An experimental study of selective intrahepatic biliary ablation with ethanol.

BACKGROUND: Few attempts have been made to investigate the feasibility of selective intrahepatic biliary ablation with absolute ethanol. METHODS: Through a catheter cannulated into the bile duct of the left lateral and median lobes (70% of total liver weight), 0.2 mL of absolute ethanol was injected into rats. RESULTS: The weight of the infused lobes decreased to less than 50% of the entire liver weight 14 days after treatment, while the weight of the noninfused lobes increased to 1.6-fold of the original value. This increase was associated with a markedly elevated Ki-67 labeling index. Both bile flow and bile acid excretion in the noninfused lobes significantly increased to more than twice the original values on Day 14. Histologically, the interlobular bile ducts of the infused lobes were destroyed. Ethanol also soaked through Glisson's capsule and destroyed hepatocytes, which were replaced by fibrous tissue and proliferating bile ductules without necrosis by Day 14. The portal veins and hepatic arteries supplying the infused lobes were structurally well preserved throughout the study period. CONCLUSION: Selective biliary infusion of ethanol can be performed safely without serious complications, achieving lobar ablation with contralateral hypertrophy of the liver.

Carbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver.

BACKGROUND AND AIMS: Liver is a major organ for heme detoxification under disease conditions, but its self-protective mechanisms against the toxicity are unknown. This study aimed to examine roles of carbon monoxide (CO), the gaseous product of heme oxygenase (HO), in ameliorating hepatobiliary dysfunction during catabolism of heme molecules in endotoxemic livers. METHODS: Vascular resistance and biliary flux of bilirubin-IXalpha, an index of HO-derived CO generation, were monitored in perfused livers of endotoxemic rats. Livers were perfused with HbO(2), which captures nitric oxide (NO) and CO, or metHb, a reagent trapping NO but not CO. RESULTS: In endotoxin-pretreated livers where inducible NO synthase and HO-1 overproduced NO and CO, HbO(2) caused marked vasoconstriction and cholestasis. These changes were not reproduced by the NO synthase inhibitor aminoguanidine alone, but by coadministration of zinc protoporphyrin-IX, an HO inhibitor. CO supplementation attenuated the events caused by aminoguanidine plus zinc protoporphyrin-IX, suggesting that simultaneous elimination of these vasorelaxing gases accounts for a mechanism for HbO(2)-induced changes. This concept was supported by observation that metHb did not cause any cholestasis; the reagent captures NO but triggers CO overproduction through rapid degradation of the heme by HO-1. CONCLUSIONS: These results suggest protective roles of CO against hepatobiliary dysfunction caused by heme overloading under stress conditions.

Angiodysplasia of the appendix.

Angiodysplasia of the gastrointestinal tract is thought to be one of the most common causes of lower gastrointestinal bleeding in the elderly, and, in the majority of cases, lesions are located in the cecum or ascending colon. The authors report an extremely rare case of appendicular angiodysplasia. A 76-yr-old woman was hospitalized with massive recurrent red anal bleeding. Selective superior mesenteric arteriography revealed an extravasation of contrast material from the appendicular artery, and this finding proved to be bleeding from an angiodysplasia of the appendix. An appendectomy was performed, and anal bleeding did not recur postoperatively. A review of the literature revealed this to be an extremely rare case of angiodysplasia.

Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver.

This study aimed to examine whether livers overexpressing heme oxygenase (HO)-1 could alter the vascular resistance through the vasorelaxing action of carbon monoxide (CO). The relationship among HO-1 expression, CO generation, and the vascular resistance was assessed in perfused rat livers pretreated with hemin, an inducer of HO-1. At 18 h after the hemin treatment, livers displayed marked increases in HO-1 expression in hepatocytes and venous CO flux and a reduction of the basal resistance. The reduction of the resistance in hemin-treated livers was canceled by administration of oxyhemoglobin, a reagent trapping both CO and nitric oxide (NO), but not by methemoglobin, which captures NO but not CO. Liposome-encapsulated oxyhemoglobin, which cannot access the space of Disse, did not cause vasoconstriction. Furthermore, these livers became less sensitive to endothelin-1, a vasoconstrictive peptide, than the untreated controls through mechanisms involving CO. On the other hand, at 12 or 24 h after the treatment when the HO-1 induction was not accompanied by CO overproduction, neither a decrease in the basal resistance nor vascular hyporeactivity to endothelin-1 was observed. These results suggest that CO overproduced in the extrasinusoidal compartment is a determinant of the HO-1-mediated vasorelaxation in the liver.

