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Post-hepatectomy portal vein thrombosis (PH-PVT) is a severe complication. The risk factors of PH-PVT after laparoscopic and open hepatectomy have not been clarified yet. We aimed to retrospectively investigate the risk factors and outcome of PH-PVT in patients with primary liver cancer. We enrolled 622 consecutive patients who underwent hepatectomy in our hospital between January 2006 and August 2016. Of 21 patients (3.4%) with PH-PVT, 7 had grade I; 13, grade II; and 1, grade III. The patients with PH-PVT were significantly older than those without PH-PVT. Of the 413 patients who underwent open hepatectomy, those who underwent a major right hepatectomy (4.1%) had a slightly higher incidence of PH-PVT. Of the 209 patients who underwent laparoscopic hepatectomy, those who underwent a left lateral sectionectomy (21.2%) and major right hepatectomy (16.7%) had high incidence rates of PH-PVT. The treatment was only observation in five patients, medication with an antithrombotic drug in 15 patients, and reoperation in one patient. PH-PVT diminished in 17 patients. Cavernous transformation and/or stenosis of the portal vein developed in three patients. The patient with grade III PH-PVT after open right hemihepatectomy underwent reoperation but died of hepatic failure. This study demonstrated that patient age, left lateral sectionectomy were risk factors of PH-PVT. Laparoscopic left lateral sectionectomy and major right hepatectomy might bring about relatively higher risk of PH-PVT. Major right hepatectomy tends to lead to severe PH-PVT. Careful handling of the PV during hepatectomy and early treatment of PH-PVT are necessary.

Background/aim Perioperative intra-abdominal infection has been reported as a risk factor for metastasis. The aim of this study was to investigate the mechanism by which peritonitis induces immunosuppression in the lung, which in turn promotes lung metastasis. Materials and methods C57BL/6 mice were intravenously administered B16F10 melanoma cells to induce lung metastasis and subsequently subjected to cecal ligation and puncture (CLP) to induce peritonitis or sham surgery. The number of lung metastatic nodules was evaluated. Cell fractions in lungs and serum cytokines after CLP were investigated. Results CLP mice showed an increased number of lung metastases compared to sham-treated mice. The fraction and number of natural killer (NK) cells in lungs of CLP mice were significantly reduced in early post-CLP phase. Myeloid-derived suppressor cells (MDSCs) in lungs were significantly decreased in CLP mice. Serum IL-6 and TNF levels were significantly elevated in CLP mice. Conclusion Peritonitis promoted lung metastasis in a murine model, which may be attributable to the impact of NK cells and MDSCs in the lungs.

The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP).Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8NAC-FP induced PD-L1 expression on ICs and CD8

Objective: The present study aimed to identify the clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with occupational cholangiocarcinoma. Methods: This study included 10 men with occupational cholangiocarcinoma who were former or current workers at a printing company in Osaka, Japan. Of the 10 patients, 2 had 2 main tumors and 1 had 3 main tumors. Twelve FDG-PET imaging findings in the 10 patients could be analyzed. We evaluated the relationships between FDG-PET imaging parameters and clinicopathological findings of occupational cholangiocarcinoma. Results: Abnormal FDG uptake was observed in 8 of the 14 main tumors, with maximum standardized uptake values ranging from 2.9 to 11.0, and the sensitivity was 57.1%. Four patients had lymph node metastases, and abnormal marrow uptake was detected in all these patients. Although precancerous lesions, such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) without any invasion, were not detected, abnormal FDG uptake was demonstrated in 2 of 4 patients with IPNB having an associated invasive carcinoma.Conclusions: Although FDG-PET may be useful for assessing tumor progression factors, such as lymph node metastasis, it cannot accurately detect precancerous lesions, such as BilIN and IPNB without invasive carcinoma.

