Radiation tolerance of partially irradiated liver in a multidisciplinary treatment for hepatoma

Radiation tolerance of the partially irradiated liver was studied in eight patients with primary hepatoma treated by a multimodal approach. Seven patients were treated by transarterial embolization therapy (TAE) with Lipiodol-MMC, and two patients were treated by operation, combined with radiotherapy. Six patients had liver cirrhosis and the other one had renal dysfunction. Respiration-gated irradiation was employed to reduce a treatment volume for seven patients. Radiation portals were carefully tailored using the embolized Lipiodol or a metal clip inserted into the tumor as references. Two or three portals were used for each patient. The treatment volume ranged from 64 to 1400 cm3. The target dose ranged from 50.4 Gy to 81.0 Gy, from 73.5 to 108.6 in TDF. Liver function tests (GOT, GPT, LDH, ALP, ChE and total Bilirubin) were examined for 30 weeks after initiation of irradiation. Three patients showed abnormal value in more than 5 tests. Of these three patients, the hepatic hilum was included in the treatment volume in two, and the tumor progressed during the observation period in two. Leukopenia and thrombopenia were observed, but these values were not below 2000 and 40000/mm3, respectively, although the thrombocyte count before irradiation was below 100000/mm3 in 7 patients. AFP titers decreased after the treatment in six out of seven patients with abnormally elevated pretreatment titer. The survival period after staring irradiation was 6.5 to 25 months. "The volume dose" did not correlate well with the degree of the liver function aggravation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinaryα 1 as an index of proximal tubular function in early infancy

Urinary ₁-microglobulin (U-A₁M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A₁M was high until day 14 and declined thereafter. It was significantly correlated with urinary ₂-microglobulin (U-B₂M) throughout the study, but not with serum A₁M on days 1 or 7. Similar to U-B₂M, U-A₁M in the clinically stable term infants with intrauterine growth retardation (n=4–7) was not elevated on days 1–7. In the sick infants who needed immediate resuscitatio at birth (n=4–8), U-A₁M as well as U-B₂M was high on days 1–7 and then decreased to normal levels, suggesting that U-A₁M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A₁M is a useful index of proximal tubular function in early infancy.     

Enflurane reduces the excitation and inhibition of dorsal horn WDR neuronal activity induced by BK injection in spinal cats

The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin (BK) injection was studied in spinal cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of decerebrate, spinal cord transected (L_1–2) cats. When 10µg of BK was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%) gave inhibitory resposes. On the other hand, when the injection of 10µg of BK into the femoral artery contralateral to the recording site was used as the noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3 (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but was depressed significantly by 2.5%. However, the inhibitory neuronal activity in WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have found that enflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection. These results suggest that the reduction of excitatory and inhibitory responses produced by noxious stimulation is likely to be the fundamental basis of the enflurane-induced anesthetic state in terms of WDR neurons.(Nagasaka H, Nakajima T, Takano Y et al.: Enflurane reduces the excitation and inhibition of dosal horn WDR neuronal activity induced by BK injection in spinal cats. J Anesth 4: 102–109, 1990)     

New hepatocellular diffusion model for analysis of hepatobiliary transport processes of drugs

A new hepatocellular diffusion model was developed to kinetically evaluate the hepatobiliary transport processes of drugs in the perfusion system, based on the physiological structure of the liver. Since the equations describing the hepatocellular diffusion phenomena were derived as image forms in the Laplace domain, the fast inverse Laplace transform (FILT) was adopted to manipulate the image equations. Cefixime and cefpiramide were selected as model drugs. The concentrations in the perfusate and the excreted amounts into the bile were simultaneously measured at appropriate intervals after the rapid administration of each drug into the portal vein. The hepatocellular diffusion model was fitted to the biliary excretion profiles from rat livers, by means of a nonlinear least squares program, MULTI(FILT). According to this model, the hepatobiliary transport process of drug is kinetically separated into three steps, that is, the diffusion into and through the hepatocytes, the transfer from the hepatocytes into the bile canaliculi, and the movement through the bile canaliculi to the outlet of bile duct. These steps are characterized by the diffusion rate constant through hepatocytes (k_dif), the permeability rate constant into the bile canaliculi (k_bmc) and the transit time through the bile canaliculi to the outlet of bile duct ( ), respectively. It was demonstrated that k_dif of cefixime (0.023min¹) was significantly smaller than that of cefpiramide (0.044 min¹), while the differences in k_bmc and were not obvious between cefixime and cefpiramide. k_bmc and of both drugs were about 1.2 min¹ and about 1.0 min, respectively. These parameters were correlated to the excretion ratio into the bile (F_bile) and the mean transit time from the sinusoid through the hepatocytes to the outlet of bile duct ( ).     

Medical economics and quality of life: Analysis of factors that influence the perception of medical cost by post-surgical breast cancer patients

Recently, the importance of achieving a balance in terms of length of life (LL), quality of life (QOL) and medical costs has been emphasized in the evaluation of cancer treatment, and it is also said that the cost should be seen from the viewpoints of both the society and the patient. Few studies, however, have been performed to investigate how the patients bear the cost and the influence of this factor. Therefore, in the present study we examined the perception of medical care cost (PMC) in 83 non-recurrent post-surgical breast cancer patients. The factors that influence the PMC were analyzed by univariate and multivariate analyses using the variables representing QOL, sociodemographic and clinical characteristics, types of therapy, and various types of medical cost. First, the results of the relationship between the variables and the PMC revealed that the patients with better QOL, especially those with better social category QOL, tended to have a lower PMC. However, no other variable had any significant associations with the PMC. Second, the results of multiple regression analyses revealed that patients with better QOL, especially those with better social category QOL, in the elderly, and/or those with higher level of education tended to show a lower PMC. In conclusion, the results of the present study suggest that, when we consider evaluating the cost of cancer treatment for postsurgical breast cancer patients, we should take into account the patients' QOL, age, and their level of education.     

The impacts of breast conserving treatment and mastectomy on the quality of life in early-stage breast cancer patients

The quality of life (QOL) in 55 early-stage breast cancer patients after surgery was prospectively assessed using a newly developed Japanese QOL questionnaire: The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The impacts of breast conserving treatment (BCT) (22 cases) and modified radical mastectomy (MRM) (33 cases) on the QOL in those subjects were compared. The overall QOL scores were evaluated during four periods (before surgery, 0–2, 3–12, and 13–24 months after surgery). The mean scores of the four categories of the QOL-ACD (activity, physical condition, psychological condition, and social relationships) were also compared. The results demonstrated that a significant improvement was observed in the overall QOL scores among the three periods after surgery (0–2, 3–12, and 13–24 months) only in the BCT group (P<0.05). There were no significant differences between the two groups in the overall QOL scores during any of the three periods after surgery, and the mean score of the ‘psychological condition’ during 0–2 months period in the BCT group was significantly lower than that in the MRM group (P< 0.05).