Tsutomu Kasugai

Lymphoscintigraphic visualization of internal mammary nodes with subtumoral injection of radiocolloid in patients with breast cancer.

ObjectiveTo determine whether subtumoral injection of radiocolloid is useful for lymphoscintigraphic visualization of the internal mammary node and in sentinel lymph node (SLN) biopsy of the axilla in breast cancer patients. Summary Background DataThe presence of retromammary lymphatics connecting to the axillary and internal mammary basins has been demonstrated by early anatomic studies. Thus, it is hypothesized that some lymph, especially that from the parenchyma under the tumor, may drain into both the axillary and internal mammary basins. MethodsPatients (n = 196) with T1-2, N0 breast cancer underwent preoperative lymphoscintigraphy with radiocolloid (technetium 99m tin colloid) injection into various sites of the breast, followed by SLN biopsy using the combined method with blue dye. Patients were divided into four groups: group A (n = 41), peritumoral injection of both radiocolloid and blue dye; group B (n = 70), periareolar radiocolloid and peritumoral blue dye; group C (n = 45), intradermal radiocolloid and periareolar blue dye; and group D (n = 40), subtumoral radiocolloid and intradermal blue dye. A retrospective analysis of 1,297 breast cancer patients who underwent extended radical mastectomy with internal mammary node dissection was also conducted to determine the relationship between vertical tumor location (superficial or deep) and frequency of axillary and internal mammary node metastases. ResultsOne patient (2%) in group A, 3 (4%) in group B, 0 (0%) in group C, and 15 (38%) in group D exhibited hot spots in the internal mammary region on lymphoscintigraphy (P < .001, group D vs. the other groups). The concordance rate of radiocolloid and blue dye methods in detection of SLNs in the axillary basin was significantly lower in group D than in the other groups. In contrast, the mismatch rate (some SLNs were identified by radiocolloid and other SLNs were identified by blue dye, but no SLN was identified by both in the same patient) was significantly higher in group D than in the other groups. In patients treated with extended radical mastectomy, positivity of axillary and internal mammary metastases was significantly higher in patients (n = 215) with deep tumors than those (n = 368) with superficial tumors. ConclusionsThese results suggest the presence of a retromammary lymphatic pathway from the deep portion of the breast to both axillary and internal mammary basins, which is distinct from the superficial pathway. Therefore, SLN biopsy with a combination of subtumoral and other (peritumoral, dermal, or areolar) injections of radiocolloid will improve both axillary and internal mammary nodal staging.

Detection of Gastric Cancer Micrometastases in Lymph Nodes by Amplification of Keratin 19 mRNA with Reverse Transcriptase‐Polymerase Chain Reaction

A sensitive method for the detection of gastric cancer micrometastases in lymph nodes was developed. The method was based on amplification of keratin 19 mRNA by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Keratin 19 RT‐PCR showed that keratin 19 mRNA was expressed in all 12 gastric cancers, but not in any of 20 normal control lymph nodes, indicating that keratin 19 mRNA is a good target of RT‐PCR for the detection of gastric cancer micrometastases in lymph nodes. Serial dilution studies of RNA extracted from gastric cancers against RNA extracted from control lymph nodes demonstrated that the detection sensitivity of the keratin 19 RT‐PCR method was one cancer cell in 103‐105 lymph node cells. Detectability of lymph node metastases was compared between keratin 19 RT‐PCR and conventional histological examination, using 100 lymph nodes obtained from 12 gastric cancer patients. Keratin 19 mRNA was detected in all of the seven lymph nodes which were historically metastasis‐positive. Of the 93 lymph nodes which were histologically metastasisnegative, 79 were found not to express keratin 19 mRNA but 14 were found to express keratin 19 mRNA, indicating that these lymph nodes contained micrometastases which could not be detected by histological examination. These results demonstrate that keratin 19 RT‐PCR is a more sensitive method than histological examination for the detection of gastric micrometastases in lymph nodes.

Sentinel node biopsy in breast cancer patients with clinically negative lymph-nodes

BackgroundThe purpose of the present study is to evaluate the usefulness of dye-guided sentinel node biopsy in breast cancer patients with clinically negative nodes and to clarify the anatomic distribution of sentinel nodes in the axilla.MethodsSentinel node biopsy was performed in patients with T1 or T2 breast cancer who had clinically negative nodes, using an indocyanin green dye-guided method. Thereafter, complete axillary dissection was performed. Sentinel node and complete axillary lymph-node dissection specimens were examined separately, and the incidence of metastases was compared.ResultsWe identified sentinel nodes in 115 (76.7%) of 150 patients with clinically negative nodes. The mean number of sentinel nodes was 1.7 (range, one to eight nodes). The mean size of sentinel nodes was 9.0 mm (range, 2.0 to 28.0 mm). Of the 31 patients who had a tumor-positive sentinel node, 14 (45.2%) patients had only the sentinel node involved. There was concordance on histological examination between sentinel node and axillary node status in 111 (96.5%) of 115 cases. Of the sentinel nodes 89.1% were located cranially to the intercostobrachial nerve and within 2 cm of the lateral edge of the pectoralis minor muscle.ConclusionsSentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable detection rate of sentinel nodes for breast cancer patients with clinically negative nodes. Most of the sentinel nodes were located near the lateral edge of the pectoralis minor muscle and cranial to the intercostobrachial nerve.