Backgrounds The prognostic value of biomarkers in metastatic colorectal cancer (mCRC) patients with liver metastases remains unclear. We assessed the difference of expression of biomarkers between primary tumors and liver metastases treated with chemotherapy in mCRC patients, as well as the prognostic value of these markers. Methods Forty-three mCRC patients with liver-limited disease from January 2007–November 2011 were analyzed. They all received resection of primary tumors followed by oxaliplatin-based chemotherapy. After chemotherapy, they all received hepatic resection. Forty-three paired primary and metastatic tumor specimens were collected to measure the messenger RNA expression of six biomarkers by the Danenberg tumor profile method (thymidylate synthase, dihydropyrimidine dehydrogenase [DPD], excision repair cross-complementing gene1, thymidine phosphorylase [TP], folylpolyglutamate synthase, and regenerating islet-derived family, member 4). Results Thirty-six patients' messenger RNA was used for analysis. All markers showed similar expression between primary and metastatic sites. The low-expression group of Danenberg tumor profile and TP in the primary tumor showed significantly higher overall survival than the high-expression group ( P P = 0.033), but for DPD and TP in liver metastases, there were no significant differences of overall survival between the two groups. The ratios of marker expression in liver metastatic site to that in primary site of DPD and TP were significantly higher in chemo-responders than in non-chemo-responders ( P = 0.034 and P = 0.022). Conclusions Biomarkers' expressions in liver metastases were similar to those in the primary tumor. DPD and TP in the primary lesion may be a prognostic factor in chemotherapy-naive mCRC patients with liver-limited disease, but those in liver tumor were not. Further validated analysis to our results would be warranted.

We evaluate surgical outcomes of intracorporeal esophagojejunostomy in laparoscopic total gastrectomy using 2 linear stapler methods.The functional end-to-end anastomosis (FEEA) method was chosen as a first choice. The overlap method was chosen in cases with esophageal invasion. We retrospectively analyzed the early and late surgical outcomes of consecutive 168 laparoscopic total gastrectomy cases from April 2011 to December 2016.The FEEA method was selected in 120 cases, and the overlap method was selected in 48 cases. The mean time of esophagojejunostomy for the FEEA and overlap method was 13.2 and 36.5 minutes, respectively. Two cases with FEEA method and 3 cases with overlap method experienced complications due to esophagojejunostomy leakage. These cases were treated without performing a reoperation. One case with FEEA method was complicated due to esophagojejunostomy stenosis. This case was endoscopically treated. Our procedures are safe and feasible.

BACKGROUND Malignant tumors inhibit antitumor immune responses, which are driven by T-regulatory cells or myeloid-derived suppressor cells (MDSCs). Since MDSCs are involved in invasion, migration, and metastasis of tumor cells, we hypothesized that MDSCs are also involved in tumor recurrence after surgical resection. MATERIALS AND METHODS C57BL/6 mice were subcutaneously inoculated with B16F10 melanoma cells in the right flank. In some experiments, established tumors were surgically resected. Peripheral blood was drawn over time, and immune cells and cytokines were evaluated using flow cytometry. RESULTS MDSCs and relevant pro-inflammatory cytokines increased in the peripheral blood of tumor-bearing mice. Moreover, the frequency of MDSCs rapidly increased in mice with tumor recurrence. CONCLUSION The frequency of MDSCs in the peripheral blood of tumor-bearing mice reflects the status of tumor progression as well as tumor recurrence. Continuous monitoring of MDSCs in the peripheral blood might be a useful indicator of tumor recurrence.

BACKGROUND/AIM The aim of this study was to evaluate the safety and effectiveness of laparoscopic surgery in elderly patients with colorectal cancer. PATIENTS AND METHODS In total, 223 patients aged

