A randomized phase III trial of postoperative adjuvant therapy for completely resected stage IA-IIIA lung cancer using an anti­angiogenetic agent: irsogladine maleate.

AIM: Although angiogenesis plays an important role in the invasion and metastasis of solid tumors, very few anti-angiogenetic drugs have been developed. Reexamining the anti-angiogenetic effects of existing drugs such as Thalidomide is another possible strategy for drug discovery. Irsogladine maleate (IM) is a drug invented to treat gastric ulcers; however, several reports have shown that IM also exerts anti-angiogenetic effects in vitro, in vivo and in humans. In order to elucidate whether treatment with IM would improve the prognoses of patients with resected lung cancer, we conducted a randomized trial. METHODS: In the control group, uracil-tegafur (250 mg/m2/day) was administered for two years to patients with resected stage IB - IIIA lung cancer, and no adjuvant therapy was administered to those with stage IA disease. In the study group, IM (4 mg/body/day) was additionally administered for two years. RESULTS: No significant differences were observed in the major prognostic factors among 305 eligible patients between the study and control groups. Adverse effects were minimal. The overall survival of the patients in the study and control groups were not statistically different. When the analysis was stratified by regimen, among the patients with resected stage IA disease, disease-specific survival in the study group was slightly higher than that in the control group; however, the difference was not significant (p=0.07). CONCLUSION: Although it could not be proven that IM improves the prognoses of resected lung cancer patients, IM might have some effect on resected stage IA disease, and another trial should be conducted.

[Evaluation for medical management on catamenial pneumothorax].

Catamenial pneumothorax (CP) is one of the clinical manifestations of endometriosis, therefore the systemic hormonal therapy is indispensable and should be the 1st choice for CP treatment. However, it is refractory and repeats a recurrence, so that a combined or sequential adjuvant treatment becomes necessary. From 2003 to 2009, 5 patients with CP were treated at our institution. All patients had right-sided pneumothorax and the history of pelvic endometriosis. By thoracoscopic examination, diaphragmatic abnormalities, such as defect, pinhole, or brown spot, were identified in all patients. We performed hormonal therapy combined with chemical pleurodesis using OK-432, as an initial treatment. Two patients have been free of recurrence for 24 and 53 months, respectively. Three patients who refused or interrupted hormonal therapy caused a recurrence, but were successfully managed with the addition of pleurodesis and continuing hormonal therapy. At present, all patients are asymptomatic with 13 to 92 months recurrence-free period. From the long-term results, our therapeutic strategy consisted of hormonal therapy and chemical pleurodesis is considered appropriate.

[Recurrence patterns and prognosis in lung cancer patients with positive pleural lavage cytology at surgery].

Recurrence patterns and prognosis in lung cancer patients with positive pleural lavage cytology (PLC) at surgery have not been completely understood. From January 2001 to October 2007, we performed PLC on 195 patients undergoing thoracotomy for lung cancer. Fourteen (7.2%) of 195 patients had positive PLC findings. Twenty seven patients who underwent limited surgery due to complication were excluded from the further investigation. Some form of recurrence was observed in 33 (21.2%) of 156 patients with negative PLC, and in 8 (66.7%) of 12 patients with positive PLC (p < 0.05). The local recurrence was observed in 13 (39.4%) of 33 patients who have recurrence with negative PLC and was observed in 4 (25%) of 8 patients who have recurrence with positive PLC (p = 0.45). The survival rate of patients with positive PLC was significantly worse than that of patients with negative PLC (p < 0.05), and was as low as that of patients with macroscopic malignant effusion. The multivariate analysis demonstrated PLC was independent prognostic factor. PLC is an easy procedure and is an important prognostic factor, and should be routinely performed in the lung cancer operation.

[The prevention and measures to complication of video-assisted thoracoscopic surgery for lung cancer patients].

