Multicentre study of perioperative versus adjuvant chemotherapy for resectable colorectal liver metastases.

Background: It is not known whether perioperative chemotherapy, compared with adjuvant chemotherapy alone, improves disease-free survival (DFS) in patients with upfront resectable colorectal liver metastases (CLM). The aim of this study was to estimate the impact of neoadjuvant 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) on DFS in patients with upfront resectable CLM. Methods: Consecutive patients who presented with up to five resectable CLM at two Japanese and two French centres in 2008-2015 were included in the study. Both French institutions favoured perioperative FOLFOX, whereas the two Japanese groups systematically preferred upfront surgery plus adjuvant chemotherapy. Inverse probability of treatment weighting (IPTW) and Cox regression multivariable models were used to adjust for confounding. The primary outcome was DFS. Results: Some 300 patients were included: 151 received perioperative chemotherapy and 149 had upfront surgery plus adjuvant chemotherapy. The weighted 3-year DFS rate was 33·5 per cent after perioperative chemotherapy compared with 27·1 per cent after upfront surgery plus adjuvant chemotherapy (hazard ratio (HR) 0·85, 95 per cent c.i. 0·62 to 1·16; P = 0·318). For the subgroup of 165 patients who received adjuvant FOLFOX successfully (for at least 3 months), the adjusted effect of neoadjuvant chemotherapy was not significant (HR 1·19, 0·74 to 1·90; P = 0·476). No significant effect of neoadjuvant chemotherapy was observed in multivariable regression analysis. Conclusion: Compared with adjuvant chemotherapy, perioperative FOLFOX does not improve DFS in patients with resectable CLM, provided adjuvant chemotherapy is given successfully.

Antecedentes: Se desconoce si la quimioterapia perioperatoria en comparación con la quimioterapia adyuvante sola mejora la supervivencia libre de enfermedad (disease­free survival, DFS) en pacientes con metástasis hepáticas de origen colorrectal (colorectal liver metastases, CLM) resecables de inicio. El objetivo de este estudio fue estimar el impacto de la neoadyuvancia con 5­fluorouracilo, leucovorina y oxaliplatino (FOLFOX) sobre la DFS en pacientes con CLM resecables desde el principio. Métodos: Se incluyeron pacientes consecutivos que presentaban hasta cinco CLM resecables en dos centros japoneses y dos centros franceses entre 2008 a 2015. Ambas instituciones francesas favorecían FOLFOX perioperatorio, mientras que los dos grupos japoneses utilizaban sistemáticamente la cirugía de entrada y quimioterapia adyuvante. Se utilizaron la probabilidad inversa del tratamiento ponderado (Inverse Probability of Treatment Weighting, IPTW) y el modelo multivariable de regresión de Cox para ajustar por factores de confusión. El resultado primario fue la DFS. Resultados: Se incluyeron 300 pacientes (grupo de quimioterapia perioperatoria n = 151 y grupo de cirugía de entrada más quimioterapia adyuvante n = 149). La DFS a los 3 años ponderada fue del 33% después de quimioterapia perioperatoria versus 27% tras cirugía de entrada (cociente de riesgos instantáneos, hazard ratio HR: 0,85; i.c. del 95% (0,62­1,16); P = 0,32). Cuando se consideró el subgrupo de pacientes que (n = 165) de manera efectiva (al menos 3 meses) recibieron FOLFOX adyuvante, el efecto ajustado de la quimioterapia neoadyuvante no fue significativo (HR: 1,19 (0,74­1,90); P = 0,48). No se observó un efecto significativo de la quimioterapia neoadyuvante en el análisis de regresión multivariable. Conclusión: En comparación con la quimioterapia adyuvante, el FOLFOX perioperatorio no mejora la DFS en CLM resecables siempre y cuando la quimioterapia adyuvante se administre de forma efectiva.

Systemic administration of histamine reduces reovirus type 2-induced insulitis in suckling DBA/1 mice.

Previously we suggested that reovirus type 2 (Reo-2) infection induced autoimmune insulitis, resulting in mild diabetes in suckling mice. The effect of histamine (a lymphocyte function suppressor) on Reo-2-induced insulitis was examined. Systemic histamine administration reduced the development of insulitis and blood glucose elevation. Endogenous interleukin-2 (IL-2) activity by splenic cells and the production of antibodies to pancreatic islet cells were reduced by histamine treatment. In addition, histamine treatment increased cyclic adenosine monophosphate (cAMP) concentrations in the plasma. These results further suggest that the insulitis seen in Reo-2 infection in suckling mice is induced by an immune reaction.

