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In recent studies, better clinical outcomes for patients with left-sided colon cancer (CC) compared with right-sided CC have been reported; however, in such investigations, the chemotherapy regimens included molecular-targeting agents. To the best of our knowledge, the impact of primary tumor location as a predictive factor in patients suffering from CC treated with cytotoxic anticancer agents alone has not been investigated. The aim of the present study was to determine the impact of the primary tumor location as a predictive factor of patients undergoing the following cytotoxic anticancer agent regimens: Leucovorin and fluorouracil + oxaliplatin (FOLFOX) or Leucovorin and fluorouracil + irinotecan (FOLFIRI), using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Between March 2008 and April 2017, tumor specimens were obtained from 133 patients suffering from colorectal cancer (CRC) who had not received preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined in FOLFOX and FOLFIRI regimens. The associations between tumor location and IR values for each condition were evaluated. In the present study, the prognosis of patients receiving palliative chemotherapy as well as treatment with molecularly-targeted agents was also investigated. There were no significant differences in the IRs (%) of the two regimens using CD-DST for right-sided tumors compared with left-sided tumors, including or excluding the rectum. The median survival times of patients with right CC and left CC who had received palliative chemotherapy and treatment with molecularly-targeted agents were 960 and 1,348 days, respectively. Primary tumor location did not represent a predictive factor for the efficacy of treatment with cytotoxic anticancer agent regimens using CD-DST. However, patients suffering from left-sided CC were revealed to exhibit better clinical outcomes compared with patients suffering from right-sided CC when molecularly-targeted agent regimens were administered. Therefore, the results of the present study suggested that molecularly-targeted agents rather than cytotoxic anticancer agents may result in improved clinical outcomes for patients with CRC suffering from left-sided tumors.

5-Fluorouracil (5-FU) dosing has traditionally been based on the body surface area (BSA) in colorectal cancer treatment. However, there is accumulating evidence that dosing based on BSA may be of limited use. The purpose of the present study was to evaluate the changes in 5-FU plasma levels and tumor response as well as the severity of adverse events in patients with cancer treated with 5-FU combined chemotherapy. The dosing amount of 5-FU was determined based on the BSA. Blood samples were collected, and 5-FU plasma levels in 15 patients with colorectal cancer were measured three times (0, 22 and 40 h before and after the start of infusion) during constant-infusion of 5-FU for 46 h by an immunoassay. 5-FU plasma levels were significantly higher at 22 and 40 h compared with at 0 h (P

We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration-time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.

For sp2 or sp3 carbon material growth, it is important to investigate the precursors or intermediates just before growth. In this study, the density of ethylene (C2 H4 ) outside the plasma discharge space and just before reaching the carbon nanotube (CNT) growth region is investigated by vacuum ultraviolet absorption spectroscopy for plasma discharge in an antenna-type remote plasma chemical vapor deposition with a CH4 /H2 system, with which the growth of very long (≈0.5 cm) CNT forests is achieved. Single-wall CNT forests have the potential for application as electrodes in battery cells, vertical wiring for high current applications, and thermal interface materials. It is observed that the plasma discharge decomposes the CH4 source gas and forms C2 Hx species, which reversibly reform to C2 H4 in the plasma-off state. In addition, the density of the formed C2 H4 has a strong correlation to the CNT growth rate. Therefore, the C2 H4 density is a good indicator of the density of C2 Hx species for CNT growth in the CH4 /H2 plasma system.

The effect of titanium (Ti) added to the top layer of an aluminum (Al)/iron (Fe)/Al (bottom) sandwich catalytic substrate was studied. The Ti caused a significant lengthening in the single-wall carbon nanotube forest produced by chemical vapor deposition (CVD). In general, particles of iron oxide on the Al/Fe/Al catalytic substrate are formed by exposure to the atmosphere during deposition process of the substrate. The particles of iron oxide are metalized during pretreatment under a reductive gas before the growth of the nanotubes with nano-sized dispersion stabilized. On this process, the metallization and the stabilization of nano-sized iron oxide particles occur on the basis of the oxygen affinity in the top aluminum oxide layer, with the ionization tendency Al > Fe. It is thought that the addition of Ti increases the oxygen affinity of the catalytic substrate, since Ti has a stronger ionization tendency than Al. After optimizing the quantity of Ti added to the top layer, we successfully fabricated a millimeter-long, small-diameter, single-wall carbon nanotube forest.

