Early identification of promiscuous attributes of aldose reductase inhibitors using a DMSO-perturbation assay.

Aldose reductase (AR) inhibitors are used clinically to treat long-term diabetic complications. Previous studies reported a series of AR inhibitory candidates, but unfortunately the mode of inhibition was poorly described due mainly to the lack of readily available methods for evaluating the specificity. The present study examined the AR inhibitory effects of novel synthetic hydantoins and their structural relatives, some of which were obtained from chemically engineered extracts of natural plants, and discovered several novel AR inhibitors with moderate inhibitory activity. The identified inhibitors were then subjected to a two-step mechanistic characterization using a detergent-addition assay and our novel dimethyl sulfoxide (DMSO)-perturbation assay. The detergent-addition assay revealed aggregation-based inhibitors, and the subsequent DMSO-perturbation assay identified nonspecific binding inhibitors. Thus, the present study demonstrates the usefulness of the DMSO-perturbation screen for identifying nonspecific binding characteristics of AR inhibitors.

[Transmanubrial Osteomuscular-sparing Approach for Resection of Superior Mediastinal Schwannoma].

Various approaches can be applied to resect superior mediastinal tumor. It is important to choose the procedure according to the location, size, and characteristics of the tumor in order to perform safe procedure surgery because of distinctive anatomy of this site. We hereby report on a case of Schwannoma of the superior mediastinum resected by the transmanubrial approach. A 67-year-old woman was referred to our department to examine an abnormal chest shadow found at a regular health checkup. Computed tomography revealed a tumor 58×52 mm in size extending from the left supraclavicular fossa to the upper border of the aortic arch. The surgery was performed under the diagnosis of neurogenic tumor using the transmanubrial approach. The tumor was resected safely and the pathological diagnosis was a Schwannoma. Transmanubrial approach was found to be quite useful in securing an adequate visual field and enabling the safe separation of blood vessels and nerves from the tumor.

[Mediastinal Mature Teratoma Necessitating Resection of Superior Vena Cava].

A 43-year-old woman was referred to our hospital for an abnormal shadow on chest X-ray. Computed tomography revealed a tumor with calcification of 9.8 cm in size at the anterior mediastinum. The infiltration into the left brachiocephalic vein and superior vena cava by tumor was suspected. Surgery was performed under a diagnosis of mature teratoma. The tumor was found to adhere firmly to superior vena cava (SVC), left brachiocephalic vein, right phrenic nerve, and the arch of the azygos vein. To ensure the blood flow, an artificial blood vessel was placed between left brachiocephalic vein and right atrium. Then SVC was clamped and the tumor was resected with the part of SVC.

[A case of bisphosphonate-associated osteonecrosis of the jaw in a patient with bone metastasis of breast cancer].

A 5 6-year-old woman underwent modified radical mastectomy for left breast cancer in 2002. Bone metastases developed in November 2005, and she received pamidronate from February 2006. Pamidronate was changed to zoledronate in November 2006. In November 2007, she was referred to a dentist for pain and swelling of the right lower gum. Conservative therapy with local irrigation and antibiotics was performed, but the lesion progressed and showed ulceration with exposed bone. She was diagnosed as bisphosphonate-associated osteonecrosis of the jaws, and zoledronate was withdrawn in January 2008. Conservative therapy was continued but the necrotic lesion caused pathological fracture and fistula. In February 2009, surgical intervention was performed for the improvement of her QOL.

[A case of premenopausal stage IV breast cancer responding to neoadjuvant endocrine therapy after chemotherapy with FEC].

A 33-year-old woman was referred to our hospital with a complaint of left breast tumor. After examinations, she was diagnosed as invasive ductal carcinoma with sternum metastasis (T2N0M1(OSS), Stage IV). The tumor was hormone receptor- positive and HER2-negative. Primary systemic chemotherapy with FEC was performed. After four courses, the efficacy was judged as a partial response (PR). After chemotherapy, endocrine therapy with goserelin and tamoxifen was performed. The efficacy of endocrine therapy was as good as that of chemotherapy. After endocrine therapy for 13 months, breast conserving-surgery was performed. After surgery, radiotherapy for left breast and sternum was performed. She continues to undergo outpatient endocrine therapy with no detectable tumor. It is suggested that neoadjuvant endocrine therapy may be useful with consideration for treatment effectiveness and the patient's quality of life.

[Two cases of breast cancer responding to primary systemic chemotherapy containing trastuzumab without surgery].

