Kimitaka Tanaka

Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohistochemical staining utilizing a tissue microarray method for HLA class I APM expression showing different expression patterns among cell lines was performed for 95 surgical specimens from patients with esophageal cancer. Prognostic factors were the down-regulation of HLA-HC, and the up-regulation of β2 microglobulin and TAP-1 in the cancer tissues. Multivariate analysis using a Cox regression model indicated that the down-regulation of HLA-HC, and up-regulation of TAP-1 in cancer tissues are independent, unfavorable prognostic factors (hazard ratio, 2.361 and 2.297; P=0.0141 and 0.0145, respectively). Although there was no significant difference in survival for selected p-stage I and II patients (n=54) in all APM components, only down-regulation of HLA-HC was an unfavorable prognostic factor by a Cox regression model for selected p-stage III and IV patients (n=41). In conclusion, the current results suggest that the down-regulation of HLA-HC in tumors is especially associated with a poor prognosis among advanced esophageal cancer patients.

Video-assisted thoracoscopic surgery lowers the incidence of adhesion to the chest wall but not to the mediastinal and interlobar pleurae.

To determine whether video-assisted thoracoscopic surgery (VATS) is associated with a lower incidence of intrathoracic adhesion after pulmonary resection, we assessed the incidence of adhesion for patients who underwent a second pulmonary resection. The site and extent of adhesion were evaluated by reviewing videotapes recorded during surgery. A significantly (P<0.05) lower rate of mediastinal or interlobar adhesion was observed in patients with pneumothorax (10%) in comparison with lobectomy (57%) or partial resection for tumors (63%), although there were no statistically significant differences in adhesion to the chest wall. There were no significant differences between VATS and thoracotomy for mediastinal or interlobar adhesion. However, a significantly (P<0.05) lower rate of adhesion to the chest wall was observed for VATS (54%) in comparison with thoracotomy (100%). Although VATS resulted in less adhesion to the chest wall than thoracotomy, there was no difference in mediastinal or interlobar adhesion.

Preoperative diagnosis of portal vein invasion in pancreatic head cancer: appropriate indications for concomitant portal vein resection

The surgical indications for patients with pancreatic head cancer (PHC) with clinical portal vein (PV) invasion (cPV) remain controversial. The present study aimed to determine the ability of computed tomography (CT) to diagnose pathological PV involvement (pPV) in PHC.

Concomitant hepatic artery resection for advanced perihilar cholangiocarcinoma: a case-control study with propensity score matching.

Whether concomitant hepatic artery resection (HAR) improves the prognosis for advanced perihilar cholangiocarcinoma remains controversial. The aim of the present study was to compare short‐ and long‐term surgical results of HAR versus standard resection (SR) for perihilar cholangiocarcinoma using propensity score matching.

Randomized controlled trial of perioperative antimicrobial therapy based on the results of preoperative bile cultures in patients undergoing biliary reconstruction.

The high frequency of surgical site infections (SSIs) after hepato‐pancreato‐biliary (HPB) surgery is a problem that needs to be addressed. This prospective, randomized, controlled study examined whether perioperative prophylactic use of antibiotics based on preoperative bile culture results in HPB surgery could decrease SSI.

Educational system based on the TAPP checklist improves the performance of novices: a multicenter randomized trial

BackgroundDespite recent developments in surgical education, obstacles including inadequate budget, limited human resources, and a scarcity of time have limited its widespread adoption. To provide systematic training for laparoscopic inguinal hernia repair, we had previously developed and validated a checklist to evaluate the recorded performance of transabdominal preperitoneal (TAPP) repair. We had also developed an educational system that included didactic materials based on the TAPP checklist and incorporated remote evaluation and feedback system. The aim of this study was to evaluate the educational impact of the TAPP education system on novice surgeons.MethodsResidents and surgeons from participating hospitals, who had performed 0 or 1 TAPP procedure, were randomly assigned to the intervention group (IG), who trained using this new educational tool, and the control group (CG), who trained using the conventional system. Their surgical videos were rated by blinded raters. All participants performed their first case prior to randomization. The primary outcome was improvement of TAPP checklist score from the first to the third case.ResultsEighteen participants from 9 institutes were recruited for this study. Seven participants in the IG and 5 participants in the CG were included in the final analysis. The participants in the IG demonstrated significant improvement in their TAPP performance (p = 0.044) from their first case to their third case, whereas their counterparts in the CG failed to make any significant progress during the same period (p = 0.581).ConclusionThe new TAPP educational system was effective in improving the TAPP performance of novice surgeons.

Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients.

Laparoscopy-Guided Transthoracic Transdiaphragmatic Radiofrequency Ablation for Hepatic Tumors Located Beneath the Diaphragm

BACKGROUND It is often difficult to perform percutaneous radiofrequency ablation (RFA) for hepatic tumors beneath the diaphragm. Diaphragmatic thermal damage is one of the fatal late complications of percutaneous transdiaphragmatic RFA. Our experience with laparoscopic transthoracic transdiaphragmatic intraoperative RFA (LTTI-RFA) for hepatic tumors beneath the diaphragm is reported. METHODS Ten patients who underwent LTTI-RFA from 2009 to 2012 were evaluated. Two cases had concomitant partial hepatectomy, and one underwent RFA for two tumors at the same time. The diagnosis was hepatocellular carcinoma in eight cases and metastatic hepatic tumors in two cases. Nine of eleven tumors were located at segments 7 and 8. Nine tumors were less than 20 mm in diameter. The patients were placed in the half left lateral decubitus position with single-lumen tube intubation. After placement of four abdominal ports, a 12-mm port was inserted in the fourth or fifth intercostal space into the diaphragm. The tumor was ablated by an RFA needle through the port. The routine follow-up consisted of laboratory tests and abdominal imaging every 3-6 months. RESULTS The median operation time for only one tumor was 137 minutes (range, 105-187 minutes). The median number of times for ablation was three. Severe postoperative complications (>Clavien-Dindo IIIa) were observed in one case (right upper limb paralysis). The median follow-up period was 35 months (range, 11-43 months). There was no local tumor progression. Recurrent hepatic tumor appearance occurred in other parts of the liver in 6 of the 11 patients. CONCLUSIONS Laparoscopic transthoracic transdiaphragmatic RFA is an acceptable procedure with a low rate of local recurrence.

Near infrared fluorescence light imaging for lymphatic flow toward para-aortic lymph node from the Calot’s triangle: A prospective exploratory study

BACKGROUND Metastasis to para-aortic lymph nodes (PAN) in hilar malignancies is considered distant metastasis. Fluorescence imaging using near infrared fluorescence light and indocyanine green (ICG-NIR imaging) are widely employed for identifying the sentinel lymph node, which might be an ideal alternative procedure for whole excisional biopsy of PAN. However, there has been no report about ICG-NIR imaging in hilar malignancies. The purpose of this study was to determine the optimal dose for indocyanine green to detect PAN and to reveal the detection rate of ICG-NIR imaging for lymphatic flow toward regional lymph nodes (RLN) or PAN from the Calots triangle. PATIENTS AND METHODS We enrolled 62 patients with hepato-pancreatic-biliary malignancies in this study. The dose of ICG was optimized in the first 15 patients and the detection rate for RLN and PAN was evaluated in the remaining 47. We observed that the optimal administered dose of ICG for detecting fluorescent signals in PAN was 5 mg/mL. RESULTS Using this dose, RLN and PAN fluorescence were detected in 29 of 42 patients. Fluorescent signals were recorded in the lymph nodes (LN) along the bile duct and the posterior surface of the head of the pancreas. We also detected PAN fluorescent signals on the right side of the aorta around the left renal vein. We recommend 5 mg/ml of ICG to visualize lymphatic flow from the hepatoduodenal ligament to PAN using ICG-NIR imaging. However, because detection rate of RLN and PAN were 69%, respectively, further improvement for this procedure will be necessary for clinical application.

Development of a novel training system for laparoscopic inguinal hernia repair

Abstract Background: Laparoscopic inguinal hernia repair is considered technically difficult. Although a simulation-based curriculum has been developed to help trainees, access to simulation training outside North America is limited. This study aimed to develop an educational system for the transabdominal preperitoneal (TAPP) approach based on the TAPP checklist, an assessment tool we had developed and validated earlier. Material and methods: Consensus within the TAPP education working group consisting of local TAPP experts, hernia experts and a surgical educator to develop educational tools and the educational system based on the TAPP checklist. The system was piloted in several institutes, and participants were surveyed on its efficacy. Results: We systematically developed an educational video and training manual explaining each item of the TAPP checklist and conveying basic knowledge of the procedure. We integrated the training tool with evaluation and feedback to develop an educational system. In a pilot study, seven trainees at five hospitals were trained using this system and found it very useful for mastering the TAPP procedure. Conclusions: We have developed a training system for TAPP procedure and successfully implemented it in several hospitals. Further research will focus on the educational value of this tool.