Improving child nutrition in disasters by developing a modeled disaster preparedness nutrition education curriculum.

In contemporary global society, largely because of climate change and other natural and human-induced hazards, disasters are an almost daily occurrence. The nutritional impact of disasters on children results in long-term physical and mental health problems. As children are one of the most vulnerable demographic groups, they must be empowered with disaster preparedness nutrition knowledge, and the skills and motivation to survive, prevent/reduce malnutrition, and maintain good health during disasters. A disaster preparedness nutrition education program (DPNEP) was developed in this study to improve children's nutrition in daily life and during disasters through student-centered education. A consultative approach was used to synthesize the knowledge of a diverse group of four experts in disaster medicine and management, public health, education, and food and nutrition sciences to reach a consensus through discussion. A model DPNEP was developed by targeting grade 4 and 5 students and using interactive teaching methods. This can lead to the implementation of continuous nutrition education to empower children to make healthy food choices in daily life and reduce the risk of disaster-nutrition-related morbidity and mortality. Furthermore, once children acquire the necessary information, they are likely to share this knowledge with their families and communities, thereby enhancing society's resilience.

Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study.

BACKGROUND: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases. METHODS: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely. RESULTS: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex. CONCLUSION: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

Plasma Osteopontin Levels is Associated with Biochemical Markers of Kidney Injury in Patients with Leptospirosis.

: Leptospirosis becomes severe, with a fatality rate of >10%, and manifests as severe lung injury accompanied by acute kidney injury. Using urine and blood samples of 112 patients with leptospirosis, osteopontin (OPN), galectin-9 (Gal-9) and other kidney-related biomarkers were measured to understand the pathological and diagnostic roles of OPN and Gal-9 in leptospirosis. Plasma levels of full-length (FL)-OPN (pFL-OPN) (p < 0.0001), pFL-Gal-9(p < 0.0001) and thrombin-cleaved OPN (p < 0.01) were significantly higher in patients with leptospirosis than in healthy controls (n = 30), as were levels of several indicators of renal toxicity: serum cystatin C (p < 0.0001), urine N-acetyl-ß-glucosaminidase (NAG)/creatinine (p < 0.05), and urine clusterin/creatinine (p < 0.05). pFL-Gal-9 levels were negatively correlated with pFL-OPN levels (r = -0.24, p < 0.05). pFL-OPN levels were positively correlated with serum cystatin C (r = 0.41, p < 0.0001), urine NAG/creatinine (r = 0.35, p < 0.001), urine clusterin/creatinine (r = 0.33, p < 0.01), and urine cystatin C/creatinine (r = 0.33, p < 0.05) levels. In a group of patients with abnormally high creatinine levels, significantly higher levels of serum cystatin C (p < 0.0001) and pFL-OPN (p < 0.001) were observed. Our results demonstrate that pFL-OPN reflect kidney injury among patients with leptospirosis.

Prognostic importance of peritoneal washing cytology in patients with otherwise resectable pancreatic ductal adenocarcinoma who underwent pancreatectomy: A nationwide, cancer registry-based study from the Japan Pancreas Society.

BACKGROUND: The importance of peritoneal washing cytology status both as a sign of irresectability and as a prognostic factor for pancreatic ductal adenocarcinoma remains controversial. The purpose of this nationwide, cancer registry-based study was to clarify the clinical implications of operative resection in patients who had positive cytology status. METHODS: Clinical data from 1,970 patients who underwent tumor resection were collected from the Pancreatic Cancer Registry in Japan. Clinicopathologic factors and overall survival curves were analyzed, and multivariate Cox proportional hazard models were evaluated. RESULTS: Among the 1,970 patients analyzed, positive cytology status was found in 106 patients and negative cytology status was found in 1,864 patients. The positive cytology status group had a greater frequency of pancreatic body and tail cancer and greater preoperative serum carbohydrate antigen 19-9 levels than the negative cytology status group (P < .001 each). The ratio of peritoneal recurrence tended to be greater in the positive cytology status group (14% vs 43%; P < .001). Overall median survival times were less in the positive cytology status group (17.5 months vs 29.4 months; P < .001). The 5-year survival rates were 13.7% and 31.1% in the positive cytology status and negative cytology status groups, respectively. Multivariate analysis of positive cytology status patients revealed that adjuvant chemotherapy was an independent prognostic factor. CONCLUSION: Positive cytology status was an adverse prognostic factor in patients who underwent resection for pancreatic ductal adenocarcinoma but did not preclude attempted curative resection. Curative resection followed by adjuvant chemotherapy may contribute to long-term prognosis in patients with positive cytology status.