The aims of the present study were to examine the relationship between the preoperative FIB-4 index and background liver fibrosis in non-tumor parts obtained from surgical specimens and to investigate whether the FIB-4 index can be a useful predictor for non-B non-C hepatocellular carcinoma (NBNC-HCC) patients treated with surgical resection (SR). A total of 118 patients with NBNC-HCC treated with SR with curative intent were analyzed. Receiver operating characteristic (ROC) curve analysis was performed for calculating the area under the ROC (AUROC) for the FIB-4 index, aspartate aminotransferase (AST) to platelet ratio index, AST to alanine aminotransferase ratio, serum albumin, total bilirubin and platelet count for cirrhosis. We also examined predictors linked to overall survival (OS) and recurrence-free survival (RFS) after SR. The mean patient age was 68.9±9.0 years (93 males and 25 females) with a median observation period of 3.2 years. In extracted surgical specimens, background liver cirrhosis (F4) was observed in 39 patients (33.1%). The mean maximum tumor size was 5.7±3.2 cm. The mean body mass index was 24.3±3.9 kg/m2. The FIB-4 index yielded the highest AUROC for cirrhosis with a level of 0.887 at an optimal cut-off value of 2.97 (sensitivity, 92.3; specificity, 69.6%). In the multivariate analysis, serum α-fetoprotein >40 ng/ml (P=0.026) was the only significant independent predictor linked to OS, while tumor number (P=0.002) and FIB-4 index >2.97 (P=0.044) were significant factors linked to RFS. In conclusion, preoperative FIB-4 index can be a useful predictor for NBNC-HCC patients who undergo SR.

Objectives: We previously reported a cluster of cholangiocarcinoma patients among proof-printing workers who were exposed to 1,2-DCP for a long term. The present study was conducted to evaluate blood parameters in these proof-printing workers during and after exposure. Methods: Health examination records during employment and after retirement were obtained for ten cholangiocarcinoma patients to analyze their blood parameters. The patients and/or their relatives were also interviewed about lifestyle and occupational history. Results: All study patients were exposed to 1,2-DCP for 6–17 years. Red blood cells, hemoglobin, hematocrit, total cholesterol, triglycerides, and fasting plasma glucose were within the standard ranges for almost all patients, but the γ-glutamyl transpeptidase (γ-GTP) levels exceeded the standard range during 1,2-DCP exposure for six patients. Two of the six patients were diagnosed with cholangiocarcinoma during 1,2-DCP exposure, and the other four patients were diagnosed 1–9 years after termination of exposure. The remaining four patients had γ-GTP levels within the standard range during 1,2-DCP exposure, but had increased γ-GTP levels thereafter, and were diagnosed with cholangiocarcinoma 4–10 years after termination of exposure. Aspartate aminotransferase and alanine aminotransferase levels started to increase following the increase in γ-GTP levels. Conclusions: Workers exposed to 1,2-DCP should be provided with periodic health examinations during and after exposure. In the examination, even small increases in γ-GTP levels should be considered a signal of early development of cholangiocarcinoma.(J Occup Health 2014; 56: 279-284)

Background An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. Methods This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. Results The cholangiocarcinoma was diagnosed at 25–45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. Conclusions The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.

The aim of this study was to compare the clinical outcomes and safety of surgical resection for hepatocellular carcinoma between patients older than 75 years of age (elderly group) and those younger than 75 years (control group).A total of 92 patients were included in the elderly group and 206 patients were included in the control group. Clinical outcomes including overall survival, recurrence-free survival, and safety were compared between these two groups after initial surgery.The mean (±SD) observation periods were 2.5 ± 1.8 years in the elderly group and 3.1 ± 2.2 years in the control group. The 1, 3, and 5-year overall survival rates after surgery were 90.0, 73.3, and 43.0%, respectively, in the elderly group and 91.0, 77.5, and 64.4%, respectively, in the control group (P=0.188). The corresponding recurrence-free survival rates were 66.3, 38.8, and 26.2%, respectively, in the elderly group and 66.3, 38.8, and 22.2%, respectively, in the control group (P=0.634). Multivariate analysis identified a total bilirubin level greater than 1.0 mg/dl (P=0.003), a serum albumin level greater than 4.0 g/dl (P=0.005), an α-fetoprotein level greater than 100 ng/ml (P0.001), and microvascular invasion (P0.001) as significant factors linked to overall survival, and tumor number (P=0.014) and microvascular invasion (P=0.008) were significant factors associated with recurrence-free survival. There was no significant difference between the two groups in terms of surgery-related serious adverse events (P0.999).Surgical resection appears to be a safe and feasible procedure for the treatment of hepatocellular carcinoma in elderly patients.

