• International Journal of Oncology
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• v.54 no.2
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• pp.744-752
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• 2019

Fewer than 20% of patients diagnosed with pancreatic cancer can be treated with surgical resection. The effects of proton beam irradiation were evaluated on the cell viabilities in Panc-1 and Capan-1 pancreatic cancer cells. The cells were irradiated with proton beams at the center of Bragg peaks with a 6-cm width using a proton accelerator. Cell proliferation was assessed with the MTT assay, gene expression was analyzed with semi-quantitative or quantitative reverse transcription-polymerase chain reaction analyses and protein expression was evaluated by western blotting. The results demonstrated that Capan-1 cells had lower cell viability than Panc-1 cells at 72 h after proton beam irradiation. Furthermore, the cleaved poly (ADP-ribose) polymerase protein level was increased by irradiation in Capan-1 cells, but not in Panc-1 cells. Additionally, it was determined that histone H2AX phosphorylation in the two cell lines was increased by irradiation. Although a 16 Gy proton beam was only slightly up-regulated cyclin-dependent kinase inhibitor 1 (p21) protein expression in Capan-1 cells, p21 expression levels in Capan-1 and Panc-1 cells were significantly increased at 72 h after irradiation. Furthermore, it was observed that the expression of DNA repair protein RAD51 homolog 1 (RAD51), a homogenous repair enzyme, was decreased in what appeared to be a dose-dependent manner by irradiation in Capan-1 cells. Contrastingly, the transcription of survivin in Panc-1 was significantly enhanced. The results suggest that RAD51 and survivin are potent markers that determine the therapeutic efficacy of proton beam therapy in patients with pancreatic cancer.

• Journal of Gastric Cancer
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• v.24 no.2
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• pp.220-230
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• 2024

Purpose: Prevention of pancreas-related complications after gastric cancer surgery is critical. Polyglycolic acid (PGA) mesh reduces postoperative pancreatic fistula formation following pancreatic resection. However, the clinical efficacy of PGA mesh in gastric cancer surgery has not been adequately investigated. Materials and Methods: This retrospective study compared the short-term outcomes between two groups: patients who underwent minimally invasive R0 gastrectomy for gastric cancer with the use of a PGA mesh (PGA group) and those without the use of a PGA mesh (non-PGA group) at the Cancer Institute Hospital, Tokyo, between January 2019 and May 2023. Propensity score matching (PSM) was performed to adjust for the possible confounding factors. Results: A total of 834 patients were initially included, of whom 614 (307 in each group) remained after PSM. The amylase levels in the drained abdominal fluid on postoperative days 1 and 3 were similar between the PGA and non-PGA groups. The PGA group had a significantly lower incidence of pancreas-related complications of Clavien-Dindo grade ≥2 than that in the non-PGA group (6.8% vs. 2.9%, P=0.025). In subgroup analyses, the odds ratio for pancreas-related complications appeared to be better in the PGA group than in the non-PGA group in patients with American Society of Anesthesiologists Physical Status Classification score of 2 or 3, those operated via a laparoscopic approach, and those undergoing procedures other than proximal gastrectomy. Conclusions: The use of PGA mesh significantly reduced pancreas-related complications after minimally invasive surgery for gastric cancer and might thus benefit patients at risk of such complications.

• Journal of Gastric Cancer
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• v.14 no.1
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• pp.58-62
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• 2014

We report an extremely rare case of primary squamous cell carcinoma of the stomach. A 69-year-old man was admitted to our hospital with a 2-month history of dysphagia and tarry stools. Endoscopic examination revealed a cauliflower-shaped protruding mass along the lesser curvature of the gastric cardia. Biopsy of the lesion revealed squamous cell carcinoma of the stomach. Computed tomography revealed a thickened stomach wall and a mass protruding into the gastric lumen. Total gastrectomy with splenectomy, distal pancreatectomy, and Roux-en-Y reconstruction was performed, together with a lower thoracic esophagectomy via a left thoracotomy. Histopathological examination of the specimen revealed well-differentiated squamous cell carcinoma of the stomach. Postoperative follow-up was uneventful for the first 18 months. However, multiple liver metastases and para-aortic lymph node metastasis developed subsequently. Despite systemic combination chemotherapy, the patient died because of progression of the recurrent tumors. Here, we review the characteristics of 56 cases of gastric squamous cell carcinoma reported in Japan.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2013.05a
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• pp.667-668
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• 2013

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7119-7123
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• 2014

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin $130mg/m^2$ and capecitabine $1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5681-5686
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• 2015

Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstline chemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.4
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• pp.363-374
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• 2022

Backgrounds/Aims: To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Methods: Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the nonNEO group (upfront surgery). Results: A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p= 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). Conclusions: A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.

