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ABSTRACT: Mucocele-like tumors (MLTs) of the breast are rare, with only 11 cases reported from Japan and 35 cases from other countries. MLTs of the breast were first described by Rosen in 1986. They are believed to be related to atypical ductal hyperplasia, ductal carcinoma, or mucinous carcinoma. It is difficult to diagnose this tumor preoperatively, and especially difficult to differentiate between benign and malignant forms. We report a case of MLT associated with ductal carcinoma in situ, which was initially diagnosed as fibroadenoma by mammography and ultrasonography, and as mucinous carcinoma by fine-needle aspiration cytology. We discuss the characteristic findings of imaging and the appropriate clinical treatment of this tumor. The characteristic image first signals the possibility of this tumor, following which the diagnosis can be confirmed by pathological examination of a fully excised tumor specimen. Breast-conserving surgery is recommended because of the low risk of high-grade malignancy, even when malignancy is confirmed, and lymph node dissection may be avoided.
Surgery Today 02/2012; 42(3):280-4. · 1.22 Impact Factor
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Journal of Clinical and Experimental Hematopathology 01/2012; 52(1):71-5.
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ABSTRACT: Estrogen receptor (ER) and progesterone receptor (PgR) status are predictive factors for the clinical and pathological response to neoadjuvant chemotherapy for operable breast cancer. However, it remains unclear as to how the proportion of ER-positive or PgR-positive tumor cells affects the response to neoadjuvant chemotherapy. We examined the correlation of the proportion of ER-positive or PgR-positive tumor cells with the clinical and pathological response to neoadjuvant chemotherapy for operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer. From April 2002 to October 2010, 103 patients received neoadjuvant chemotherapy containing epirubicin and taxane in our clinic. A clinical response was observed in 86 (83%) patients, and a pathological complete response (pCR) was observed in 16 (16%) patients. Fourteen (30%) of 46 patients with ER-negative tumors achieved pCR and 15 (26%) of 57 patients with PgR-negative tumors achieved pCR. Patients with more than 30% ER-positive tumor cells or more than 1% PgR-positive tumor cells did not achieve pCR. No significant correlation was observed between pCR and the menopausal status, tumor size, grade and Ki-67 expression. In univariate analysis, pCR was associated with the ER status (p=0.001), PgR status (p=0.0001) and chemotherapy regimens (p=0.03). Multivariate analysis revealed that ER and PgR status were significant factors for pCR, and patients with ER-negative tumors were 18.6 times more likely to achieve pCR than those with greater than or equal to 30% ER-positive tumor cells (p=0.006; 95% confidence interval 2.3-149.9). We demonstrated a predictive significance of the proportion of ER-positive or PgR-positive tumor cells in the response to neoadjuvant chemotherapy for operable HER2-negative breast cancer. ER-negativity (<1%) was a significant predictive factor for achieving pCR in multivariate analysis. Conversely, patients with more than 30% ER-positive tumor cells or more than 1% PgR-positive tumor cells may not achieve pCR.
Experimental and therapeutic medicine 01/2012; 3(1):66-71.
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ABSTRACT: We report an autopsy case of a patient with Sjögren's syndrome (SjS) who presented with rapid progressive pulmonary fibrosis following the onset of diffuse alveolar hemorrhage (DAH) without cryoglobulinemia. Despite early and aggressive immunosuppressive therapy, pulmonary fibrosis progressed and the patient succumbed to his illness. An autopsy was performed and revealed DAH and interstitial pneumonia with a fibrotic nonspecific interstitial pneumonia pattern. We could not find any previously-reported underlying causes of DAH. The findings from this case suggest that DAH can occur as a pulmonary manifestation of SjS as well as other connective tissue diseases or vasculitis.
Internal Medicine 01/2012; 51(3):295-9. · 0.94 Impact Factor
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ABSTRACT: A 57-year-old man was admitted to our hospital with a complaint of perineal pain. He was diagnosed as advanced rectal cancer with an invasion of prostate, and we conducted neoadjuvant capecitabine, oxaliplatin, bevacizumab and radiation therapy. After chemoradiation therapy, the tumor regressed to an ulcerative lesion without invasion of the prostate. Abdominoperineal resection was then performed without radical resection. The tumor regressed to an ulcer and only a few cancer cells were detected in the submucosal layer pathologically.