The impact of antibodies to hepatitis B core antigen (anti-HBc) on survival after curative surgical resection (SR) for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to examine the relationship between anti-HBc positivity and survival of HCV-related HCC patients who underwent curative SR. A total of 222 patients with HCV-related, hepatitis B surface antigen (HBsAg)-negative HCC who underwent curative SR were analyzed. They included 119 anti-HBc-positive patients (53.6%) and 103 anti-HBc-negative patients (46.4%). Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the two groups. The median follow-up periods in the anti-HBc-positive and anti-HBc-negative groups were 3.4 years (range, 0.3-10.9 years) and 3.2 years (range, 0.5-10.9 years), respectively. The 1-, 3- and 5-year cumulative OS rates were 88.8, 70.2 and 50.0%, respectively, in the anti-HBc-positive group and 95.8, 77.1 and 61.7% in the anti-HBc-negative group (P=0.300). The corresponding RFS rates were 68.7, 33.0 and 20.0%, respectively, in the anti-HBc-positive group and 74.4, 38.5 and 16.5% in the anti-HBc-negative group (P=0.482). Multivariate analyses identified serum albumin ≥3.8 g/dl (P=0.005) and the presence of microvascular invasion (P

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.

Laparoscopic liver resection (LLR) has been widely performed throughout the world. Although prospective registry studies to clarify the safety of LLR have been feasible, no prior multicenter prospective study has addressed this issue. We have conducted a multicenter prospective cohort study to reveal the current status of LLR in Japan.From April 2015 to March 2016, candidates for LLR were preoperatively enrolled at 12 institutions. The primary end-point was surgical safety, which was evaluated based on surgical factors and on short-term and midterm outcomes.A total of 102 patients were enrolled. Planned laparoscopic procedures included 96 pure laparoscopies, 1 hand-assisted laparoscopy, and 5 hybrid techniques. Non-anatomical partial resection or left lateral sectionectomy were performed in almost all cases. The median duration of surgery was 221 min. The median blood loss was 80.5 mL. Conversion was required for four patients (3.9%). The 90-day postoperative morbidities with grades more severe than II in the Clavien-Dindo classification were observed in six patients (5.9%). The median postoperative hospital stay was 9.5 days. No cases involved reoperation or mortality.Minor resection of LLR has been performed safely. To ensure the safe dissemination of LLR, including for major resection, a larger multicenter prospective study is required.

Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease.Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated.Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients.The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.

For the application of invariant natural killer T (iNKT) cells in cancer therapy, the CD40-CD40L interaction is indispensable in administering alpha-galactosylceramide (αGalCer). We hypothesized that CD40 plays an important role in dendritic cells (DC) pulsed with αGalCer (DCGs) in the treatment of lung metastases.Wild-type (WT) and CD40(-/-) mice were treated with DCGs isolated from WT or CD40(-/-) mice in a B16F10 lung metastases model and NK and NKT cell activity in lungs and the spleen were examined.DCG treatment improved WT mice survival but CD40(-/-) hosts received no survival benefit. Conversely, attenuation of a therapeutic effect in mice treated with CD40(-/-) DCGs was not observed. The functional activities of NK and NKT cells in DCG-treated CD40(-/-) mice were partially suppressed.Host CD40 is essential for DCG treatment to have a therapeutic effect on B16F10 lung metastases.

