Prevalence and molecular characteristics of DNA mismatch repair protein-deficient sebaceous neoplasms and keratoacanthomas in a Japanese hospital-based population.

BACKGROUND: Muir-Torre syndrome (MTS) is currently considered as a clinical variant of Lynch syndrome (LS). The clinical significance of the screening of patients with MTS-associated cutaneous tumors for the identification of LS has not yet been established. In addition, the prevalence and molecular characteristics of mismatch repair (MMR) protein deficiency in such tumors has scarcely been investigated in the Japanese population. METHODS: Immunohistochemistry (IHC) for MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from 16 sebaceous neoplasms (SNs) resected from 13 patients and 32 keratoacanthomas (KAs) resected from 31 patients at our institution between January 2005 and March 2014. Tumors showing MMR protein loss were further subjected to genetic analysis for detecting the presence of germline and/or somatic alterations of the MMR genes to identify the precise molecular mechanisms underlying the protein loss. RESULTS: Among the 16 SNs resected from 13 patients, eight SNs resected from five patients (38.5%) showed loss of expression of MMR proteins (MLH1/PMS2 loss, one patient; MSH2/MSH6 loss, four patients). Genetic analyses showed a pathogenic germline MSH2 mutation in one patient, somatic hypermethylation of the MLH1 promoter region in one patient, and somatic alterations of MSH2 without detectable germline mutations of MSH2 in three patients. None of the KAs examined in the study showed any loss of MMR protein expression. CONCLUSIONS: The efficacy of routine screening of cutaneous neoplasms known to be associated with MTS by IHC for MMR proteins to identify LS may be fairly limited. MMR protein loss as determined by IHC in SNs is not always diagnostic of LS, and appears, in most cases, to be a result of somatic inactivation of the MMR genes.

Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

PURPOSE: To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. METHODS: Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. RESULTS: A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). CONCLUSION: The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

Polymorphisms of GSTP1, ERCC2 and TS-3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients.

The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5-fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA-repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or invader techniques. These included a 28-bp tandem repeat in the 5'-untranslated region (UTR) and 6-bp deletions in the 3'-UTR of thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR; Ala677Val), glutathione S-transferase π (GSTP1; IIe105Val), GST θ1 (GSTT1; deletion) and GST µ1 (GSTM1; deletion) and the two DNA-repair genes, excision repair cross-complementing-1 (ERCC1; Asp118Asn) and ERCC2 (Lys751Gln). The correlation between these polymorphisms and the clinical outcome, including drug response, progression-free survival (PFS), overall survival (OS) and the incidence of peripheral neuropathy, were evaluated. Patients with the GSTP1-105 A/A genotype had poor responses to mFOLFOX6 treatment compared with those with the GSTP1-105 A/G and G/G genotypes (P=0.01). The median PFS of patients with the ERCC2-751 A/A genotype tended to be longer than that of patients with the ERCC2-751 A/C genotype (P=0.05). Patients with the TS-3'-UTR -6/-6 genotype had a significantly longer OS compared with patients with other genotypes (P=0.003). A statistically significant association between the incidence of peripheral neuropathy higher than grade 2 and the GSTP1-105 (P=0.03) and GSTM1 genotypes (P=0.02) was identified by multivariate logistic regression analyses. Results demonstrated that polymorphisms in GSTP1-105, ERCC2-751 and the 3'-UTR of TS may be a statistically significant predictors of clinical outcome. GSTP1-105 and GSTM1 genotypes may be useful markers of severe peripheral neuropathy in MCRC patients treated with 5-FU/oxaliplatin as first-line chemotherapy.

Comparison of three different minimally invasive procedures of distal gastrectomy for Nonoverweight patients with T1N0-1 gastric cancer.

