AIM： To determine the timing of mortality after onset of severe acute pancreatitis （SAP） and the course of the disease in a large series of patients. METHODS： From July 1996 to June 2005, all ...patients diagnosed with acute pancreatitis at Chang Gung Memorial Hospital, Taipei, Taiwan were retrospectively studied. Three thousand two hundred and fifty episodes of acute pancreatitis were recorded in 2248 patients （1431 males and 817 females; median age, 55.6 years; range, 18-97 years）. Mortality was divided into two groups： early death （≤ 14 d after admission）, and late death （〉 14 d after admission）. The clinical features of patients in these two groups were compared. RESULTS： Although the overall mortality rate of acute pancreatitis was 3.8% （123/3250）, mortality rate of SAP was as high as 16.3% （105/643）. Of those 105 SAP mortalities, 44 （41.9%） deaths occurred within the first 14 d after admission and 61 （58.1%） occurred after14 d. Incidence of early death did not significantly differ from that of late death. The co-morbidities did not contribute to the timing of death. Early deaths mainly resulted from multiple organ failure. Late deaths were mainly caused by secondary complication of infected necrosis. Intraabdominal bleeding significantly caused higher mortality in late death. CONCLUSION： Approximately half （42%） of SAP deaths occur within 14 d and most were due to multiple organ failure. The late deaths of SAP were mostly due to infected necrosis.
Cholangiocarcinoma (CCA) is a devastating disease due to no effective treatments available. Since the non-mineral functions of vitamin D emerges, 1α,25(OH)
D
, the active form of vitamin D, has been ...applied in anti-cancer researches. In this study, we demonstrated that both the 1α,25(OH)
D
analog, MART-10, and 1α,25(OH)
D
possessed anti-growth effect on human CCA cells with MART-10 much more potent than 1α,25(OH)
D
. The growth inhibition of both drugs were mediated by induction of G0/G1 cell cycle arrest through upregulation of p27 and downregulation of CDK4, CDK6, and cyclin D3. Human neutrophil gelatinase associated lipocalin (NGAL) was found to be involved in 1α,25(OH)
D
and MART-10 meditated growth inhibition for CCA as knockdown of NGAL decreased Ki-67 expression in SNU308 cells and rendered SNU308 cells less responsive to 1α,25(OH)
D
and MART-10 treatment. Vitamin D receptor (VDR) knockdown partly abolished MART-10-induced inhibition of NGAL and cell growth in SNU308 cells. The xenograft animal study demonstrated MART-10 could effectively repressed CCA growth in vivo without inducing obvious side effects. The IHC examination of human CCA specimen for VDR revealed that higher VDR expression was linked with better prognosis. Collectively, our results suggest that MART-10 could be a promising regimen for CCA treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Whether gastric adenocarcinoma (GC) patients with adjacent organ invasion (T4b) benefit from aggressive surgery involving pancreatic resection (PR) remains unclear. This study aimed to clarify the ...impact of PR on survival in patients with locally advanced resectable GC. Between 1995 and 2017, patients with locally advanced GC undergoing radical-intent gastrectomy with and without PR were enrolled and stratified into four groups: group 1 (G1), pT4b without pancreatic resection (PR); group 2 (G2), pT4b with PR; group 3 (G3), positive duodenal margins without Whipple's operation; and group 4 (G4), cT4b with Whipple's operation. Demographics, clinicopathological features, and outcomes were compared between G1 and G2 and G3 and G4. G2 patients were more likely to have perineural invasion than G1 patients (80.6% vs. 50%,
< 0.001). G4 patients had higher lymph node yield (40.8 vs. 31.3,
= 0.002), lower nodal status (
= 0.029), lower lymph node ratios (0.20 vs. 0.48,
< 0.0001) and higher complication rates (45.2% vs. 26.3%,
= 0.047) than G3 patients. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly longer in G1 than in G2 (28.1% vs. 9.3%,
= 0.003; 32% vs. 13%,
= 0.004, respectively). The 5-year survival rates did not differ between G4 and G3 (DFS: 14% vs. 14.4%,
= 0.384; OS: 12.6% vs. 16.4%,
= 0.321, respectively). In conclusion, patients with T4b lesion who underwent PR had poorer survival than those who underwent resection of other adjacent organs. Further Whipple's operation did not improve survival in pT3-pT4 GC with positive duodenal margins.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary Objective Pancreatic ductal adenocarcinoma is one of the most malignant types of cancer. This study evaluated the 3-year and 5-year surgical outcomes associated with the cancer and determined ...whether statistically identified factors can be used to predict survival. Methods This retrospective review was conducted from 1995 to 2010. Patients who had resectable pancreatic ductal adenocarcinoma and received surgical treatment were included. Cases of hospital mortality were excluded. The relationships between several clinicopathological factors and the survival rate were analyzed. Results A total of 223 patients were included in this study. The 3-year and 5-year survival rates were 21.4% and 10.1%, respectively, and the median survival was 16.1 months. Tumor size, N status, and resection margins were independent predictive factors for 3-year survival. Tumor size independently predicted 5-year survival. Conclusion Tumor size is the most important independent prognostic factor for 3-year and 5-year survival. Lymph node status and the resection margins also independently affected the 3-year survival. These patient outcomes might be improved by early diagnosis and radical resection. Future studies should focus on the tumor biology of this aggressive cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of adjuvant chemotherapy in pathological T3N0M0 (pT3N0M0) gastric cancer (GC) remains unclear. The aim of this study was to analyze the prognostic factors of patients with pT3N0M0 GC and to ...clarify which ones could benefit from adjuvant chemotherapy. A total of 137 patients with pT3N0M0 GC were recruited between 1994 and 2020. Clinicopathological factors and adjuvant chemotherapy regimens were retrospectively collected. Prognostic factors of disease-free survival (DFS) and cancer-specific survival (CSS) were determined using univariate and multivariate analyses. The chemotherapy group was younger (
= 0.012), had had more lymph nodes retrieved (
= 0.042) and had higher percentages of vascular invasion (
= 0.021) or perineural invasion (
= 0.030) than the non-chemotherapy group. There were no significant differences in DFS (
= 0.222) and CSS (
= 0.126) between patients treated with or without adjuvant chemotherapy. Stump cancer, tumor size and perineural invasion were associated with higher rates of recurrence. Tumor size was an independent prognostic factor for DFS (hazard ratio, 4.55; confidence interval, 1.59-12.99;
= 0.005) and CSS (hazard ratio, 3.97; confidence interval, 1.38-11.43;
= 0.011). Tumor size independently influenced survival outcomes in pT3N0M0 patients who underwent radical surgery with and without adjuvant chemotherapy.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, ...leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA.
Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied.
IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial-mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients.
Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment.
: Although melatonin treatment following trauma‐hemorrhage or ischemic reperfusion prevents organs from dysfunction and injury, the precise mechanism remains unknown. This study tested whether ...melatonin prevents liver injury following trauma‐hemorrhage involved the protein kinase B (Akt)‐dependent heme oxygenase (HO)‐1 pathway. After a 5‐cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure approximately 40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), or melatonin plus phosphoinositide 3‐kinase (PI3K) inhibitor wortmannin (1 mg/kg). At 2 hr after trauma‐hemorrhage, the liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and aspartate aminotransferase levels were significantly increased compared with sham‐operated control. Trauma‐hemorrhage resulted in a significant decrease in the Akt activation in comparison with the shams (relative density, 0.526 ± 0.031 versus 1.012 ± 0.066). Administration of melatonin following trauma‐hemorrhage normalized liver Akt phosphorylation (0.993 ± 0.061), further increased mammalian target of rapamycin (mTOR) activation (5.263 ± 0.338 versus 2.556 ± 0.225) and HO‐1 expression (5.285 ± 0.325 versus 2.546 ± 0.262), and reduced cleaved caspase‐3 levels (2.155 ± 0.297 versus 5.166 ± 0.309). Coadministration of wortmannin abolished the melatonin‐mediated attenuation of the shock‐induced liver injury markers. Our results collectively suggest that melatonin prevents hemorrhagic shock‐induced liver injury in rats through an Akt‐dependent HO‐1 pathway.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Background Approximately, 50% of all gastric cancer patients are aged >70 y. Although curative surgery is the treatment of choice, many geriatric patients die of surgical complications. ...Therefore, we aimed to evaluate the impact of radical surgery on the survival outcome of geriatric patients with resectable gastric cancers. Methods About 488 patients diagnosed with resectable gastric cancers, aged ≥70 y, between January 2007 and December 2012 at Chang Gung Memorial Hospital (CGMH) Linkou branch were included in this study. Using univariate and multivariate analyses, possible prognostic variables for survival outcome were assessed in 445 patients (91.2%) treated with radical surgery (OP group) and 43 (8.8%) receiving conservative treatment (non-OP group). The impact of radical surgery on survival outcomes was evaluated according to CGMH scores. Results On multivariate analysis, surgical resection with subtotal gastrectomy and CGMH score were the only independent prognostic factors for both overall and cancer-specific survival. The median survival time was 43 mo for the entire cohort. The OP group had significantly better survival outcome than the non-OP group (median survival, 50.3 versus 16.2 mo, P < 0.001). The median survival times for patients with CGMH scores ≤20 were 64.1 and 20.0 mo ( P < 0.002) and those for patients with CGMH scores >20 were 13.8 and 10.4 mo ( P = 0.18) in the OP and non-OP groups, respectively. Conclusions Surgical resection and CGMH score are independent prognostic factors for overall and cancer-specific survival; the CGMH score might be a prognostic indicator of surgical outcome in geriatric patients with resectable gastric cancers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of digestive cancer. Recurrence within one year after surgery is inevitable in most PDAC patients. Recently, cluster of ...differentiation 44 (CD44) has been shown to be associated with tumor initiation, metastasis and prognosis. This study aimed to explore the correlation of CD44 expression with clinicopathological factors and the role of CD44 in predicting early recurrence (ER) in PDAC patients after radical surgery.
PDAC patients who underwent radical resection between January 1999 and March 2015 were enrolled in this study. Tumor recurrence within 6 months after surgery was defined as ER. Immunohistochemical staining was performed with anti-CD44 antibodies. The association between clinicopathological parameters and CD44 expression was analyzed. Predictors for ER were also assessed with univariate and multivariate analyses.
Overall, 155 patients were included in this study. Univariate analysis revealed CA19-9 levels (p=0.014), CD44 histoscores (H-scores; p=0.002), differentiation (p=0.010), nodal status (p=0.005), stage (p=0.003), vascular invasion (p=0.007), lymphatic invasion (p<0.001) and perineural invasion (p=0.042) as risk factors for ER. In multivariate analysis, high CA19-9 levels and CD44 H-scores and poor differentiation independently predicted ER.
High CA19-9 levels, CD44 H-scores and poor differentiation are independent predictors for ER in PDAC patients undergoing radical resection. Therefore, the determination of CD44 expression might help in identifying patients at a high risk of ER for more aggressive treatment after radical surgery.
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