Osamu Ike

Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded

BACKGROUND We analyzed the operative outcome of extensive surgery for invasive thymoma, especially in those with thymomas invading the superior vena cava, the left innominate vein, or both. METHODS We treated 41 patients with invasive thymoma, including 34 stage III, 5 stage IVa, and 2 stage IVb thymomas. Thirty-eight patients received radiotherapy preoperatively or postoperatively. In 12 patients with invasion of the superior vena cava or innominate vein, we performed angioplasty, reconstruction, or both. RESULTS The overall 5-year survival rate was 77% and the 10-year survival rate was 59%. In the stage III group, there was a significant difference between those with complete and those with incomplete resection. Ten of 12 patients who had angioplasty with or without reconstruction of the superior vena cava or innominate vein survived without recurrence of the tumors. CONCLUSION Angioplasty and vascular reconstruction are recommended because successful treatment for invasive thymomas depends on complete resection of the tumors.

Time trends and survival after operations for primary lung cancer from 1976 through 1990

To assess the time trends and survivals after operations for primary lung cancer, the cases of 845 consecutive patients who underwent thoracotomy between 1976 and 1990 were retrospectively reviewed by groups corresponding to year of the operation (the early period was 1976 to 1980, n = 208; the middle period was 1981 to 1985, n = 291, and the late period was 1986 to 1990, n = 346). The 5-year survivals at the early, the middle, and the late periods were 31.5%, 39.0%, and 54.0%, respectively, with significant improvement particularly at the late period (p < 0.05 for the early period vs the middle period, p < 0.01 for the early or middle period vs the late period); the improvement was caused by increase in the ratio of patients with stage I disease (20.7% at the early period, 32.0% at the middle period, 44.2% at the late period), increase in the rates of complete tumor resection with lymph node dissection (57.2%, 68.0%, 74.3%, respectively), and decrease in the rates of operation-related death (3.8%, 3.4%, 0.9%, respectively). The postoperative prognosis of patients with stage II disease at the late period (5-year survival 74.8%) showed significant improvement compared with the other periods. Moreover, the prognosis of patients with stage IIIa, pN2 disease (5-year survival 41.5%) showed significant improvement, which was caused by the significant decrease in patients with pT3 N2 M0 disease and poor prognosis.

Controlled cisplatin delivery system using poly(D,L-lactic acid)

Cisplatin (CDDP)-containing poly(D,L-lactic acid) microspheres (CDDP-MS) and beads (CDDP-B) with an average molecular weight of the oligomer of 1.2 x 10(4) and 4% CDDP loading were prepared. In Tris buffer, 95% of CDDP disappeared from CDDP-MS within 3 d. In vitro and in vivo, CDDP-B released CDDP for 30-57 d, and for 21-42 d, respectively. The other CDDP-B with an average oligomer molecular weight of 9.6 x 10(3) with 5% lactic acid monomers, that contained 4% CDDP, showed a two-phase CDDP release pattern and CDDP disappeared within 41 d in vitro, and within 21 d in vivo. Histologically, tissue necrosis surrounding the CDDP-B was not severe.

Clinical Experience with Lung-Imaging Fluorescence Endoscope (LIFE) in Patients with Lung Cancer

Abstract: British Columbia Cancer Research Center developed a new technique for detection of lung cancer with a device called the lung-imaging fluorescence endoscope (LIFE). Our aim was to confirm whether LIFE system would be useful in diagnosis of dysplasia of bronchial mucosa and lung cancer. Thirty patients with suspected lung cancer were included in this study. All patients underwent bronchoscopic examination by LIFE following examination by the conventional white-light bronchoscope. Pathological examination was performed for the abnormal areas detected by white-light or fluorescence bronchoscopic examination. Malignant tumors were diagnosed in 12 patients by both conventional bronchoscopy and LIFE; one dysplasia was also diagnosed by conventional bronchoscopy. The LIFE system diagnosed malignancy in four regions and one dysplasia that conventional bronchoscopy could not. Malignant lesions diagnosed by conventional bronchoscopy at three locations were proved later by the LIFE system to be benign. The sensitivity and specificity of the conventional bronchoscope for detection of dysplasia and cancer were 65% and 71%, respectively. The LIFE systems sensitivity was 90% and its specificity was 77.4%. No complications related to the LIFE system were detected throughout the course of this study. We conclude that the LIFE system can detect minute malignant lesions which are commonly non-detectable by conventional bronchoscopy without any complications. This method may be applicable in the screening of high risk groups for lung cancer.