Serum iron levels have been reported to increase following the administration of various anticancer drugs. An increase in serum iron levels during therapy with leucovorin and fluorouracil plus oxaliplatin (FOLFOX) or leucovorin and fluorouracil plus irinotecan (FOLFIRI) was also observed. The aim of this study was to investigate the correlation between serum iron levels and prognosis in advanced colorectal cancer (CRC) patients treated with FOLFOX/FOLFIRI ± molecularly-targeted drugs. Serum iron levels were measured prior to and at 48 h after treatment with FOLFOX/FOLFIRI ± molecularly-targeted drugs in 72 advanced CRC patients, all of whom succumbed to the disease between December, 2005 and February, 2012. No patients received radiotherapy. Taking the median rate of increase in serum iron levels as the cut-off value in each therapy, the patients were divided into cohort I (increase rate greater than the cut-off value in at least one therapy) or cohort II (increase rate less than the cut-off value in all therapies). The χ2 test and the t-test were used to compare patient characteristics between the two cohorts. Prognosis was evaluated between the two cohorts using the Kaplan-Meier method, the log-rank test and the Cox proportional hazards regression analysis. No significant bias in patient characteristics (including the frequency of chemotherapy or number of patients treated with molecularly-targeted drugs) was observed between the two cohorts. Serum iron levels were transiently elevated following treatment (P

Colorectal cancer is a prevalent malignancy worldwide, and investigations are required to elucidate the underlying carcinogenic mechanisms. Amongst these mechanisms, de novo carcinogenesis and the adenoma to carcinoma sequence, are the most understood. Metastasis of colorectal cancer to the liver often results in fatality, therefore, it is important for any associated risk factors to be identified. Regarding the treatment of the disease, it is important to manage not only the primary colorectal tumor, but also the liver metastases. Previously, through gene variation analysis, chromosomal loss has been indicated to serve an important role in liver metastasis. Such analysis may aid in the prediction of liver metastasis risk, alongside individual responses to treatment, thus improving the management of colorectal cancer. In the present study, we aimed to clarify a cause of the liver metastasis of colorectal cancer using comparative genomic hybridization analysis. A total of 116 frozen samples were analyzed from patients with advanced colorectal cancer that underwent surgery from 2004 to 2011. The present study analyzed mutations within tumor suppressor genes non-metastatic gene 23 (NM23), deleted in colorectal carcinoma (DCC) and deleted in pancreatic carcinoma, locus 4 (DPC4), which are located on chromosomes 17 and 18 and have all been reported to affect liver metastasis of colorectal cancer. The association between chromosomal abnormalities (duplication and deletion) and liver metastasis of colorectal cancer was evaluated using comparative genomic hybridization. Cluster analysis indicated that the group of patients lacking the long arm of chromosome 17 demonstrated the highest rate of liver metastasis. No significant association was observed between the frequency of liver metastases for synchronous and heterochronous colorectal cancer cases and gene variation (P=0.206). However, when these liver metastasis cases were divided into the synchronous and heterochronous types, the ratio of each was significantly different between gene variation groups, classified by the existence of the 17q deletion (P=0.023). These results indicate that the deletion of 17q may act as a predictive marker of liver metastasis in postoperative states.

A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6). Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m2 + leucovorin at 200 mg/m2 + fluorouracil as a 400 mg/m2 bolus followed by infusion of 2400 mg/m2 over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician. mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3–4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable. The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.