Age- and gender-related changes in ligament components.

The age- and gender-related changes in extracellular matrix components (elastin, elastin cross-links, fibrillin, collagen and glycoprotein) and mineral components (calcium, Ca; phosphorus, P) in human lumbar yellow ligaments were investigated using samples obtained from surgical specimens. The mineral (Ca and P) contents increased with ageing (r = 0.703 and r = 0.772, respectively), whereas the contents of matrix components tended to decrease with ageing (elastin r = -0.261, elastin cross-links r = -0.213, fibrillin r = 0.494; collagen r = -0.322 and glycoprotein r = -0.143). Comparison of the male and female groups revealed that the ligament elastin content and elastin cross-links decreased in the male group, whereas the ligament collagen content decreased in the female group significantly in an age-dependent manner (r = -0.788, r = -0.753 and r = -0.721, respectively). These findings demonstrate age- and gender-related changes in mineral and matrix components (especially elastin and collagen) in the lumbar yellow ligaments in the Japanese population. It is suggested that elastin and collagen metabolism in ligaments changes both with age and according to gender.

X-Serrate-1 is involved in primary neurogenesis in Xenopus laevis in a complementary manner with X-Delta-1.

Notch, Delta and Serrate encode transmembrane proteins that function in cell fate specification in the Drosophila melanogaster embryo. Here we report gene expression patterns and functional characterization of a Xenopus Serrate homolog, X-Serrate-1. The isolated cDNA encoded a transmembrane protein with a Delta/Serrate/LAG-2 domain, 16 epidermal growth factor-like repeats and a cysteine-rich region. Expression of X-Serrate-1 was observed ubiquitously from unfertilized egg to tadpole, but an upregulation occurred in the tailbud stage embryo. Adult expression was found in eye, brain, kidney, heart, spleen and ovary. Whole-mount in situ hybridization revealed that the organ-related expression in eye, brain, heart and kidney occurred from an early stage of rudiment formation. Overexpression of X-Serrate-1 led to a reduction of primary neurons, whereas an intracellularly deleted form of X-Serrate-1 increased the number of primary neurons. Although the function of X-Serrate-1 in primary neurogenesis was quite similar to that of X-Delta-1, expression of X-Serrate-1 and X-Delta-1 did not affect each other. Co-injection experiments showed that wild-type X-Serrate-1 and X-Delta-1 suppressed overproduction of primary neurons induced by dominant-negative forms of X-Delta-1 and X-Serrate-1, respectively. These results suggest that X-Serrate-1 regulates the patterning of primary neurons in a complementary manner with X-Delta-1-mediated Notch signaling.

Cross-linked hyaluronate hydrogel prevents adhesion formation and reformation in mouse uterine horn model.

The aim of this study was to evaluate the efficacy of cross-linked hyaluronate hydrogel (HA gel) as an adjuvant for postoperative adhesion prevention, in a mouse uterine horn model. In experiment 1 uterine horns were abrased with iodine. HA gel was applied to the injured surface before closure in the treatment group. In experiment 2, after injuring the uterine horns, three stitches were placed at equal distances around the uterine horns to appose the injured medial surfaces of the two horns during healing. HA gel was inserted between the uterine horns in the treatment group. In experiment 3 prevention of adhesion reformation was assessed. After lysis of adhesions that were induced as in experiment 2, HA gel was introduced between the serosal surfaces of apposing uterine horns. Untreated animals served as controls in each experiment. Statistical analysis was carried out using Student's t-test. The adhesion score was significantly lower in the HA gel group on the 14th day compared with controls in all the experiments: in experiment 1, 0.3 +/- 0.4 versus 1.7 +/- 1.2; in experiment 2, 0.9 +/- 1.0 versus 2.6 +/- 0.5; and in experiment 3, 1.5 +/- 0.9 versus 2.2 +/- 0.6 respectively. Cross-linked HA gel significantly reduced de-novo adhesions (P< 0.03) and adhesion reformation (P < 0.03).

Installation and experience of an automatic scheduling system for multiple diagnostic examinations: in search of maximum utilization of regional health care resources.