Biodegradation and antitumour effect of adriamycin-containing poly(l-lactic acid) microspheres

Adriamycin-containing poly (L-lactic acid) microspheres were prepared to develop a slow-releasing and long-acting adriamycin delivery system. An almost constant release of adriamycin from the adriamycin-containing poly(L-lactic acid) was achieved in Tris buffer and adriamycin disappeared within 20 d. Adriamycin was not detected in serum for up to 14 d, when the suspension of the adriamycin-containing poly(L-lactic acid) microspheres was injected into lung parenchyma, the femoral muscles of rabbits or the peritoneal cavity of mice. However, adriamycin remained in the rabbit muscles for up to 10 d under formation of scar tissue. When free adriamycin was added to P815 tumour cells in culture, the cell survival rate decreased with the exposure time. The treatment with the adriamycin-containing poly(L-lactic acid) microspheres showed a higher survival rate for mice bearing P815 tumour cells than with free adriamycin. In addition, the systemic side effects were insignificant when the adriamycin-containing poly(L-lactic acid) microspheres were given to mice instead of free adriamycin.

Surgical treatment of small cell carcinoma of the lung: advantage of preoperative chemotherapy

To assess the effect of chemotherapy on postoperative survival of patients with small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto University between 1976 and 1991 were retrospectively reviewed. Seventeen patients (37.0%) received chemotherapy prior to as well as after surgery (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery (adjuvant therapy group), and the other six received no chemotherapy (non-chemotherapy group). The 5-year survival rate of patients with c-Stage I or II disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be higher, although with no statistical significance, than that in the adjuvant therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c-Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not satisfactory (10.0%), was significantly higher than that in the adjuvant therapy group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5 years. Moreover, multivariate analysis showed that failure to employ preoperative chemotherapy was the strongest prognostic factor causing a poor prognosis (P = 0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II disease postoperatively proved to have mediastinal lymph node involvement (pN2-3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the advantage of preoperative chemotherapy and the discrepancy between c- and p-stage, sufficient chemotherapy prior to surgery should be employed, and may realize a good prognosis in patients with c-Stage I or II disease. In contrast, patients with c-Stage III disease are not appropriate as candidates for surgery even if preoperative chemotherapy is performed.

Pulmonary mucosa-associated lymphoid tissue lymphoma 8 years after resection of the same type of lymphoma of the liver

A 64-year-old woman presented with hepatic and pulmonary tumors of mucosa-associated lymphoid tissue lymphoma occurring 8 years apart. The present case carries the possibility of pulmonary metastasis of hepatic lymphoma or double primary lymphoma. Mucosa-associated lymphoid tissue lymphomas tend to develop in the extranodal primary organ, rarely developing systemically among extranodal organs as in our case. Our experience is useful in understanding the progress and outcome of mucosa-associated lymphoid tissue lymphoma.

Pharmacokinetics of cisplatin in analbuminemic rats.

