Modified Socratic Method (planned and executed by Takada) for medical education: Grade II Acute Cholecystitis of Tokyo Guidelines 2018 as an example case.

BACKGROUND: Socratic method, which is an educational method to promote critical thinking through a dialogue, has never been practiced in a large number of people at the academic societies. METHODS: Modified Socratic method was performed for the first time as an educational seminar using an example case of moderate acute cholecystitis based on the evidence described in Tokyo Guidelines 2018. We adopted a method that Takada had been modifying for many years: the instructor first knows the degree of recognition of the audience, then the instructor gives a lecture in an easy-to-understand manner and receives questions from the audience, followed by repeated questions and answers toward a common recognition. RESULTS: Using slides, video, and an answer pad, 281 participants including the audience, instructors and moderators came together to repeatedly ask and answer questions in the five sessions related to the case scenario. The recognition rate of the topic of Critical View of Safety increased significantly before vs after this method (53.0% vs 90.3%). The seminar had been successfully performed by receiving a lot of praise from the participants. CONCLUSION: This educational method is considered to be adopted by many academic societies in the future as an effective educational method.

AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons.

The discovery of mutations within genes associated with autosomal recessive Parkinson's disease allowed for the identification of PINK1/Parkin regulated mitophagy as an important pathway for the removal of damaged mitochondria. While recent studies suggest that AKT-dependent signalling regulates Parkin recruitment to depolarised mitochondria, little is known as to whether this can also regulate PINK1 mitochondrial accumulation and downstream mitophagy. Here, we demonstrate that inhibition of AKT signalling decreases endogenous PINK1 accumulation in response to mitochondria depolarisation, subsequent Parkin recruitment, phosphorylation of ubiquitin, and ultimately mitophagy. Conversely, we show that upon stimulation of AKT signalling via insulin, the mitophagy pathway is increased in SHSY5Y cells. These data suggest that AKT signalling is an upstream regulator of PINK1 accumulation on damaged mitochondria. Importantly, we show that the AKT pathway also regulates endogenous PINK1-dependent mitophagy in human iPSC-derived neurons.

Anti-tumor efficacy of a novel CLK inhibitor via targeting RNA splicing and MYC-dependent vulnerability.

The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025. Mechanistically, the level of CLK2 expression correlated with the magnitude of global skipped exons in response to T-025 treatment. MYC activation, which altered pre-mRNA splicing without the transcriptional regulation of CLKs, rendered cancer cells vulnerable to CLK inhibitors with synergistic cell death. Finally, we demonstrated in vivo anti-tumor efficacy of T-025 in an allograft model of spontaneous, MYC-driven breast cancer, at well-tolerated dosage. Collectively, our results suggest that the novel CLK inhibitor could have therapeutic benefits, especially for MYC-driven cancer patients.

National Clinical Database feedback implementation for quality improvement of cancer treatment in Japan: from good to great through transparency.

The National Clinical Database (NCD) of Japan was established in April, 2010 with ten surgical subspecialty societies on the platform of the Japan Surgical Society. Registrations began in 2011 and over 4,000,000 cases from more than 4100 facilities were registered over a 3-year period. The gastroenterological section of the NCD collaborates with the American College of Surgeons' National Surgical Quality Improvement Program, which shares a similar goal of developing a standardized surgical database for surgical quality improvement, with similar variables for risk adjustment. Risk models of mortality for eight procedures; namely, esophagectomy, partial/total gastrectomy, right hemicolectomy, low anterior resection, hepatectomy, pancreaticoduodenectomy, and surgery for acute diffuse peritonitis, have been established, and feedback reports to participants will be implemented. The outcome measures of this study were 30-day mortality and operative mortality. In this review, we examine the eight risk models, compare the procedural outcomes, outline the feedback reporting, and discuss the future evolution of the NCD.

Biliary tract cancer registry in Japan from 2008 to 2013.

BACKGROUND: The present study analyzed biliary tract cancer patients registered from 2008 to 2013 in Japan and evaluated the outcomes of biliary tract cancer. METHODS: A total of 18,606 patients were registered from 2008 to 2013. Cases were analyzed with regard to patient survival according to contiguous extent of the primary tumor (T), node metastasis, and tumor stage using the 3rd English edition of the Japanese classification of the biliary tract cancers. RESULTS: Five-year survival rates were 39.8% for gallbladder cancer, 24.2% for perihilar bile duct cancer, 39.1% for distal bile duct cancer, and 61.3% for ampullary region cancer. Significant differences were observed between newly introduced subdivisions in the new Japanese classification for all tumoral sites except gallbladder cancer. The survival rate in patients with #13a metastasis was significantly higher than in patients with distant lymph node metastasis. CONCLUSIONS: The new Japanese classification adopted the 7th edition of staging system developed by the Union for International Cancer Control staging system. However, numerous aspects of these classification systems remain unvalidated. The present analysis demonstrated the significance of a proportion of T factor subdivisions and classifications of regional lymph nodes in cases of gallbladder cancer in the new Japanese classification.

