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.     

The role of hepatocyte growth factor activator inhibitor (HAI)‐1 and HAI‐2 in endometrial cancer

Hepatocyte growth factor activator inhibitors (HAI‐1 and HAI‐2) are Kunitz‐type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI‐1 and HAI‐2 in endometrial cancer. We investigated the biological functions of HAI‐1 and HAI‐2 using KLE and HEC‐251 endometrial cancer cell lines, thus HAI‐1 and HAI‐2 were examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. HAI‐1 and HAI‐2 showed potential inhibitory effects on cell proliferation, migration and cellular invasion by reduction of matriptase and hepsin expression. This in turn led to an increase in the levels of E‐cadherin and Slug, and a reduction in the levels of Vimentin, SIP1, Snail and Twist, and hence ER and PR signal transduction in endometrial cancer cells. The levels of HAI‐1 and HAI‐2 expression were significantly decreased in endometrial cancer specimens relative to the corresponding normal endometrium specimens. Low HAI‐1 and HAI‐2 expression was a significant predictor for a poor prognosis compared with high HAI‐1 and HAI‐2 expression. These findings indicate that HAI‐1 and HAI‐2 could be considered as therapeutic targets and used as favorable prognosis markers for endometrial cancer.     

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.     

Pseudo-Meigs' syndrome caused by ovarium metastasis from colorectal cancer

Pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancer is extremely rare. The clinical symptoms of pleural effusion and ascites that are characteristics of pseudo-Meigs' syndrome are quite similar to those of terminal-stage colon cancer. Therefore, recognizing the clinical characteristics of pseudo-Meigs' syndrome is important. We investigated the prognosis and clinicopathological factors including age, location of the primary cancer, histology, wall depth, curative degree, synchronous/metachronous, unilateral/bilateral, lymph node metastasis, peritoneal dissemination, serum CEA level, venous invasion, and lymphatic invasion, in 5 cases of pseudo-Meigs' syndrome (PM group) and compared these findings with those of 10 cases with ovarian metastasis from colorectal cancer (control group) without pseudo-Meigs' syndrome. No significant differences were found between the PM group and the control group. The three-year survival rate was 37.5% in the PM group and 10% in the control group (logrank test, p=0.19). In the present study, no significant differences in any of the clinicopathological factors examined in this study were seen between the PM and control groups. However, we found that the surgical resection of ovarian metastasis in patients with pseudo-Meigs' syndrome improved the prognosis, similar to the situation for ovarian metastasis from colorectal cancer.     

Successfully resected an isolated extraperitoneal metastasis of sigmoid colon cancer--a case report

We herein report an extremely rare operative case of an isolated extraperitoneal metastasis of colon cancer. A female patient had undergone a sigmoidectomy for ileus due to sigmoid colon cancer when she was 40 years old. Peritoneal metastasis, 5 mm in diameter, was on the sigmoid colon mesentery and she was histologically diagnosed as Stage IV. She received fluorouracil-based adjuvant chemotherapy for 24 months. Serum CEA increased gradually from 36 months after the operation, and CT scan demonstrated bilateral ovarium tumors. Bilateral oophorectomy was performed at 44 months after the operation. Serum CEA decreased temporarily, but increased again. Serum CEA increased in spite of giving UFT/LV, so we changed to mFOLFOX6 therapy. Serum CEA decreased until it reached to a normal range after 9 courses, and stopped mFOLFOX6 therapy. Four months later, serum CEA increased again and PET-CT demonstrated a 3 cm mass with calcification in pelvic, and accumulation of FDP. Serum CEA decreased until it reached to a normal range after a resection of extraperitoneal mass. A histological examination of the tumor revealed a moderately differentiated adenocarcinoma similar to colon cancer. She has been well without recurrence 77 months after the first operation.     

Phase II study of carboplatin and gemcitabine as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: a report from the Central Japan Lung Study Group, CJLSG 0503 trial

Background

The aim of this phase II study was to evaluate the feasibility and safety of a carboplatin and gemcitabine combination regimen in the treatment of completely resected non-small cell lung cancer (NSCLC).