Phyllodes Tumor of the Breast: Pathology, Histogenesis, Diagnosis, and Treatment.

Phyllodes tumor of the breast is histologically unique in that it is composed of epithelial and stromal components. The histogenesis of this disease has remained largely unknown but recently we have obtained interesting information through clonal analysis, and have been able to show a difference in the histogenesis between phyllodes tumor and fibroadenoma. Elucidation of histogenesis would definitely improve our understanding of the biological behavior of this disease and also help to establish the most appropriate treatment strategy. The pathology, histogenesis, diagnosis, and treatment of phyllodes tumor are reviewed in this paper. Our hypothesis on the histogenesis of this disease is also presented.

Leiomyosarcoma of the breast: A case report and review of the literature about therapeutic management

We experienced a leiomyosarcoma of the breast in an 18-year-old female. No specific treatment has been established. In order to clarify appropriate therapeutic management methods, the limited data available from our and previous case reports were assessed. A leiomyosarcoma of the breast must be excised with a negative margin. If the tumor size is large and an adequate margin, greater than 3-cm margin around the excised tumor, is not achieved due to anatomical constraints, radiotherapy may be indicated.

Effect of tamoxifen on pS2 expression in human breast cancers.

pS2 protein expression is induced by estrogen through estrogen receptors (ER), and is known to be inhibited by antiestrogen in the breast cancer cell line MCF-7. The present study was undertaken to determine whether pS2 expression may be inhibited by the antiestrogen tamoxifen (TAM) human breast cancer. pS2 expression was immunohistochemically investigated in 22 patients treated preoperatively with TAM and in 45 without TAM treatment (control group). Immunostaining was considered positive when 10% of tumor cells showed cytoplasmic staining. We found that 94% of the pS2-positive tumors were ER-positive (ER+), and there was a significant association between the two proteins (p < 0.0001). In ER+ tumors, pS2 expression was seen in only 21% (3 of 14) of the TAM+ group, compared to 70% (16 of 23) of the control group. Statistical analysis of these data indicated a high likelihood (p = 0.006) of TAM treatment being associated with inhibition of pS2 expression in human breast cancers.

Malignant Seeding of the Lumpectomy Cavity upon Breast-Conserving Surgery

One of the etiologic factors involved in local recurrence after breast-conserving surgery may be malignant seeding of the wound during the lumpectomy procedure. A total of 340 patients with stage I and II breast cancer were entered into the study. Of these, 270 patients received breast-conserving surgery (BCS group), and the other 70 patients underwent mastectomy (control group). After resection, lavage cytology was performed at the surgical wound. There were 55 patients (20.4%) who showed positive lavage cytology in the BCS group. In the control group, there were only 3 patients (4.3%) with positive cytology. Positivity was significantly higher in the former group (p = 0.00064). Patients with evidence of cutting across cancer lesions showed significantly higher positive rates in lavage cytology (p < 0.00001). Positivity in lavage cytology was significantly higher in patients with positive surgical margins evaluated by frozen sections (p = 0.0017), touch cytology (p < 0.0001) and formalin-fixed, paraffin-embedded sections (lateral or medial margin; p = 0.0036, anterior and posterior margin: p = 0.0210). The positivity was also significantly higher in patients with an extensive intraductal component (p < 0.0001), and less than or equal to 50 (p = 0.0061) years of age. Multivariate analysis revealed that the highest relative risk factor for positive cytology was evidence of cutting across cancer lesions (relative risk = 8.166; p < 0.00001).

Sentinel Node Biopsy in Breast Cancer

Axillary lymphnode dissection (ALND) for breast cancer patients provides local control and information for the determination of the type of adjuvant therapy. The benefit of axillary surgery itself for survival is considered to be limited to patients with positive nodes. Sentinel node biopsy is a recently developed, minimally invasive technique for precisely predicting axillary nodal status. As this technique has less morbidity and greater accuracy than ALND, it replaces ALND for patients with node negative breast cancer. In this report, we outline the current status of sentinel node biopsy for breast cancer patients and introduce our preliminary results.