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D J Li

Publications and source records attributed to D J Li.

67 records · Page 4Linked to original sources

Responses of RIF tumors to heat and drugs: dependence on tumor size.

The effects of hyperthermia and drugs on RIF tumors of three sizes were studied in C3H mice. The animals were treated with bleomycin, carmustine, or a combination of both drugs and with or without concomitant localized hyperthermia. The hyperthermia dose was 44 degrees C for 30 minutes for each treatment. Each animal was given two treatments, 7 days apart. The tumors were classified according to approximate size: 0.1, 0.3, or 0.7 cm3. Among the animals bearing the smaller tumors, no cures were observed. Growth delay measurements indicated that heat and drugs had approximately additive effects. Several cures were seen among the animals bearing medium- and large-sized tumors. Our results indicate that medium and large tumors may respond better to the combination treatment than small tumors.

Animals↗

Thermometric analysis of intra-cavitary hyperthermia for esophageal cancer.

Thermometric analysis was carried out in 51 patients with esophageal cancer treated with intra-cavitary hyperthermia combined with radio chemotherapy, to test whether temperature index (T20, T50) and T90) could be used as an indicator for tumour control. Hyperthermia was administered by intra-cavitary microwave applicator. The T20, T50 and T90 were deducted from the temperature sensors T0 and T3 situated at the center of the tumour surface and 3cm from it. Eighteen patients with local control > or =36 months were named long term control patients (LC), 24 patients with local recurrence within 24 months (LR) (there were no events occurring between 24 and 36 months) and nine patients died of metastasis without local recurrence (DM). The overall survival rates were 80.4 +/- 5.6% at 1 year, 38.3 +/- 6.9% at 3 years and 31 +/- 6.7% at 5 years, respectively. Chi-square test showed no influence of the number of hyperthermia sessions on the local control (p > 0.25). The 5-year local control rate was 18.8% for the patients with T90 < 43 degrees C and 45% for those with T90 > or = 43 degrees C (p < 0.01). The average T90 was 43.76 +/- 0.74 degrees C for the LC patients and 43.17 +/- 0.57 degrees C for those LR (p = 0.024). The mean T90 was higher than 43 degrees C in 94.4% of LC, whereas in 58.8% of LR. The study suggested that T90 was a good parameter for thermal dose in the intracavitary hyperthermia for the treatment of esophageal cancer.

Adult↗

Thermodamage, thermosensitivity and thermotolerance of normal swine oesophagus.

The normal swine oesophagus was heated using an intracavity microwave radiator for 30 min at 45, 46, 47, 48 and 49 degrees C. The animals were sacrificed 48 h or 30 days later. The degree of heat injury was evaluated on an histological score system with a maximum possible damage score of 100 per cent. The acute heat injury (48 h after heating) at these temperatures was 2, 17, 40, 50 and 67 per cent respectively. The main feature of acute heat damage was degenerative necrosis or thrombosis of blood vessels at the oesophageal wall. This occurred only in one out of nine cases at 45 and 46 degrees C heating, but in seven out of nine cases at 48 and 49 degrees C. The main feature of late heat damage was fibrosis. The score of chronic damage for the above groups was 12, 23, 30, 34 and 51 per cent, respectively. When animals were preheated at 44 degrees C for 30 min and then reheated at 45-49 degrees C 4 h later, we found that preheating could provide about 2 degrees C protection. From the above data, we suggest that 45 degrees C and 30 min heating is a safe dose for normal oesophageal tissue.

Adaptation, Physiological↗

Acute heat injury to the normal swine rectum.

Intracavitary hyperthermia was applied to the rectum of normal pigs at 43 degrees, 44 degrees, 45 degrees, 46 degrees, 47 degrees and 48 degrees C for 30 min. A score of temperature-induced histological changes of each specimen was made 48 h after heating. The scores from each specimen and temperature were used for regression analysis. Judging from the regression lines of the scores obtained for rectum and oesophagus, we conclude that the thermosensitivity of the rectum is about 1 degree C higher than that of the oesophagus. It suggested that 43 degrees C/30 min could be a safe dose for normal rectum. The thermosensitivity of swine rectum is discussed.

Animals↗

Enhancement of nitrocaphane cytotoxicity by hyperthermia in vitro.

