[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.

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.

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.

[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.

An extremely rare case of neuromuscular and vascular hamartoma of the appendix.

BACKGROUND: Neuromuscular and vascular hamartoma is a rare lesion of the small intestine, with only 26 cases reported since its initial description in 1982. No occurrence of hamartoma in the appendix has been reported until now. CASE PRESENTATION: A 60-year-old man had been suffering from longstanding right lower quadrant pain. Abdominal computed tomography showed a slight swelling of the appendix as the possible cause of his pain. Laparoscopic appendectomy with partial resection of the cecum was performed for diagnostic and therapeutic purposes. An 18 × 10-mm lesion located on the tip of the appendix was found in the resected specimen. Pathological examination showed that the lesion was covered with normal mucosa and consisted of adipose tissue, smooth muscle fibers, small vessels, and neural fibers. These findings were consistent with neuromuscular and vascular hamartoma of the appendix. CONCLUSION: This is the first report of neuromuscular and vascular hamartoma arising from the appendix.

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.

A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study.

PURPOSE: The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC. METHODS: Patients received oxaliplatin (100 mg/m2, day 1), capecitabine (1700 mg/m2 per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m2 for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m2, day 1 and, thereafter, 250 mg/m2 every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD). RESULTS: Twelve patients received a median of 7 cycles of therapy (range 2-10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m2. Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases. CONCLUSIONS: The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m2. The observed response rate was promising and warrants further investigation.

Mismatch Repair Protein Deficiency Is a Risk Factor for Aberrant Expression of HLA Class I Molecules: A Putative "Adaptive Immune Escape" Phenomenon.

Accumulating evidence indicates that immune checkpoint inhibition-mediated cancer immunotherapies greatly improve the prognosis of certain types of cancer. This approach is now becoming a standard therapy, joining surgery, radiotherapy, and chemotherapy. Because the costs of antibody drugs are now a socioeconomic burden in many countries, an urgent need in cancer immunotherapy is the identification of relevant biomarkers that can predict therapy efficacy. Recent studies have reported that colorectal adenocarcinoma with hereditary or sporadic deficiency in mismatch repair (MMR) proteins has high antigenicity and that detection of these proteins could be a promising way to estimate clinical response. In this study of 135 patients with colorectal cancer, we used immunohistochemistry to investigate the correlation between deficiency in MMR proteins and expression of human leukocyte antigen (HLA) class I molecules, a prerequisite of cytotoxic T-cell-based immunotherapy. Interestingly, MMR protein deficiency was an independent risk factor for the impaired expression of HLA class I molecules (odds ratio (OR)=10.44, 95% confidence interval (CI)=3.15-34.62, p<0.001), suggesting the existence of a putative entity that we have named "adaptive immune escape". Moreover, our results might provide a potential novel biomarker for the selection of patients who would respond to cancer immunotherapies. At the same time, the results suggest that we have to overcome the impaired expression of HLA class I molecules to further improve the cure rate of cancer immunotherapies.

ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway.

Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive. In this study, we aimed to determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and increased the sphere-forming ability and resistance to a chemotherapeutic reagent. The opposite phenomena were observed by gene knockdown using siRNA. Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and activation of the pathway was cancelled by gene knockdown of galectin-3. The results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.

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.

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.

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.

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.

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.

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.

A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer.

PURPOSE: The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC). METHODS: Patients received oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2 to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD). RESULTS: Twelve patients received a median of 6.5 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m(2). The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively. CONCLUSIONS: XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.

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.

Claudin-4 binder C-CPE 194 enhances effects of anticancer agents on pancreatic cancer cell lines via a MAPK pathway.

The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) modulates the tight junction protein claudin and disrupts the tight junctional barrier. It also can enhance the effectiveness of anticancer agents. However, the detailed mechanisms of the effects of C-CPE remain unclear in both normal and cancerous cells. The C-CPE mutant called C-CPE 194 binds only to claudin-4, but the C-CPE 194 mutant called C-CPE m19 binds not only to claudin-4 but also to claudin-1. In the present study, to investigate the mechanisms of the effects of C-CPE on claudin expression, the tight junctional functions and the cytotoxicity of anticancer agents, human pancreatic cancer cells, and normal human pancreatic duct epithelial cells (HPDEs) were treated with C-CPE 194 and C-CPE m19. In well-differentiated cells of the pancreatic cancer cell line HPAC, C-CPE 194 and C-CPE m19 disrupted both the barrier and fence functions without changes in expression of claudin-1 and -4, together with an increase of MAPK phosphorylation. C-CPE 194, but not C-CPE m19, enhanced the cytotoxicity of the anticancer agents gemcitabine and S-1. In poorly differentiated pancreatic cancer cell line PANC-1, C-CPE 194, but not C-CPE m19, decreased claudin-4 expression and enhanced MAPK activity and the cytotoxicity of the anticancer agents. In normal HPDEs, C-CPE 194 and C-CPE m19 decreased claudin-4 expression and enhanced the MAPK activity, whereas they did not affect the cytotoxicity of the anticancer agents. Our findings suggest that the claudin-4 binder C-CPE 194 enhances effects of anticancer agents on pancreatic cancer cell lines via a MAPK pathway.