Resection of an intrapulmonary solitary fibrous tumor in the center of the middle lobe: a case report.

A 75-year-old female patient was referred to our hospital due to an abnormal shadow detected by chest X-ray. Computed tomography scans revealed a well-circumscribed nodule measuring 28 mm between B4 and B5 in the right middle lobe. Because the tumor was in the center of right middle lobe, a middle lobe resection was performed. The tumor was located within the lung and there were no obvious pleural surface changes. Postoperative histological findings showed 34-mm firm and round tumor, and well circumscribed without involving the visceral pleura. The pathologic examination revealed proliferating spindle-shaped cells with a random fascicular arrangement with continuity to the pulmonary interstitium. Not much cellular atypia was observed. Immunohistochemical staining indicated that the tumor was positive for STAT6, CD34. The final diagnosis was an intrapulmonary benign solitary fibrous tumor (SFT). Even benign intrapulmonary SFTs that have been completely resected may later become malignant and recur, and careful follow-up is necessary.

[A case of liver metastasis of breast cancer responding to letrozole].

The patient was a 68-year-old woman who had a right mastectomy performed in another hospital in 1987. Her right breast tumor was histologically diagnosed IDC and ER(-), with an uncertain PgR and HER2. Tamoxifen was administered as adjuvant therapy for five years after surgery. Because she had abdominal pain in January, 2007, she consulted her family doctor. At that doctor's hospital, metastatic tumors of the liver were found, and she was therefore referred to our hospital. A liver biopsy of the tumor was conducted in our hospital, and hormone therapy was also conducted because her cancer status was ER(+), PgR(+), HER2(0), and was not life-threatening. Hormone therapy had a good effect on the tumor. ER, PgR and HER2 expression might make the difference between a primary tumor and a metastatic one, as in this case. Therefore, we should perform biopsies on metastatic tumors to determine the best treatment method. There is a possibility that hormone therapy will become an effective therapeutic procedure for breast cancer patients who are hormone receptor positive, are not in a life threatening situation, and have had a long, disease-free survival. We reported one case in which the aromatase third generation inhibitor letrozole was effective for treating liver metastases of breast cancer.

[A case of multidrug-resistant breast cancer associated with multiple hepatic and bone metastases for which cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy proved effective].

A 51-year-old patient had recurrent breast cancer with liver metastases. After mastectomy, she received CEF and many kinds of hormone therapy and chemotherapy after recurrence. Her liver metastases had been controlled by CMF therapy for 9 months. CMF therapy is good at maintaining the QOL of recurrent patients during treatment because of less toxicity and is even useful for multidrug-resistant tumors like this patient with liver metastases after anthracycline and taxane treatment. CMF is thought to be still useful after development of new drugs for recurrent breast cancer.

In vitro evaluation of dose-response curve for paclitaxel in breast cancer.

BACKGROUND: The dose-response curve for anticancer agents cannot be evaluated by studying patients directly. To investigate individual differences in the dose-response curve for paclitaxel in breast cancer, we utilized the histoculture drug response assay (HDRA) technique. MATERIALS AND METHODS: Twenty specimens obtained from breast cancer patients who underwent surgical resection were used in this study. The inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve, using non-linear least squares analysis with the fitting equation y=A(1-1/(1+exp(B(x-log(C))))), where A denotes maximal response; B, slope factor; and C, ED50. RESULTS: A dose-response curve was obtained in all tumors. The mean value (+/-SD) of maximum response, slope factor, and ED50 were 90.2+/-5.5%, 9.4+/-4.3, and 36.8+/-17.2 microg/ml, respectively. The slope factor was higher in nuclear grade 3 tumors compared with nuclear grade 1 and 2 tumors. CONCLUSION: An individual dose-response curve for paclitaxel in breast cancer can be obtained using the HDRA technique. Nuclear grade 3 tumors appeared to have more uniform chemosensitivity to paclitaxel compared with nuclear grade 1 and 2 tumors.

Data acquisition for the histoculture drug response assay in lung cancer.

OBJECTIVE: Application of the histoculture drug response assay for lung cancer was investigated by using data acquired from lung cancer specimens. METHODS: From May 1994 through February 2005, histoculture drug response assay data were obtained from 359 lung cancer specimens held in our institute. We examined chemosensitivities of the tissues to cisplatin, doxorubicin, mitomycin C, 5-fluorouracil, docetaxel, paclitaxel, etoposide, irinotecan, and gemcitabine. Cutoff inhibition rates were determined with each drug for non-small cell lung cancer and were used to calculate predictabilities for chemotherapy responses. RESULTS: The evaluability of the histoculture drug response assay was high at 97.4%. Good predictability, including true-positive and true-negative rates of 73.2% and 100%, respectively, with an accuracy of 83.0%, was observed. CONCLUSION: The histoculture drug response assay appears to be applicable to non-small cell lung cancer for the prediction of responses to chemotherapy.

Radiofrequency ablation therapy in patients with breast cancers two centimeters or less in size.