The aim of the present study was to evaluate the influence of preoperative transcatheter arterial chemoembolization (TACE) on survival after surgical resection (SR) for hepatocellular carcinoma (HCC). Two hundred and thirty-five HCC patients who underwent SR with curative intent were analyzed. Overall survival (OS), recurrence-free survival (RFS) and complication rates were compared between the TACE (n=110) and control groups (n=125). Moreover, TACE subjects were classified into TACE responders (n=85) and TACE non-responders (n=25), according to the therapeutic efficacy of pretreatment TACE, and the factors contributing to OS and RFS after SR were analyzed using univariate and multivariate analyses. The 1-, 3- and 5-year OS rates were 87.4, 76.0 and 62.5%, respectively, in the TACE group and 94.9, 79.0 and 57.8%, respectively, in the control group (P=0.674). The corresponding RFS rates at 1, 3 and 5 years were 73.3, 48.9 and 33.2%, respectively, in the TACE group and 73.3, 29.4 and 16.3%, respectively, in the control group (P=0.062). No TACE-related serious adverse events (SAEs) were observed. There were no significant differences between the groups in terms of surgery-related SAEs (P=0.714), operation time (P=0.881), blood loss during surgery (P=0.334) and hospitalization period (P=0.447). Multivariate analyses identified TACE responder, TACE non-responder, total bilirubin ≥1 mg/dl, serum albumin ≥4 g/dl, pretreatment α-fetoprotein (AFP) level ≥100 ng/ml and microscopic vascular invasion as significant prognostic factors linked to OS. TACE non-responder, tumor number (multiple) and pretreatment AFP level ≥100 ng/ml were significant adverse prognostic factors linked to RFS. In conclusion, TACE is a safe procedure in patients with HCC, and the efficacy of TACE prior to surgery may be associated with clinical outcomes after SR.

Background/Aims We evaluated the prognostic value of the pretreatment elevation of tumor markers for hepatocellular carcinoma (HCC) in patients who underwent curative treatment. Methods We studied 801 patients who had been diagnosed as initial HCC and fulfilled the following criteria: maximum tumor size, ⩽3cm; number of tumors, ⩽3; remnant liver function, Child-Pugh class A or B; treated by hepatectomy or locoregional thermal ablation (LTA); and alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma carboxy prothrombin (DCP) were measured at diagnosis. We analyzed the effects of elevated tumor markers on patient survival in these 2 distinct groups with different types of treatment, i.e. hepatectomy and LTA. Results By multivariate analysis in 345 patients who underwent hepatectomy, no tumor marker significantly affected decreased survival rate. In the 456 patients who underwent LTA, the elevation of AFP-L3 ( p =0.0171) and DCP ( p =0.0004) significantly affected decreased survival rate; DCP elevation had the strongest effect on patient survival. Conclusions The prognostic value of pretreatment tumor marker elevation was different in patients who underwent the curative treatment according to the type of treatment. Pretreatment elevation of AFP-L3 and DCP had prognostic values only in patients treated with LTA.

A total of 37 patients were surgically treated for a colorectal perforation between May 2006 and December 2013. The patients were divided into 2 groups: those with perforation due to colorectal cancer(colorectal cancer group, n=12) and those with perforation due to benign colorectal disease(non-colorectal cancer group, n=25). We examined the influence that onset near the perforation had on colorectal cancer clinical outcome. There was no significant difference in patient backgrounds between the two groups. In the colorectal cancer group, curative resections were performed in eight of the cases (67%), while there were 7 cases (58%) of regional lymph node dissection and all patients received a stoma without bowel anastomosis. In the colorectal cancer group, 1 patient (8%) died of a pulmonary embolism after surgery, whereas 2 patients (8.3%) in the non-colorectal cancer group died of sepsis after surgery. Nine of those patients (75%) received adjuvant chemotherapy. Four patients survived without recurrence. Prompt judgment of the disease severity and selection of optical surgical procedures including tumor resection and regional lymph node dissection is important for colorectal cancer perforation, and an adjuvant setting for the purpose of the long-term survival is necessary.