Video-assisted thoracoscopic surgery (VATS) for patient with lung cancer is seemed to be more genetic in future. It is because of small wound, little ache and short hospitalization. However, dissection of lymph-nodes is necessary since it is lung cancer. Because the thoracoscopic lobectomy is performed in the limited space, troubles those we cannot predict can happen. So surgical techniques of to prevent troubles are important. And this is the first step to avoid postoperative complication. It is necessary that to grasps a state of the patient and not to leave perioperative troubles.

[Spontaneous regression of thymoma; report of a case].

A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor. Extended thymo-thymectomy was performed via median sternotomy. The tumor was in the right lobe of the thymus. Pathologically the tumor was diagnosed as a mixed type non-invasive thymoma, but some parts of the tumor cells were necrotic. This is the 10th case of spontaneous regression of thymoma reported in the Japanese literature.

[Catamenial pneumothorax due to diaphragmatic endometriosis; report of a surgical case].

A 27-year-old female was complained repeated right pneumothorax. Each episode was obviously related to the onset of menstruation, suggesting catamenial pneumothorax. Thoracoscope revealed the presence of several fistulas in the central tendon of the diaphragm. Partial resection of the diaphragm including these lesions was performed under thoracoscopic procedure. Microscopic examination of the excised specimen showed endometriosis. The patient was followed without hormonal therapy, but recurrent pneumothorax occurred. For the catamenial pneumothorax, hormonal treatment is considered necessary even after surgical treatment.

[Subdiaphragmatico-mediastinal lipoma through the foramen of Bochdalek; report of a surgical case].

A 53-year-old man was admitted to our hospital for evaluation of chest abnormal shadow at the left cardiophrenic angle. Computed tomography (CT) scan revealed a homogeneous mass of fatty density on the left diaphragm. Magnetic resonance imaging (MRI) demonstrated a well-demarcated tumor mass with a fatty signal intensity and, in the sagittal view, the mass showed continuity into the retroperitoneal fatty tissue. Extirpation of the tumor was performed under thoracoscopic procedure. The tumor was adhesive closely to diaphragm and extended into the retroperitoneal space through the foramen of Bochdalek. Pathologically the tumor was diagnosed as a mature lipoma. This tumor was considered to originated from the retroperitoneal fatty tissue under the diaphragm and to herniate into the mediastinum through the foramen of Bochdalek.

[Pulmonary actinomycosis mimicking of mucosa-associated lymphoid tissue lymphoma by frozen section examination: report of a case].

A 59-year-old man was admitted to our hospital for hemoptysis. Chest X-ray films showed a mass shadow in the left lower lobe. Any definitive diagnosis could not be made after examinations including sputum culture and bronchial cytology. Exploratory thoracotomy was performed since malignancy was not excluded. During the operation, mucosa-associated lymphoid tissue (MALT) lymphoma was suspected based on the pathological findings of the frozen section. The permanent section of the resected specimen contained colonies of actinomycetes in the bronchus, and the peripheral region demonstrated marked infiltration of lymphocytes and plasma cells through the interstitium of alveolar walls and peri-bronchovascular sheath, with many lymphoid follicles. This case revealed pulmonary actinomycosis coexisted with lymphocytic interstitial pneumonia (LIP). We concluded that lymphoproliferative disease should be considered another candidate for the differential diagnosis from pulmonary actinomycosis.

[Clinical experience of gelatin-resorcin-formal (GRF) glue for acute empyema with bronchopleural fistula].

Gelatin-resorcin-formal (GRF) glue is a new biological adhesive agent with the advantage of sealing efficacy. We report a successful closure of bronchopleural fistula using this agent. A 77-year-old man underwent cavernostomy for lung aspergillosis. After surgery, he developed methicillin-resistant staphylococcus aureus (MRSA)-empyema with bronchopleural fistula. Thoracoplasty and muscular plombage were performed for filling up the cavity and closure of bronchial fistula. But the fistula relapsed 3 days after surgery. GRF glue was injected into the residual cavity, then air-leakage was completely disappeared with tight adhesion of cavity wall. We consider this agent is useful material for the closure of bronchopleural fistula.

