Expression of interferon alpha/beta receptor in human hepatocellular carcinoma.

Interferon-alpha (IFNalpha) plays a crucial role in the antiproliferation and immunoregulatory activity through the specific cell surface receptor, interferon-alpha/beta receptor (IFNalpha/betaR). We examined the immunohistochemical expression of IFNalpha/betaR in 91 hepatocellular carcinoma (HCC), HCV-related chronic hepatitis (n=38) and cirrhosis (n=53), dysplastic nodules (n=5), and normal liver (n=9). The level of IFNalpha/betaR increased in chronic hepatitis and cirrhosis compared with normal liver. All the dysplastic nodules showed moderate or high expression. In HCCs, 26% (24/91) of patients showed high IFNalpha/betaR expression while the remaining 38% (35/91) showed moderate, and 35% (32/91) no or faint expression. Clinicopathological survey demonstrated a significant correlation between IFNalpha/betaR expression and differentiation of carcinoma (P=0.0008) although there was no correlation between IFNalpha/betaR expression in HCC and survival or disease-free survival. Thus, IFNalpha/betaR was expressed not only in chronic hepatitis or liver cirrhosis but in HCC and its expression was significantly correlated with tissue differentiation of carcinoma.

Clinical application of quantitative analysis for detection of hematogenous spread of hepatocellular carcinoma by real-time PCR.

In order to detect a hematogenous spread of tumor cells in patients with hepatocellular carcinoma, reverse transcription-polymerase chain reaction assay has been used. In this study, we quantified alpha-fetoprotein (AFP) messenger RNA by real-time PCR approach using LightCyclertrade mark technique. AFP messenger RNA in the blood from 23 hepatocellular carcinoma patients undergoing hepatic resection, 31 healthy volunteers, 10 patients with liver cirrhosis and 5 patients underwent hepatectomy except for hepatocellular carcinoma was quantitated. In the real-time PCR, fluorescence was undetectable in any of the controls. On the contrary, fluorescent signals were detected in 10 out of 39 blood specimens collected from 23 HCC patients. AFP-positive status was significantly associated with the existence of multiple intrahepatic nodules. Out of 8 cases with AFP-positive status, intra- and/or extra-hepatic recurrence has been observed in 3 cases. The quantities of AFP messenger RNA in these 3 cases were relatively high among 8 cases with AFP-positive status. AFP messenger RNA was detectable by newly developed real-time PCR approach with LightCycler and it is suggested that this approach could be applicable in detection of small amounts of tumor cells in the blood of HCC patients.

[Pharmacokinetic and clinical studies on ceftriaxone in the field of obstetrics and gynecology].

Ceftriaxone (CTRX) was studied regarding its penetration into the adnexa uteri and uterine tissues, as well as its utility and safety in the treatment of patients with obstetric and gynecologic infections. The results obtained are summarized below. 1. When 1 g of CTRX was administered by intravenous bolus injection, Cmax in tissues of adnexa uteri and uterus ranged from 42.2 to 80.5 micrograms/g, Tmax ranged from 0.42 to 0.81 hour, and the AUC ranged from 314.9 to 606.9 micrograms.hr/g. Thus, drug penetration into these tissues was good. 2. Clinical efficacy of CTRX was evaluated in 29 obstetric and gynecological patients. The clinical efficacy was good in all cases. 3. Bacteriological effects of CTRX were very good, and 90% of the organisms isolated before treatment were eradicated. 4. Laboratory testing revealed an occurrence of mild eosinophilia in 1 case.

[Experimental and clinical studies of ceftazidime in the field of obstetrics and gynecology].

Ceftazidime (CAZ) was studied for its transference into adnexa uteri and uterine tissues as well as for its effects and safety on gynecological infections. The results obtained are as follows: Peak levels of CAZ were obtained in the tissues of adnexa uteri and uteri at 15--30 minutes after one shot intravenous injection of CAZ 1 g, and relatively high concentrations were maintained for several hours. In the treatment of 33 cases of gynecological infections, the clinical efficacy of CAZ was assessed as excellent in 13 cases and effective in 20 cases. As for the bacteriological effects of CAZ, 95.5% of clinically isolated organisms were eradicated. The laboratory tests performed before and after administration of CAZ revealed rise in GOT, GPT values in 2 cases and eosinophilia in 1 case. However, these cases were all mild and required no particular measures.

[Clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology].

Efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) was studied on gynecological infections. The results obtained are as follows: In the treatment of 31 cases of gynecological infections, the clinical efficacy of SBT/CPZ was assessed as excellent in 9 cases and effective in 22 cases. As for the bacteriological effects of SBT/CPZ, clinically isolated organisms were completely (100%) eradicated. In comparison with MICs of CPZ, SBT/CPZ was found to show a combined effect on Gram-negative and Gram-positive organisms in the order mentioned, but this effect was not observed against anaerobes. The combined effect of SBT/CPZ on beta-lactamase producing bacteria was also investigated in the same manner. As a result, SBT/CPZ was found to exert a combined effect on beta-lactamase strains of S. aureus, S. epidermidis, E. coli, B. catarrhalis and B. fragilis. The laboratory tests performed before and after administration of SBT/CPZ revealed rise in GOT and GPT values in 1 case, GPT values in 2 cases and eosinophil in 1 case. However, these rises were all mild and required no particular measures.

[Preclinical and clinical studies on aztreonam in the field of obstetrics and gynecology].

Penetration of aztreonam (AZT) into the uterus and the adnexal tissues and usefulness and safety of AZT for obstetric and gynecologic infections were studied with the following results. By one shot intravenous injection of AZT 1 g, the uterus and the adnexal tissues showed favorable penetration with Cmax 27.0-48.5 micrograms/g, AUC 29.4-84.9 micrograms X hr/g and Tmax 0.10-0.44 hours. MIC50, MIC80 and MIC90 of AZT for Gram-negative bacteria measured prior to administration were very low being 0.10 micrograms/ml, 0.20 micrograms/ml and 1.56 micrograms/ml, respectively. Clinical effect of AZT for 30 infection cases in obstetrics and gynecology was evaluated according to an overall efficacy criteria resulting in "good" for all the cases. With regard to microbiological effect, 90.9% of the pathogens isolated prior to the administration were eliminated by AZT. During and after the administration of AZT, side effect due seemingly to AZT was not observed in subjective and objective symptoms and laboratory values.

[Pharmacokinetic and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology].

Imipenem/cilastatin sodium (MK-0787/MK-0791) was studied for its penetration into the adnexa uteri and uterine tissue, as well as for its clinical efficacy in the treatment of patients with obstetric and gynecologic infections. The following results were obtained. When 500 mg/500 mg of MK-0787/MK-0791 was administered by an intravenous drip infusion, peak levels of MK-0787 in tissues of adnexa uteri and uterus ranged from 14.6 micrograms/g to 25.8 micrograms/g, Tmax ranged from 0.55 hour to 0.98 hour, and the AUC ranged from 25.6 micrograms X hr/g to 45.2 micrograms X hr/g. Thus, the penetration of the drug into these tissues was good. Clinical efficacy of MK-0787 was evaluated in 30 patients in the field of obstetrics and gynecology. The clinical efficacy was excellent or good in all patients. Bacteriological effects of MK-0787/MK-0791 were very good, and 90% of the organisms detected before the treatment were eradicated. The antimicrobial activity of MK-0787 was tested against pathogens isolated before, during and after the treatment. Mean MIC80 values of MK-0787 were 0.39-0.78 micrograms/ml against all Gram-positive bacteria, 0.20-0.39 micrograms/ml against all Gram-negative bacteria, and less than or equal to 0.10-0.20 micrograms/ml against all anaerobic bacteria. The antimicrobial activity of MK-0787 appeared very good. No side effects or abnormal laboratory findings were observed except a slight elevation of S-GPT in 1 patient.

[Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology].

