Masato Matsuyama

Prognostic value of neutrophil-lymphocyte ratio and level of C-reactive protein in a large cohort of pancreatic cancer patients: a retrospective study in a single institute in Japan.

OBJECTIVE Recent studies suggest that systemic inflammatory response is closely associated with cancer patient prognosis. Although several inflammatory prognostic markers have been proposed, the data to support their validity are lacking in large Japanese cohorts. METHODS This is a retrospective study to examine the prognostic value of inflammatory markers, such as C-reactive protein, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and modified Glasgow prognostic scale, in pancreatic cancer. Selection criteria were admittance to hospital between January 2008 and December 2012, histologically confirmed adenocarcinoma, diagnosis of invasive ductal pancreatic cancer compatible by computed tomography imaging, and followed-up until death or for 180 days or longer. The primary end point was overall survival, which was measured from the day of histological diagnosis. RESULTS There were 440 patients who met the selection criteria. Of the 440 cases, 200 (45.5%) received curative resection (166 Stage I/II and 34 Stage III patients), 237 (53.9%) received chemotherapy (4 Stage I/II, 92 Stage III and 141 Stage IV patients), and the remaining 3 received palliative care. Univariate and multivariate regression analyses revealed that advanced computed tomography stage, high level of C-reactive protein (0.45 mg/dl or greater), neutrophil-lymphocyte ratio (2.0 or greater) and CA19-9 level (1000 U/ml or greater) were significantly associated with worse prognosis. CONCLUSIONS We verified the results of previous studies, and showed that neutrophil-lymphocyte ratio and C-reactive protein also had prognostic value in a large Japanese PC cohort.

Ultrasound-guided vs endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer diagnosis

AIM To clarify the effectiveness and safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of pancreatic cancer (PC). METHODS Patients who were diagnosed with unresectable, locally advanced or metastatic PC between February 2006 and September 2011 were selected for this retrospective study. FNA biopsy for pancreatic tumors had been performed percutaneously under extracorporeal ultrasound guidance until October 2009; then, beginning in November 2009, EUS-FNA has been performed. We reviewed the complete medical records of all patients who met the selection criteria for the following data: sex, age, location and size of the targeted tumor, histological and/or cytological findings, details of puncture procedures, time from day of puncture until day of definitive diagnosis, and details of severe adverse events. RESULTS Of the 121 patients who met the selection criteria, 46 had a percutaneous biopsy (Group A) and 75 had an EUS-FNA biopsy (Group B). Adequate cytological specimens were obtained in 42 Group A patients (91.3%) and all 75 Group B patients (P = 0.0192), and histological specimens were obtained in 41 Group A patients (89.1%) and 65 Group B patients (86.7%). Diagnosis of malignancy by cytology was positive in 33 Group A patients (78.6%) and 72 Group B patients (94.6%) (P = 0.0079). Malignancy by both cytology and pathology was found in 43 Group A (93.5%) and 73 Group B (97.3%) patients. The mean period from the puncture until the cytological diagnosis in Group B was 1.7 d, which was significantly shorter than that in Group A (4.1 d) (P < 0.0001). Severe adverse events were experienced in two Group A patients (4.3%) and in one Group B patient (1.3%). CONCLUSION EUS-FNA, as well as percutaneous needle aspiration, is an effective modality to obtain cytopathological confirmation in patients with advanced PC.

Outcomes and Tolerability of Systemic Chemotherapy for Pancreatic or Biliary Cancer Patients Aged 75 Years or Older

BACKGROUND The incidence of pancreatic or biliary tract cancer is increasing in our aging population, but little is known of treatment outcomes in elderly patients with pancreatic or biliary tract cancer. PATIENTS AND METHODS Patients with pancreatic or biliary tract cancer who received chemotherapy in our institute between September 2007 and August 2009 were retrospectively reviewed to compare treatment outcomes between the elderly (aged 75 years or older) and the younger patients. Data were collected of patient backgrounds, adverse events and dose intensity within the first two cycles and overall survival time. RESULTS Of the 102 who met the inclusion criteria, 19 were elderly who were introduced to full dose chemotherapy. Medication for their comorbidities was required in 15 (79%) of the 19 elderly patients and in 27 (33%) of 83 younger patients. The frequencies of haematological adverse events of grades 3 or 4 were 42% and 39%, and those of non-haematological adverse events were 21% and 16%, for the elderly and younger, respectively. Similar dose intensities were delivered to the elderly and younger. Also, similar proportions of elderly and younger received dose reductions. There was no difference in overall survival between the elderly and the younger. CONCLUSION No clear difference in treatment outcomes was seen between the elderly and the younger patients who received gemcitabine alone. Gemcitabine chemotherapy appears to be safe and the same treatment effect was seen even in older patients with pancreatic or biliary tract cancer.

Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

BACKGROUND We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. MATERIALS AND METHODS We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. RESULTS Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. CONCLUSIONS Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

Genome-wide association study-identified SNPs (rs3790844, rs3790843) in the NR5A2 gene and risk of pancreatic cancer in Japanese.

We genotyped 2 SNPs (rs3790844 T/C and rs3790843 G/A) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The SNPs were in linkage disequilibrium (r2 = 0.80). For rs3790843, the multivariable-adjusted OR was 0.75 (95% CI: 0.41–1.36) and 0.60 (95%CI: 0.33–1.08) for subjects with the AG and AA genotype, respectively, compared to subjects with the GG genotype. The per allele OR was 0.78 (0.62–0.99) (P = 0.046). For rs3790844, the multivariable-adjusted OR was 0.65 (95% CI: 0.37–1.14) and 0.47 (95%CI: 0.27–0.83) for subjects with the CT and CC genotype, respectively, compared to subjects with the TT genotype. The per allele OR was 0.70 (0.56–0.89) (P = 0.003). Our case-control study found that rs3790843 and rs3790844 in the NR5A2 gene are associated with pancreatic cancer risk in Japanese subjects. The direction of association is consistent with the prior findings from GWASs.

A transcatheter arterial chemotherapy using a novel lipophilic platinum derivative (miriplatin) for patients with small and multiple hepatocellular carcinomas.

Background/purpose Miriplatin is a platinum complex developed to treat hepatocellular carcinoma (HCC) through administration into the hepatic artery as a sustained-release formulation suspended in lipiodol. A single-institute pilot study was conducted to investigate the antitumor efficacy of miriplatin infusion therapy for small and multiple HCCs. Materials and methods Small HCCs sized 2 cm or less, judged to be inadequate for curative treatment, were indicated for transcatheter arterial miriplatin infusion therapy. We prospectively investigated the course of patients treated with miriplatin between March 2010 and September 2010. Efficacy was evaluated by computed tomography at 4–8 weeks and the overall evaluation was carried out more than 3 months after treatment. Results The study included 14 patients, of whom 13 were evaluable for efficacy. Of the 13 patients, one (8%) showed a complete response and three (23%) showed a partial response, with an overall response rate of 31%. Grade 3/4 hematological toxicity including thrombocytopenia was not seen. Increases to grade 3/4 in aspartate aminotransferase and alanine aminotransferase were observed for nonhematological toxicity. Irreversible deleterious changes in hepatic function were not seen. Conclusion Miriplatin infusion therapy showed safe and moderate effects on small HCCs. However, transarterial chemoembolization as a standard therapy cannot be replaced. We await the results of an ongoing study of transarterial chemoembolization with miriplatin.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study: Preoperative hilar biliary drainage

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large‐scale multicenter study to compare ENBD and EBS in this setting.

Enteral stent placement for malignant afferent loop obstruction by the through-the-scope technique using a short-type single-balloon enteroscope

Background and study aims  A short-type single-balloon enteroscope with a 3.2-mm working channel makes it possible to insert an enteral stent by the through-the-scope technique in patients with malignant afferent loop obstruction. Here, we report five cases of malignant afferent loop obstruction treated with endoscopic enteral stenting. We also propose a new classification for three types of malignant afferent loop obstruction. Type 1: The obstruction site is located distal to the papilla or the bilioenteric anastomosis. Type 2: The obstruction site is located at the papilla or the bilioenteric anastomosis. Type 3: The obstruction site is located between the bilioenteric and pancreaticoenteric anastomosis. The patients with type 1 and 3 were simply treated by inserting an enteral stent endoscopically. The patient with type 2 was treated with an endoscopic enteral stent for malignant afferent loop obstruction and with percutaneous transhepatic biliary stenting for malignant biliary obstruction. Although double stenting for type 2 remains a difficult endoscopic procedure, the endoscopic approach has become the standard approach for malignant afferent loop obstruction.

The impact of modified Glasgow Prognostic Scale as a predictor of survival advantage by FOLFIRINOX in metastatic pancreatic cancer.

440 Background: The superiority of FOLFIRINOX (FFX) therapy over gemcitabine (Gem) alone in patients with metastatic pancreatic cancer (mPC) has been demonstrated in ACCORD11. However, this combina...