• Journal of Gastric Cancer
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• v.12 no.2
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• pp.120-125
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• 2012

Purpose: Mechanical stapler is regarded as a good alternative to the hand sewing technique, when used in gastric reconstruction. The circular stapling method has been widely applied to gastrectomy (open orlaparoscopic), for gastric cancer. We illustrated and compared the hand-sutured method to the circular stapling method, for Billroth-II, in patients who underwent laparoscopy assisted distal gastrectomy for gastric cancer. Materials and Methods: Between April 2009 and May 2011, 60 patients who underwent laparoscopy assisted distal gastrectomy, with Billroth-II, were enrolled. Hand-sutured Billroth-II was performed in 40 patients (manual group) and circular stapler Billroth-II was performed in 20 patients (stapler group). Clinicopathological features and post-operative outcomes were evaluated and compared between the two groups. Results: Nosignificant differences were observed in clinicopathologic parameters and post-operative outcomes, except in the operation times. Operation times and anastomosis times were significantly shorter in the stapler group (P=0.004 and P<0.001). Conclusions: Compared to the hand-sutured method, the circular stapling method can be applied safely and more efficiently, when performing Billroth-II anastomosis, after laparoscopy assisted distal gastrectomy in patients with gastric cancer.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.358-363
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• 2012

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine protein kinase, plays an important role in wide variety of developmental events. NLK phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional complex and suppresses wnt signaling pathway through inhibition of ${\beta}$-catenin/TCF complex interaction. However, the function of NLK in gastric carcinogenesis has not been investigated. In the present study, we have examined whether the NLK gene is involved in the development and/or progression of gastric cancers. NLK expression was analyzed by immunohistochemical staining in 153 advanced gastric cancer specimens. Immunhistochemical analysis showed increased expression of NLK in 91 (59.5%) out of 153 gastric cancer specimens. Statistically, there was no significant relationship between altered expression of NLK protein and clinicopathological parameters, including tumor differentiation, location, lymph node metastasis. We identified that mRNA and protein expression of NLK was significantly up-regulated in human gastric cancer tissues compare to corresponding normal gastric tissues. In addition, we found that human gastric cancer cell lines exhibited relatively high expression of NLK, as compared with normal gastric cells. The results of this study suggest that aberrant regulation of NLK may contribute to the development or progression of gastric cancers and serve as a potential biomarker for advanced gastric cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1789-1795
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• 2016

Background: Breast cancer is the commonest female cancer worldwide and its propensity to metastasize negatively impacts on therapeutic outcome. Several clinicopathological parameters with prognostic/predictive significance have been associated with metastatic suppressor expression levels. The role of metastatic suppressor gene (MSG) KiSS1 in breast cancer remains unclear. Our goal was to investigate the possible clinical significance of KiSS1 breast cancer. Materials and Methods: The study was conducted on 87 histologically proven cases of breast cancer and background normal tiisue. Quantitative reverse transcriptase polymerase chain reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein levels, respectively, for correlation with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation and finally with median overall survival (OS). Results: Our study revealed (i) KiSS1 levels were generally elevated in breast cancer vs normal tissue (P < 0.05). (ii) however, a statistically significant lower expression of KiSS1 was observed in metastatic vs non metastatic cases (P = 0.04). (iii) KiSS1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) but not other studied parameters. (iv) Lastly, a significant correlation between expression of KiSS1 and median OS was found (P = 0.04). Conclusions: Conclusively, less elevated KiSS1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative KiSS1 expression may require a more intensive therapeutic strategy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4571-4575
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• 2012

Introduction and Purpose: The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. Materials and Methods: One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. Results: Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. Conclusion: Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7635-7638
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• 2013

Background: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. Materials and Methods: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. Results: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was $58.7{\pm}1.1$. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). Conclusions: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7651-7656
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• 2013

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7533-7537
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• 2014

Background: Breast cancer (BC) is the most frequent cancer type, and the leading cause of death from cancer among women in Israel. The Bedouin-Arab (BA) population in southern Israel is characterized by a high rate of consanguinity, common hereditary disorders, and transition from a semi-nomadic, traditional society to a more sedentary and urbanized society. In this hospital-based study, the demographic and the clinicopathological characteristics of BC in BA were compared with Jewish patients. Materials and Methods: 85 BA patients treated at the Soroka Medical Center, Beer Sheba, during the years 2004-2012, were studied and compared with 180 consecutive Jewish patients treated during the year 2007. Clinicopathological features compared included age, menopausal state, number of births, a history of BC in first-degree relatives, tumor size (T), extent of lymph-node involvement (N), distant metastases (M), stage, grade, estrogen and progesterone receptor (ER/PR), and Her2 status. Types of treatment, relapse rate and site, as well as outcome were also studied. Cox's regression models were applied for studying disease-free, and overall survival. Results: Compared with Jewish patients, BA patients were younger (average age $49{\pm}12$ yrs vs $59{\pm}13$, p<0.001), had a lower rate of BC in first-degree relatives (p<0.001), and a larger number of births ($6{\pm}4.2$ vs $2.5{\pm}1.9$, p<0.001). BA patients had larger tumors (p=0.02), more extensive lymph-node involvement (p=0.002), and more advanced stage (p=0.003). Grade, ER, PR, and Her2 status were similar in the two ethnic groups. Relapse type was most commonly systemic in BA patients (p=0.05), and loco-regional in Jewish patients (p=0.02). Median survival was 63, and 35 months for Jewish and BA patients, respectively (log-rank test, p=0.02). In Cox multivariate analysis, stage and PR status (HR-0.14, p<0.0001; HR-3.11, p=0.046), but not ethnicity, influenced overall survival. Conclusions: BC presents a decade earlier, and with more advanced disease in BA compared with Jewish patients. Biologic parameters including grade, ER, PR, and Her2 status were similar in both groups. Although prognosis was worse in BA than in Jewish patients, it was affected only by stage and PR status, but not by ethnicity.