Gan to kagaku ryoho. Cancer & chemotherapy 09/2011; 38(9):1545-7.
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American Journal of Hematology 07/2011; 86(7):609. · 4.67 Impact Factor
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ABSTRACT: Trastuzumab demonstrates significant clinical benefits in HER2-positive metastatic breast cancer (MBC), and recent clinical trials suggest that trastuzumab should be continued in combination with other chemotherapy beyond progression. There is an urgent need to assess if patients could substantially benefit from continuing trastuzumab-based therapy.
We reviewed 91 patients with HER2-positive MBC treated with trastuzumab and investigated correlations between survival and clinical response to first trastuzumab-based therapy and biological markers, time to first tumor progression (1st TTP), response rate (RR), estrogen receptor (ER), Ki-67, and p53 overexpression.
With a median follow-up of 33 months, 76 patients had received two or more lines of consecutive trastuzumab-based therapy. Median 1st TTP was 8.6 months; patients who received trastuzumab with chemotherapy had a longer 1st TTP and better RR than those without chemotherapy. In terms of survival after first progression, patients with a longer 1st TTP (≥ 8.6 months) had significantly better survival compared with those who had a shorter 1st TTP (24.3 months vs. 15.4 months, P = 0.024), and multivariate analysis revealed that 1st TTP was a significant prognostic factor (HR 0.44, 95% CI 0.23-0.82, P = 0.01). There were no correlations between survival and ER or Ki-67; however, there was a correlation with p53 overexpression (HR 1.92, 95% CI 1.01-3.64, P = 0.045).
1st TTP is a significant prognostic factor for patients who receive subsequent trastuzumab-based therapy. This factor should be considered when determining the efficacy of continuing trastuzumab or switching to another anti-HER2 therapy beyond progression.
International Journal of Clinical Oncology 05/2011; 16(6):694-700. · 1.41 Impact Factor
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ABSTRACT: A 67-year-old man underwent right hemi-colectomy for ascending colon cancer in 2007. One year later, he was diagnosed as early gastric cancer, and endoscopic submucosal dissection was performed. Pathologically, cancer cells were detected on the vertical margin, so we conducted distal gastrectomy. A dissected lymph node around the hepatic artery was histologically proved to contain adenocarcinoma cells. The cancer cells were positive for CK20. Colon cancer cells were also positive for CK20 but gastric cancer cells were focally positive for CK20. This pattern of CK staining suggested the ascending colon cancer metastasized to a gastric regional lymph node.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2011; 38(3):473-5.
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ABSTRACT: Trastuzumab has shown significant clinical benefits in patients with operable and metastatic HER2-positive breast cancer. However, the biological mechanism of the additional effect of trastuzumab administered in combination with conventional chemotherapy is poorly understood. We performed a retrospective analysis of 55 patients with HER2-positive breast cancer treated with anthracycline and taxane (chemotherapy alone; CT), or trastuzumab in combination with taxane-based chemotherapy (CT+T) for neoadjuvant chemotherapy. We determined the therapeutic efficacies [clinical (CR) and pathological complete responses (pCR)] and changes in the proportion of positive cells for each biomarker pre- to post-neoadjuvant chemotherapy for each treatment regimen. Clinical-CR and quasi-pCR rates defined as the absence of invasive tumors or only a few remaining invasive tumor cells were 6.9 and 31.0% in the CT group and 46.2 and 65.4% in the CT+T group, respectively. In the CT group, the proportion of estrogen receptor (ER)-/progesterone receptor (PgR)-positive cells decreased significantly following treatment (ER, 73.5 vs. 50.9%; P=0.02). Changes in the proportion of ER-/PgR-positive cells were not noted in the CT+T group (ER, 81.9 vs. 80.3%; P=0.61), although a relatively greater decrease in the proportion of Ki-67-positive cells was found in the CT+T group than that in the CT group (-26.5 vs. -13.7%). These findings indicate that CT+T inhibits ER-negative and Ki-67-positive breast cancer cells. In conclusion, trastuzumab sensitized ER-negative proliferative cells to cytotoxic chemotherapy. This finding may indicate an additional clinical effect of trastuzumab when administered in combination with conventional chemotherapy as neoadjuvant chemotherapy for HER2-positive breast cancer.
