Over-expression of TNNI3K is associated with early-stage carcinogenesis of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a devastating disease with very poor prognosis due to late diagnosis and resistance to traditional chemotherapies and radiotherapies. Herein, thioacetamide (TAA)-induced rat CCA model and CGCCA cell line were used; we aim to study the cytogenetic features during tumoral development of CCA and uncover the mystery regarding carcinogenesis of CCA. The Array comparative genomic hybridization analysis, in silico method, gene knockdown, Western blot, cell count proliferation assay, clonogenecity assay, and IHC staining were applied in this study. Array comparative genomic hybridization analysis was performed on all different TAA-induced phases of rat tissues to reveal the certain pattern, +2q45, +Xq22, -12p12, have been identified for the tumor early stage, where involve the gene TNNI3K. In addition, 16 genes and 3 loci were associated with rapid tumor progression; JAK-STAT signaling pathway was highly correlated to late stage of CCA. In silico database was used to observe TNNI3K was highly express at tumor part compared with normal adjacent tissue in CCA patients from TCGA dataset. Furthermore, the growth of TNNI3K-knockdown SNU308 and HuCCT1 cells decreased when compared with cells transfected with an empty vector cell demonstrated by proliferation and colonogenecity assay. Besides, over expression of TNNI3K was especially confirmed on human CCA tumors and compared with the intrahepatic duct stone bile duct tissues and normal bile duct tissues (P < 0.001). Our findings might uncover the mystery regarding carcinogenesis of CCA, and provide the potential genetic mechanism to the clinicians some ideas for the patients' treatment.

Melatonin Attenuates Acute Pancreatitis-Induced Liver Damage Through Akt-Dependent PPAR-γ Pathway.

BACKGROUND: Despite melatonin treatment diminishes inflammatory mediator production and improves organ injury after acute pancreatitis (AP), the mechanisms remain unknown. This study explores whether melatonin improves liver damage after AP through protein kinase B (Akt)-dependent peroxisome proliferator activated receptor (PPAR)-γ pathway. METHODS: Male Sprague-Dawley rats were subjected to cerulein-induced AP. Animals were treated with vehicle, melatonin, and melatonin plus phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin 1 h following the onset of AP. Various indicators and targeted proteins were checked at 8 h in the sham and AP groups. RESULTS: At 8 h after AP, serum alanine aminotransferase/aspartate aminotransferase levels, histopathology score of hepatic injury, liver myeloperoxidase activity, and proinflammatory cytokine production were significantly increased and liver tissue adenosine triphosphate concentration was lower compared with shams. AP resulted in a marked decrease in liver Akt phosphorylation and PPAR-γ expression in comparison with the shams (relative density, 0.442 ± 0.037 versus. 1.098 ± 0.069 and 0.390 ± 0.041 versus ± 1.080 0.063, respectively). Melatonin normalized AP-induced reduction in liver tissue Akt activation (1.098 ± 0.054) and PPAR-γ expression (1.145 ± 0.083) as well as attenuated the increase in liver injury markers and proinflammatory mediator levels, which was abolished by coadministration of wortmannin. CONCLUSIONS: Collectively, our findings suggest that melatonin improves AP-induced liver damage in rats, at least in part, via Akt-dependent PPAR-γ pathway.

Effects of cholecystectomy on recurrent biliary complications after endoscopic treatment of common bile duct stone: a population-based cohort study.

BACKGROUND: The aim of this study was to evaluate the benefits of cholecystectomy on mitigating recurrent biliary complications following endoscopic treatment of common bile duct stone. METHODS: We used the data from the Taiwan National Health Insurance Research Database to conduct a population-based cohort study. Among 925 patients who received endoscopic treatment for choledocholithiasis at the first admission from 2005 to 2012, 422 received subsequent cholecystectomy and 503 had gallbladder (GB) left in situ. After propensity score matching with 1:1 ratio, the cumulative incidence of recurrent biliary complication and overall survival was analyzed with Cox's proportional hazards model. The primary endpoint of this study is recurrent biliary complications, which require intervention. RESULTS: After matching, 378 pairs of patients were identified with a median follow-up time of 53 (1-108) months. The recurrent rate of biliary complications was 8.20% in the cholecystectomy group and 24.87% in the GB in situ group (p < 0.001). In the multivariate Cox regression analysis, the only independent risk factor for recurrent biliary complications was GB left in situ (hazard ratio [HR] 3.55, 95% CI 2.36-5.33). CONCLUSIONS: Cholecystectomy after endoscopic treatment of common bile duct stone reduced the prevalence of recurrent biliary complications.

