Clinical significance of circulating tumor cells in peripheral blood from patients with gastric cancer.

BACKGROUND: The authors hypothesized that circulating tumor cells (CTCs) in patients with gastric cancer are associated with prognosis and disease recurrence. In this study, they evaluated CTCs in gastric cancer and clarified the clinical impact of CTCs. METHODS: In total, 265 consecutive patients with gastric cancer were enrolled. Fourteen patients were excluded from the analysis, including 12 patients who another cancer and 2 patients who refused the treatment. The remaining 251 patients were divided into 2 groups: 148 patients who underwent gastrectomy (the resection group) and 103 patients who did not undergo gastrectomy (the nonresectable group). Peripheral blood samples were collected before gastrectomy or chemotherapy. A proprietary test for capturing, identifying, and counting CTCs in blood was used for the isolation and enumeration of CTCs. RESULTS: CTCs were detected in 16 patients (10.8%) from the resection group and in 62 patients (60.2%) from the nonresectable group. The overall survival rate for the entire cohort was significantly lower in patients with CTCs than in those without CTCs (P < .0001). In the resection group, relapse-free and overall survival in patients with CTCs was significantly lower than in patients without CTCs (P < .0001). It was noteworthy that the expression of CTCs was an independent factor for determining the overall survival of patients with gastric cancer in multivariate analysis (P = .024). In the nonresectable group, the overall survival rate was significantly lower in patients with CTCs than in those without CTCs (P = .0044). CONCLUSIONS: The evaluation of CTCs in peripheral blood may be a useful tool for predicting tumor progression, prognosis, and the effect of chemotherapy in patients with gastric cancer.

Clinical implication of HLA class I expression in breast cancer.

BACKGROUND: Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified. METHODS: A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed. RESULTS: The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval. CONCLUSION: The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.

Immediate breast reconstruction using autologous free dermal fat grafts provides better cosmetic results for patients with upper inner cancerous lesions.

PURPOSE: Although breast-conserving therapy (BCT) is the standard form of treatment for early-stage breast cancer, in patients with small breasts cosmetic results can be poor, especially when the lesion is located on the inner upper quadrant area. This study analyzes our use of autologous free dermal fat grafts (FDFGs) for immediate breast reconstruction. METHODS: A total of 23 patients who received a partial mastectomy for an inner upper quadrant lesion from 1992 to 2006 at Kagoshima University Hospital were retrospectively divided into three groups according to the reconstructive procedure that was used for the defect after partial mastectomy: immediate reconstruction using an autologous FDFG from the lower abdomen (group FDFG); patients receiving only rotation and fixation of the parenchymal adipose tissue or gland to repair the defect (group GL); and a third group who underwent immediate reconstruction using a miniflap of the latissimus dorsi (group LD). RESULTS: The total duration of surgery in group FDFG was significantly shorter than in group LD (P < 0.01). The mean volume of blood lost in group FDFG was significantly lower than in group LD (P < 0.01). The breast retraction assessment (BRA) of group FDFG was significantly better than for the patients in groups GL and LD (P < 0.01). The total score using the ABNSW system for cosmetic assessment was significantly better in group FDFG than in group GL (P < 0.01). Similarly, the total score in group FDFG using the assessment by the Japanese Breast Cancer Society was significantly higher than that in group GL (P < 0.01). CONCLUSION: Immediate breast reconstruction for a defect after a partial mastectomy of an upper inner quadrant malignant lesion using FDFG can be especially useful for patients with small breasts.

Oncoplastic surgery for Japanese patients with ptotic breasts.

BACKGROUND: Oncoplastic techniques, which combine the concepts of oncologic and plastic surgery, are becoming more common, especially in Western countries, however, only a few case reports have been published in Japan. We report the results of oncoplastic surgery for Japanese patients with early breast cancer in the lateral quadrant area. METHODS: In eight patients, their breasts were ptotic, and each lesion was diagnosed to be suitable for breast-conservative surgery, we performed oncoplastic surgery combining reduction-type partial mastectomy with nipple-areola recentralization. RESULTS: The total operation period ranged from 112 to 290 min with the mean period being 189 min. For the six patients who received contralateral mirror image reduction surgery and recentralization of the nipple-areola complex, the reconstruction period ranged from 80 to 230 min with the mean period being 102 min. For two patients who underwent oncoplastic surgery to the treated breast only, the reconstruction periods were 40 and 60 min, respectively. The weights of the resected tissue of the treated breast ranged from 60 to 306 g whereas that of the contralateral breast ranged from 70 to 302 g. Postoperative seroma after axillary dissection was observed in one case. CONCLUSIONS: Oncoplastic surgery for patients with ptotic breasts was successfully performed and may become more popular in Japan in the near future.

