Effects of phthalates on normal human breast cells co-cultured with different fibroblasts.

Whether or not phthalates play a role in breast carcinogenesis remains to be determined. The goal of this study was to explore the effects of phthalates on the growth of normal MCF-10A breast cells modulated by breast fibroblasts. Fibroblasts were derived from normal mammary tissue adjacent to both estrogen receptor (ER) positive and negative primary breast cancers, which were grown separately from nontumorigenic MCF-10A epithelial cells. MCF-10A co-culture cells were treated with 10 nM 17ß-estradiol (E2), Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP) (10 and 100 nM). After incubation for 120 hours, the cells were harvested and extracted for MTT assay. Western blot analysis was used to evaluate the proliferative pathway proteins and the effects on ER α. Only fibroblasts from ER (+) breast cancer significantly stimulated proliferation of MCF-10A cells. Exposure of the co-culture to E2, BBP, DBP, DEHP, and E2 combined with one of these phthalates resulted in significantly increased cell proliferation, as well as proliferating cell nuclear antigen (PCNA) and ER α expressions. The present study demonstrates that phthalates express a significant influence in fibroblast-epithelial interactions, similarly to the effects of E2 on breast cells. The effects of phthalates on normal breast cells depend upon ER modulating actions. In breast carcinogenesis, phthalates should be considered as having endocrine disrupting potential, even at low concentrations.

Higher body weight and distant metastasis are associated with higher radiation exposure to the household environment from patients with thyroid cancer after radioactive iodine therapy.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan.Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment.A total of 43 patients (18 men and 25 women; mean age 51 ±â€Š13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ±â€Š0.304 (0.088-1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004-1.134]) and distant metastases based on I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938-44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment.Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.

Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer.

BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization. RESULTS: TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts. CONCLUSION: Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.

miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), a primary liver malignancy, is the most common cancer in males and fourth common cancer in females in Taiwan. HCC patients usually have a poor prognosis due to late diagnosis. It has been classified as a complex disease because of the heterogeneous phenotypic and genetic traits of the patients and a wide range of risk factors. Micro (mi)RNAs regulate oncogenes and tumor suppressor genes that are known to be dysregulated in HCC. Several studies have found an association between downregulation of miR-122, a liver-specific miRNA, and upregulation of paternally expressed gene 10 (PEG10) in HCC; however, the correlation between low miR-122 and high PEG10 levels still remains to be defined and require more investigations to evaluate their performance as an effective prognostic biomarker for HCC. METHODS: An in silico approach was used to isolate PEG10, a potential miR-122 target implicated in HCC development. miR-122S binding sites in the PEG10 promoter were evaluated with a reporter assay. The regulation of PEG10 by miR-122S overexpression was examined by quantitative RT-PCR, western blotting, and immunohistochemistry in miR-122 knockout mice and liver tissue from HCC patients. The relationship between PEG10 expression and clinicopathologic features of HCC patients was also evaluated. RESULTS: miR-122 downregulated the expression of PEG10 protein through binding to 3'-untranslated region (UTR) of the PEG10 transcript. In miR-122 knockout mice and HCC patients, the deficiency of miR-122 was associated with HCC progression. The expression of PEG10 was increased in 57.3 % of HCC as compared to paired non-cancerous tissue samples. However, significant upregulation was detected in 56.5 % of patients and was correlated with Okuda stage (P = 0.05) and histological grade (P = 0.001). CONCLUSIONS: miR-122 suppresses PEG10 expression via direct binding to the 3'-UTR of the PEG10 transcript. Therefore, while PEG10 could not be an ideal diagnostic biomarker for HCC but its upregulation in HCC tissue still has predictive value for HCC prognosis.

PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo.

Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor gene and frequently mutated or lost in breast cancer, possesses the negative regulation function over the PI3K/Akt/mTOR pathway. PTEN insufficiency has been associated with advanced breast cancer and poor prognosis of breast cancer patients. Recently, target therapies aimed at PI3K/Akt/mTOR pathway to treat breast cancer have got popularity. However, the exact effect of PTEN on breast cancer cells is still not well understood. This study demonstrated that PTEN knockdown in MCF-7 cells strengthened the downstream gene expressions, including p-Akt, p-ERK1/2, p-mTOR, p-p70s6k, and p-GSK3ß. PTEN knockdown MCF-7 cells had increased cell growth and Ki-67 expression. Further Western blot demonstrated that p27 was repressed obviously with p21 slightly inhibited and CDK1, 2, 4, 6, cyclin A, and Cdc25C were upregulated in MCF-7 PTEN knockdown cells, leading to the higher growth rate. More importantly, PTEN knockdown MCF-7 cells had higher tumorigenesis and tumor growth in vivo. From our current work, we provided more detailed PTEN-mediated mechanisms to stimulate ER+ breast cancer cell growth. Our result may pave the way for further target therapy development used alone or in combination with other drugs for ER+ breast cancer with PTEN insufficiency.

Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan.

Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.

A procalcitonin-based algorithm to guide antibiotic therapy in secondary peritonitis following emergency surgery: a prospective study with propensity score matching analysis.

BACKGROUND: Procalcitonin (PCT)-based algorithms have been used to guide antibiotic therapy in several clinical settings. However, evidence supporting PCT-based algorithms for secondary peritonitis after emergency surgery is scanty. In this study, we aimed to investigate whether a PCT-based algorithm could safely reduce antibiotic exposure in this population. METHODS/PRINCIPAL FINDINGS: From April 2012 to March 2013, patients that had secondary peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. PCT levels were obtained pre-operatively, on post-operative days 1, 3, 5, and 7, and on subsequent days if needed. Antibiotics were discontinued if PCT was <1.0 ng/mL or decreased by 80% versus day 1, with resolution of clinical signs. Primary endpoints were time to discontinuation of intravenous antibiotics for the first episode and adverse events. Historical controls were retrieved for propensity score matching. After matching, 30 patients in the PCT group and 60 in the control were included for analysis. The median duration of antibiotic exposure in PCT group was 3.4 days (interquartile range [IQR] 2.2 days), while 6.1 days (IQR 3.2 days) in control (p < 0.001). The PCT algorithm significantly improves time to antibiotic discontinuation (p < 0.001, log-rank test). The rates of adverse events were comparable between 2 groups. Multivariate-adjusted extended Cox model demonstrated that the PCT-based algorithm was significantly associated with a 87% reduction in hazard of antibiotic exposure within 7 days (hazard ratio [HR] 0.13, 95% CI 0.07-0.21, p < 0.001), and a 68% reduction in hazard after 7 days (adjusted HR 0.32, 95% CI 0.11-0.99, p  =  0.047). Advanced age, coexisting pulmonary diseases, and higher severity of illness were significantly associated with longer durations of antibiotic use. CONCLUSIONS/SIGNIFICANCE: The PCT-based algorithm safely reduces antibiotic exposure in this study. Further randomized trials are needed to confirm our findings and incorporate cost-effectiveness analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000601831.

Effects of estradiol and progestogens on human breast cells: regulation of sex steroid receptors.

OBJECTIVES: To examine the effects of 17ß-estradiol (E2) and progestogens, used in hormone therapy, on estrogen receptors (ER), progesterone receptors (PR), and human breast tumor cell growth. MATERIALS AND METHODS: MCF-7 cells were incubated in pure E2 (1 nM and 10 nM) as well as in E2 in conjunction with 10 nM progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NET), and cyproterone acetate (CPA). Cell proliferation, apoptosis, expression of caspase-3, and both ER and PR isoforms were evaluated. RESULTS: Caspase-3 was significantly diminished in cultures with only E2, whereas ERα significantly increased. A significant increase of caspase-3 in addition to the entire abolishment of E2-induced augmentation of ERα was observed in 1 nM E2 plus MPA and 10 nM E2 plus NET, whereas PR isoform B (PRB) was significantly increased. The ratios of apoptosis: proliferation significantly increased in 1 nM E2 plus progestogens (except P4) and 10 nM E2 plus NET. The changes of the PRA/PRB ratio were inversely related to the changes of the apoptosis to proliferation ratio. Significant increase of ERß and PRB was noted in the E2 plus MPA or NET, in addition to a significant increase of ERα and decrease of PRA in the E2 plus CPA, as well as an increase of ERα and decrease of PRA and PRB in the E2 plus P4. CONCLUSIONS: The combination of E2 and various progestogens resulted in diverging effects on ERs and PRs expressions, which induced different effects on MCF-7 cell growth. Compared with P4, aberrant hormone and biological activity of synthetic progestin, by way of altered receptor expression, may be an important factor in affecting breast cell growth.

Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol.

BACKGROUND: Diagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria. METHODS/DESIGN: We will include cross-sectional studies that consecutively or randomly recruit target populations. We will search the Cochrane Library, Medline, Embase, Science Citation Index, and the Chinese National Knowledge Infrastructure. We will also search the MEDION and ARIF databases to identify diagnostic systematic reviews that include primary studies. Reference lists of relevant reviews will be searched for additional trials. Language restrictions will not be applied. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two authors will apply the QUADAS-2 assessment to all the included studies, and any discrepancies will be resolved by the third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. When possible, we will use the bivariate random-effects model or the Rutter and Gatsonis hierarchical summary receiver operating characteristic model for statistical analysis. To investigate heterogeneity, we will include study designs, population characteristics, test characteristics, and types of reference standard as the study-level variables. DISCUSSION: Our systematic review will allow patients, clinicians, and researchers to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of early-stage HCC and the potential roles of these diagnostic biomarkers in the existing diagnostic pathways.Systematic Review Registration: PROSPERO 2013; CRD42013003879.

Evaluation of the potential therapeutic role of a new generation of vitamin D analog, MART-10, in human pancreatic cancer cells in vitro and in vivo.

Pancreatic cancer is a lethal disease with no known effective chemotherapy and radiotherapy, and most patients are diagnosed in the late stage, making them unsuitable for surgery. Therefore, new therapeutic strategies are urgently needed. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is known to possess antitumor actions in many cancer cells in vitro and in vivo models. However, its clinical use is hampered by hypercalcemia. In this study, we investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. We demonstrate that MART-10 is at least 100-fold more potent than 1α,25(OH)2D3 in inhibiting BxPC-3 cell proliferation in a time- and dose-dependent manner, accompanied by a greater upregulation of cyclin-dependent kinase inhibitors p21 and p27 and a greater downregulation of cyclin D3 and cyclin-dependent kinases 4 and 5, leading to a greater increase in the fraction of cells in G0/G1 phase. No induction of apoptosis and no effect on Cdc25 phosphatases A and C were observed in the presence of either MART-10 or 1α,25(OH)2D3. In a xenograft mouse model, treatment with 0.3 µg/kg body weight of MART-10 twice/week for 3 weeks caused a greater suppression of BxPC-3 tumor growth than the same dose of 1α,25(OH)2D3 without inducing hypercalcemia and weight loss. In conclusion, MART-10 is a promising agent against pancreatic cancer growth. Further clinical trial is warranted.

Effect of parenteral selenium supplementation in critically ill patients: a systematic review and meta-analysis.

BACKGROUND: It is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to assess the efficacy of parenteral selenium supplementation on clinical outcomes. METHODS/PRINCIPAL FINDINGS: Randomized trials investigating parenteral selenium supplementation administered in addition to standard of care to critically ill patients were included. CENTRAL, Medline, EMBASE, the Science Citation Index, and CINAHL were searched with complementary manual searches. The primary outcome was all-cause mortality. Trials published in any language were included. Two authors independently extracted data and assessed trial quality. A third author was consulted to resolve disagreements and for quality assurance. Twelve trials were included and meta-analysis was performed on nine trials that recruited critically ill septic patients. These comprised 965 participants in total. Of these, 148 patients (30.7%) in the treatment groups, and 180 patients (37.3%) in control groups died. Parenteral selenium treatment significantly reduced all-cause mortality in critically ill patients with sepsis (relative risk [RR] 0.83, 95% CI 0.70-0.99, p = 0.04, I(2) = 0%). Subgroup analyses demonstrated that the administration schedule employing longer duration (RR 0.77, 95% CI 0.63-0.94, p = 0.01, I(2) = 0%), loading boluses (RR 0.73, 95% CI 0.58-0.94, p = 0.01, I(2) = 0%) or high-dose selenium treatment (RR 0.77, 95% CI 0.61-0.99, p = 0.04, I(2) = 0%) might be associated with a lower mortality risk. There was no evidence of adverse events. CONCLUSIONS/SIGNIFICANCE: Parenteral selenium supplementation reduces risk of mortality among critically ill patients with sepsis. Owing to the varied methodological quality of the studies, future high-quality randomized trials that directly focus on the effect of adequate-duration of parenteral selenium supplementation for severe septic patients are needed to confirm our results. Clinicians should consider these findings when treating this high-risk population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2011; CRD42011001768.