• Journal of Gastric Cancer
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• v.19 no.1
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• pp.121-131
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• 2019

Purpose: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. Materials and Methods: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED ($P_{NED}$) and demographic and clinicopathological parameters. Results: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. $P_{NED}$, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff $P_{NED}$ was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher $P_{NED}$. Tumors with ${\geq}10%$ NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. Conclusions: GC with ${\geq}10%$ NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

• Korean Journal of Radiology
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• v.24 no.12
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• pp.1190-1199
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• 2023

Objective: This study aimed to investigate the feasibility of ultrafast magnetic resonance imaging (MRI) and radiomic features derived from breast MRI for predicting the upstaging of ductal carcinoma in situ (DCIS) diagnosed using percutaneous needle biopsy. Materials and Methods: Between August 2018 and June 2020, 95 patients with 98 DCIS lesions who underwent preoperative breast MRI, including an ultrafast sequence, and subsequent surgery were included. Four ultrafast MRI parameters were analyzed: time-to-enhancement, maximum slope (MS), area under the curve for 60 s after enhancement, and time-to-peak enhancement. One hundred and seven radiomic features were extracted for the whole tumor on the first post-contrast T1WI and T2WI using PyRadiomics. Clinicopathological characteristics, ultrafast MRI findings, and radiomic features were compared between the pure DCIS and DCIS with invasion groups. Prediction models, incorporating clinicopathological, ultrafast MRI, and radiomic features, were developed. Receiver operating characteristic curve analysis and area under the curve (AUC) were used to evaluate model performance in distinguishing between the two groups using leave-one-out cross-validation. Results: Thirty-six of the 98 lesions (36.7%) were confirmed to have invasive components after surgery. Compared to the pure DCIS group, the DCIS with invasion group had a higher nuclear grade (P < 0.001), larger mean lesion size (P = 0.038), larger mean MS (P = 0.002), and different radiomic-related characteristics, including a more extensive tumor volume; higher maximum gray-level intensity; coarser, more complex, and heterogeneous texture; and a greater concentration of high gray-level intensity. No significant differences in AUCs were found between the model incorporating nuclear grade and lesion size (0.687) and the models integrating additional ultrafast MRI and radiomic features (0.680-0.732). Conclusion: High nuclear grade, larger lesion size, larger MS, and multiple radiomic features were associated with DCIS upstaging. However, the addition of MS and radiomic features to the prediction model did not significantly improve the prediction performance.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.176-185
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• 2004

Purpose: Rapidly progressive glomerulonephritis (RPGN) is a clinicopathologic entity characterized by extensive crescent formation and rapid deterioration of renal function within few months. For better understanding of its clinical course and designing better treatment strategies, a clinicopathological study of childhood RPGN was performed. Methods: The clinical manifestations and pathological findings were reviewed retrospectively in 12 children who were diagnosed as having RPGN by clinical manifestations and renal biopsy during a period from 1991 to 2003. Several clinicopathological parameters were analyzed as prognostic factors. Results: Among a total of 12 patients, 4 were male and 8 were female. The median onset age was 11.5 years(range 5.5-14.6 years), and the median period of follow-up was 25 months(range 7 months-6.6 years). According to the pathological classification, 10 patients (83%) were type II RPGN(immune-complex mediated glomerulonephritis), 2 patients were type III RPGN(pauci-immune glomerulonephritis), and none was type I RPGN(anti-glomerular basement membrane nephritis). All patients were treated with oral steroid in various combinations with methylprednisolone pulse therapy(10 patients, 83%), cyclophosphamide(8 patients, 67%), or plasmapheresis(4 patients, 33%). Clinical outcomes of 12 patients were complete remission in 1(8%), end-stage renal disease in 2(17%), chronic renal insufficiency with persistent proteinuria in 2(17%), and normal renal function with persistent proteinuria in 7(58%) at the last follow-up. Poor prognosis is associated with increased serum creatinine level, severe anemia and younger age at the time of diagnosis. Conclusion: Immune-complex mediated glomerulonephritis is the major cause RPGN in children and most cases showed improvement of renal function with aggressive management. For better understanding of this rare disease, a prospective multicenter study should be done.