Utility of the GeneSearch breast lymph node assay for the rapid evaluation of sentinel lymph nodes in breast cancer.

BACKGROUND: The potential for reducing the need for second surgery for axillary lymph node dissection (ALND) has made the intraoperative evaluation of sentinel lymph nodes (SLNs) attractive. The goal of the current study was to evaluate the clinical application of the breast lymph node (BLN) assay, a real-time reverse transcriptase-polymerase chain reaction assay for SLN metastases, by comparing this test with routine pathologic examination. METHODS: A total of 117 patients with breast cancer underwent breast surgery with SLN biopsy. Each SLN was cut in half along the plane of the longest dimension. Half of each lymph node was examined by the 2 markers of the BLN assay, mammaglobin and cytokeratin 19, and the other half was examined by hematoxylin and eosin staining (H&E) and immunohistochemical staining (IHC) for pancytokeratins. RESULTS: A total of 204 SLNs were obtained from 117 patients. H&E staining identified metastases in 31 SLNs (15.2%), and IHC staining detected metastases in 6 SLNs; 40 SLNs from 32 patients were found to be positive for metastasis using the BLN assay. The assay results were correlated with the pathologic diagnoses by H&E and IHC staining (P<.001). The sensitivity of the BLN assay compared with pathologic findings classified according to the TNM classification was 95.7% for macrometastases, 60.0% for micrometastases, and 55.6% for isolated tumor cells. CONCLUSIONS: The 2-marker BLN assay performs in a manner that is comparable to, and analyzes more tissue than, routine pathologic examination. Therefore, clinical intraoperative use of the BLN assay for SLNs may result in a reduction in the need for second surgery for ALND.

The utility of rapid diagnosis of lymph node metastasis in gastric cancer using a multiplex real-time reverse transcription polymerase chain reaction assay.

BACKGROUND: Lymph node metastasis is the most important prognostic factor in gastric cancer. However, diagnosis by hematoxylin and eosin staining or immunohistochemistry is not always sufficient for the detection of cancer cells because only representative number of slices are examined. Cancer cells may, therefore, be missed by traditional histological methods. Recently, reverse transcription polymerase chain reaction (RT-PCR) methods have been introduced for improved detection of cancer cells. The purpose of this study was to evaluate the utility of a prototype RT-PCR assay run on the Cepheid SmartCycler system compared to conventional RT-PCR using the LightCycler system. PATIENTS AND METHODS: Forty-seven overt metastatic lymph nodes from 8 patients with advanced gastric cancer and 22 benign lymph nodes from patients without malignant tumor who received surgery were obtained with informed consent. We examined the lymph nodes by RT-PCR, using markers for CEA and CK19 and the LightCycler and SmartCycler systems. RESULTS: In the singlex assay, the sensitivity of CEA and CK19 was 91.5 and 70.2% in the LightCycler system, and 97.9 and 95.7% in the SmartCycler system, respectively. In the multiplex assay, the sensitivity was 91.5% in the LightCycler system and 100% in the SmartCycler system, respectively. CONCLUSION: In this study, rapid diagnosis using RT-PCR by the SmartCycler system had higher accuracy for detecting lymph node metastasis than the conventional LightCycler system. The SmartCycler system is more effective for the diagnosis of lymph node metastasis in gastric cancer when run with the prototype assay.

Synchronous bilateral breast cancer in a male patient following hormone therapy for prostate cancer.

We report an unusual case of bilateral, synchronous breast cancer in a male patient who had a history of estrogen therapy for prostate cancer. A 64-year-old Japanese man was diagnosed with T1N0M0 prostate cancer and received a total prostatectomy. Twenty months after the resection, the patient developed multiple bone metastases, and received radiation therapy, systemic chemotherapy, and hormone therapy for 15 months. After completing this treatment, he was diagnosed with T1N0M0 primary breast cancer in his left breast and underwent a modified mastectomy. Five months after the mastectomy he received systemic chemotherapy followed by estrogen therapy because of the progression of prostate cancer. Three months after this treatment, he was diagnosed with T1N0M0 primary breast cancer in his right breast. To the best of our knowledge, this is a rare case of synchronous bilateral male breast cancer following hormone therapy for prostate cancer.

Immediate reconstruction using thoracodorsal adipofascial flap after partial mastectomy.

BCT (breast conserving therapy) has become a standard strategy for breast cancer and ensures local control and acceptable cosmetic results. However, an insufficient resection margin may increase local recurrence if too much attention is paid to cosmesis. Here, we describe a simple technique for reconstruction of the defect on the outer upper part of the breast with early breast cancer using thoracodorsal adipofascial flap.

