Determinant Factors on Differences in Survival for Gastric Cancer Between the United States and Japan Using Nationwide Databases.

BACKGROUND: Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the United States. We examined the determinant factors of the high survival in Japan compared with the United States. METHODS: We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a United States population-based cancer registry data from 2004-2010. We estimated 5-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined. RESULTS: Five-year relative survival in Japan was 81.0%, compared with 45.0% in the United States. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. CONCLUSION: Although the wide differences in GC survival between Japan and United States can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.

Optimal extent of lymph node dissection for remnant advanced gastric carcinoma after distal gastrectomy: a retrospective analysis of more than 3000 patients from the nationwide registry of the Japanese Gastric Cancer Association.

BACKGROUND: No guidelines are available for defining the extent of lymph node (LN) dissection in patients with remnant gastric carcinoma (RGC). Hence, this retrospective study aimed to determine the optimal extent of LN dissection in patients with RGC. METHODS: We retrospectively evaluated the therapeutic outcomes of node dissection for RGC from a nationwide registry. When the metastatic rate or 5-year survival rate exceeded 10%, dissection was recommended. We calculated the dissection index by multiplying the incidence of metastasis at that nodal station by the 5-year survival rate of patients with metastasis at the station. A dissection index of > 1.0 was considered significant. RESULTS: We included 1133 patients with RGC (T2-T4 tumor) who had undergone distal gastrectomy as the primary surgery for the evaluation of the survival benefit of nodal dissection. Any regional node station was considered significant. When the primary surgery was for malignant disease, the index was high for Nos. 3 (10.2), 7 (9.5), 1 (7.1), and 9 (8.0) nodes. For nodes at the splenic hilum, the index value was 4.4, which was higher than that for the perigastric nodes (Nos. 4sa and 4sb). The index for No. 10 nodes was the highest (10.5) when tumors involved a greater curvature. CONCLUSIONS: The therapeutic strategy for RGC remains the same, regardless of the histology of the primary disease during the initial surgery. Total gastrectomy and dissection of the perigastric LNs (Nos. 1-4), suprapancreatic LNs (Nos. 7-9 and 11), and LNs at the splenic hilum (No. 10) are justified.

Surgical outcomes of elderly patients with Stage I gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association.

BACKGROUND: The proportion of elderly patients undergoing surgery for gastric cancer is increasing. However, limited number of therapeutic outcomes in the elderly has been reported. Here we examined the surgical results based on a nationwide survey of elderly patients who underwent surgery for Stage I gastric cancer. METHODS: Data from 68,353 Stage I patients who underwent gastrectomy between 2001 and 2007 were retrospectively collected. The accumulated data were reviewed and analyzed by the Japanese Gastric Cancer Association registration committee. We first classified the patients as those aged ≤ 74 years and ≥ 75 years. We further classified those patients aged ≥ 75 years into groups by 5-year increments to examine their short- and long-term postoperative outcomes. RESULTS: Patients aged ≥ 75 years accounted for 46.5%. The 30-day mortality rate was < 0.7% for any age group, but for those aged ≥ 75 years, the 60-day and 90-day mortality rates were 0.9-2.3% and 1.2-5.1%, respectively. An examination of long-term survival indicated that, as the class of age increased, the 5-year overall survival (OS) was 47.0-93.1% and disease-specific survival (DSS) was 91.4-98.2%, respectively. Although high DSS rates of ≥ 90% were found for all age groups, OS only accounted for ≤ 82% of patients aged ≥ 75 years. CONCLUSION: Among elderly patients with Stage I gastric cancer, deaths due to other diseases were frequently observed in the long term. Thus, for elderly patients, it may be appropriate to reconsider the treatment strategy with respect to the balance between the invasiveness of the treatment and the prognosis.

Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007).

