Yozo Kokawa

Evaluation of axillary lymph node status in breast cancer with MRI

BackgroundWe performed a retrospective study to establish the optimal radiological criteria for axillary lymph node metastases from breast cancer by measuring all dissected nodes, and to determine whether magnetic resonance imaging (MRI) could reliably reveal axillary involvement.MethodsPathological findings and MRI scans of 202 patients with invasive breast cancer were re-viewed. The long- and short-axis dimensions of all level I and II lymph nodes were measured micro-scopically, and then the long-to-short axis (L/S) ratio of each node was calculated. These parameters were compared with pathological nodal status to define radiological criteria for axillary involvement. MRI was carried out using T1-weighted spin-eho sequences in the coronal and sagittal planes. On MRI, every detected lymph node was measured and the shape of the nodal cortex was also examined. Then the diagnostic ability of MRI was assessed using these morphologic criteria.ResultsOn histopathological examinations of 4043 dissected lymph nodes, a long-axis dimension of 10 mm or larger combined with a long-to-short axis ratio of less than 1.6 was the most accurate criteria for predicting lymph node metastases. On MRI, eccentric cortical hypertrophy was seen in only metas-tatic axillae. When these morphologic features were used as criteria for malignancy, MRI had a sensi-tivity of 79%, a specificity of 93%, and an accuracy of 88%. In 16 of 17 false-negative axillae, MRI showed normally sized lymph nodes (<10 mm).ConclusionOur study indicates that MRI is a useful diagnostic method for the evaluation of axillary nodal status, but is limited in the detection of small metastatic lymph nodes.

Increased expression of integrin α3β1 in highly brain metastatic subclone of a human non‐small cell lung cancer cell line

To clarify the roles of integrin and extracellular matrix (ECM) in the process of non‐small cell lung cancer (NSCLC) brain metastasis, we established an in vivo model of brain metastasis of human NSCLC cell line EBC‐1/original in athymic mice, and established highly brain metastatic subclone EBC‐1/brain and highly bone metastatic subclone EBC‐1/bone. Integrin expression of these subclones was evaluated by flow cytometry. In vitro cell attachment, migration and proliferation assays with ECMs were performed using these subclones. Expression of integrin α3 subunit was higher in EBC‐1/brain than in both EBC‐1/original and EBC‐1/bone. In vitro cell attachment, migration, and proliferation assays revealed that EBC‐1/brain had higher affinity and higher reactivity to laminin than EBC‐1/original and EBC‐1/bone. Blocking of integrin α3β1 significantly (P<0.05) decreased brain metastasis by EBC‐1/brain. Interaction of integrin α3β1 and laminin plays important roles in the process of brain metastasis of non‐small cell lung cancer.

A case of granulomatous mastitis mimicking breast carcinoma

A 58-year-old woman presenting with idiopathic granulomatous mastitis mimicking breast carcinoma is described. The mass was elastic, hard and painless, and located in the upper outer quadrant of the right breast. Fine needle aspiration cytology did not provide any diagnostic information. Mammography, ultrasonography and magnetic resonance imaging (MRI) strongly suggested malignancy. Excisional biopsy was performed for definitive diagnosis, and idiopathic granulomatous mastitis was demonstrated histopathologically. Neither wound complication nor recurrence has been identified in the patient, although corticosteroids were not used post operatively. We reviewed the literature, and found that our present case is rare in older patients, and that mammography, ultrasonography and MRI provide little information for differentiating between granulomatous mastitis and carcinoma.

Expression of Bcl-2, but not Bax, correlates with estrogen receptor status and tumor proliferation in invasive breast carcinoma

Bcl‐2 and Bax have been demonstrated to be associated with apoptosis in breast carcinoma, and the ratio between Bax and Bcl‐2 seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl‐2, Bax and the proliferative activity of breast carcinoma. The purpose of this study was to investigate the significance of apoptosis‐related genes bcl‐2 and Bax and their correlation with expression of p53, tumor proliferation defined by MIB‐1 expression and estrogen receptor status. Immunohistochemistry was performed to determine Bcl‐2, Bax, p53, estrogen receptor (ER) and MIB‐1 expression in paraffin‐embedded tissues of 177 invasive breast cancers. Expression of the anti‐apoptotic protein Bcl‐2 was not correlated with the pro‐apoptotic Bax. Bcl‐2 immunostaining displayed a negative correlation with increasing histologic grade, p53 and MIB‐1 (P< 0.0001, P< 0.05 and P< 0.0001, respectively) and a positive correlation with rising ER immunostaining (r = 0.305, P< 0.0001). Conversely, expression of the apoptosis‐promoting protein Bax did not correlate with increasing histologic grade, p53, MIB‐1 or ER status. Neither Bcl‐2 expression nor Bax expression correlated with age, menopausal status, tumor size, histologic type or axillary lymph node status. These results imply that Bcl‐2 is associated with good prognostic markers and the regulation of Bax is complex and does not necessarily correlate with mutant p53 status in breast cancers.