Aetiology and risks factors associated with the fatal outcomes of childhood pneumonia among hospitalised children in the Philippines from 2008 to 2016: a case series study.

OBJECTIVE: Pneumonia remains the leading cause of hospitalisations and deaths among children aged <5 years. Diverse respiratory pathogens cause acute respiratory infections, including pneumonia. Here, we analysed viral and bacterial pathogens and risk factors associated with death of hospitalised children. DESIGN: A 9-year case series study. SETTING: Two secondary-care hospitals, one tertiary-care hospital and one research centre in the Philippines. PARTICIPANTS: 5054 children aged <5 years hospitalised with severe pneumonia. METHODS: Nasopharyngeal swabs for virus identification, and venous blood samples for bacterial culture were collected. Demographic, clinical data and laboratory findings were collected at admission time. Logistic regression analyses were performed to identify the factors associated with death. RESULTS: Of the enrolled patients, 57% (2876/5054) were males. The case fatality rate was 4.7% (238/5054), showing a decreasing trend during the study period (p<0.001). 55.0% of the patients who died were either moderately or severely underweight. Viruses were detected in 61.0% of the patients, with respiratory syncytial virus (27.0%) and rhinovirus (23.0%) being the most commonly detected viruses. In children aged 2-59 months, the risk factors significantly associated with death included age of 2-5 months, sensorial changes, severe malnutrition, grunting, central cyanosis, decreased breath sounds, tachypnoea, fever (≥38.5°C), saturation of peripheral oxygen <90%, infiltration, consolidation and pleural effusion on chest radiograph.Among the pathogens, adenovirus type 7, seasonal influenza A (H1N1) and positive blood culture for bacteria were significantly associated with death. Similar patterns were observed between the death cases and the aforementioned factors in children aged <2 months. CONCLUSION: Malnutrition was the most common factor associated with death and addressing this issue may decrease the case fatality rate. In addition, chest radiographic examination and oxygen saturation measurement should be promoted in all hospitalised patients with pneumonia as well as bacteria detection to identify patients who are at risk of death.

Combination of longitudinal pancreaticojejunostomy with coring-out of the pancreatic head (Frey procedure) and distal pancreatectomy for chronic pancreatitis.

PURPOSE: The Frey procedure is an effective surgery for chronic pancreatitis (CP) patients who have pancreatic head lesions with dilation of the main pancreatic duct. However, pancreatic tail lesions can cause relapsing pancreatitis after the procedure. Therefore, additional distal pancreatectomy (DP) might complement the therapeutic effect of the Frey procedure in controlling inflammation of the pancreatic tail. The Frey procedure with DP (Frey + DP) is indicated for inflammatory lesions in the pancreatic head and tail. In this study, we assessed the usefulness of Frey + DP using the retrospective clinical data of our cases. METHODS: The clinical outcomes were compared between CP patients who underwent the Frey procedure (N = 44) and Frey + DP (N = 13) from January 2005 to April 2016. RESULTS: Frey + DP showed similarly good therapeutic effects to the Frey procedure with regard to the postoperative stay, morbidity, mortality, pain relief and nutrition, although the Frey + DP had a longer operative time, more bleeding and higher incidence of diabetes mellitus than the Frey procedure because of the additional DP. One patient in the Frey group received additional DP because of recurrent pain due to the tail lesion. CONCLUSION: Frey + DP can be a promising treatment for CP patients with pancreatic head and tail lesions.

Chronic Gastritis Due to Helicobacter Pylori Associated with Increased Serum Levels of CA54/61: A Report of Three Cases.