BACKGROUND: The aim of this retrospective study was to investigate the tumor characteristics, surgical details, and survival distribution of surgically resected cases of gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. METHODS: Data from 118,367 patients with primary gastric carcinoma who underwent resection between 2001 and 2007 were included in the survival analyses. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The median age of the patients was 67 years. The proportions of patients with pathological stage (Japanese Gastric Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%, 11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who were treated by resection was 71.1%. The 5-year overall survival rates of patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were 91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease-specific survival rates in the patients with pT1 (mucosa) disease after D1+ dissection of lymph node station no. 7 (D1 + α), D1+ dissection of lymph node station nos. 7, 8, and 9 (D1+ ß), and D2 lymphadenectomy were 99.4%, 99.6%, and 99.1% respectively. The 5-year disease-specific survival rates in the patients with pT1 (submucosa) disease after D1 + α, D1 + ß, and D2 lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. CONCLUSION: Detailed analyses of the data from more than 100,000 patients show the recent trends of the outcomes of gastric cancer treatment in Japan and provide baseline information for use by medical communities around world.

Inhibitory effects of local anesthetics on the proteasome and their biological actions.

Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein degradation, however the mechanisms remain elusive. Here, we show that the clinically used LAs pilsicainide and lidocaine bind directly to the 20S proteasome and inhibit its activity. Molecular dynamic calculation indicated that these LAs were bound to the ß5 subunit of the 20S proteasome, and not to the other active subunits, ß1 and ß2. Consistently, pilsicainide inhibited only chymotrypsin-like activity, whereas it did not inhibit the caspase-like and trypsin-like activities. In addition, we confirmed that the aromatic ring of these LAs was critical for inhibiting the proteasome. These LAs stabilized p53 and suppressed proliferation of p53-positive but not of p53-negative cancer cells.

Gastric cancer treated by endoscopic submucosal dissection or endoscopic mucosal resection in Japan from 2004 through 2006: JGCA nationwide registry conducted in 2013.

BACKGROUND: The Japanese Gastric Cancer Association (JGCA) initiated a new nationwide gastric cancer registry in 2008 and reported the treatment outcomes of patients with primary gastric cancer who underwent surgical therapy in 2001 and 2003. However, the outcomes of endoscopic therapy have not been reported yet. METHODS: The JGCA conducted a retrospective nationwide registry in 2013 to investigate the short-term and long-term outcomes of endoscopic mucosal resection or endoscopic submucosal dissection in patients with gastric cancer treated from January 2004 through December 2006. This registry used a computerized database with terminology in accordance with the JGCA classification (13th and 14th editions) and the Japanese Gastric Cancer Treatment Guidelines from 2010. RESULTS: Accurate data on 12,647 patients were collected from 126 participating hospitals and analyzed. The treatment procedure was endoscopic submucosal dissection in 81% of the patients and endoscopic mucosal resection in 19%. En bloc and R0 resections were achieved in 89% and 79% of the patients respectively. The total proportion of patients who underwent curative resection was 69.2%; 43.8% of patients underwent curative resection for absolute indication lesions, and 25.4% underwent curative resection for expanded indication lesions. Emergency surgery was performed to treat bleeding or perforation in very few patients (0.3% and 0.4% respectively). The 5-year follow-up rate after endoscopic resection was 70%. The 5-year overall survival rate was 91.6% in patients with absolute indications and 90.3% in patients with expanded indications after curative resection and 86.5% in patients who underwent noncurative resection. The 5-year disease-specific survival rates were 99.9%, 99.7%, and 98.7% in patients with absolute indications who underwent curative resection, patients with expanded indications who underwent curative resection, and patients who underwent noncurative resection respectively. CONCLUSION: Endoscopic resection of gastric cancer resulted in favorable short-term and long-term outcomes nationwide in Japan. Further efforts to increase the follow-up rate are needed.

Lung adenocarcinoma may be a more susceptive subtype to a dendritic cell-based cancer vaccine than other subtypes of non-small cell lung cancers: a multicenter retrospective analysis.

OBJECTIVE: The J-SICT DC Vaccine Study Group provides dendritic cell (DC) vaccines for compassionate use under unified cell production and patient treatment regimens. We previously reported beneficial effects of DC vaccines on the overall survival of 62 patients with advanced non-small cell lung cancer (NSCLC) in a single-center analysis. Here, we extended analysis to 260 patients with NSCLC who were treated at six centers. METHODS: Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks. RESULTS: The mean survival time (MST) from diagnosis was 33.0 months (95 % confidence interval [CI]: 27.9-39.2), and that from time of first vaccination was 13.8 months (95 % CI 11.4-16.8). An erythema reaction at the injection site that was ≥30 mm in diameter was correlated most strongly with overall survival from the first vaccine (≥30 vs. < 30 mm: MST 20.4 vs. 8.8 months, P < 0.001). We reported a similar finding in our previous analysis of patients with advanced pancreatic cancer. Interestingly, although such findings were common between patients with adenocarcinoma and those with other subtypes, the former group experienced significantly prolonged overall survival and a higher response rate for erythema (56.3 vs. 37.3 %, respectively, P = 0.014). CONCLUSIONS: This is the first multicenter study that suggests a possible clinical benefit of DC vaccines for patients with advanced NSCLC, especially those with adenocarcinoma. These findings suggest a specific potential responder population for DC vaccines and warrant further investigation in well-controlled prospective randomized trials.