Expression of Bcl-2 but not Bax or p53 correlates with in vitro resistance to a series of anticancer drugs in breast carcinoma

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast carcinomas was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the drugs killing was significantly higher than that of Bcl-2-positive tumors. No relationship between Bax or p53 immunoreactivity and sensitivity for any of anticancer drugs studied was demonstrated. Immunohistochemical results regarding Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a series of anticancer drugs and might be therapeutically useful as an indicator of response to adjuvant chemotherapy for breast cancer.

Bisphosphonate therapy for bone metastases from Breast Cancer: Clinical results and a new therapeutic approach

BackgroundWe evaluated the usefulness of bisphosphonate (BIS) monotherapy, the safety of rapid infusion of BIS and the efficacy of BIS-sequential therapy for bone metastases from breast cancer.Patients and MethodsTwenty-nine patients with bone metastasis or invasion were treated with BIS monotherapy. Each BIS (pamidronate 30 mg, alendronate 10 mg, or incadronate 10 mg) was infused over 30 minutes every two weeks a median of 12 times.ResultsWith BIS therapy, five patients (17%) showed partial response of the bone lesions, and eighteen patients (64%) had pain relief. Of the nine patients treated with BIS-sequential therapy, one (11%) showed a partial response of the bone metastases, three (33%) had pain relief, and one (11%) showed a decrease in the serum tumor marker level.ConclusionBIS therapy is effective against bone metastases from breast cancer, and rapid infusion of BIS is both safe and convenient for patients. BIS-sequential therapy can be a unique therapeutic option in some cases.

Clinical efficacy of bisphosphonate therapy for bone metastasis from breast cancer

Bisphosphonates inhibit osteoclastic bone resorption and are being used as treatment for bone metastases from breast cancer. Intravenous bisphosphonate therapy can significantly reduce skeletal related events (SREs) when administered concurrently with chemotherapy or endocrine therapy. In addition, intravenous bisphosphonate monotherapy is also able to alleviate cancer induced bone pain, and to improve bone metastases in some patients. Oral bisphosphonates are not routinely used for the treatment of bone metastases due to their low bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than pamidronate, is now in phase II clinical studies in Japan, and may alter the role of oral bisphosphonates in the treatment of bone metastasis from breast cancer. The ASCO guidelines recommend that patients with osteolytic bone metastases be treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate and systemic therapy. In addition, it is also recommended that current standards of care for cancer pain, analgesics and radiotherapy, should not be replaced with bisphosphonate therapy.

Clinical outcome of immediate breast reconstruction using a silicone gel-filled implant after nipple-preserving mastectomy

In order to evaluate the safety of silicone gel-filled implants for breast reconstruction in terms of cancer control, we reviewed 122 patients with postoperative stage I and II breast cancer who were treated by nipple-preserving mastectomy and immediate breast reconstruction using a silicone implant, and compared them with 92 controls treated by nipple-preserving mastectomy alone.Twelve complications requiring surgical management occurred in the 122 reconstructions (9.8%). Two implants were replaced, and 10 implants were removed. These 10 cases were excluded from survival analysis. The mean follow-up duration was 78 months in the 112 patients with breast reconstruction, and 55 months in the controls. There were no significant differences in the overall, disease-free, and locoregional disease-free survival rates between the two groups. In the reconstruction group, recurrence occurred in 14 patients. Five of them had locoregional recurrence alone, and are surviving free of disease following local resection. By the last follow-up, there was no incidence of secondary cancer at any site, including the contralateral breast cancer or connective tissue disease in the both group.Our results do not support the hypothesis of a detrimental effect of breast reconstruction using silicone gel-filled implants after mastectomy for breast cancer.

A case of serum CEA disappearance curve after resection of breast carcinoma.

