Effect of 8-MHz radiofrequency-capacitive regional hyperthermia with strong superficial cooling for unresectable or recurrent colorectal cancer.

A well-known disadvantage of a radiofrequency-capacitive device for deep-seated tumours is preferential heating of the subcutaneous fat tissue. The authors previously developed the hyperthermia with their own external cooling unit and achieved strong superficial cooling, and reported its usefulness for the reduction of the preferential heating. The purpose of the present study was to evaluate the effect of hyperthermia with strong superficial cooling on the treatment results for unresectable or recurrent colorectal cancers. From 1986 to 2002, 44 patients with primary unresectable or locally recurrent colorectal cancer treated with thermoradiotherapy were analysed retrospectively. The patients with obesity as a subcutaneous fat thickness more than 3 cm, a high age or other serious complications did not undergo therapy. The results were compared between 17 cases with strong superficial cooling treated after 1997 (Group A) and 27 cases without strong superficial cooling treated before 1996 (Group B). Significant differences in thermometry data of T(max), T(ave) and T(min) were noted between Groups A (45.3, 44.4 and 43.6 degrees C, respectively) and B (42.9, 42.0 and 41.1 degrees C, respectively) (p<0.01). Complete response plus partial response rates were better for Group A than for Group B (59 versus 26%, p = 0.05). Multivariate analysis by logistic regression to evaluate the effects of certain factors on complete response plus partial response was strongly correlated with strong superficial cooling (p<0.05). The median survival times for overall survival were 24.3 months for Group A and 17.1 months for Group B (p<0.05). Eight-megahertz radiofrequency-capacitive regional hyperthermia with strong superficial cooling is potentially useful for improving treatment results in unresectable or recurrent colorectal cancers.

[Postintubation tracheal stenosis; problems associated with choice of management].

We experienced a case with tracheal stenosis due to postintubation damage, or so-called cuff stenosis. A 50-year-old man who attempted suicide by pounding nails into his head and chest using carpenter's tools was treated by endotracheal intubation and immediately underwent emergency surgery in July 2000. The patient was placed on artificial ventilation with oral endotracheal intubation, and a tracheostomy was performed 4 days after the operation. After that, his respiration recovered and he was weaned from the respirator. He was discharged 22 days after surgery with no respiratory symptoms. Two days after discharge, he complained of wheezing and dyspnea. Medical examination revealed that the cervical trachea had a severe circumferential stenosis 2.5 cm from the second tracheal cartilage. On retrospective inspection, the region of stenosis was compatible with the cuff site of the endotracheal tube used for the emergency operation. At first we tried nonoperative treatment, considering his mental state. However, we found that surgical treatment was ultimately necessary. A 2.5 cm sleeve resection of the trachea (5 tracheal cartilage rings) was performed, followed by end-to-end suture using 21 stitches with 4-0 MEDIFIT C thread. Pathologically, the surgical specimen showed degeneration and necrosis of tracheal cartilage with excessive growth of granulation tissue. These findings revealed that the etiologic basis of the tracheal stenosis was attributed to pressure necrosis by the cuff. The postoperative course was uneventful. Sixteen months after the surgery, the granulation tissue had not recurred, and problematic stenosis was not visible in the trachea. In this report, we discussed a reasonable management of postintubation tracheal stenosis. Tracheoplasty has been proposed as the most reliable method for treating tracheal stenosis. However, the best treatment in each case is still somewhat controversial because various nonoperative treatment methods are recently available, including laser phototherapy, argon plasma coagulation, mechanical dilatation, stent replacement, and drug treatment. Therefore, it is very important to judge properly the absolute indication for surgical treatment. If granulations are removed successfully by the above-described nonoperative methods, attempts at repair lead only to regrowth of granulation tissue as long as there is necrotic tracheal cartilage. Thus, the determinant of treatment methods is whether postintubation damage extends to tracheal cartilage or not. For now, there is no accurate diagnostic study for viability of cartilage preoperatively. In the literature, symptoms due to airway stenosis occurred rapidly within one month in the case of patients with necrosis of tracheal cartilage. We concluded that the period between extubation and development of symptoms is very informative in the management of postintubation tracheal stenosis. Surgical approaches should be selected for a patient with a rapid and progressive course after extubation when the patient can tolerate it.

Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas.

The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression.

Colon-specific delivery of budesonide with azopolymer-coated pellets: therapeutic effects of budesonide with a novel dosage form against 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats.

The objective of this study was to achieve colon-specific delivery of budesonide using azopolymer-coated pellets and to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. After oral administration of azopolymer-coated pellets containing budesonide, a significant increase was observed in the therapeutic effects of the drug accompanied by a decrease in its systemic adverse effects when compared with oral administration in saline or rectal administration by enema. In addition, with the use of the colon-specific oral dosage form the dose of budesonide could be reduced. These results suggested that azopolymer-coated pellets may be a useful dosage form for the colon-specific delivery of budesonide as an anti-inflammatory steroid drug to bring about the healing of TNBS-induced colitis in rats.

Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study.

The results of radiotherapy combined with hyperbaric oxygen in 9 patients with malignant glioma were compared with those of radiotherapy without hyperbaric O2 in 12 patients. This is the first report of a pilot study of irradiation immediately after exposure to hyperbaric O2 in humans. All patients receiving this treatment showed more than 50% regression of the tumor, and in 4 of them, the tumors disappeared completely. Only 4 out of 12 patients without hyperbaric O2 showed decreases in tumor size, and all 12 patients died within 36 months. So far, this new regimen seems to be a useful form of radiotherapy for malignant gliomas.

[Combined radiotherapy and hyperthermia for Pancoast tumor].

