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Abstract We report a case of advanced hepatocellular carcinoma (HCC), successfully treated by a combination therapy of α-interferon (IFN-α) and tegafur/uracil (UFT). A 44-year-old Japanese man who underwent a partial hepatectomy for HCC developed tumor recurrence in the liver 10 months after surgery. Transcatheter arterial chemoembolization (TAE) was performed twice within 7 months, but was ineffective. Later, multiple metastatic lesions appeared in the liver, lung and spine. Following the third TAE, a combination therapy of IFN-α (10 × 10 units, i.m., t.i.w.) and UFT (300 mg, p.o.d.) was started. The treatment resulted in a fall in serum PIVKA-II (protein induced by vitamin K antagonism) levels from 906 mAU to normal levels and a complete resolution of all lung nodules within 6 months. At the latest follow up 24 months after the initiation of combination treatment, the patient was working full-time and showed no evidence of tumor relapse. A combination therapy of IFN-α and UFT may be promising for the treatment of advanced HCC. [ABSTRACT FROM AUTHOR]

Background Pathological examination is essential to determine the cancer stage in colorectal cancer (CRC) patients, and histological examination of lymph nodes plays a pivotal role in the staging process. We previously reported a new fat-dissociation method (FM) to detect lymph nodes from surgically resected mesentery. It can reduce a fat volume of the mesentery and visualize a structure of vessels and lymph nodes. In this study we examined the effectiveness of the FM compared with a conventional palpation method in CRC. Methods A single center, open-label, randomized controlled study was performed at Osaka International Cancer Institute (OICC) in Japan from January, 2014, to December, 2014. Randomization was done via a computer-generated permuted-block sequence, and was stratified by surgical procedures and the dissection area of lymph nodes (ie, D2 or D3). Primary endpoint was set at the time to search lymph nodes. Secondary endpoint was set at the number of lymph nodes and 5-year overall survival (OS). Results 130 patients were enrolled to this study and randomly assigned in a one to one ratio: 65 to the FM group and 65 to the conventional palpation (CP) group. Searching time were 15.9 (±0.6) minutes in the FM group and 45.1 (±1.5) minutes in the CP group (P < 0.001). In CP group there was correlation between BMI and searching time (P = 0.047). Numbers of lymph nodes were 21.5 (±1.9) in the FM group and 19.6 (±1.4) in the CP group (P = 0.546). In right-side CRC, the number of lymph nodes was more in the FM group (32.6±4.5) than the CP group (21.7±2.6) (P = 0.030). 5-year OS rate was 87% in the CP group and 86% in the FM group (P = 0.952). Conclusions A new fat-dissociation method could reduce the time for searching lymph nodes without reducing number of lymph node. It is effective in high BMI patients and right-side CRC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage., Methods: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer., Results: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality., Conclusions: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: The D-dimer test is a simple test frequently used in routine clinical screening for venous thromboembolism (VTE). The Cancer-VTE Registry was a large-scale, multicenter, prospective, observational study in Japanese patients with cancer. This study aimed to clarify the relationship between D-dimer level at cancer diagnosis (baseline) and the incidence of events during cancer treatment (1-year follow-up period)., Methods: This was a post hoc sub-analysis of patients from the Cancer-VTE Registry whose D-dimer levels were measured at baseline. The incidence of events during the 1-year follow-up period was evaluated stratified by baseline D-dimer level. Adjusted hazard ratios for D-dimer level and events during the follow-up period were evaluated., Results: Among the total enrolled patients, baseline D-dimer level was measured in 9020 patients. The mean ± standard deviation baseline D-dimer level was 1.57 ± 3.94 µg/mL. During the follow-up period, the incidence of VTE, cerebral infarction/transient ischemic attack (TIA)/systemic embolic events (SEE), bleeding, and all-cause death increased with increasing baseline D-dimer level. The incidence of all-cause death increased with increasing D-dimer level regardless of cancer stage. The adjusted hazard ratio of all-cause death was 1.03 (95% confidence interval: 1.02-1.03) per 1.0-µg/mL increase in baseline D-dimer level., Conclusions: Increases in D-dimer levels were associated with a higher risk of thrombotic events, such as VTE and cerebral infarction/TIA/SEE, during cancer treatment. Furthermore, higher D-dimer levels at cancer diagnosis were associated with a higher mortality rate, regardless of cancer stage., (© 2024. The Author(s).)

Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual's taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene, TAS2R38 , with the bitter compound 6-n-propylthiouracil (PROP). We precisely detected the threshold of PROP bitter perception by conducting the modified two-alternative forced-choice (2AFC) procedure with the Bayesian staircase procedure of the QUEST method and examined genetic variation in TAS2R38 in a Japanese population. There were significant differences in PROP threshold between the three TAS2R38 genotype pairs for 79 subjects: PAV/PAV vs AVI/AVI, p < 0.001; PAV/AVI vs AVI/AVI, p < 0.001; and PAV/PAV vs PAV/AVI, p < 0.01. Our results quantified individual bitter perception as QUEST threshold values: the PROP bitter perception of individuals with the PAV/PAV or PAV/AVI genotypes was tens to fifty times more sensitive than that of an individual with the AVI/AVI genotype. Our analyses provide a basic model for the accurate estimation of taste thresholds using the modified 2AFC with the QUEST approach.

Background: Preoperative chemoradiation therapy is a promising strategy for pancreatic cancer. Peritoneal recurrence is a major recurrence pattern after surgery for pancreatic cancer following preoperative chemoradiation therapy, even in patients with negative peritoneal lavage fluid cytology. Previous reports have indicated that the detection of carcinoembryonic antigen mRNA by reverse transcription polymerase chain reaction is useful for evaluating subclinical tumor cell dissemination in peritoneal lavage fluid., Methods: Patients with resectable and borderline resectable pancreatic cancer treated with preoperative gemcitabine-based chemoradiation therapy and subsequent surgery were enrolled in this study. In all patients, a conventional cytologic examination of peritoneal lavage fluid from laparotomy confirmed the negative peritoneal cytology status. Carcinoembryonic antigen mRNA was detected in the peritoneal lavage fluid at laparotomy using reverse transcription polymerase chain reaction. Recurrence patterns and survival were evaluated in association with the carcinoembryonic antigen mRNA status in the peritoneal lavage fluid., Results: The peritoneal lavage fluid from 57 of the 237 patients (24%) was carcinoembryonic antigen mRNA(+). The carcinoembryonic antigen mRNA(+) patients had a significantly higher incidence of peritoneal recurrence than the carcinoembryonic antigen mRNA(-) patients (36% vs. 15%, P < .001). The 5-year survival rates of the carcinoembryonic antigen mRNA(+) and carcinoembryonic antigen mRNA(-) patients were 31% and 51%, respectively (P = .037). A multivariable analysis for survival revealed that borderline resectability, positive nodal status, and positive carcinoembryonic antigen mRNA status were independent variables for impaired survival., Conclusion: Carcinoembryonic antigen mRNA(+) status was associated with a significantly increased incidence of peritoneal recurrence in patients with pancreatic cancer treated with preoperative chemoradiation therapy, resulting in impaired survival., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Patients with cancer are at higher risk of venous thromboembolism (VTE) than the general population as the malignancy itself and treatment modalities, including medication and surgery, contribute to the risk of developing VTE. Furthermore, patients with cancer developing VTE have a worse prognosis than those without cancer. There are no multicentre prospective data on the occurrence and treatment of VTE in patients with cancer in Japan, and data on the outcomes, complications and incidence of VTE in these patients have not been reported. In addition, Japanese patients with cancer are traditionally treated with unfractionated heparin or warfarin; however, the use of direct oral anticoagulants, which became available in 2014, has not been sufficiently examined in this patient group. Therefore, this multicentre, prospective registry has been designed to capture VTE data from Japanese patients presenting with six cancer types., Methods and Analysis: This registry will enrol 10 000 patients with colorectal, lung, stomach, breast, gynaecological (including endometrial, cervical, ovarian, fallopian tube and peritoneal) or pancreatic cancer between March 2017 and March 2019 and follow them for 1 year. We plan to collect data on the incidences of symptomatic VTE, bleeding events, stroke, systemic embolic events, incidental VTE requiring treatment in patients, overall survival and symptomatic VTE event-free survival., Ethics and Dissemination: All patients will provide written informed consent. Data will remain anonymous and will be collected using an online electronic data capture system. Study protocol, amendments and informed consent forms will be approved by the institutional review board/independent ethics committee at each site prior to study commencement. Results will be disseminated at national meetings and published in peer-reviewed journals., Trial Registration Number: UMIN000024942., Competing Interests: Competing interests: All authors have received personal fees from Daiichi Sankyo during the conduct of study. KF has received research grants from Daiichi Sankyo. TK and KI are employees of Daiichi Sankyo., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We would like to introduce a semi-automated registration system for the National Clinical Database. Japan Surgery Society runs the National Clinical Database since January 2011. And automated registration system is long-awaited due to the number of cases and diverse items to register. Well-known database management system, FileMakerPro enabled collecting and registering the items to the web-site automatically. Still some items need to copy one by one, but after filling the data, all data would be input to the web page for registration. Merit for this automated system is increasing not only the efficiency of administration work but the quality and the usefulness of this database. This paper is to report the outline of the registration system to the NCD database.