Single-walled carbon nanotube (SWNT) forest synthesis using antenna-type remote plasma chemical vapor deposition (ARPCVD) is presented. A series of synthesis using carbon monoxide gas as carbon feedstock reveals that the remote conditions, in other words, distance between an antenna and a substrate affects the quality of nanotube significantly. That is, far distance geometry on ARPCVD creates high-quality SWNTs. It motivates us to use same methodology for the synthesis using CH4/H2 previously proven to make long SWNT forests. Finally, along the methodology, we achieve to make SWNT forest with high-quality and small diameter successfully. This study offers an important suggestion to embody SWNT forests with both length and quality using remote plasma CVD.

The effectiveness of cetuximab (Cmab) against KRAS p.G13D mutant-type tumors has been reported. In this study, we report a case of metastatic ascending colon cancer harboring a KRAS p.G13D mutation in a 65-year-old female. Considering the absence of symptoms and the post-operative risk of respiratory system complications due to multiple lung metastases, particularly at the entrance to the left main bronchus, anticancer drug therapy was selected as first-line therapy. With informed consent, FOLFOX4 [folinic acid (FOL), fluorouracil (F) plus oxaliplatin (OX)] + Cmab therapy was administered as preoperative chemotherapy. A good preoperative response was obtained to the chemotherapy, with a metastatic lesion disappearing from the entrance to the left main bronchus. Subsequent resection was performed successfully with no post-operative complications. Although a histopathological examination of the resected tissue specimen revealed residual cancer cells, it also showed the marked efficacy of the chemotherapy regimen used. In this study, we describe a case of metastatic ascending colon cancer harboring a KRAS p.G13D mutation in which the patient responded well to first-line therapy with FOLFOX4 + Cmab.

Understanding the electrical contact properties of carbon nanotube (CNT) ends is important to use the high conductance of CNTs in the CNT on-axis direction in applications such as through-silicon via structures. In this study, we experimentally evaluated the contact resistivity between single-/multi-walled CNT ends and a metal nanoprobe using conductive atomic force microscopy (C-AFM). To validate the measured end contact resistivity, we compared our experimentally determined value with that obtained from numerical calculations and reported values for side contact resistivity. The contact resistivity normalized by the length of the CNT ends was 0.6–2.4 × 106 Ω nm for single-walled CNTs. This range is 1–2 orders of magnitude higher than that determined theoretically. The contact resistivity of a single-walled CNT end with metal normalized by the contact area was 2–3 orders of magnitude lower than that reported for the resistivity of a CNT sidewall/metal contact. For multi-walled CNTs, the measured contact resistivity was one order of magnitude higher than that of a CNT forest grown by remote plasma-enhanced chemical vapor deposition, whereas the contact resistivity of a top metal electrode was similar to that obtained for a single-walled CNT forest.

FOLFOX4 and FOLFIRI are effective regimens for the treatment of advanced colorectal cancer, and their use together with molecular targeting drugs has recently become more common. In the present study, we evaluated the changes in the serum iron levels of patients undergoing FOLFOX4 or FOLFIRI therapy alone or in combination with bevacizumab (BV). The serum iron level was increased 48 h after therapy and was restored to baseline 2 weeks afterwards in colorectal cancer patients who received FOLFOX4 or FOLFIRI alone or in combination with BV. This transient increase in serum iron was observed repeatedly during chemotherapy. The serum iron level was 71.66±28.96 μg/dl (mean ± standard deviation) before treatment and significantly increased to 186.82±83.17 μg/dl (p

The purpose of this study was to determine the effect of the addition of oxaliplatin (l-OHP) or irinotecan (SN-38) to 5-fluorouracil (5-FU) using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to establish whether leucovorin plus 5-FU should be administered in combination with l-OHP (FOLFOX) or SN-38 (FOLFIRI) in individualized first-line chemotherapy for the treatment of advanced colorectal cancer (CRC). Specimens of primary tumors were obtained from 24 CRC patients who had received no preoperative chemotherapy. CD-DST was performed, and the inhibition rate (IR) was obtained under multiple incubation conditions. The effects of addition of l-OHP or SN-38 were evaluated for the same area under the concentration curve (AUC) of 5-FU based on linear regression analysis. Approximate expression and correlation coefficients (5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=72 and 5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=144) were y=0.94x+8.53 (R(2)=0.95, p

