imiquimod cream and C02 laser vaporization in vulvar intraepithelial neoplasia (VIN) 2/3 treatment.

To compare the use of topical 5% imiquimodt (IMQ) cream or CO2 laser vaponization as the treatment of vulvar inmraepithelial lesions (VIN) 2/3 and to evaluate the degrees of residual or recurrent lesions. Twenty-nine women with VIN 2/3 were separated into two groups, according to the proposed treatments. All were submitted to collection of vulvar swabs for DNA genotyping of human papillomavirus (HPV), vulvoscopy, and biopsy of the found lesions. After treatment they were followed up in quarterly consultations to (until) possible appearance of new lesions or along one year. The findings were similar in effectiveness and presence of residual or recurrent lesions on the performed treatments. However, patients treated with topical 5% IMQ cream had less severe lesions in histological recurrence when compared to those submitted to the CO2 laser vaporization. The effectiveness of topical 5% IMQ cream was similar to that of CO2 laser vaporization. There was no difference between the treatments for the presence of residual or recurrent lesions. However, patients who received IMQ had less aggressive lesions than those submitted to the treatment with CO2 laser vaporization.

Extraperitoneal Laparoscopic Radical Nephroureterectomy and Lymph Node Dissection in Modified Supine Position

To explore the feasibility of extraperitoneal laparoscopic radical nephroureterectomy (EL-RNU) and lymph node dissection in a modified supine position for managing urothelial carcinomas in the renal pelvis or in the upper two-thirds of the ureter. Consecutively from January 2014 to October 2015, 15 patients with high-risk urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter underwent EL-RNU and extraperitoneal laparoscopic lymph node dissection (EL-LND). Clinical and pathologic data, histologic nodal status, perioperative complications, and recurrence data were collected. All of the 15 patients were treated with EL-RNU and EL-LND in a modified supine position, and none was converted to open surgery. The mean operation time was 178 ± 18 minutes. The mean estimated blood loss was 140 ± 40 mL. The mean postoperative intestinal function recovery time was 2 days. The mean postoperative hospitalization was 7 ± 1 days. Pathologic studies revealed positive lymph nodes in 3 patients (20%). The mean number of harvested lymph nodes was 12 ± 3. No local recurrence and distant metastasis were found after a median follow-up of 14.4 months (7-23 months). EL-RNU and EL-LND in the modified supine position are mini-invasive and feasible for patients with urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter. Good exposure and dissection of the abdominal aorta and inferior vena cava and the integrity of the peritoneum are key to the operational success of this approach.

Clinicopathological parameters associated with histological background and recurrence after surgical intervention of vocal cord leukoplakia.

Histological examination of biopsy shows usefulness in the diagnosis of vocal cord leukoplakia; however, in considerable amount of cases, the examination cannot provide definitive diagnosis of malignancy from benign conditions such as hyperplasia and dysplasia. The present work therefore was aimed to identify clinicopathological factors and molecular markers predictive of recurrence and malignant transformation of vocal cord leukoplakia.Clinical data of 555 cases of vocal cord leukoplakia enrolled from July 1999 to June 2014 were analyzed. The cohort consisted of keratosis (n = 137), hyperplasia (n = 139), dysplasia (n = 177), and primary (n = 10) and invasive (n = 46) carcinoma. Correlations between patients’ backgrounds, clinicopathological factors, molecular markers (p53, p16, Ki67, cytokeratin, and proliferating cell nuclear antigen), and histology backgrounds were examined using by Pearson Chi-squared or Fisher exact test. Reflux symptom index (RSI) and reflux finding score (RFS) before and after treatment were compared using Wilcoxon signed-rank test. Risk factors for disease recurrence were identified using Cox proportional hazards models of multivariate analysis. Time to recurrence was analyzed using log-rank test of Kaplan–Meier method.In the present cohort, alcohol drinking was found associated with GRBAS grade (P = .0258) and the site (P = .0298) of leukoplakia. For the different disease types, chief complaint (P = .0179), GRBAS grade (P = .0101), mucosal wave (P < .0001), and molecular markers p53 (P < .0001) and Ki67 (P < .0001) were identified as correlates. RSI and RFS were significantly lowered by surgical intervention. A single side of leukoplakia was predictive of a lower risk of recurrence (odds ratio, 0.378; 95% confidence interval, 0.197–0.723; P = .0033). Absence of mucosal wave was associated with a shorter time-to-recurrence (P = .0357).The present work identified clinicopathological factors and molecular markers associated with the different histology of vocal cord leukoplakia, and also the prognostic factor for the low risk of recurrence after surgery.