Oncology letters 03/2011; 2(2):303-308. · 0.11 Impact Factor
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ABSTRACT: In breast cancer, ER/PgR, HER2, and Ki-67 are important biological markers for predicting prognosis and making effective treatment decisions. In addition, changes in markers due to relapse are also clinically experienced; however, the frequency and clinical significance are still not fully understood. Thus, changes in markers and their correlations with prognosis were investigated.
Out of the patients with relapse from 1997 to March 2011, there were 97 consecutive patients from whom the lesion was resected and evaluated by immunostaining. The biopsy sites were chest wall, lymph node, ipsilateral breast tumor recurrence, lungs, bones, ovaries and brain. The markers sought were ER, PgR, HER2, p53 and Ki-67.
The hormone receptor positive rate from the primary tumor to recurrence decreased from 63.9% to 57.7% and from 56.7% to 43.3% for ER and PgR, respectively. Changes in the positive/negative evaluation were seen at the rate of 10.3% and 25.8% for ER and PgR, respectively. The Ki-67 index increased significantly from a mean of 29.1% at primary tumor to 36.3% at relapse. When divided into 2 groups (< 50% and ≥50%), changes were seen in 24.7%. On the other hand, the rates of changes in HER2 and p53 positivity were 14.4% and 12.4%. The changes in subtypes were seen in 25%, however, the lowest rate of change was seen in the triple negative cases. Although there was no notable difference in the rate of change between disease-free interval (DFI) and PgR, Ki-67, p53 and HER2, there was a significant difference in the change rates in the ER. A multivariate analysis revealed that the status of distant metastasis and PgR level at relapse, and Ki-67 levels at primary tumor were all significant factors.
Estrogen receptor and PgR decreased while Ki-67 increased due to relapse; however, the rate of change was high for PgR and Ki-67. Change in the subtypes was seen in 25%. In addition, PgR at relapse and Ki-67 at primary tumor were significant factors for post-relapse prognosis while PgR becoming negative was a poor prognostic factor. These findings are important for making effective treatment decisions.
World Journal of Surgical Oncology 01/2011; 9:131. · 1.12 Impact Factor
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International journal of hematology 10/2010; 92(3):547-9. · 1.17 Impact Factor
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ABSTRACT: The choice of adjuvant systemic therapy is based on targeted therapy in line with the St. Gallen Consensus meeting. In addition to the traditional parameters, the panel recommended the use of proliferation markers and multigene assays. The purpose of the present study was to evaluate the clinical significance of proliferative activity using the Ki-67 index as a prognostic marker and as a predictor of recurrence time in breast cancer patients. The Ki-67 index was measured in 3,652 cases with primary breast cancer from 1987 to 2009. Out of these patients, 2,638 cases were evaluated simultaneously for estrogen receptor, progesterone receptor and HER2 from 1997, and these were analyzed as a prognostic factor according to their subtypes. The Ki-67 index exhibited a wide range of 1-99%, with a median of 20%, and cases were divided into 2 or 3 index groups; <20% and ≥20% (and ≥50%). The median Ki-67 index of tumors with luminal A was 17%, and that of luminal B type tumors was 29%. The Ki-67 index of HER2 tumors was 40% and that of triple negative tumors was 50%. A higher Ki-67 index significantly correlated with a higher grade of malignancy. Patients with a higher Ki-67 index had significantly lower disease-free survival (DFS) and overall survival rates. Moreover, there was a significant difference in the recurrence time. Multivariate analysis revealed that the Ki-67 index was a significant factor for DFS, irrespective of nodal status, and that Ki-67 was a significant marker only in luminal A type tumors. Furthermore, luminal A type cases with high Ki-67 had a similar DFS as the luminal B type cases. A higher Ki-67 index (≥20%) significantly correlated with other biological markers, poorer prognosis and early recurrence, particularly in luminal A type tumors. It is important to take the Ki-67 index into consideration in the treatment and follow-up of breast cancer patients.