We have evaluated the 5-fluorouracil sensitivity of cancer cells from colorectal cancer patients using the collagen gel droplet embedded drug sensitivity test under multiple drug concentrations and contact durations. After converting drug concentration and contact time to the area under the curve (AUC) and plotting against the growth inhibition rate, the correlation between AUC and the growth inhibition rates was approximated to the logarithmic regression curve. In this study, to further validate the reliability of the regression curve, the growth inhibition rate was calculated from the regression curve and the actual growth inhibition rate was compared at AUC of 48 mug h/ml. No significant difference was observed in the growth inhibition rates between the two groups by paired t-test (P=0.590). A strong positive correlation was found between the two groups by regression analysis (y=0.7555x+10.514, R=0.8236). This result strongly suggests that in-vitro antitumor effect of 5-fluorouracil depends on the AUC in colorectal cancer and the AUC-inhibition rate curve is reliable. We can obtain the inhibition rate from AUC and vice versa using the AUC-inhibition rate curve. We can also calculate the individualized AUCIR50, AUC value that gives 50% growth inhibition, using the AUC-inhibition rate curve. This could be useful to establish individualized chemotherapy using the collagen gel droplet embedded drug sensitivity test.

INTRODUCTION: We previously investigated the effects of sodium ferrous citrate (SFC) on neutrophils in vitro, and revealed that SFC inhibited neutrophil functions such as superoxide production and chemotaxis. Salazosulphapyridine (SASP) and predonizolone (PSL) are widely used for treatment of ulcerative colitis (UC). In this study, we evaluated the actions of SASP or PSL on the functions of neutrophils. Moreover, we evaluated the combined effects of SASP or PSL and SFC on neutrophil functions.METHODS: Neutrophils were incubated with SASP or PSL in the absence or presence of SFC. For determination of superoxide production, neutrophils were further stimulated with phorbol myristate acetate (PMA), complement-opsonized zymosan (OPZ) or N-formyl-menthionyl-leucyl-phenylalamine (fMLP). The superoxide production was measured on the basis of superoxide dismutase-inhibitable cytochrome c. Neutrophil migration was measured by a Boyden chamber assay using zymosan-activated serum (C5a) as a chemotactic factor. To examine the expression of CD11b and CD62L, neutrophils were stimulated with fMLP, and then incubated with phycoerythrin-labeled anti-CD11b and FITC-labeled anti-CD62L monoclonal antibodies, and the expression of CD11b and CD62L were analyzed by flow cytometry.RESULTS: SASP dose-dependently inhibited the superoxide production induced by all stimuli examined, whereas, PSL did not affect the superoxide production. SASP and PSL inhibited chemotaxis toward C5a in a dose-dependent fashion. Furthermore, SASP and PSL inhibited the fMLP-induced up-regulation of CD11b and down-regulation of CD62L. Interestingly, the combinats on the SASP or PSL and SFC exerted the strong inhibitory actions on the superoxide production and neutrophil migration compared with SASP and PSL alone.CONCLUSIONS: The present observations suggest that the combined administration of SASP or PSL with SFC may have a potential to reduce mucosal injury by suppressing neutrophil functions in UC.

