Masataka Amisaki

Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C

BACKGROUND Pancreatic cancer (PC) is the most lethal malignancy among solid tumors, and the most common risk factor for its development is cigarette smoking. Atypical protein kinase C (aPKC) isozymes function in cell polarity, proliferation, and survival, and have also been implicated in carcinogenesis. However, the involvement of aPKC in PC progression and the effect of nicotine, a major component of cigarette smoke, on the biological activities of aPKC remain to be fully elucidated. METHODS We investigated the effects of nicotine on the proliferation, migration and invasion of the human PC cell lines Panc1 and BxPC3. We analyzed aPKC localization and activity by immunohistochemistry and in vitro kinase assays, respectively, to assess their involvement in the regulation of PC progression. Moreover, we examined the effect of nicotine on implanted peritoneal tumors of PC cells in mice. RESULTS Nicotine enhanced cell proliferation, migration and invasion in Panc1 and BxPC3 cells. In nicotine-treated PC cells, the aPKC was significantly activated. We also found that nicotine induced phosphatidylinositol 3-kinase (PI3K) signal activation, and a specific inhibitor of the nicotine acetylcholine receptor (nAChR) as well as knockdown of nAChR prevented nicotine-mediated Akt phosphorylation and aPKC activation. In a peritoneal dissemination model of PC, nicotine-treated mice had larger tumors and increased numbers of nodules. Immunohistochemistry showed enhanced expression levels of aPKC and phosphorylated Akt in nodules from nicotine-treated mice. CONCLUSIONS AND GENERAL SIGNIFICANCE Nicotine induces aberrant activation of aPKC via nAChR/PI3K signaling in PC cells, resulting in enhancement of cellular proliferation, migration and invasion.

Internal supravesical hernia repaired via the anterior approach alone: A case report

Highlights • Internal supravesical hernia is very rare.• Most previous reports performed closure of the hernial sac by open laparotomy.• We could successfully repair intraoperatively-diagnosed internal supravesical hernia by the anterior approach alone.

Differences in quality of surgery for advanced gastric cancer between institutions

SummaryBackgroundGastric cancer is one of the most common diseases in Japan, and surgery for gastric cancer is conducted in many general hospitals. However, there has been little investigation of the differences between institutions in terms of postoperative results in gastric cancer patients. This study aimed to compare the quality of treatment for gastric cancer between university hospital and general hospital.MethodsWe previously performed a multicenter trial in patients with stage II or III gastric cancer who underwent curative surgery followed by adjuvant S-1 chemotherapy. We selected 39 patients with similar backgrounds from this cohort: 16 from the Tottori University Hospital and 23 from a general hospital (Tottori Prefectural Central Hospital). Quality of surgery, postoperative patient nutrition and immunity, relapse-free survival, and overall survival were compared between the two groups.ResultsOperation time was significantly longer, but postoperative hospital stay was significantly shorter in the university group. Postoperative neutrophil/lymphocyte ratio and prognostic nutritional index improved significantly in the university group but remained unchanged in the general-hospital group. Relapse-free survival and overall survival both were better in the university group compared with the general-hospital group, although the difference in relapse-free survival was not significant.ConclusionsSurgery and follow-up for advanced gastric cancer should be conducted by trained surgeons and gastric cancer specialists.

The attenuation value of preoperative computed tomography as a novel predictor for pancreatic fistula after pancreaticoduodenectomy

PurposePancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management.MethodsSeventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients’ perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HUmin, HUmax, and HUmean, respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HUSD) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria.ResultsThe PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HUSD (odds ratio 3.092; 95% CI 1.018–9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001–1.00022) as significant risk factors for PF.ConclusionsThe HUSD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

Prognostic value of postoperative complication for early recurrence after curative resection of hepatocellular carcinoma