BACKGROUND: Non-surgical ablation is an attractive approach as a local control method for breast cancer. The purpose of this study was to investigate the complications and efficacy of radiofrequency ablation (RFA) therapy for breast cancer. METHODS: A total of 52 patients with breast cancer were enrolled. The mean tumor size was 1.3 cm (range, 0.5-2.0 cm). Under general anesthesia, RFA was done with a Cool-tip RF system after sentinel node biopsy. All patients received one session of RFA, for a maximum time of 30 minutes for the first 29 patients and 15 minutes for the following 23 patients when so-called 'break', i.e. stopping the delivery of radiofrequency, did not occur. Postoperative cytological evaluation was done 3-4 weeks after operation. Adjuvant therapy consisted of chemo- and/or endocrine-therapy and radiotherapy (50 Gy). RESULTS: The mean time of RFA was 12 minutes (5-25 minutes). One patient (2%) was troubled with a skin burn just above the ablated field. No patient had viable cancer cells on post-operative cytological evaluation. No recurrence developed 15 months on the average after RFA (6-30 months). Cosmesis after RFA was excellent in 43 patients (83%), good in 6 (12%), and fair in 3 (6%). CONCLUSION: RFA can be safely used for breast cancer and provides good local control and excellent cosmesis to patients with small breast cancers.

Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations.

BACKGROUND: Although radioisotopic procedures are commonly used to detect sentinel lymph nodes in breast cancer surgery, these procedures are often problematic and not necessarily suitable for lung cancer surgery. METHODS: Our previous study revealed that the mediastinal sentinel lymph node, defined as the regional mediastinal lymph node, consisted of nodes 2, 3, or 4 in right upper lobe cancers; 3, 7, or 8 in right lower lobe cancers; 4, 5, or 7 in left upper lobe cancers; and 4, 7, or 8 in left lower lobe cancers. On the basis of these findings, we pathologically investigated one representative lymph node at each of the 3 levels dissected during surgical intervention in 69 patients with non-small cell lung cancer from September 1993 through December 2002. Fifty-eight patients with lung cancer underwent lobectomies with limited mediastinal lymph node dissection according to this strategy. RESULTS: Mediastinal lymph node recurrence was observed in only one patient during 41 +/- 25 months (maximum, 98 months) of follow-up. The cancer-specific 5-year survivals were 96.6% in patients with pathologic stage IA disease (n = 31) and 67.4% in patients with stage IB disease (n = 16). CONCLUSION: These results suggested that limited mediastinal lymph node dissection is applicable to patients with non-small cell lung cancer whose regional mediastinal lymph nodes are not metastatic.

[Cut-off level of docetaxel, paclitaxel and gemcitabine in histoculture drug response assay for non-small cell lung cancer].

Cut-off levels of docetaxel (DOC), paclitaxel (PAC), and gemcitabine (GEM) in histoculture drug response assay are determined by data acquisition of non-small cell lung cancer. Inhibition rates were 47.5 +/- 22.2% in DOC (n=181), 66.6 +/- 25.1% in PAC (n=57), and 25.4 +/- 18.4% in GEM (n=63), respectively. Cut-off levels were determined as 50% in DOC, 60% in PAC, and 30% in GEM. The positive rates such as 47.5% in DOC, 68.4% in PAC, and 33.3% in GEM were obtained.

[Dose response curve of paclitaxel measured by histoculture drug response assay].

Dose response curves of paclitaxel were measured by histoculture drug response assay (HDRA) in 11 lung cancer patients. Inhibition rates of paclitaxel at several concentrations were measured and fitted to the sigmoid dose response curve, using non-linear least square analysis, with fitting equation y=A (1-1/(1+exp (b (x-log (ED50)). Parameters A, b, and ED50 were 88.3+/-6.0 (80.0-100.0) %, 9.57+/-4.32 (2.25-15.0), and 26.8+/-8.1 (15.0-41.0) microg/ml, respectively. The parameter b was lower in well-differentiated tumors compared with moderately and poorly-differentiated tumors. Dose response curves of paclitaxel could be measured by HDRA in lung cancer. This method provides us more information for drug sensitivity than the usual HDRA method. This may lead to the improved accuracy of HDRA.

[Anastrozole-resistant breast cancer responsive to exemestane--a case report].

We describe a postmenopausal woman suffering from advanced breast cancer with pleural effusion. She had prior anastrozole therapy, and was referred to our hospital with dyspnea. The use of exemestane, a highly selective steroidal aromatase inhibitor (25 mg daily), successfully induced remission of pleural effusion. Exemestane is a useful treatment for postmenopausal woman with advanced breast cancer, which is refractory to anastrozole.

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)=(C0-Cp)exp(-kt)+Cp, where C(t) was the postoperative CEA level, t was the number days after surgery, C0 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.

[Histoculture drug response assay for solitary fibrous tumor--a case report].