BACKGROUND The bacterial pathogen Helicobacter pylori (H. pylori) can cause chronic gastritis. CA54/61 is a serum tumor marker that has been shown to be positive in the several types of human malignancy. However, the association of between chronic gastritis due to H. pylori and elevated serum levels of CA54/61 has not been previously reported. This report is of three cases of increased serum levels of CA54/61 associated with H. pylori chronic gastritis. CASE REPORT Case 1 was a 44-year-old Japanese woman with a serum CA54/61 level of 138 U/ml (normal level: 12 U/ml). Following treatment and eradication of H. pylori the serum CA54/61 level decreased to 14 U/ml. Case 2 was a 73-year-old Japanese man with a serum level of less than 2 U/ml before completion of successful eradication therapy of H. pylori with a small peak of 30 U/ml after therapy. Case 3 was a 54-year-old Japanese man who maintained a serum CA54/61 level of approximately 20 U/ml before and until 603 days after eradication therapy. None of the three patients had malignancy, which is usually suggested by this serum marker. CONCLUSIONS These three case reports suggest the possibility of an association between chronic gastritis involving H. pylori infection and an elevated serum level of CA54/61. It is possible that the inflammatory gastric mucosal cells supply CA54/61 to the bloodstream. However, further studies are required to confirm the association between serum levels of CA54/61 and H. pylori chronic gastritis and the underlying mechanisms of this association.

Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study.

We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study. We randomly assigned HLA-A*02:01- or HLA-A*24:02-positive patients with advanced PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to detect WT1-specific cytotoxic T lymphocytes (WT1-CTL). Of 91 patients enrolled, 85 were evaluable (GEMWT1: n = 42; GEM: n = 43). GEMWT1 prolonged progression-free survival [PFS; hazard ratio (HR), 0.66; P = 0.084] and improved overall survival rate at 1 year (1-year OS%; GEMWT1: 35.7%; GEM: 20.9%). However, the difference in OS was not significant (HR: 0.82; P = 0.363). These effects were particularly evident in metastatic PDAC (PFS: HR 0.51, P = 0.0017; 1-year OS%: GEMWT1 27.3%; GEM 11.8%). The combination was well tolerated, with no unexpected serious adverse events. In patients with metastatic PDAC, PFS in the DTH-positive GEMWT1 group was significantly prolonged, with a better HR of 0.27 compared with the GEM group, whereas PFS in the DTH-negative GEMWT1 group was similar to that in the GEM group (HR 0.86; P = 0.001). DTH positivity was associated with an increase in WT1-CTLs induced by the WT1 vaccine. GEM plus the WT1 vaccine prolonged PFS and may improve 1-year OS% in advanced PDAC. These clinical effects were associated with the induction of WT1-specific immune responses. Cancer Immunol Res; 6(3); 320-31. ©2018 AACR.

Health-related quality of life in a randomised phase III study of gemcitabine plus S-1, S-1 alone and gemcitabine alone for locally advanced or metastatic pancreatic cancer: GEST study.

OBJECTIVE: This study was performed to compare health-related quality of life (HRQOL) of gemcitabine plus S-1 (GS), S-1 alone and gemcitabine alone as first-line chemotherapy for locally advanced or metastatic pancreatic cancer in the GEST (Gemcitabine and TS-1 Trial) study and to assess the impacts of adverse events and tumour response on HRQOL. METHODS: Patients were randomly assigned to receive gemcitabine alone (1000 mg/m2 weekly for 3 of 4 weeks), S-1 alone (80, 100 or 120 mg/day twice daily for 4 of 6 weeks) or GS (gemcitabine at 1000 mg/m2 weekly plus S-1 at 60, 80 or 100 mg/day twice daily for 2 of 3 weeks). HRQOL was assessed using the EuroQoL-5D (EQ-5D) questionnaire at baseline and weeks 6, 12, 24, 48 and 72. EQ-5D scores, quality-adjusted life months (QALMs), quality-adjusted progression-free months (QAPFMs) and time until definitive HRQOL deterioration (TUDD) were compared among the three groups. The impacts of adverse events and tumour response on EQ-5D scores were analysed. RESULTS: Including EQ-5D scores after death as 0, the mean profile was significantly better in the GS than gemcitabine group (difference, 0.069; p=0.003), but not the S-1 group (difference, -0.011; p=0.613). The mean profiles until death were similar in the three groups. QALMs, QAPFMs and TUDD were significantly longer in the GS than gemcitabine group (p<0.001, p<0.001 and p=0.004, respectively), but not the S-1 group (p=0.563, p=0.741 and p=0.701, respectively). Fatigue, anorexia and tumour response were significantly associated with changes in EQ-5D scores. CONCLUSIONS: GS achieved better HRQOL than gemcitabine alone, resulting a good balance between overall survival and HRQOL benefits. S-1 alone provides HRQOL similar to that provided by gemcitabine alone. Preventing fatigue and anorexia and maintaining better response would improve HRQOL.

