Applicability of DPI formulations for novel neurokinin receptor antagonist.

A novel triple neurokinin receptor antagonist (TNRA) could have pharmaceutical efficacy for asthma and/or chronic obstructive pulmonary disease. TNRA is potentially developed as inhalation medicine. The aim of this investigation was to evaluate the applicability of dry powder inhaler (DPI) formulation for TNRA. DPI formulation containing lactose was used for this feasibility study. Mechanofusion process for surface modification was applied on lactose particles to prepare four different DPI formulations. The mixture of TNRA and lactose was administered to rats intratracheally using an insufflator. The deposition pattern and blood concentration profile of TNRA were evaluated. Although there was no significant difference in deposition on deep lungs between the four formulations, DPI formulations containing mechanofusion-processed lactose showed longer T(max) and t(1/2) and higher AUC(0-infinity) and MRT compared to that containing intact lactose. On the other hand, the contact angle measurement showed that the mechanofusion process decreased the polar part of the surface energy of the lactose. Therefore, the prolongation of the wetting of the formulated powder mixture seemed to delay the dissolution of TNRA deposited in respiratory tract. It was concluded that DPI formulation containing mechanofusion-processed lactose could be suitable for inhalation of TNRA.

High dorsal drainage routes of Spiegel's lobe.

BACKGROUND/PURPOSE: The venous drainage from Spiegel's lobe to the terminal portion of the hepatic veins has been described in the literature, but its morphology remains unclear. METHODS: We examined 42 dissected liver specimens and 38 cast specimens. RESULTS: In 8 of the 42 dissected liver specimens and 5 of the 38 cast specimens we found atypical but thick (over 3 mm) caudate veins that drained Spiegel's lobe and emptied into the terminal portion (along the most proximal 5-mm course) of the middle hepatic vein (MHV) or the inferior vena cava (IVC) near the MHV terminal (less than 10 mm from the MHV). We termed these the superior caudate vein. This vein ran upward between the caudate portal branches of the left and hilar bifurcation origins or through the territory of the left origin. The superior caudate vein, consistently coexisted with the typical vein(s). We also found several analogues of the superior caudate vein, such as the cranially shifted opening of the typical caudate vein and relatively thick proximal tributaries of the MHV from Spiegel's lobe. CONCLUSIONS: Although the superior caudate vein, if present, seemed to have a large role in the venous drainage of the lobe, its incidence seemed to be too low for clinical relevance.

Conservation treatment intensified with an anti-estrogen agent and CAF chemotherapy for stage I and II breast cancer.

In order to improve both cosmetic results and survival rates, we performed breast-conservation treatment (BCT) intensified with tamoxifen and CAF chemotherapy to 218 out of 224 patients who visited our department with the desire of breast-conservation between August 1989 to December 1998. Of these patients, 68 presented with tumors of stage I, and another 122 stage II. All patients were administered tamoxifen (for pre-menopausal women) or tremifene (for post-menopausal women) orally: tamoxifen and tremifene administration was started just after confirmation of the breast cancer based on the findings of fine-needle aspiration cytology. All patients underwent lumpectomy with or without axillary dissection (level I and II). For patients with T2 tumors, the lumpectomy was performed following two to four times of CAF chemotherapy. Following conservative surgery, patients were treated with radiation therapy to the intact breast and ipsilateral axilla to a total dose of 4400 cGy with a conedown to a total median dose of 5300 cGy. At the end of March 1999, the mean follow-up time was 49.0 months. In spite of high-positivity (approximately 30%) of microscopically surgical margin, local recurrence rate is considerably low, and only 2 patients experienced local recurrence. Cause-specific survival rate for patients of stage I is 100%, and that of stage II is 91.7% at 5 years. The cosmetic results of therapy were also considered good.

Stromal sarcoma of the breast with lung metastasis successfully treated by radiotherapy: report of a case.

We report herein the case of a 42-year-old woman in whom a solitary lung metastasis from stromal sarcoma of the breast was effectively treated by radiotherapy. The original breast tumor had been extirpated in a local hospital, and she was subsequently referred to our outpatient clinic for nonsurgical treatment. Pathological examination of the breast tumor had confirmed a diagnosis of stromal sarcoma. Radiation and systemic chemotherapy for the remnant disease were administered at our hospital; however, 8 months later, local recurrence and a solitary lung metastasis were recognized on a chest X-ray. A second lumpectomy of the recurrent breast tumor along with radiation for the lung metastasis and systemic chemotherapy were performed. After a 4-year disease-free period, there is still no sign of recurrence. This case serves to demonstrate the effectiveness of radiotherapy for the treatment of lung metastasis from stromal sarcoma of the breast.