• Korean Journal of Radiology
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• v.23 no.3
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• pp.322-332
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• 2022

Objective: CT plays a central role in determining the resectability of pancreatic cancer, which directs the use of neoadjuvant therapy. This study aimed to assess the diagnostic accuracy of CT in predicting circumferential resection margin (CRM) involvement in patients with resectable or borderline resectable pancreatic head cancer. Materials and Methods: Seventy-seven patients who were scheduled for upfront surgery for resectable or borderline resectable pancreatic head cancer were prospectively enrolled, and 75 patients (38 male and 37 female; mean age ± standard deviation, 68 ± 11 years) were finally analyzed. The CRM status was evaluated separately for the superior mesenteric artery (SMA) and posterior and superior mesenteric vein/portal vein (SMV/PV) margins. Three independent radiologists reviewed the preoperative CT images and evaluated the resection margin status. The reference standard for CRM status was pathologic examination of pancreaticoduodenectomy specimens in an axial plane perpendicular to the axis of the second portion of the duodenum. The diagnostic accuracy of CT was assessed for overall CRM involvement, defined as involvement of the SMA or posterior margins (per-patient analysis), and involvement of each of the three resection margins (per-margin analysis). The data were pooled using a crossed random effects model. Results: Forty patients had pathologically confirmed overall CRM involvement in pancreatic cancer, while CRM involvement was not seen in 35 patients. For overall CRM involvement, the pooled sensitivity and specificity were 15% (95% confidence interval: 7%-49%) and 99% (96%-100%), respectively. For each of the resection margins, the pooled sensitivity and specificity were 14% (9%-54%) and 99% (38%-100%) for the SMA margin, 12% (8%-46%) and 99% (97%-100%) for the posterior margin; and 37% (29%-53%) and 96% (31%-100%) for the SMV/PV margin, respectively. Conclusion: CT showed very high specificity but low sensitivity in predicting pathological CRM involvement in pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2841-2846
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• 2012

Background: Many studies have investigated the association between the MDM2 promoter SNP309 T/G polymorphism and liver cancer risk, but inconsistencies make drawwing definitive conclusions difficult. Methods: We therefore searched main databases for articles relating MDM2 SNP309 T/G polymorphism to risk of liver cancer in humans and estimated summary odds ratio (OR) with 95% confidence intervals (95% CI) to assess the possible association in a meta-analysis. Results: The main analysis revealed no significant heterogeneity, and the pooled ORs of fixed-effects were all significant (for G versus T, OR = 1.59, 95% CI 1.42-1.78; for GG versus TT, OR = 2.45, 95% CI 1.93-3.12; for GT versus TT, OR = 1.70, 95% CI 1.38-2.09; for GG versus GT, OR = 1.49, 95% CI 1.24-1.79; for GG and GT versus TT, OR = 1.95, 95% CI 1.61-2.38; for GG versus TT and GT, OR = 1.73, 95% CI 1.46-2.07). Subgroup analyses by ethnicity and sensitivity analyses both showed associations to remain significant. Conclusion: The present meta-analysis of available data showed a significant association between the MDM2 SNP309 T/G polymorphism and liver cancer risk, the MDM2 SNP309 G allele contributing to increased risk in both Asians and Caucasians in a graded, dose-dependent fashion.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1841-1844
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• 2012

Background: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy has limited impact on overall survival (OS) so that eligible patients should be selected carefully. The aim of this study was to analyze prognostic factors for survival in Turkish advanced pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving gemcitabine (Gem) alone or gemcitabine plus cisplatin (GemCis). Methods: This retrospective evaluation was performed for patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and who received gemcitabine between December 2005 and August 2011. Twenty-seven potential prognostic variables were chosen for univariate and multivariate analyses to identify prognostic factors associated with survival. Results: Among the 27 variables in univariate analysis, three were identified to have prognostic significance: sex (p = 0.04), peritoneal dissemination (p =0.02) and serum creatinine level (p=0.05). Multivariate analysis by Cox proportional hazard model showed only peritoneal dissemination to be an independent prognostic factor for survival. Conclusion: In conclusion, peritoneal metastasis was identified as an important prognostic factor in metastatic pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving Gem or GemCis. The findings should facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.