Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

Expression of Apurinic/Apyrimidinic Endonuclease 1 in Colorectal Cancer and its Relation to Tumor Progression and Prognosis.

BACKGROUND/AIM: Over-expression of apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated to be associated with cancer progression, chemo- and radioresistance in various cancers. This study examined the expression of APE1 and its relation to tumor progression and prognosis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: We investigated 193 patients with CRC who received curative surgery for whom formalin-fixed and paraffin-embedded blocks were available, and long-term tumor-specific survival rate analysis was possible. The expression of APE1 was investigated by reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry in CRC and lymph node tissues. The apoptosis, proliferation, and angiogenesis of CRC cells were determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and immunohistochemical staining for Ki-67 and CD34 antibodies. RESULTS: APE1 was over-expressed in CRC and metastatic lymph node tissues compared with normal colorectal mucosa and non-metastatic lymph node tissues. Over-expression of APE1 was significantly associated with advanced stage, lymphovascular invasion, perineural invasion, deeper tumor invasion, lymph node metastasis, distant metastasis, and poor survival. Multivariate analysis demonstrated that APE1, perineural invasion, and lymph node metastasis were the independent prognostic factors associated with overall survival. The mean Ki-67 labeling index value of APE1-positive tumors was significantly higher than that of APE1-negative tumors. However, there was no significant association between APE1 expression and the apoptotic index or microvessel density. CONCLUSION: Over-expression of APE1 is significantly associated with tumor progression and poor survival in patients with CRC. Therefore, APE1 may be a novel biomarker and present a potential prognostic factor for CRC.

Variability of oral/taste sensitivity to fat: An investigation of attribution from detection threshold methods with repeated measurements.

Accumulating psychophysical evidence suggests substantial individual variability in oral/taste sensitivity to non-esterified, long-chain fatty acids (NEFA), which is commonly referred to as fat taste or oleogustus. Recent studies have sought to determine its associations with human factors such as body mass index (BMI) and food preferences, as it has been claimed that excessive fat consumption is related to several health conditions, including obesity. Yet, the findings are controversial. On the other hand, it has been noted that considerable variability also occurs based on the methodology used to measure the fatty acid taste. Specifically, learning effects have been observed over repeated measurements of the detection threshold of NEFA, yet there has been no methodology available to take into account these learning effects. Accordingly, in the present study, a novel methodology using a descending-block dual reminder A-Not A (DR A-Not A) method with a warm-up has been proposed to measure the NEFA detection threshold based on the signal detection theory and considering NEFA taste learning effects over repeated sessions. Homogeneous subjects (young adult Korean females within the normal BMI range, non-vegetarians) were randomized to either the novel descending-block DR A-Not A method or ascending triangle method that is commonly used for fat perception studies. Pure oleic acid emulsions were used as fat taste stimuli to be discriminated from pure mineral water. Each subject completed 14 repeated visits. For the ascending triangle method, 14 thresholds were determined using a stopping rule, while for the novel method, 7 thresholds were determined each per two consecutive days, using a criterion of a lower limit of 50% confidence interval of d' = 0.5, considering the practical aspects of taste studies in food sensory science. Based on the group median results of the last two visits, the variability of the detection thresholds was reduced using the novel descending-block DR A-Not A method due to better learning effects over repeated sessions. This shows the potential of the descending-block DR A-Not A threshold method for further studies on oral/taste sensitivity to fat.

Primary squamous cell carcinoma of the ovary accompanied by transition of a mucinous borderline ovarian tumor.

This report describes a woman with a rare primary squamous cell carcinoma of the ovary accompanied by transition of a mucinous borderline ovarian tumor. A woman in her late 40s was referred for abdominal discomfort, which worsened during defecation. Pelvic magnetic resonance imaging showed a multiloculated cystic lesion in the left adnexa measuring approximately 7.5 × 9.5 × 7.0 cm. An intraoperatively obtained frozen biopsy sample of the mass in the left ovary was positive for malignancy, resulting in a surgical staging operation. The tumor was composed of squamous cell carcinoma and mucinous borderline tumor. There was no evidence of capsular invasion or invasion of other internal organs, including pelvic and para-aortic lymph nodes (0/41). Immunohistochemistry showed that the tumor was diffusely positive for cytokeratin 7, cytokeratin 20, Ki-67, and P40 but negative for P16. After a debulking operation, the patient has been monitored regularly without adjuvant therapy owing to final surgical staging of the tumor as stage IA.

Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer.