Predictive risk factors for peritoneal recurrence after pancreatic cancer resection and strategies for its prevention.

PURPOSE: To evaluate the risk factors for peritoneal recurrence (PR) of pancreatic adenocarcinoma and to discuss the appropriate management strategies. METHODS: We reviewed the medical records of 236 patients who underwent pancreatectomy for pancreatic adenocarcinoma. We then compared the clinicopathological characteristics of patients with vs. those without PR. The independent risk factors for PR were defined using the Cox proportional hazards regression model. RESULTS: The median survival of patients with PR was 13.3 months after surgical treatment. The PR group had a significantly higher incidence of portal vein resection, longer operative time (≥648 min), greater blood loss (≥2179 mL), blood transfusion, tumor size, portal vein invasion, artery invasion, pancreatic nerve plexus invasion, and histological grade. Multivariate analysis revealed that excessive blood loss (≥2179 mL; P = 0.010), artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive blood loss was also strongly related to tumor size (P = 0.018). CONCLUSIONS: Local invasion and tumor size-related factors suggested the possibility of intraoperative dissemination at the time of tumor resection. Preoperative treatment and an operative procedure to prevent tumor exposure may help prevent PR.

MK2461, a Multitargeted Kinase Inhibitor, Suppresses the Progression of Pancreatic Cancer by Disrupting the Interaction Between Pancreatic Cancer Cells and Stellate Cells.

OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRß) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRß, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRß and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry. In addition, the effect of MK2461 on PCC-PSC interaction was investigated using PSCs prepared from pancreatic cancer tissues. RESULTS: In PSCs, PDGFRß and MET were upregulated compared with other receptor tyrosine kinases. Conditioned medium from PSCs promoted the proliferation of PCCs, and vice versa. Moreover, MK2461 suppressed the effects of conditioned medium on PCCs and PSCs. Finally, MK2461 significantly inhibited tumor growth in mice coinjected with PCCs and PSCs. CONCLUSIONS: The PDGFRß and MET may play a critical role in the interaction between PCCs and PSCs, which was modulated by MK2461. Therefore, MK2461 may have therapeutic potential in the treatment of pancreatic cancer.

Locally advanced pancreatic cancer successfully treated by distal pancreatectomy with celiac axis resection (DP-CAR) after S-1 with radiation therapy followed by gemcitabine/nab-paclitaxel therapy: a case report.

BACKGROUND: The prognosis for pancreatic cancer remains dismal because many patients are diagnosed with unresectable cancer at the initial diagnosis. Recently, conversion surgery was reported as an effective treatment for initially unresectable pancreatic cancer with a favorable response to non-surgical treatment lasting over 240 days. Here, we describe a case of locally advanced pancreatic cancer (LAPC) successfully resected after treatment with S-1 and radiation followed by gemcitabine/nab-paclitaxel therapy. CASE PRESENTATION: A 73-year-old man with LAPC was referred to our hospital. Computed tomography findings revealed a 2.5-cm mass in the pancreatic body that had invaded the celiac artery, common hepatic artery, and splenic artery. Superior mesenteric artery (SMA) encasement was not observed, but tumor abutment over 180° with the main tumor was detected. Staging laparoscopy showed no findings of distant metastasis, and washing cytology revealed no malignancy. He was diagnosed with unresectable pancreatic cancer. Treatment with S-1 with radiation therapy followed by gemcitabine with nab-paclitaxel was performed. Six months after the initial treatment, the tumor size had decreased to 1.2 cm, and encasement of the main artery was diminished. Though abutment to the main artery, including the SMA, was still detected, distal pancreatectomy with celiac artery resection was performed. The histopathological findings around the celiac artery revealed fibrous changes with an Evans classification of grade IIb. There was no residual cancer at the periphery; thus, R0 resection was achieved. The patient has been healthy and without recurrence for more than 12 months since the initial treatment. CONCLUSIONS: Gemcitabine/nab-paclitaxel therapy revealed high response rate for metastasic pancreatic cancer (PC), but the effect for LAPC proposing conversion surgery was not well discussed. In this case, we achieve R0 resection combined with chemoradiation therapy and gemcitabine/nab-paclitaxel therapy. This regimen was also effective for LAPC and may be used to increase the population of conversion surgery by its high response rate.