We installed a scheduling system that optimally schedules multiple appointments for various diagnostic examinations for a patient based on patient characteristics, disease characteristics and conditions, characteristics of diagnostic examinations, possible interactions between two successive examinations, and features and availability of diagnostic equipment. The system consists of four client terminals, 12 laboratory terminals, and one server. After the run-in period, the system started operation in July 2000. A total of 14353 examinations involving 11447 patients were managed over 7 months. On average, approximately 82 patients per day underwent approximately 103 examinations. On average, 16.1 patients a day requested 2 or more examinations in a scheduling session (approx. 2.3 examinations/patient; maximum 5 examinations for a single patient). After reading the request sheet(s) (OCR sheet(s)), suggested time/date slots of examination(s) were displayed on the client terminal within 10 seconds. The average time required for a patient to establish his or her schedule was approximately 2 minutes. Thus, the system greatly mitigated the load on health care professionals in scheduling appointments for examinations. In general, patients had a positive impression of the system. Furthermore, networking through these health care facilities and implementing this automatic scheduling system as a centralized appointment system can easily establish a "virtual diagnostic examination center" that fully utilizes the diagnostic equipment and staff available at community health care facilities. We estimate that approximately 30% of the diagnostic examinations in a health care facility can be referred to another facility in this cooperative system.

A preliminary report of the treatment of blue nevus with dermal injection of riboflavin and exposure to near-ultraviolet/visible radiation (ribophototherapy).

Dye lasers are useful for treating pigmented skin lesions, but their equipment is expensive and bulky. A simple and cheap phototherapy would be acceptable to dermatologists for treating pigmented skin lesions such as nevus of Ota. We investigated as a pilot study whether dermal injection of riboflavin and exposure to near-ultraviolet/visible radiation (ribophototherapy) decreases the dermal pigment of blue nevi which are recalcitrant to laser therapy. The therapeutic efficacy was assessed by comparison of the amount of dermal pigment in hematoxylin-eosin specimens taken before and after treatment. Pigmentation of the nevus became faint to the depth of 1 mm with little noticeable epidermal change after 21 treatments. At the deeper dermis somewhere between 3 and 4 mm from the epidermis, ballooning degeneration of the dermal cells was observed in hematoxylin-eosin specimens. Ribophototherapy is hopeful for treating pigmented skin lesions.

Influence of finishing on the electrochemical properties of dental alloys.

Dental alloy surface finishing procedures of may influence their electrochemical behavior, which is used to evaluate their corrosion resistance. We examined the polarization resistance and potentiodynamic polarization profile of the precious-metal alloys, Type 4 gold alloy and silver-palladium alloy, and the base-metal alloys, nickel-chromium alloy, cobalt-chromium alloy, and CP-titanium. Three types of finishing procedure were examined: mirror-finishing using 0.05 micron alumina particles, polishing using #600 abrasive paper and sandblasting. Dissolution of the alloy elements in 0.9% NaCl solution was also measured and compared with the electrochemical evaluation. The corrosion resistance of the dental alloys was found to relate to finishing as follows: The polarization resistance and potentiodynamic polarization behavior revealed that the corrosion resistance improved in the order of sandblasting, #600-abrasive-paper polishing, and mirror-finishing. While the corrosion potential, critical current density and passive current density varied depending on the type of finishing, the transpassive potential remained unchanged. The influence of finishing on the corrosion resistance of precious-metal alloys was less significant than on that of base-metal alloys. A mirror-finishing specimen was recommended for use in evaluation of the corrosion resistance of various dental alloys.

A new matrix protein family related to the nacreous layer formation of Pinctada fucata.

We have isolated a new matrix protein family (N16) which is specific to the nacreous layer of the Japanese pearl oyster, Pinctada fucata, and have cloned and characterized the cDNAs coding for the components. Analysis of the deduced amino acid sequence revealed that N16 showed no definitive homology with other proteins. The in vitro studies of the crystallization clarified that N16 induced aragonite crystals when fixed on the substrate but inhibited crystal formation without it. The aragonite crystals showed platy morphology different from those formed inorganically, and long intervals of incubation resulted in crystalline layers highly similar to the nacreous layer.

A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion.

Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.

Increased uncoupling protein2 mRNA in white adipose tissue, and decrease in leptin, visceral fat, blood glucose, and cholesterol in KK-Ay mice fed with eicosapentaenoic and docosahexaenoic acids in addition to linolenic acid.

