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Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography–tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

There has been a renewal of interest in controlling “nanoarchitectures,” and a considerable number of studies have been conducted on designing of novel materials to meet these applications. Some special types of polymers, for example, have emerged as a very useful class of polymers and have their own special chemical properties and applications in various areas. These polymers are coined with different names, based on their physical or chemical properties, like stimuli-responsive or environmentally sensitive or smart or intelligent polymers. We shall use the name smart polymers for such polymer systems in this chapter. The characteristic feature that actually makes them “smart” is their ability to respond to very slight changes in the surrounding environment. The uniqueness of these materials lies not only in the fast macroscopic changes occurring in their structure but also that these transitions are reversible. The responses are manifested as changes in one or more of the following: shape, surface characteristics, solubility, formation of an intricate molecular assembly, a sol-to-gel transition, and others. The environmental trigger behind these transitions can be either change in temperature or pH shift, increase in ionic strength, presence of certain chemicals, etc. More recently, changes in electric and magnetic field, light or radiation forces have also been reported as stimuli for these polymers. In this chapter, I describe some biomedical applications of smart polymers.

We have developed a new embolic agent, thermoreversible gelation polymer (TGP). This polymer is unique in that solidification occurs at body temperature. The utility of this new liquid embolic agent for the treatment of large experimental aneurysms was evaluated angiographically TGP remains liquid at temperatures below the sol-gel transition temperature (TT) and becomes gelatinous above the TT. TGP can also be used to slowly deliver biologically active substances such as growth factors or engineered cells. In this study, TGP was mixed with radiopaque material without solvent. Bilateral common carotid arteries of swine (n=5) were used for surgical creation of lateral aneurysms, then 1 aneurysm in each animal was embolized using TGP without any protection device. The remaining untreated aneurysm in each animal was used as a control. All aneurysms were successfully embolized using TGP. No distal migration of TGP was observed when aneurysms were embolized without using protection devices. TGP can be safely used to embolize experimental aneurysms. Embolization of aneurysms with a protection device needs to be evaluated. Further modifications such as mechanical stability and use as a drug delivery system will be necessary prior to the clinical application of TGP.

We have developed a new BiCMOS LSI for "Surround," which has all of the functions required of a surround decoder. The audio delay function has been realized by means of a 12 k-bit, on-chip SRAM and a new adaptive delta modulator (ADM) using analog-digital mixed circuits. We have, also, developed a BiCMOS process technology which is most suitable for the analog-digital LSI. >

BACKGROUND AND PURPOSE: Although neuroembolization has recently spread quickly, sufficient attention has not been focused on the associated radiation exposure. The purpose of this research was to evaluate the patient9s entrance skin dose (ESD) during neuroembolizations in 6 institutions. MATERIALS AND METHODS: This study was approved by all of the 6 institutional review boards, and all of the patients gave informed consent. This study included a total of 103 consecutive neuroembolizations in the 6 institutions. Patient ESDs during the procedures were evaluated by using caps that had 44 radiosensitive indicators adherent to the surface. The patient ESDs were calculated from the color difference of the indicators. To check for effects on the scalp, clinical follow-up was performed at 1-2 days, 2 weeks, and 3 months after the procedure. RESULTS: The averages of total fluoroscopic time, total number of digital subtraction angiography frames, and dose area product were 67.1 ± 41.6 minutes, 883 ± 626, and 257 ± 150 Gy × cm 2 , respectively. The average maximum ESD for each patient was 1.9 ± 1.1 Gy (range, 0.4–5.6 Gy; median, 1.5 Gy). The average maximum ESDs of each institution ranged from 1.0 to 2.4 Gy. Epilation was observed in 6 patients. CONCLUSIONS: The maximum ESDs during neuroembolizations exceed the thresholds for radiation skin injuries in some cases.

5-fluorouracil (5-FU) is a basic agent used in chemotherapy. The aim of this study is to investigate the gene expression of 5-FU anabolic and catabolic enzymes in hepatocellular carcinoma (HCC) and non-tumor tissue, respectively to increase our knowledge of resistant mechanisms to 5-FU in HCC. The relative mRNA level of orotate phosphoribosyltransferase (OPRT), ribonucleotide reductase (RNR), dihydropyrimidine dehydrogenase (DPD) and target enzyme thymidylate synthase (TS), were analyzed in 30 matched samples of HCC (T) and non-tumor tissue (NT) using quantitative RT-PCR. The expression of OPRT, RNR-M1, RNR-M2 and TS is significantly higher in T compared with in NT (1.3-fold increase, 1.6-fold, 7.1-fold, 1.9-fold, respectively), but that of DPD showed no difference between T and NT. Our results show that HCC should not be treated with 5-FU alone because of its instability in liver.

