• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2239-2244
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• 2014

Objective: To investigate the effects of secondary left-sided portal hypertension (LSPH) on the radical operation rate of patients with pancreatic cancer and systemically evaluate the prognosis of patients with LSPH secondary to pancreatic cancer after radical surgery. Materials and Methods: The data of patients with pancreatic cancer who underwent laparotomy over a 15-year period in Department of Hepatobiliary Surgery of Chinese PLA Air Force General Hospital from Jan. 1, 1997, to Jun. 30, 2012 was retrospectively reviewed. Results: A total of 362 patients with pancreatic cancer after laparotomy were selected, including 73 with LSPH and 289 without LSPH. Thirty-five patients with LSPH (47.9%) and 147 without non-LSPH (50.9%) respectively underwent radical operations. No significant difference was found between these two groups regarding the total resection rate and stratified radical resection rate according to different pathological types and cancer locations. The mean and median survival time of patients after radical operation in LSPH group were $13.9{\pm}1.3$ months and 14.8 months, respectively, while those in non-LSPH group were $22.6{\pm}1.4$ months and 18.4 months, respectively(P<0.05). Conclusions: Radical operations for pancreatic cancer and secondary LSPH are safe and effective. Because high-grade malignancy and poor prognosis are closely associated, the decision for radical surgery should be made more meticulously for the patients with pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5243-5248
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• 2013

Background: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. Methods: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. Results: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Conclusion: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.2
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• pp.141-150
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• 2023

Pancreatic carcinosarcoma is a very rare malignancy with a poor prognosis. Because of these characteristics, a treatment strategy for it has not been established yet. The aim of this study was to establish a therapeutic strategy for pancreatic carcinosarcoma. We reviewed data of a 65-year-old female patient who was diagnosed with pancreatic carcinosarcoma through endoscopic ultrasound-guided fine needle aspiration biopsy before surgery. For literature review, we searched PubMed using terms of "Pancreatic" or "Pancreas" and "carcinosarcoma" or "carcinosarcomatous". The patient received 11 cycles of neoadjuvant treatment with leucovorin, fluorouracil, irinotecan, oxaliplatin and pembrolizumab because the tumor was borderline resectable. She underwent stereotactic ablative body radiotherapy (SABR) with 35 Gy in 5 fractions, followed by robotic pylorus-preserving pancreaticoduodenectomy. After surgery, the patient received adjuvant chemotherapy in the same regimen as before surgery. She is alive without any recurrence. Among 48 patients within 33 available papers, the median survival time was 15 months. The survival rate of patients who received adjuvant chemotherapy tended to be higher than that of those who did not receive adjuvant chemotherapy, although the difference was not statistically significant (median survival, 47 vs. 15 months; p = 0.485). Three patients who received neoadjuvant chemotherapy had a survival period of 13-23.5 months. Surgery with lymphadenectomy, adjuvant therapy, and neoadjuvant therapy are thought to help improve survival outcomes. Modern treatment approaches for conventional pancreatic ductal adenocarcinoma could be applied to pancreatic carcinosarcoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4261-4265
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• 2013

Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictor of survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy after operative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimed to assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated with gemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1 expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that high RRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56, 95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) than low RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests that high RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker for gemcitabine response and prognosis in pancreatic cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.5977-5982
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• 2014

Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced by findings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.71-75
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• 2016

Pancreatic cancer is a leading cause of fatality worldwide. Several population studies have been conducted on genetic diagnosis of pancreatic cancer but the results from epidemiologic studies are very limited. CYP17A gene has a role in disease formation but its influence on pancreatic cancer is unclear. A polymorphism in the 5'UTR promoter region of CYP17A1-34T/C (A1/A2) has been associated with multiple cancers. The aim of the current study was to assess associations of this polymorphism and socio-demographic risk factors with pancreatic cancer. A total of 255 and 320 controls were enrolled in the study, and were genetically analyzed through PCR-RFLP. Statistical analysis was conducted with observed genotype frequencies and odds ratios (ORs) and 95% CIs were estimated using unconditional logistic regression. The impact of socio-demographic factors was accessed through Kaplen-Meir analysis. According to our results, the A2/A2 genotype was significantly associated with pancreatic cancer (OR=2.1, 95%CI = 1.3-3.5). Gender female (OR=2.6, 95%CI=1.8-3.7), age group 80s/80+ years (OR=2.2, 95% CI=1.2-4), smoking both former (OR=4.6, 95% CIs=2.5-8.8) and current (OR=3.6, 95% CI=2-6.7), and family history (OR=7.1; 95%CI = 4.6-11.4) were also found associated with increased risk. Current study suggests that along with established risk factors for pancreatic cancer CYP17A1-34T/C may play a role. However, on the basis of small sample size the argument cannot be fully endorsed and larger scale studies are recommended.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4501-4507
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• 2013