BACKGROUND/AIM: Engulfment and cell motility 1 (ELMO1) plays a crucial role in the process of migration, chemotaxis, and metastasis of tumor cells. ELMO1 has been implicated in the pathogenesis of various cancers. However, the distinct function of ELMO1 in colorectal cancer (CRC) is unclear. We determined whether ELMO1 affects the oncogenic behavior of CRC cells and investigated its prognostic value in CRC patients. MATERIALS AND METHODS: We investigated the impact of ELMO1 on tumor cell behavior using small interference RNA (siRNA) in CRC cell lines, including SW480 and DLD1. The expression of ELMO1 was investigated by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) in cancer tissues and sera obtained from CRC patients. RESULTS: ELMO1 knockdown suppressed tumor cell proliferation in SW480 and DLD1 cells. ELMO1 knockdown-induced apoptosis through up-regulation of caspase-3, -7, and PARP activities and down-regulation of the anti-apoptotic Mcl-1 protein. ELMO1 knockdown-induced cell-cycle arrest by decreasing cyclin D1, cyclin-dependent kinase 2, 4 and 6, and the 25C cell division cycle (CDC25C). ELMO1 knockdown suppressed tumor cell invasion and migration. The expression of E-cadherin was increased, while that of Vimentin and Claudin 1 decreased following ELMO1 knockdown. The phosphorylation levels of PDK1, Akt, and GSK-3ß and were down-regulated after ELMO1 knockdown. The expression of ELMO1 was found up-regulated in cancer tissues and sera taken from CRC patients. ELMO1 expression was significantly associated with tumor stage, lymph node metastasis, distant metastases, and poor survival. CONCLUSION: ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.

Clinical outcomes of palliative self-expandable metal stent placement in right- and left-sided malignant colon obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

Differences in clinical outcomes according to the time interval between the bridge to surgery stenting and surgery for left-sided malignant colorectal obstruction.

BACKGROUND: Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO. METHODS: Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2-3 weeks), and group 3 (interval >3 weeks). RESULTS: Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival. CONCLUSIONS: A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.

Predictors of clinical outcomes of self-expandable metal stent treatment for malignant colorectal obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

ABSTRACT: There has been increased use of self-expandable metal stents (SEMS) in treating malignant colorectal obstruction (MCO). The aim of this study was to investigate factors that are associated with the outcomes of SEMS placement for MCO.Clinical data from patients who underwent SEMS placement for MCO at 6 hospitals in Honam province of South Korea between 2009 and 2018 were reviewed retrospectively. Eight hundred two patients were identified and their data were analyzed. Technical success, clinical success, complications, and predictors of outcome were included as main outcome measures.Technical and clinical success rates were 98.8% (792/802) and 90.1% (723/802), respectively. Complications including stent migration, stent occlusion due to tumor ingrowth and outgrowth, perforation, bacteremia/fever, and bleeding occurred in 123 (15.3%) patients. In multivariate regression analyses, procedure time was significantly associated with the technical success of SEMS placement (P = .001). Longer length of obstruction, the use of covered stent, and longer procedure time were significant independent predictive factors for the clinical success of SEMS placement (odds ratio [OR] 0.974 (95% confidence interval [CI] 0.950-0.990); P = .043, OR 0.255 (95% CI 0.138-0.471); P < .001, and OR 0.957 (95% CI 0.931-0.984); P = .002, respectively). Stage IV colorectal cancer and the use of covered stent were significant independent predictive factors for the development of complications after SEMS placement (OR 2.428 (95% CI 1.407-4.188); P = .001 and OR 3.329 (95% CI 2.060-5.378); P < .001, respectively).Longer length of obstruction, the use of covered stent, and longer procedure time were associated with lower clinical success rates. Having stage IV colorectal cancer and the use of covered stents were associated with an increased risk of complications.

A Disintegrin and Metalloprotease 12 Promotes Tumor Progression by Inhibiting Apoptosis in Human Colorectal Cancer.

A disintegrin and metalloprotease 12 (ADAM12) has been implicated in cell growth, tumor formation, and metastasis. Therefore, we evaluated the role of ADAM12 in colorectal cancer (CRC) progression and prognosis, and elucidated whether targeted downregulation of ADAM12 could lead to therapeutic sensitization. The effect of ADAM12 on tumor cell behavior was assessed in CRC cell lines, CRC tissues, and a mouse xenograft model. ADAM12 overexpression enhanced proliferation, inhibited apoptosis, and acted as positive regulator of cell cycle progression in CRC cells. Phosphorylation of PTEN was decreased and that of Akt was increased by ADAM12 overexpression. These results were reversed upon ADAM12 knockdown. ADAM12 overexpression was significantly associated with the cancer stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival in CRC patients. In a mouse xenograft model, tumor area, volume, and weight were significantly greater for the ADAM12-pcDNA6-myc-transfected group than for the empty-pcDNA6-myc-transfected group, and significantly lower for the ADAM12-pGFP-C-shLenti-transfected group than for the scrambled pGFP-C-shLenti-transfected group. In conclusion, ADAM12 overexpression is essential for the growth and progression of CRC. Furthermore, ADAM12 knockdown reveals potent anti-tumor activity in a mouse xenograft model. Thus, ADAM12 may serve as a promising biomarker and/or therapeutic target in CRC.