Laparoscopic-assisted distal gastrectomy has recently come to be a standard procedure for the treatment of early gastric cancer (1 - 5) in select patients. The minimal invasiveness associated with laparoscopic procedures for the resection of gastrointestinal cancer has been repeatedly explained in part by the short incision that is required. (6 - 11) We used two different approaches to perform distal gastrectomies for the resection of gastric cancer as minimally invasive alternatives to a standard laparoscopic approach prior to our surgical team's complete mastery of the skills required for laparoscopic oncological surgery for gastric cancer. (9 , 12) If the minimal invasiveness associated with laparoscopic-assisted gastrectomy can be explained by the small incision, a gastrectomy via a small incision without the use of a pneumoperitoneum may provide a similar outcome in patients. However, to our knowledge, such a comparison has not been previously made. We compared the minimal invasiveness of three different approaches (minilaparotomy, minilaparotomy approach with laparoscopic assistance, and standard laparoscopic-assisted approach) to performing a distal gastrectomy for T1N0-1 gastric cancer in nonoverweight patients (body mass index, ≤ 25 kg/m(2)) performed within a limited study period.

[Theoretical background of our original single-incision laparoscopic-assisted surgery technique for colon cancer via a periumbilical approach].

We assessed the theoretical background of our original single-incision laparoscopic-assisted surgery( SILS) technique involving a periumbilical approach. The subjects included 10 cases who underwent periumbilical SILS colectomy and had their surgical wounds photographed before and after skin incision between September 2009 and October 2010. Using an image analyzer, we estimated the theoretical oval area after a 3/4-circumferential periumbilical skin incision, the actual oval area after placement of the wound retractor, and the length of the skin incision. The mean oval area after the placement of the wound retractor was 2.9 times (range: 1.6-5.0 times) larger than that of the theoretical area. The square of the length of the skin incision positively correlated with the actual oval area created by placing the wound retractor( p=0.04, r=0.67). There were 5 patients, whose actual oval area was ≤700 mm2, and thus required additional radial skin incision( s)( 1 in 3 cases, 2 in 1 case and 3 in 1 case). When performing our original SILS via the periumbilical approach, the area of the actual surgical window can be predicted by measuring the distance from the center of the umbilicus to its edge.

[Effect of chemotherapy in primary tumor of MSI-H colon cancer aged 50 years or younger].

Microsatellite instability( MSI) in colorectal carcinoma is reportedly associated with resistance to 5-fluorouracil-based chemotherapy. Moreover, colorectal cancer patients aged ≤ 50 years could potentially have Lynch syndrome. In the present study, we examined 11 colorectal cancer patients with unresectable Stage IV disease who underwent resection of the primary tumor between January 2006 and December 2012. The relationship between the MSI status and the efficacy of first- line oxaliplatin-based chemotherapy was retrospectively examined. The MSI status included MSI-H in 1 patient, MSS-L in 2 patients, and MSS in 8 patients. The MSI-H in 1 patient was associated with familial adenomatous polyposis. Following chemotherapy, among 8 MSS patients, 3 showed stable disease (SD) and 1 showed partial response (PR). Moreover 2 MSH-L patients and 1 MSI-H patient showed progressive disease (PD) after chemotherapy. However, additional data collection is required to determine the effect of oxaliplatin-based chemotherapy for MSS-H or MSS-L colorectal patients aged ≤ 59 years.

[Clinical outcome of Stage IV colorectal cancer on the basis of the seventh edition of the TNM classification].

Recent advances in chemotherapy for stage IV colorectal cancer have improved clinical outcome. According to the seventh edition of the TNM classification of colorectal cancer, stage IV is classified into stage IVA and stage IVB. In this study, we assessed the clinical validity of this classification as a prognostic factor. The subjects were 170 patients with stage IV colorectal cancer(stage IVA, n=78; stage IVB, n=92)treated between January 2006 and December 2011 at our institute. Of 92 patients with stage IVB, peritoneal carcinomatosis alone was recognized in 21 patients. The median survival periods for patients with stage IVA and IVB were 29.2 and 16.1 months, respectively( p=0.13). The median survival period for patients with peritoneal carcinomatosis alone was 37.6 months, and there was no difference between survival in patients with stage IVA and those with peritoneal carcinomatosis alone. Our present results suggest that it may be reasonable and useful to classify peritoneal carcinomatosis alone into stage IVA instead of stage IVB in clinical practice.