Changes in the findings of dynamic MRI by preoperative CAF chemotherapy for patients with breast cancer of stage II and III: pathologic correlation.

Preoperative neoadjuvant chemotherapy is essential for treatment of patients with breast cancer who have a large tumor mass and/or regional lymph node involvement, in terms of both tumor shrinkage and further improvement of the survival rate. In order to safely perform breast-conservation treatment for these patients, a detailed diagnostic procedure for precisely evaluating the therapeutic response is needed. Dynamic magnetic resonance imaging (MRI) is thought to be important in the evaluation of responses to neoadjuvant therapy in patients with considerably large tumors, however, few studies have detailed the changes, as depicted by dynamic MRI, that can be expected with neo-adjuvant chemotherapy. The purpose of this study was to document the changes that occur in response to neoadjuvant chemotherapy and to correlate them with the pathological findings observed in the surgical specimen. The study was performed at Kochi Medical School Hospital from 1995 to 1998. The series consisted of 31 patients with stage II and III breast cancer. Prior to and after 1-5 courses of neoadjuvant chemotherapy, dynamic MRI examinations were performed. Eight of the time-intensity curves for the 10 grade 1a tumors flattened during neoadjuvant chemotherapy, while two remained the same. Six of the curves flattened for the 14 grade 1b tumors, 7 remained the same, and one spiked. And for the seven grade 2 tumors, two of the curves flattened and five remained the same (p=0.0340). In the five grade 1 tumors, the mean after/before normalized peak signal intensity ratio was 0.42+/-0.22. In the 18 grade 2 and 8 grade 3 tumors, the mean normalized signal intensity ratios were 0.59+/-0.28, 0.88+/-0.10, respectively (p<0.05). In the 15 tumors that showed shrinkage of the linear enhancement during neo-adjuvant chemotherapy, 10 had no remarkable intraductal spreading and 9 had a negative surgical margin. In the 16 tumors that had no shrinkage of the linear enhancement during chemotherapy, 13 had remarkable intraductal spreading and 12 had a positive surgical margin (p<0.05). It is concluded that dynamic MRI is a valuable tool for determining tumor response and predicting a positive surgical margin. Breast-conservation treatment can be performed for these patients by meticulous assessment using such detailed diagnostic procedures after local tumor control by combined chemotherapy with high dose-intensity.

Conservation treatment intensified with tamoxifen and CAF chemotherapy for subareolar breast cancers.

Formerly, patients with subareolar breast cancers have not been good candidates for breast-conservation treatment (BCT) in Japan. However, recently it was reported that patients with subareolar cancers were good candidates for this treatment. In order to improve both cosmetic results and survival rates, we performed BCT for 27 patients with subareolar breast cancers following pre-operative CAF chemotherapy and tamoxifen administration. From August 1989 to June 1998, we performed BCT for 200 out of 206 patients who visited our hospital with the desire of breast-conservation. Of these patients, 27 presented with tumors within 2 cm of the nipple areolar complex. For 26 of these 27 patients, breast-conserving surgery was performed following two to four times of CAF chemotherapy, and another one patient did not undertake any surgical resection. Following the surgery, patients were treated with radiation therapy to the intact breast and ipsilateral axilla to a total dose of 4,400 cGy with electron conedown to a total dose of 5,300 cGy. Their primary tumors were at T4bN0 in 1 case, T2N1b in 5 cases, T2N0 in 18 cases, and T1cN0 in 3 cases. Tamoxifen was administered to all the patients. CAF chemotherapy was performed six times for stage I patients, and eight times for stage II patients in total. For one patient with direct tumor invasion to the nipple, intraarterial infusion chemotherapy was performed following radiation therapy and CAF chemotherapy, without any surgical resection. For another 26 patients, breast-conserving surgery was performed, and 5 of them underwent lumpectomy under local anesthesia on an outpatient basis. For these 26 patients, the microscopic surgical margin was positive for 8 patients, close for 6 patients, negative for 10 patients, and unknown for 2 patients. All patients are alive with no evidence of disease after a follow-up of approximately 47 months on average, and all of their cosmetic results are estimated as excellent or good. It is concluded that BCT intensified with preoperative CAF chemotherapy and tamoxifen for subareolar breast cancers is a satisfying treatment modality in terms of both cosmetic results and survival rates.

