Chronic hypernatremia derived from hypothalamic dysfunction: impaired secretion of arginine vasopressin and enhanced renal water handling.

We analyzed the disorder of water metabolism in a 32 year-old female with chronic hypernatremia. She had meningitis at 4 years, and ventriculo-peritoneal shunt operation at 13 years because of normal pressure hydrocephalus. At 14 years hypernatremia of 166 mmol/l was initially found and thereafter hypernatremia ranging from 150 to 166 mmol/l has been persisted for the last 18 years. Physical and laboratory findings did not show dehydration. Urine volume was 750-1700 ml per day and urinary osmolality (Uosm) 446-984 mmol/kg, suggesting no urinary concentrating defect. Plasma arginine vasopressin (AVP) levels ranged from 0.4 to 1.2 pmol/l despite hyperosmolality of 298 through 343 mmol/kg under ad libitum water drinking. There was no correlation between plasma osmolality (Posm) and plasma AVP levels, but Uosm had a positive correlation with Posm (r=0.545, P < 0.05). Hypertonic saline (500 NaCl) infusion after a water load increased Uosm from 377 to 679 mmol/kg, and plasma AVP from 0.2 to 1.3 pmol/l. There was a positive correlation between Posm and plasma AVP levels in the hypertonic saline test (r=0.612, P<0.05). In contrast, an acute water load (20 ml/kg BW) verified the presence of impaired water excretion, as the percent excretion of the water load was only 8.5% and the minimal Uosm was as high as 710 mmol/kg. Urinary excretion of aquaporin-2 remained low in concert with plasma AVP levels. No abnormality in pituitary-adrenocortical function was found. These results indicate that marked hypernatremia is derived from partial central diabetes insipidus and elevated threshold of thirst, and that enhanced renal water handling may contribute to maintenance of body water in the present subject.

Cisplatin-based chemotherapy for postoperative recurrence in non-small cell lung cancer patients: relation of the in vitro chemosensitive test to clinical response.

The usefulness of the in vitro chemosensitivity test, the collagen gel droplet embedded culture drug- sensitivity test (CD-DST, Int J Oncol 11: 449, 1997), in cisplatin-based combined chemotherapy for postoperative recurrent tumors in non-small cell lung cancer (NSCLC) patients was retrospectively analyzed. CD-DST data for cisplatin (or carboplatin), etoposide, 5-fluorouracil, mitomycin C, and vindesine were obtained in 311 surgically resected primary lesions. Of them, 25 patients were practically treated with first-line cisplatin- or carboplatin-based chemotherapy for postoperative initial recurrence. Nine (36%) of them responded to the combined chemotherapy for recurrent lesions, including one with complete remission, whereas 16 did not, with no change in 5 and progression in 11. Seven (70%) of 10 patients receiving combined chemotherapy using two or three in vitro sensitive chemoagents showed good responses, whereas there was no responder among the patients receiving chemotherapy including no in vitro sensitive chemoagents. In particular, of 11 patients showing good sensitivity to cisplatin or carboplatin on CD-DST, 8 (73%) responded to chemotherapy, whereas only one (7%) of 14 patients showing cisplatin- or carboplatin-resistance on CD-DST was a responder. Thus, CD-DST results for the chemoagents, especially cisplatin or carboplatin, correlated with chemotherapeutic response, indicating that the CD-DST analysis of surgically resected primary NSCLC tumors is a practically useful indicator of the clinical effect of first-line cisplatin-based combined chemotherapy for postoperative recurrence.

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.