[Metachronous lung cancer: indication and outcome].

Although lobectomy is the standard surgical treatment for primary lung cancer, it is unclear whether lobectomy will be benefit for patients with metachronous lung cancer. The purpose of this study is to evaluate the difference of benefit between lobectomy and limited resection at second lung resection. Forty-eight patients, who had already undergone lobectomy due to primary lung cancer, undergoing second lobectomy (n = 30) or limited resection (n = 18) for metachronous lung cancer were investigated. The over-all 5-year survival rate of second operation was 51.9%. Although there was no significant difference of 5-year survival rates between lobectomy and limited resection, 50.4% and 49.4%, respectively, lobectomy for T1N0 subset prolonged the survival compared to limited resection, 5-year survival rates, 69.6% and 31.7%, respectively. However, lobectomy resulted in more postoperative complications and less preservation of lung function. Lobectomy should be considered the surgical procedure of choice for patients with metachronous T1N0 lung cancer when lung function is preserved.

Prefabricated thin flap using the transversalis fascia as a carrier.

To harvest a thin flap from the groin and hypogastric area, the authors developed a new prefabricated flap using the transversalis fascia as a carrier. The transversalis fascia is a very thin and abundantly vascularized tissue nourished by the deep inferior epigastric vessels. Flap prefabrication was performed by inserting the transversalis fascia between the thinly undermined skin flap and the tissue expander placed beneath the skin flap, followed by a pretransfer delay procedure around the flap. After a 3-week interval, the flap was transplanted with no complications, such as congestion and thrombus of anastomosis. By using this technique, it was possible to elevate an equally thin flap from the groin and hypogastric area while avoiding morbidity of the donor site.

Clinical application of the free thin anterolateral thigh flap in 31 consecutive patients.

In this retrospective study, 31 reconstructions using thin anterolateral thigh flaps and six cadaveric dissections of the thigh were investigated in consideration of the anatomic variations of the perforator vessels in the adipose layer, the safe area of flap circulation, and the clinical indications. Three variations of the perforator vessel course in the adipose layer were predicted correctly. The safe radius of a thin anterolateral thigh flap with a thickness of 3 to 4 mm was determined to be approximately 9 cm from the point where the perforator met the skin. The use of a thin anterolateral thigh flap for reconstruction of the neck, axilla, anterior tibial area, dorsum of the foot, circumference on the ankle, forearm, and dorsum of the hand was therefore recommended.

The significance of surgery for bulky N2 small-cell lung cancer: a clinical and in vitro analysis of long-term survivors.

Until recently, stage III small-cell lung cancer (SCLC) has not been considered an indication for surgical treatment, however, stable subculture has become possible in about 80% of the patients with SCLC in our hospital. Therefore, we have been performing surgery for all patients with cStage I-III resectable tumors and giving combined-modality therapy based on the sensitivity assay in vitro since April 1982. In the present study, we reviewed 30 consecutive patients with cStage III and pStage III SCLC, including 27 with N2 disease who underwent surgery between 1982 and 1992, 7 of whom (23%) survived disease-free for over 5 years. We examined the cell characteristics in vitro and the actual treatment of five patients with bulky N2 lesions, four of whom were long-term survivors and one of whom died 11 months after surgery, as controls for comparison with the long-term survivors. Based on the results of the cell characteristics in vitro, SCLC was determined to be a heterogeneous tumor. Thus, surgical excision of the primary tumor with adjuvant therapy might be necessary to achieve long-term survival and maintain good performance status, and to improve quality of life in patients with bulky N2 SCLC by eliminating drug-resistant tumor cells within the primary tumor.

Long-term survival of a patient with stage IV pulmonary large cell carcinoma achieved by combined-modality therapy: report of a case.