Papid Growing Fibroadenoma in an Adlescent.

INTRODUCTION: We report a case of rapidly growing fibroadenoma. PATIENT: A 13-year-old girl consulted the outpatient clinic regarding a left breast mass. The mass was diagnosed as fibroadenoma by clinical examinations, and the patient was carefully monitored. The mass enlarged rapidly with each menses and showed a 50% increase in volume four months later. Lumpectomy was performed. The tumor was histologically diagnosed as fibroadenoma organized type and many glandular epithelial cells had positive immunohistochemical staining for anti-estrogen receptor antibody in the nuclei. CONCLUSION: The estrogen sensitivity of the tumor could account for the rapidgrowth.

Rapid growing fibroadenoma in an adolescent.

INTRODUCTION: We report a case of rapidly growing fibroadenoma. PATIENT: A 13-year-old girl consulted the outpatient clinic regarding a left breast mass. The mass was diagnosed as fibroadenoma by clinical examinations, and the patient was carefully monitored. The mass enlarged rapidly with each menses and showed a 50% increase in volume four months later. Lumpectomy was performed. The tumor was histologically diagnosed as fibroadenoma organized type and many glandular epithelial cells had positive immunohistochemical staining for anti-estrogen receptor antibody in the nuclei. CONCLUSION: The estrogen sensitivity of the tumor could account for the rapid growth.

Changes in significance of axillary lymph node dissection for patients with breast cancer.

Axillary lymph node dissection has been a routine part of breast cancer treatment for more than 100 years. As so few patients have been shown to have positive nodes, more consideration should be given to eliminating axillary node dissection for duct carcinoma in situ (DCIS) and T1a lesions. And for patients with T1/2N0M0 cancer of the breast, lumpectomy alone without axillary dissection followed by radiation therapy of the intact breast and regional lymph nodes should be a reasonable treatment without any arm morbidity. Between September 1989 and September 1994, we have treated 40 breast cancer patients with this method and no local recurrence nor distant metastasis has been encountered so far. Therefore, it is concluded that axillary dissection should be performed routinely only for N1b lesions and larger.

[Wegener's granulomatosis--report of four cases including two in patients who died of myocardial infarction].

The prognosis for Wegener's granulomatosis (W-G) is good if it is diagnosed early and a combination of corticosteroids and cytotoxic drugs is given. During the past fourteen years, we were encountered four cases of W-G, three were systemic and one was limited. Of the three patients, with systemic disease, two died of myocardial infarction caused by a delay in diagnosis and one died of fulminant renal and respiratory failure. Only the one patient with a limited form of the disease survived for more than 5 years. We emphasize the importance of early diagnosis with consideration of the systemic features of W-G.

Early experiences of breast-conservation treatment combined with tamoxifen and CAF chemotherapy for breast cancer of stages I and II.

A total of 39 patients with breast cancer of stages I and II received breast-conservation treatment (BCT) combined with tamoxifen and systemic chemotherapy (CAF) from August 1989 to March 1993. All of these patients visited the outpatient clinic of the Department of Radiology of Kochi Medical School Hospital, with an obvious desire to undertake BCT. During this period, another two patients with the same desire were treated with modified radical mastectomy, because of obviously positive surgical margins in frozen sections obtained at surgery. The percentage of patients treated by BCT was, therefore, 95.1%. All of the patients were females, and their average age was 49.9 years. Thirty-six of these 39 patients underwent lumpectomy, and another three patients with large-sized tumor or suspected extensive intraductal component underwent quadrantectomy or wide local excision. Nineteen of these 39 patients who were over 70 years old or had no clinically detectable axillary lymph node swelling received tangential field radiotherapy to their ipsilateral axillary region instead of axillary dissection. At the end of May 1993, the mean follow-up time was 22.4 months. Until now, one patient (T2N1M0, stage IIB) has died of distant metastases of breast cancer to bone, liver, lung, and brain, and another patient, aged 81, died of pneumonia with no evidence of breast cancer progression. The overall survival rates were, therefore, 100% (30/30), 90.0% (18/20), and 75.0% (6/8) at 1 year, 2 years, and 3 years, respectively. Cause-specific survival rates were 100% (30/30), 94.7% (18/19), and 85.7% (6/7) at 1, 2, and 3 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Living related liver transplantation.

Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.