A 49-year-old male was referred to our hospital because of an abnormal shadow in his left lower lung field on chest X-ray. Magnetic resonance imaging scans revealed a large mass on the left diaphragm. The tumor was surgically extirpated. The tumor, encapsulated and growing from the center of the left diaphragm, measured 18 x 8 x 4 cm and weighed 440 g. Microscopic examination revealed a solitary fibrous tumor with mitotic activity of 7/ 50 hpf. Immunohistochemically, the tumor was negative for cytokeratin, s-100 protein, desmin, and alpha-smooth muscle actin, while positive for vimentin and CD34. On a histoculture drug response assay using the resected tissue, the tumor was sensitive to 5-FU, adriamycin, mitomycin C and docetaxel, and resistant to cisplatin, irinotecan, and gemcitabine.

[Histoculture drug response assay guided concurrent chemoradiotherapy for lung metastasis from adrenocortical carcinoma--a case report].

A 50-year-old woman underwent surgical resection of a left adrenocortical carcinoma in April 2000. Bilateral pulmonary metastases and abdominal lymph node metastasis were detected in June 2001. After radiation therapy for the abdominal lymph node metastasis, a pulmonary metastatic lesion was thoracoscopically resected. The specimen was subjected to histoculture drug response assay (HDRA), and results revealed that this tumor was sensitive for cisplatin. We therefore performed concurrent chemoradiotherapy including cisplatin for the residual pulmonary metastatic lesion; a complete response was then obtained. Standard protocols of chemotherapy are often absent for malignant tumors, such as in this case, with low incidences. HDRA seems useful for chemotherapy agent selection in cases of rare malignant tumors.

Increased expression of integrin alpha3beta1 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 alpha3 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 alpha3beta1 significantly (P < 0.05) decreased brain metastasis by EBC-1/brain. Interaction of integrin alpha3beta1 and laminin plays important roles in the process of brain metastasis of non-small cell lung cancer.

[Successful management of malignant pericardial effusion with weekly paclitaxel therapy in a lung adenocarcinoma patient].

A 67-year-old woman had undergone lobectomy and mediastinal lymphadenectomy on December 17, 1999, for lung adenocarcinoma. On June 29, 2001, the patient was readmitted because of acute deterioration of diabetic chronic renal failure due to cardiac dysfunction. Serum CEA level was high at 724 ng/ml. Chest X-ray and ultrasound suggested the presence of pericardial effusion, which was managed with pericardial drainage. Cytological examination revealed malignant cells (class V) in the effusion. Therefore, the patient was suffering from carcinomatous pericarditis. After the introduction of hemodialysis, the patient was treated with weekly paclitaxel therapy. Each cycle consisted of 3 weeks of therapy followed by a 1-week treatment break. Weekly paclitaxel therapy (11 infusions) brought about a normalization of the elevated CEA levels and a good control of the pericardial effusion. The patient has developed neither tumor progression nor reelevation of serum CEA levels for 12 month with no further therapy.

Time course of carcinoembryonic antigen after resection of lung cancer: a predictor of recurrence.

UNLABELLED: We investigated whether the early postoperative time course of carcinoembryonic antigen (CEA) level after resection of lung cancer could be used to predict patients' prognosis. Fifty-three lung cancer patients were included in this study. Postoperative serum CEA levels were calculated by means of non-linear least-squares fitting to the equation C(t) = (C(0)-C(p))exp(-kt) + C(p), where C(t) is postoperative CEA level, t is days after surgery, C(0) is CEA level at postoperative time 0, C(p) is CEA level at plateau, and k is the rate constant of elimination. Postoperative CEA production (P(p)) was calculated as C(p) multiplied by k. C(p) and P(p) represent the numbers of residual tumor cells after surgery. More residual tumor cells yield higher values of C(p) and P(p), and result in earlier recurrence. RESULTS: Kinetic parameters could be obtained for 30 patients whose preoperative CEA levels were sufficiently elevated. Cutoff levels as predictors for recurrence were 1.1 ng/ml for C(p) and 0.9 ng/ml/day for P(p). The accuracy of prediction of recurrence using these cutoff levels was 79% with C(p) and 89% with P(p). A very poor prognosis was observed for patients with P(p) over 0.9 ng/ml/day. CONCLUSION: Analysis of the time course of changes in CEA levels after resection of lung cancer appears to be useful for predicting patient prognosis. C(p) and P(p) are very precise predictors of recurrence.

[Histoculture drug response assay (HDRA) guided induction concurrent chemoradiotherapy for mediastinal node-positive non-small cell lung cancer].

To improve the response to chemotherapy for non-small cell lung cancer (NSCLC), effective drugs should be selected for each patient. In 1994 we introduced histoculture drug response assay (HDRA) for NSCLC patients. For clinical N2 patients, biopsy of mediastinal lymph node is performed both for histological diagnosis and for HDRA. Induction concurrent chemoradiotherapy is then performed using HDRA positive chemotherapy agents. We have treated three patients with this strategy. HDRA could be performed using mediastinal lymph node biopsy specimens. Tumor reduction rates of these patients were 80.4%, 85.3%, and 57.1%. Their histological responses were Ef.3, Ef.2, and Ef.1b, respectively. Complete resection was done in all patients. This strategy appeared to be useful in NSCLC patients with mediastinal lymph node metastasis.

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.