Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

[A Case of Rhabdomyolysis Caused by Oxaliplatin during Postoperative Adjuvant Chemotherapy].

The patient was a 50-year-old male. At the age of 48 years, he had undergone total gastrectomy and right hemicolectomy simultaneously for gastric and ascending colon cancers. Since adjuvant chemotherapy has become common practice for patients with ascending colon cancer, capecitabine was administered for 6 months. One year and 6 months after the surgery, he was diagnosed with recurrence of the ascending colon cancer at the anastomotic site and underwent local colectomy. Considering he was pathologically diagnosed as pT4a, mFOLFOX6 therapy was prescribed as postoperative adjuvant chemotherapy. On the day the 11th course of treatment was initiated, the patient complained of weakness; however, his blood test results showed no abnormalities; therefore, he was followed-up as an outpatient. Three days later, he presented to the hospital with exacerbated symptoms and was diagnosed with rhabdomyolysis due to a marked increase in CK(2,031 U/L). Rhabdomyolysis was determined to be the adverse effect of oxaliplatin because out of all the drugs prescribed to the patient, this condition is listed as a side effect only in oxaliplatin's package insert. Fortunately, outpatient treatment was enough to alleviate rhabdomyolysis. Subsequently, adjuvant chemotherapy was completed without oxaliplatin. The patient has been followed-up without recurrence for 9 months after the surgery.

[A Case of Extramural Growth-Type Ileocecal Colon Cancer].

A woman in her 80s was diagnosed with an abdominal mass during physical examination. Contrast-enhanced computed tomography(CT)revealed a tumor with contrast enhancement outside the ileocecal region of the intestine, and the ileocolic artery penetrated the tumor. No tumor was detected by colonoscopy. An endoscope could not be passed through due to an ileocecal valve stenosis. A biopsy of the ileocecal valve revealed only lymphocyte hyperplasia without adenocarcinoma components. Barium enema examination demonstrated no influx of the contrast medium from the cecum into the oral side of the intestine. Since a gastrointestinal stromal tumor in the ileocecal region was suspected, laparotomy was performed in the ileocecal region owing to the preoperative diagnosis of suspected malignant lymphoma, revealing a 5-cm elastic hard tumor outside the ileocecal wall. The tumor could not be separated from the intestinal tract. Histopathological examination revealed no lesion on the mucosal surface, although poorly differentiated adenocarcinoma infiltrated from the submucosa to the serosa. Thus, the patient was diagnosed with extramural growth-type ileocecal colon cancer. This disease is relatively rare but need to be kept in mind.

[A Case of Transverse Colon Cancer Complicated by Eosinophilic Granulomatosis with Polyangiitis].

A man in his 50s had undergone steroid therapy for eosinophilic granulomatosis with polyangiitis(EGPA). Since an examination for malignant tumors revealed type 0-Ⅰsp(cT1aN0M0)and type 2(cT2N0M0)lesions in the proximal and mid- transverse colon, respectively, he was referred to our department. Endoscopic resection was performed on the proximal lesion. After the confirmation of curative resection, laparoscopic partial colectomy(transverse colon)and D3 lymph node dissection were performed on the mid-transverse lesion. Because of the patient's favorable postoperative course, he was discharged from the hospital on POD17. Since steroids and immunosuppressants may cause immunological abnormalities and malignant tumors, such patients should be strictly followed up.

Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study.

BACKGROUND: For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. METHODS: We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin-eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. RESULTS: Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). CONCLUSIONS: This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding.

ERO1-α is an oxidizing enzyme that exists in the endoplasmic reticulum and is induced under hypoxia. It reoxidizes the reduced form of protein disulfide isomerase that has oxidized target proteins. We found that ERO1-α is overexpressed in a variety of tumor types. MHC class I H chain (HC) has two disulfide bonds in the α2 and α3 domains. MHC class I HC folding is linked to the assembly of MHC class I molecules because only fully disulfide-bonded class I HCs efficiently assemble with ß2-microglobulin. In this study, we show that ERO1-α associates with protein disulfide isomerase, calnexin, and immature MHC class I before being incorporated into the TAP-1-associated peptide-loading complex. Importantly, ERO1-α regulates the redox state as well as cell surface expression of MHC class I, leading to alteration of susceptibility by CD8(+) T cells. Similarly, the ERO1-α expression within cancer cells was associated with the expression level of MHC class I in colon cancer tissues. Thus, the cancer-associated ERO1-α regulates the expression of the MHC class I molecule via oxidative folding.

OSNA-Assisted Molecular Staging in Colorectal Cancer: A Prospective Multicenter Trial in Japan.