Toward the embodiment of in-situ gas sensors capable of simultaneous measurement of composition, temperature and pressure, this paper presents (1) spectrum measurement of O/sub 2/-N/sub 2/ with various mixing ratio at 60 GHz band, (2) derivation of concentration dependent spectrum model, and (3) the diagnosis of temperature, pressure and concentration using the derived model and downhill simplex.

We have developed a new embolic agent, thermoreversible gelation polymer (TGP). This polymer is unique in that solidification occurs at body temperature. The utility of this new liquid embolic agent for the treatment of large experimental aneurysms was evaluated angiographically. TGP remains liquid at temperatures below the sol-gel transition temperature (TT) and becomes gelatinous above the TT. TGP can also be used to slowly deliver biologically active substances such as growth factors or engineered cells. In this study, TGP was mixed with radiopaque material without solvent. Bilateral common carotid arteries of swine (n=5) were used for surgical creation of lateral aneurysms, then 1 aneurysm in each animal was embolized using TGP without any protection device. The remaining untreated aneurysm in each animal was used as a control. All aneurysms were successfully embolized using TGP. No distal migration of TGP was observed when aneurysms were embolized without using protection devices. TGP can be safely used to embolize experimental aneurysms. Embolization of aneurysms with a protection device needs to be evaluated. Further modifications such as mechanical stability and use as a drug delivery system will be necessary prior to the clinical application of TGP.

A case of sinus pericranii was reported. A 5-year-old boy was admitted to our hospital, complaining of scalp mass located at the midparietal region. He was noticed to have had it since 3 years before. The mass decreased in size under mild compression, and during standing position, but increased in size due to lying down. Magnetic resonance imaging (MRI) demonstrated a mass with mixed signal intensity on the T1 weighted image and high signal intensity on the T2 weighted image. Gd-DTPA study showed irregular enhancement. Cerebral angiogram showed no communication between the mass and the superior sagittal sinus. Neither did direct injection of contrast medium into the mass revealed any communication. 3D-CT demonstrated three tiny bone defects beneath the mass. Open surgery revealed that the mass existed between the galea aponeurotica and the periosteum, which had a small communication with the emissary vein. Pathological examination showed a multiple lobular cyst with endothelial wall lining. This case report highlighted the fact that sinus pericranii with minimal communication with the dural sinus can be treated by removal of the mass and closure of the cranial bone abnormalities with bone wax without craniotomy.

We investigated the potential role of mitochondrial manganese superoxide dismutase (Mn-SOD) in protective activity against irradiation by analyzing cell viability by a colony formation assay and by detecting apoptosis in stably human Mn-SOD gene-transfected HLE, a hepatocellular carcinoma cell line. We found that overexpression of Mn-SOD reduced the levels of reactive oxygen species in the mitochondria and intracellular phospholipid peroxidation product (4-hydroxy-2-nonenal) and prevented cell death. The production of intracellular nitric oxide after irradiation was not changed by Mn-SOD overexpression. The results suggested that Mn-SOD might play an important role in protecting cells against radiation-induced cell death by controlling the generation of mitochondrial reactive oxygen species and intracellular lipid peroxidation.

We report a case of an anterior and posterior-inferior cerebellar artery (AICA-PICA) aneurysm. The patient was a 62-year-old woman who suffered from sudden onset of severe headache and nuchalgia. Computed tomography (CT) scan revealed subarachnoid hemorrhage in the ambient cistern and blood clots in the 3rd and 4th ventricles. Vertebral angiography demonstrated an aneurysm located at the distal segment of the left AICA-PICA. Three demensional CT scan was very useful for the decision concerning surgical strategy. The patient underwent bilateral occipital craniectomy and the aneurysm was clipped successfully via the midline suboccipital approach. Her postoperative course was uneventful. Postoperative angiography showed successful clipping of the aneurysm. Distal AICA-PICA aneurysm is a very rare disease and only one case has been reported in the literature. The clinical features, CT findings, and surgical approach of distal AICA-PICA aneurysms are briefly discussed while reviewing the literature.