The effects of n-3 polyunsaturated fatty acids (n-3PUFA) on obesity and diabetes were examined using KK-Ay mice fed with perilla oil (P), soybean oil (S), or lard (L), and those containing 30% fish oil (PF, SF, or LF), containing eicosapentaenoic acid (EPA = 9.9%) and docosahexaenoic acid (DHA = 18.0%). Perilla oil contained the largest proportion of linolenic acid (LNA = 61.9%). Computerized tomography (CT) scans showed narrower areas of visceral fat in the abdominal cross sections of groups given fish oil (PF, SF, and LF) and lower leptin levels (p < 0.05-p < 0.001) compared with controls (P, S, and L), without significant changes in energy intake and body weight. The highest plasma n-3PUFA content (21.31 +/- 0.35%) was attained with PF. This group contained 2.6-fold more plasma DHA (p < 0.001), and expressed 2.7-fold more UCP2 mRNA in white adipose tissue (p < 0.01) than in the P group. The epididymal fat pad (p < 0.05) weighed less, and levels of blood glucose (p < 0.05) and total cholesterol (p < 0.01) were reduced in PF compared with P.

Total body bone development during early childhood in very low birth weight infants without cerebral palsy and mental retardation.

Total body bone mineral density was measured by dual energy X-ray absorptiometry in 52 children who were very low birth weight (VLBW) infants without cerebral palsy and mental retardation (postconceptional age, from 10 mo to 6 y and 6 mo). VLBW infants in this study seemed to show compensatory acceleration of total body bone development, catching up with the control group during early childhood. However, in VLBW infants with at least one of the three factors such as total parenteral nutrition for 1 week or more, assisted ventilation for 1 week or more, or oxygen therapy for 28 d or more in their early stage after birth, adequate mineral supplementation might be especially important for long-term bone development.

Effect of n-3 fatty acid supplementation on lipid peroxidation and protein aggregation in rat erythrocyte membranes.

Human erythrocytes in the circulation undergo dynamic oxidative damage involving membrane lipid peroxidation and protein aggregation during aging. The present study was undertaken to determine the effect of n-3 fatty acid supplementation on lipid peroxidation and protein aggregation in the circulation and also the in vitro susceptibility of rat erythrocyte membranes to oxidative damage. Wistar male rats were fed a diet containing n-6 fatty acid-rich safflower oil or n-3 fatty acid-rich fish oil with an equal amount of vitamin E for 6 wk. n-3 Fatty acid content in erythrocyte membranes of rats fed fish oil was significantly higher than that of rats fed safflower oil. The degree of membrane lipid peroxidation and protein aggregation of rats fed fish oil was not significantly higher than that of rats fed safflower oil when the amounts of phospholipid hydroperoxides, thiobarbituric acid-reactive substances, and detergent-insoluble protein aggregates were measured. When isolated erythrocytes were oxidized under aerobic conditions in the presence of Fe(III), the degree of membrane lipid peroxidation of erythrocytes from rats fed fish oil was increased to a greater extent than that of rats fed safflower oil, whereas the degree of membrane protein aggregation of both groups was increased in a similar extent. Hence, n-3 fatty acid supplementation did not affect lipid peroxidation and protein aggregation in membranes of circulating rat erythrocytes, and the supplementation increased the susceptibility of isolated erythrocytes to lipid peroxidation, but not to protein aggregation, under the aerobic conditions. If a sufficient amount of vitamin E is supplied, n-3 fatty acid supplementation may give no undesirable oxidative effects on rat erythrocytes in the circulation.

Surface reaction between titanium castings and investments.

The selection of investments suitable for titanium castings is critical because the surface-reacted layer greatly affects their mechanical properties. This study analyzed the interfacial zone of titanium castings obtained from various commercial investments and examined the relationship between the surface-reacted layer and the hardness. CP titanium disks (20 mm diameter, 1 mm thick, n = 5) were cast using eight commercial casting systems and investments for titanium casting: two alumina-based investments (T-invest, CD-titan investment), two spinel-based investments (Titanmold, Titavest MZ), three zirconia-based investments (Asahivest-D, Titaniumvest EX, Tycast investment TM), and a magnesia-based investment (Selevest CB). The Vickers hardness of cast disks in cross-section was tested at 50 microns intervals from the surface to 0.5 mm in depth. The cross-section was observed metallurgically, and an elemental mapping measurement of the reacted layer was conducted under the EPMA. The Vickers hardnesses at 50 microns from the surface of the specimens ranged 312 to 624 and were significantly different among the investments (p < 0.01). The thickness of the reacted layer, rich in O, Si, Al, Zr, Mg, and P, ranged from 10 to 60 microns. No correlation was seen between the thickness of reacted layer and the hardness (p > 0.05). However, the specimens cast with alumina-based and zirconia-based investments were harder than the spinel-based and magnesia-based investments at 500 microns. Although the free energies of metal oxide formation of alumina and zirconia were lower than titania, these data suggest that silica, alumina and zirconia were reduced by contact with molten titanium. Accordingly, silicon, aluminum and zirconium diffused to the interior of the titanium castings and changed their mechanical properties.