BACKGROUND: We previously reported that the one-step nucleic acid amplification (OSNA) assay provided a judgment performance for colorectal cancer equivalent to a 2-mm-interval histopathological examination of lymph nodes (concordance 97.1 %, n = 385 lymph nodes). In this prospective multicenter study, we uncovered an OSNA-assisted pathology to detect lymph node metastasis. METHODS: A total of 204 (50 stage I, 74 stage II, and 80 stage III) colorectal cancer patients. All 4324 lymph nodes were examined by the standard histology (one-slice H&E staining) and 1925 lymph nodes (44.5 %) of them were also subject to the OSNA analysis. RESULTS: The concordance rate between 1 slice hematoxylin/eosin and OSNA assay was 95.7 % (1,842/1925 lymph nodes). The sensitivity and specificity of the OSNA assay were 86.2 % (125/145) and 96.5 % (1717/1780), respectively. Among 124 node-negative patients (pN0), the respective upstaging rates of pStages I, IIA, IIB, and IIC were 2.0 % (1/50), 17.7 % (11/62), 12.5 % (1/8), and 25 % (1/4). OSNA-positive patients had deeper invasion to the colonic wall and severe lymphatic invasion (P = 0.048 and P = 0.004, respectively). The sum of the quantitative results of OSNA and total tumor load increased as the number of metastasized lymph nodes increased: 1550 copies/µL in pN0, 24,050 copies/µL in pN1, and 90,600 copies/µL in pN2. CONCLUSIONS: The present study on colorectal cancer provided fundamental data regarding OSNA-assisted pathology of lymph node metastasis in Japan.

Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

Evaluation of the validity of chemotherapy-induced nausea and vomiting assessment in outpatients using the Japanese version of the MASCC antiemesis tool.

PURPOSE: The Multinational Association of Supportive Care in Cancer (MASCC) developed the MASCC antiemesis tool (MAT) as a tool for chemotherapy-induced nausea and vomiting (CINV) assessment and subsequently published its Japanese version in 2010. We evaluated the validity of CINV assessment in outpatients using the Japanese version of MAT. METHODS: Patients administered highly or moderately emetogenic chemotherapy in the outpatient chemotherapy unit of our hospital were included in the study. The study was designed as a prospective two-period crossover observational study to evaluate the correlation between the daily patient diary and the Japanese version of MAT in terms of CINV onset. We examined with a focus on reliability of the Japanese version of MAT particularly in the description of the delayed phase of nausea and vomiting. RESULTS: Patient descriptions of CINV onset in a total of 116 cycles in 58 patients (two cycles/patient) were analyzed. The CINV incidence indicated by the patient diary was similar to that by the Japanese version of MAT. The concordance rate between the two tools in the same patients was 86.2 % for CINV onset in the delayed phase. The nausea score was also similar between the two tools regarding the mean and variance, showing a strong correlation with a correlation coefficient of 0.71. CONCLUSIONS: The results of the study showed that the Japanese version of MAT is a highly reliable tool for CINV assessment, indicating that it is valid for assessing CINV in outpatients.

Oncological benefit of primary tumor resection with high tie lymph node dissection in unresectable colorectal cancer with synchronous peritoneal metastasis: a propensity score analysis of data from a multi-institute database.

BACKGROUND: Peritoneal metastasis is recognized as a predictor of poor prognosis in patients with colorectal cancer, and whether surgical intervention for peritoneal metastasis has any clinical benefit has remained controversial. The purposes of this study were to identify prognostic factors in cases of unresectable colorectal cancer with synchronous peritoneal metastasis and to clarify the impacts of primary tumor resection with high tie lymph node dissection. METHODS: A multi-institutional retrospective analysis was conducted of 579 patients who underwent resection of the primary tumor for unresectable colorectal cancer with peritoneal metastasis between 1991 and 2007. For these 579 patients, clinicopathological variables were analyzed for prognostic significance using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. RESULTS: Multivariate analysis revealed hematogenous metastasis (p < 0.001), histology of the tumor (p = 0.006), postoperative chemotherapy (p < 0.001), and lymph node dissection (p = 0.001) as independent prognostic factors. In the propensity-matched cohort, patients treated with high tie lymph node dissection showed a significantly better overall survival than those with low tie lymph node dissection (median overall survival 13.0 vs. 11.5 months; p = 0.041). CONCLUSIONS: It is suggested that primary tumor resection with high tie lymph node dissection favorably affects survival, even in unresectable colorectal cancer with peritoneal metastasis.

Prognostic value of HLA class I expression in patients with colorectal cancer.