The detectability of early liver injury induced by irradiation was studied using magnetic resonance (MR) imaging enhanced with superparamagnetic iron oxide (SPIO), a tissue-specific contrast agent against the reticuloendothelial system (RES). In rat, 3 days after focal irradiation (0-10 Gy), MR imaging was performed and specimens were obtained to observe the phagocytic function of RES. The irradiated portion of the liver was visualized with a clear demarcation from the nonirradiated part by SPIO-enhanced MR images as a decrease in negative enhancement reflecting the function of RES (P0.05), whereas this was impossible with nonenhanced MR images. Significant regression was observed as a dose-related change of the signal intensity in the irradiated portion on SPIO-enhanced MR images (R = 0.867, P0.0001). SPIO-enhanced MR imaging was reliable for detecting the range and extent of liver injury a few days after low-dose irradiation, and it may be a useful procedure for verifying the target area in clinical cases of radiation therapy.

To anticipate the prognosis and choose therapy for patients with relatively early-stage HCCs, we elucidate the natural course of such patients. Thirty cirrhotic patients with small hepatocellular carcinoma (HCC)3 cm in size and not receiving anti-cancer treatment were followed by sonography for periods of 6-48 mots. The growth speed varied considerably from case to case, with an average of 6.5+/-5.7 months of doubling time (DT). Growth speed of small HCC is significantly related to histological differentiation of tumors: a slow-growing HCC tends to be well-differentiated and a rapid-growing HCC moderately- or poorly-differentiated. Furthermore, there was a tendency to grow without changing from nodular type in slow-growing HCCs and to multiple nodular or massive types in intermediate- and rapid-growing HCCs. The survival rates of these untreated HCC patients showed a 1-yr survival of 90.7%, a 2-yr survival of 55.0%, and a 3-yr survival of 12.8%. Factors significantly influencing survival of these patients were serum total bilirubin level and DT. This study will provide invaluable data for diagnosing and treating for small HCCs.

Features of enhanced color flow images of small hepatocellular carcinoma (HCC) were studied to elucidate their usefulness in evaluating tumor hemodynamics. Enhanced color Doppler using the contrast agent "SH/TA508" was performed on 16 patients, 13 with HCC, 1 with regenerative nodule, and 2 with hemangiomas, in whom the size of the tumor were smaller than 30 mm. Enhanced color flow appearance was compared with angiographic findings. Significant improvement in the detection of color flow signals was obtained in small HCC using SH/TA508, from 33% in pre-contrast to 92% in post-contrast (p0.005). Three patterns of enhanced color flow images, which were related to the angiographic findings, were observed. Enhanced color flow imaging promises to be a useful method for evaluating tumor vascularity noninvasively, and to contribute to the elucidation of the hemodynamics in liver tumor.

Four patients with advanced hepatocellular carcinoma were treated by repeated arterial infusion of zinostatin stimalamer (SMANCS). Every 4 weeks, 4 mg of SMANCS and 4 ml of Lipiodol were administered via the proper hepatic artery using an implantable arterial port. Three patients with advanced liver cirrhosis (Child B or C) could no longer be treated after 2 or 3 courses of SMANCS infusion because of hepatic failure. In the remaining patient also with compensated liver cirrhosis (Child A), a partial response was observed after 5 courses of chemo-infusion, but we discontinued infusion of SMANCS because of hepatic failure. To assess the usefulness of SMANCS for repeated arterial chemo-infusion by the port, we evaluated 103 patients with advanced HCC treated by Lipiodol emulsion mixed with 70 mg of epirubicin (EPI) using a port. An average course was 11 arterial infusions, and the overall response rate was 40%. One-year survival rates were 62% in Child A, 59% in Child B, and 53% in Child C. Compared with Child A and B patients, both elevation of serum total bilirubin levels and decrease of serum albumin levels were observed after 9 months in Child C patients. In conclusion, SMANCS may have more severe hepatic toxicity in comparison with Lipiodol emulsion mixed with EPI.