BACKGROUND AND PURPOSE: The inflammatory bowel diseases(IBD) such as ulcerative colitis(UC) are intractable diseases of unknown origin. The mucosal injury of UC is presumed to be partly caused by reactive oxygen species(ROS) produced by neutrophils. Chronic inflammation of UC results in chronic anemia, to which iron is given. In this study, to evaluate the effect of sodium ferrous citrate(SFC) on neutrophil functions, we measured superoxide generation and migration of neutrophils treated with SFC in vitro.METHODS: Superoxide generation induced by phorbol myristate acetate(PMA), opsonized zymosan(OPZ) and N-formyl-menthionyl-leucyl-phenylalanine(fMLP) was determined based on the superoxide dismutaseinhibitable cytochrome c reduction. To further clarify the inhibitory mechanism of SFC, the membrane fraction was isolated and NADPH-dependent superoxide production was measured. Moreover, neutrophil migration was evaluated with a Boyden chamber assay using zymosan-activated serum (C5a) as a chemoattractant.RESULTS: SFC dose-dependently inhibited the superoxide production induced by all the stimuli examined. Similarly, SFC-treatment inhibited the activity of NADPH oxidase in the membrane fraction of neutrophils. In addition, SFC suppressed chemotaxis toward zymosan-activated serum in a dose-dependent fashion.CONCLUSIONS: In this study, we revealed that SFC could suppress neutrophil functions such as superoxide generation (NADPH oxidase activity) and migration. During episodes of IBD, stimulated neutrophils are accumulated in inflamed mucosa via the migration through vascular endothelium, where they release ROS such as superoxide. Thus, the present observations suggest that SFC may have a potential to reduce mucosal injury by suppressing migration and ROS generation by neutrophils in UC.

目的:抗ヒトOrotate Phosphoribosyl Transferase(OPRT)抗体を用いたOPRT免疫組織化学染色とOPRT酵素活性,臨床病理学的背景因子およびOPRT翻訳領域にあるsingle nucleotide polymorphisms(SNPs)との関連性について検討した.対象:2003年12月から2004年7月までに当科で外科的切除された大腸癌35例とした.成績:OPRT活性は癌部が正常部に比べて有意に高値を示した(p

INTRODUCTION: Mesalazine(Pentasa) is widely used for ulcerative colitis(UC). However, the anti-inflammatory actions of Mesalazine are not fully understood. In this study, we evaluated the actions of Mesalazine in vitro on the functions of neutrophil, a major inflammatory cell. Furthermore, we evaluated the combined effects of Mesalazine and sodium ferrous citrate(SFC) on neutrophil functions, since SFC is clinically administered to UC patients together with Mesalazine for treatment of chronic anemia associated with UC. METHODS: Superoxide production by neutrophils was measured on the basis of superoxide dismutaseinhibitable cytochrome c reduction. Preincubated neutrophils were stimulated with fMLP, PMA or complement-opsonized zymosan particles. Cytochrome c reduction was calculated by the absorbance difference at 550 nm. Neutrophil migration was measured by a Boyden chamber assay with using zymosan-activated serum (C5a) as a chemotactic factor. Neutrophils were preincubated in the presence of 0.01-0.5mM Mesalazine and then incubated with fMLP. The cells were further incubated with phycoerythrin (PE)-labeled anti-CD11b monoclonal antibody, and the expression of CD11b was analyzed by flow cytometry. Neutrophils were preincubated with 5μg/ml SFC and 0.01-0.1mM Mesalazine, and superoxide generation and migration were measured.RESULTS: Mesalazine dose-dependently inhibited the superoxide production induced by PMA and fMLP at > 0.05 mM. Furthermore, Mesalazine inhibited chemotaxis toward zymosan-activated serum in a dosedependent fashion. Moreover, 0.5mM Mesalazine inhibited the fMLP-induced up-regulation of CD11b expression. Interestingly, Mesalazine combined with SFC inhibited the superoxide generation and migration by neutrophils, compared with Mesalazine alone. Thus, the present observations suggest that a combined administration of Mesalazine and SFC may have a potential to reduce mucosal injury by suppressing neutrophil functions (migration, ROS generation and expression of adhesion molecule) in UC.