Surgical anatomy of the right hepatic artery in Rouviere's sulcus evaluated by preoperative multidetector-row CT images.

BACKGROUND: Lymph node dissection in Rouviere's sulcus (RS) is essential during left-sided hepatectomy and caudate lobectomy for hilar cholangiocarcinoma. However, the small segmental or subsegmental arteries (SA/SSA) are often encountered in RS and must be preserved to prevent critical complications, such as liver infarction or liver failure. The aim of this study is to elucidate the anatomy of SA/SSA around RS, which should be understood preoperatively. METHODS: Between January 2008 and April 2013 from a total of 124 consecutive patients with hilar cholangiocarcinoma, preoperative multidetector-row computed tomography (MDCT) images were obtained at our institution and evaluated. The bifurcation patterns of the SA/SSA, the courses of the posterior SA/SSA and the bifurcation site of the SA/SSA were investigated using MDCT images. RESULTS: The typical form, in which right hepatic artery (RHA) bifurcated into the anterior (Aant) and posterior (Apost) hepatic artery and thereafter, Aant/Apost bifurcated into the SA and SSA, was observed in 75 patients (60.5 %). On the other hand, the atypical forms, in which the SA/SSA were independently branched off from RHA before the main bifurcation of the Aant and Apost, were observed in 43 patients (34.7 %). The prior branched arteries supplied the whole or ventral area of segment VI (A6 or A6a) in 11 patients (8.9 %), which was most commonly observed in the atypical form. 15 patients (34.9 %) of the 43 patients with atypical form had partially supraportal posterior branches, that showed early-bifurcated posterior SA/SAA following supraportal course, while the other posterior SA/SSA followed infraportal course. The SA/SSA were extrahepatically bifurcated in 82 patients (66.1 %), comprised of all 43 atypical form and 39 of typical form, while the SA/SSA were intrahepatically bifurcated in remaining 36 patients of typical forms (29.0 %). CONCLUSION: The extrahepatic bifurcation of the SA/SSA from RHA was relatively common. The early-bifurcated SA/SSA was often observed (34.7 % of total cohort) and, in 34.8 % of those atypical forms, posterior SA/SSA from RHA followed a supraportal course. The detailed preoperative knowledge of the anatomy, including SA/SSA, is crucial for left-sided hepatectomy for hilar cholangiocarcinoma.

Clinicopathological Characteristics of Young Patients With Pancreatic Cancer: An Analysis of Data From Pancreatic Cancer Registry of Japan Pancreas Society.

OBJECTIVES: The aim of this study was to determine the characteristics of patients with pancreatic ductal adenocarcinoma younger than 40 years. METHODS: Data from the Japan Pancreas Society's nationwide Pancreatic Cancer Registry were analyzed retrospectively. Clinicopathological characteristics were compared in patients who were grouped according to age, namely, younger than 40 years versus 40 years and older. RESULTS: Of the 36 145 patients in the database, the younger group included 526 (1.5%) patients. A family history of pancreatic cancer was not more frequent in the younger group. The frequency of Union Internationale Contre le Cancer T4 and M1 were both significantly higher in younger patients, resulting in a higher percentage of patients with Union Internationale Contre le Cancer stage IV. Pancreatectomy was performed less frequently in the younger group, and R0 resection was also less frequent. The overall survival rate was significantly better in the older group, whereas in surgically resected patients, the overall survival and recurrence-free survival rates were not different between the 2 groups. CONCLUSIONS: Younger patients with pancreatic adenocarcinoma were more often diagnosed at advanced stages, and the overall survival rate was worse than that in older patients. Family genetic background and the prognoses of patients who underwent surgery were similar between the 2 groups.

Telomerase activity in pancreatic juice differentiates pancreatic cancer from chronic pancreatitis: A meta-analysis.