In order to investigate the mechanism of recurrence of hepatocellular carcinoma (HCC), 322 patients with HCCs (size:or = 3 cm) treated by percutaneous ethanol injection (PEI), transcatheter arterial embolization (TAE) or radiation therapy were evaluated. Cumulative recurrent rates of new lesions after the initial therapy were 25% (1-year), 57% (2-year) and 71% (3-year). In 116 patients whose tumors were multiple at the time of initial therapy, the recurrent rates were higher compared with 206 patients with a single tumor. In 228 of all patients, new lesions were observed in the noncancerous liver after initial therapy. We observed a single new lesion in 67% of the 134 patients, whose HCC was single at the time of initial therapy. In the remaining 33% of these patients, multiple new lesions were observed. As for the recurrence site, we found new lesions at a different segment of the liver from the initial HCC in 52% of these 134 patients. In the patients with multiple recurrent HCCs, the survival rates were lower in comparison with the patients whose recurrent HCC was single. In the patients whose new lesions were found within 1 year after the initial therapy, the survival rates were also lower compared with the patients whose new lesions were not detected during 1 year. In conclusion, the mechanism of multicentric occurrence may be closely correlated with the intrahepatic recurrence of HCC in consideration of the high incidence of recurrent rates of HCCs and their recurrent pattern.

We studied 710 patients with hepatocellular carcinoma(HCC) who underwent non-surgical treatment. Multivariate analysis demonstrated that four factors, the number of tumors, tumor size, portal vein tumor thrombus and the severity of liver dysfunction (Child's classification) before treatment were found to be significant for the prognosis of patients and that severity of liver dysfunction was the most significant factor. of 179 patients with small HCC who underwent percutaneous ethanol injection (PEI), the severity of liver dysfunction was the most significant factor contributing to the prognosis. The prognosis of HCC is influenced by many factors. We conclude that early detection of tumors followed by early therapy is the most important.

Seventy-one patients with untreated hepatocellular carcinoma (111 tumors) were studied angiographically to investigate the pathological features of multiple carcinoma. The 111 tumors comprised 23 lesions resected from 14 patients and 88 lesions measuring 3 cm or less in diameter detected in 57 patients who did not undergo resection. Hemodynamically, major lesions exhibited an increase in frequency of tumor angiogenesis and intensity of tumor stain with an increase in diameter. Analysis of angiographic features of tumors measuring 2 cm or less in diameter revealed a greater vascularity in intrahepatic metastatic foci than in primary foci, demonstrating a difference between them. When multiple tumors were classified into the isolated, concentric or disseminated type in terms of the pattern of their distribution, their angiographic findings suggested that min or lesions of the concentric or disseminated type might represent local metastases spread from the primary focus, and that those of the isolated type might represent multicentric occurrence in the liver.

Percutaneous ethanol injection (PEI) was performed on 183 tumors in 147 patients with small hepatocellular carcinoma (HCC), of no larger than 3 cm in size and less than three in number, during 9 years and 4 months between August 1983 and December 1992. The 1-, 3- and 5-year survival rates of all 147 patients calculated by the Kaplan-Meier method were 96.3%, 62.5% and 40.7% respectively. Multivariate analysis (Cox's proportional hazard model) demonstrated that the most significant factor contributing to the prognosis of the patients was the severity of liver dysfunction (clinical stage) before treatment. Recurrence was seen in different areas of the liver from the original lesion in 26.9% in one year and 61.5% in three years. Multivariate analysis demonstrated that the most significant factor contributing to the recurrence was the number of tumors before treatment. Regrowth of the original tumor occurred in two patients (1.4%). There was no serious complication due to PEI. To evaluate the therapeutic effect of PEI, contrast-enhanced CT with intravenous bolus injection was considered to be indispensable. We conclude that PEI can be indicated in most patients with small HCC and is also effective.

We performed periodical examinations by ultrasonography (US) and serum alpha-fetoprotein in 272 patients with liver cirrhosis (male, 167; female, 105) over long follow-up periods (1985. 1-1992.9). The average period was 1934 days, and we prospectively studied the early detection of hepatocellular carcinoma (HCC). HCC was detected in 78 patients during the periods, with the average cumulative incidence rate being per year 7%. Tumor size at detection was 15mm or less in diameter in 37.2% HCC patients and 30mm or less in 89.7%. In spite of frequent ultrasonic examinations, it was difficult to detect small sized HCCs in blind spots of US or in the liver with the rough parenchymal echo pattern. Predictive factors important for development of HCC were analyzed using Cox's proportional hazards model. It showed that significant factors were serum AFP level, liver parenchymal echo pattern and small mass lesions (ultrasonic appearance) of the liver.