We describe herein the case of a 59-year-old-man with stage IV pulmonary large cell carcinoma and a giant brain metastasis, in whom two sublines with different growth characteristics and drug sensitivities in vitro were established from the primary tumor. Disease-free survival for more than 5 years after surgery was achieved by combined-modality therapy together with surgery to remove the primary tumor, radiation to the brain metastasis, and chemotherapy to presumed hematogenous dissemination. Subline 1 proliferated in a monolayer of epithelial-like cells, while subline 2 showed a floating colony pattern of proliferation, resembling the typical growth characteristics of small cell lung cancer (SCLC) cells in vitro. Subline 2 was sensitive to a number of drugs, namely, vincristine (VCR), cyclophosphamide (CPM), adriamycin (ADR), and cisplatin (CDDP), whereas subline 1 was resistant to many drugs. The patient was treated with a combination of 44 Gy of whole-brain irradiation and a number of cycles of chemotherapy comprised of ADR, VCR, and CPM, followed by CDDP, VCR, and CPM, based on the results of sensitivity testing of the subline 2 cells. As a result, the patient has been disease-free for more than 5 years postoperatively. In conclusion, this case report serves to demonstrate that meticulous combined-modality treatment taking tumor heterogeneity in human cancers into account may be necessary to achieve breakthroughs in current cancer therapy for advanced lung cancer.

[A case of right B2 hillar lung cancer treated by sleeve segmentectomy].

A 47-year-old male, a heavy smoker, was referred to our hospital after Class IV was detected by screening of sputum cytology. His chest X-ray film showed no abnormalities, but bronchoscopy revealed a small nodular lesion at the orifice of right B2. Squamous cell carcinoma was diagnosed by transbronchial biopsy. The clinical stage was I (T1N0M0), and S2 sleeve segmentectomy with lymph node dissection (R 2 b) was performed. The pathological stage was I (T1N0M0), and it was confirmed as early hilar lung cancer. There were no post operative complications and he is well without any evidence of recurrence 5 months after surgery. It may well be considered that this segmental bronchoplastic procedure is useful for cases with early stage squamous cell carcinoma of the segmental bronchus to preserve pulmonary function.

Combined modality therapy including surgery for stage III small-cell lung cancer on the basis of the sensitivity assay in vitro.

Fifty-nine consecutive patients with clinical stage (cStage) I-III resectable small-cell lung cancer (SCLC) underwent surgery with adjuvant chemotherapy based on an in vitro sensitivity assay between April 1982 and March 1992. In 42 (71%) of these patients, a stable passage of cancer cells from resected specimens was possible and the sensitivity of these cultured SCLC cells to anticancer drugs was examined by the MTT method. In the sensitivity assay, vincristine (VCR) showed the most intense specific efficacy for SCLC, followed by cyclophosphamide (CPM) and cisplatin (CDDP). The 5-year survival rates for pathological stage (pStage) I, pStage II, and pStage III were 55%, 33%, and 23%, respectively. The 5-year survival of the patients with pStage III operated on in the first 5 years was 7% (1/14). On the other hand, 6 of the 16 pStage III patients (38%) operated on during the second 5-year period, who were generally treated with pre- and postoperative adjuvant chemotherapy combined with three drugs, survived over 5 years. In conclusion, these results suggest that combined modality therapy including surgery is necessary, and adjuvant chemotherapy combined with VCR, CPM, and CDDP may be useful in the treatment of Stage III SCLC disease, for the purpose of achieving a long-term survival with both a good performance status and quality of life for the patients.

Long-term survival of a poor-risk octogenarian following wedge resection under VATS for small-cell lung cancer: report of a case.

