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.

A new and efficient method to generate human IgG monoclonal antibodies reactive to cancer cells using SCID-hu mice.

Human monoclonal antibodies (mAbs) are very useful for treatment of cancer, but they are difficult to obtain since immunization of humans is not a practical proposition at present. As an approach to circumvent this problem, we have simultaneously inoculated cancer tissues and regional lymph node cells obtained from lung cancer patients into SCID mice to allow in vivo stimulation of human lymphocytes against autologous cancer tissues. Human immunoglobulins, especially IgG, were observed in the SCID-hu sera, and some showed high reactivity to lung cancer cell lines. Testing of human B-lymphoblastoid cell lines obtained from SCID-hu spleen and thymus for antibody activity revealed 16-45% of them to be reactive to lung cancer cells. These percentages are high as compared with previous reports. Furthermore, we could establish 4 human IgG mAbs reactive to lung cancer cell lines. These results indicate successful stimulation of specific human lymphocytes in vivo, which thereby enables efficient generation of human monoclonal antibodies using SCID-hu mice.

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.

Inflammatory pseudotumor of the liver in children: report of cases and review of the literature.

Two pediatric cases of inflammatory pseudotumor of liver were reported and compared with seven previously reported cases. Clinical presentation was variable but often consisted of fever and vague abdominal symptoms. These two cases were considered to be clinically malignant because angiographically one showed hypervascularity and the other showed the portal vein draining into the lesion to be occluded. There are four previous reports of similar cases complicated with occlusive phlebitis within and around the lesion. All but two of the reported cases underwent major hepatectomy or liver transplantation. However, because of the benign nature of the lesion, the treatment might be more conservative after adequate diagnostic procedures, including needle biopsy, are applied.

[Clinical study on postoperative infections caused by methicillin-resistant Staphylococcus aureus after gastrointestinal surgery].

We studied 308 postoperative infections (216 patients) after gastrointestinal surgery during 1987-1991, to elucidate the incidence of postoperative infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and its correlation to clinical background factors. Results were as follows: (1) MRSAs were isolated from 25.9% out of 216 patients or 22.4% out of 308 infections. (2) The isolation rate of MRSA was significantly high in infectious enterocolitis (64.7%, p < 0.001), intraabdominal infections (52.5%, p < 0.001) and respiratory tract infections (35.3%, p < 0.05). On the other hand, it was significantly low in bacteremias (9.28%, p < 0.001), wound infections (13.6%, p < 0.05) and urinary tract infections (3.33%, p < 0.05). (3) MRSAs were found more frequently in male (p < 0.05), younger patients (p < 0.05) and patients with malignant disease (p < 0.10). Whereas no difference was recognized between patients with or without complication. (4) The isolation rate of MRSA by the kind of antibiotics used after surgery, was 0% (0/20, the 1st generation cephems), 17.2% (10/58, the 2nd generation cephems) and 54.5% (48/88, the 3rd generation cephems). Significant differences were found among each group (p < 0.05, p < 0.001). (5) During 1990-1991 when the 1st generation cephems were used frequently, MRSAs were found significantly lower in frequency than during 1987-1989 (p < 0.05). Especially a marked decrease in the rate of MRSA (51.4% to 8.33%, p < 0.05) was seen among patients after upper gastrointestinal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[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.

[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.

[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.

[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.

[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.

[Experience with surgery for metachronous double cancer originated from thymus and lung].

A case with thymic cancer who developed pulmonary cancer ten years after the initial surgery was reported. A 50-year-old man was admitted to our hospital due to SVC syndrome. Chest X-ray examinations including venogram showed a mass lesion at the superior mediastinum. The patient underwent surgical removal and reconstruction of SVC, followed by radio-chemotherapy. The histologic diagnosis was thymic squamous cell carcinoma. He was admitted to our hospital again ten years after the initial surgery under the diagnosis of pneumonia. Bronchoscopic examination revealed nodular lesions at the right upper lobe bronchus and lower lobe bronchus, those lesions were diagnosed with squamous cell carcinomas cytologically. Right pneumonectomy was performed and the diagnosis was confirmed pathologically. Postoperative course was uneventful as of 10 months after the operation. It was concluded that this case showed metachronous double cancer of the thymus and the lung, as well as synchronous multiple bronchogenic carcinomas, which, to our knowledge, has never been reported yet.

[An experience of video-assisted thoracoscopic surgery for an intrapulmonary needle under CT-guided marking].

A 46-year-old female visited a near hospital, complaining of repeating skin eruption with spontaneous remission. A chest X-ray and CT examinations revealed a needle in the left S6, about 5 mm in length, which was suspected of causing the eruption. She was admitted to our hospital for operation. After CT-guided marking, video-assisted thoracoscopic surgery was performed. Because the needle was too small to be palpable, we decided to respect of it with the lung surrounding the marker and clamped the lung, followed by finding the needle finally. The analysis of the removed needle showed that it contained lead and tin besides iron, nickel and chromium, which are components of stainless steel. Although dermatological examination could not reveal the relation between the needle and the eruption, it has never recurred since the operation. It is thought that CT-guided marking is very useful for resection of an intrapulmonary needle and that a foreign body should be removed for the possibility of being harmful.

[Surgical treatment of lung cancer over 80 years of age: investigation from post operative complications].

Seventeen patients with lung cancer over 80 years were treated surgically from 1983 through 1993 in our department. Thirteen patients were male and four were female. The histology of the tumor was adenocarcinomas, squamous, large and small cell carcinomas, in 9, 6, 1 and 1 cases, respectively. More than single lobectomy was performed in each patient. Unilateral pulmonary occlusion test was applied in patients whose expected contralateral FEV1.0/BSA was less than 800 ml.m2, or expected residual FEV1.0/BSA was less than 850 ml.m-2. Postoperative cardiovascular complications, such as PAT, PAC, PVC or Af, were seen in 9 patients, respiratory problems, namely, sputa retention, retained secretions or atelectasis, in 7 patients. Blood chemistry and hematology were performed for about three weeks after operations, and found increases in serum transaminases, and leukocytosis. However, there were no operative death. We conclude that some patients over 80 years of age are candidates for surgery after careful cardiopulmonary preoperative evaluation.

[Two cases of clear cell tumor of the lung].

We report two cases of benign clear cell tumor of the lung, which were found as well-circumscribed lesions on chest X-ray films without any symptoms, and removed surgically. Light microscopy showed proliferation of clear cells filled with glycogen in both cases. Immunohistochemical examination performed in a case suggested that the tumor cells might be associated to a derivation from neural and/or smooth muscle cells, because of positive staining for NSE and SMA. In another case, the tumor formed a necrotic cavity, which could be detected by the preoperative MRI examination. This report might introduce a note of caution for the pathologic and radiographic diversity of this disease.