Orotate phosphoribosyl transferase (OPRT) is the main enzyme that involves in phosphoribosylation of 5-fluorouracil (5-FU), an essential step that leads to tumor growth inhibition. In our study, the prognostic relevance of OPRT, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in resectable colorectal cancer (CRC) patients treated by oral 5-FU were compared to further clarify the prognostic value of OPRT. Tumor tissue was collected from 90 CRC patients and the patients were followed for 5.2 years (Median). TS, DPD and OPRT activities in the extract of tumor tissue were determined enzymatically. The cut-off value of OPRT (0.147 nmol/(min mg), TS (0.044 pmol/mg) and DPD (72.10 pmol/(min mg) were determined by maximal chi(2) method. Among these 5-FU metabolic enzymes, only high OPRT group demonstrated significantly better disease-free survival (DFS) (p = 0.0152) and better overall survival (p = 0.0078). In Cox regression analysis, node status (p < 0.0005) and OPRT (p = 0.044) were significant factors for DFS. OPRT activity in tumor tissue was a predictor of prognosis in resectable CRC patients treated by oral 5-FU-based adjuvant chemotherapy, and was useful to pick-up high risk patients independent from known prognosis factors.

AIMS To elucidate the mechanism of marked stromal fibrosis in strictured colorectal carcinomas (SC) that cause complete ileus. METHODS AND RESULTS Sixteen cases of SC and 29 cases of non-strictured colorectal carcinoma (NSC) were studied. These carcinomas showed similar clinicopathological features except for bowel stricture. The stricture index (SI) showing the degree of bowel stricture was 59.8 +/- 12.1% in SC versus 20.8 +/- 24.6% in NSC (P < 0.001). The fibrosis index (FI), defined to reflect the extent of stromal fibrosis, was 56.3 +/- 8.8% in SC versus 21.9 +/- 10.6% in NSC (P < 0.001). COX-2+ myofibroblasts were detected in 13 cases (81.3%) in SC versus eight cases (27.6%) in NSC (P < 0.01). The COX-2+ myofibroblast density was 276.7 +/- 181.1 cells/mm(2) in SC versus 26.6 +/- 52.7 cells/mm(2) in NSC (P < 0.001). When all cases were divided into two groups with and without COX-2+ myofibroblasts, the SI was 48.8 +/- 19.1% in those with COX-2+ myofibroblasts versus 24.8 +/- 29.3% in those with COX-2- myofibroblasts (P < 0.001). CONCLUSION COX-2+ myofibroblasts may play an important role in extensive bowel stricture in colorectal carcinomas.

We encountered a patient with acute gastric mucosal injury caused by ingestion of a chlorinated fungicide. Approximately 15 h after the episode of ingestion, endoscopic views were compatible with the acute gastric mucosal lesion of severe degree throughout the stomach. At that time, endoscopic biopsy showed congestion in the epithelial layer of the mucosa, along with lymphocytic infiltration that had likely existed from the onset of the condition. On the third day, the mucosal lesion looked more serious with peculiar hemorrhagic folds, and biopsy revealed exfoliation of the epithelial surface and neutrophilic infiltration in the stroma of the epithelial layer. On the seventh day, endoscopic images showed persistence of the lesion, but biopsy demonstrated the development of regenerating epithelium along with a marked reduction in infiltration of neutrophils and edema in the stroma.

There are few reports about postoperative outcome of penoplasty (PP). We present the results of mid- to long-term follow-up of PP performed for congenital megaprepuce (CMP). Data from 65 CMP cases treated by PP performed by a single surgeon from 2000 to 2014 were collected prospectively. All cases were treated using the technique reported by Cuckow (Pediatric surgery. Springer, Berlin, pp 543–554, 2006). Mean age at PP was 5.9 years (range 0.4–13.9). All cases presented as infants and some 12 cases (18.5 %) had PP when 10 or more years old. There were no intra- and postoperative complications. Mean duration of follow-up was 3.6 years (range 0.1–17.5). Duration of follow-up was 4 years or less in 48 (73.8 %), 5–9 years in 13 (20.0 %), and 10 or more years in 4 (6.2 %). While postoperative penile cosmesis was good in 63/65 (96.9 %) cases without scrotal deformity, 2/65 (3.1 %) had redundant penile skin excised upon the recommendation of the treating surgeon even though the patients and parents were unconcerned. Mid- to long-term follow-up of our PP cases shows that outcome is cosmetically acceptable and stable.