Carbon monoxide-mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver.

This study aimed to examine whether acetaminophen (AAP), an anti-inflammatory agent producing hepatocellular damages with its overdose, evokes hepatocellular dysfunction through mechanisms involving carbon monoxide (CO) generated by heme oxygenase (HO). In perfused rat livers, CO and bilirubin were determined in venous perfusate and bile samples as indices of heme degradation. Biliary excretion of transportally injected horseradish peroxidase was also determined to assess paracellular junctional permeability and vesicular transport across hepatocytes. AAP at 20 mmol/L induced a transient choleresis, followed by a reduction of bile output. Under these circumstances, the release of CO and bilirubin IXalpha, terminal products of the HO-mediated heme degradation, became 2. 5-fold greater than the control. The rate of CO production appeared stoichiometric to the degradation rate of microsomal cytochrome P-450. Mechanisms for the AAP-induced cholestasis involved an increase in the junctional permeability that coincided with a reduction of vesicular transport across hepatocytes. Clotrimazole, a cytochrome P-450 inhibitor, or zinc protoporphyrin IX, an HO inhibitor, but not copper protoporphyrin IX, which did not inhibit HO, attenuated these AAP-induced changes. Furthermore, administration of CO at concentrations comparable with those induced by AAP elicited a marked elevation of the paracellular junctional permeability concurrent with a reduction of transcellular vesicular transport, mimicking effects of the AAP administration. Thus, CO serves as a putative regulator of hepatocellular function that is overproduced through acute heme degradation during xenobiotic transformation.

Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver.

Although discontinuous total parenteral nutrition (d-TPN) has recently been favored for clinical use over continuous total parenteral nutrition (c-TPN) to ameliorate liver dysfunction, mechanisms for the protection against postoperative liver dysfunction remain unknown. This study aimed to examine differences in mitochondrial function in d-TPN- and c-TPN-pretreated livers during ischemia-reperfusion. Rat livers pretreated with d-TPN or c-TPN were perfused with Krebs-Ringer buffer and were exposed to 25% low-flow hypoxia followed by reperfusion. Intrahepatic mitochondrial membrane potential (triangle up) and cell viability were assessed by dual-color digital microfluorography using rhodamine 123 (Rh123) and propidium iodide (PI), respectively. In response to hypoxia, livers pretreated with c-TPN, d-TPN, and an ordinary chow diet exhibited a significant triangle up reduction among the entire lobules. Upon reperfusion, the regional triangle up values further decreased in the c-TPN liver, whereas those in the d-TPN-treated or chow-treated livers displayed a rapid recovery toward the control levels. The severity of cell injury did not differ among the groups, showing that the reperfusion-induced triangle up drop in the c-TPN-pretreated liver is not a consequence of cell injury. Differences in the triangle up drop among the groups appear to occur irrespective of those in the glycogen storage, because the livers undergoing d-TPN display a marked triangle up recovery even when reperfused at the end of a fasted state. These results indicate that c-TPN, but not d-TPN, jeopardizes mitochondrial re-energization and suggest that a circadian pattern of the TPN serves as a potentially beneficial strategy to reduce the risk of postischemic mitochondrial dysfunction in the liver.

CT diagnosis of intraductal papillary neoplasm of the pancreas in comparison with histopathologic findings.