BACKGROUND: Prognostic factors are useful for determination of the therapeutic strategy and follow-up examination after curative operation in cancer treatment. The immunological state of the host can influence the prognosis for cancer patients as well as the features of the cancer. Human lymphocyte antigen (HLA) class I molecules have a central role in the anti-cancer immune system. Therefore, we focused on the HLA class I expression level in cancer cells to investigate its prognostic value in patients with colorectal cancer. METHODS: We reviewed the clinical pathology archives of 97 consecutive patients with stage II colorectal cancer who underwent curative operation at the Sapporo Medical University, Japan, from February 1994 to January 2005. Fifty-six high-risk patients had adjuvant chemotherapy. The cancer cell membrane immunoreactivity level for HLA class I expressed by EMR8-5 was classified into three categories (positive, dull, and negative). In this study, the cases were divided into two groups: "positive" and "dull/negative". HLA class I expression level and clinicopathological parameters were evaluated with the Pearson χ (2) test. Survival analysis was assessed by the Kaplan-Meier methods, and the differences between survival curves were analyzed using the log-rank test. RESULTS: Immunohistochemical study of HLA class I revealed the following. There were 51 cases that were positive, 40 were dull, and six negative. The HLA class I expression level had no significant correlation with other clinicopathological parameters, except for gender. Univariate and multivariate analyses related to disease-free survival (DFS) revealed that tumor location, HLA expression level, and venous invasion were significant independent prognostic factors (P < 0.05). The 5-year DFS rates in HLA class I positive group and in the dull/negative group were 89% and 70%, respectively. For high-risk patients with adjuvant chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 84% and 68%, respectively. For low-risk patients without the chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 100% and 71%, respectively. CONCLUSIONS: Our study concluded that the HLA class I expression level might be a very sensitive prognostic factor in colorectal cancer patients with stage II disease.

Impact of aging on morbidity and mortality after liver resection: a systematic review and meta-analysis.

Surgery involving elderly patients is becoming increasingly common due to the rapid aging of societies all over the world. The objective of this study was to elucidate the prognostic differences between elderly and young patients who undergo liver resection. A systematic review based on the PRISMA flow diagram was conducted. Ovid Medline and PubMed were used to search for relevant literature published between January 2000 and March 2013, and the modified MINORS score was used to assess the methodological quality. In cases of hepatocellular carcinoma and miscellaneous liver tumors, the morbidity and mortality rate did not differ significantly between the elderly and young patients. For patients with colorectal metastatic liver cancer, the mortality of the young patients was 2.7 times lower than that of elderly patients. Our review of high-quality retrospective studies was able to elucidate the clinical risks of age on the outcomes after liver surgery in specific patient populations.

Clinical feasibility of laparoscopic lateral pelvic lymph node dissection following total mesorectal excision for advanced rectal cancer.

PURPOSE: To evaluate the technical feasibility, safety and oncological outcomes of laparoscopic lateral pelvic lymph node dissection in patients with advanced low rectal cancer. METHODS: Laparoscopic lateral pelvic lymph node dissection was performed in 18 patients from November 2009 to September 2012. The data regarding the patient demographics, surgical outcomes and short-term oncological outcomes were analyzed. RESULTS: In all 18 patients, the procedures were completed without conversion to open surgery. The mean length of the operation was 603.7 min (473-746 min). The mean number of harvested lateral pelvic lymph nodes was 16.9 (7-27), and five patients (27.8 %) had lymph node metastases. The postoperative mortality and morbidity rates were 0 and 16.7 %, respectively. Three patients developed Grade 2 urinary retention. No local recurrence had developed after a mean follow-up period of 23.6 months. CONCLUSION: Laparoscopic lateral pelvic lymph node dissection is technically feasible, safe and oncologically acceptable within the limitations of the short-term follow-up period.

Questionnaire survey for the development and publication of cancer clinical practice guidelines in Japan.

PURPOSE: To understand the current situation of the development and publication of cancer clinical practice guidelines and discuss an ideal structure in future. METHODS: A questionnaire survey pertaining to the development and publication of cancer clinical practice guidelines was conducted with funding by a Health and Labour Sciences Research Grant. Respondents included presidents and chairpersons of academic societies developing guidelines and members of the Cancer Guidelines Committee of the Japan Society of Clinical Oncology who were specialists in various cancer sites. RESULTS: Concerning the question of funding for the development and publication of the guidelines, 80.7 % of respondents indicated that partial public funding is required. As for the flow of public funds, 80.4 % of respondents thought that funds should be distributed appropriately to each academic society by a third-party organization. Regarding the question about the publication of the guidelines, 82.5 % of respondents replied that a comprehensive publication site needs to be established. In terms of the choice of organization that would be responsible for setting up and managing this site, the responses varied as follows: "a newly established organization" (38.3 %); "Center for Cancer Control and Information Services" (29.8 %); "Japan Society of Clinical Oncology" (23.4 %); and "Medical Information Network Distribution Service" (23.4 %) (multiple answers allowed). CONCLUSION: While the guidelines should be developed voluntarily by each academic society, partial public funding is also considered to be necessary for maintaining the continuous revision process. As for the publication of the guidelines, the establishment of a new comprehensive publication site would improve user convenience.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2010 and March 2011].