In patients with advanced colorectal cancer (CRC), a transient significant increase of serum iron is observed during chemotherapy with leucovorin and fluorouracil plus oxaliplatin (FOLFOX) or leucovorin and fluorouracil plus irinotecan (FOLFIRI). Serum iron may be a useful and convenient predictor of the response to chemotherapy; however, the mechanism underlying its increase has not been fully elucidated. Accordingly, the mechanism underlying the elevation of serum iron during chemotherapy was investigated in 20 patients with advanced CRC who were treated between September, 2012 and July, 2013. The levels of iron, ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), hepcidin-25, interleukin (IL)-6 and soluble transferrin receptor (sTfR) were measured before and 48 h after chemotherapy. The serum levels of iron and hepcidin-25 were found to be significantly increased after chemotherapy (P

As nasal tube insertion is minimally effective for the management of ileus caused by cancer in the left colon, emergency operations are often necessary for such cases. Recently, a new preoperative colonoscopic procedure, designed with the aim of avoiding emergency operations, was invented. This method, termed colonoscopic retrograde bowel drainage (decompression) (CRBD), can be described as follows : After confirming the lesion colonoscopically, the drainage (decompression) tube is inserted beyond the obstructive lesion along a guide wire or dilator. This method was applied in 17 patients (11 males and 6 females), with an average age 66.8 years (range 44-88 years), one with descending colon cancer, 9 sigmoid colon cancer, 5 rectal cancer and 2 Schnitzler metastasis. The interval from CRBD to surgery was 11.5 days. During this period, preoperative examinations and complete preparation of the colon could be performed. This allowed surgery to be performed electively with the patient in satisfactory condition. The most important benefit of CRBD is that a forward view of obstructive lesions can be obtained with a colonoscope. This direct view procedure reduces the risk of complications. Thus, in properly selected cases, CRBD may allow emergency surgery to be avoided. We conclude that CRBD should be attempted as the initial treatment, before proceeding to surgery.

A case of gastric cancer with sarcoid reaction in the surrounding lymph nodes is reported. The infiltration of T cell was demonstrated in the lymph nodes with sarcoid reaction, tissue of the gastric cancer, and the surrounding tissue of it. Additionally activated lymphocytes, mainly T cells increased in peripheral blood. It appeared that T cells were activated. And a possibility of the tumor immunization through sarcoid reaction is indicated.

Recently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally administered to mice 24h after the administration of menthol for 2 days, and the plasma warfarin concentration was measured. In the menthol administration group, the area under the blood concentration time curve of warfarin was decreased by approximately 25%, while total clearance was increased to 1.3-fold compared to the control group. The hepatic cytochrome P450 (CYP) 2C protein expression level in the menthol administration group was significantly increased compared to that in the control group. An increase in the nuclear translocation of constitutive androstane receptor (CAR) was also observed. The addition of menthol to human hepatic cells, HepaRG cells, caused an increase in the mRNA expression level of CYP2C9. The results of this study revealed that menthol causes an increase in CYP2C expression levels in the liver, which leads to an enhancement of warfarin metabolism, resulting in a decreased anticoagulant effect of warfarin. It was also suggested that menthol acted directly on the liver and increased the expression level of CYP2C by enhancing the nuclear translocation of CAR.

左側大腸における癌性イレウスに対して保存的治療によりイレウスを解除したのち一期的手術が可能となれば理想的である.本論文では大腸内視鏡を用い経肛門的に左側大腸閉塞部位口側へ減圧チューブを留置する腸管減圧術を試みた11例について検討した.減圧チューブの留置は11例中9例に成功した.不成功2例は減圧術試行中穿孔を起こした症例と5型のS状結腸癌でガイドワイヤーの挿入ができなかった症例である.また減圧チューブ留置にもかかわらず十分な減圧ができず準緊急手術となった症例が1例認められた.減圧チューブ挿入の際の要点は, 閉塞部位が大腸内視鏡にて正面視できることである.閉塞部位が正面視できない場合や, 閉塞部位の癌が全周性でない場合のガイドワイヤー挿入の際には細心の注意が必要であると思われた.本法は緊急手術回避においても有用であり, まず試みるべき方法の一つであると思われた.