A Case of Metastatic Melanoma in the Liver Mimicking Hepatocellular Carcinoma.

The liver is one of the most common sites of metastasis. Although most metastatic liver cancers are hypovascular, some hypervascular metastases, such as those from melanoma, need to be differentiated from hepatocellular carcinoma (HCC) because they may show similar radiologic findings due to their hypervascularity. We encountered a case of multinodular liver masses with hyperenhancement during the arterial phase and washout during the portal venous and delayed phases, which were consistent with imaging hallmarks of HCC. The patient had a history of malignant melanoma and had undergone curative resection 11 years earlier. We performed a liver biopsy for pathologic confirmation, which revealed a metastatic melanoma of the liver. Metastatic liver cancer should be considered if a patient without chronic liver disease has a history of other primary malignancies, and caution should be exercised with hypervascular cancers that may mimic HCC.

Engulfment and cell motility 1 promotes tumor progression via the modulation of tumor cell survival in gastric cancer.

BACKGROUND/AIM: Engulfment and cell motility 1 (ELMO1) protein has been implicated in phagocytosis of apoptotic cells, cell migration, neurite outgrowth, cancer cell invasion and metastasis, and poor prognosis in various cancers. We investigated the role of ELMO1 in mediating the oncogenic behavior of gastric cancer (GC) cells. We also investigated the correlation between expression of ELMO1 in GC tissues and various clinicopathological parameters. METHODS: We studied the impact of ELMO1 on tumor cell behavior using the pcDNA-myc vector and small interfering RNA in AGS and SNU1750 GC cell lines. We performed western blotting and immunohistochemistry to investigate the expression of ELMO1 in GC cells and tissues. RESULTS: ELMO1 overexpression inhibited apoptosis via the modulation of PARP, caspase-3 and caspase-7 in GC cells. ELMO1 overexpression led to significant increase in the number of migrating and invading GC cells. The expression of E-cadherin decreased and that of Snail increased in GC cells upon ELMO1 overexpression. Phosphorylation of PI3K/Akt and GSK-3ß was increased and that of ß-catenin was decreased upon ELMO1 overexpression in GC cells. These results were reversed after ELMO1 knockdown. ELMO1 expression was significantly associated with tumor size, cancer stage, lymph node metastasis and survival. ELMO1-positive tumors had significantly higher mean of Ki-67 labeling index than ELMO1-negative tumors. There was no significant relationship between ELMO1 expression and the mean value of the apoptotic index. CONCLUSIONS: Our results indicate that ELMO1 promotes tumor progression by modulating tumor cell survival in human GC.

Clinical outcomes of endoscopic resection for colorectal laterally spreading tumors with advanced histology.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) are large, flat neoplasms that are usually treated using different endoscopic techniques based on their morphology, size, and histology. The aim of this study was to evaluate the clinical outcomes of LSTs with advanced histology treated by endoscopic resection. METHODS: A total of 246 LSTs with advanced histology [i.e., high-grade dysplasia (HGD) and adenocarcinoma (AC)] treated by endoscopic resection [i.e., endoscopic mucosal resection (EMR), EMR-precutting (EMR-P), and endoscopic submucosal dissection (ESD)] were enrolled. Clinicopathological characteristics were collected by review of patient's medical records. RESULTS: The en bloc resection and R0 resection rates were 75.6% and 85.0%, respectively. The bleeding and perforation rates were 10.2% and 2.4%, respectively. The frequency of cancerous pit pattern and bleeding was significantly higher in LSTs with AC than in LSTs with HGD. The R0 resection rate in LSTs with HGD was significantly higher than that in LSTs with AC. The frequency of cancerous pit patterns in LST cases with submucosal AC was significantly higher than those with intramucosal AC. The mean size of the LSTs was significantly larger in ESD group than in EMR or EMR-P groups. The frequencies of nodular mixed subtype, cancerous pit patterns, and en bloc resection rates were significantly higher in the ESD group than in the EMR or EMR-P groups. However, the frequency of perforation was significantly higher in EMR-P group than in EMR or ESD groups. CONCLUSIONS: These results indicate that ESD is a more acceptable treatment approach for resection of colorectal LSTs of larger size, with nodular mixed subtype, having a cancerous pit pattern or AC, using either en bloc or curative resection methods, compared to EMR or EMR-P procedures.

