A multicenter Phase II study evaluating the efficacy, safety and pharmacokinetics of trastuzumab emtansine in Japanese patients with heavily pretreated HER2-positive locally recurrent or metastatic breast cancer.

OBJECTIVE: Trastuzumab emtansine significantly improved progression-free survival and overall survival when compared with lapatinib-capecitabine in pretreated human epidermal growth factor receptor 2-positive advanced breast cancer. However, data in Japanese populations are limited. METHODS: In the single-arm Phase II JO22997 study, Japanese patients with human epidermal growth factor receptor 2-positive inoperable locally advanced/recurrent or metastatic breast cancer previously treated with at least one prior chemotherapy regimen for locally advanced/recurrent or metastatic breast cancer and trastuzumab in any setting received 3.6 mg/kg trastuzumab emtansine every 3 weeks until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was Independent Review Committee-assessed objective response rate. Secondary endpoints included progression-free survival, overall survival, safety and pharmacokinetics. RESULTS: The objective response rate in 73 treated patients was 38.4% (90% confidence interval, 28.8-48.6%), exceeding the prespecified boundary for an objective response rate > 20%. After 6.5 months' median follow-up, median progression-free survival was 5.6 months (95% confidence interval, 4.6-8.2). After 28.9 months' median follow-up, median overall survival was 30.5 months (95% confidence interval 25.2-not reached). There were no treatment-related deaths. The most common Grade 3/4 adverse events were thrombocytopenia (22%) and aspartate aminotransferase elevations (14%). Thrombocytopenia did not require platelet transfusion and typically recovered before the next cycle. There were no substantial differences in trastuzumab emtansine or trastuzumab pharmacokinetic parameters between this study and previous data from non-Japanese patients. CONCLUSIONS: JO22997 results suggest high activity of trastuzumab emtansine in Japanese patients, a safety profile consistent with previous studies in non-Japanese patients, no new safety signals and no evidence of pharmacokinetic differences between Japanese and non-Japanese populations. These results support trastuzumab emtansine therapy for Japanese patients with chemotherapy- and trastuzumab-pretreated human epidermal growth factor receptor 2-positive locally advanced/recurrent or metastatic breast cancer.

First-line bevacizumab in combination with weekly paclitaxel for metastatic breast cancer: efficacy and safety results from a large, open-label, single-arm Japanese study.

UNLABELLED: Despite extensive evaluation of first-line bevacizumab-containing therapy in randomized trials in locally recurrent/metastatic breast cancer (LR/mBC), data from Japanese populations are limited. We conducted a phase II study exclusively in Japanese patients to evaluate bevacizumab combined with weekly paclitaxel. Patients with HER2-negative measurable LR/mBC who had received no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg, days 1 and 15, in combination with paclitaxel 90 mg/m(2), days 1, 8, and 15, repeated every 4 weeks, until disease progression, unacceptable toxicity, or patient/physician decision. Co-primary endpoints of this single-arm open-label phase II study were progression-free survival (PFS) and safety. A total of 120 patients (median age 55 years) received study therapy. At the time of data cut-off, the median duration of therapy was 11.1 months (range 0.5-24.7 months). Median PFS was 12.9 months (95% CI: 11.1-18.2) according to Independent Review Committee assessment and 14.9 months by investigator assessment. Median PFS was 9.6 months in the subgroup of 38 patients with triple-negative LR/mBC. The overall response rate was 74% (95% CI: 64.5-81.2%). Median overall survival (OS) was 35.8 months (95% CI: 26.4-not estimated) and the 1-year OS rate was 88.9% (95% CI: 83.2-94.6). The regimen was well tolerated and the safety profile was generally consistent with previous reports of bevacizumab-paclitaxel combination therapy. Grade 3 hypertension was reported in 17% of patients. Grade 4 hypertension, grade 3/4 proteinuria, and gastrointestinal perforation were absent. There were no new bevacizumab safety signals. In 50 patients (42%), treatment was continued for ≥ 1 year. CONCLUSION: The high activity of first-line bevacizumab in combination with weekly paclitaxel observed in our study confirms the results of the E2100 trial. Our results suggest that the activity and tolerability of first-line bevacizumab-containing regimens demonstrated in E2100 can be reproduced in Japanese populations.