[Clinical significance of serum anti-p53 antibody measurement for colorectal cancer].

We investigated the usefulness of serum anti-p53 antibody (anti-p53) measurement for the diagnosis of colon cancer. carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and anti-p53 were measured by enzyme-linked immunosorbent assay in 375 colorectal cancer patients and 115 healthy volunteers(control group). When the cut-off level of the serum anti-p53 antibody was set to 1.3 U/mL, 114 (30.4%) of the colorectal cancer patients tested positive. Twelve positive cases(10.4%) were recognized in the control group. The median levels of anti-p53 were 0.69 U/mL(0.69- 10,610) and 0.69 U/mL (0.69-19.5) in the colorectal cancer patients and control group, respectively. The positive rates of CEA level (cut-off value 6.7 ng/mL) and CA19-9 level (cut-off value 37 U/mL) were 40.0% and 18.9%, respectively. Of these tumor markers, positive cases with only anti-p53 were observed in 60 patients (16%). The positive rate of all markers examined was 61.6%. No significant correlation was observed between the level of anti-p53 and other markers. The positive rates of anti-p53 in each stage of the colon cancer patients were as follows: stage 0 and I, 19.4%; stage II, 27.0%; stage III,36.1%; and stage IV,61.0%. The positive rate of anti-p53 was higher than that of CEA and CA19-9 in the early stages of colorectal cancer. Furthermore, a combination of these markers improved the diagnosis of colorectal cancer by approximately 60%. These results suggest that the measurement of anti-p53 is useful for diagnosis of colorectal cancer in clinical practice.

[The clinical significance of serum anti-p53 antibody as a monitoring marker in colorectal cancer].

We examined alterations in the level of serum anti-p53 antibody(S-p53 Ab) in colorectal cancer patients who underwent curative resection and analyzed the usefulness of S-p53 Ab as a monitoring marker for postoperative observation. The measurement of S-p53 Ab was performed preoperatively and postoperatively in 16 stage II/III colorectal cancer patients with a high level of S-p53 Ab. A time course analysis of both S-p53 Ab and CEA levels was performed in 6 of these patients who were carcinoembryonic antigen (CEA) positive. The median S-p53 Ab level was 29.9 U/mL and the half-life of the S-p53 Ab level was 40.3 days. In 4(25%) cases, the level of S-p53 Ab recovered to within normal limits by 79-142 days. When the half-lives of S-p53 Ab and CEA were analyzed in 6 patients who were both S-p53 Ab and CEA positive, the half-lives of S-p53 Ab and CEA were 32.3 and 13.2 days, respectively. In the case of recurrence with liver metastasis after resection of ascending colon cancer, the S-p53 Ab level did not respond quickly while the CEA level increased. Therefore, it is difficult to use the level of S-p53 Ab as a marker for monitoring treatment, and priority should be given to the examination of CEA and imaging modality.

[Predictive value of Köhne's index on the efficacy of FOLFIRI regimen in the treatment of unresectable liver metastatsis of colorectal cancer].

The aim of this retrospective study was to analyze the predictive value of Köhne's index on the efficacy of FOLFIRI regimen in the treatment of unresectable liver metastasis of colorectal cancer. The subjects were 44 patients with unresectable liver metastasis from colorectal cancer treated with FOLFIRI regimen as second-line, for all of whom oxaliplatin-based regimen had previously failed. Bevacizumab was concomitantly used in 23 patients. Classification of the Köhne's index revealed high risk in 22 patients, intermediate risk in 7 patients, and low risk in 15 patients. The response rate was 13.6% in the patients with high risk(H group) and 27.3% in the patients with intermediate or low risk(non-H group)(p=0.45). The disease control rate was 50% in the H group and 68.2% in the non-H group (p=0.36). In the H group, the median progression -free survival time was 4.1 months and in the non-H group it was 7.1 months (p=0.33). Compared with the H group, the non-H group showed significantly better overall survival (10.8 months vs 23.9 months, p=0.03). None of the patients has received hepatectomy (conversion therapy). These results suggest that the predictive value of Köhne's index is limited in terms of the effect of shrinkage of liver metastases, including conversion therapy.

