Intrathoracic chemothermotherapy following panpleuropneumonectomy for pleural dissemination of invasive thymoma.

We report a case of pleural dissemination of invasive thymoma, which was successfully treated with intrathoracic chemothermotherapy following panpleuropneumonectomy. Intrathoracic chemothermotherapy in combination with surgery may be a hopeful adjuvant treatment to control pleural disseminated lesions of invasive thymoma.

Long-term results of postoperative intrathoracic chemo-thermotherapy for lung cancer with pleural dissemination.

BACKGROUND: To overcome the poor prognosis of lung cancer with pleural dissemination, the authors developed postoperative intrathoracic chemo-thermotherapy (PICT). In this report, they present the long-term results for 31 consecutive patients who underwent resection, followed by PICT for lung cancer with pleural dissemination between April 1985 and December 1991. METHODS: Among the patients, there were 26 cases of adenocarcinoma, 3 cases of squamous cell carcinoma, and 1 case each of large and adenosquamous cell carcinoma. Twenty-four of these patients had an initial diagnosis of pleural involvement at thoracotomy. The other seven patients had massive malignant effusion at the time of the initial diagnosis. PICT was started between days 10 to 14 postoperatively. When possible, three courses of this procedure were administered at intervals of 5-7 days. RESULTS: The 5-year cumulative and 5-year local relapse-free survival rates were 24.6% and 76.3%, respectively. The 3-year and 5-year cumulative survival rates for 14 patients without mediastinal lymph node involvement were 68.4% and 42.7%, respectively. Those rates for 17 patients with mediastinal lymph node involvement were 22.7% and 0%, respectively. The 3-year survival rate in the former group was significantly better than that in the latter group. CONCLUSIONS: These results strongly suggest that in patients with pleural dissemination, PICT may be beneficial for regional disease control and improvement of survival, particularly for patients without mediastinal lymph node involvement.

[Chemo-thermotherapy of radiation-induced squamous cell carcinoma in anterior chest wall].

A 62-year-old woman had visited our hospital with the large and deep ulcer formation on the left anterior chest wall. A biopsy of the ulcerous lesion established the diagnosis of a squamous cell carcinoma which might be induced by the irradiation after mastectomy. Although a wide resection of the chest wall including left arm was performed, it was impossible to resect completely. After then, she had operations for local recurrence for three times in three years. However, cure was not obtained, and residual lesions gradually enlarged and all layers of the anterior chest wall was replaced with tumor tissues. Conventional chemotherapy using ftorafur and mitomycin C was not effective. Therefore, we tried combined therapy with intravenous administration of cisplatin (CDDP) and vindesine (VDS), and local hyperthermia using radiofrequency (RF) wave. A total number of 11 courses of this treatment modality was carried out at once a week intervals. The tumor-temperature was maintained at the range of 40-43 degrees C for 40 min in each treatment session. Chemotherapeutic agents were administered simultaneously with hyperthermia. After these treatments, the recurrent tumor was markedly reduced, and epithelization of the ulcer was recognized from the surrounding normal skin. The residual tumor was then resected completely. The operative wound was successfully closed by surrounding normal tissue mobilization. She is in good postoperative condition. We concluded that the chemo-thermotherapy is safe and promising therapeutic modality for such invasive squamous cell carcinoma, and the normal tissues are not affected. Furthermore, this approach will expand the scope of radical resection for such an uncontrollable tumor.

Development of postoperative intrathoracic chemo-thermotherapy for lung cancer with objective of improving local cure.

From April 1985 through March 1988, 24 lung cancer patients with carcinomatous pleuritis were treated with a new combined treatment modality consisting of pulmonary resection and postoperative intrathoracic chemo-thermotherapy (PICT). They consisted of 15 male patients and nine female patients. A majority of the patients (79%%) had adenocarcinoma. The PICT was started 10 to 14 days after the operation. Immediately after a bolus intrathoracic injection of cisplatin (CDDP) 50-100 mg, thermotherapy was carried out using 13.56-MHz or 8.00-MHz radiofrequency waves for 60 minutes. The peripleural temperature was precisely monitored in 20 patients. The temperature was successfully maintained above 42 degrees C for 40 minutes in each of two or three treatment courses in 13 patients, with no complications. However, in the other seven patients the therapy resulted in incomplete treatment because of development of a side effect. Cytologic examination of the pleural effusion, which was performed after the completion of PICT, gave a negative result in 16 of 20 patients examined. The median follow-up period was 16 months. Local relapse was recognized in only three cases who received incomplete treatment or in whom no temperature measurement was performed. The overall survival of the treated patients (n = 24) was significantly prolonged in comparison with a historical control group treated by surgery only (n = 17) or exploratory thoracotomy (n = 11). Of those 17 patients treated by surgery only, ten patients (59%) died of local relapse. These results suggest that this new treatment modality consisting of pulmonary resection and PICT is useful for the treatment of lung cancer patients with carcinomatous pleuritis, especially in the light of improved local control.

[Local chemo-hyperthermotherapy of recurrent rectal cancer].

Local radiofrequency hyperthermia combined with chemotherapy was performed on five patients with pelvic recurrence of rectal cancer. Relief of pain was obtained in all four patients with uncontrolled pelvic pain due to recurrent rectal cancer. In some patients, CEA levels of peripheral blood were decreased and tumor necrosis was proved histologically. These results suggest that this combined therapy may be useful for patients with pelvic recurrence of rectal cancer.

[Postoperative local thermo-chemotherapy in control of residual pleural diseases after resection of primary lung carcinoma--regulation of dissemination].