CONCLUSION: The existence of excrescent nodules in the cystic component of intraductal papillary neoplasms (IPN) on computed tomography (CT) is useful for differentiating between malignant and benign lesions. BACKGROUND: We sought to evaluate the ability of CT to differentiate malignant from benign lesions in IPN of the pancreas. METHODS: CT findings in 20 cases of IPN (11 benign and 9 malignant lesions) were compared with histopathological findings from subsequent surgery. RESULTS: The size of the cystic portion on CT did not correlate with the malignant potential of the lesion. Seven (78%) of 9 malignant lesions had excrescent nodules on CT, whereas 1 (9%) of 11 benign lesions did.

CT evaluation of small polypoid lesions of the gallbladder.

BACKGROUND/AIMS: The ability of CT to differentiate small polypoid lesions of the gallbladder was evaluated. MATERIAL AND METHODS: CT followed by cholecystectomy was performed in 20 patients with small polypoid lesions (< or = 20mm) of the gallbladder measured by preoperative ultrasonography. Detectability of the lesions on both unenhanced and enhanced CT, and the configuration and density of the polypoid lesions on enhanced CT were evaluated in comparison with histopathology. RESULTS: Unenhanced CT detected 8 of 20 polypoid lesions (40%), whereas enhanced CT detected all lesions. All the cholesterol polyp (n = 9) and hyperplastic polyp (n = 2) were not detected on unenhanced CT. Configurations of the polypoid lesions were classified into three types; pedunculated, sessile, and mass forming type. All of cholesterol polyp and hyperplastic polyp were demonstrated as pedunculated type, and adenomyomatosis (n = 2) as mass forming type in all lesions, respectively. Two of adenoma were seen as pedunculated type in one and as mass forming type in the other. Adenocarcinoma (n = 5) was depicted as sessile type in four lesions and as pedunculated type in one. The density of the lesions compared with the liver parenchyma on enhanced CT was not specific. CONCLUSIONS: The configuration of polypoid lesions depicted on enhanced CT and visualization of them on unenhanced CT are helpful in differentiating neoplastic lesions which should be resected from other benign lesions.

Clinicopathological Characteristics of Non-palpable Breast Cancer Presenting as Axillary Mass.

We present the clinical and pathological findings of non-palpable breast cancer presenting an axillary mass in 8 patients at the National Cencer Center Hospital and in 89 cases previously reported in Japan. Mammography and ultrasonography were positive in 26.4% and 26.8% of cases, respectively. 82(94.3%) of 87 patients underwent mastectomy as a local control. In 19(30.6%) of 62 patients, the pathological size of the lesion was less than 5 mm. In 15 patients primary tumors could not be identified pathologically. The number of nodes involved ranged from 1-55 with a median of 5. There was no significant correlation between the number of involved nodes and the size of the axillary mass, nor between the number of involved nodes and the pathological size of the primary breast lesion. The 5-year survival rate was 59.4%. There was no statistically significant difference in 5-year survival rates between occult breast cancer and palpable breast cancer in each nodal category. Only the number of involved nodes was a reliable prognostic factor. Unlike palpable breast cancer, the pathological size of the primary tumor was not a predictor of prognosis. In this respect, the biological behavior of occult breast cancer is quite different from that of palpable breast cancer.

Multiple angiomyolipomas of the liver (case report).

Angiomyolipoma of the liver is an extremely rare type of tumor and reported cases are few and far between. This case study reports on a 37-year-old woman who suffered from multiple angiomyolipomas of the liver. Ultrasonography (US) and computed tomography (CT) initially revealed the existence of two tumors located in the right lobe of the liver and measuring 20 x 15 mm and 8 x 7 mm in size. The patient underwent partial resections of the liver. Histopathologic examination of both the resected specimens revealed angiomyolipoma. This is the first reported case of multiple angiomyolipomas of the liver. Furthermore, the lesions of our case study were small in size and rich in fat component. Under such conditions, preoperative examination resulting in an angiomyolipoma diagnosis is difficult even with the aid of imaging modality and needle biopsy techniques.