Methods

Patients with completely resected pathologically documented stage IB, II or IIIA NSCLC were treated with carboplatin and gemcitabine. Chemotherapy consisted of 4 cycles of carboplatin at an area under the curve of 5 (level 1) or 4 (level 2) on day 1 combined with gemcitabine 1,000 mg/m² on days 1 and 8 every 3 weeks. The primary endpoint of this study was the completion rate of 4 cycles.

Results

Twenty patients were treated, and the patient’s demographics were: median age 61 years (range 51–74), gender male (n = 13, 65%)/female (n = 7, 35%), stage IB (n = 8, 40%), IIA (n = 1, 5%), IIB (n = 6, 30%), IIIA (n = 5, 25%). Seventeen patients (85%, 95% confidence interval 64.0–94.8) received the planned 4 cycles of the chemotherapy regimen at level 1 every 3 weeks. Among the 3 patients who failed to complete 4 cycles, the reasons for stopping were refusal (n = 1), thrombocytopenia (n = 1) and rash (n = 1). The main adverse effects were hematological toxicity as well as grade 3/4 neutropenia and thrombocytopenia (which occurred in 65% and 40% of the patients, respectively).

Conclusions

Adjuvant chemotherapy with a carboplatin and gemcitabine combination regimen has an acceptable toxicity profile, and the majority of patients completed 4 cycles of therapy.     

Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study

Background  

Whether the administration of calcium (Ca) and magnesium (Mg) can reduce oxaliplatin-related neurotoxicity remains controversial. In addition, little is known about the effects of Ca/Mg on the blood level of platinum or objective tumor progression.     

A pilot study of combination chemotherapy with paclitaxel, pirarubicin, and carboplatin (TPC) for endometrial carcinoma

Background  

Although anthracyclines are considered as being among the most potent chemotherapeutic agents for endometrial carcinoma, the majority of institutions in Japan prefer a combination of paclitaxel and carboplatin (TC) for treating this disease. We retrospectively evaluated the efficacy and feasibility of combined paclitaxel, pirarubicin, and carboplatin (TPC) therapy for endometrial carcinoma.     

Comparison of ferucarbotran‐enhanced fluid‐attenuated inversion‐recovery echo‐planar,T2‐weighted turbo spin‐echo,T2*‐weighted gradient‐echo,and diffusion‐weighted echo‐planar imaging for detection of malignant liver lesions

Purpose:

To compare the diagnostic accuracy of superparamagnetic iron oxide (SPIO)‐enhanced fluid‐attenuated inversion‐recovery echo‐planar imaging (FLAIR EPI) for malignant liver tumors with that of T2‐weighted turbo spin‐echo (TSE), T2*‐weighted gradient‐echo (GRE), and diffusion‐weighted echo‐planar imaging (DW EPI).

Materials and Methods:

SPIO‐enhanced magnetic resonance imaging (MRI) that included FLAIR EPI, T2‐weighted TSE, T2*‐weighted GRE, and DW EPI sequences was performed using a 3 T system in 54 consecutive patients who underwent surgical exploration with intraoperative ultrasonography. A total of 88 malignant liver tumors were evaluated. Images were reviewed independently by two blinded observers who used a 5‐point confidence scale to identify lesions. Results were correlated with results of histopathologic findings and surgical exploration with intraoperative ultrasonography. The accuracy of each MRI sequence was measured with jackknife alternative free‐response receiver operating characteristic analysis. The sensitivity of each observer with each MRI sequence was compared with McNemar's test.

Results:

Accuracy values were significantly higher with FLAIR EPI sequence (0.93) than with T2*‐weighted GRE (0.80) or DW EPI sequences (0.80) (P < 0.05). Sensitivity was significantly higher with the FLAIR EPI sequence than with any of the other sequences.

Conclusion:

SPIO‐enhanced FLAIR EPI sequence was more accurate in the diagnosis of malignant liver tumors than T2*‐weighted GRE and DW EPI sequences. SPIO‐enhanced FLAIR EPI sequence is helpful for the detection of malignant liver tumors. J. Magn. Reson. Imaging 2010;31:607–616. ©2010 Wiley‐Liss, Inc.