The first report of multicenter validation study on curebest 95GC breast, a multi-gene assay to predict prognosis of node negative and ER positive breast cancer patients.

e12107 Background: Curebest™ 95GC Breast (95GC) is one of the multi-gene assays to predict prognosis of node negative and estrogen receptor (ER) - positive breast cancer patients, developed using 95 gene-set without overlap with that used in Oncotype DXⓇ(ref 1). It has been shown to have the capability to classify the “intermediate” patients determined using Recurrence Online (microarray-based simulation model for Oncotype DXⓇ) but was validated only using the data from single institute and public database. Here we report the result of the first multi-center validation study for this multi-gene assay. Methods: ER-positive and T1-2/N0/M0 breast cancer patients who received adjuvant hormonal therapy were enrolled retrospectively. Fresh frozen tissues were applied to the assay, resulting classification into “L” and “H”, which was used for the validation on 5 year recurrence free survival (5Y-RFS) data of each patient. Results: 73 cases out of 150 enrolled cases were eligible and analyzed. 46 patients were classified as “L” whose 5Y-RFS was 96.5% (95%CI:89.5-98.9) while 27 patients were classified as “H” whose 5Y-RFS was 79.0% (95%CI:63.6-88.5). There was a statistically significant difference between RFS of “L” and “H” group by Log-Rank test (p = 0.0016). Significant association with 95GC were seen in histological grade (p = 0.0012), Recurrence Online (p &lt; 0.001) and PAM50 (p &lt; 0.001). The assay could classify the patients of histological grade 2, intermediate group by Recurrence Online (RS &gt; 17, RS &lt; 31) and Luminal B patients into “L” and “H”. Conclusions: Curebest™ 95GC Breast was well validated by this first multi-centered retrospective study on 5Y-RFS of the ER positive, node-negative patients who received only hormonal therapy in adjuvant setting. This result indicates the usefulness of 95GC as a novel multi-gene assay, as it can classify target patients into 2 groups, “H” and “L” according to predicted prognosis of 5Y-RFS. Reference: 1. Naoi et al. Breast Cancer Res Treat (2011) 128:632-641

Complex ultrasound with strain elastography in the diagnosis of local recurrence of breast cancer

Aim. To evaluate the capacities of complex ultrasound with the use of gray scale and color coded Doppler and strain elastography in the diagnosis of local recurrence of breast cancer and to determine the position of each method in the diagnostic algorithm. &#x0D; Methods. Complex ultrasound of 76 female patients with suspected local recurrence of breast cancer was performed. The study included 83 masses. Ultrasound of preserved part of the breast, postoperative scar and soft tissues of the patient’s chest was performed with the use of high frequency linear 5-12 MHz transducer of Accuvix XG scanner (Samsung Medison, South Korea). The mass was considered malignant if it had 3 and more suspicious ultrasound features in gray scale regimen or 2 and more suspicious features in gray scale regimen combined with 3 or more color stains in color coded Doppler or with elastograms types 4 and 5. According to morphologic results the masses were divided into 2 groups. The first group included 48 masses in which according to cytologic and histologic studies recurrence of breast cancer was found, the second group included 35 masses in which tumor growth was not revealed morphologically. &#x0D; Results. Complex ultrasound was accurate in 90.4%. Sensitivity and specificity were 89.6 and 91.4%, respectively. &#x0D; Conclusion. Complex ultrasound with the use of strain elastography is a highly informative method that in most cases allows diagnosing local recurrence of breast cancer.

Histologic surveillance after liver transplantation due to autoimmune hepatitis.

Autoimmune hepatitis (AIH) often recurs after liver transplantation (LT). Our aim was to evaluate the recurrence rate of AIH after LT, impact of AIH recurrence on survival and fibrosis progression, and find risk factors for AIH recurrence. Forty-two patients with AIH prior to LT with ≥1 protocol biopsy ≥1year post-LT were included with a median follow-up of 5.0years (1.0-17.0). Follow-up liver biopsies were re-evaluated for AIH recurrence, fibrosis progression, and cirrhosis development. A histological recurrence of AIH was diagnosed in 15 (36%) patients at a median of 5years of follow-up. Recurrent AIH lead to progressive fibrosis (METAVIR stage 3-4) in two but did not cause a single patient or graft loss. Transaminases were normal in three patients with recurrent AIH (20%). AIH recurrence was more common in patients with no overlapping cholangitis (OR 1.44, P=.021). Immunosuppression without antimetabolite increased the risk of AIH recurrence (OR 1.47, P=.018). Patient and graft survival rates at 1, 5, and 10years were 94%, 86%, and 86% and 91%, 77%, and 74%. AIH recurrence did not affect survival. AIH recurrence occurs in 36% in 5years, but does not affect patient or graft outcome.