The first case was a 40-year-old woman who was referred to our hospital with a complaint of left breast tumor. She was diagnosed as invasive ductal carcinoma (T2N0M0, Stage IIA). The tumor was ER-negative, PR-negative and HER2-positive. After primary systemic chemotherapy with 6 courses of 5-fluorouracil+epirubicin+cyclophosphamide(FEC)and 3 courses of weekly paclitaxel (PTX)+trastuzumab, the efficacy of chemotherapy was judged as a complete response (CR). After chemotherapy, radiotherapy for her left breast was performed without surgery. At 21 months after CR, local efficacy was judged as CR, but liver and bone metastases appeared, and were treated by capecitabine and trastuzumab. The efficacy of chemotherapy was judged as a partial response (PR). The second case was a 26-year-old woman referred to our hospital with a complaint of right breast tumor. She was diagnosed as invasive lobular carcinoma (T2N0M0, Stage IIA). The tumor was ER-positive, PR-negative and HER2-positive. After primary systemic chemotherapy with 4 courses of FEC and 6 courses of docetaxel+trastuzumab, the efficacy of chemotherapy was judged as CR. Then, 4 courses of weekly PTX+trastuzumab were performed. After chemotherapy, radiotherapy for her right breast was performed without surgery. The efficacy of treatment was judged as CR for 15 months.

[Primary malignant melanoma of the esophagus--detection of circulating tumor cells].

Primary malignant melanoma of esophagus (PMME) is a rare tumor; therefore, the prognostic factors, predictive factors, and difference in biological behaviors of cutaneous melanoma and primary esophageal squamous cell carcinoma remain uncertain. Although we did not adopt a standard therapeutic strategy, we performed surgical resection, chemotherapy, immunotherapy, and radiotherapy either alone or in combination; all procedures resulted in poor outcomes. A 67-year-old woman presented with a swallowing disorder. An esophagogastroduodenoscopy was performed, leading to diagnosis of PMME. According to the Japanese Classification of Esophageal Cancer, the pathological stage was T1b, ly0, v0, N0, M0, stage I . KIT immunostaining was focally positive. After subtotal esophagectomy, adjuvant chemotherapy was performed, but the malignant melanoma relapsed in the mediastinum and the patient died 10 months after diagnosis. We serially monitored the patient using several new modalities, including PET/CT, metabolites of melanin: 5-S-CD, and circulating tumor cells (CTCs) by reverse transcription-polymerase chain reaction to identify the melanoma-specific gene. To our knowledge, this is the first report of a case in which CTCs in PMME were detected.

[A case of stage IV breast cancer with large cancer ulcer responding to combination therapy of capecitabine and medroxyprogesterone acetate and cyclophosphamide].

A 53-year-old woman suffering from nausea and vomiting was admitted to our hospital. There was a large ulcer from her left anterior chest to her right side chest. After pathological examination from the ulcer, she was diagnosed as breast cancer, scirrhous carcinoma. The estrogen and progesterone receptors were positive in the tumor. HER2 score was 1+ in the tumor. The stage was T4bNxM1(OTH). Uterine metastases of the breast cancer caused obstructive nephropathy. Ureteral obstruction was treated by urinary tract catheter. After improvement of renal failure, chemotherapy with 5-FU+epirubicin+cyclophosphamide (FEC) and docetaxel was performed. The efficacy was judged as stable disease (SD). For third-line chemotherapy, she was then treated with oral combination chemoendocrine therapy with capecitabine and medroxyprogesterone acetate. After the combination chemoendocrine therapy, the local tumor was remarkably reduced. With added cyclophosphamide, the partial response (PR) continued for 19 months. She died of peritonitis carcinomatosa and pleuritis carcinomatosa. No adverse reactions occurred with the combination chemoendocrine therapy. It is suggested that this oral combination chemoendocrine therapy may be useful with consideration for treatment effectiveness and the quality of life of the patient.

[A case of bilateral T4 breast cancer with different responses to chemotherapy].

It is recognized that hormone receptors and HER2 are important as prognostic factors in breast cancer. Moreover, it seems likely that hormone receptors and HER2 are important predictive factors for response to chemotherapy in breast cancer. We report a case of bilateral T4 breast cancer with different expression for hormone receptors and HER2. The patient was a 67-year-old woman. The Stage was T4bN2aM0, respectively. The right tumor was negative for hormone receptors and positive for HER2, while the left tumor was positive for hormone receptors and negative for HER2. After primary chemotherapy with FEC, paclitaxel and docetaxel, the efficacy for the right local tumor was judged as cCR. However, brain metastases appeared and were treated by resection and radiation. The efficacy for the left tumor was judged as PR. Modified radical mastectomy with axillary lymph node dissection was performed. The patient has survived with no recurrence.