It is rare that adenomyomatous change occurs in the stomach. We experienced a case of submucosal tumor of the cardiac part of the stomach presenting adenomyomatous change in the greater part of the lesion. An 82-year-old man was seen at the hospital because of difficulty in swallowing which started in around August, 1993. Upper gastrointestinal endoscopy revealed a submucosal tumor at the cardiac part of the stomach and the patient was admitted on December 7, 1993. After admission polypectomy was tried, but it was impossible because the tumor was too large. The patient appeared to be a candidate for operation. Under left thoracolaparotomy the lower part of the esophagus and cardiac part were excised. After the operation the patient experienced poor appetite for a temporal regurgitation, but thereafter his clinical course was uneventful. He was dischaged from the hospital on November 22, 1993. Histopathologically the excised specimen revealed a rare adenomyomatous proliferation in the submucosal layer. Specific immunostaining disclosed diffused coexistence of deeply stained myofiber and glandular tissue.

The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) regimens with or without molecularly-targeted drugs are widely used as first-line chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether FOLFOX or FOLFIRI is administered first is not significant, however, it is essential that full administration of the targeted dosages of all 3 drugs, 5-FU, l-OHP and SN-38, is achieved. However, this is not always possible and second-line chemotherapy must be abandoned in certain cases. Where possible, the most effective regimen should be selected as the first line of treatment. The aim of this study was to determine whether first-line chemotherapy may be individualized using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Specimens of primary tumors were obtained from 43 CRC patients who had received no preoperative chemotherapy. Informed consent to measure drug sensitivity was obtained from all patients. The CD-DST allows evaluation of drug sensitivity using isolated, 3-dimensionally cultured tumor cells in a small collagen gel droplet. The CD-DST was performed and the growth inhibition rate (IR) was obtained under incubation conditions (5-FU with l-OHP at 6.0 and 3.0 μg/ml, or 5-FU with SN-38 at 6.0 and 0.2 μg/ml, respectively, for 24 h). The cumulative distributions of the growth IRs under each condition were evaluated based on the evidence that the clinical response rates to FOLFOX and FOLFIRI were almost the same. Individualization of first-line treatment was possible in all patients, with FOLFOX and FOLFIRI showing higher efficacy in 26 and 15 patients, respectively, and equal efficacy in 2 cases. This method has the potential to facilitate the establishment of individualized first-line chemotherapy for CRC and improve the prognosis in such patients.

We have previously reported the 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer (CRC) patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Moreover, the area under the concentration curve (AUC) and growth inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was approximated to the logarithmic curve. In the present study, we used the AUC-IR curve to calculate the individualized AUCIR50, the AUC value that imparts 50% growth inhibition. Individual AUCIR50 was calculated in CRC patients, and its distribution was evaluated. The cumulative distribution of individual AUCIR50 was regressed over two lines (logarithmic scale). Among the 45 resectable CRC patients, those who achieved more than the individual AUCIR50 during post-operative 5-FU-based chemotherapy demonstrated a trend towards better disease-free survival compared to those who did not achieve AUCIR50. Of the Dukes' D patients (n=10), those who achieved more than twice the individual AUCIR50 during post-operative 5-FU-based chemotherapy demonstrated significantly better survival rates (p=0.05) than those who did not. In this study, the distribution of the individual AUCIR50 suggested that approximately 6% of patients demonstrated very low 5-FU sensitivity. Therefore, the individual AUCIR50 was useful in classifying good, intermediate and poor 5-FU response. Achievement of the individual AUCIR50 may be a prerequisite for individualized 5-FU-based adjuvant chemotherapy. As well, the early achievement of twice the individual AUCIR50 may indicate an improved prognosis in Dukes' D patients. The individual AUCIR50 using CD-DST is useful in determining the individualized chemotherapy of CRC patients, thus CD-DST has the potential to facilitate the establishment of individualized chemotherapy for CRC.