The effect of protein binding on the pharmacokinetics of cisplatin (cis‐diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats, which genetically lack albumins, in comparison with normal rats. CDDP was reported to highly bind to serum components, and the major binder was thought to be an albumin. However, there were no significant differences in the serum disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP to analbuminemic rats as compared with normal rats. The total body clearance, Cltot, of platinum in normal rats was 48.7±22.0 mL h−1 (5 mg kg−1), 55.9±4.04 mL h−1 (10 mg kg−1) and 49.0±3.57 mL h−1 (20 mg kg−1), whereas Cltot in analbuminemic rats was 52.0±8.48 mL h−1 (5 mg kg−1), 62.9±10.8 mL h−1 (10 mg kg−1) and 62.8±6.81 mL h−1 (20 mg kg−1). The serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection were higher in both groups of rats who received CDDP than those of pre‐dose level. However, there were no significant differences in the renal function tests between analbuminemic rats and normal rats. The binding of CDDP to the serum samples obtained from analbuminemic rats and normal rats was measured by a centrifuging filtration method. The binding percentages were 68.0±5.9% (2.0 μg mL−1), 56.8±4.1% (5.0 μg mL−1) and 64.6±4.4% (10.0 μg mL−1) in analbuminemic rats and 52.9±3.5% (2.0 μg mL−1), 52.2±3.4% (5.0 μg mL−1), 56.9±1.9% (10.0 μg mL−1) in normal rats. Higher binding percentages were obtained in analbuminemic rats than in normal rats. In vitro binding studies under the two incubation conditions (5 min and 2 h) showed that the binding percentages of CDDP to serum proteins were 59.2±3.2% (5 min) and 72.3±6.5% (2 h) for albumin, 42.3±1.9% (5 min) and 39.5±2.5% (2 h) for α1‐acid glycoprotein (AAG) and 51.7±5.3% (5 min) and 49.2±1.9% (2 h) for γ‐globulin. From these studies, it was elucidated that albumin is not the major ligand in the rat serum and that other proteins also have important roles in the pharmacokinetics of CDDP. Copyright

Organ distribution of cisplatin after intraperitoneal administration of cisplatin-loaded microspheres

The aim of this study was to clarify the organ distribution of cisplatin (CDDP) after intraperitoneal (i.p.) administration of cisplatin-loaded microspheres (CDDP-MS). The distribution of CDDP to normal organs lying in the peritoneal cavity after i.p. administration of CDDP-MS was assessed by comparing with subcutaneous administration to non-cancerous mice. The organ distribution of CDDP after i.p. administration of CDDP-MS shows that CDDP released from microspheres was distributed to the organs lying in the peritoneal cavity and in the retroperitoneum. These are mainly from the systemic circulation, but are not directly from the organ surface. The distribution of CDDP to tumors was evaluated in sarcoma180 tumor-bearing mice by comparing with a bolus injection. The CDDP-MS delivered CDDP to tumors more effectively than did bolus injection. The distribution of CDDP-MS in the peritoneal cavity was in accord with the tumor distribution. This concordance and sustained exposure of CDDP to the tumors might play a critical role in enhancing the CDDP accumulation in tumors. It is concluded that CDDP-MS have a distinct regional pharmacokinetic advantage for peritoneal carcinomatosis, and that i.p. administration of CDDP-MS is an effective treatment for peritoneal carcinomatosis.

Long-Term Remission after Brachytherapy with External Irradiation for Locally Advanced Lung Cancer

Three cases are reported who received brachytherapy with external irradiation for inoperable lung cancer and have shown long-term remission. The diseases were adenoid cystic carcinoma, recurrent adenocarcinoma and squamous cell carcinoma. The associated symptoms were severe cough and dyspnea in all 3 cases. They received 60 Gy of external irradiation. After an interval of 2 weeks, 6 Gy at a radius of 1 cm from the center of the source was delivered by iridium-192. They received 2–4 fractions at 1-week intervals. On termination of brachytherapy, complete response was observed in all cases. In 1 case, bronchial stenosis due to radiation-induced fibrosis was observed, but was successfully treated by bronchial stent. Cough and dyspnea disappeared, and all patients have been rendered asymptomatic for the last 2 years. Local disease was well controlled in 2 cases; however, minimal local recurrence was observed after a 2-year follow-up in 1 case.