[A case of breast cancer with repeated cardiac dysfunction due to trastuzumab].

Here we present a case of breast cancer in which cardiac dysfunction had previously been observed on trastuzumab(TRS) administration; the condition then improved but reoccurred on readministration of TRS. A 52-year-old woman received preoperative chemotherapy for StageIIIC left breast cancer(fluorouracil, epirubicin and cyclophosphamide followed by docetaxel and TRS), and then underwent partial mastectomy and axillary lymph node dissection. For adjuvant therapy, she received endocrine therapy and TRS. Radiation therapy was administered to the left residual breast. The patient complained about palpitation in the 5th cycle of TRS, and left ventricle ejection fraction(LVEF)decreased to 45.3% from 64%. Therefore, we stopped TRS administration. Palpitation improved, and LVEF increased to 53% after 2 months. TRS was administered again; however, palpitation reoccurred and LVEF decreased to 44%. TRS administration was once again discontinued. However, according to the HERA trial report regarding patients with a history of anthracycline and radiation therapy, TRS administration could be resumed when LVEF is greater than 50%, but we should be more careful during readministration of TRS.

Feasibility of prior administration of cyclophosphamide in TC combination treatment.

BACKGROUND: TC (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) q3w) combination is used for neoadjuvant/adjuvant chemotherapy in primary breast cancer. The incidence of allergic reaction is reportedly more common in patients who receive docetaxel before cyclophosphamide. This study aims to determine the significance of cyclophosphamide and docetaxel administration sequence. METHODS: Prospective analysis was performed of 49 consecutive patients treated with TC for stage I-IIB breast cancer from March 2010 to June 2011. Premedication was administered with granisetron, dexamethasone, and chlorpheniramine. Patient charts were reviewed for completion rate and adverse events. Two-tailed Fisher exact test was used to evaluate adverse events between prior cyclophosphamide and prior docetaxel. RESULTS: Of 49 patients, 26 received docetaxel prior to cyclophosphamide and 23 received cyclophosphamide before docetaxel. There were no differences in patient characteristics between the two groups. Completion rates were 95.6 % in the prior cyclophosphamide group, and 100 % in the prior docetaxel group. The relative dose intensities of docetaxel and cyclophosphamide were 94.5 and 94.8 % in the prior cyclophosphamide group, and 98.5 and 98.7 % in the prior docetaxel group (p < 0.01). In the prior cyclophosphamide group, severe neutropenia occurred in 96 % of patients, but in only 46 % of patients in the prior docetaxel group (p < 0.01). Significantly fewer cases of skin eczema (27 versus 61 %), nausea (8 versus 48 %), stomatitis (23 versus 61 %), and diarrhea (4 versus 30 %) were observed in the prior docetaxel group as compared with the prior cyclophosphamide group (p < 0.01). Decreased incidences of fatigue (50 versus 65 %) and edema (19 versus 35 %) were found in the prior docetaxel group (p < 0.05). No difference was observed in allergic reaction or neuropathy between the two groups. CONCLUSION: Patients receiving cyclophosphamide prior to docetaxel were at increased risk of several toxicities as compared with patients receiving docetaxel prior to cyclophosphamide in TC combination therapy.

Feasibility and toxicity of docetaxel before or after fluorouracil, epirubicin and cyclophosphamide as adjuvant chemotherapy for early breast cancer.

BACKGROUND: The tolerance and safety associated with the administration order of the anthracycline and taxane drugs have not been evaluated. PATIENTS AND METHODS: Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The feasibility and toxicity were evaluated in the following regimens--arm A, 3 courses of fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) followed by 3 courses of docetaxel 100 mg/m(2) (DOC); arm B, 3 courses of DOC followed by 3 courses of FEC. RESULTS: Forty-two patients were registered. The relative dose intensity was 94.2 % for FEC and 97.8 % for DOC in arm A, and 98.9 % for DOC and 95.2 % for FEC in arm B. In arm A, grade 3 or higher hematological toxicity was observed in nine patients, and febrile neutropenia developed in three patients with FEC. In arm B, grade 3 or higher hematological toxicity was observed in seven patients, but febrile neutropenia was not noted in any patient. CONCLUSION: The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early breast cancer. However, DOC followed by FEC might be more tolerable. Further studies will maximize the results obtained with DOC followed by FEC.