Preclinical Efficacy and Safety Assessment of an Antibody-Drug Conjugate Targeting the c-RET Proto-Oncogene for Breast Carcinoma.

PURPOSE: The RET proto-oncogene has been implicated in breast cancer, and the studies herein describe the preclinical and safety assessment of an anti-RET antibody-drug conjugate (ADC) being developed for the treatment of breast cancer. EXPERIMENTAL DESIGN: RET protein expression was analyzed in breast tumor samples using tissue microarrays. The fully human anti-RET antibody (Y078) was conjugated to the DM1 and DM4 derivatives of the potent cytotoxic agent maytansine using thioether and disulfide linkers, respectively. The resulting compounds, designated Y078-DM1 and Y078-DM4, were evaluated for antitumor activity using human breast cancer cell lines and established tumor xenograft models. A single-dose, 28-day, safety study of Y078-DM1 was performed in cynomolgus monkeys. RESULTS: By immunohistochemistry, RET expression was detected in 57% of tumors (1,596 of 2,800 tumor sections) and was most common in HER2-positive and basal breast cancer subtypes. Potent in vitro cytotoxicity was achieved in human breast cancer cell lines that have expression levels comparable with those observed in breast cancer tissue samples. Dose-response studies in xenograft models demonstrated antitumor activity with both weekly and every-3-weeks dosing regimens. In cynomolgus monkeys, a single injection of Y078-DM1 demonstrated dose-dependent, reversible drug-mediated alterations in blood chemistry with evidence of on-target neuropathy. CONCLUSIONS: RET is broadly expressed in breast cancer specimens and thus represents a potential therapeutic target; Y078-DM1 and Y078-DM4 demonstrated antitumor activity in preclinical models. Optimization of the dosing schedule or an alternate cytotoxic agent with a different mechanism of action may reduce the potential risk of neuropathy. Clin Cancer Res; 21(24); 5552-62. ©2015 AACR.

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. METHODS: Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidence-based approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. RESULTS: The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. CONCLUSIONS: This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via http://www.jshbps.jp/en/guideline/biliary-tract2.html.

Updated clinical practice guidelines for the management of biliary tract cancers: revision concepts and major revised points.

BACKGROUND: In 2008, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) launched the clinical practice guideline for the management of biliary tract cancers. JSHBPS decided to revise these guidelines for distribution of updated points concerning the treatment of biliary tract cancers. METHODS: To make clearer recommendations, we introduced the concepts of Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, in which the strength of recommendations are decided considering not only quality of evidence, but also balance of benefits and harms/burdens, patients' preferences, and cost benefits. RESULTS: We emphasize the importance of the dynamic contrast enhanced multiple row detector CT (MDCT) in the diagnosis of biliary tract and gallbladder carcinomas. For biliary drainage, we suggest to perform endoscopic approaches instead of percutaneous approach to avoid complications. Regarding the surgical treatments, we included new clinical questions about the importance of combined vascular resection, intraoperative histological examination of the bile duct resection margin, and the combined extrahepatic bile duct resection for the gallbladder carcinoma. We also discussed details about premalignant lesions and non-neoplastic lesions in pathology section. CONCLUSION: With this major revision, we expect that the Japanese standards of treatments of these diseases are recorded and reported in the universal language.

Classification of biliary tract cancers established by the Japanese Society of Hepato-Biliary-Pancreatic Surgery: 3(rd) English edition.

The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html.

Revision concepts and distinctive points of the new Japanese classification for biliary tract cancers in comparison with the 7(th) edition of the Union for International Cancer Control and the American Joint Committee on Cancer staging system.