[A case of recurrent breast cancer with multiple liver metastases responding to combination therapy of capecitabine and MPA].

The patient was a 68-year-old woman who underwent left partial mastectomy on February 1999. The stage was T2N1. There were positive for estrogen and progesterone receptors in the tumor. After operation, adjuvant therapy consisting of oral administration of tamoxifen and radiation was performed. On February 2005, she felt dyspnea and right femoral pain. After examinations, she was diagnosed as recurrent breast cancer with pleuritis carcinomatosa and bone metastasis. The patient was treated with oral administration of anastrozole and pamidronate disodium 90 mg intravenously every 4 weeks, radiation of her right femur, and OK-432 injection into the intrapleural cavity. On November 2005, she felt general fatigue and anorexia. CT examination revealed multiple liver metastases. She was treated with oral combination chemoendocrine therapy with capecitabine (2,400 mg/day) and MPA (600 mg/day). After the four courses, multiple liver metastases were remarkably reduced in the CT findings. After twelve courses, the partial response continued. No adverse reactions occurred except for gain in weight of grade 1. It is suggested that this oral combination chemoendocrine therapy may be useful for recurrent breast cancer with consideration for treatment effectiveness and the quality of life of the patient.

Anomalous V2 of the left pulmonary vein detected using three-dimensional computed tomography in a patient with lung cancer: A case report.

We report one of the rare anatomical variations of the pulmonary vein wherein the left V2 drained into the inferior pulmonary vein. A 63-year-old man was referred to our hospital because of an abnormal shadow in the left lower lung field that was noted on chest X-ray. Computed tomography (CT) revealed a tumor in the left lower lobe. A biopsied tumor specimen was diagnosed as an adenocarcinoma, and thus, left lower lobectomy was performed. Preoperative three-dimensional CT revealed that an anomalous V2 of the left lung drained from the superior segment into the inferior pulmonary vein. This variation type was confirmed during thoracoscopic left lower lobectomy. We were able to perform left lower lobectomy with the preservation of the anomalous V2. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. It is important to identify anatomical variations of the pulmonary vein and reliably preserve and process the affected area to prevent postoperative complications.

[A case of rectal cancer with multiple liver metastases responding to TS-1].

A 63-year-old woman was referred to our hospital with complaints of anal pain, constipation and abdominal distention caused by a rectal tumor. After examinations, she was diagnosed as rectal cancer with multiple liver metastases. The CEA level was 70.0 ng/ml and the CA19-9 level was more than 5,000 U/ml at admission. To prevent bowel obstruction, low anterior resection of the rectum was performed. At 34 days after operation, TS-1 chemotherapy was started as outpatient treatment (each course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the CEA level was reduced to 3.3 ng/ml and the CA19-9 level to 15 U/ml, both under the normal value. After the second course, administration was discontinued due to diarrhea, and restarted as a daily oral administration of 80 mg TS-1. After the five courses, the CEA level was 4.0 ng/ml and the CA19-9 level was 4 U/ml, both under the normal value. Multiple liver metastases had remarkably reduced in the CT findings. The patient continues to undergo outpatient treatment with good QOL.

Paraneoplastic extralimbic encephalitis associated with thymoma: a case report.

Here we a report a rare case of extralimbic encephalitis associated with thymoma. A 66-year-old woman was admitted to our hospital with cramping in her right leg and inability to walk. Magnetic resonance imaging of the brain showed multifocal high intensity signals on T2 flare images in the cerebral cortex, and chest computed tomography showed a 5-cm anterior mediastinal mass, which was considered to be a thymoma. We speculated that she had paraneoplastic encephalitis associated with thymoma. She underwent a thymectomy and was diagnosed with type B1 thymoma. On postoperative day 6, her neurological symptoms began to improve. On postoperative day 31, she was discharged without complications. Limbic encephalitis is a paraneoplastic neurological syndromeassociated with thymoma, but extralimbic encephalitis has been described in the literature very rarely. We report the case of extralimbic encephalitis associated with thymoma along with a literature review.

[A case of ganglioneuroblastoma occurring in the superior mediastinum in an adult].

We report a case of ganglioneuroblastoma occurring in the superior mediastinum in adult. A 63-year-old man was admitted to our hospital for detailed investigation of an abnormal shadow on his chest radiograph. Chest radiography and CT imaging showed a left superior mediastinal tumor. Histopathologically, the tumor was identified as a ganglioneuroblastoma. Although ganglioneuroblastomas occur predominantly in children, 3 cases have been reported in adults in Japan. Incidentally, this is the first reported case of ganglioneuroblastoma occurring in the superior mediastinum in Japan.