Experimental and therapeutic medicine 01/2010; 1(5):747-754.
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ABSTRACT: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In recent years several biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were discovered to be predictive factors for the effectiveness of NAC to help individualize treatment. In this retrospective study, we focused on Ki-67 as a biological marker and examined the correlation between Ki-67 and chemosensitivity, and the prognosis after the start of treatment.
Between July 1996 and March 2008, 148 patients with tumors ≥ 3 cm in diameter or lymph node metastases received NAC and surgery. The items investigated were ER/PgR and Ki-67 from core needle biopsy. The treatment regimens were EC in 36 cases, ET in 51 cases, and FEC-DOC in 61 cases. The patients with FEC-DOC regimen had smaller tumors and higher Ki-67 values than the others.
Clinical response (cCR + cPR) was 79.7%, and the pathological complete response (pCR) was 14.2%. Multivariate analysis revealed that Ki-67 was significantly related to pCR. Moreover, there was no pathological responder in cases with Ki-67 < 25%. The Ki-67 values significantly decreased after NAC (median from 45.0 to 17.5%). Patients with cCR had significantly lower Ki-67 values after NAC than those with cPR, cSD, and cPD. There was a significant difference in the Ki-67 value in terms of the presence and the absence of recurrence (median 26.0% with recurrence vs. 12% without recurrence). The disease-free survival (DFS) rate after the start of treatment was significantly higher in the patients with Ki-67 < 12% after NAC than those with Ki-67 ≥ 12%.
The Ki-67 value before NAC was a significant predictive factor for the effectiveness of NAC. The Ki-67 values after NAC significantly decreased and correlated with clinical response and DFS. Therefore, higher Ki-67 values (≥ 25%) before NAC as well as lower values (<12%) after NAC might be clinically significant for treating patients.
Breast Cancer 09/2009; 17(4):269-75. · 1.36 Impact Factor
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ABSTRACT: An 88-year-old female was admitted to our hospital due to a right breast tumor and biclonal gammopathy (IgG-lambda and IgA-lambda). CT scan showed systemic lymphadenopathy. Tumor specimens were comprised of medium-sized atypical lymphocytes. Lymphoepithelial lesions and plasmacytic differentiation were observed. The atypical lymphocytes were positive for CD20, CD79a, Bcl-2, CD5 and negative for CD10, Cyclin D1. Moreover, the cells expressed IgG-lambda or IgA-lambda. We diagnosed the patient's disease as lymphoplasmacytic lymphoma (LPL). Although biclonal gammopathy with IgM elevation has been reported in LPL patients, this is the first case of IgG+IgA type biclonal gammopathy.
[Rinshō ketsueki] The Japanese journal of clinical hematology 05/2009; 50(4):309-12.
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ABSTRACT: A 71-year-old male consulted our hospital complaining of right tonsil enlargement. Tonsillectomy was performed. Histological analysis demonstrated AL amyloid deposits obliterating the tonsillar structures. Foreign body giant cell reaction and morphologically normal plasma cells mainly containing light chain lambda were present around the amyloid. Serum immunoglobulin levels were normal and M-proteins were not detected. Urinary test for Bence Jones proteins was negative. Bone marrow aspirates did not demonstrate any signs of multiple myeloma. Amyloidosis of the stomach, colon, heart, and skin was ruled out. We report an extremely rare case of amyloidosis localized in the tonsil and review the literature.
[Rinshō ketsueki] The Japanese journal of clinical hematology 01/2009; 49(12):1628-30.
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ABSTRACT: Neoadjuvant chemotherapy (NAC) is the standard therapy for locally advanced breast cancer. Recently, several studies have revealed that clearance of axillary lymph node involvement is an independent factor for survival irrespective of the response of the primary lesion. However, in daily practice, it is difficult to fully examine every lymph node that has been surgically sampled, in view of pathology laboratory workload and cost. Therefore, in the present study, we adopted the more clinically relevant categorization of evaluating postoperative axillary lymph node status and retrospectively studied its significance in predicting patients' survival.
