Minako Nagai

Effects of pancrelipase on nonalcoholic fatty liver disease after pancreaticoduodenectomy

Postoperative nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has recently become recognized. However, the pathoetiology of postoperative NAFLD is largely unknown. Furthermore, the optimal treatment has not been established. The aim of this prospective study was to clarify whether pancrelipase, which contains digestive pancreatic enzymes, could reverse NAFLD.

Prognostic Significance of Muscle Attenuation in Pancreatic Cancer Patients Treated with Neoadjuvant Chemoradiotherapy

BackgroundEmerging evidences have gradually revealed the skeletal muscle attenuation (MA) was not only reflected the accumulation of lipids in skeletal muscle but also associated with physiological and pathological states. The aim of this study was to evaluate the impact of MA on the prognosis of pancreatic cancer patients treated with neoadjuvant chemoradiotherapy (NACRT).MethodsEighty-three patients with pancreatic cancer who received NACRT were enrolled. Patients were divided according to their Hounsfield units of the skeletal muscle at the third lumbar vertebra in CT. The lower quartile was defined as MA group and the remainder as control group.ResultsThere was no significant difference in overall survival between pre-NACRT MA and control groups. In contrast, patients with post-NACRT MA had a significantly poorer prognosis than patients without. The patients in the post-NACRT MA group were significantly older than patients in the control group. There were no significant differences in most clinicopathological and perioperative factors between both groups. However, patients with post-NACRT MA had a longer hospital stay than patients without. Furthermore, the incompletion rate of the proposed adjuvant chemotherapy was significantly higher in the MA group than control. Importantly, multivariate analysis indicated that post-NACRT MA was an independent prognostic factor.ConclusionsMuscle attenuation may have a significant impact in pancreatic cancer patients treated with multimodal therapy. Therefore, our data may provide new insights into perioperative patient care to improve the prognosis of resectable pancreatic cancer.

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer.

PurposeMuch attention has been paid to preoperative treatment as a new strategy especially for borderline resectable pancreatic cancer (BRPC). The purpose of this study was to define the optimal indication of neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer.MethodsWe analyzed consecutive 184 patients who had undergone pancreatic resection in Nara Medical University Hospital. Resectability status was classified by NCCN guidelines. Full-dose gemcitabine with concurrent radiation was used as NACRT. We evaluated 85 patients treated with NACRT in comparison with 99 patients without NACRT as control.ResultsThe regimen of NACRT was well tolerated and feasible. The perioperative outcomes were almost comparable. The postoperative complications were significantly less frequent in NACRT group than non-NACRT group. The pathological effects on both resectable and borderline tumors were favorable in NACRT group compared to non-NACRT group. The overall survival of resectable pancreatic cancer was significantly better than that of BRPC regardless of whether the patients were treated with or without NACRT. The prognosis of the patients with NACRT in resectable tumors was significantly better than without, while there was no significant difference in BRPC. Furthermore, multivariate analysis of various factors in the patients with NACRT identified resectability status and completion of adjuvant chemotherapy as independent prognostic factors.ConclusionsNACRT did not improve the prognosis of the patients with BRPC, although it induced substantial pathological antitumor effect. In contrast, the prognosis of resectable pancreatic cancer treated with NACRT was favorable. Therefore, resectable pancreatic cancer may be good indication for multimodal treatment including NACRT.

Factors associated with failure to complete adjuvant chemotherapy in pancreatic cancer

BACKGROUND The importance of completing adjuvant chemotherapy in pancreatic cancer is becoming recognized. However, the clinicopathological factors associated with failure to complete adjuvant chemotherapy remain unclear. METHODS A total of 135 patients were analyzed to identify the factors associated with failure to complete adjuvant chemotherapy. RESULTS Ninety patients completed planned adjuvant chemotherapy, whereas 45 patients failed to complete adjuvant chemotherapy. Lower preoperative prognostic nutritional index, intraoperative blood transfusion, and organ and/or space surgical site infection, and advanced tumor stage were associated with failure to complete adjuvant chemotherapy. Neoadjuvant chemoradiotherapy was associated with significantly lower prognostic nutritional index, less incidence of organ and/or space surgical site infection, and earlier tumor stage, suggesting the conflicting effects of neoadjuvant chemoradiotherapy on completing adjuvant chemotherapy. CONCLUSIONS Several clinicopathological factors including patient conditions and perioperative events were associated with failure to complete adjuvant chemotherapy.

Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer

BackgroundNectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans. Recent studies have also suggested some roles for Nectin-4 in several human cancers. However, the precise roles and clinical relevance of Nectin-4 in tumors are largely unknown.MethodsNectin-4 expression was investigated in 123 patients with pancreatic cancer by immunohistochemistry. Furthermore, we investigated the association of Nectin-4 in pancreatic cancer with tumor proliferation, angiogenesis and immunity by using immunohistochemistry and siRNA interference method.ResultsPatients with high Nectin-4 expression had poorer postoperative prognosis than those with low expression. Importantly, multivariate analysis indicated that Nectin-4 expression had a significant independent prognostic value in pancreatic cancer (HR = 1.721, 1.085-2.730; P = 0.021). Tumor Nectin-4 expression was significantly correlated with Ki67 expression. In addition, siRNA-mediated gene silencing of Nectin-4 significantly inhibited the cell proliferation in human pancreatic cancer cells, Capan-2 and BxPC-3. Furthermore, Nectin-4 expression was also positively correlated with VEGF expression and intratumoral microvessel density. However, there were no significant correlations of tumor Nectin-4 expression with tumor-infiltrating T cells.ConclusionNectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer.

Importance of resectability status in neoadjuvant treatment for pancreatic cancer

Much attention has been paid to neoadjuvant treatment (NAT) as a new strategy especially for borderline resectable pancreatic cancer (BRPC). However, the optimal indication of NAT remains undetermined.

Potential role of surgical resection for pancreatic cancer in the very elderly

BACKGROUND There is increasing need to evaluate the surgical indication of pancreatic cancer in very elderly patients. However, the available clinical data are limited, and the optimal treatment is still controversial. The aim of this study was to evaluate the benefit of pancreatic resection in pancreatic cancer patients over the age of 80. METHODS Between 2005 and 2012, 26 octogenarian patients who received pancreatic resection and 20 who received chemotherapy for pancreatic cancer were retrospectively reviewed. Clinicopathological factors, chemotherapy administration status, and survival were compared. Univariate and multivariate analysis of prognostic factors for survival was performed. RESULTS Postoperative major complication rate was 8%, with no mortality. The one-year survival rate and median survival time of the surgery and chemotherapy groups were 50% and 45%, and 12.4 months and 11.7 months, respectively (P = 0.263). Of the 26 resected cases, 6 completed the planned adjuvant chemotherapy treatment course. The median survival time of those 6 completed cases was significantly longer than that of the 20 not completed cases (23.4 versus 10.0 months, P = 0.034). Furthermore, a multivariate analysis of the 26 resected cases showed that distant metastasis (HR 3.206, 95%CI 1.005-10.22, P = 0.049) and completion of the planned adjuvant therapy (HR 4.078, 95%CI 1.162-14.30, P = 0.028) were independent prognostic factors of surgical resection. CONCLUSIONS Surgical resection was safe, but not superior to chemotherapy for pancreatic cancer in octogenarians. In the very elderly, only selected patients may benefit from pancreatic resection.

Prognosis after surgical treatment for pancreatic cancer in patients aged 80 years or older: a multicenter study.

The optimal therapeutic strategy for very elderly pancreatic cancer patients remains to be determined. The aim of this study was to clarify the role of pancreatic resection in patients 80 years of age or older.

Do pancrelipase delayed-release capsules have a protective role against nonalcoholic fatty liver disease after pancreatoduodenectomy in patients with pancreatic cancer? A randomized controlled trial.

The aim of this randomized controlled trial (RCT) was to investigate whether pancrelipase protects against nonalcoholic fatty liver disease (NAFLD) development after pancreatoduodenectomy in patients with pancreatic cancer better than conventional pancreatic enzyme supplementation.

Impact of Smoking on Pancreatic Cancer Patients Receiving Current Chemotherapy.

Objective Smoking may affect pharmacokinetics of chemotherapeutic agents and hemodynamics of the smokers, thereby influencing adverse events and efficacy of chemotherapy in patients with pancreatic cancer (PC). The aim of this study was to clarify how smoking totally affected patients with PC receiving current chemotherapy. Methods We evaluated the impact of smoking status on the performance of chemotherapy and survival in 262 patients with PC including 158 resectable and 104 unresectable PC. Results There were more male and younger patients in current smokers than in nonsmokers. In unresectable PC, current smokers had more metastatic tumors than locally advanced tumors compared with nonsmokers. In current smokers receiving chemotherapy, the baseline white blood cell count, neutrophil count, and hemoglobin concentration were significantly higher in current smokers than in nonsmokers. Furthermore, grades 3 to 4 neutropenia was observed more often in nonsmokers than smokers. On the other hand, the performance and efficacy of the planned adjuvant chemotherapy were similar between smokers and nonsmokers. More importantly, there was no significant difference in overall prognosis between smokers and nonsmokers receiving chemotherapy. Conclusions Smoking status has no significant impact on the efficacy of current chemotherapy for both resectable and unresectable PC.