Detection of isolated ipsilateral regional lymph node recurrences by F18-fluorodeoxyglucose positron emission tomography-CT in follow-up of postoperative breast cancer patients.

Imaging diagnostic methods except for mammograms are not recommended for follow-up of postoperative breast cancer patients in order to detect small recurrences because of the poor survival improvement in earlier randomized trials. However, the use of new imaging modalities may improve survival by detection of small isolated regional lymph node recurrences which are potentially curable. Between April 2006 and December 2008, we used PET-CT to find small recurrences in follow-up of 1,907 postoperative breast cancer patients. A total of 3,280 PET-CT imagings were performed. The median age at PET-CT imaging was 58 years, with a median 48-month interval from definitive surgery to the PET-CT imaging. Twenty-two patients were found to have isolated ipsilateral regional recurrences only by PET-CT (axillary node recurrences in 6, infraclavicular node recurrences in 5, supraclavicular node recurrences in 6, and parasternal node recurrences in 5). All of those recurrences were missed by palpation or were nonpalpable. The pathological lymph node status at the definitive surgery for the primary breast cancer of 22 patients with the isolated ipsilateral regional lymph node recurrences was positive in 17 patients. If patients are limited to those who had pathologically positive node(s) at definitive surgery, the incidence of patients with isolated regional lymph node recurrences found only by PET-CT would be 2.6% (17/663 patients). Seventeen other asymptomatic cancers including contralateral breast cancers were found only by PET-CT. Early detection of isolated loco-regional recurrences of breast cancer is suggested to result in improved survival. Therefore, the use of PET-CT in follow-up of postoperative node-positive breast cancer patients may improve their survival because of early detection of isolated regional lymph node recurrences which are still potentially curable, and screening of other asymptomatic cancers.

Efficacy and safety of S-1 in patients with metastatic breast cancer: retrospective review in a single institution.

BACKGROUND: It is extremely difficult to bring about a complete cure of metastatic breast cancer: the purpose of treatment is to prolong the patient's survival while maintaining their quality of life (QOL). The current retrospective study was conducted to find whether S-1, an orally administered 5-FU agent, can produce a therapeutic result in patients with recurrent metastatic breast cancer while maintaining their QOL. METHODS: Among the patients who were diagnosed at our institution to have recurrent metastatic breast cancer between November 2001 and December 2008, those who were treated with S-1 were selected and their records retrospectively reviewed. RESULTS: The analysis was conducted on 33 patients. The median number of regimens that these patients underwent was 2 (range 0-6). The overall response rate (ORR), clinical benefit rate (CBR), median time to treatment failure and overall survival were 30%, 42%, 152 days and 338 days, respectively. Among the 11 patients who were treated with S-1 in the first or the second line, ORR and CBR were 45.5 and 63.6%, respectively. Toxicity more than grade 3, leucopenia, neutropenia diarrhea, mucositis, and hand-foot syndrome were found in only 3%. CONCLUSION: S-1 is well-tolerated by patients, promising a therapy while maintaining their QOL. When applied in the early stage of a disease in particular, the agent promises a very effective anti-tumor effect.

Effects of toremifene and tamoxifen on lipid profiles in post-menopausal patients with early breast cancer: interim results from a Japanese phase III trial.