The study cohort consisted of 35 locally advanced breast cancer patients who are treated with concomitant epirubicin-docetaxel. The clinicopathological factors used for analysis were as follows: ERalpha, PgR, p53, HER2, pathological response (in the primary tumor), and axillary lymph node status at surgery. With regard to axillary lymph node status, we categorized patients into two groups: those with pathological lymph node involvement at surgery (pLNI) and those without. Using multivariate analysis, we evaluated the significance of these factors in predicting disease-free survival after surgery.
The median follow-up period was 23.4 months (range 4.3-45.4). Multivariate analysis showed significantly reduced disease-free survival associated with pLNI (P = 0.005).
pLNI is an excellent prognostic factor for locally advanced breast cancer patients treated with concomitant epirubicin-docetaxel. Use of our criteria may enable large numbers of oncologists to participate in new studies of high-risk cohorts who are refractory to NAC.
Breast Cancer 06/2008; 16(1):42-8. · 1.36 Impact Factor
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ABSTRACT: Breast cancer is characterized by hormone dependency, and endocrine therapy is a key treatment in breast cancer. Recently, targeted therapies such as Trastuzumab treatment for HER2-positive breast cancer has been important. Triple-negative (TN) breast cancer is characterized by lack of expression of estrogen receptor (ER) and progesterone receptor (PgR), and the absence of HER2 protein overexpression, and so there is no targeted therapy for this subtype. In this study, we examined the biological and prognostic characteristics in TN breast cancer.
Between January 1998 and September 2006, 1,552 patients with primary breast cancer were investigated retrospectively in this study and ER, PgR and HER2 status were evaluated in all cases. Furthermore, p53 overexpression and Ki67 values were examined immunohistochemically.
Patient distribution according to ER, PgR or HER2 status was as follows: ER and PgR positive: 57.9%, and ER and PgR negative: 25.1%. With regards to the HER2 status, HER2 positive was 23.3%, and triple negative (TN) was 14.0%. TN breast cancer has a high proliferation rate, high nuclear grade and frequent p53 overexpression. Patients with TN tumors had a significantly poorer disease-free survival (DFS) than those with non-TN tumors. After recurrence the overall survival (OS) rate in TN cases was significantly lower than that of the non-TN cases. Multivariate analysis revealed that TN was a significant factor for DFS and OS after recurrence.
TN breast cancer is a rare subtype with a high proliferation rate and a high nuclear grade, p53 overexpression, and lower DFS/OS. To improve the prognosis of TN breast cancer, a new effective strategy needs to be developed.
Breast Cancer 04/2008; 15(4):303-8. · 1.36 Impact Factor
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ABSTRACT: HER2 expression is an important prognostic and predictive factor of treatment efficacy in breast cancer. Trastuzumab, in particular, is a key drug in the treatment of HER2-positive recurrent breast cancer. However, the difference in treatment efficacy between trastuzumab monotherapy and combination therapy with chemotherapy is unclear. In order to elucidate this point, both treatments were compared in terms of efficacy by metastatic site, time to progression (TTP), and survival.
The subjects were 1,471 breast cancer patients who had been evaluated for HER2 expression between 1998 and March 2006; 74 of these had recurrent breast cancer that had been treated with trastuzumab. Of these 74 patients, 39 received trastuzumab alone and 45 trastuzumab in combination with chemotherapy. The items of investigation were clinical effect, TTP, survival, biological markers such as ER/PgR, proliferation (Ki67) or p53 overexpression, nuclear grade, performance status (PS), lymph node metastasis, and tumor size.
The HER2-positive rate was 23.3%, and the degree of malignancy in these HER2-positive patients was high; postoperative disease-free survival (DFS) was low. However, this tendency was clear in patients with hormone-responsive breast cancer. In patients with hormone-non-responsive breast cancer, HER2 negativity had a significantly higher Ki67 value, and there was no difference in DFS between patients with HER2-positive and -negative tumors. Among the 74 patients with recurrent breast cancer, the response rate to trastuzumab was 64.9%; however, among patients who received the combination treatment, the response rate was 86%. In patients with liver metastasis, the effect of trastuzumab alone was low, but that of the combination treatment was significantly high. TTP was 5.7 months and 15.9 months with trastuzumab alone and the combination therapy, respectively. Furthermore, a significant difference was seen in post-treatment survival; however, there was no significant difference in survival after a recurrence. In the multivariate analysis on factors for TTP, PS, clinical effect, and combination treatment were significant. However, good PS and early treatment were the significant factors in post-treatment survival.