[Clinical outcomes in refractory colorectal cancer patients with wild-type K-ras treated with bevacizumab and oxaliplatin-based chemotherapy as a first-line treatment].

The clinical outcomes, including adverse events, in 34 unresectable advanced colorectal cancer patients with wild-type K-ras, who were treated with bevacizumab and oxaliplatin-based chemotherapy as a first-line treatment, were analyzed for confirmation of the effectiveness and safety of this treatment. The response rate of the patients was 44% (complete remission, 2 patients; and partial remission, 13 patients). The median progression-free survival and overall survival in these patients was 11.1 and 25.1 months, respectively. Adverse events of greater than grade 3 were observed in 18 patients. Of these patients, 10 exhibited grade 3/4 neutropenia, and 6 had peripheral neuropathy. Our results were similar to those of randomized phase III trials from abroad, including those using anti-epidermal growth factor receptor antibody, with respect to effectiveness and safety. Furthermore, patients with liver metastasis had poor prognosis compared to those with metastasis to organs other than the liver. Further analysis will be required to better understand these results.

[Adjuvant chemotherapy comprising modified FOLFOX6 after curative resection of synchronous or metachronous metastasis from colorectal cancer].

PURPOSE: This retrospective study evaluated the outcome of adjuvant chemotherapy comprising modified FOLFOX6 (mFOLFOX6) after potentially curative metastasectomy from colorectal cancer. PATIENTS AND METHODS: The subjects were 40 patients with colorectal cancer who underwent potentially curative metastatectomy without any prior chemotherapy between December 2003 and November 2011. Patient background, type of adjuvant chemotherapy, and prognosis were examined. RESULTS: Adjuvant chemotherapy was given in 30 patients (mFOLFOX6, n=26; oral fluoropyrimidines, n=4). The median relapse-free survival tended to be longer in patients treated with mFOLFOX6 compared to those treated with fluoropyrimidines (28.5 months vs 14.8 months; p=0.11). The median overall survival did not differ significantly between the 2 groups (37.9 months vs 31.3 months, p=0.56). When the analysis was restricted to patients treated with mFOLFOX6, no significant differences were found in relapse-free survival (p=0.46), overall survival (p=0.29), and frequency of adverse events during chemotherapy(Grade 3, p=0.32) between patients with synchronous metastasis(n=11) and those with metachronous metastasis (n=15). CONCLUSION: These results suggest that mFOLFOX6 might contribute to prolonging the time to relapse and that the timing of developing metastasis(synchronously or metachronously) may not have any effect on the outcome of adjuvant mFOLFOX6.

[Prediction of the efficacy of first-line oxaliplatin-based chemotherapy for unresectable liver metastases of colorectal cancer by Köhne's index].

PURPOSE: This retrospective study was undertaken to examine the usefulness of Köhne's index(KI) for predicting the efficacy of first-line oxaliplatin-based chemotherapy for unresectable liver metastases of colorectal cancer. PATIENTS AND METHODS: The subjects were 84 patients with unresectable liver metastases of colorectal cancer in whom first-line oxaliplatin- based chemotherapy was administered. The outcome of treatment was analyzed in relation to the KI. RESULTS: The patients were classified into 3 groups: high risk group (n=12), intermediate risk group (n=20), and low risk group (n=52). There were no significant differences between the groups with regard to response rate, disease control rate, disease-free survival, overall survival, and the rate of conversion to hepatic metastatectomy. CONCLUSION: Our results suggest that KI might not be useful for predicting the efficacy of first-line oxaliplatin-based chemotherapy for unresectable liver metastases of colorectal cancer.

Usefulness of sennoside as an agent for mechanical bowel preparation prior to elective colon cancer surgery.