The aim of this study was to compare the efficacy between the use of transnasal and transanal tube decompression and self-expanding metallic stents (SEMS) as a bridge to surgery for obstructive colorectal cancer.Of a total of 42 patients with obstructive colorectal cancer, 29 were managed with transnasal or transanal tubes and 13 were managed by SEMS.The management duration to surgery in the stent group was longer than that in the tube group (18 vs 11 days; p.05). More patients in the stent group could be discharged and take food or liquid normally. There was no difference in overall complications including anastomotic leakage, surgical side effects, or primary anastomosis. Perforation occurred in 2 patients in the tube group, while stent migration occurred in 1 patient in the stent group. There was no difference in complications between 2 groups.SEMS as a bridge to surgery for obstructive colorectal cancer could improve patients' quality of life during the preoperative period. Evaluations of the complications during decompression are needed for both methods.

Background and Aim: Preoperative hepatic function was evaluated using technetium-99 m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin (Tc-GSA) and a scintillation camera to detect hepatic Tc-GSA uptake by the asialoglycoprotein receptor. Methods: Sixty-two preoperative patients with liver cancer, including hepatocellular and cholangiocellular carcinomas, were studied, using two-parameter two-compartment model analysis. This model is simpler than either the three- or five-compartment model, both of which are accurate but which require complicated analysis and enormous calculation. The parameters k1 and k2 represented the transfer rate constant from the blood to the liver and from the liver to the blood, respectively. We calculated k1, k2, and k1/k2 from time-radioactivity curves of the heart and liver as well as VLmg, which represented the maximal amount of Tc-GSA in the liver. Results: The results were compared to those of conventional liver function analysis using Tc-GSA (the index of blood clearance (HH15) and the receptor index (LHL15)) or indocyanine green (ICGR15). Both HH15 and LHL15 were significantly correlated with k1, k1/k2, and VLmg. In addition, they closely correlated with the results of ICGR15 and some serum hepatic function tests (aspartate aminotransferase, choline esterase, albumin, platelet). The pathological grading for liver cirrhosis also correlated with k1, k1/k2, and VLmg. From a clinical point of view, VLmg had a significant correlation with the Child–Pugh score. Conclusions: These results suggest that this new compartment analysis will be useful in evaluating liver function, as it is accurate, simple and convenient. © 2003 Blackwell Publishing Asia Pty Ltd

We aimed to examine the relationship between the preoperative GSA index [uptake ratio of the liver to the liver plus heart at 15 min (LHL15) to uptake ratio of the heart at 15 min to that at 3 min (HH15) ratio] calculated from 99mTc‑labeled diethylene triamine pentaacetate-galactosyl human serum albumin (99mTc-GSA) scintigraphy and background liver fibrosis and to investigate whether the GSA index can be a useful predictor in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients treated with surgical resection (SR). A total of 213 HCV-related HCC patients were analyzed. Receiver operating characteristic (ROC) curve analysis was performed for calculating the area under the ROC (AUROC) for nine noninvasive parameters including GSA index, indocyanine green retention at 15 min, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, serum albumin, total bilirubin, platelet count and prothrombin time for cirrhosis. We also examined predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) after SR in univariate and multivariate analyses. There were 153 males and 60 females with the mean age of 69.9 years. The median observation periods were 2.8 years. The mean maximum tumor size was 4.1 cm. HH15 ranged from 0.452 to 0.897. LHL15 ranged from 0.669 to 0.982. The mean value of the GSA index was 1.41. Among the nine parameters, the GSA index yielded the highest AUROC for cirrhosis with a level of 0.786 at an optimal cut-off value of 1.37 (sensitivity, 65.9%; specificity, 79.0%). In multivariate analyses, the GSA index was an independent predictor (P0.001) linked to RFS and it had a marginal significance in terms of OS (P=0.074). In conclusion, the preoperative GSA index can be a useful predictor in HCV-related HCC patients treated with SR.