Pleural dissemination was proved by intraoperative histodiagnosis in 11 of 121 patients who underwent pulmonary resection for non-small cell carcinoma of the lung between April, 1985 and December, 1986. To control such intrathoracic residual diseases, we devised a means of local thermo-chemotherapy. Ten of 11 patients were treated with intrapleurally administrated cisplatin (50-100mg, bolus) combined with simultaneous radiofrequency hyperthermia (13.56 MHz) for 2 to 3 weeks after surgery. Courses were repeated at 5-to 7-day intervals. Eight patients had N2-disease, one N1 and the other NX. Eight were adenocarcinomas. Thermal burn of the chest wall with hyperkalemia was observed in only one patient who received thermotherapy at the over a magnetrode power of 450 watts for 50 minutes. In the other 9, side effects were minimal under the thermotherapy to obtain a peripleural temperature beyond 42 degrees C. Of the 10 patients, three lived more than 12 months after treatment. Although distant metastases were recognized in 6 cases, none had local recurrence for the median follow-up period of 6 months. One patient had metastasis to the contralateral supraclavicular lymph nodes. Because there was no evidence of intrathoracic recurrences in this patient, radical neck dissection were performed 15 months after the initial operation. This experience warrants further investigation of thermo-chemotherapy as a treatment for controlling pleural dissemination after resection of primary tumor.

Membrane phospholipids alter nutrient transport and drug toxicity in tumorigenic fibroblasts.

The phospholipid polar head group composition of LM cell plasma membranes was nutritionally altered by choline analogue supplementation. Phosphatidylcholine (PC), normally 60% of total phospholipid, was depleted by 60 to 90% in membranes from cells cultured with N, N'-dimethylethanolamine (DME), N-monomethylethanolamine (ME), and ethanolamine (E). Enrichment of LM cell membranes with choline analogues, such as DME-, ME-, and E-containing phospholipids, decreased the transport of [3H]thymidine, [3H]2-deoxy-D-glucose, and [14C]3-O-methylglucose. Conversely, no change in the transport of [3H] uridine or [14C]aminoisobutyric acid was observed. The toxicity of antineoplastic drugs such as 5-fluorouracil, but not daunorubicin, doxorubicin, or methotrexate, was enhanced threefold in cells enriched with phospholipid containing choline or DME as compared to ME or E. Arrhenius plots of Na+-K+-ATPase activity demonstrated a characteristic temperature at 29 degrees C in plasma membranes from choline-fed cells, while those from analogue-fed cells showed an additional break at 20 degrees C and had higher energies of activation below this temperature. In addition, choline analogue supplementation altered the protein composition of the plasma membrane. The results reported herein demonstrate that nutritional alteration of LM fibroblast plasma membrane phospholipid polar head group composition affects several transport processes and toxicity of some anticancer drugs.

[Chemo-hyperthermotherapy following thoracic surgery].

Local radiofrequency hyperthermia combined with chemotherapy was performed on patients with thoracic malignancy, who had under gone non-curative resection because of disseminated pleural involvement or positive surgical margin, and who had metastatic lesions (after curative surgery). In some patients, subjective symptoms were decreased or tumor necrosis was proved cytologically. This therapy may therefore be useful for patients with thoracic malignancy.

Retention of acyl groups in LM cell fibroblasts with altered phospholipid composition.

Incorporation and loss of membrane lipids were measured in murine fibroblasts grown in suspension culture with [2-14C]acetate in a chemically defined medium devoid of serum or lipid. Greater than 98 and 94% of the 14C present in the phospholipids and neutral glycerides respectively was found in the fatty acyl groups. During a 3-day growth period LM fibroblasts lost 65% of their 14C-labelled acyl groups from the phospholipids and 36% from the neutral lipids. Selective retention of 14C in individual isolated phospholipid and neutral lipid species occurred only in phosphatidylethanolamine. Retention of acyl groups in the phospholipids or neutral glycerides was not a property of LM suspension cultured fibroblasts. Supplementation of the LM cells with choline analogues, such as N,N'-dimethylethanolamine, N-monomethylethanolamine, or ethanolamine instead of choline, decreased the loss of 14C-labelled fatty acids from phospholipid and neutral lipid. Ethanolamine supplementation resulted in increased loss of 14C from desmesterol as well as decreased incorporation of 14C into desmosterol. Thus, polar head group manipulation affected acyl group composition, acyl group retention, and sterol metabolism in suspension cultured LM cells.

Manipulation of fatty acid composition of membrane phospholipid and its effects on cell growth in mouse LM cells.

Fatty acid composition of the phospholipids of mouse LM cells grown in suspension culture in serum-free chemically defined medium was modified by supplementing the medium with various fatty acids bound to bovine serum albumin. Following supplementation with saturated fatty acids of longer than 15 carbons (100 micron) profound inhibition of cell growth occurred; this inhibitory effect was completely abolished when unsaturated fatty acids were added at the same concentration. Supplementing with unsaturated fatty acids such as linoleic acid, linolenic acid or arachidonic acid had no effect on the cell growth. Fatty acid composition of membrane phospholipids could be manipulated by addition of different fatty acids. The normal percentage of unsaturated fatty acids in LM cell membrane phospholipids (63%) was reduced to 35--41% following incorporation of saturated fatty acids longer than 15 carbon atoms and increased to 72--82% after addition of unsaturated fatty acids. A good correlation was found between the unsaturated fatty acid content of membrane phospholipids and cell growth. When incorporated saturated fatty acids reduced the percentage of unsaturated fatty acids in membrane phospholipids to less than 50%, severe inhibition of the cell growth was found. Simultaneous addition of an unsaturated fatty acid completely abolished this effect of saturated fatty acids. The results suggest that maintenance of membrane fluidity by unsaturated fatty acids in membrane phospholipids is critical to membrane integrity and cell growth.