Abnormal development of intrinsic innervation in murine embryos with anorectal malformations.

INTRODUCTION: Constipation, soiling, and incontinence are common problems after definitive repair of anorectal malformations (ARMs) in children. We studied the expression of substance P (SP), vasoactive intestinal peptide (VIP), and c-kit in the rectum of murine embryos with or without ARMs at later developmental stages. METHODS: On the 9th embryonic day (E9), pregnant Institute of Cancer Research mice were fed etretinate, a synthetic vitamin A analogue (60 mg/kg), whereas controls were fed only with sesame oil. Embryos were excised between E14 and E18, and prepared for histological examination. The SP, VIP, and c-kit expressions were examined by immunohistochemical staining for the SP, VIP, and c-kit antigens, respectively. RESULTS: On E14 and E15, the expression levels of the anti-SP and anti-VIP antibodies in the rectum did not differ between the control and etretinate-treated group. However, as compared to the controls, a decreased SP and VIP immunoreactivity was observed in the circular muscle layer of the rectum between E16 and E18. On the other hand, on E14 and E15, the expression of anti-c-kit antibody in the rectum did not differ between the etretinate-treated and control group. However, c-kit immunoreactivity was slightly higher in the circular muscle layer of the rectum in the controls on E16 and E17, and considerably higher on E18 than that of the muscle layer in the etretinate-treated group. CONCLUSION: At later developmental stages, the expression levels of SP, VIP, and c-kit reduced in the circular muscle layer of the rectum in mice with etretinate-induced ARMs. This result indicates that reduced SP, VIP, and c-kit expression levels in the circular muscle layer may cause severe constipation in children who develop severe ARMs after definitive surgery.

Indocyanine green fluorescence imaging system for sentinel lymph node biopsies in early breast cancer patients.

PURPOSE: This study presents a new method that enables the detection of sentinel lymph nodes (SLN) with high sensitivity using indocyanine green (ICG) fluorescence imaging. METHODS: This study enrolled 128 patients with clinically node-negative breast cancer. Fluorescence imaging was obtained after ICG was injected into the areola. Subcutaneous lymphatic channels were immediately visible. RESULTS: Lymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel was 60%, two channels were 24%, and three channels were 16%. The number of fluorescence SLN ranged from 1 to 6, and blue-dyed SLN ranged from 0 to 3. In the latter, SLN were not identified in 44 patients. Nineteen patients had pathologically identified lymph node metastases. All of them were recognized by fluorescence imaging, but 8 patients had lymph nodes with metastases were not identified by dye method. CONCLUSION: This ICG fluorescence imaging technique is feasible and safe for detecting SLN in a less invasive manner than conventional mapping, with real-time observations.

[Adjuvant trastuzumab can be infused safely over 30 minutes].

UNLABELLED: It has been thought that there is a possibility that infusion speed generally affects the manifested frequency of infusion reaction and its strength. The infusion prescription time of trastuzumab should be over 90 minutes according to the package insert. In the infusion US, is possible over 30 minutes after the second time. We sought to evaluate the safety and tolerability of trastuzumab administered as a 30-minute infusion. PATIENTS: Eighteen patients of HER2-positive breast cancer were treated, and their age ranged from 37 to 65 years old(median, 54 years old). METHOD: PATIENTS were infused with 8 mg/kg of trastuzumab over 90 minutes and, if tolerated, all subsequent maintenance doses of 6 mg/kg are over 30 minutes. RESULT: The infusion times for 30 minutes were twice to 17 times(16 times the median). Mild infusion reactions were seen in 2 cases at the time of the initial prescription, but the infusion reaction was not judged from the prescription for 30 minutes. Mild eczema was admitted by 3 cases after prescription. No decline in cardiac function was seen. CONCLUSION: Our data strongly suggest that trastuzumab can be safely infused over 30 minutes for 6 mg/kg maintenance doses. However, it is thought that the number of cases will increase in future, and confirmation is necessary.

[Feasibility of FEC 100 followed by DOC 100 as adjuvant chemotherapy for breast cancer].