Thirteen patients with Pancoast tumor were treated with combined radiotherapy and hyperthermia from April 1987 to December 1992. Radiotherapy was performed using 10 MV X-rays, and all patients received a total dosage of 40-118 Gy with conventional fractionation. Hyperthermia was performed once or twice a week within 30 minutes after each irradiation, using 8 MHz RF capacitive heating equipment (Thermotron RF-8). Partial response, defined as 50% or more regression of the tumor, was observed in 7/13 (54%) patients, and the median survival time was 25.2 months. Results of 14 patients treated with irradiation alone from July 1980 to December 1992 were also evaluated, and were used as a historical control. The partial response was 4/14 (29%) and the median survival time was 7.3 months. Radiotherapy combined with hyperthermia is an effective modality for treating Pancoast tumors.

[Thermal distribution in the agar phantom by a new intracavitary RF applicator for prostate gland].

Some studies suggest that the prostate gland is one of the most difficult portions of the body to heat up even by radio frequency (RF) capacitive heating, which is well established as a useful means for deep regional hyperthermia because of its non-uniform power absorption. We have developed a new type of intracavitary applicator for RF capacitive heating which can be connected to an 8 MHz RF heating device (Thermotron-RF8). The applicator is a balloon-type catheter which is filled with electrolyte, such as physiological saline, 3% saline or 3% ferrous sulfate solution, and then put between a pair of regular RF capacitive heating electrodes. The heating characteristics of the applicator were examined by using an agar phantom that is electrically equivalent to muscles. When the applicator was connected to the electrode of the RF generator with a copper cord, the balloon filled with electrolyte operated as an inner electrode. The effective hot area around the balloon of the catheter was observed, and the size of the hot area was changed by the kinds of electrolytes used and their concentration. With this adaptive technique, it is possible to maintain an adequate thermal distribution at a tumor in the uterus, urinary bladder and rectum, as well as the prostate gland.

Pancoast tumour treated with combined radiotherapy and hyperthermia--a preliminary study.

Six patients with Pancoast (superior sulcus) tumours were treated with combined radiotherapy and hyperthermia from April 1986 to December 1989. Radiotherapy was performed using 10 MV X-ray, and all patients received total doses of 60-74 Gy, in five fractions per week, during 5.5-15 weeks. Hyperthermia was performed once or twice a week within 30 min after each irradiation, using 8 MHz RF capacitive heating equipment (Thermotron RF-8). Partial response, defined as 50% or more regression of the tumour, was observed in four of the six patients. Three patients are alive 30, 28, and 14 months after their treatments. Radiotherapy combined with hyperthermia appears to be a promising and effective means for treating Pancoast tumours.

[Clinical results of hyperthermia alone in the treatment of refractory human tumors].

Retrospective analysis of patients with refractory tumors which were treated with hyperthermia alone in five institutions was performed. Hyperthermia was applied to 30 refractory tumors including 19 deep-seated tumors for a total of 427 sessions by 8 MHz or 13.56 MHz radiofrequency capacitive heating devices. Of the 30 tumors treated, 3 (10%) showed complete regression and 2 (7%) more than 50% regression. Although tumor regression was observed in small tumors, large deep-seated tumors did not respond to heat alone. Thus, response rate of hyperthermia alone was lower than expected, although subjective improvement by hyperthermia was noted in 53% patients. We consider that hyperthermia should be combined with radiation or chemotherapy whenever possible.

[Combined radiotherapy and local external hyperthermia in advanced cancer--animal experiment and clinical study].

The response of a mouse's foot to heat was studied. Transplanted syngeneic tumor, C3H mouse mammary carcinoma, was treated with irradiation and hyperthermia in a waterbath. The tumor did not disappear in any of the mice treated with radiotherapy with a dose of 20 Gy alone, but disappearance of the tumor was observed in 11 of 15 and 6 of 8 of the mice treated with combined therapy of irradiation and hyperthermia. There was a significant difference between these two groups. Synergistic effect was confirmed (P less than 0.001, P less than 0.005). Hyperthermia using Thermotron RF-8 was performed on 19 patients (5 bladder cancers, 3 uterine cancers, 3 rectal cancers, 4 soft tissue tumors, 2 oral cancers, 1 biliary tract cancer, 1 renal cancer) between April, 1986 and December, 1986. They were irradiated with a daily dose of 1.5-2.0 Gy, 5 times a week and hyperthermia was performed within 30 minutes after each irradiation once or twice a week. Intratumoral temperature was kept at 43 degrees C-45 degrees C. Temperature over 41 degrees C was maintained in most patients. Clinical response was assessed by tumor regression rates. Partial response a (PRa), defined as 80% or more regression in tumor volume, was obtained in 1 bladder cancer patient and PRb, defined as 50% to less than 80% regression, was obtained in another 5 patients. Side effects were observed in all patients including mild skin burn, nausea and diarrhea. Rectovaginal fistula developed in 1 patient. Combined radiotherapy and hyperthermia seems to be useful in advanced cancer patients.

[Evaluation of chemotherapy of breast cancer (2). Clinical evaluation of the blood and tissue concentrations of FT-207 following intrarectal administration].

In order to examine the transfer of antitumor drug in breast cancer after administration of FT-207 suppository, FT and 5-FU concentrations in blood, tumor tissues, normal tissues and axillary lymph nodes were determined respectively. FT and 5-FU concentrations in tumor tissues were higher than those in normal tissues or lymph nodes in every cases, and there was a significant difference between FT and 5-FU concentration in blood and tumor tissues. Blood levels of FT and 5-FU remained quite constant at 16 and 20 hours after administration, respectively. Accordingly, it was suggested that the administration of FT-207 suppository to breast cancer was very effective as an adjuvant chemotherapy.