Cefpimizole (AC-1370) was studied for its transference into adnexa uteri and uterine tissues as well as for its effects and safety on gynecological infections. The results obtained are as follows: Peak levels of AC-1370 were obtained in the antecubital vein and uterine artery at 10 minutes, in the tissues of adnexa uteri and uteri about 30 minutes after one shot intravenous injection of AC-1370 1 g, and relatively high concentrations were maintained for several hours. In the treatment of 30 cases of gynecological infections, the clinical efficacy of AC-1370 was assessed as effective in all cases. As for the bacteriological effects of AC-1370, 77.6% of isolated organisms were eradicated and 90% of all cases were effective. Side effects and abnormal laboratory findings due to AC-1370 were not observed during and after administration.

[Clinical trial of cefpiramide in the gynecological field].

Cefpiramide (CPM) was administrated intramuscularly to 27 cases of gynecological infections to evaluate its clinical efficacy and safety and the following results wee obtained. CPM was effective to all the cases of gynecological infections, and excellent was seen in 14 cases and good was seen in 13 cases. CPM eliminated 75% of clinical isolates. Laboratory tests were performed to blood samples and functions of liver and kidney before and after CPM treatment. Elevation of GPT was observed in 2 cases but required no treatment.

[Pharmacokinetic, bacteriological and clinical studies on cefuzonam in the field of obstetrics and gynecology].

The distribution of cefuzonam (CZON, L-105) into the uterus and uterine adnexa was investigated and the usefulness and the safety of CZON in obstetric and gynecological infections were studied. The results are summarized as follows: 1. Following one shot intravenous injection of CZON 1 g, a good distribution of the drug into tissues of uterus and uterine adnexa was observed, with Cmax values of 15.7-33.9 micrograms/g, Tmax of 7.3-34.0 minutes and AUC values of 18.7-35.3 micrograms X hr/g. 2. In all of the 30 cases of obstetric and gynecological infections treated, CZON was evaluated effective. 3. Bacteriologically, 93.9% of total bacteria that had been isolated were eliminated by the administration of the drug. 4. Against all the strains of bacteria isolated before the treatment and replaced bacteria, MIC50, MIC80 and MIC90 of CZON were 0.20 micrograms/ml, 12.5 micrograms/ml and 25 micrograms/ml, respectively, showing low values. 5. Subjective and objective findings and clinical laboratory test values during and after the trial showed no side effects associated with CZON.

[Acute angle-closure glaucoma after total hip replacement surgery].

Acute angle-closure glaucoma is a rare complication of surgery. We experienced a case of postoperative acute glaucoma after total hip replacement under general anesthesia. A 49-year-old female without signs or symptoms of glaucoma was premedicated with the intramuscular administration of secobarbital, atropine and ranitidine. Following rapid induction with thiopental and vecuronium, anesthesia was maintained with N2O-O2-sevoflurane. PGE1 was administered intravenously for induced hypotension during the surgery. Hemorrhagic shock with a systolic blood pressure of 60 mmHg continued for 15 min during the surgery. Large amounts of fluid and ephedrine were required for treating this hypotensive episode. Vecuronium was reversed by bolus injection of neostigmine and atropine at the end of surgery. Soon after recovery from anesthesia, she complained of pain and blurred vision in her both eyes. The consulting ophthalmologist made a diagnosis of acute glaucoma due to high intraocular pressure (IOP). Treatment with glycerol and pilocarpine had no effect on the elevated IOP. The laser iridotomy performed on her at 5th and 7th post-operative days improved her vision completely. The post-operative glaucoma may cause serious permanent loss of vision. An early diagnosis of this post-operative complication and its treatment with drugs and surgery should be emphasized.

[A case of malignant hemangioendothelioma of the lung with rapid growth of pulmonary metastasis].

Malignant hemangioendothelioma of the lung is very rare and difficult to diagnose. The growth is rapid and the prognosis is very unfavorable. We report an operated case of the disease with rapid growth of pulmonary metastasis. The silver, vimentin and factor VIII stainings were available for diagnosis of this disease. The 46-year-old female patient died of bleeding from the pulmonary metastasis eight months after the operation without other distant metastasis. Even if a lung tumor is pointed out and thought to be benign, frequent follow up is necessary. Furthermore, we recommend positive lung biopsy by thoracotomy or video-assisted-thoracic-surgery.