Background: Recurrence patterns after hepatic resection has been poorly understood in view of tumor blood flow drainage (TBFD) area. Our goal was to clarify the recurrence patterns after anatomical versus nonanatomical hepatic resection for hepatocellular carcinoma (HCC)., Methods: A total of 424 consecutive patients with HCC, who were treated by curative resection (R0) at our hospital from 2001 to 2012, were evaluated. Among these, we compared the outcomes of the anatomical resection group (AR group, n = 243) and the nonanatomical resection group (NR group, n = 181). We performed an analysis of the recurrence patterns of HCC based on the preoperative CT during hepatic arteriography in these 424 patients., Results: Preoperative liver function was better in the AR group than the NR group (P < 0.001), and tumor size was larger in the AR group than the NR group (P < 0.001). HCC recurrence was recorded in 145 patients (59.7 %) of the AR group and 102 patients (56.4 %) of the NR group with no significant differences between the two groups (P = 0.590). The incidences of extrahepatic and intrahepatic recurrence (solitary/multiple) were similar between the two groups. In addition, the rate of recurrences by local dissemination, either recurrences in the same subsegment in the NR group or recurrences in the TBFD area in the AR group, was sufficiently low (1.4 %) as to be considered negligible., Conclusions: The incidence and patterns of HCC recurrence were similar between the anatomical and nonanatomical resection. Recurrence by local dissemination may be considered to be negligible in both surgical methods.

Background: The optimal surgical resection method in patients with HCC to minimize the risk of local recurrence has not yet been determined. The aim of this study was to compare the prognosis following anatomical versus non-anatomical hepatic resection for hepatocellular carcinoma (HCC)., Methods: Consecutive patients with HCC without macroscopic vascular invasion, treated by curative resection between 1981 and 2012 at Osaka Medical Centre, were included in this retrospective study. The outcomes of patients selected by propensity score matching were compared., Results: Some 1102 patients were included, 577 in the anatomical and 525 in the non-anatomical resection group. By propensity score matching, 329 patients were selected into each group. Demographic, preoperative and tumour variables were similar between the propensity score-matched groups, including tumour size, tumour multiplicity, α-fetoprotein level and 15-min indocyanine green retention rate at 15 min. The incidence of microvascular invasion was higher in the matched anatomical resection group (P = 0·048). Stratified analysis of recurrence-free and overall survival rates revealed no statistically significant differences between the two propensity score-matched groups (P = 0·704 and P = 0·381 respectively). There was also no significant difference in the early recurrence rate within 2 years after resection between these groups (P = 0·726). Subset analysis of the early recurrence-free survival rate in patients with and without microvascular invasion revealed no significant differences between the groups (P = 0·312 and P = 0·479 respectively)., Conclusion: The resection method had no impact on the risk of HCC recurrence or survival., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Preoperative prediction of the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) following surgical treatment remains quite difficult and controversial. We attempted to identify the preoperative and postoperative predictors of the overall survival rates inpatients with ICC in order to clarify the appropriate indications for surgical resection of ICC., Patients and Methods: We retrospectively investigated the clinicopathological features of ICC and outcome of surgical resection in 111 consecutive patients who underwent surgical treatment at our hospital between 1980 and March 2012. Both preoperative factors and operatively confirmed factors were evaluated as potential risk factors for determination of the post-surgical prognosis., Results: Curative resection (R0) was performed in 72 patients (64.9 %). The 1- and 3-year overall survival rates were 85.0 and 59.7 % in the R0 group. Two preoperative factors [hilar invasion as recognized by computed tomography(HR 3.16, P = 0.020) and multiple intrahepatic tumors (HR 7.09, P = 0.0002)] and two operatively confirmed factors [multiple intrahepatic tumors (HR 9.17,P = 0.0009) and lymph node metastasis as confirmed by final histology (HR 6.41, P = 0.003)] were identified as significant risk factors adversely influencing the overall survival rate after surgery. Furthermore, solitary, small(\5 cm) and peripheral ICCs were associated with a very low probability of lymph node metastasis., Conclusions: Preoperatively diagnosed hilar invasion,multiple intrahepatic tumors and histologically confirmed lymph node metastasis were the main determinants of an adverse postoperative prognosis in patients with ICC.Lymph node dissection could be omitted for patients with solitary, small and peripheral ICCs.