Intramammary sentinel lymph node in patients with breast cancer: report of four cases.

To analyze breast cancer patients with intramammary sentinel lymph node, we reviewed T1-T2N0 breast cancer patients who underwent sentinel lymph node mapping using radioisotope methods. Intramammary sentinel lymph (ISN) nodes were detected in 4 of 166 patients. Three of four ISNs were present in completely different quadrants of the breast from those of primary lesions. Although two patients had no involved nodes, including ISNs, the remaining two with T2 tumor had metastasis of ISNs alone with resulting upstaging. We should keep in mind the presence of intramammary SN in regions apart from the primary tumor, particularly when performing breast conservative surgery.

Detection of micrometastases in sentinel node navigation surgery for gastric cancer.

Although lymph node metastasis is one of the important prognostic factors for patients with gastric cancer, the clinical significance of micrometastasis remains controversial. In the 6th edition of the TMN classification, micrometastases were classified as micrometastasis (MM) and isolated tumor cells (ITC) according to its greatest dimension. The accurate diagnosis of micrometastases is required when considering less invasive surgery, especially in early stage of gastric cancer. Since generating useful information about micrometastases by conventional RT-PCR is time-consuming, this procedure is not useful for rapid diagnosis during surgery. Recently some new methods of genetic diagnosis have reduced the amount of time required to obtain information about micrometastases in lymph nodes to 30-40 min. Such methodology can be clinically applied during less invasive surgery. The sentinel node (SN) concept has recently been applied to gastric cancer and SN navigation surgery (SNNS) is ideal for reduction of lymphadenectomy in patients with early gastric cancer. However, we should think about some conditions to establish SN concept for gastric cancer: the particle size of radioisotope, relationship between metastatic area and RI uptake, and the diagnosis of micrometastases by various method such as histological examination, immunostaining and RT-PCR. Here, we described the current status of MM and ITC in the lymph nodes and the SN concept in gastric cancer.

Oncoplastic surgery after mammary reduction and mastopexy for bilateral breast cancer lesions: report of a case.

We report a case of bilateral breast cancer lesions treated successfully by partial oncoplastic surgery. A 46-year-old Japanese woman presented with a small mass in the right breast. Mammography showed neither a mass nor calcification in the right breast; however, an irregular-shaped mass lesion was shown in the left breast. Ultrasonography and fine-needle aspiration biopsy revealed ductal carcinoma in situ in the inner-upper quadrant of the right breast and invasive ductal carcinoma in the outer-upper quadrant of the left breast. We considered that it would be difficult to obtain a good symmetrical outcome after partial mastectomy for the bilateral breast lesions because of the asymmetrical location of each lesion and her ptotic breasts. Thus, we performed bilateral partial resection, followed by an inferior pedicle reduction mammaplasty-type operation, with and without axillary lymphadenectomy, and achieved good cosmetic and oncologic results.

Analysis of T-helper type 1 and 2 cells and T-cytotoxic type 1 and 2 cells of sentinel lymph nodes in breast cancer.

The immune suppression of sentinel lymph node (SN) is directly influenced by primary tumors. It has been reported that the T-helper type 1 (Th1) to T-helper type 2 (Th2) ratio or T-cytotoxic type 1 (Tc1) to T-cytotoxic type 2 (Tc2) ratio of lymph node lymphocytes could be used to evaluate direct immunological circumstances. We attempted to evaluate the Th1 to Th2 cell and Tc1 to Tc2 cell balance in SN and non-SN and to clarify the immunological status of sentinel nodes in breast cancer. To evaluate this balance, SN and non-SN were identified by radioguided methods and lymph node lymphocytes were collected, and prepared for flow cytometry. The Th1 to Th2 and Tc1 to Tc2 ratio were calculated by 3-color flow cytometry. The ratio of SN and non-SN was compared. The results demonstrated that SN was detected in 24 out of 24 patients (100%). As regards the correlation between SN and non-SN in the same patients, the Th1 to Th2 ratio in SN was significantly lower than that in non-SN for all patients (p<0.05). Among clinicopathological factors, a larger tumor diameter, histology and nodal involvement affected the decreased Th1 to Th2 ratio in SN significantly (p<0.05). We reached the conclusion that the increasing immunosuppressive conditions derived from the tumor may deteriorate the Th1 to Th2 ratio of SN in an earlier stage as compared with non-SN. According to the tumor extension and nodal involvement, the Th1 to Th2 ratio in SN was significantly suppressed. The current result supports that mainly helper T-cell paralysis occurred first in SN and this seems to be a favorable condition in forming lymph node metastases in SN. Moreover, the immunologic interaction between the primary site and regional lymph nodes may serve as useful criteria for identifying sentinel nodes.