Background The purpose of this study was to validate the Beppu nomogram, which predicts disease-free survival (DFS) after resection of colorectal liver metastases, and to investigate the efficacy of neoadjuvant chemotherapy based on the nomogram-predicted recurrence risk. Methods We retrospectively analyzed 234 patients with colorectal liver metastases who underwent a hepatic resection at eight hospitals between 2005 and 2010. Results The nomogram c-index of all the patients was 0.59. The observed and the predicted 3-year DFS showed good agreement. When the patients were divided into two groups who received or did not receive pre-hepatectomy chemotherapy (PHC), the c-index of the patients who received PHC was inferior to that of the patients who did not (0.56 and 0.61, respectively). In patients who received PHC, DFS among the quintiles clustered by the nomogram score indicated no significant differences (P = 0.25), unlike in patients who did not receive PHC (P < 0.0001). Surprisingly, in patients with no risk factors for recurrence, neoadjuvant chemotherapy provided significantly lower DFS than no neoadjuvant chemotherapy (3-year DFS: 42.9% vs. 80.0%, P = 0.03). Conclusions The nomogram validation was shown to be moderately predictive. PHC decreased the performance of the nomogram and might produce no DFS benefit in patients with low recurrent risk.

The clinical benefits of conversion chemotherapy followed by liver resection for initially unresectable colorectal liver metastases are still controversial. The criteria for unresectability vary from one team to another. To clarify this issue, we retrospectively assessed the survival and characteristics of metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) who underwent conversion therapy. Our criteria for resectability depended on the size of the remnant liver volume (>30 %) and expected function after removal of all metastases. Between December 2007 and September 2011, a total of 115 patients were diagnosed as having mCRC with LLD and received chemotherapy. Among them, 47 had tumors that were initially diagnosed as resectable. They underwent hepatic resection after chemotherapy (resected group). Of the 67 tumors were initially diagnosed as unresectable, 12 became resectable after chemotherapy (conversion group), leaving 55 tumors that remained unresectable after chemotherapy (unresected group). The median follow-up was 25.2 months. Hepatic resection was more invasive in the conversion group than in the resected group. Median disease-free survival was significantly higher in the resected group than in the conversion group (p = 0.013). Overall survival (OS) was also higher in the resected group, but the difference was not significant (p = 0.36). However, OS was significantly higher in the conversion group than in the unresected group (p = 0.034). Multivariate analysis of the resected and conversion groups showed that OS was significantly negatively influenced by abnormal carcinoembryonic antigen levels at surgery (p = 0.037) and a hospital stay >30 days (p = 0.009). Our results showed that conversion chemotherapy could contribute to longer OS in mCRC patients with LLD.

The impact of obesity on survival after curative treatment for non-B non-C hepatocellular carcinoma (NBNC-HCC) remains unclear. This study examined the prognostic impact of obesity in patients who received curative therapy for NBNC-HCC.A total of 260 patients with NBNC-HCC who underwent curative therapy were analyzed. They included 116 obese patients (44.6%) with a body mass index (BMI)25 kg/m² (obesity group) and 144 control patients (55.4%) with a BMI25 kg/m² (control group). Overall survival (OS) and recurrence-free survival (RFS) rates were compared.The median observation periods in the obesity and control groups were 3.1 and 3.0 years, respectively. The 1-, 3- and 5-year cumulative OS rates were 93.9%, 77.3% and 56.0% in the obesity group, and 98.8%, 77.3% and 62.1% in the control group, respectively (p = 0.955). The corresponding RFS rates were 74.6%, 28.0% and 19.0% in the obesity group, and 70.0%, 44.3% and 28.9%, in the control group, respectively (p = 0.128). Multivariate analyses identified a serum albumin4.0 g/dL (hazard ratio [HR], 1.759; 95% confidence interval [CI], 1.007-3.074; p = 0.047) and des-γ-carboxy prothrombin100 mAU/mL (HR, 0.396; 95% CI, 0.243-0.646; p0.001) as independent factors linked to OS. Alkaline phosphatase300 IU/L (HR, 0.549; 95% CI, 0.367-0.823; p = 0.004) and gamma-glutamyl transferase100 IU/L (HR, 0.679; 95% CI, 0.471-0.978; p = 0.038) were significant adverse predictors linked to RFS.Obesity does not affect survival in patients with NBNC-HCC after curative therapy.