Carcinoembryonic antigen (CEA) elimination kinetics after tumor resection were measured in a case of breast cancer. A 45-year-old woman with a left breast carcinoma underwent surgery after neoadjuvant chemotherapy. The serum CEA level before surgery was 34.3 ng/ml. After sequential monitoring of serum CEA levels, postoperative serum CEA elimination kinetics were calculated using non-linear least square analysis with the fitting equation C(t) = (CO — Cp)exp(-kt) + Cp, where C(t) was the postoperative CEA level, t was the number days after surgery, CO was the CEA level at postoperative time zero, Cp was the CEA at plateau, and k was the rate constant of elimination.Cp was calculated as 6.9 ng/ml, which was above the cut-off level and indicated residual malignancy. After adjuvant chemotherapy, CEA normalized to 1.8 ng/ml. In breast cancer patients with high preoperative serum CEA levels, our analytical method for CEA elimination might be useful for the detection of residual malignancies.

Removal of an endobronchial foreign body using an ultrathin flexible bronchoscope and a novel suction system.

To the Editor: Foreign body aspiration in children is a serious condition and a pediatric emergency. If the diagnosis is delayed, complications such as persistent pneumonia, recurrent attacks of bronchospasm, lung abscess, recurrent hemoptysis, and bronchiectasis may develop, necessitating surgical intervention.1 We report a case of a persistent pneumonia of 3 weeks duration in an infant from aspiration of peanuts that was successfully managed by using an ultrathin flexible bronchoscope and a handmade suction system and a balloon catheter. Three weeks before the admission, a healthy 8-monthold boy suffered with productive cough and fever and was diagnosed with acute bronchitis. Despite the medical treatment, his symptoms persisted. A chest computed tomography (CT) scan revealed findings suggestive of a foreign body in the left main bronchus and a left lower lobe pneumonia (Fig. 1A). Under general anesthesia, an ultrathin flexible bronchoscope, 2.2mm in diameter (BFN20; Olympus, Tokyo, Japan) was inserted into the endobronchial tree through the endotracheal tube, 4.5 Fr in diameter. There was a thick white discharge in the left main bronchus and a foreign body, which was a piece of peanut, was observed. The scope was too slim and had no suction port. We made a handmade suction system by placing a small cut over the proximal end of a conventional suction catheter and inserted the bronchoscope into the tubing (Fig. 1B). We attempted to aspirate the foreign body with this modified suction device. However, it resulted in fragmentation of the peanut emitting moderate amount of white discharge from the distal airways (Fig. 1C). A 5.2 Fr balloon angioplasty catheter was then passed by the side of the bronchoscope placing the balloon distal to the foreign body. The balloon was then inflated with air and used to push the foreign body in a retrograde manner (pull). This maneuver allowed the foreign body to be brought proximally without further fragmentation. A split portion of the peanut was easily removed using the suction. (Fig. 1D). Patient’s symptoms promptly resolved, and there was no further recurrence of his pneumonia. Foreign body aspiration is a common pediatric emergency. More than 80% of cases of foreign body aspiration occur during early childhood, with a peak incidence between the ages of 10 and 24 months.2 Only 17.2% of patients with proven foreign bodies did not have an eyewitness to the aspiration episode, and only 20% of foreign bodies are radiopaque. Most of the aspirated foreign bodies in the pediatric age group are food particles, especially nuts or seeds. The diagnosis of a pediatric airway foreign body is more difficult because the patients are unable to communicate and delay in the treatment is not uncommon.3 The bronchoscopic removal of a foreign body among infants is not without challenges as fragmentation or distal migration of the foreign body can occur.4,5 Traditionally, rigid bronchoscopy was the procedure of choice for the removal of foreign bodies in children.6 However, flexible bronchoscopy is increasingly being used for the indication.7,8 Flexible bronchoscope has many advantages compared with rigid bronchoscope. Most importantly, its small diameter and flexibility enable to reach foreign bodies located in distal airways, which are difficult to access with a rigid bronchoscope. Second, flexible bronchoscope may allow simultaneous retrieval of fluids, especially mucus or blood clots, without requiring separate suction catheter.8 When the diagnosis is delayed, such as in our case, and if the foreign body is nuts or seeds, fragmentation is likely with the use of rigid instruments. We always perform the flexible bronchoscopy first before giving consideration to the rigid scope. The weakness of the ultrathin flexible bronchoscope could be the lack of a suction port, as one in our case. Our handmade suction system appeared to be useful to overcome this weak point. Flexible bronchoscopy combined with our handmade suction system and balloon catheter might come handy in similar situations. Disclosure: There is no conflict of interest or other disclosures. LETTERS TO THE EDITOR