Background: Venous thromboembolism (VTE) has been considered to be a rare surgical complication in Japan., Aim: To investigate the incidence and risk factors of VTE in Japanese patients undergoing major abdominal surgery., Methods: A prospective, multi-center epidemiological study was conducted from December, 2001 to August 2002 in 39 medical institutes throughout Japan. A total of 173 patients with general (n = 128), gynecologic (n = 23), and urologic (n = 22) surgery were analyzed. For the diagnosis of deep vein thrombosis (DVT), bilateral venography was performed in all patients. Lung ventilation/perfusion scintigraphy was carried out in patients suspected of pulmonary thromboembolism (PTE)., Results: There were 36 patients with distal DVT (20.8%) and five patients with proximal DVT (2.9%). One patient was diagnosed as PTE. Overall, VTE was diagnosed in 42 patients (24.3%). By univariate analysis, only age (60 years or older) was identified as a significant risk factor in the whole study population. When analyzed by the stepwise multiple logistic regression model, female gender, operation site, age, and operation time were four risk factors found to be significant. The incidence of VTE was closely related to the number of risk factors that patients had. As many as 44% of patients with three or four risk factors developed VTE while those with one or two risk factors showed about a 17% incidence of VTE. Four patients lacking any risk factors did not develop VTE., Conclusions: Venous thromboembolism is common in Japanese patients undergoing major abdominal surgery. Pharmacologic thromboprophylaxis is considered essential, particularly in those patients with multiple, potential risk factors.

Background: Hepatoma-derived growth factor (HDGF) is involved in hepatocarcinogenesis, as well as in liver development and regeneration. This study investigated the correlation of HDGF expression with differentiation and prognosis of hepatocellular carcinoma (HCC)., Methods: HDGF expression in 100 patients with HCC (81 men and 19 women) with ages ranging from 34 to 81 years (median, 61 years) receiving surgical treatment was analyzed by immunohistochemistry. HDGF messenger RNA expression was evaluated in 10 cases by reverse transcription-polymerase chain reaction. The immunostaining pattern in HCCs was categorized as a positive HDGF index (showing positive staining in >90% of tumor cells in both nucleus and cytoplasm) or a negative HDGF index (all others)., Results: Twenty-seven cases (27%) showed a positive and 73 (73%) showed a negative HDGF index. HDGF messenger RNA expression was significantly higher in four cases with a positive HDGF index than in six with a negative index. Cases with well-differentiated histological characteristics showed a higher rate of positive HDGF index than those with a poorly differentiated subtype. Univariate and multivariate analysis revealed significantly poorer disease-free and overall survivals in patients with a positive HDGF index compared with patients with a negative index., Conclusions: These findings suggest the potential utility of HDGF immunohistochemistry in determining the prognosis of HCC.

Incidence of venous thromboembolism (VTE), which had been considered a relatively rare disease in Japan, has been on the increase in recent years as eating habits have become more similar to those of the West. We have investigated the recent incidence data of perioperative pulmonary thromboembolism (PTE) in Japan and have established guidelines for the prevention of VTE. Recommended thromboprophylaxis is early ambulation for low risk group, elastic stocking (ES) or intermittent pneumatic compression (IPC) for moderate risk group, IPC or low dose unfractionated heparin (LDUH) for high risk group, and LDUH + IPC or LDUH + ES for highest risk group. The management fee for PTE prophylaxis was established and covered by health insurance in April 2004. Surprisingly, the incidence of perioperative PTE decreased just after this guideline was issued. After accumulation of further evidence and application of pharmacological agents, such as low molecular weight heparin, we will establish the advanced guidelines in the future.