A novel model for simultaneous study of neointestinal regeneration and intestinal adaptation.

The use of autologous grafts, fabricated from tissue-engineered neointestine, to enhance insufficient compensation of intestinal adaptation for severe short bowel syndrome is a compelling idea. Unfortunately, current approaches and knowledge for neointestinal regeneration, unlike intestinal adaptation, are still unsatisfactory. Thus, we have designed a novel model of intestinal adaptation with simultaneous neointestinal regeneration and evaluated its feasibility for future basic research and clinical application. Fifty male Sprague-Dawley rats weighing 250-350 g underwent this procedure and sacrificed at 4, 8, and 12 weeks postoperatively. Spatiotemporal analyses were carried out by gross, histology, and DNA/protein quantification. Three rats died of operative complications. In early experiments, the use of hard silicone stent as tissue scaffold in 11 rats was unsatisfactory for neointestinal regeneration. In later experiments, when a soft silastic tube was used, the success rate increased up to 90.9%. Further analyses revealed that no neointestine developed without donor intestine; regenerated lengths of mucosa and muscle were positively related to time postsurgery but independent of donor length with 0.5 or 1 cm. Other parameters of neointestinal regeneration or intestinal adaptation showed no relationship to both time postsurgery and donor length. In conclusion, this is a potentially important model for investigators searching for solutions to short bowel syndrome.

Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report.

Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture--a case report.

Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.

Dual-colour chromogenic in-situ hybridization is a potential alternative to fluorescence in-situ hybridization in HER2 testing.

AIM: Dual-colour chromogenic in-situ hybridization (dc-CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc-CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer. METHODS AND RESULTS: Two hundred and twenty-eight invasive breast carcinomas arranged in tissue microarrays were analysed in parallel with dc-CISH, fluorescence in-situ hybridization (FISH), and immunohistochemistry. Of 227 tumours with available FISH and dc-CISH results, HER2 amplification and non-amplification were detected in 49 (21.6%) and 178 (78.4%) tumours, respectively, by both assays. The concordance between dc-CISH and FISH results showed 100% agreement (κ-coefficient=1.00). Immunohistochemically, 162 (71%), 25 (11.0%) and 41 (18%) tumours were scored 0/1+, 2+, and 3+, respectively. The corresponding results with both FISH and dc-CISH demonstrated HER2 amplification in two (3.2%), nine (36%) and 38 (93%) tumours, respectively. Complete consensus among these three methods was observed in 197 cases, representing 98% of all 3+ and 0/1+ tumours (κ-coefficient=0.92). Confirmatory testing of 25 2+ tumours showed complete consensus between FISH and dc-CISH. CONCLUSIONS: dc-CISH is a promising alternative to FISH in HER2 testing, and the single-institute incidence of HER2 amplification in breast cancer in Taiwan is 21.2%.

19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells.

The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)(2)D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH)(2)D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3) (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH)(2)D(3) in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH)(2)D(3) in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G(0)/G(1) phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)(2)D(3) or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH)(2)D(3) and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted.

A simple novel model to predict hospital mortality, surgical site infection, and pneumonia in elderly patients undergoing operation.