Ultrasound is now widely used in the diagnosis of liver diseases. Applications of ultrasound in the diagnosis of liver cirrhosis are reviewed in this paper. Characteristic findings of liver cirrhosis in ultrasound are nodular liver surface, round edge, and hypoechoic nodules in liver parenchyma which represent regenerative nodules of cirrhotic liver. Detection of hypoechoic nodule more than 10 mm is important in the early diagnosis of hepatocellular carcinoma. Detection of splenomegaly, ascites, and portosystemic collaterals is possible by ultrasound. Evaluation of portosystemic collaterals is beneficial in the management of esophagogastric varices and portosystemic encephalopathy. Ultrasound is useful in the non-invasive diagnosis and long-term management of cirrhotic patients.

Percutaneous ethanol injection (PEI) was applied to 162 lesions in 133 patients with hepatocellular carcinomas (HCC) 3 cm or less in diameter (small HCC) between Aug. 1983 and Apr. 1992. Histological findings in resected specimen for which PEI had previously been performed before surgery showed that PEI could completely necrotize an HCC of 32 mm in diameter. The antitumoral effect by PEI could correctly be evaluated by enhanced CT. The 1-, 3-, 5- and 7-year survival rates after PEI calculated by the Kaplan-Meier method were 95.9%, 60.5%, 36.9% and 21.7%, respectively. The survival rate of post-PEI patients with I or II grade in clinical stage was better than that of those with III. Recurrence occurred in hepatic areas different from the original lesion in 27.8% in one year and 63.6% in three years after PEI, rates quite similar to those of recurrence after surgical resection for HCCs of 3 cm or less in diameter. For such recurrence, PEI alone was then repeated in half of the 76 patients. Complications caused by PEI were not serious and did not necessitate intensive care. Because of its anti-tumor therapeutic effect and minimal damage to the liver, PEI might be considered a viable alternative to surgery for most patients with small HCC.

We evaluated the usefulness of percutaneous biopsy under sonographic control and histological examination in the early diagnosis of hepatocellular carcinoma (HCC) in comparison with CT and angiography. 121 patients in whom hepatic nodules 3cm or smaller in size were found by ultrasound as suspected HCC underwent percutaneous biopsy, CT and angiography. 118 patients were finally diagnosed as HCC. Correct diagnosis of HCC was obtained by each modality in relation to tumor size as follows: 87.3% by histological examination, 55.1% by CT, 52.5% by angiography. However, the diagnostic capability of these modalities for HCC 1.5cm or smaller in size was as follows: 88.5% by histological examination, 34.6% by CT, and 23.1% by angiography. Cytology using a biopsy specimen was performed in 26 patients and it showed a positivity of 61.5%. In conclusion, for a definitive diagnosis of small HCC 1.5cm or less in size, the current imaging modalities have some limitations. On the other hand, percutaneous biopsy and histological examination are the most reliable and indispensable for making a definite diagnosis of small HCC.

The diagnostic value of angiography for small hepatocellular carcinoma was evaluated in comparison with histology, contrast-enhanced computed tomography, and ultrasonography. A total of 120 patients with small hepatocellular carcinoma (less than 3 cm in size) were examined. The definitive detection rate for primary tumors less than 2 cm in size was 44.9% by angiography, while it was 68.6% for primary tumors between 2 cm and 3 cm in size. When the primary tumor was less than 2 cm in size and without tumor vessels on angiography, it tended to be of Edmondson's grade 1 and to show fatty change. When the primary tumor was less than 2 cm in size and without tumor stain while non-cancerous parenchyma showed irregular stain, it tended to be of Edmondson's grade 1 and normotrabecular type. Angiography was found to be of particular value in detecting satellite tumors with a nodular parenchymal echo pattern in non-cancerous areas, because ultrasonography often fails to differentiate these satellite tumors from non-affected parenchyma.