OBJECTIVE: We retrospectively evaluated the usefulness of sennoside as an agent for mechanical bowel preparation prior to elective colon cancer surgery. METHODS: A total of 86 patients were given 12 mg of sennoside on the evening prior to resective surgery for colon cancer, followed by intravenous antimicrobial prophylaxis used on the day of surgery or until postoperative day 2. RESULTS: The incidence of surgical site infection in the study group was 4.7%, which was comparable to that in the historical control patients (3.5%, p>0.99), who had received polyethylene glycol for mechanical bowel preparation prior to colon surgery. On multivariate logistic regression analysis, only body mass index (p=0.04) was an independent significant factor affecting the surgical site infection. The intraoperative spillage was not influenced by the presence of stenosis, although the amount of fecal matter was higher in the upstream colon segment (p<0.01) and downstream segment (p=0.07) in patients with a stenotic lesion occupying more than two-thirds of the lumen (n=29) than in those without such severe stenosis (n=57). CONCLUSION: Sennoside seems to be an acceptable agent for mechanical bowel preparation even in patients with stenosis.

[The clinical outcome of mFOLFOX6 treatment for colorectal cancer patients who underwent resection of liver metastasis -comparison between synchronous and metachronous liver metastasis].

Only a few reports have suggested the efficacy of adjuvant chemotherapy including oxaliplatin based regimens following surgical resection of liver metastases from colorectal cancer. Since an administration of mFOLFOX6 was approved to medical insurance for advanced colorectal cancer as adjuvant chemotherapy, we applied mFOLFOX6 treatment (6 to 12 courses) to the patients who underwent curative resection of colorectal liver metastasis. The subjects were 14 patients who underwent curative resection for synchronous or metachronous colorectal liver metastasis and received mFOLFOX6 treatment postoperatively from January 2006 to January 2011. We retrospectively analyzed the patient's characteristics, relapse free survival, overall survival, and adverse events in these patients. Synchronous liver metastasis was found in 5 patients, while metachronous liver metastasis was observed in 9 patients. There were no significant differences between these patients in terms of clinical characteristics, the relapse free survival and overall survival. All patients had some adverse events including bone-marrow suppression and diarrhea. Especially, grade 3 or higher bone-marrow suppression were recognized in 6 patients (42.8%). Neurologic toxicity (≤ grade 2) was observed in 10 patients (71.4%). Adjuvant chemotherapy with mFOLFOX6 treatment following surgical resection of synchronous or metachronous liver metastasis was safely administered. We will further examine the benefit of mFOLFOX6 treatment for the patients who undergo a surgical resection of liver metastasis in the future.

[Prediction of the efficacy of modified FOLFOX6 therapy according to the mRNA levels of thymidylate synthase (TS), excision repair cross-complementing-1 and -2( ERCC-1 and ERCC-2) and methylenetetrahydrofolate dehydrogenase( MTHFD) in the primary lesion of colorectal cancer].

The aim of this study was to determine whether mRNA levels of thymidylate synthase (TS), excision repair cross-complementing -1 (ERCC-1), excision repair cross-complementing-2 (ERCC-2) and methylenetetrahydrofolate dehydrogenase( MTHFD) mRNA in the primary tumor could predict a tumor response in patients with unresectable liver metastasis from colorectal cancer treated with mFOLFOX6 therapy as a first-line treatment. Eighteen patients with unresectable liver metastasis from colorectal cancer treated with mFOLFOX6 therapy as a first-line treatment were enrolled in this study. There were no significant differences between the response rate and these enzymes mRNA levels. In ERCC-1 and MTHFD mRNA expression, the progression-free survival time tended to be longer in patients with low levels than in patients with high levels( ERCC-1: p=0.08, MTHFD: p=0.07). The progression-free survival time was significantly longer in patients with both ERCC-1 and MTHFD mRNA were low levels than in patients with other( p=0.03). The levels of ERCC-1 and MTHFD were low in patients who could perform a conversion therapy. There were no significant differences between an overall survival time and these enzymes mRNA levels. In this study, the ERCC-1 and MTHFD mRNA expression may be useful for the prediction of progression-free survival time in patients with unresectable liver metastasis from colorectal cancer treated with mFOLFOX6 therapy.

[The Relationship between the efficacy of mFOLFOX6 treatment and the expression of TS, DPD, TP, and ERCC-1 in unresectable colorectal cancer].