BACKGROUND/AIMS: Predicting models of operative morbidity and mortality in the geriatric population are important in the prevention of adverse surgical outcomes. METHODS: A retrospective review of medical records was performed for patients over 80 years of age who underwent gastrointestinal surgery from 1998 to 2008. RESULTS: 215 patients were identified with a mean age of 83.7 years. Overall morbidity and mortality rates were 48.8 and 14.4%, respectively. Multivariate logistic regression analysis revealed that serum albumin levels [odds ratio (OR) = 0.367, p = 0.0267], postoperative pneumonia (OR = 3.471, p = 0.0101), hollow organ perforation or anastomosis combined with leakage (OR = 7.600, p = 0.0126), and preoperative systemic inflammatory response syndrome (OR = 3.186, p = 0.0323) were significant predictors of hospital mortality. Moreover, albumin (OR = 0.270, p = 0.0002) and physical disability (OR = 3.802, p = 0.0009) were significant predictors of postoperative pneumonia, and albumin (OR = 0.491, p = 0.0212) and enterotomy (OR = 3.335, p = 0.0208) were significant predictors of surgical site infections. CONCLUSION: This study provides novel predicting models to identify the elderly surgical patients at high risk, who should receive more intensive preventive and perioperative care.

Prospective randomized study for comparison of open surgery with laparoscopic-assisted placement of Tenckhoff peritoneal dialysis catheter--a single center experience and literature review.

BACKGROUND: The ideal method for catheter placement in patients undergoing peritoneal dialysis remains debatable. This prospective study intends to clarify whether laparoscopic assisted percutaneous puncture is superior to open surgery. MATERIALS AND METHODS: From 2002 to 2006, 77 patients receiving first catheter placement were enrolled and randomized to either an open group of 40 patients or a laparoscopic group of 37 patients. Patient characteristics, operation-related data, procedural complications, and clinical outcome were compared by using the statistical software SPSS ver. 11.5 (SPSS, Chicago, IL). RESULTS: Laparoscopy had a longer operative time (68.32+/-31.90 versus 46.68+/-15.99 min; P<0.001), shorter wound length (1.69+/-0.46 versus 2.34+/-0.84 cm; P<0.001), and higher costs (P<0.001) compared with open surgery. Laparoscopy tended to have a higher incidence of pericannular bleeding (21.6% versus 7.5%) and a lower rate of early catheter migration (2.7% versus 15.0%), but its early/late/overall complication rate did not statistically differ. No surgical mortality occurred. Rate and cause of overall mortality or catheter dropout did not statistically differ. Catheter longevity was equivalent in both groups. CONCLUSIONS: Laparoscopic assisted percutaneous puncture exhibited no superiority to open surgery. As a matter of fact, open surgery's shorter operative time and reduced equipment requirement can increase cost-effectiveness. Therefore, conventional open surgery is recommended for most patients with primary catheter placement.

Multifocal intraductal papillary mucinous neoplasm of the pancreas--a case report.

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas (IPMNs). IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively "new" but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head (75%) while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-year-old male diagnosed with IPMN (carcinoma in situ) in the pancreatic head and a branch duct type IPMN (duct atypia) in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.

Pancreaticoduodenectomy versus Frey's procedure for chronic pancreatitis: preliminary data on outcome and pancreatic function.

PURPOSE: Several surgical treatments have been proposed for treating chronic pancreatitis (CP), including standard pancreaticoduodenectomy (PD), pylorus-preserving PD, Beger's procedure, and Frey's procedure; however, few studies have compared pre- and postoperative pancreatic function in patients undergoing surgery for CP. METHODS: Between 1996 and 2003, 42 patients with CP underwent pancreatic head resection; as PD in 17 and as Frey's procedure in 25. Frey's procedure was chosen if the pancreatic duct was dilated more than 5 mm. We conducted this prospective, nonrandomized study to compare the pre- and postoperative status after PD or Frey's procedure by evaluating pancreatic function and symptom relief. RESULTS: The demographic features, surgical morbidity, and mortality were similar in the two groups. Pancreatic exocrine function improved, pain subsided, and complications of the adjacent organs resolved after surgery in both groups. Similar postoperative endocrine and exocrine functional results were observed in both groups. Frey's procedure was associated with a significantly shorter hospital stay than PD (10.6 versus 15.4 days, respectively; (P < 0.0001)). CONCLUSION: There were no significant difference in operative time, surgical morbidity, or mortality rates between PD and Frey's procedure. Both procedures were equally effective in terms of pain relief, improvement of pancreatic exocrine function, and control of complications affecting the adjacent organs; however, Frey's procedure was associated with a significantly shorter hospital stay.