[A Large Number of Circulating Tumor Cells(CTCs)Can Be Isolated from Samples Obtained by Using Leukapheresis Procedures].

We hypothesized that a large number of circulating tumor cells(CTCs)may be isolated from samples obtained by using the leukapheresis procedures that are utilized to collect peripheral blood mononuclear cells for dendritic cell vaccine therapy. We utilized the CellSearch System to determine the number of CTCs in samples obtained by using leukapheresis in 7 patients with colorectal cancer, 5 patients with breast cancer, and 3 patients with gastric cancer. In all patients, a large number of CTCs were isolated. The mean number of CTCs per tumor was 17.1(range 10-34)in colorectal cancer, 10.0(range 2-27)in breast cancer, and 24.0(range 2-42)in gastric cancer. We succeeded in culturing the isolated CTCs from 7 patients with colorectal cancer, 5 patients with breast cancer, and 3 patients with gastric cancer. In conclusion, compared to conventional methods, a large number of CTCs can be obtained by using leukapheresis procedures. The molecular analyses of the CTCs isolated by using this method should be promising in the development of personalized cancer treatments.

Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer. METHODS: Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints. RESULTS: Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B. CONCLUSIONS: Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer.

BACKGROUND: The aim of this retrospective study was to clarify the safety and efficacy of dendritic cell (DC)-based immunotherapy targeting synthesized peptides, Wilms tumor 1 (WT1) and Mucin 1, cell surface associated (MUC1) for biliary tract cancers (BTCs). METHODS: Sixty-five patients who had nonresectable, recurrent, or metastatic BTCs and received the DC-based immunotherapy were selected for the study. DCs were pulsed with WT1 and/or MUC1. The adverse events (AEs) and clinical responses were examined. RESULTS: No serious treatment-related AEs were observed. Median survival time (MST) from diagnosis and from the first vaccination was 18.5 and 7.2 months, respectively. By multivariate Cox proportional hazard analysis, the significant independent factors were found to be (1) combined chemotherapy, (2) albumin level ≥4.0 g/dL before vaccination, (3) C-reactive protein level <0.5 mg/dL before vaccination, and (4) fever after vaccination. The MST from the first vaccination with or without chemotherapy was 8.2 and 5.3 months, respectively (P = 0.016), and MST for the patients with prognostic nutritional index ≥40 and <40 was 8.1 and 5.0 months, respectively (P = 0.023). CONCLUSIONS: Although a small uncontrolled nonrandomized study, DC-based immunotherapy for BTCs was safe and produced a clinical response for the patients who underwent chemotherapy and maintained a good nutrition status.

Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry.

BACKGROUND: The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008. METHODS: From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed. RESULTS: The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. CONCLUSIONS: Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.

Progression from laparoscopic-assisted to totally laparoscopic distal gastrectomy: comparison of circular stapler (i-DST) and linear stapler (BBT) for intracorporeal anastomosis.