HEp-2 cells were treated with hyperthermia (39-44 degrees C) and nitrocaphane (NC) at various time intervals. A 1 h exposure to 39 degrees C and 41 degrees C was non-lethal to cells, but it did potentiate the cell killing of NC (1.0 micrograms/ml). It was further shown that the sequence between heat and the drug can affect cell survival. Cell killing effect was decreased when heat was given before or after administration of drug. In contrast the simultaneous administration of these two modalities was synergistic. Maximal thermotolerance of HEp-2 cells was developed using an 8-h interval at 37 degrees C between the cell exposures to two equal thermal doses (44 degrees C, 30 min). HEp-2 cells became thermotolerant when preheated for 30 min at 44 degrees C followed by a 10-h interval at 37 degrees C. The thermotolerant cells showed resistance to subsequent heat at 44 degrees C (D0 = 2.26 h, control D0 = 0.38 h), to subsequent NC treatment, and to heat combined with NC. However, in the thermotolerant cells, cytotoxicity of NC was still enhanced by hyperthermia.

Antineoplastic Agents↗

Late heat damage in normal swine rectum: a comparison of thermosensitivity of rectum and oesophagus.

The normal swine rectum was heated using an intracavitary microwave radiator for 30 min at 43, 44, 45, 46, 47, and 48 degrees C. The animals were sacrificed 30 days later. The degree of heat injury was evaluated on a histological score system with a maximum possible damage score of 36 (100%). The scores for late damage were 8, 21, 23, 54, 58, and 74%, respectively. The 50% maximum damage was 45.8 +/- 0.5 degrees C/30 min. With the same score system, the heat damage to the oesophagus, which we have calculated previously, was evaluated and compared with that of the present data. The heat damage at the same temperature applied to the lumen was more severe in the rectum than that of the oesophagus. There was a roughly 2-3 degrees C difference in thermosensitivity between these two organs.

Animals↗

Design of intracavitary microwave applicators for the treatment of uterine cervix carcinoma.

A 915 MHz intracavitary applicator was designed to heat tumours in the cervical and upper vaginal regions. The applicator has a 3.5-turn helical coil wound around the distal 19 mm of a dielectric rod 43 mm long and 30 mm in diameter. For treating uterine cancer, a 2450 MHz, 4 mm diameter helical applicator was made by replacing 6 cm of the outer conductor of a coaxial cable with six turns of copper wire soldered to the outer conductor. The heating patterns were determined thermographically in a muscle phantom. The maximum heating rates were 0.42 and 0.83 degrees C/W-min, respectively, for the 915 and 2450 MHz applicators. Intracavitary temperature distributions in the upper vagina, cervix and uterus were measured at the surface of the applicators with thermocouples. The average temperature was 46.0 +/- 2.1 degrees C (S.D.) at mid-tumour and 44.5 +/- 0.8 degrees C at the tumour periphery. The maximum temperature, up to 51.5 degrees C, was measured at the surface of the cervical applicator. The majority of the patients (28/30) tolerated the investigational treatment without burns or pain. Rectal temperatures were also monitored. The location of the hot-spot (40.7 degrees C) in the rectum, 5-7 cm above the anus, corresponded to the tip of the cervical applicator (47.1 degrees C).

Diathermy↗

A pilot study of intracavitary hyperthermia combined with radiation in the treatment of oesophageal carcinoma.

Twenty-five patients with primary squamous cell carcinoma of the oesophagus were treated with intracavitary hyperthermia combined with external beam radiation and intraluminal radiation at Nanjing Jinling Hospital, China. External beam radiation was given with a 6-MV X-ray; 1.8-2.0 Gy per fraction and five fractions per week; this brought the total dose to 60 Gy. Two weeks later, hyperthermia was applied with 915 MHz microwave intracavitary applicators, which were designed at the City of Hope. Temperature measurements were obtained while moving fibreoptic temperature sensors at 1.0 cm intervals in each of the six peripheral channels of the applicator. Hyperthermia was applied for 1 h before and after the intraluminal radiation. Intraluminal radiation was provided by low dose-rate iridium-192 ribbons in the same intracavitary applicator, giving 30 Gy at 0.75 cm from the applicator surface. The 3-month post-treatment responses showing complete response, partial response, no change and progressive disease were 60% (15/25), 24% (6/25), 8% (2/25) and 8% (2/25) respectively. The median follow-up time was 17 months (range 4-29 months). The 1- and 2-year overall survival rates were 72% (18/25) and 32% (8/25) respectively, and disease-free survival rates were 47 and 30% respectively. The median overall survival and disease-free survival periods were 17 and 10 months respectively. Fourteen patients had local recurrence (either at the primary site or in the lymph node) or had local progression, and five developed metastases. The median duration of the onset of local recurrence or of local progression was 9.5 months (range 0-20 months); the median of distant metastases was 8 months (range 2-16 months). Seventeen patients died. Of these, 15 died of cancer: six with local recurrence alone, four with local progression primary cancer alone, three with distant metastases alone, and two with both local and distant failure. Two patients with complete response of the primary disease died of other diseases. The toxicity was mild. According to the mucous reaction scoring criteria of the Radiation Therapy Oncology Group, the acute toxicity grades I, II, III and IV were 0% (0/25), 20% (5/25), 48% (12/25) and 32% (8/25) respectively. The major late complication was a mild oesophagus fibrosis and difficult swallowing. No serious side effects (grade IV), fistulas or perforations were seen. These results indicate that this method is safe and feasible for treating oesophageal carcinoma.