Differentiation of the Follicular Variant of Papillary Thyroid Carcinoma From Classic Papillary Thyroid Carcinoma: An Ultrasound Analysis and Complement to Fine-Needle Aspiration Cytology.

OBJECTIVES: It is difficult to establish a diagnosis of the follicular variant of papillary thyroid carcinoma (PTC) using fine-needle aspiration cytology (FNAC). Preoperative features on ultrasound (US) imaging are different between follicular PTC and classic PTC. This study developed a risk score system to differentiate follicular PTC from classic PTC and to correlate the risk score of follicular PTC with its FNAC categories and pathologic features. METHODS: The US features, FNAC results, and pathologic reports of 156 follicular PTC nodules and 152 classic PTC nodules from 296 patients with PTC along with their clinical characteristics were reviewed retrospectively. A risk score system based on US features was developed by multivariate logistic regression to differentiate classic PTC from follicular PTC nodules. The risk scores were then correlated with the FNAC category and pathologic features of the nodules. RESULTS: The US risk score (5 × echogenicity + 3 × calcifications + 3 × marginal regularity) had an area under the receiver operating characteristic curve of 0.85 and a cutoff value of 8.0, with specificity of 87% and sensitivity of 69% for predicting a classic PTC nodule. The follicular PTC nodules with low Bethesda categorization (I-III) had a median US risk score of 6 (range, 0-11), which was higher than that of nodules with high categorization (IV-VI; median, 3; range, 0-11). CONCLUSIONS: The US risk score may be useful in differentiating classic PTC from follicular PTC and complementary to FNAC in identifying follicular PTC.

Caffeic Acid Phenethyl Ester Induces N-myc Downstream Regulated Gene 1 to Inhibit Cell Proliferation and Invasion of Human Nasopharyngeal Cancer Cells.

Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells. In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC.

Spatiotemporal expression of foxo4, foxo6a, and foxo6b in the developing brain and retina are transcriptionally regulated by PI3K signaling in zebrafish.

The forkhead box subclass O (FoxO) family of proteins is a group of highly evolutionary conserved transcription factors that regulate various cellular processes and embryonic development. Dysregulated expressions of FOXO genes have been identified in numerous tumors and genetic disorders. The expression of FOXO/Foxo, particularly FOXO4/Foxo4 and FOXO6/Foxo6, in the developing nervous system has not been fully characterized. Here, we identified zebrafish foxo4, foxo6a, and foxo6b homologs and demonstrated that all three genes were expressed in the developing nervous system. foxo4, foxo6a, and foxo6b displayed ubiquitous expression in the brain and later in distinct brain tissues. In addition, these three genes were expressed in different retinal layers in a time-dependent manner. Furthermore, the mRNA expression of all three genes was significantly downregulated after treatment with a selective PI3-kinase (PI3K) inhibitor, LY294002. Our results suggest that foxo4, foxo6a, and foxo6b play important roles in the developing brain and retina and that the transcriptional levels of these genes are regulated by PI3-kinase signaling.

Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway.

Although melatonin attenuates the increases in inflammatory mediators and reduces organ injury during trauma-hemorrhage, the mechanisms remain unclear. This study explored whether melatonin prevents liver injury after trauma-hemorrhage through the p38 mitogen-activated protein kinase (MAPK)-dependent, inducible nitrite oxide (iNOS)/hypoxia-inducible factor (HIF)-1α pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), melatonin plus p38 MAPK inhibitor SB203580 (2 mg/kg), or melatonin plus the melatonin receptor antagonist luzindole (2.5 mg/kg). At 2 h after trauma-hemorrhage, histopathology score of liver injury, liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and asparate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the p38 MAPK activation compared with that in the sham-treated animals. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression and attenuated cleaved caspase 3 and receptor interacting protein kinase-1 levels. Coadministration of SB203580 or luzindole abolished the melatonin-mediated attenuation of the trauma-hemorrhage-induced increase of iNOS/HIF-1α protein expression and liver injury markers. Taken together, our results suggest that melatonin prevents trauma-hemorrhage-induced liver injury in rats, at least in part, through melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway.NEW & NOTEWORTHY Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression, which was abolished by coadministration of SB203580 or luzindole. Melatonin prevents trauma-hemorrhage-induced liver injury in rats via the melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway.