BACKGROUND: Billroth I (B-I) gastroduodenostomy is an anastomotic procedure that is widely performed after gastric resection for distal gastric cancer. A circular stapler often is used for B-I gastroduodenostomy in open and laparoscopic-assisted distal gastrectomy. Recently, totally laparoscopic distal gastrectomy (TLDG) has been considered less invasive than laparoscopic-assisted gastrectomy, and many institutions performing laparoscopic-assisted distal gastrectomy are trying to progress to TLDG without markedly changing the anastomosis method. The purpose of this report is to introduce the technical details of new methods of intracorporeal gastroduodenostomy using either a circular or linear stapler and to evaluate their technical feasibility and safety. METHODS: Seventeen patients who underwent TLDG with the intracorporeal double-stapling technique using a circular stapler (n = 7) or the book-binding technique (BBT) using a linear stapler (n = 10) between February 2010 and April 2011 were enrolled in the study. Clinicopathological data, surgical data, and postoperative outcomes were analyzed. RESULTS: There were no intraoperative complications or conversions to open surgery in any of the 17 patients. The usual postoperative complications following gastroduodenostomy, such as anastomotic leakage and stenosis, were not observed. Anastomosis took significantly longer to complete with DST (64 ± 24 min) than with BBT (34 ± 7 min), but more stapler cartridges were needed with BBT than with DST. CONCLUSIONS: TLDG using a circular or linear stapler is feasible and safe to perform. DST will enable institutions performing laparoscopic-assisted distal gastrectomy with circular staplers to progress to TLDG without problems, and this progression may be more economical because fewer stapler cartridges are used during surgery. However, if an institution has already been performing δ anastomosis in TLDG but has been experiencing certain issues with δ anastomosis, converting from δ anastomosis to BBT should be beneficial.

Impact of dendritic cell vaccines pulsed with Wilms' tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers.

PURPOSE: Dendritic cell (DC)-based vaccines have been expected to serve as new therapeutic approaches for advanced non-small cell lung cancers (NSCLCs); however, their clinical outcomes have not been fully elucidated. We report a single-centre clinical study analysing factors affecting the survival of patients with advanced NSCLCs who received DC vaccines pulsed with or without Wilms' tumour protein-1 (WT1) peptide. METHODS: Among 62 patients with previously treated inoperable or postoperatively relapsed NSCLCs who met the inclusion criteria, DCs from 47 (76%) patients who showed HLA-A2402/0201/0206 were pulsed with one or more corresponding WT1 peptide antigens. DC vaccines were intradermally injected biweekly. RESULTS: Clinical responses based on response evaluation criteria in solid tumours (RECIST) were found in 31 (50%) patients at 3 months after the first DC vaccine (complete response: 1 (1.6%), partial response: 4 (6.5%), stable disease: 26 (41.9%)). Median survival time was 27 months (82% in 1 year and 54% in 2 years) from initial diagnosis, and that was 12 months (48% in 1 year and 22% in 2 years) from the first DC vaccination. Importantly, multivariate analyses revealed that only two factors, blood haemoglobin and the use of WT1 peptides, significantly affected the overall survival of patients from both initial diagnosis and first vaccination. CONCLUSIONS: This study is the first to suggest that DC vaccines pulsed with WT1 may hold a significant impact to prolong the overall survival of patients with advanced NSCLCs.

Pilot study of preoperative immunonutrition with antioxidants in living donor liver transplantation donors.

INTRODUCTION: Previous studies have demonstrated that oxidative stress by mediating the excessive production of reactive oxygen species is involved in tissue damage and organ failure during and after surgery. The impact of the preoperative immunonutrition including antioxidants on the postoperative course of patients undergoing hepatic surgery was investigated in this pilot study. PATIENTS AND METHODS: Twenty-three living donor liver transplantation (LDLT) donors were randomly assigned to either an experimental (AO) group, received a commercial supplement enriched with antioxidant nutrients for each of the 5 days immediately prior to surgery while maintaining normal food intake, or a control (CT) group, administered no supplement. Antioxidative capacity was measured by spectrophotometry of patient serum using a free-radical analytical system. RESULTS: The antioxidative capacity of 90.9% patients in the AO group increased after immunonutrition. Compared to the CT group, the AO group was found to have higher antioxidant capacity and transferrin levels; lower WBC, lymphocyte, and neutrophil counts; and briefer duration of postoperative fever during the postsurgical period. No significant differences were found between the 2 groups regarding the nutritional parameters; liver functioning parameters; immunological parameters; intraoperative factors; postoperative outcomes. CONCLUSION: Preoperative immunonutrition including antioxidants might play a beneficial role in improving postsurgical immunological response but the modest biological advantage was not associated with any significant clinical outcome.

Repeat hepatectomy for intrahepatic recurrence of cholangiolocellular carcinoma.