BACKGROUND/OBJECTIVE: To evaluate the usefulness of genetic markers in pancreatic juice (PJ), and the combination of these markers with telomerase activity in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis. METHODS: We conducted a meta-analysis for the diagnostic utility of the four major altered genes in PDAC (KRAS, CDKN2A/p16, TP53, and SMAD4/DPC4), telomerase activity, and a combination assay using PJ samples. A literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. Data were pooled and presented as diagnostic sensitivity and specificity with 95% confidence intervals (CIs). RESULTS: Thirty-nine studies fulfilled the inclusion criteria. Pooled estimates of KRAS analysis were as follows: sensitivity was 0.67 (95% CI, 0.63-0.71) and specificity, 0.82 (95% CI, 0.79-0.85). For telomerase activity analysis, sensitivity was 0.82 (95% CI, 0.76-0.87) and specificity, 0.96 (95% CI, 0.90-0.99). The other three tumor suppressors demonstrated low sensitivity. The data did not suggest any publication bias. A combined analysis of KRAS and telomerase activity showed a higher diagnostic sensitivity (0.94; 95% CI, 0.83-0.99) than KRAS alone. A combined analysis of telomerase activity and cytology revealed more reliable diagnostic accuracy than telomerase activity alone, with high sensitivity (0.88; 95% CI, 0.74-0.96) and specificity (1.00; 95% CI, 0.91-1.00). CONCLUSIONS: The most reliable marker in PJ samples for diagnosis of PDAC was telomerase activity. Telomerase activity can play a central role in diagnostic analysis using PJ samples, and can increase diagnostic accuracy when combined with KRAS mutations or cytological examination.

Clinical outcome of elderly patients with unresectable pancreatic cancer treated with gemcitabine plus S-1, S-1 alone, or gemcitabine alone: Subgroup analysis of a randomised phase III trial, GEST study.

BACKGROUND: In the GEST study of unresectable pancreatic cancer, S-1 demonstrated non-inferiority compared to gemcitabine, but gemcitabine plus S-1 (GS) did not show superiority over gemcitabine for overall survival (OS). We performed subgroup analysis of these data focused on the efficacy and safety of these regimens as a first-line treatment for elderly patients. METHODS: Elderly patients (≥ 70 years, n = 261) treated for unresectable pancreatic cancer (GS: n = 90, S-1: n = 85 and gemcitabine: n = 86) were analysed. RESULTS: No significant differences between the GS, S-1, or gemcitabine groups in OS (median: 10.2, 8.0 and 8.5 months, respectively) or objective response rates (27.6%, 25.3% and 14.3%, respectively) were noted. Grade ≥ III adverse haematological events were observed more frequently in GS-treated than in S-1- or gemcitabine-treated elderly patients (p < 0.001 and p = 0.016, respectively). Four of 8 patients aged ≥ 80 years experienced serious adverse events. CONCLUSIONS: S-1 and gemcitabine are both efficacious options for treatment of elderly patients with unresectable pancreatic cancer. Conversely, first-line treatment of elderly patients with GS should only be used after careful consideration.

Effect of Hospital Volume on Surgical Outcomes After Pancreaticoduodenectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the relationship between hospital volume and outcome after pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: Previous reviews for the hospital volume-outcome relationship after pancreatic resection were limited owing to clinical or methodological heterogeneity, resulting from differences in surgical procedures and high-volume hospital (HVH) definitions across studies. METHODS: We conducted a rigorous meta-analysis on the influence of hospital volume on various outcomes after PD using strict inclusion criteria and single cutoff values for HVHs. RESULTS: Thirteen studies based on nationwide databases from 11 countries, and including 58,023 patients in total, were included in this study. The overall pooled odds ratio (OR) for mortality favoring the HVH group was 2.37 [95% confidence interval (CI): 1.95-2.88] with high heterogeneity (I = 63%). We therefore classified all included studies into categories according to the cutoff values for HVH as defined in each individual study. The pooled OR for each category of 1 to 19, 20 to 29, and ≥30 PDs per year was 1.94, 2.34, and 4.05, respectively. There were significant differences among these categories (I = 58.9%, P = 0.09). The 2 former categories showed no statistical interstudy heterogeneities. The data did not suggest publication bias. These trends persisted in all subgroup analyses. Postoperative length of stay in the HVH group was significantly shorter with mild interstudy heterogeneity. CONCLUSIONS: This meta-analysis included studies from different countries with disparate health care systems and provided strong evidence for an inverse association between higher hospital volume and lower mortality after PD. Variations in HVH cutoff values across studies majorly influenced the overall heterogeneity.