OBJECTIVE: Toremifene and tamoxifen have been used for adjuvant therapy in post-menopausal patients with breast cancer in Japan. Dyslipidemias are common in post-menopausal women. However, limited data are available on the effects of these agents on lipid profiles in Japanese patients. The Japan Toremifene Cooperative Study Group has been conducting a Phase III randomized trial of post-menopausal patients with breast cancer. One of its secondary endpoints is to confirm the effects of these agents on serum lipid profiles. METHODS: The subjects were post-menopausal Japanese patients who had undergone surgery for early breast cancer. Toremifene or tamoxifen was administered for 2 years. Lipid levels were measured before and up to 24 months after initiation. RESULTS: Compared with baseline, at 24 months, the toremifene group (n = 123) showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001), and significantly increased high-density lipoprotein cholesterol levels (P < 0.001). Their triglyceride levels were not affected (P = 0.677). The tamoxifen group (n = 120) also showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001); no significant changes occurred in high-density lipoprotein cholesterol (P = 0.297) or triglyceride levels (P = 0.120). CONCLUSIONS: Distinct differences between two selective estrogen receptor modulators on lipids were observed. Toremifene improved lipid profiles, particularly as an enhancer of high-density lipoprotein cholesterol. To a large extent, tamoxifen improved low-density lipoprotein cholesterol levels. The impact of these improved lipid profiles on the risk of cardiovascular diseases needs further confirmation.

Determination of indication for sentinel lymph node biopsy in clinical node-negative breast cancer using preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging.

OBJECTIVE: Sentinel node biopsy (SNB) is indicated for axillary lymph node metastasis-negative cases (N0), but clarification of the indication may increase treatment efficiency. Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may have a high positive predictive value in diagnosis of axillary lymph node metastasis. METHODS: Ninety-two breasts/axillae were analyzed retrospectively in 90 patients (median age 54.6-year old, median primary tumor 1.7 cm). FDG-PET/computed tomography was used to indicate SNB in N0 cases. Axillary lymph node dissection (ALND) was performed in cases that were axillary lymph node metastasis-positive (PET N+) on FDG-PET/CT. RESULTS: Seventy-four (80.4%) and 18 (19.6%) of the 92 axillae were diagnosed as metastasis-negative (PET N0) and PET N+, respectively, by FDG-PET/CT. SNB was performed in 51 of the 74 PET N0 axillae. ALND was performed in 23 PET N0 axillae (at the patients' request) and in all 18 PET N+ axillae. Of the 74 PET N0 axillae, 14 were metastasis-positive (pN+) and 60 were pN0 pathologically, and of the 18 PET N+ axillae, 13 were pN+ and five were pN0. The sensitivity and specificity of FDG-PET/CT for diagnosis of axillary metastasis were 48.1 and 92.3%, respectively, and the positive and negative predictive values were 72.2 and 81.1%, respectively. CONCLUSION: The positive detection rate on FDG-PET/CT was insufficient for determining an indication of SNB. However, use of an appropriate cut-off for SUV(max) (the positive rate was 90.9% with a cut-off of 2.0) and exclusion of surgically biopsied cases may achieve a clinically applicable positive detection rate.

Factors associated with health-related quality-of-life in breast cancer survivors: influence of the type of surgery.

OBJECTIVE: To determine if health-related quality-of-life (QOL) differences existed between breast cancer (BC) survivors receiving mastectomy and those receiving breast-conserving treatment (BCT). Factors associated with QOL in long-term BC survivors were also identified. METHODS: One hundred patients who had previously undergone BC surgery and were alive without recurrence for >5 years were asked to answer the patient-administered questionnaires to assess their QOL (Functional Assessment of Cancer Therapy scale-Breast: FACT-B) and psychological distress (Hospital Anxiety and Depression Scale: HADS). Of them, 93 responded to the questionnaires affirmatively. RESULTS: Although none of the QOL scores were related to the surgical procedures, statistically significant relationships were found between age and the scores of FACT-General and social/family well-being (SWB), and between the educational status and scores of SWB in univariate analyses. There was no statistically significant relationship between psychological distress and each factor examined. In multivariate analyses, significant correlations were established between scores of the FACT-BC subscale (FACT-BCS) and the type of surgery and between those on the FACT SWB subscale and age at study or educational status. Namely, patients who had undergone BCT, younger patients and patients with higher educational background scored higher QOL. CONCLUSIONS: Among the BC survivors, those who underwent BCT experienced significantly but slightly better QOL than those who received mastectomy in FACT-BCS assessments. Younger patients and patients with higher educational backgrounds experienced significantly better SWB.