It has been reported that thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and excision repair cross-complementing-1 (ERCC-1) were useful markers to predict the efficacy of anti cancer agents including 5-fluorouracil (5-FU) and oxaliplatin for unresectable advanced colorectal cancer. In this study, we analyzed the relationship between the expression of these enzymes and the clinical significance in 49 Stage IV colorectal cancer patients who received mFOLFOX6 as a first-line treatment and evaluated the usefulness of these enzymes for predicting the efficacy of mFOLFOX6. There was no relationship between the expression of each enzyme and response rate. The progression-free survival of the patients with low TP expression was significantly longer than that of the patients with high TP expression( p<0.01). In the analysis of overall survival, the patients with low TP or low DPD expression were better than that with high TP expression or high DPD expression (p=0. 04, p=0. 04, respectively). Our results indicated that TP and DPD expression would be a useful marker to predict the efficacy of mFOLFOX6 in the patients with unresectable colorectal cancer.

Impact of prior abdominal surgery on curative resection of colon cancer via minilaparotomy.

PURPOSE: To evaluate the impact of prior abdominal surgery on curative resection of colon cancer via a minilaparotomy approach. METHODS: Feasibility, safety, and oncological outcomes were evaluated retrospectively in 263 patients scheduled to undergo curative resection of colon cancer via a minilaparotomy approach, defined as a skin incision of ≤ 7 cm, between September 2000 and March 2009. RESULTS: Abdominal adhesions were found in 59 (77.6%) of 76 patients who had undergone prior abdominal surgery (PAS group) and in 4 (2.1%) of 187 patients who had not (control group). The success rate of the minilaparotomy approach was 92.1% in the PAS group and 97.3% in the control group (P = 0.08). The incidence of extending the minilaparotomy wound for adhesiolysis was significantly higher in the PAS group than in the control group (6.6% vs 0.5%; P < 0.01). The two groups did not differ significantly in terms of the types of surgery, pathological stage, body mass index, operative time, blood loss, incidence of postoperative complications, length of postoperative hospital stay, and disease-free survival. CONCLUSIONS: These results suggest that prior abdominal surgery might require an extension of the minilaparotomy incision but that it does not seem to contraindicate a minilaparotomy approach for curative colectomy.

[The expression of thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) protein in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy].

Thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) were known to be important biomarkers to predict a tumor response to 5-fluorouracil (5-FU) and oxaliplatin, but the relationship between these expressions and tumor response were still unclear. The aim of this study was to determine whether the expression of TS and ERCC-1 protein predict a tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy as first-line treatment. Fifty patients with unresectable colorectal cancer treated with mFOLFOX6 therapy were enrolled in this study. The expression of TS and ERCC-1 protein in primary cancer cells were examined using immunohistochemistry. There were no significant differences between response rate and the expression of TS or ERCC-1 protein (TS: p>0.99, ERCC-1: p= 0.50). There were no significant differences between progression-free survival time and the expression of TS or ERCC-1 protein (TS: p=0.60, ERCC-1: p=0.60). In this study, the expression TS and ERCC-1 protein may not be useful for the prediction of tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy.

[Clinical path for mFOLFOX6 describing criteria for reduction and suspension of drugs].

Clinical path for executing mFOLFOX6 in an outpatient chemotherapy room was settled on for the aim of standardization and common information with medical staffs about mFOLFOX6. The feature of this clinical path is described doses of drugs, results of laboratory examination, criteria for deciding adverse effects, common adverse effects and management, criteria for reduction and suspension of oxaliplatin and 5-fluorouracil. Patients before induction of the clinical path were compared with patients after that about relative dose intensity (RDI), reasons why treatments were suspended and progression-free survival (PFS). Fifty eight patients after induction were significantly higher RDI of oxaliplatin than 108 patients before induction (p=0.04). There were no significant differences about a frequency of suspension due to adverse effects (p=0.18) and PFS (p=0.74). The clinical path that we settled on was considered useful not only for common information with medical staffs but also for standardization.