A 68-year-old man underwent a partial resection of the liver and lymph node dissection for a tumor, 3.0 cm in diameter, in S4 of the liver under the diagnosis of cholangiocellular carcinoma (CCC). The histological diagnosis was cholangiolocellular carcinoma (CoCC) and lymphatic permeation and venous invasion were recognized. Seven months after surgery, CT demonstrated two recurrent nodules in S7 and S8 of the liver, then a partial resection of the liver was performed. The gross and pathological findings were the same as the previously resected tumor. Four months after the second operation, CT demonstrated dilated intrahepatic bile ducts and lymph node swelling of the hepatic hilum. The patient died of disease thirteen months after the first operation. On the basis of the clinical and pathological features of this case, we consider that CoCC clinically resembles CCC and prognosis may be unfavorable, although it has characteristic pathological findings. It is still controversial whether CoCC should be accepted as a separate entity. The significance of repeat hepatectomy for recurrence and adjuvant chemotherapy should be clarified to improve the prognosis of CoCC.

Prognostic effects of oral anti-cancer drugs as adjuvant chemotherapy for 2 years after gastric cancer surgery.

PURPOSE: We conducted this retrospective study to evaluate the effectiveness of giving oral anti-cancer drugs for 2 years as postoperative adjuvant chemotherapy to gastric cancer patients. METHODS: The subjects were 76 patients with stage II and III gastric cancer, who underwent curative surgery between 1989 and 2008. We divided the 20 years chronologically into the UFT term (1989-2003) and the S-1 term (2004-2008). The patients from each term were then divided into three groups according to the length of drug administration; namely, the surgery alone group, the 1-year group, and the 2-year group. RESULTS: The survival time of the 2-year group was better than that of the surgery alone group, not only in the UFT term, but also in the S-1 term (P = 0.0224). Longer relapse-free survival was evident in the S-1 term, especially for the 2-year group (P = 0.0110). A multivariate analysis showed both the stage of the cancer and 2 years of postoperative adjuvant chemotherapy to be independent factors predictive of prolonged survival (P = 0.0040 and P = 0.0022, respectively). CONCLUSIONS: The 2-year administration of oral anti-cancer drugs as postoperative adjuvant chemotherapy might improve the outcome of stage II, III gastric cancer patients. Randomized control trials are warranted to prove the effectiveness of this 2-year regimen.

Different incidence of synchronous liver metastasis between proximal and distal colon cancer.

PURPOSE: The clinicopathological features of colon cancer differ between proximal and distal sites; however, the influence of tumor location on liver metastasis has not been fully examined. The aim of this study was to evaluate the differences in the features of liver metastasis between proximal and distal colon cancer. METHODS: The clinicopathological data from 931 colon cancer patients who were treated surgically were examined retrospectively using a multivariate analysis. RESULTS: The incidence of synchronous liver metastasis was 7.1% (31/438) in proximal colon patients and 11.6% (57/493) in distal colon patients. Both univariate and multivariate analyses showed distal colon cancer to be a risk factor for synchronous liver metastasis. CONCLUSION: The incidence of synchronous liver metastasis differs between proximal and distal colon cancer.

Role of tumor-associated macrophages in the progression of hepatocellular carcinoma.

Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs.

Effect of intra-abdominal absorbable sutures on surgical site infection.

PURPOSE: To establish whether the rates of surgical site infection (SSI) in gastrointestinal surgery are affected by the type of intra-abdominal suturing: sutureless, absorbable material (polyglactin: Vicryl), and silk. METHODS: We conducted SSI surveillance prospectively at 25 hospitals. RESULTS: The overall SSI rate was 14.4% (130/903). The SSI rates in the sutureless, Vicryl, and silk groups were 4.8, 14.8, and 16.4%, respectively, without significant differences among the groups. In colorectal surgery, the SSI rate in the Vicryl group was 13.9%, which was significantly lower than that of the silk group (22.4%; P = 0.034). The incidence of deeper SSIs in the Vicryl group, including deep incisional and organ/space SSIs, was significantly lower than that in the silk group (P = 0.04). The SSI rates did not differ among the suture types overall, in gastric surgery, or in appendectomy. CONCLUSION: Using intra-abdominal absorbable sutures instead of silk sutures may reduce the risk of SSI, but only in colorectal surgery.

Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer.

PURPOSE: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy. METHODS: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test. RESULTS: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors. CONCLUSIONS: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.