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To evaluate the benefits of performing laparoscopic cholecystectomy (LC) in patients with cirrhosis, data on 13 patients with liver cirrhosis who underwent cholecystectomy for gallstones between 1989 and 1995 were retrospectively collected from charts filed at Fukuoka City Hospital. These 13 patients were classified into two groups; one, comprised of 7 who underwent LC, and anothe, comprised of 6 who underwent open cholecystectomy (OC). No statistical differences were observed in the duration of surgery or the intraoperative blood loss between the two groups; however, the C-reactive protein (CRP) level in the serum was significantly higher in the OC group than in the LC group. LC was followed by a significantly earlier resumption of a normal diet (P

A 51-year-old male with a recurrent medullary thyroid carcinoma (MTC) showed high serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) but with concomitant normocalcemia. The CT activities of the patient's serum in vivo (hypocalcemic activity in rats) and in vitro (cyclic AMP-increasing activity in cultured human mammary tumor, T47D) were much lower than those expected from the patient's CT level. High performance liquid chromatography (HPLC) with radioimmunoassay (RIA) detection gave a broad spectrum of molecular weights of CT-like polypeptides in the 3 kDa to 200 kDa range with separation from CEA, suggesting that the mechanism for CT production in MTC is an obscure one.

Objective: To predict disseminated microscopic foci or occult micrometastases in the peritoneal cavity in patients with gastric cancer. Design: Randomly selected patients with gastric cancer had peritoneal washings performed at the beginning of laparotomy. Patients: Thirty-nine patients with gastric carcinoma and 10 patients with other benign disease as a control group. Setting: Inpatients in a surgical department. Interventions: The concentration of collagen type IV in the irrigated peritoneal fluid was measured radioimmunologically. Intraoperative peritoneal cytologic examination and measurements of carcinoembryonic antigen (CEA) levels were also performed. Main Outcome Measurements: Results of the quantitative analyses of the collagen type IV concentrations as related to the clinicopathological characteristics and comparison of these results with regard to those of the peritoneal cytologic examination and CEA and collagen type IV levels. Results: There were eight patients with elevated collagen type IV concentrations. They had carcinomas with serosal invasion (pT3 and pT4) and metastatic spread (pN2, M1). Patients with clinically evident peritoneal disseminated metastases had significantly higher collagen type IV concentrations compared with those without metastases. The collagen type IV levels were more sensitive than peritoneal cytologic examination or CEA values in detecting disseminated metastases. There was an early peritoneal recurrence in the form of ovarian metastases in one patient with negative cytologic results and an elevated collagen type IV level. Linear regression analysis showed a statistically significant correlation between the collagen type IV and CEA levels. Conclusion: Quantitative detection of abnormal collagen type IV levels may be useful for predicting the presence of disseminated metastases in patients with gastric cancer. (Arch Surg. 1995;130:769-773)

background To determine a feasible postoperative adjuvant chemotherapy for patients with hepatocellular carcinoma, orally-administered chemotherapy (OC) and prophylactic lipiodolization (selective regional cancer chemotherapy using lipid contrast medium plus an anticancer drug) (PL) were compared prospectively. patients and methods Forty-eight patients who had undergone hepatic resection from 1989 to 1992 were divided into three groups: the control group (n = 19), given no chemotherapy; the OC group (n = 12), given 300 to 400 mg/d of 5-FU derivatives (either 1-hexylcarbamoyl-5-fluorouracil or uracil and tegafur, mean total dosage: 188 g, mean administrative duration: 18 months); and the PL group (n = 17), who underwent prophylactic lipiodolization 1.8 times on average using a 44-nig mean dose of epirubicin per treatment. results No statistical differences were found either in the 25 variables studied as a background analysis, or among the survival curves of the 3 groups. Recurrence was found in 23 remnant livers of the 48 patients. The 3-year, disease-free survival rate was 15%, 50%, and 86% in the control, OC, and PL groups, respectively. The disease-free survival curve of the PL group was significantly higher compared to either the control ( P = 0.001) or the OC group ( P = 0.025). conclusions Prophylactic lipiodolization was found to be an effective treatment for patients with hepatocellular carcinoma for reducing intrahepatic recurrence after resection.

We synthesized 14C-warfarin hexadecyl ether (14C-WHE) by addition of a palmityl moiety to the hydroxyl group at the 4-position of 14C-warfarin, a compound known to bind to serum albumin. 14C-WHE preferentially bound to the lipoproteins, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), in mouse plasma both in vitro and in vivo. 14C-Warfarin mainly concentrated in the liver immediately after intravenous administration to mice bearing M5076 sarcoma, and was found at only low concentrations in other tissues including the tumour. 14C-WHE highly distributed to the tumour, adrenal, and spleen, as well as the liver. These tissues coincided with those in which human 125I-LDL was vigorously incorporated. The results indicate that chemical modification of an agent, giving it high lipophilicity, will enable it to bind to lipoproteins after intravenous administration. These modifications raise the possibility of lipoproteins as endogenous targeting carriers into tumour cells, which have high LDL-receptor activity.