Ultrasound examination is useful for prediction of histologic type in invasive ductal carcinoma of the breast.

The aim of this study was to estimate the histologic type of invasive ductal carcinoma of the breast according to the ultrasound (US) criteria and to identify the high-risk patients for lymph node metastases. An acceptable preoperative diagnosis of lymph node metastasis is essential when performing the reduction of lymphadenectomy. The positive relationship between histology and prognosis has been reported in breast cancer. However, few reports have examined the relationship between preoperative US findings and histology. Ultrasound examination was performed in 252 patients with invasive ductal carcinoma (91 papillotubular, 54 solid-tubular and 107 scirrhous carcinoma). Risk factors for nodal metastasis were analyzed in clinicopathological findings. After nine criteria were defined based on US findings, all tumors were classified into US histologic type. According to the multivariate analysis, lymph node metastases was significantly associated with tumor size (p < 0.001), histology (p < 0.001) and age (p = 0.038). Histology was an important risk factor for nodal metastasis, especially in scirrhous carcinoma. When comparing the US classification and histology, the accuracy rate of US for papillotubular, solid-tubular and scirrhous type was 75%, 78% and 75%, respectively. To predict the scirrhous carcinoma with frequent nodal metastasis, US criteria such as the larger ratio of depth-to-width, boundary echo and attenuation of the back echo was important. It is important to preoperatively estimate the histologic type by tumor property using US. Our US classifications may be useful to pick up high-risk patients for nodal metastasis in invasive breast cancer.

Stromal sarcoma with features of giant cell malignant fibrous histiocytoma.

We report a case of primary giant cell malignant fibrous histiocytoma (GCMFH) of the breast. A 56-year-old Japanese woman presented with a firm mass in the right breast. Mammography and ultrasonography revealed a well-circumscribed and lobulated mass in the upper outer quadrant of the right breast, indicative of a benign breast tumor or mucinous carcinoma. Magnetic resonance imaging revealed a restricted breast tumor without intraductal spread. Computed tomography and bone scintigraphy found no sites of distant metastases. Fine needle aspiration biopsy showed several clusters of atypical cells associated with numerous multinucleated giant cells. Breast-conserving surgery with axillary lymph nodes dissection was performed. Histological examination showed primary GCMFH of the breast. No metastases were identified in any of the 15 left axillary lymph nodes resected and surgical margins were free from tumor cells. The tumor was negative for both estrogen and progesterone receptor. Neither adjuvant chemoendocrine therapy nor postoperative radiotherapy was given, and the patient has remained disease free for 30 months postoperatively. To our knowledge, only 30 cases of primary MFH of the breast have been reported in the literature.

Immediate reconstruction using inframammary adipofascial flap of the anterior rectus sheath after partial mastectomy.

Treatment of early breast cancer using breast conservative therapy (BCT) usually ensures local control and acceptable cosmetic results. To repair defects caused by partial mastectomy in the lower region of the breast, some reconstruction should be used. We developed a procedure involving the cranial based adipofascial (anterior rectus sheath) flap from immediately below the inframammary area for the reconstruction of defect due to partial mastectomy for patients with early breast cancer. In this procedure, a skin incision is made at the inframammary line, and the inframammary skin area is undermined. A tongue shaped flap composed of the subcutaneous fat and the anterior sheath of rectus abdominis muscle is pulled up and a C-shaped flap is rotated, gathered, and inserted to reconstruct the breast defect.

Sudden hemorrhage without skin invasion in a patient with breast cancer: a case report and literature review.

We report a rare case of sudden hemorrhage caused by breast cancer. A 70-year-old Japanese woman noted fresh bleeding from her left breast. On physical examination, continuous hemorrhage accompanied by an open cavity was observed in the left breast. Mammography and ultrasonography revealed a well-circumscribed mass, with solid and cystic components, that was highly suggestive of intracystic breast carcinoma with direct skin invasion. Computed tomography and bone scintigraphy showed no distant metastasis. Aspiration biopsy of the lesion showed several clusters of adenocarcinoma cells. Modified radical mastectomy was performed with a presumptive diagnosis of stage III B left breast cancer. Invasive ductal carcinoma without skin invasion was diagnosed histologically. To the best of our knowledge, only 6 other cases of sudden hemorrhage caused by breast cancer without skin invasion have been reported in Japan. We review the literature and discuss the clinical characteristics of this unusual phenomenon.