Bacteria isolated from surgical infections during the period from April 2010 to March 2011 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 631 strains including 25 strains of Candida spp. were isolated from 170 (81.7%) of 208 patients with surgical infections. Four hundred and twenty two strains were isolated from primary infections, and 184 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus avium was highest, followed by Streptococcus spp. such as Streptococcus anginosus and Staphylococcus spp. such as Staphylococcus aureus, in this order, from primary infections, while Enterococcus spp. such as E. faecalis and E. faecium was highest, followed by Staphylococcus spp. such as S. aureus from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Pseudomonas aeruginosa in this order, and from surgical site infection, E. coli and R aeruginosa were most predominantly isolated, followed by E. cloacae and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rates of Parvimonas micra, Eggerthella lenta, Streptococcus constellatus, Gemella morbillorum, and Collinsella aerofaciens were the highest from primary infections, and the isolation rate from surgical site infection was generally low. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by, Bacteroides fragilis and Bacteroides ovatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides thetaiotaomnicron, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant S. aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents - Special references to bacteria isolated between April 2011 and March 2012].

Bacteria isolated from surgical infections during the period from April 2011 to March 2012 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 785 strains including 31 strains of Candida spp. were isolated from 204 (78.8%) of 259 patients with surgical infections. Five hundred and twenty three strains were isolated from primary infections, and 231 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp. and Staphylococcus spp., in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa, K. pneumoniae, and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Collinsella aerofaciens, Lactobacillus acidophilus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated, followed by P micra and L. acidophilus, in this order. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroidesfragilis was the highest from primary infections, followed by Bilophila wadsworthia, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides vulgatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides caccae, B. thetaiotaomicron, Bacteroides ovatus and B. wadsworthia, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant Staphylococcus aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed. We should carefully follow up B. wadsworthia which was resistant to various antimicrobial agents, and also Bacteroides spp. which was resistant to many ß-lactams.

Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer.

BACKGROUND: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. METHODS/DESIGN: The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients' clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. DISCUSSION: A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the "personalized therapy" in adjuvant chemotherapy for colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013.

Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study.

BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I−III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I−III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10−4.55) p = 0.0269) of the patient's gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.

Laparoscopic hepatectomy: a systematic review, meta-analysis, and power analysis.

PURPOSE: A previous meta-analysis study demonstrated that bleeding and the duration of the hospital stay following laparoscopic hepatectomy (Lap) were significantly smaller and shorter, respectively, than for patients undergoing an open approach (Op). The aim of the present study was to re-evaluate perioperative variables and adverse outcomes in patients undergoing Lap versus (vs) Op after 2000. METHODS: A PubMed and Ovid Medline search identified clinical studies that compared the outcomes of Lap vs Op patients after 2000. A meta-analysis and power analysis were performed. RESULTS: Operative time was not significantly different between the two approaches (95% confidence interval [CI]: -0.063 to 0.992). Patient bleeding in the Lap group was significantly lower than in the Op group (95% CI: -1.027 to -0.390). Complications with Lap patients were significantly less frequent (95% CI: 0.231-0.642), and the duration of the hospital stay for Lap patients was significantly shorter (95% CI: -0.950 to -0.530) than for Op patients. Only one paper presented 80% power with 0.05 α-errors in all four outcomes, whereas four studies did not have sufficient statistical power. CONCLUSIONS: The clinical benefits of Lap include a smaller incidence of complications and a shorter duration of hospital stay at the current time. Several studies had too few cases to sufficiently evaluate these factors, although other studies were appropriately analyzed.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2009 and March 2010].

Bacteria isolated from surgical infections during the period from April 2009 to March 2010 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 671 strains including 16 strains of Candida spp. were isolated from 174 (79.1%) of 220 patients with surgical infections. Four hundred and eleven strains were isolated from primary infections, and 244 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by Bacteroides fragilis, Bacteroides ovatus and Bacteroides thetaiotaomicron, and from surgical site infection, B. fragilis was most predominantly isolated, followed by B. ovatus, B. wadsworthia and B. thetaiotaomicron, in this order. In this series, we noticed no vancomycin-resistant Gram-positive cocci, nor multidrug-resistant P. aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.