Protecting effect of a green tea percolate and its main constituents against gamma ray-induced scission of DNA.

Gamma ray-induced scission of puC18 plasmid DNA prepared from E. coli was examined in the presence of a green tea percolate and its main constituents, L-ascorbic acid (used as the sodium salt) and (-)-epigallocatechin gallate. Each of these showed a protecting effect against DNA scission. The relationship between the protecting effect against DNA scission and the scavenging effect of the hydroxyl radical was examined, and is discussed from the viewpoint of interaction with DNA.

Cloning and characterization of human type 2 and type 3 inositol 1,4,5-trisphosphate receptors.

We have cloned cDNAs coding for human type 2 and type 3 and part of type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs). The complete nucleotide sequences for type 2 and type 3 receptors were determined and the pharmacological properties of the latter were characterized. Human type 2 and type 3 IP3Rs are 2701 amino acids and 2671 amino acids long, respectively, and have significant sequence homologies as well as structural similarities including the six membrane-spanning regions near the C-termini when compared with the rat or mouse counterpart. COS-7 cells transfected with human type 3 IP3R showed characteristic inositol 1,4,5-trisphosphate (IP3)-binding properties with Kd values of 28.8 nM. The order of potency of competition with IP3 was Ins(1,4,5)P3 (IP3) > Ins(2,4,5)P3 > Ins(1,3,4,5)P4 > Ins(1,2,3,4,5,6)P6. Type 2 and type 3 IP3Rs were mapped to human chromosomes 12p11 and 6p21, respectively, by in situ hybridization. cDNA cloning of the human IP3Rs allowed us to identify the types of the receptor expressed in various human hematopoietic and lymphoma cell lines. The type 3 receptor was present in all of cell lines tested, while the type 1 or 2 receptor was expressed in only particular cell types. The differential expression of the IP3R types could confer the cell-specific regulation on the IP3/Ca2+ signalling.

Angiotensin II-induced endothelium-dependent relaxation of fowl aorta.

In the domestic fowl, angiotensin II (ANG II) decreases blood pressure in vivo and causes endothelium-dependent relaxation of aortic smooth muscles in vitro. To characterize ANG II-induced vasorelaxation, we compared endothelium-dependent vasodilatory effects of [Asp1,Val5]-ANG II (fowl ANG II) and acetylcholine (ACh) with the endothelium-independent vasorelaxing effect of sodium nitroprusside (SNP) on isometric tension of fowl aortic rings. Hemoglobin (Hb), gossypol, and N omega-nitro-L-arginine methyl ester (L-NAME), inhibitors for endothelium-derived relaxing factor (EDRF) in mammalian blood vessels, partially inhibited vasorelaxation induced by ANG II and ACh in fowl. Hb also markedly attenuated SNP-induced vasorelaxation, but not 8-bromoguanosine 3',5'-cyclic monophosphate-induced relaxation. 3,4,5-Trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) or the removal of Ca2+ from the bathing medium attenuated the ACh-induced relaxation but did not significantly reduce vasorelaxation induced by ANG II or SNP. In the zero Ca2+ medium, aortic rings showed tachyphylaxis to ACh, while ANG II caused tachyphylaxis regardless of the presence or absence of external Ca2+. Furthermore, pretreatment of the ring with a high dose of ACh abolished the vasorelaxation response to ANG II, suggesting that ACh and ANG II may share a common Ca2+ pool. Calmidazolium, a calmodulin antagonist, abolished the vasorelaxation induced by ANG II and ACh but not that by SNP. Comparison of the vasodilatory effects of several ANG II analogues on fowl aortic rings showed an approximate potency order of [Asp1,Val5]-ANG II = [Asp1,Ile5]-ANG II > [Asn1,Ile5]-ANG II = [Sar1,Ile5]-ANG II > [Val5]-ANG III.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical studies on chronic prostatitis and prostatitis-like syndrome. (5) Evaluation of prostatitis complicated by anal disease].