The effect of trastuzumab in patients with recurrent breast cancer who received the combination treatment was significantly high and TTP was long. However, this was not a significant factor in terms of overall survival. In particular, a good PS and early treatment were important in post-treatment survival.
Breast Cancer 02/2008; 15(1):57-64. · 1.36 Impact Factor
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ABSTRACT: Mina53 (mina) was identified as a gene, which is directly induced by the oncogene c-myc. Elevated expression of Mina53 protein was found in >80% of colon cancer and esophageal squamous cell carcinoma (ESCC). Patients with high expression of Mina53 had shorter survival, suggesting the prognostic usefulness of Mina53. We studied Mina53 expression in lymphoma subtypes to examine its diagnostic significance and its possible role in lymphoma-genesis. Surgical cases of 28 lymphoma and 4 non-neoplastic tissues were stained immunochemically using anti-Mina53 monoclonal antibody. Mina53 expression correlated well with c-Myc expression in lymphoma, suggesting that c-Myc is a controlling factor for mina53 expression also in lymphomas. Although the expression of Mina53 as well as c-Myc was less frequent in lymphoma compared with those of colon and ESCC, increased expression of Mina53 was found in Burkitt-like lymphoma (1/1), Hodgkin's lymphoma (3/5), diffuse large B cell lymphoma (DLBCL) (5/13), lymphomas with a transition from follicular to DLBCL (1/2), with none in follicular (0/4) and T cell lymphoma (0/3). Analyses of the data suggested that Mina53 was frequently expressed in aggressive types of B cell lymphoma. To get more information about the expression of Mina53 in DLBCL, which most frequently occurs among lymphomas, we analyzed the expression of Mina53 in another 21 DLBCL specimens, which were in more advanced stages than those described above. The expression level of Mina53 correlated to the international prognostic index (IPI) values with statistical significance (r=0.477, P=0.0275). Notably, in this group, Mina53 expression did not correlate with c-Myc expression, suggesting that other factor(s) besides c-Myc largely affect the expression of Mina53 in advanced DLBCL. These results suggest that although Mina53 expression is not prominent in lymphoma in general, it may be related to tumor progression of B cell lymphoma.
Oncology Reports 10/2007; 18(4):841-8. · 1.84 Impact Factor
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ABSTRACT: Hormone receptor status has been one of the most important factors in predicting the response to endocrine therapy in breast cancer patients. However, half of those patients with estrogen receptor-positive tumors do not respond to endocrine therapy. There have been no universal factors for predicting resistance to endocrine therapy in this population. Recently, p53 status has been extensively used as a predictive factor for response to systemic therapy, because tumor cells lacking p53 function do not respond to systemic therapy due to a failure in apoptosis. We therefore studied the relationship between the efficacy of endocrine therapy and biological factors, including p53.
The expression of p53, Ki67, and human epidermal growth factor receptor (HER)2 was examined by immunostaining in the primary tumors of 53 patients who received endocrine therapy for recurrent or advanced breast cancer. The following clinical factors were also analyzed: site treated, disease-free interval, and response to first-line endocrine therapy. To evaluate the significance of these factors, time to endocrine therapy failure (TTEF), or the total duration of sequential endocrine therapies was adopted as representing the clinical outcome.
The median TTEF was 16.1 months (range, 2.5-89.9 months). Multivariate analysis showed significantly reduced TTEF associated with no response to first-line endocrine therapy (P = 0.006 and P = 0.002 in all patients and in recurrent patients, respectively) and associated with positive p53 expression (P = 0.066 and P = 0.004, respectively).
p53 expression status was a significant molecular marker as well as the response to first-line endocrine therapy for predicting TTEF in recurrent breast cancer with hormone-sensitive disease.
International Journal of Clinical Oncology 01/2007; 11(6):426-33. · 1.41 Impact Factor