Caveolin-1 is a scaffold protein on the cell membrane. As the main component of caveolae, caveolin-1 is involved in many biological processes that include substance uptake and transmembrane signaling. Many of these processes and thus caveolin-1 contribute to cell transformation, tumorigenesis, and metastasis. Of particular interest are the dual rolesof tumor suppressor and oncogene that caveolin-1 appear to play in different malignancies, including pancreatic cancer. Therefore, analyzing caveolin-1 regulators and understanding their mechanisms of actionis key to identifying novel diagnostic and therapeutic tools for pancreatic cancer. This review details the mechanisms of action of caveolin-1 regulators and the potential significance for pancreatic cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5133-5139
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• 2013

Background: Perineural invasion (PNI) has been reported as one of the sources of locoregional recurrence in resected pancreatic cancer (PC). However the impact of PNI in resected pancreatic cancer remains controversial. The purpose of this study was to determine the association between PNI status and clinical outcomes. Methods: Publications were identified which assessed prognostic significance of PNI status in resected pancreatic cancer up to February 2013. A meta-analysis was performed to clarify the association between PNI status and clinical outcomes. Results: A total of 21 studies met the inclusion criteria, covering 4,459 cases. Analysis of these data showed that intrapancreatic PNI was correlated with reduced overall survival only in resected pancreatic ductal adenocarcinoma (PDAC) patients (HR=1.982, 95%CI: 1.526-2.574, p=0.000). Extrapancreatic PNI was correlated with reduced overall survival in all resected pancreatic cancer patients (HR=1.748, 95%CI: 1.372-2.228, p=0.000). Moreover, intrapancreatic PNI status may be associated with tumor recurrence in all resected pancreatic cancer patients (HR=2.714, 95%CI: 1.885-3.906, p=0.000). Conclusion: PNI was an independent and poor prognostic factor in resected PDAC patients. Moreover, intrapancreatic PNI status may be associated with tumor recurrence.

• Korean Journal of Plant Resources
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• v.26 no.6
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• pp.673-677
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• 2013

In order to examine the effects of Korean cucurbitaceous plants on sonic hedgehog pathway and growth of cancer cells with over-activated hedgehog pathway, we measured the sonic hedgehog conditioned medium (shh-CM) induced alkaline phosphatase (ALP) activity and cell viability of pancreatic cancer cell lines by treatment of cucurbitaceous plants. Among the tested cucurbitaceous plants, Actinostemma lobatum Maxim, Cucumis sativus L., Momordica charantia L., Schizopepon bryoniaefolius Maxim and Trichosanthes kirilowii Max, var. japonica Kitam showed the potent inhibitory effects (> 50 % at $20{\mu}g/mL$) on shh-CM induced ALP activity. We also evaluated the cell viability of pancreatic cancer cells treated with the cucurbitaceous plants. The tested cucurbitaceous plants showed the very weak effects on cancer cell proliferation but, T. kirilowii Max, var. japonica Kitam presented the inhibitory effect of 72.7 % on the proliferation of pancreatic cancer cells at $20{\mu}g/mL$. Taken together, we screened the effects of Korean cucurbitaceous plants on shh-CM induced ALP activity and cell viability of pancreatic cancers to search for the modulators of the hedgehog pathway leading to the inhibition of cancer cell proliferation. T. kirilowii Max, var. japonica Kitam, among the tested cucurbitaceous plants, showed the inhibitory effects on the shh-CM induced ALP activity and the proliferation of pancreatic cancer cells.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.3
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• pp.317-321
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• 2023

Gastric cancer is very common. Many patients have undergone radical gastric cancer surgery in Korea. Recently, the number of cases with secondary cancer occurring in other organs such as periampullary cancers is increasing as survival rate of gastric cancer patients increases. There are some clinical issues in managing patients with periampullary cancer who have undergone radical gastrectomy previously. Considering that pancreatoduodectomy (PD) has two phases (i.e., resection and reconstruction), it can be very complicated and controversial to perform safe and effective reconstruction following PD in patients with a previous radical gastrectomy. In this report, we present our experiences of uncut-Roux-en-Y fashioned reconstruction in PD for patients with a previous radical gastrectomy and discuss its technical characteristics and potential advantages.