To estimate the effectiveness of hepatic resection on hepatocellular carcinoma (HCC) in the elderly.Comparison with younger patients.A municipal hospital and a large university hospital in Japan.The study included 39 patients (ageor = 70 years [the elderly group]) and 229 patients (age70 years [the younger group]) who underwent hepatic resection from April 1985 to March 1993. The preoperative clinical features (Child's classification, association of cirrhosis and liver functions) were comparable between two groups. The positive rate for hepatitis C virus antibody was higher in the elderly group (88% vs 59%; P = .016).Morbidity and survival following operation and the pathological features of HCC.The incidence of postoperative hepatic failure was higher in the elderly group (10% vs 2%; P = .018). However, the incidence of operative death in the elderly group (5% vs 1%) as well as the incidence of other postoperative complications and rates of long-term survival (75.9% vs 51.6% at 5 years) and disease-free survival (30.4% vs 31.0% at 5 years) were similar to those in the younger group. The pathological features of HCC were identical between the two groups.The outcome of surgical treatment of HCC in the elderly group was satisfactory when compared with that in the younger group.

The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo [b]thiophene-6-carboxylate), a thromboxane A2 synthase inhibitor, on changes in arachidonic acid metabolism were investigated in the lung of actively sensitized guinea pigs. Antigen challenge enhanced the production of thromboxane A2 as well as histamine and peptide leukotrienes in lung fragments. Exogenous leukotriene D4 also stimulated significant thromboxane A2 production in the non-sensitized lung in vitro. CS-518 was effective in preventing the thromboxane A2 production induced by either antigen or leukotriene D4, and the IC50 values were 90 and 7.5 ng/ml (320 and 27 nM), respectively. CS-518 markedly potentiated the production of prostaglandin E2 and I2 with slight inhibition of leukotriene formation, but indomethacin significantly stimulated leukotriene production. When CS-518 was administered orally, it induced long-lasting inhibition of thromboxane A2 production and potentiation of prostaglandin I2 production in guinea pig lung. Thus, CS-518 not only inhibited thromboxane production but also improved the change in arachidonic acid metabolism in the guinea pig bronchoalveolar tissue during allergic reaction in vivo as well as in vitro, which suggests amelioration of the asthmatic condition.

We investigated whether or not the liver dysfunction in patientst reated with troglitazone (TG) is related to polymorphism in UDP-glucuronosyltransferases (UGTs), which are partially responsiblef or TG metabolism. In the toxicologicasl tudy of TG using Gunn rats, which are hereditarily deficient in the UGT1 family, the metabolic profile of TG in Gunn rats was very similar to that of Wistar rats, the parent strain of Gunn rats, and no sign of the liver dysfunction was observed in both rats. UGTs involved in TG glucuronidation in rats and humans have been characterized. The experiments using liver microsomes of Gunn rats suggestedt hat the enzymer esponsible for glucuronidation in rats was UGT2B2, an androsterone UGT, by inhibition studies. In humans, contribution of UGT1A1 was estimatedto be about 30% of the total TG glucuronidation by UGTs, using human liver microsomes and recombinant UGTs. Other UGT1 and UGT2 enzymes seem to be responsible for the remaining 70% of TG glucuronidation. The multiplicity of UGTs involved in TG glucuronidation in humans may even allow patients lacking bilirubin UGT (UGT1A1) activity to metabolize TG to the glucuronide. These observation suggest that the polymorphism of UGT is not the reason for the liver dysfunction induced by the TG treatment.

Recent analysis of the structure-function relationship of human PTH-related peptide (hPTHrP) has led to the discovery that its direct inhibitory activity on osteoclastic bone resorption resides fully in the 107-111 sequence of the peptide, as assessed by a bone resorption assay using isolated rat osteoclasts. Here we report that hPTHrP-(107-111) is inactive in neonatal mouse calvariae in culture. hPTHrP-(107-111), at doses of 10(-12)-10(-6) M and incubation periods up to 96 h, did not affect either basal or agonist-stimulated 45Ca release from prelabeled neonatal mouse calvariae, while salmon calcitonin was a potent and powerful inhibitor of both basal and stimulated 45Ca release from bone. Moreover, salmon calcitonin, but not hPTHrP-(107-111), inhibited the increase in osteoclast number in hPTHrP-(1-34)-treated bones. Furthermore, hPTHrP-(107-139) also failed to inhibit 45Ca release and the hPTHrP-(1-34)-induced increase in osteoclast number in this organ culture model when tested under conditions identical to those for hPTHrP-(107-111). The addition of indomethacin to hPTHrP-(107-111)- or hPTHrP-(107-139)-treated bones was without effect, excluding the possibility that the direct inhibitory activity of these peptides on osteoclasts is ablated by a prostaglandin-mediated mechanism. Although the mechanism underlying the apparent inability of the carboxyl-terminal PTHrP fragments to inhibit osteoclastic bone resorption in neonatal mouse calvariae is unknown, it may involve the complex microenvironment of osteoclasts in intact bone, which contains a large variety of cell types other than osteoclasts.