Clinicopathological characteristics and outcomes in stage I-III mucinous gastric adenocarcinoma: a retrospective study at a single medical center.

BACKGROUND: The clinicopathological characteristics and outcomes of mucinous gastric adenocarcinoma (GC) remain unclear. We report the clinicopathological features and prognosis of patients with mucinous histology who underwent radical-intent gastrectomy. METHODS: We reviewed the medical records of 1470 patients with pathologically proven undifferentiated GC undergoing radical-intent gastrectomy between 1995 and 2007. The patients were stratified into three groups according to their histological type: mucinous carcinoma (MC), signet ring cell carcinoma (SRCC), and poorly differentiated carcinoma (PDC). Clinicopathological factors affecting prognosis were collected prospectively and analyzed. RESULTS: In stage III MC, the age and size were significantly greater and larger than in SRCC and PDC; a lower proportion of perineural invasion was identified in MC, and female predominance was noted in SRCC in comparison with MC and PDC. The cumulative overall survival rates of stage I-III GC patients with MC were significantly superior compared to those with PDC, but not SRCC. Stage III GC patients with MC had a better prognosis than those with SRCC or PDC; the difference in survival was not evident in stages I or II. CONCLUSIONS: Thus, MC presents with different clinicopathological features and prognosis from SRCC and PDC. The patients with stage III gastric MC had favorable outcomes.

The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo.

Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.

The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential.

Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), the newly-synthesized 1α,25(OH)2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.

25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3.

Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 µg/kg or 20 µg/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA.

Pain relief from combined wound and intraperitoneal local anesthesia for patients who undergo laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for gallbladder lesions, but it is not a pain-free procedure. This study explored the pain relief provided by combined wound and intraperitoneal local anesthetic use for patients who are undergoing LC. METHODS: Two-hundred and twenty consecutive patients undergoing LC were categorized into 1 of the following 4 groups: local wound anesthetic after LC either with an intraperitoneal local anesthetic (W + P) (group 1) or without an intraperitoneal local anesthetic (W + NP) (group 2), or no local wound anesthetic after LC either with intraperitoneal local anesthetic (NW + P) (group 3) or without an intraperitoneal local anesthetic (NW + NP) (group 4). A visual analog scale (VAS) was used to assess postoperative pain. The amount of analgesic used and the duration of hospital stay were also recorded. RESULTS: The VAS was significantly lower immediately after LC for the W + P group than for the NW + NP group (5 vs. 6; p = 0.012). Patients in the W + P group received a lower total amount of meperidine during their hospital stay. They also had the shortest hospital stay after LC, compared to the patients in the other groups. CONCLUSION: Combined wound and intraperitoneal local anesthetic use after LC significantly decreased the immediate postoperative pain and may explain the reduced use of meperidine and earlier discharge of patients so treated.

Role of Akt/HO-1 pathway in estrogen-mediated attenuation of trauma-hemorrhage-induced lung injury.

BACKGROUND: Despite advances in intensive care medicines, hemorrhagic shock leading to multiple organ failure remains the major causes of death in the injured host. Although studies have shown that 17ß-estradiol (E2) prevents trauma-hemorrhage-induced lung damage, it remains unknown whether protein kinase B (Akt)/heme oxygenase (HO)-1 plays any role in E2-mediated lung protection after trauma-hemorrhage. MATERIALS AND METHODS: After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ∼40 mm Hg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 kg/mg), E2 plus phosphoinositide 3-kinase inhibitor LY294002 (5 mg/kg), or LY294002. At 2 h after trauma-hemorrhage or sham operation, lung tissue myeloperoxidase activity, wet-to-dry-weight ratio, inflammatory mediators, and apoptosis were measured. Lung Akt, HO-1, and cleaved caspase-3 protein levels were also determined. RESULTS: E2 attenuated the trauma-hemorrhage-induced increase in lung myeloperoxidase activity, edema formation, inflammatory mediator levels, and apoptosis, which was blocked by co-administration of LY294002. Administration of E2 normalized lung Akt phosphorylation and further increased HO-1 expression and decreased cleaved caspase-3 levels after trauma-hemorrhage. Co-administration of LY294002 prevented the E2-mediated attenuation of shock-induced lung injury. CONCLUSIONS: Our results collectively suggest that Akt-dependent HO-1 upregulation may play a critical role in E2-meditated lung protection after trauma-hemorrhage.