Combined Modality Therapy↗

Effect of i.v. glucose versus combined i.v. plus oral glucose on human tumour extracellular pH for potential sensitization to thermoradiotherapy.

The purpose of this study was to determine whether intravenous or combined intravenous plus oral glucose administration was more effective inducing acute tumour acidification. Seventeen nondiabetic patients at the Henan Tumour Hospital with superficial tumour deposits of various histologies and size were administered, after fasting, either 50 g glucose intravenously (i.v., in 100 ml over 10 min) or 50 g i.v. glucose (in 100 ml over 10 min) combined with 100 g oral glucose (in 200 ml; i.v. + oral). Extracellular tumour pH (pHe) was determined with one or two indwelling needle combination pH microelectrodes. Blood glucose concentration was determined every 15-20 min by finger stick with Chem-Strips and a Glucometer. Ten patients received i.v. glucose, and seven patients received i.v. + oral glucose. Blood glucose rose to 430 +/- 15 mg/dL in both groups. However, the rate of clearance of blood glucose was greater for the i.v. glucose than for the i.v. + oral glucose group (p < 0.00002), and thus the blood glucose levels remained elevated longer after i.v. + oral than after i.v. glucose administration. Relative to the initial fasting blood glucose concentration, blood glucose was -2 +/- 7 mg/dL at 110 min after glucose administration by the i.v. route, whereas, blood glucose relative to initial values was 143 + 23 mg/dL by 110 min after glucose administration by the i.v. + oral route, p = 0.000004. The initial pHe values in the two groups of tumours were similar, 7.34 +/- 0.09 (6.78-7.71) and 7.35 +/- 0.08 (6.99-7.61), respectively. After i.v. glucose, tumour acidification occurred in nine of ten patients (-0.16 + 0.02 pH unit, range -0.24 to -0.05), and after i.v. + oral glucose tumour acidification occurred in six of seven patients (-0.19 +/- 0.07 pH unit, range -0.43 to -0.06). When the initial fasting blood glucose concentration was in excess of 82 mg/dL, all patients (12/12) exhibited tumour acidification during hyperglycaemia, whereas, only 3/5 patients exhibited tumour acidification when the initial blood glucose concentration was less than 82 mg/dL (p = 0.07). The time to maximum decrease in tumour pHe was significantly shorter after i.v. + oral glucose than after i.v. glucose (e.g., 67 +/- 11 versus 102 +/- 8 min, p = 0.02) and correlated with the rate of clearance of blood glucose (p = 0.02, r = 0.55). Larger tumours tended to exhibit a greater decrease in pHe (p = 0.08, r = 0.04). The only side effects of hyperglycaemia were transient nausea and increased urinary output. The effect of hyperglycaemia induced by administration of 200 g oral glucose was similar to i.v. administration in that 83% of tumours exhibited acidification of 0.14 +/- 0.02 pH unit by 91 +/- 7 min. We conclude that i.v. and i.v. + oral glucose administration are equally effective inducing tumour acute acidification, but no more effective than 200 g oral glucose, for investigation of hyperglycemic sensitization to thermoradiotherapy.

Administration, Oral↗

A proposed new paracentesis electrode for the measurement of foetal auditory brain stem response: a preliminary report.

A proposed new electrode for measurement of foetal auditory brain stem response (ABR) is presented, the structure of which resembles a syringe needle. It can be placed subdermally in the head of the guinea pig foetus through the wall of the maternal abdomen. In the anterior end of the electrode a special device similar to a hook is situated. The device may be controlled from outside the maternal abdomen. In comparison with the placement of electrodes through the surgical incision, its placement is simple and injury to tissue is relatively small. It is not only firmly fixed in the subcutaneous tissue of the foetus to satisfy the need for the measurement of foetal ABR, but is easily removed from the foetus. To our knowledge no other similar electrode has been reported.

Animals↗