BACKGROUND: The 3(rd) English edition of the Japanese classification of the biliary tract cancers (JC) is now available in this journal. The primary aim of this revision is to provide all clinicians and researchers with a common language of cancer staging at an international level. On the other hand, there are several important issues that should be solved for the optimization of the staging system. METHODS: Revision concepts and major revision points of the 3(rd) English edition of the JC were reviewed. Furthermore, comparing with the 7(th) edition of staging system developed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), distinctive points in the JC was discussed. RESULTS: In this edition of the JC, the same stage groupings as those in the UICC/AJCC staging system were basically adopted. T, N, and M categories were also identical in principle with those in the UICC/AJCC staging system, although slight modifications were proposed as the "Japanese rules". As distinctive points, perihilar cholangiocarcinomas and ampullary region carcinomas were clearly defined. Intraepithelial tumor was discriminated from invasive carcinoma at ductal resection margins. Classifications of site-specific surgical margin status remained in this edition. Histological classification was based on that in the former editions of the JC, but adopted some parts of the World Health Organization classification. CONCLUSIONS: The JC now share its staging system of the biliary tact carcinomas with the UICC/AJCC staging system. Future validation of the "Japanese rules" could provide important evidence to make globally standardized staging system.

Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey.

INTRODUCTION: Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey. PATIENTS AND METHODS: During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era. RESULTS: Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00'-07') compared with former period (90'-99'). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %). CONCLUSIONS: The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.

Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese Society of Pancreatic Surgery.

BACKGROUND: Optimal treatment types and prognosis for patients with borderline resectable pancreatic cancer (BRPC) remain unclear because of the lack of studies involving large series of patients. METHODS: We retrospectively analyzed various prognostic factors for 624 BRPC (pancreatic head/body) patients treated from June 2002 to May 2007, by distributing questionnaires to member institutions of the Japanese Society of Pancreatic Surgery in 2010. BRPC was defined according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2009). RESULTS: Among 624 patients, 539 (86.4 %) underwent curative-intent resection, showing an R0 resection rate of 65.9 %. The 3- and 5-year survival rates were 16.1 and 9.9 % in all patients, 22.8 and 12.5 % in the resected patients, and 4.4 and 0 % (P < 0.0001) in the unresected patients, respectively. The following factors influencing survival in all patients were selected as independent prognostic factors using multivariate analysis: major arterial involvement on imaging study; preoperative treatment; surgical resection; and postoperative chemotherapy. Among the resected cases, multivariate analysis revealed that major arterial involvement and remnant tumor status were independent prognostic factors. CONCLUSION: BRPC included two distinct categories of tumors influencing survival: those with portal vein/superior mesenteric vein invasion alone and those with major arterial invasion, which was the most exacerbating factor in the analysis.

Gallbladder bed resection or hepatectomy of segments 4a and 5 for pT2 gallbladder carcinoma: analysis of Japanese registration cases by the study group for biliary surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

PURPOSE: Hepatectomy of segments 4a and 5 (S4a+5) is the recommended treatment for pT2 gallbladder cancer. However, gallbladder bed resection is also occasionally used. Using nationwide data from the Japanese Biliary Tract Cancer Registry and a questionnaire survey, we retrospectively compared these 2 methods of treatment. METHOD: The study involved 85 patients with pT2, pN0 gallbladder cancer (55 treated with gallbladder bed resection, and 30, with S4a+5 hepatectomy). The prognosis and mode of tumor recurrence following treatment were analyzed retrospectively, with overall survival as the endpoint. RESULTS: The 5-year survival rate did not differ significantly between the 2 groups. Univariate analysis showed that bile duct resection and perineural tumor invasion were significant prognostic factors, but the extent of hepatectomy, location of the major intramural tumor, regional lymph node excision, and histological type were not. Multivariate analysis identified perineural tumor invasion as a significant prognostic factor. Recurrence occurred most frequently in both lobes than S4a+5 of the liver following gallbladder bed resection. CONCLUSION: In the present study of cases of Japanese Biliary Tract Cancer Registry, it was not possible to conclude that S4a+5 hepatectomy was superior to gallbladder bed resection.

Distal pancreatectomy with en bloc celiac axis resection performed while monitoring hepatic arterial flow by using a transonic flowmeter during operation.

BACKGROUND/AIMS: Pancreatic body cancer often involves the common hepatic artery and/or the celiac axis, and is regarded as an unresectable disease. Hepatic blood flow must be monitored while performing distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for managing the progression of pancreatic body cancer. We first confirmed a safe level of blood flow by monitoring hepatic venous oxygen saturation (ShvO2) to prevent hepatic ischemia caused by occlusion of the common hepatic artery. However, this method is technically difficult and a long period of time is required to insert the catheter. Thus, we monitored hepatic arterial flow by using a transonic flowmeter in the hepatic artery during operation. METHODOLOGY: Between April 1992 and January 2011, 14 patients underwent DP-CAR. In 6 of these 14 patients we measured ShvO2. In 2 of the 14 patients, a transonic flowmeter was used for determining the hepatic arterial flow during operation. RESULTS: There were no complications during this operation. Operation time when the blood flow was monitored using a transonic flowmeter was less than that when ShvO2 was measured. CONCLUSIONS: Monitoring the transonic flowmeter hepatic artery is a useful and quick method for real-time evaluation of hepatic circulation during operation.