Risk factors for procedure-related complications after endoscopic resection of colorectal laterally spreading tumors.

Colorectal laterally spreading tumors (LSTs) are large and flat elevated neoplasms with diameters of at least 10 mm. Endoscopic resection of LSTs, with their large size and broad base, is difficult and dangerous compared with the resection of polypoid neoplasms. This study aimed to determine the risk factors for procedure-related complications including bleeding and perforation after endoscopic resection of LSTs.Patients with colorectal LST undergoing endoscopic resection at 5 university hospitals in Honam Province of South Korea were enrolled, and their records about patients, lesions, and procedure parameters associated with the occurrence of complications were reviewed retrospectively. Logistic regression analysis was performed to identify risk factors for complications.The frequency of comorbidities in bleeding group was significantly higher than in the no bleeding group. The frequency of bleeding was significantly higher in lesions with adenocarcinoma than in lesions with low or high-grade dysplasia. The frequency of bleeding was significantly higher in piecemeal resection than in en bloc resection. The frequency of perforation was significantly higher in endoscopic mucosal resection-precutting (EMR-P) than in endoscopic mucosal resection (EMR) or endoscopic submucosal dissection. The mean procedure duration was significantly longer in the perforation group than in the no perforation group. On multivariate analysis, patient comorbidity and histologic grade of the lesion were significant independent risk factors for bleeding, whereas EMR-P was a significant independent risk factor for perforation after endoscopic resection.This study demonstrated that patient comorbidity and histologic grade of lesion were significant independent risk factors for bleeding, and EMR-P was a significant independent risk factor for perforation after endoscopic resection of colorectal LSTs.

Liver abscess caused by Clostridium haemolyticum infection after transarterial chemoembolization for hepatocellular carcinoma: A case report.

RATIONALE: Liver abscesses caused by Clostridium species infection are extremely rare. PATIENT CONCERNS: The authors report the first case of a liver abscess due to Clostridium haemolyticum, which occurred after transarterial chemoembolization (TACE) for hepatocellular carcinoma, in a 76-year-old woman who presented with right upper quadrant pain and fever. DIAGNOSES: Computed tomography of the abdomen after the second TACE showed an air-filled abscess around a compact, lipiodolized lesion in the right hepatic lobe. Pus culture showed the growth of C haemolyticum. INTERVENTIONS: Broad-spectrum antibiotics, including piperacillin/tazobactam and metronidazole, were administered, and a percutaneous 10-French pigtail catheter for pus drainage and culture was inserted in the liver abscess. OUTCOMES: Despite administering intensive treatments, she presented with rapid deterioration in mental status, liver function, and infection markers. She was transferred to the local hospital for palliative conservative treatment. LESSONS: Clostridia infections, including those involving C haemolyticum, are extremely rare, but should be considered as one of the causative organisms of liver abscess formation after TACE because of its rapid and fatal clinical course.

Prognostic significance of the concomitant existence of lymphovascular and perineural invasion in locally advanced gastric cancer patients who underwent curative gastrectomy and adjuvant chemotherapy.

OBJECTIVE: In this study, we evaluated the prognostic significance of the concomitant existence of lymphovascular invasion and perineural invasion in patients with advanced gastric cancer. METHODS: A total of 206 consecutive patients with Stage II or III gastric cancer who underwent curative D2 gastrectomy and adjuvant chemotherapy from April 2004 to December 2011 were analyzed. Patients were classified into four groups according to the presence (+) or absence (-) of lymphovascular invasion and perineural invasion: lymphovascular invasion-/perineural invasion- (n = 33), lymphovascular invasion+/perineural invasion- (n = 31), lymphovascular invasion-/perineural invasion+ (n = 54) and lymphovascular invasion+/perineural invasion+ (n = 88). RESULTS: A total of 136 patients (66.0%) received 5-fluorouracil plus cisplatin adjuvant chemotherapy and 70 patients (34.0%) received TS-1. During the median follow-up period of 35.18 months, the median disease-free survival times for lymphovascular invasion-/perineural invasion-, lymphovascular invasion+/perineural invasion- and lymphovascular invasion-/perineural invasion+ were not reached at the time of analysis; however, median disease-free survival for lymphovascular invasion+/perineural invasion+ was the worst (36.73 months, P = 0.001). The median overall survival in the four groups was also not reached at the time of analysis; however, median overall survival with lymphovascular invasion+/perineural invasion+ was the poorest (P = 0.002). In a multivariate analysis, lymphovascular invasion+/perineural invasion+ was an independent prognostic factor for both disease-free survival (hazard ratio = 1.940, 95% confidence interval 1.157-3.252, P = 0.012) and overall survival (hazard ratio = 2.973, 95% confidence interval 1.561-5.662, P = 0.001). CONCLUSIONS: The concomitant existence of lymphovascular and perineural invasion has a significant prognostic impact on disease-free survival and overall survival in patients with Stage II or III gastric cancer.