We describe herein the case of an 81-year-old man who has remained disease-free for more than 3 years after undergoing a wedge resection of cStage I small-cell lung cancer (SCLC) under video-assisted thoracoscopic surgery (VATS), with no adjunct chemotherapy or radiotherapy. The patient had compromised pulmonary function and was a poor surgical risk. As he could not have endured a conventional lobectomy or intensive chemotherapy, a nonanatomical wedge resection of the area of lung involved by the primary tumor was carried out under VATS. Cancer cells from the resected tumor were cultured and the growth characteristics and sensitivity to 12 anticancer drugs were examined. The majority of primary cultured cells proliferated in a monolayer, like paving stones, resembling the growth pattern of non-small-cell carcinoma cells in vitro. The subcultured cells were resistant to most of the drugs, but showed weak sensitivity to cisplatin (CDDP), adriamycin (ADR), and vincristine (VCR). Therefore, the patient was discharged with no adjunct postoperative therapy and was followed up at an outpatient clinic. He has remained alive and disease-free for more than 3 years. Thus, we considered that performing wedge resection under VATS for a primary tumor could be appropriate treatment for selected patients with cStage I SCLC in a peripheral region, especially if they are elderly and a poor surgical risk.

The establishment of sublines with opposite chemosensitivity from a patient with pulmonary large cell carcinoma and the implementation of treatment based on tumor heterogeneity.

Two sublines were established from the primary tumor of a patient with pulmonary large cell carcinoma. These two sublines had different growth characteristics in vitro and different tumor tissue structure in nude mice, and opposite drug sensitivities. Subline 1 was sensitive to a number of drugs, while its sensitivity to cisplatin (CDDP) was not very strong. In contrast, subline 2 was resistant to many drugs, but showed very strong sensitivity to CDDP. When the patient developed recurrence, he was first treated with CDDP-based chemotherapy based on the sensitivity of subline 2, followed by methotrexate-based treatment on the basis of sensitivity for subline 1. Complete remission (CR) was achieved after this alternating chemotherapy. To our knowledge, this is the first report of sublines with opposite sensitivity being established from the same tumor, achieving CR by the treatment of each subline.

[A case report of double roentgenographically occult lung cancer revealed by postsurgical pathological study].

A 66-year-old man admitted to our hospital as a roentgenographically occult lung cancer (ROLC) detected by sputum cytology of class IV. A differential brushing of all branches of the bronchi was performed and squamous cell carcinoma was detected only from the right B8 segmental bronchus. Right lower lobectomy was performed and the microscopic findings of surgical specimen revealed the squamous cell carcinomas were seen at not only B8 bronchus but also B7 bronchus. The frequency of multicentricity of ROLC is reported to be high, and a differential bronchial brushing of all bronchi is a very powerful method to diagnose synchronous multiple lung cancer. However, we failed to detect a cancer lesion of B7 segmental bronchus in this case. Since, the outcomes of surgical treatments for either synchronous or metachronous multiple primary lung cancer are satisfactory, limited surgical treatments might be appropriate as an initial treatment for a ROLC.

The marked anticancer effect of combined VCR, MTX, and indomethacin against drug-resistant recurrent small cell lung carcinoma after conventional chemotherapy: report of a case.

In a previous study, we discovered that indomethacin was an effective modulator of the sensitivity of pulmonary carcinoma cells to vincristine (VCR), methotrexate (MTX), adriamycin (ADR), and etoposide (VP-16). We describe herein the case of a 61-year-old-man with multiple brain, lung, liver, and bone metastases from small cell lung carcinoma (SCLC) that recurred after intensive chemotherapy, who showed no signs of remission following conventional chemotherapy. The general condition of the patient deteriorated until he required morphine sulfate to control his severe diffuse pain. In an attempt to improve this patient's quality of life (QOL), he was discharged from hospital and treated at the outpatient clinic with modulation therapy using indomethacin as an anodyne instead of morphine sulfate. Signs of almost complete remission to only one cycle of combination therapy with VCR, MTX, and indomethacin were observed without any obvious adverse effects. This case report serves to demonstrate that modulation therapy combined with VCR, MTX, and indomethacin may be useful in the treatment of patients with drug-resistant recurrent SCLC.