UNLABELLED: As adjuvant chemotherapy for breast cancer, the addition of taxane to regimens containing anthracycline has been shown to be effective. However, in Japan, it is not probability yet as for safety. We examined the feasibility of FEC 100 followed by DOC 100 as adjuvant chemotherapy for breast cancer. METHODS: Node-positive breast cancer patients or node-negative high-risk patients were eligible. The treatment completion rate and toxicity were evaluated in 3 courses of FEC 100 mg/m2 followed by 3 courses of DOC 100 mg/m2. RESULTS: Twenty-one patients were registered and completion rate was 100%. The relative dose intensity (RDI) was 94.2% for FEC 100 and 97.8% for DOC 100. Grade 3 or higher neutropenia observed in 38% and febrile neutropenia developed in 14%. Non-hematological toxicities were slight. CONCLUSION: The regimen of FEC 100 followed by DOC 100 was safe in adjuvant chemotherapy for breast cancer in our country.

Occult breast cancer with EDTA-dependent pseudothrombocytopenia -a case report-.

A case of occult breast cancer with pseudothrombocytopenia (PTCP) is reported. A 50-year-old woman was consulted with a left axillary tumor. Ductal carcinoma was found by the core needle biopsy, and no primary lesion was detected. Her preoperative platelet count, obtained from an ethylene diamine tetraacetic acid (EDTA) sampling bottle, was 3.1 x 10(4) per mL, but she had no history of bleeding problems. A heparinized blood sample showed a normal platelet count of 390 x 10(4) per mL. These findings suggested a diagnosis of occult breast cancer with EDTA-dependent PTCP, and level II axillary lymph node dissection was performed. She received adjuvant chemotherapy and radiotherapy, but she died 2 years and 5 months after the surgery because of lung and brain metastases. Awareness of the phenomenon and knowledge of the underlying physiological principles will enable surgeons to manage patients with EDTA-dependent PTCP appropriately.

[An effective case of liver metastasis of breast cancer treated with capecitabine + docetaxel combination therapy using vitamin B6].

Capecitabine + docetaxel combination therapy proves highly effective against the advanced or recurrent breast cancer. Therefore, it has been investigated as a first-line treatment for metastatic breast cancer. Hand-foot syndrome (HFS), a typical side effect of capecitabine, decreases the QOL of patients and sometimes prevents further medication using capecitabine. A 56-year-old woman who had liver, bone and local skin metastases two years after her left breast cancer operation, was treated with capecitabine + docetaxel combination therapy. Severe HFS disturbed the continuation of the therapy. Some other chemo-therapies were attempted after discontinuing the therapy; however, the metastases progressed. Finally, we tried to prevent HFS with vitamin B6 and started the capecitabine + docetaxel combination therapy. HFS was controlled completely. The liver tumor disappeared in MRI and CT images after 18 courses. In this case, vitamin B6 seemed to be effective to control HSF and allow continuation of capecitabine + docetaxel combination therapy.

Peripheral nerve regeneration by transplantation of BMSC-derived Schwann cells as chitosan gel sponge scaffolds.

It is said that bone marrow stromal cells (BMSCs) are able to differentiate into different kinds of cells, including Schwann cells, under relevant conditions (Dezawa et al., Eur J Neurosci 2001;14:1771-1776). In the previous paper, we demonstrated that chitosan gel sponge is one of the effective scaffolds for regenerating axons of the rat sciatic nerve (Ishikawa et al., J Biomed Mater Res A 2007;83:33-40). In the present study, we examined whether BMSC-derived Schwann cells with chitosan gel sponges were one of the effective scaffolds for peripheral nerve regeneration in rats. BMSC-derived cells with Schwann cell characteristics were labeled by green fluorescent protein using a retrovirus. An 8-mm gap was made by removing a nerve segment from the rat peripheral nerve, and chitosan gel sponges containing BMSC-derived Schwann cells were grafted, sandwiching the proximal and distal stumps of the transected nerve. Rats were sacrificed at 7, 14, and 28 days, and 2 and 4 months after transplantation. Immunohistochemistry demonstrated that regenerating axons were found near transplanted Schwann cells 7 days after surgery and extended into the host distal nerve segment at 14 days after surgery. Electron microscopy showed that transplanted Schwann cells formed myelin sheaths on regenerating axons 1 month after transplantation. The mean diameter of myelinated fibers was increased from 2.58 mum at 2 months to 2.84 mum at 4 months postsurgery. This study indicates that chitosan gel sponges containing BMSC-derived Schwann cells have strong potentiality as a graft that can be used for peripheral nerve regeneration.

Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation.

Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.