Phase II study of gemcitabine monotherapy as a salvage treatment for Japanese metastatic breast cancer patients after anthracycline and taxane treatment.

OBJECTIVE: This Phase II study was conducted to evaluate efficacy and safety of gemcitabine monotherapy in anthracycline and taxane pre-treated Japanese metastatic breast cancer patients. METHODS: At Step 1, twelve patients were divided into two groups of six patients each and the dose-limiting toxicity was evaluated at gemcitabine 1000 and 1250 mg/m(2) to determine the dose for Step 2. At Step 2, an additional 56 patients were assessed for efficacy and safety of gemcitabine monotherapy. Patients were treated with gemcitabine on days 1 and 8 of a 21-day cycle and explored incidence of adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, overall response rate (RR), time to progression disease and overall survival time. RESULTS: Gemcitabine 1250 mg/m(2) was determined as the dose for Step 2. Adverse events reported in this study were similar in type, frequency and toxicity grades as seen in other tumor types. Of the 62 patients at 1250 mg/m(2), 1 complete response (1.6%), 4 partial response (6.5%) and 20 stable disease (32.3%) were achieved, yielding an RR of 8.1% (95% CI: 2.7%, 17.8%). Median time to progression was 92.0 days (range: 29-651 days). The median survival time was 17.8 months (95% CI: 14.9 months to incalculable). CONCLUSION: Gemcitabine at 1250 mg/m(2) on days 1 and 8 of a 21-day cycle was tolerable and can be a salvage treatment option for Japanese metastatic breast cancer patients previously treated with anthracyclines and taxanes.

Evaluation of video-assisted thoracoscopic surgery for pulmonary metastases: 11-years of experience.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has been applied to pulmonary resection for pulmonary metastases, the clinical validity of this approach remains controversial. The purpose of this study was to evaluate the validity and problems of VATS for pulmonary metastasectomy. METHODS: From January 1993 to December 2003, VATS for pulmonary metastasectomy was performed in 53 resections for 48 patients at our institution. The medical records of these patients were retrospectively reviewed. RESULTS: The primary tumor was colorectal cancer in 23 patients, renal cell carcinoma in 6, breast cancer in 6, germ cell tumor in 5, head and neck cancer in 2, and others in 6. Thirty-six cases had a solitary lesion, 8 had unilateral multiple lesions, and 9 had bilateral multiple lesions. The following procedures were performed: 7 lobectomies, 5 segmentectomies, and 41 wedge resections. There was no major postoperative morbidity related to VATS. At a median follow-up period of 29.0 months, 13 patients were alive without recurrences. The 3-year overall survival rate and the 3-year intrathoracic disease-free survival rate were 59.8% and 33.4%, respectively. Five cases had recurrence at the surgical stump or at the port sites, but these recurrences have not been found in the recent period since June 1997. Intrathoracic recurrences within 3 months after VATS occurred in four. CONCLUSION: VATS for pulmonary metastases is not superior to the conventional open thoracotomy and is not recommended as a standard procedure. Further studies with a larger number of cases performed by skilled surgeons familiar with VATS are needed.

Efficacy and tolerability of weekly paclitaxel in combination with high-dose toremifene citrate in patients with metastatic breast cancer.

Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80 mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120 mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.

Primary extranodal non-Hodgkin's lymphoma of the common bile duct manifesting as obstructive jaundice: report of a case.