Middle-segment-preserving pancreatectomy for biliary-pancreatic tumors.

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasm (IPMN) and pancreatic endocrine tumors can develop at multiple sites of the pancreas at the same time, sometimes necessitating total pancreatectomy. When low-grade pancreatic malignancy is treated surgically, preservation of function to improve long-term QOL is emphasized. For low grade malignancy tumor of the pancreatic head and tail, we performed middle- segment-preserving pancreatectomy (MSPP), with resection of the pancreatic head and tail alone, resulting in favorable QOL. METHODOLOGY: MSPP was performed for 4 patients. Intraoperative blood loss, hospital stay, postoperative complications, histopathological findings and prognosis were examined. RESULTS: Mean intraoperative blood loss was 1255 +/- 365g, mean hospital stay 61 +/- 53 days, and mortality 0%. Postoperatively, pancreatic fistula was observed in 3 patients, but subsided with conservative treatment. In one patient with diabetes preoperatively, diabetes was exacerbated postoperatively, necessitating insulin treatment. No postoperative onset of diabetes was observed. Percent change in body weight during the postoperative 6 month period from preoperative weight was 93 +/- 6.3%. One patient died of malignant lymphoma 1 year and 4 months after surgery. The other patients are alive and socially active. CONCLUSION: MSPP enables maintenance of good QOL long after surgery for malignancy affecting the head and tail of the pancreas.

[Pancreatoduodenectomy for invasive carcinoma of the head of the pancreas with ligation of the inferior pancreaticoduodenal artery performed first].

The ideal surgical procedure for treating pancreatic cancer achieves radical excision in a minimally invasive manner and allows rapid transition to adjuvant chemotherapy. If the afferent artery to the pancreatic head is not ligated until the latter half of the surgery, congestion of the pancreaticoduodenal vein may occur, leading to phleborrhagia and increased intraoperative hemorrhage. Ligation of the afferent artery, i.e., the inferior pancreaticoduodenal artery (IPDA), in the first half of the surgery may prevent the occurrence of hemorrhage due to congestion. Early ligation of the IPDA is also useful in ensuring the success of radical dissection of the plexus around the superior mesenteric artery or the no. 14 lymph node. We have been performing pancreaticoduodenectomies with antecedent IPDA ligation since 2005 and have found that the percentage of R0 versus R1 and R2 has increased compared with that when standard pancreaticoduodenectomies were performed. Preemptive ligation of the IPDA early in pancreaticoduodenectomy for invasive pancreatic cancer is a useful method for reducing blood loss and achieving R0 resection in a thorough yet efficient manner.

Robot-assisted laparoscopic pancreatic surgery.

BACKGROUND: In the field of gastroenterological surgery, laparoscopic surgery has advanced remarkably, and now accounts for most gastrointestinal operations. This paper outlines the current status of and future perspectives on robot-assisted laparoscopic pancreatectomy. METHODS: A review of the literature and authors' experience was undertaken. RESULTS: The da Vinci Surgical System is a robot for assisting laparoscopy and is safer than conventional endoscopes, thanks to the 3-dimensional hi-vision images it yields, high articular function with the ability to perform 7 types of gripping, scaling function enabling 2:1, 3:1, and 5:1 adjustment of surgeon hand motion and forceps motions, a filtering function removing shaking of the surgeon's hand, and visual magnification. By virtue of these functions, this system is expected to be particularly useful for patients requiring delicate operative manipulation. CONCLUSIONS: Issues of importance remaining in robot-assisted laparoscopic pancreatectomy include its time of operation, which is longer than that of open surgery, and the extra time needed for application of the da Vinci compared with ordinary laparoscopic surgery. These issues may be resolved through accumulation of experience and modifications of the procedure. Robot-assisted laparoscopic pancreatectomy appears likely to become a standard procedure in the near future.