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.

MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1α,25-Dihydroxyvitamin D(3) in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells.

Hormone antagonist therapy for estrogen receptor positive (ER+) breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1α,25(OH)(2)D(3) analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D(3 )(MART-10), on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,25(OH)(2)D(3) in inhibiting cell growth in a dose- and time-dependent manner. MART-10 is also much more potent in arresting MCF-7cell cycle progression at G(0)/G(1) phase as compared to 1α,25(OH)(2)D(3), possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,25(OH)(2)D(3) in causing cell apoptosis, likely through a higher BAX/Bcl expression ratio and the subsequent cytochrome C release from mitochondria to cytosol. Based on our in vitro findings, MART-10 could be a promising vitamin D analog for the potential treatment of breast cancer, for example, ER+ patients, to decrease the tumor relapse rate and the side effect on bone caused by antihormone regimens. Thus, further in vivo animal study is warranted.

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.

Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer.

BACKGROUND: Pancreatic adenocarcinoma (PCA) is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors. METHODS: We retrospectively reviewed the medical files of 688 patients (422 men and 266 women) who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection. RESULTS: A carbohydrate antigen 19-9 (CA 19-9) level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl), radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival. CONCLUSIONS: Besides traditional imaging studies, preoperative CA 19-9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well-differentiated tumors predict the favorable prognosis of PCA patients after resection.

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.

Hepatocellular carcinoma and vitamin D: a review.

The non-classical actions of vitamin D, namely antiproliferation, pro-differentiation, pro-apoptosis, anti-inflammation, and immune regulation, have received great attention during the past decade. Increasing evidence from epidemiological studies showing the inverse association between vitamin D status and incidence of many forms of cancer as well as biochemical studies has suggested that vitamin D deficiency may play a role in the cause and progression of these types of cancer. Recently, vitamin D and its analogs have been deemed as potential regimen to treat a variety of cancers alone or in combination with other drugs. Although, the epidemiologic evidence regarding the association of vitamin D and hepatocellular carcinoma (HCC) is still inconclusive, biochemical evidence clearly indicates that HCC cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss the current status of HCC and its treatment, the source, metabolism, functions, and the mechanism of actions of vitamin D, and the biochemical studies of vitamin D analogs and their implications in the prevention and treatment of HCC.

Surgical management in metastatic gastrointestinal stromal tumor (GIST) patients after imatinib mesylate treatment.

PURPOSE: Imatinib mesylate (IM) demonstrates substantial efficacy in most patients with metastatic gastrointestinal stromal tumors (GISTs). However, progression of GIST eventually develops and emerges as a challenge. To assess the role of surgery in the multidisciplinary management of GISTs, we studied the surgical outcomes in GIST patients receiving IM. MATERIALS AND METHODS: Between 2001 and May 2009, 161 metastatic GIST patients received IM. Among them, 35 patients undergoing 38 surgeries were investigated. Patients were categorized based on extent of disease before surgery (responsive or stable disease (PR, SD), local progression (LP), and generalized progression (GP)). Each tumor was investigated for genetic alteration before and after surgery. RESULTS: Disease status before surgery was significantly associated with surgical result. Gross tumor clearance was achieved in 42.9% of patients with responsive disease, but only 4.8% of those with focal resistance and 0% of those with disease progression (P = 0.022). GIST patients with PR, SD, and LP had significant better 2-year progression-free survival and overall survival than those with GP. Secondary mutations tended to be found more frequently in GIST patients with LP after surgery than those with response (10/21 (47.6%) vs. 2/14 (14.3%); P = 0.07), indicating that surgery may prevent potential development of secondary mutation in GIST patients with response. Secondary kit mutations were also found more frequently with primary exon 11 mutation than those with exon 9 mutation (38.7% vs. 16.7%; P = 0.394). CONCLUSIONS: Surgery may benefit selected GIST patients with PR, SD, and LP, especially for patients with LP because patients with LP had comparable survival to that of patients with responsive lesion. Surgery may prevent potential development of secondary mutations in selected patients with response after IM treatment. Secondary kit mutation was found more frequently in GIST patients with a primary kit exon 11 mutation than those with a primary kit exon 9 mutation.