Five patients with abdominal tuberculous lymphadenitis were studied by ultrasound. The final diagnosis of tuberculosis was based on open biopsy in 2 patients, neck lymph node biopsy in 1, needle biopsy under ultrasound control in 2. Low-echoic and iso-echoic abdominal lymph nodes were seen in all patients and a mixed echoic lymph node was found in one of them. Enlarged, round or oval, lymph nodes were conglomeratically observed along the common hepatic artery, in the hepatoduodenal ligament and along the abdominal aorta. The size of the lymph node was found to be 20-70 mm. In one case, compression of the portal trunk and the common bile duct due to a large lymph node was observed, and arterioportography showed hepatopetal collateral veins. In the other case, multiple mass lesions in the liver and the spleen were observed. In the 4 patients who were observed by ultrasound at 2 months after anti-tuberculosis therapy, enlarged lymph nodes decreased and 3 of them changed from low-echo to iso-echo in the echo pattern. Of the 4 patients who were followed for more than 4 months, lymph nodes disappeared in 2 at 4 months and in one at 12 months. The remaining patient showed residual nodes which decreased in half at 8 months. Ultrasound is now used commonly in the examination of the abdomen, and there are cases of abdominal lymph nodes swelling due to varied diseases. In this study, there were no characteristic ultrasonographic findings in abdominal tuberculous lymphadenitis. So, it is difficult to diagnose the cause of abdominal lymph node swelling by only ultrasound.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonograms of 282 cases of hepatocellular carcinoma (HCC) less than 5 cm in size were examined. Among these, 73 cases of resected or biopsied HCCs were compared in terms of their pathologic findings and sonograms. Low echoic pattern was the more common among smaller HCCs, and low echoic periphery pattern tended to prevail with increasing size. The pathologic factors of fatty change and clear cell formation are responsible for elevating the echo level. Among HCCs less than 2 cm, the low echoic group is more differentiated than the iso-echoic group by Edmondson's classification. "Lateral acoustic shadow", "nodule in nodule", and "septum" are characteristic findings in HCC by sonography, and they correspond to the pathologic findings. However, "posterior echo enhancement" was not seen to be specific for HCC, as it was also observed with similarly frequency in hemangiomas.

Hepatocellular carcinoma epidemiology has undergone great changes in Japan. Life span, new diagnostic procedures and viral infections obtained through intravenous injections have contributed to these changes. The aetiological aspects and clinical features of HCC should be reappraised to account for the current use of techniques such as US and CT in the early diagnosis of HCC. In Japan most HCC seem to be HBV and/or HCV associated whereas small HCC seem to be HCV-associated more so than large HCC. The usual clinical symptoms and signs are somewhat useless and of limited value while the newer techniques permit an early clinical diagnosis of small HCC. This diagnostic advancement has also permitted a remarkable progression in HCC therapy.

Hepatocellular carcinoma (HCC) arises in patients with chronic liver diseases, particularly liver cirrhosis.

A case of hepatic and splenic metastases of lung cancer infused with LAK cells and anticancer drugs from hepatic artery with total implantable port (Port-A-Cath: Pharmacia, Incorp.) was reported. A 56-year-old male was admitted to our hospital because of general fatigue, jaundice, pleural effusion and elevation of transaminase caused by hepatic and splenic metastases of lung carcinoid. Abdominal ultrasonography revealed 6 hepatic metastatic foci 10-35 mm in diameter and splenic metastases. The patient received 5 courses of MMC infusion, CPA (2 courses) and epirubicin, CDDP (3 courses), and 5 courses of LAK cells (total 1.4 x 10(10)) with IL-2 and OK-432. Eight months after initiation of treatment, jaundice and pleural effusion disappeared, transaminase returned to the normal level and the condition of the patient improved. Although the response of hepatic metastases to the treatment was NC, the size of a splenic metastasis decreased from 35 x 55 mm to 24 x 35 mm (PR).

We investigated development of hepatocellular carcinoma (HCC) in 90 patients with liver cirrhosis by follow up study for a period from 6 months to three and half years, making special reference to ultrasound-findings of the parenchyma of the liver. Liver cirrhosis was classified into four types and two, non-nodular and nodular, groups according to low-echoic nodules distributed in the parenchyma. The development of HCC was higher at the rate of incidence in patients of the nodular group than those of the non-nodular. It was more closely related with the male in patients of the non-nodular group, and both the old age and the advanced hepatic injury in those of the nodular group. A rise of the level of serum AFP during a period of the follow up was not observed in relation to the development of HCC and seemed to be ineffective for detection of carcinoma small sized. The echo-types of the parenchyma in liver cirrhosis were most significantly correlated with the development of HCC in comparison with the other etiologic factors.