Primary non-Hodgkin's lymphoma (NHL) of the common bile duct (CBD) manifesting as obstructive jaundice is extremely rare: to our knowledge, only 22 cases of primary NHL arising from the CBD have been reported. The patient in this case report was a 63-year-old man who presented with obstructive jaundice. Abdominal sonography, positron emission tomography, and computed tomography showed a mass with abnormal 18-fluorodeoxyglucose uptake in pancreatic head. Magnetic resonance cholangiopancreatography demonstrated a strictured segment of the CBD with proximal bile duct dilatation. We performed pancreaticoduodenectomy for a presumptive diagnosis of pancreatic head carcinoma or cholangiocarcinoma of the CBD. However, the histological diagnosis was a primary, diffuse, large B-cell lymphoma of the CBD. He received three courses of combination chemotherapy, including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The patient remains well, without evidence of tumor recurrence, 8 months after surgery. In summary, primary NHL of the CBD, despite its rarity, should be considered in the differential diagnosis of obstructive jaundice. An accurate histopathologic diagnosis and complete surgical resection, followed by combination chemotherapy plus rituximab may be effective.

[A case of recurrent breast cancer with extensive liver metastasis successfully treated with endocrine therapy].

A 5 6-year-old woman, who underwent breast-conserving surgery and radiation (60 Gy) therapy in July, 1992, at the age of 40, was diagnosed with pT1aN0M0, pStage I. She was administered tamoxifen (TAM) as adjuvant therapy. However, she underwent microdochectomy for DCIS in her contralateral breast in June, 1998. TAM was given till August, 1999. In June, 2006, at the age of 54, 14 years after initial surgery, CT revealed extensive liver masses which were diagnosed as liver metastasis by liver biopsy. Receptor status was positive for ER and PgR, and negative for HER2. AC was started as a first-line chemotherapy ( 4 courses), but did not prove effective. She refused second-line chemotherapy, so letrozole was selected, and subsequently resulted in PR of the liver metastasis. However, 8 months later, with a liver metastasis relapse, exemestane followed by tamoxifen, medroxyprogesterone acetate, and high-dose toremifene were administered sequentially, resulting in long-time disease control. In conclusion, endocrine therapy might be an effective option even in a visceral crisis, if metastatic tumors have showed slow growth and there is positive hormone receptor status.

[Correlations between hormonal receptor and HER2 status or nuclear grades and response rate in breast cancer treated with neoadjuvant chemotherapy of docetaxel alone].

BACKGROUND: Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 10-35% of the patients don't benefit from this treatment. This study was designed to evaluate predictive values of biological markers in response of breast cancers treated with docetaxel alone as neoadjuvant chemotherapy. METHODS: 36 patients received the planned four courses of preoperative docetaxel(60-75 mg/m(2)) every 3 weeks. We evaluated the relationship between the response rate to neoadjuvant chemotherapy and hormonal receptor, HER2 status or nuclear grades. RESULTS: Clinical response rate was 57.2%. Pathological complete response rate was 5.6%. Clinical response rate by each factors were as follows; 9(50%)in ER-positive tumors, 10(66.7%)in ERnegative( p=0.27), 7(50%)in PgR-positive, 12(63.3%)in PgR-negative(p=0.34), 5(55.6%)in HER2-positive, 14 (58.3%)in HER2-negative(p=0.71), 4(50%)in tumors of low nuclear grade and 13(65%)in ones of high nuclear grade(p=0.38). CONCLUSION: The possibility that tumors with negative hormonal receptors or of high nuclear grade tend to respond to neoadjuvant chemotherapy with docetaxel alone more likely was suggested. It is thought breast cancers respond to neoadjuvant chemotherapy of docetaxel alone regardless of HER2 status.

Phase III study to evaluate the use of high-dose chemotherapy as consolidation of treatment for high-risk postoperative breast cancer: Japan Clinical Oncology Group study, JCOG 9208.