[Hepatic arterial chemotherapy for liver cancer over a period of 8 years].

Hepatic arterial chemotherapy was performed for 27 patients with primary (3), metastatic liver cancer (21), and 3 other cases, over a period of 8 years. Chemotherapy was performed by intermittent hepatic arterial infusion of 5-FU or FAM (in case of metastatic tumor from colorectal cancer), FAM (from gastric cancer), and CDDP or Farmorubicin (HCC). Hepatic resection was performed in 10 cases of metastatic tumor from colorectal cancer, and 8 cases of 10 were curative operation. The 5-year survival rates of curative liver resection group, and non-curative liver resection or non-resection group were 57.1% and 12.5%, respectively. As is the case with metastatic cancer from gastric cancer, pancreatic cancer, and hepatocellular carcinoma (HCC), the prognosis was poor except for one CR case of HCC. We concluded that hepatic arterial chemotherapy may be recommended for a curative resected case of liver metastasis from colorectal cancer.

[A case of liver metastasis of gastric leiomyosarcoma successfully treated by transarterial hepatic chemo-embolization and intra hepato-arterial chemotherapy repeated with infusion-a-port].

The patient was a 68-year-old male, who underwent total gastrectomy for giant leiomyosarcoma of the stomach and then had multiple hepatic metastases one year and six months later. Thus, transarterial hepatic chemo-embolization therapy with Lipiodol, adriamycin and gelfoam was given. Moreover, using a reservoir catheter and infusion arterial port, intermittent arterial infusion therapy with adriamycin, cyclophosphamide, and vincristine was attempted. In the metastasis lesion where there were rich blood vessels, Lipiodol was accumulated and the tumor was reduced on abdominal CT. The result indicated the efficacy of this treatment.

[Partial liver resection with small skin incision for multidisciplinary treatment of hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is likely to be detected as multiple intrahepatic metastases, and trans-arterial embolization (TAE) is the treatment of choice. However, other therapy is needed when TAE is not effective for a tumor. We performed partial liver resection with small skin incision in two such patients. One patient had two HCCs of segment 6 (S6) and S7, and TAE was performed twice. However, HCC of S7 was viable, and we partially resected the tumor of S7. In the other patient, HCC was multiple in segment 6 and 7. TAE was performed three times, and in segment 6 we detected a tumor which grew into the extrahepatic space and seemed uneffected by TAE. We performed a partial resection of liver segment 6. After 3 months, TAE was repeated in the latter. The operation time was about three hours, and no blood transfusion was performed. Two of the patients were discharged on the 13th postoperative day. We concluded that partial liver resection with small skin incision was useful for one case of multidisciplinary treatment for hepatocellular carcinoma.

[Microwave tissue coagulation therapy with mini-laparotomy for hepatocellular carcinoma].

Recently microwave tissue coagulation therapy (MCT) has been established as a therapeutic procedure for hepatocellular carcinoma (HCC). The route of approach to penetrate the tumor is two-fold: By the percutaneous route (PMCT) or by conventional laparotomy. PMCT has the advantage of less invasive therapy, however, it is not applicable to a tumor that cannot be detected by ultrasonography. Therefore, we tried MCT with mini-laparotomy. The patient was a 57-year old man with HCC located in the S6 subsegment. The operation was performed at the semi-right side up position, and laparotomy was done by skin incision of 12 cm in the right hypochondral area. MCT was performed about 30 times, with an output of 60 watts for 45 seconds at a time. Abdominal CT image showed a low-density area of 7 x 4 cm on the 18th postoperative day. Slight damage to the liver and no obvious complications were observed. We concluded that a much wider range-coagulation than PMCT was able to be obtained by MCT with mini-laparotomy, and postoperative quality of life was better than MCT with conventional laparotomy.

[A patient with hepatocellular carcinoma and portal vein thrombosis in 1st branch who was treated by transcatheter arterial embolization].