Therapeutic effects of a combination therapy (TAE and irradiation) and a radiation therapy alone were evaluated comparatively in 54 patients with HCCs. Twenty eight patients of them underwent external X-irradiation with a linear accelerator after TAE and the remaining twenty six did irradiation alone. The incidence of partial response was 82.1% in the combination therapy and 69.2% in the radiation therapy. The cumulative rates of survival in the combination therapy were 70.8% (1-year), 37.1% (3-year), and 27.9% (5-year), which were higher than those in the radiation therapy. The cumulative rates of recurrence in the former were lower than those in the latter. The prognoses after the both treatments were poor in the patients with advanced liver cirrhosis (Child C). In the patients with HCCs smaller than 5 cm in diameter or accompanied by portal vein thrombi, the combination therapy was superior to TAE alone in the cumulative rates of survival. It is considered from the above results that the combination therapy is useful in the patients with HCCs when properly selected.

Two hundred and eighty-two patients with HCC including 89 with tumors 2 cm or smaller in size and 193 of 2-5 cm were studied on clinical and pathological findings and correlated with the value of various diagnostic imaging modalities. There were apparent differences in histological findings of HCC between 2 cm or smaller in size and larger ones; the former had much less invasion of malignant cells to the extracapsule and portal vein neighbouring the HCC than the latter. In 83 patients with HCCs 2 cm or less in diameter AFP level was normal (less than 20 ng/ml) in 39.8%, 20-200 ng/ml in 44.6% and more than 200 ng/ml in only 15.6%. Detectability of HCC measuring 2 cm or less by various imaging modalities was as follows: 97.8% by US, 54% by X-ray computed tomography (CT), 61.6% by magnetic resonance imaging (MR) and 75.4% by angiography. There was considerable limitation of imaging modalities in making a definitive diagnosis of the smaller HCCs, particularly in the differentiation from regenerative nodules of liver cirrhosis. Tissue biopsy under ultrasound control provided a correct diagnosis in 36 out of 41 patients (87.8%) with HCCs 2 cm or less in size, a better ratio than for aspiration biopsy.

Percutaneous ethanol injection (PEI) was carried out for 109 lesions in 85 patients with hepatocellular carcinoma (HCC) smaller than 3 cm in diameter during the period from Dec. 1982 to Mar. 1989. Therapeutic effect of PEI on HCC was evaluated by ultrasound showing that 15 of 68 HCCs disappeared and the remaining 53 HCCs decreased in size with regression rates ranging from 8% to 88% at 6 months after PEI. Survival rates from PEI calculated by the Kaplan-Meier method showed a 1-yr survival of 92%, a 2-yr survival of 81%, a 3-yr survival of 61%, a 4-yr survival of 55%, and a 5-yr survival of 41%. These survival rates were better than those of patients with HCCs smaller than 3 cm in size who had not received anti-cancer treatment (p less than 0.05).

Recently, small hepatocellular carcinoma (HCC) has been detected reliably by real-time ultrasound (US), and the rate of detection is increasing, particularly in patients with cirrhosis of the liver. At present, surgical resection is believed to be the most effective treatment of small HCC, but is often not indicated because of the associated liver dysfunction. While transcatheter arterial embolization and systemic chemotherapy are recommended when resection is not feasible, their usefulness has not been reliably established in patients with small HCC.

Owing to the recent advancement of ultrasonographic instruments, we can now easily detect variously sized hypoechoic nodules as well as coarse echo pattern in cirrhotic liver. Based on the size and distribution of such hypoechoic nodules, we classified echo patterns of liver parenchyma into four types as follows. Type 0: Homogeneous echo pattern. Type I: Coarse echo pattern with no distinct hypoechoic nodules. Type II: Echo pattern showing scattered hypoechoic nodules sized 3 approximately 5 mm. Type III: Echo pattern showing scattered hypoechoic nodules sized more than 5 mm. In the present study, all the 25 patients of normal liver showed type 0, 29 of 42 patients with chronic hepatitis showed type 0 and the remained 13 type I. In 65 patients with liver cirrhosis, 54 (83.1%) were classified as type I, II, or III. The grade of parenchymal echo pattern was significantly correlated with the severity of liver cirrhosis. In addition, the parenchymal patterns proved to be very useful in diagnosis of liver cirrhosis, presenting overall accuracy value of 81.8%. The value was the highest compared with those of other diagnostic factors on ultrasonograms. Immersion experiment with autopsied liver specimens evidenced that hypoechoic nodules on ultrasonogram represent regenerative nodules of cirrhotic liver. It was also revealed that the parenchymal echo patterns closely corresponded to gross or histologic findings of the liver.