BACKGROUND Postoperative complications may adversely affect oncological outcomes. The aim of this study was to evaluate the impact of postoperative complications on early-phase recurrence after curative resection for hepatocellular carcinoma (HCC). METHODS We included 145 HCC patients who underwent initial and curative resection between January 2004 and December 2013. Postoperative complications of grade III or higher based on Clavien-Dindo classification were defined as clinically relevant postoperative complications. Recurrence within two years after hepatectomy was defined as early-phase recurrence. RESULTS Thirty-eight patients (26%) developed postoperative complications. The only predictive factor for postoperative complication was longer operative duration (P = 0.037). The disease-specific survival rate of patients with complication was lower than that of patients without complications (P = 0.015). Early-phase recurrence was observed in 20/38 (53%) patients who suffered postoperative complications and 36/107 (34%) patients with no complications, which was statistically significant (P = 0.039). Multivariate analysis identified four factors contributing to early-phase recurrence: high serum AFP level (P = 0.042), multiple tumors (P < 0.001), poor differentiation (P = 0.036) and presence of postoperative complication (P = 0.039). CONCLUSIONS Postoperative complication is an independent prognostic factor for early-phase recurrence after curative resection of HCC. Close observation of patients with postoperative complications may be a necessary treatment strategy for HCC.

The Combination of Neutrophil–to–lymphocyte Ratio and Serum Carbohydrate Antigen 19-9 Level as a Prognostic Indicator in Patients with Recurrent Pancreatic Cancer

Background/Aim: We retrospectively investigated the relationship between prognosis and combined neutrophil–to–lymphocyte ratio (NLR) and serum carbohydrate antigen 19-9 (CA19-9) levels in patients with recurrent pancreatic cancer. Patients and Methods: We enrolled 66 patients whose pancreatic cancer recurred. Results: Based on ROC analysis results, the patients were divided into NLRHigh (NLR ≥1.69) or NLRLow (NLR <1.69), and into CA19-9High (CA19-9 ≥107.95 U/ml) or CA19-9Low (CA19-9 <107.95 U/ml). When the patients were grouped by combined NLR and CA19-9, their 2-year survival rates were NLRLow/CA19-9Low: 58.7%; NLRLow/CA19-9High or NLRHigh/CA19-9Low (grouped together): 11.2%; and NLRHigh/CA19-9High: 0% (p<0.0001). Finally, in multivariate analysis, the combination of NLR and serum CA19-9 level was an independent prognostic factor in patients with recurrent pancreatic cancer. Conclusion: The combination of NLR and serum CA19-9 level is a useful prognostic indicator for recurrent pancreatic cancer.

Pilot Study of Probe-based Confocal Laser Endomicroscopy with Fluorescein-dripping Method for Liver Tumors

Background/Aim: Probe-based confocal laser endomicroscopy (pCLE) is a novel diagnostic technique that can provide real-time imaging of tissues at the cellular level. In this study, pCLE was applied to liver tumors and its diagnostic value was evaluated. Patients and Methods: Ten patients who underwent hepatectomy for liver tumors were evaluated with pCLE from February to May 2017. Immediately after liver resection, pCLE evaluation was performed in the operating room as an ex vivo study. The newly-adopted “fluorescein-dripping method” was used for the observation. Results: First, the optimal fluorescein exposure time for the surface of liver was defined in the fluorescein-dripping method. Next, the distinctive findings in the cancerous region were investigated. The characteristic appearance of irregular arrangements of concentrated cells under fluorescein dripping was observed in six of seven hepatocellular carcinoma (HCC) tumors. Conclusion: In all HCC specimens, discrimination of the cancerous region from normal liver was possible with pCLE.

Focal nodular hyperplasia that mimicked a liver metastasis from a soft tissue sarcoma: a case report

BackgroundImaging modalities (computed tomography (CT), ultrasonography, and magnetic resonance imaging (MRI)) have only limited ability to distinguish liver focal nodular hyperplasia (FNH) from metastatic liver tumors. Here, we report a patient who underwent surgery for benign FNH that mimicked a liver metastasis from soft tissue sarcoma (STS).Case presentationA 23-year-old man with a history of several surgeries for metastatic abdominal STS, developed a hepatic tumor accompanying peritoneal STS recurrence. He was diagnosed with a metastatic liver tumor from the STS, based on imaging studies for the hepatic tumor that showed a growing hypervascular lesion and hypo-intensity in hepatic phase on dynamic CT and MRI. However, when the liver and peritoneal tumors were resected, histological diagnosis showed the hepatic tumor to be benign liver FNH.ConclusionsAlthough FNH should be considered as a differential diagnosis for hypervascular hepatic tumors, it has few typical findings, and its appropriate management is controversial. A lesion strongly suspected of being a metastatic liver tumor might require surgical resection.