We analyzed the incidence of anal disease in patients with nonbacterial prostatitis (NBP) or with prostatitis-like syndrome (PLS), and evaluated the clinical efficacy. The complicated rate of anal disease in these patients was 29.7% (31.8% for NBP and 28.1% for PLS), and the overall incidence of active anal disease was 15.4% (16.2% for NBP and 14.8% for PLS), it yielded a significantly higher complicated rate than other urological disease (p less than 0.01). The most common type of anal disease was hemorrhoids, especially piles. The clinical cure rate for anal disease in NBP patients was 71.4%, and in PLS patients was 58.2%. The high incidence of hemorrhoids (especially piles) was in these patients by clinico-statistical observation suggests that the development of anal disease may be etiologically correlated with NBP and PLS. Furthermore, we noted that Kampo treatment (Keisibukuryogan) was useful in the treatment of prostatitis complicated by anal disease, especially when combined with anti-hemorrhoidal suppositories against active anal disease in PLS patients (p less than 0.05).

Clinical evaluation of the sedative effect of HEMA solution on the hypersensitivity of dentin.

The sedative effect of the dentin primer, 35% hydroxyethyl methacrylate (HEMA) solution, on dentin hypersensitivity was clinically evaluated. Exposed root surfaces of teeth were cleaned with neutralized 0.5 mol/L EDTA and treated with 35% HEMA solution followed by the application of a commercial dentin bonding agent. The extent of sedation was estimated by comparison of the responses before and after treatment to irritation by a cold water spray, compressed air blast and scratching with an explorer. The degree of the response to these irritations was decreased significantly upon the combined application of HEMA and commercially available dentin bonding agents though it was still ineffective in nearly 30% of the 48 cases tested.

[Cytological and histological effects of regional hyperthermia and radiation in cancer of the uterine cervix].

Hyperthermia is known to produce tumor-specific effect. Its combination with radiotherapy has been found to enhance antitumor effect and hyperthermia is a new modality of cancer treatment. Here, we report a cytological and histopathological study of the effects of hyperthermia on uterine cervical cancer. Our subject cases were 63 patients with cervical cancer (squamous cell carcinoma). Thirteen cases were treated with hyperthermia. Of these, the clinical stage was I b in 2, stage II in 10, stage III in 1. Before radical operation, external irradiation was given at 40Gy. with Lineac. During this period, the lesion was treated with hyperthermia at 42-45 degrees C for 30-60 min. with a 13.56 MHz RF capacitive heating system "Endoradiotherm 100A" (Kureha Chemical Industry CO. Ltd.) and an intraluminal applicator designed for uterine cervix. The control cases received radiotherapy alone before radical operation. There were 15 cases in Stage I b, 19 in stage II, and 16 in stage III. After the completion of radiotherapy, radical hysterectomy was performed in all cases. The effects of irradiation on the lesion were compared cytologically and histologically for different doses. The evaluation of the irradiation damage in cancer cells in the cytological study was based on findings such as intracytoplasmic vacuolation, the formation of giant nuclei, intranuclear vacuolation and formation of polynuclei. The degree of irradiation damage was classified into 5 grades from Do (little irradiation effect) to Dx (no viable cancer cells remaining), and the irradiation effect in the histopathological study was classified in to 8 grades from Grade 0 to Grade IVC according the Oboshi and Shimosato's classification. Cytological changes at 10Gy. were rated as D3 (relatively extensive irradiation damage in cancer cells) in 38.5% of the hyperthermia group, as compared to about 20% in the control groups. The cases rated Grade II B histologically made up 38.5% of the hyperthermia group: this grade was about 10% in the control groups. This suggests that radiation was more effective in the hyperthermia group than in the control groups, as was also suggested by the cytological results. With irradiation at 30Gy., cytological changes were rated as Dx in 61.5% of the hyperthermia group, as compared to 25.0-26.7% of the control groups. Histological results were Grade III, with only cancer cells regarded as non-viable observed, in 38.5% of the hyperthermia group and Grade IV, with no cancer cells, in another 23.1%. In the control groups, there were no cases with Grade IV, and those with Grade III totalled 12.5-26.7%.(ABSTRACT TRUNCATED AT 400 WORDS)