A randomized controlled trial was conducted to evaluate the efficacy of high-dose chemotherapy (HDC) as consolidation of the treatment of high-risk postoperative breast cancer. Patients under 56 years of age with stage I to IIIB breast cancer involving 10 or more axillary lymph nodes were eligible. The primary endpoint was relapse-free survival (RFS). Between May 1993 and March 1999, 97 patients were enrolled, and two patients became ineligible. The median age of the 97 patients was 46 years (range 27-55 years), and 72 (74%) were premenopausal. The median number of involved axillary nodes was 16 (range 10-49). All patients had undergone a radical mastectomy. Major characteristics were well balanced between the treatment arms. Forty-eight patients in the standard-dose (STD) arm received six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen. Forty-nine patients were assigned to undergo HDC with cyclophosphamide and thiotepa after six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen; however, 15 of these patients (31%) did not undergo HDC. HDC was well tolerated without any treatment-related mortality. At a median follow-up of 63 months, the 5-year RFS of 47 eligible patients in the STD arm and 48 eligible patients in the HDC arm was 37% and 52% on an intent-to-treat basis, respectively (P = 0.17). Five-year overall survival of all randomized patients was 62% for the STD arm and 63% for the HDC arm (P = 0.78). Although the prespecified values of the two arms were not so accurate as to allow detection of the observed difference, no advantage of HDC was observed in terms of RFS or overall survival.

Contrast-enhanced CT evaluation of clinically and mammographically occult multiple breast tumors in women with unilateral early breast cancer.

BACKGROUND: Magnetic resonance imaging mammography is performed to determine the extent of lesions and to detect occult lesions, but preoperative diagnosis by breast computed tomography (CT) is less common. METHODS: We performed a retrospective study of detection of mammographically occult multiple lesions using breast CT. The subjects were 407 female patients (median age: 56 years old; median tumor size: 1.9 cm) with breast cancer who underwent preoperative, contrast-enhanced breast CT. RESULTS: CT detected 73 incidental-enhanced breast nodules (median size: 0.8 cm) in 73 patients that were undetectable by conventional methods. Age, size of the main lesion or laterality of lesions did not differ between patients with and without incidental nodules, but the frequency of mastectomy was significantly higher in those with incidental nodules. Of the 73 incidental nodules, 22 (30%) were in the same quadrant as the main lesion, 26 (36%) were in other quadrants and 25 (34%) were in the opposite breast. On qualitative diagnosis by CT, 48 were suspected to be malignant (66%), 17 benign (23%) and eight non-specific (11%). In histological evaluation of 44 of the 48 nodules suspected to be malignant, 24 were malignant (invasive carcinoma: 22, non-invasive carcinoma: 2); of seven of the 17 nodules suspected to be benign, all were benign; and of three of the eight non-specific nodules, one was non-invasive carcinoma. The discovery rate of clinically and mammographically occult multiple lesions by preoperative breast CT was 6%. CONCLUSION: We conclude that breast CT is useful for the detection of occult lesions and choice of surgical procedure.

Long-term outcome after laparoscopic wedge resection for early gastric cancer.

BACKGROUND: Laparoscopic wedge resection (LWR) can be applied for the management of early gastric cancer without the risk of lymph node metastasis. Although LWR for early gastric cancer is one of the minimally invasive procedures, its radicality in cancer therapy is controversial. This study aimed to evaluate the long-term outcomes after LWR. METHODS: Data on 43 consecutive cases of LWR performed for preoperatively diagnosed mucosal gastric cancer were analyzed retrospectively in terms of long-term outcomes. RESULTS: No postoperative deaths occurred after LWR. Histologically, resected specimens showed submucosal invasion in 11 cases (26%) and positive surgical margins for cancer in 4 cases (9%). Three patients (7%) showed local recurrence near the staple line, and one patient (2%) died due to the local recurrence, but no lesional lymph node or distant recurrence occurred. The overall 5-year survival rate was 88%. The gastric remnant after LWR developed metachronous multiple gastric cancer in five cases (12%). CONCLUSIONS: The findings show a relatively high incidence of positive surgical margin, local recurrence, and gastric remnant cancer after LWR. Although LWR can be performed for properly selected patients, periodic postoperative endoscopic examination is necessary to detect metachronous multiple gastric cancer and local recurrences.