Predictive risk factors for clinically relevant pancreatic fistula analyzed in 1,239 patients with pancreaticoduodenectomy: multicenter data collection as a project study of pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND/PURPOSE: It is important to predict the development of clinically relevant pancreatic fistula (grade B/C) in the early period after pancreaticoduodenectomy (PD). This study has been carried out as a project study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHPBS) to evaluate the predictive factors associated with clinically relevant pancreatic fistula (grade B/C). METHOD: The data of 1,239 patients from 11 medical institutions who had undergone PD between July 2005 and June 2009 were retrospectively analyzed to review patient characteristics and perioperative and postoperative parameters. RESULTS: A drain amylase level >4,000 IU/L on postoperative day (POD) 1 was proposed as the cut-off level to predict clinical relevant pancreatic fistula by the receiver operating characteristic (ROC) curve. The sensitivity, specificity, and accuracy of this cut-off level were 62.2, 89.0, and 84.8%, respectively. A multivariate logistic regression analysis revealed that male [odds ratio (OR) 1.7, P = 0.039], intraoperative bleeding >1,000 ml (OR 2.5, P = 0.001), soft pancreas (OR 2.7, P = 0.001), and drain amylase level on POD 1 >4,000 IU/L (OR 8.6, P < 0.001) were the significant predictive factors for clinical pancreatic fistula. CONCLUSION: The four predictive risk factors identified here can provide useful information useful for tailoring postoperative management of clinically relevant pancreatic fistula (grade B/C).

Selection and analysis of anti-cancer antibodies for cancer therapy obtained from antibody phage library.

The search for effective antibodies (Ab) for curable cancer immunotherapy has been a quest of many research groups in order to find an effective target that exists on the cancer cell surface. So far there have been no conclusive answers to shed light on the search. This study therefore aimed to bridge the gap of cancer therapy. Screening against 49 kinds of cell lines belonging to 11 kinds of solids cancers was performed. Isolation and characterization for approximately 4200 monoclonal antibodies (mAb) was also performed thereafter. Of those mAb 488 clones that turned out to bind to 29 tumor-associated antigens (TAA) were subjected to immunohistochemical (IHC) analyses. Selection of target antigens (Ag) and a potential antibody for cancer therapy was conducted prior to clinical examinations. In order to find predictably effective targets for therapeutic Ab against solid cancers, expression of the Ag on the surface of cancer and normal cells was extensively examined by IHC analyses using fresh cancer specimens resected from patients. In this study, the tendencies of all staining patterns and distribution of the Ab are reported. While all of the TAA appeared to be involved in tumorigenesis, their expression was not restricted to some specific tumor types but rather randomly distributed among various cancers. Some kinds of Ab including anti-epidermal growth factor receptor (EGFR) and anti-human epidermal growth factor receptor 2 (HER2) indicated the frequency of expression in normal cells was generally low. We concluded that identification of 488 mAb and the accumulated results of IHC analyses in this study could be the key for further therapeutic Ab against cancers. The targets that showed cancer-specific expression are expected to be better for therapeutic Ab than the other Ab. Moreover, further investigation into the growth of cancer cell lines using full human IgG form of Ab shows available efficacy in specific cases.

Cholecystectomy using single-incision laparoscopic surgery with a new SILS port.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) offers the potential advantages of reduced postoperative pain and a lower incidence of port-site complications. Moreover, careful attention to closure can reduce the scarring after surgery. Consequently, this method is a promising technique for reducing postoperative pain, decreasing complications, and improving cosmesis. We have performed cholecystectomy in eight patients by SILS. The umbilicus was the point of entry to the abdomen in all patients. METHODS: Between May 2009 and October 2009, 31 patients underwent cholecystectomy at our hospital. The umbilicus was the point of entry to the abdomen in all patients. Three SILSs were performed using a new SILS port, and five SILSs were performed by the conventional method in which three ports are inserted into the umbilicus; the remaining ten patients underwent multiple-incision laparoscopic cholecystectomy (standard cholecystectomy). The results for the patients who underwent standard cholecystectomy, conventional SILS, and SILS using the new port were compared using the Mann-Whitney U test. The data are expressed as mean +/- standard deviation. RESULT: Of the eight cholecystectomies carried out, three were performed by SILS using the new port. No complications or mortalities were associated with this technique. The mean operating times for conventional SILS, SILS with the new port, and standard cholecystectomy were 154 +/- 57, 120 +/- 11, and 100 +/- 51 min, respectively; these inter-group differences are not significant. The blood loss in conventional SILS, SILS with the new port, and standard cholecystectomy was 9 +/- 16, 1, and 6.1 +/- 11 g, respectively; these inter-group differences are not significant. All umbilical incisions were concealed within the umbilicus. CONCLUSION: Cholecystectomy performed using SILS with the new port is a safe and feasible approach with reasonable operation times.