The association between oxidative stress and bone mineral density according to menopausal status of Korean women.

OBJECTIVE: The aim of this study is to investigate the association between oxidative stress and bone mineral density (BMD) according to menopausal status of Korean women. METHODS: A total of 2,232 women who visited to the health promotion center at Pusan National University Hospital between 2010 and 2014 were included in this cross-sectional study. Laboratory tests, such as uric acid, albumin, total bilirubin, which were evaluated as a natural antioxidants. Homocysteine also was evaluated as a factor associated with oxidative stress. Correlation analyses and partial correlation coefficient between BMD scores and laboratory parameters associated with oxidative stress according to menopausal status were performed with Pearson test. RESULTS: By correlation analysis, uric acid had only positive correlation with femur and lumbar BMD in premenopausal and postmenopausal group. But albumin and bilirubin, which were the other natural antioxidants, had no correlation with BMD except total bilirubin with femur BMD in postmenopausal group. Homocysteine had negative correlation with femur BMD in postmenopausal group. But there were different results in partial correlation coefficient adjusted by age and BMI. In premenopausal group, uric acid was still positive correlation with femur and lumbar BMD, whereas in postmenopausal group homocysteine had no correlation with femur BMD, total bilirubin and uric acid had no correlation with lumbar BMD. At the multiple logistic regressions, only age and menopause status, uric acid had correlation with BMD. CONCLUSION: In this study, homocysteine had no correlation with BMD. But in natural antioxidant, uric acid had only positive correlation with BMD.

Combination of percutaneous radiofrequency ablation and systemic chemotherapy are effective treatment modalities for metachronous liver metastases from gastric cancer.

This study evaluated the efficacy of percutaneous radiofrequency ablation (RFA) for the treatment of metachronous liver metastases of gastric cancer. We enrolled a total of 44 patients who underwent percutaneous RFA for the treatment of metachronous liver metastases after resection of a primary gastric adenocarcinoma from January 2002 to November 2011. The primary endpoint of this study was overall survival (OS) and recurrence-free survival (RFS) after RFA. Systemic chemotherapy was combined with RFA in 40 patients; the OS and RFS of the patients with liver-only metastasis who underwent RFA and chemotherapy were 20.9 months (95% CI 18.4-23.4) and 9.8 months (95% CI 9.2-10.5), respectively. On multivariate analysis, the factors independently, negatively associated with OS were extrahepatic metastatic lesions (HR 12.6, 95% CI 3.7-42.9; p=0.001), no chemotherapy (HR 43.3, 95% CI 7.4-251.3; p=0.001), and tumor number≥2 (HR 2.6, 95% CI 1.2-5.9; p=0.015). The factors independently, negatively associated with RFS were extrahepatic metastatic lesions (HR 3.6, 95% CI 1.6-7.8; p=0.003) and bilobar intrahepatic distribution (HR 3.9, 95% CI 1.5-9.9; p=0.001). The efficacy of percutaneous RFA for metachronous liver metastases of gastric cancer is limited to patients with a single, unilobar metastasis without extrahepatic metastatic lesions. Combined systemic chemotherapy is very important for the prolongation of OS.

Rapidly progressing primary splenic angiosarcoma with fatal hemorrhagic event.

Primary angiosarcoma of the spleen is an extremely rare malignancy. Splenic angiosarcoma is difficult to diagnose, and treatment is often challenging. The prognosis is dismal, with a mean survival of less than 1 year. Currently, no standard treatment methods have been established. Anecdotal reports suggest that early diagnosis and prompt splenectomy followed by cytotoxic chemotherapy can be effective treatment modalities. We report a case of rapidly progressing primary splenic angiosarcoma with multiple liver and bone metastases and a fatal hemorrhagic outcome.

Class III ß-tubulin is a predictive marker for taxane-based chemotherapy in recurrent and metastatic gastric cancer.

BACKGROUND: Class III ß-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. METHODS: We reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients' response to chemotherapy, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS. CONCLUSIONS: TUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.