We report a patient with hepatocellular carcinoma (HCC) with portal vein thrombosis in the 1st branch who was treated by transcatheter arterial embolization (TAE) and survived more than 3 years. A 58-year old male was diagnosed as having unresectable massive type HCC in the area of S8 with portal vein thrombosis from the P8 branch to the right portal branch. He was treated by TAE via the anterior branch of right hepatic artery. One week later, localized hepatic infarction in the anterior segment was recognized. Five months later, the portal vein thrombosis had disappeared and become necrotic. After 3 years and 4 months, he died of a relapse of a gastric varix, but with no portal thrombosis and a well controlled intra-hepatic recurrence that was treated by repeated TAE. This case suggests that TAE might be effective for cases of HCC with portal vein thrombosis in the 1st branch, if the liver function and portal flow are suitable.

[Neoadjuvant intraarterial chemotherapy for ten cases of inflammatory breast cancer by Seldinger's methods].

The conventional methods (CM) of intraarterial (IA) chemotherapy for inflammatory breast cancer were catheterizations from superior epigastric and brachial artery under general anesthesia. Since 1997, we selected the Seldinger's methods (SM) for ten cases of the disease to control local effects and simplify the technique. Complications of the SM were slight, and side effects were equal to those with CM. The postoperative pathological findings of the SM showed the direct effects of chemotherapy to tumor cells (degenerative and necrotic changes) as compared with the embolism-like effects of CM. But the overall histological effects of chemotherapy by SM were almost equal to those for CM. The strong points of the SM were as follows: 1) More selective IA chemotherapy is available, 2) one can find the passage of the aim vessels and no trouble related to catheter, 3) general anesthesia is not necessary, and the techniques are simple, 4) the wounds are not remarkable. The disadvantages are as follows: 1) Patients must rest the day of IA chemotherapy, 2) in 20% of the procedures, one can not search the vessels, and 3) in 4 cases complications of stiffness of Mj or Mn pectral muscles were found. In future, we expect more effective results by dose escalation or combination chemotherapy.

Effects of intravenous mepivacaine on renal sympathetic nerve activity in the cat during nitrous oxide and nitrous oxide-halothane anesthesia.

BACKGROUND AND OBJECTIVES: Because hemodynamic responses to systemic mepivacaine may be influenced by sympathetic change and concurrent general anesthesia, the authors directly measured renal sympathetic nerve activity (RSNA) during intravenous administration of mepivacaine in subseizure through seizure doses under N2O-O2 and N2O-O2-halothane anesthesia. METHODS: Thirty-four cats were randomly assigned to five groups. Groups I-A, I-B, and I-C received incremental subseizure doses of intravenous mepivacaine (2 mg/kg, 5 mg/kg, and 10 mg/kg). Groups II-A and II-B received intravenous infusion of mepivacaine (4 mg/kg/min). Anesthesia was maintained with N2O(70%)-O2 in groups I-A, I-C, and II-A, and with N2O(70%)-O2-halothane (1%) in groups I-B and II-B. Cats in group I-C had undergone total baroreceptor denervation. Heart rate (HR), mean arterial pressure (MAP), and RSNA were measured. RESULTS: In group I-A, MAP did not significantly change with intravenous mepivacaine, though RSNA and HR significantly decreased (P < .05) respectively with 5 mg/kg i.v. and 10 mg/kg i.v. mepivacaine. In group I-C, HR, MAP, and RSNA did not change significantly. In group I-B, HR and MAP decreased with bolus intravenous doses of mepivacaine in a dose-dependent fashion, but RSNA did not change significantly. All cats in group II-A developed seizure by mepivacaine infusion at mean total dose of 28.9 +/- 4.2 mg/kg without significant changes in HR, MAP, or RSNA. In group II-B, mepivacaine infusion resulted in circulatory collapse at mean total dose of 34.3 +/- 4.6 mg/kg without seizure or significant RSNA change. CONCLUSIONS: The authors conclude that intravenous mepivacaine induces occasional depression in HR and RSNA during N2O-O2 anesthesia, but in addition induces dose-related circulatory depression during N2O-O2-halothane anesthesia via nonsympathetic mechanism(s).