Laparoscopic colectomy for colorectal cancer patients with previous abdominal surgery.

BACKGROUND/AIMS: Laparoscopic colectomy has been widely accepted as a standard operation for colorectal cancer. The use of this procedure for patients with previous abdominal surgery is now well established. The aim of this study was to evaluate the peri-operative and long-term outcomes of such patients, and to compare them to patients without previous surgery. METHODOLOGY: Data on a consecutive 121 cases of laparoscopic colectomy performed for colorectal cancer from 1995-1999 in Shikoku Cancer Center were analyzed retrospectively for peri-operative and long-term outcomes. RESULTS: Twenty one cases (17%) of laparoscopic colectomy were performed for colorectal cancer patients with previous surgery. Although the operation time for the previous surgery group was significantly longer than that of the control group, there was no significant difference in the peri-operative complications and the overall survival between the 2 groups. CONCLUSIONS: Although the previous abdominal surgery increases the time it takes to perform the laparoscopic colectomy, the peri-operative and long-term outcomes were comparable to those from patients without previous surgery.

Relation between cancer cellularity and apparent diffusion coefficient values using diffusion-weighted magnetic resonance imaging in breast cancer.

PURPOSE: The purpose of this study was to examine the relation between cancer cellularity and the apparent diffusion coefficient (ADC) value using diffusion-weighted magnetic resonance imaging in breast cancer. MATERIALS AND METHODS: The subjects were 27 women who had undergone operation for breast cancer. There were 27 breast cancer lesions, 24 of which were invasive ductal carcinoma (IDC) and 3 of which were noninvasive ductal carcinoma (NIDC). RESULTS: The mean ADC values of IDC, NIDC, and normal breasts were 1.07 +/- 0.19 .10(-3), 1.42 +/- 0.17 .10(-3), and 1.96 +/- 0.21 .10(-3) mm(2)/s, respectively. The mean ADC values of IDC and NIDC were significantly different from that of normal breasts (P < 0.001 each). The mean ADC values were also significantly different between IDC and NIDC (P < 0.001). There was no correlation between the ADC value and cancer cellularity. CONCLUSION: The mean ADC values for breast cancer were significantly different from that of normal breasts. The mean ADC value for breast cancer did not significantly correlate with cancer cellularity but did correlate with histological types.

[Efficacy of vinorelbine monotherapy in advanced and metastatic breast cancer].

Vinorelbine is a newanti-cancer drug that is available for advanced or metastatic breast cancer, approved by the Japanese Ministry of Health, Labour and Welfare in May 2005. At present, we evaluated the efficacy and safety of vinorelbine in our hospital. 51 patients were treated with vinorelbine since April 1, 2006 to August 20, 2007. Average age was 55.9 years old and period of treatment was 161.9 days. Average number of previous treatments was 2.2, and 37 patients(72.6%)were treated with anthracyclines and taxanes. The response rate was 19.6%, there was one complete responder, and nine partial responders. Especially, the response rate was 16.2% in patients pretreated with anthracyclines and taxanes. The major toxicity was grade 3 or 4 neutropenia(15.7%), and superficial phlebitis(7.8%). Vinorelbine will be a standard treatment agent for patients pretreated with anthracyclines and taxanes.

Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin.

BACKGROUND: The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases. METHODS: The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed. RESULTS: Median age was 45 years old (range 28-75) and tumor size was 1-17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1-273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P = 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01-0.743, P = 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P = 0.0139). CONCLUSION: Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.