Clinicopathological Features of Type 2 Autoimmune Pancreatitis in Japan: Results of a Multicenter Survey.

OBJECTIVE: The aim of the study was to clarify clinicopathological features of type 2 autoimmune pancreatitis (AIP) in Japan; a multicenter survey was carried out. METHODS: The first screening collected patients with pancreatitis whose pancreatic tissue samples were available and who fulfilled at least 1 of the following 3 criteria as possible type 2 AIP: (1) histological presence of granulocytic epithelial lesion, (2) age of 50 years or younger, and (3) association of ulcerative colitis, Sjogren syndrome, and/or primary biliary cirrhosis. Patients with histologically confirmed type 1 AIP were also collected as a control. Clinical information was gathered by questionnaire. RESULTS: A histological re-evaluation identified 8 patients with type 2 AIP and 20 with type 1 AIP. Three of the latter had intralobular neutrophilic infiltration. Factors more frequent in type 2 included age younger than 40 years, abdominal pain, and elevation of serum amylase and lipase, whereas patients with type 1 more frequently showed jaundice, elevated serum IgG and IgG4, presence of autoantibodies, association of IgG4-related disease, sclerosing cholangitis and diabetes mellitus, and imaging findings of intrapancreatic biliary stenosis and extrapancreatic biliary dilatation. CONCLUSIONS: The clinical features of type 2 AIP in Japan were similar to those of western countries. Intralobular neutrophilic infiltration in type 1 is a potential pitfall, especially in the biopsy-based diagnosis.

Silencing of LRRFIP1 reverses the epithelial-mesenchymal transition via inhibition of the Wnt/ß-catenin signaling pathway.

The canonical Wnt/ß-catenin signaling pathway has been shown to promote the epithelial-mesenchymal transition (EMT), which is a crucial process in multiple embryonic developmental processes and the progression of carcinomas. We recently provided evidence that leucine-rich repeat flightless-1-interacting protein 1 (LRRFIP1) promotes cancer metastasis and invasion. In the present study, we identified the signaling elements targeted by LRRFIP1 for promotion of the EMT in pancreatic and lung cancer. LRRFIP1 silencing reversed the EMT, as shown by increased expression of E-cadherin (an epithelial marker) and decreased expression of vimentin (a mesenchymal marker). Silencing of LRRFIP1 up-regulated phosphorylation of ß-catenin and decreased its nuclear localization by targeting the ß-catenin destruction complex. The expression of ß-catenin and E-cadherin in the plasma membrane fraction was increased in LRRFIP1 silenced cancer cells, and the migration and invasion capabilities were strongly inhibited. In addition, this protein was highly expressed at the invasion front of malignant tissue collected from pancreatic cancer patients. Consequently, our data strongly suggested that LRRFIP1 played an important role in the invasion of carcinoma cells. Our data provide experimental evidence that LRRFIP1 is an attractive candidate for targeted therapy in human cancers.

Feasibility Assessment of Modified FOLFOX-6 as adjuvant treatment after resection of liver metastases from colorectal cancer: analyses of a multicenter phase II clinical trial (Miyagi-HBPCOG Trial-001).

BACKGROUND/AIMS: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer. METHODOLOGY: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS). RESULTS: We enrolled 49 cases and analyzed adverse events in 48 cases, since in one patient cancer recurred before starting treatment. As to the relative dose intensity, 5-FU was 78.8%, and oxaliplatin was 75.9%. Adverse events of Grade 3 and above includ- ed 18 cases of neutropenia (37.5%), 4 cases of sensory neuropathy (8.3%), 4 cases of thrombocytopenia (8.3%) and 4 cases of allergy (8.3%), and there were no cases of fatality caused by adverse events. The most difference of adverse event compared with MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) was thrombocytopenia. The 2-year DFS was 59.2% (95% CI: 36.7-78.4) in the 49 enrolled cases. CONCLUSION: mFOLFOX6 after hepatectomy was tolerable. And mFOLFOX6 also seemed to improve DFS. mFOLFOX is one of the options for such patients and appears promising as an adjuvant treatment.