The incidence of venous thromboembolism (VTE) is rapidly increasing in Japan. Ideally, the guidelines for its prevention should be based on solid evidence, but there are few clinical data on the prevalence and prophylaxis of VTE in Japan. Comprehensive, standard guidelines for the prevention of VTE were recently established by applying the risk-prophylaxis relationship of the sixth American College of Chest Physicians (ACCP) consensus recommendations. Since patients undergoing cancer surgery make up a relatively homogenous, "highest-risk" group, we could precisely evaluate the difference in VTE risk between Japan and the West. The risk of clinical PE in Japanese cancer surgery was found to be one or two risk levels lower than that in the West. Therefore the Japanese risk stratification was set to be one level lower than that in the sixth ACCP guidelines. For prophylaxis, the recommendations of the Japanese guidelines are basically identical to those of the sixth ACCP guidelines. Since the present guidelines are not sufficiently based on Japanese evidence, they should be reviewed in a prospective, nationwide epidemiologic study. In this review article, the theoretical background of and future perspectives on the Japanese guidelines are discussed.

The true incidence of pulmonary embolism (PE) after general surgery in Japan is unknown. We searched the PubMed and Japana Centra Revuo Medicina 1985-2002 databases, entering "surgery" and "pulmonary embolism" or "thromboembolism", and reviewed the reported incidence of clinical PE associated with general surgery in Japan. The overall incidence of PE after general surgery was 0.33%. Fatal PE was reported in 0.08% of the surgical population and the mortality rate of patients with PE was 31%. The incidence of PE after cancer surgery ranged from 0.57% after colon malignancy to 3.85% after pancreatic cancer surgery, and was significantly higher than that after surgery for noncancerous conditions (0.20%). The incidence of PE after various cancer operations corresponded to a moderate or high risk, as defined by the 6th American College of Chest Physicians consensus recommendations. There was no significant difference in the incidence of PE after laparoscopic and open abdominal surgery. The incidence of PE was four to six times lower in patients who had received mechanical prophylaxis, although the difference was not significant. In conclusion, the incidence of PE in Japanese surgical patients is not as low as previously thought. Perioperative prophylaxis against venous thromboembolism is important, but its benefits need to be confirmed by prospective clinical studies.

A molecular analysis of protein S deficiency in three unrelated Japanese patients was performed. An approximately 50% reduction in both functional and immunologic levels of protein S was detected in the plasmas from two unrelated patients, designated protein S Osaka 1 and protein S Osaka 2. An approximately 50% reduction in the functional level, but a normal immunologic level of protein S, was detected in plasma from a third patient, designated protein S Osaka 3. All of the exons and exon/intron junctions of the protein S gene were studied using a strategy combining polymerase chain reaction amplification and rapid non-radioactive single-strand conformational polymorphism analysis. We identified a G-to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation resulted in the substitution of Gly for Ser at position 295 in the sex hormone-binding globulin-like region. In protein S Osaka 2, a G-to-C change at the position of the 3' end of exon III was identified, leading to the amino acid substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3, an A-to-G change in exon II was identified, leading to the substitution of Lys9 by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu mutation causes type II deficiency.

Our retrospective study has shown that hyperlipidemia is a novel etiologic factor in deep-vein thrombosis (DVT) and that most of the idiopathic DVT patients were hyperlipidemic (Thrombosis Research 79, 147-151, 1995). The aim of our current study is to analyze the interrelationship between hyperlipidemia and DVT by means of a case-control study. A series of lipid parameters were analyzed using serum from 109 patients with deep vein thrombosis (DVT). One hundred nine age- and sex-matched subjects served as controls. Diagnosis of hyperlipidemia was made if the serum cholesterol level was above 220 mg/dL or if the triglyceride level was above 150 mg/dL. Among several types of hyperlipidemia examined, the risk factor associated with the highest estimated odds ratio was carriage of hypercholesterolemia associated with hypertriglyceridemia (odds ratio 5.1) followed in order by hypercholesterolemia without hypertriglyceridemia (odds ratio 2.6) and hypertriglyceridemia without hypercholesterolemia (odds ratio 0.9). These findings support the hypothesis that hypercholesterolemia plays an important role in the pathogenesis of DVT.

The responsiveness of platelets only to epinephrine was markedly impaired in 23/140 (16%) healthy Japanese. The impaired responsiveness was not altered by changes in time and environment. Circulating level of catecholamines did not affect the responsiveness of platelets to epinephrine. A pilot family study indicated a possible familial nature of the defect. 3H methyl-yohimbine binding studies indicated that this defect was due to the decreased number of alpha 2 adrenergic receptor. Despite the defect, the potentiating effect of epinephrine on platelet aggregation stimulated by a low dose of ADP was normal. This abnormality is not apparently associated with any bleeding disorders and the clinical implication is unknown at present. It is, however, essential to acknowledge the prevalence of such defect in pursuing research on platelets stimulated by epinephrine.