Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Hepatic arterial infusion chemotherapy using percutaneous catheter placement with an implantable port: assessment of factors affecting patency of the hepatic artery

OBJECTIVE: To assess the factors affecting patency of the hepatic artery during hepatic arterial infusion chemotherapy (HAIC) with an implantable port system inserted percutaneously. PATIENTS AND METHODS: Ninety patients with malignant hepatic tumours were given HAIC using percutaneous catheter placement. An end-hole catheter was inserted into the hepatic artery (conventional method) in 41 patients. An end-closed and side-hole catheter was used in 49 patients, in which the catheter tip was fixed in the gastroduodenal artery and the side hole was placed in the common hepatic artery (fixed catheter-tip method). The patency of the hepatic artery was evaluated with computed tomography (CT) arteriography using the implantable port system and angiography. Then, the factors affecting hepatic arterial patency were analysed. RESULTS: Hepatic arterial occlusion was observed in 15 patients (17%). The overall patency of the hepatic artery was 86.9%, 78.4% and 51.5% at 6 months, 1 year and 2 years, respectively. The patency rate of the hepatic artery was significantly higher in patients with catheter placement using fixed catheter-tip method than those using conventional method (P = 0.01), and in patients without transcatheter arterial chemoembolization (TACE) prior to catheter placement than those with prior TACE (P = 0.01). When the variables affecting patency of the hepatic artery were studied together by multivariate analyses, the important factors were the method of catheter placement and the presence or absence of prior TACE. CONCLUSION: We consider that it is important for long-term patency of the hepatic artery during HAIC to use fixed catheter-tip method for percutaneous catheter placement instead of conventional method, and to select patients without prior TACE.     

New monitoring strategies during shock

Disturbances in tissue perfusion and oxygenation are known to occur during shock. To treat shock properly, it is necessary to have a good understanding of its pathophysiological characteristics. By monitoring cardiac output and oxygen delivery, we can assess the systemic oxygen transport to the tissues, while mixed venous oxygen saturation provides an index of the systemic oxygen balance between oxygen delivery and consumption. However, because a redistribution of blood volume and flow occurs in shock, the use of systemic monitoring alone does not allow an assessment of regional oxygenation in the various organs. Monitoring of hepatic and jugular venous oxygen saturation enables us to assess the adequacy of regional tissue oxygenation in the liver and brain, respectively, while monitoring intramucosal pH (pHi) is useful not only to assess regional oxygenation in the splanchnic organs, but also to predict complications and to evaluate the clinical outcome. The use of near-infrared spectroscopy may allow simultaneous, noninvasive monitoring of regional tissue oxygenation and energy levels. There exists a wide variety of viable options for the monitoring of shock, both systemically and regionally. This increases the chances of successful treatment.     

Prognostic Significance of Proliferating Cell Nuclear Antigen (PCNA) in Squamous Cell Carcinoma of the Esophagus

Proliferating cell nuclear antigen (PCNA) has been shown tobe of prognostic significance in some gastrointestinal tumors.Immunohistochemical analysis was performed to determine whetherPCNA is useful for predicting the outcome of patients with squamouscell carcinoma of the esophagus. Using a mouse monoclonal antibody,PC 10, the expression of PCNA was studied in resected squamouscell carcinomas of the esophagus from 59 patients who had undergonecurative esophagectomy. None had received any preceding therapy.The proliferation rate was assessed in terms of the percentageof the PCNA-positive nuclear area relative to the total areaof cancer nuclei using a cell analysis system (CAS). Clinicopathologicalvariables including PCNA staining were assessed in relationto prognosis. Survival rate was obtained by the Kaplan-Meiermethod. The PCNA indices (percentage of the positive nucleararea) of the tumors varied from 4.4% to 96.2%. Among the clinicopathologicalvariables, only tumor size (5 cm) and depth of invasion werecorrelated significantly with PCNA index (P<0.05). Microscopically,PCNA was stained in non-keratinized cells but not in keratinizedcells. However the histological grade was not correlated withPCNA index. The survival rate was significantly worse in patientswith high PCNA indices (40%) than in those with low indices(<40%) (P<0.05). However, multivariate analysis revealedthat PCNA index was not an independent prognostic factor.     

Delirious episodes induced by intravenous administration of clomipramine associated with an acute increase in its plasma concentrations

The aim of this paper is to describe two cases of clomipramine-induced delirium. One 61-year-old and one 67-year-old female depressive patients became delirious after beginning intravenous clomipramine injections in addition to their oral clomipramine administrations. Their plasma levels of both clomipramine and its metabolite, desmethylclomipramine, were acutely increased about twofold during delirium. The intravenous clomipramine administrations were discontinued. Their delirious state was gradually improved after stopping the intravenous clomipramine administrations. These findings suggest that acute increases of plasma levels of clomipramine and desmethylclomipramine after intravenous clomipramine injections might be related to the appearance of the delirious episodes.     

Treatment by corticosteroid and plasma exchange in 5 cases of renal cholesterol embolic disease

Cholesterol arterial embolization is a systemic disease resulting from cholesterol crystal embolization to multiple organs, including the kidney, skin, brain, eye, gastrointestinal tract and extremities. In general, it is associated with high morbidity and mortality, but no optimal treatment has yet been developed. In this paper, we report five patients with cholesterol atheroembolic renal failure. In three of the five patients, combined therapy with corticosteroids and plasma exchange was performed. The three patients survived. On the other hand, the two remaining patients died of multifactorial causes. In this report, the literature on steroid therapy for cholesterol atheroembolic renal disease is reviewed and the efficacy of combined therapy by use of corticosteroids and plasma exchange is evaluated.     

Regression of a presumed meningioma with the antiestrogen agent mepitiostane. Case report

This 68-year-old woman underwent a distal gastrectomy for gastric cancer in August 1994. A presumed meningioma of the falx was found incidentally on a staging examination of the gastric cancer, but the meningioma was not treated with surgery. Instead, after gastrectomy the patient received tegafur as adjuvant chemotherapy until February 1996, when she was readmitted to the hospital because of loss of appetite and emaciation but with no recurrence of the gastric cancer. A computerized tomography scan obtained during this second admission showed no change in the meningioma. To improve her general condition, tegafur was discontinued and she was started on a course of the antiestrogen agent mepitiostane. Administration of mepitiostane for approximately 2 years resulted in a marked regression (73%) of the meningioma. This is the first reported case of a presumed meningioma that regressed as a result of use of the antiestrogen agent mepitiostane.     

Local epinephrine release in the rabbit myocardial interstitium in vivo

Although several investigations have suggested cardiac epinephrine (Epi) release, local Epi release in the myocardial interstitium in vivo has not been measured. Using cardiac microdialysis in the rabbit, we measured dialysate Epi and norepinephrine (NE) concentrations as indices of myocardial interstitial Epi and NE levels, respectively. Exocytotic release induced by local administration of KCl (100 mM) through the dialysis probe increased Epi to 24.2 +/- 13.2 pg/ml from a control value of 3.2 +/- 3.6 pg/ml (P < 0.01, n = 6). Non-exocytotic release induced by the local administration of tyramine (10 microg/ml) also increased Epi to 34.6 +/- 15.3 pg/ml (p < 0.05 from control, n = 6). We conclude that Epi can be released via both exocytotic and non-exocytotic release mechanisms from the heart.