We aimed to examine the relationship between antibodies to hepatitis B core antigen (anti-HBc) positivity and survival in patients with non-B non-C hepatocellular carcinoma (NBNC-HCC) who underwent curative treatment.A total of 260 patients with NBNC-HCC who underwent curative therapy were analyzed. They included 124 anti-HBc-positive patients (47.7%) and 136 anti-HBc-negative patients (52.3%). Overall survival (OS) and recurrence-free survival (RFS) rates were compared.The 3-year cumulative OS rates were 75.9% in the anti-HBc-positive group and 82.3% in the anti-HBc-negative group (p=0.069). The corresponding RFS rates were 29.8% in the anti-HBc-positive group and 43.0% in the anti-HBc-negative group (p=0.001). Multivariate analyses identified anti-HBc positivity (p=0.006), aspartate aminotransferase ≥ 40 IU/l (p=0.037) and des-γ-carboxy prothrombin ≥ 100 mAU/ml (p=0.046) as significant adverse predictors were linked to RFS.Anti-HBc positivity can be a useful predictor for recurrence in patients with NBNC-HCC after curative therapy.

Objectives The present study was conducted to investigate the relationship between occupational chemical exposure and incidence of cholangiocarcinoma among workers in the offset colour proof-printing section of a small printing company in Osaka, Japan. Methods We identified 51 men who had worked in the proof-printing room, and 11 men who had worked in the front room for at least 1 year between 1991 and 2006. We interviewed them about the chemicals they used, and estimated their levels of exposure to chemicals. We also investigated the medical records of 11 cholangiocarcinoma patients, and calculated the standardised mortality ratio (SMR) from 1991 to 2011. Results Workers used 1,2-dichloropropane (1,2-DCP) from approximately 1985 to 2006, and dichloromethane (DCM) from approximately 1985 to 1997/1998. Exposure concentrations were estimated to be 100–670 ppm for 1,2-DCP and 80–540 ppm for DCM among the proof-printing workers. All 11 patients were pathologically diagnosed with cholangiocarcinoma. Ages at diagnosis were 25–45 years, and ages at death were 27–46 years among the six deceased individuals. The primary cancer site was the intrahepatic bile duct for five patients, and the extrahepatic bile ducts for six. All patients were exposed to 1,2-DCP for 7–17 years and diagnosed with cholangiocarcinoma 7–20 years after their first exposure. Ten patients were also exposed to DCM for 1–13 years. The SMR for cholangiocarcinoma was 2900 (expected deaths: 0.00204, 95% CI 1100 to 6400) for all workers combined. Conclusions These findings suggest that 1,2-DCP and/or DCM may cause cholangiocarcinoma in humans.

We examined the prognostic value of pre-treatment C-reactive protein (CRP) after surgical resection (SR) for hepatocellular carcinoma (HCC).A total of 298 patients with HCC who underwent SR were analyzed. They were categorized into a CRP-positive group (group A: CRP0.2 mg/dl, n=130) and a CRP-negative group (group B: CRP0.2 mg/dl, n=168). Overall survival (OS) and recurrence-free survival (RFS) were compared.The 1- and 3-year cumulative OS rates were 87.0% and 68.3% in group A and 95.9% and 81.1% in group B (p=0.194). The corresponding RFS rates were 61.6% and 30.3% in group A and 77.2% and 44.9% in group B (p=0.004). In multivariate analysis, the pre-treatment CRP level was a significant prognostic factor linked to RFS (p=0.046).Pre-treatment CRP levels may be a useful predictor of recurrence after SR for HCC.

The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases.Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy.Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95% CI 38.13-75.73] and 25.07 months [95% CI 17.87-32.26], respectively; P0.001). The median disease-free survival was 20.2 [95% CI 8.82-31.65] months in the resected group.Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM.

Background The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC). Methods We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests. Results The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013). Conclusions PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.

A 75-year-old woman was seen because of a painful breast mass. Tc-99m sestamibi scintimammography showed uptake in the mass, suggesting malignancy. The mass ulcerated spontaneously and discharged. Mycobacterium tuberculosis was positive on examination of the discharge.