Masanori Kon

Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis.

Objective: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, “an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium” in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. Background: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. Methods: Paclitaxel was administered i.v. at 50 mg/m2 and i.p. at 20 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). Results: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47–22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. Conclusions: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma

BackgroundAberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC.MethodsWe studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting.Results/ConclusionHigh ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.

Effects of implementing an “enhanced recovery after surgery” program on patients undergoing resection of hepatocellular carcinoma

PurposeTo evaluate the effects of implementing an “enhanced recovery after surgery” (ERAS) program on the feasibility, safety, and effectiveness of extensive and potentially curative liver resection for hepatocellular carcinoma (HCC).MethodsWe compared clinicopathologic factors, surgical factors, and outcomes of patients who underwent extended hepatectomy (defined as resection of more than two sections) for HCC, before and after the introduction of an ERAS program.ResultsOperating times and postoperative hospital stay were significantly shorter, and total volume infused during surgery was significantly lower, for the ERAS group than for the control group. Although the ERAS group had a significantly lower percentage of patients with retention of abdominal drainage, this group had a higher frequency of abdominal paracentesis in patients without intraoperative abdominal drainage. Oral dietary intake and the ability to walk steadily resumed significantly earlier in the ERAS group. Postoperative serum concentrations of albumin and cholinesterase were significantly higher in the ERAS group than in the control group.ConclusionsThe ERAS program was feasible and effective for patients with chronic liver disease undergoing extended liver resection for HCC, because it allowed earlier oral dietary intake and promoted faster postoperative recovery.

Experimental results of 2D depth-depth matching algorithm based on depth camera Kinect v1

In the last year, we proposed a smart transcription algorithm. In the algorithm, a real liver is always captured by 3D depth camera. As contrasted with this, its virtual liver is represented by a polyhedron with STL (Standard Triangulated Language) format (Stereo-lithography) via DICOM (Digital Imaging and Communication in Medicine) data captured by MRI (Magnetic Resonance Imaging) and/or CT (Computed Tomography) scanner. By comparing a depth image in a real world and the Z-buffer in its virtual world, we quickly identify translation/rotation differences between real and virtual livers in GPU (Graphics Processing Unit). Then by a randomized steepest descent method based on the differences, we can quickly copy real lever motion to virtual liver motion. In this paper, this performance (motion precision and calculation time) of the proposed algorithm is ascertained in several kinds of experiments based on the depth camera Kinect v1. This is the first challenge to use our smart algorithm running in a 3D real environment.

Virtual Liver Surgical Simulator by Using Z-Buffer for Object Deformation

Virtual surgical simulator which is using computer graphics is much popular system than before. It is generally used in the medical areas, such as medical hospital or medical university. The simulator uses virtual organ models like liver, brain and so on. These models are usually based on the scanning data from patients and are used as volume models. Fortunately, the volume model is familiar with its cutting or deforming operation in a surgical system. For this reason, there are many kinds of surgical simulation or navigation systems using the volume model. However, visual reality of the volume model is not sufficient for human being including doctors. This means that the doctors cannot identify shape or location of a target organ from volume objects. In order to overcome this, we should use the translating method, such as marching cubes method and so on, for getting precisely polygon models which is included normal vectors of volume object. However, the method is quite time consuming and consequently the doctors cannot operate the virtual model in real-time.

Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion

Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Here, we showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. At tumor initiation and during tumor propagation in the colon, the descendants of Lgr5-positive cells clonally proliferated to form clusters. Clonal analysis using ubiquitous multicolor lineage tracing revealed that colon tumors derived from Lgr5-positive cells were monoclonal in origin but eventually merged with neighboring tumors, producing polyclonal tumors at the later stage. In contrast, the origin of small intestine tumors was likely polyclonal, and during cancer progression some clones were eliminated, resulting in the formation of monoclonal tumors, which could merge similar to colon tumors. These results suggest that in proliferating intestinal neoplasms, Bmi1- or Lgr5-positive cells represent a population of cancer stem cells, whereas Lgr5-positive cells also function as cells-of-origin for intestinal tumors.

Comparison of Anatomic and Non-anatomic Hepatic Resection for Hepatocellular Carcinoma

The aim of the present study was to compare the prognostic impact of anatomic resection (AR) versus non‐anatomic resection (NAR) on patient survival after resection of a single hepatocellular carcinoma (HCC).

Tracking a Real Liver Using a Virtual Liver and an Experimental Evaluation with Kinect v2

In this study, we propose a smart transcription algorithm for translation and/or rotation motions. This algorithm has two phases: calculating the differences between real and virtual 2D depth images, and searching the motion space defined by three translation and three rotation degrees of freedom based on the depth differences. One depth image is captured for a real liver using a Kinect v2 depth camera and another depth image is obtained for a virtual liver (a polyhedron in stereo-lithography (STL) format by z-buffering with a graphics processing unit). The STL data are converted from Digital Imaging and Communication in Medicine (DICOM) data, where the DICOM data are captured from a patient’s liver using magnetic resonance imaging and/or a computed tomography scanner. In this study, we evaluated the motion precision of our proposed algorithm based on several experiments based using a Kinect v2 depth camera.

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.

Redefining the R1 resection in patients with pancreatic ductal adenocarcinoma.

Most cases of pancreatic ductal adenocarcinoma (PDAC) are lethal. Margin‐negative surgical resection is a mainstay of treatment and the only chance of a cure. Differences in pathological reporting, surgical technique, definitions of resection margin, and group stratification all affect outcome analyses. Furthermore, there are controversial issues influencing the clinical interpretation of resection margin after pancreatectomy. There is no standardized definition of margin involvement in resected specimens of PDAC. The non‐standardized pathologic approach explains the wide range of positive resection margin rates (13–71%) that have previously been reported. A standardized pathologic evaluation needs to be developed for proper assessment of resection margin after oncologic pancreatectomy. This manuscript reviews the current controversial issues in assessing resection margin in order to enhance understanding of the current status and potential role of pathological evaluation in patients with PDAC.