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After many changes, Buerger's disease stands as an independent clinicopathologic entity, but a better understanding of Buerger's disease has been impeded by the lack of unanimous diagnostic criteria of the disease. Since specificity of Buerger's disease is characterized by peripheral ischemia of an inflammatory nature and with a self-limiting course, diagnostic criteria of Buerger's disease should be discussed from clinical point of view. Our clinical criteria for the diagnosis of Buerger's disease are: (1) smoking history; (2) onset before the age of 50 years; (3) infrapopliteal arterial occlusions; (4) either upper limb involvement or phlebitis migrans; and (5) absence of atherosclerotic risk factors other than smoking. Confident clinical diagnosis of Buerger's disease may be made only when all five requirements have been fulfilled. A set of strict and well-defined clinical diagnostic criteria is essential for any study of Buerger's disease to ensure the homogeneity of the selected patient population for valid comparisons.

We report an initial case of pyothorax-associated pleural lymphoma (PAPL) in which the level of interleukin 6 (IL-6) was remarkably high in the pleural fluid contaminated with tumor cells; at the same time Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected in the lymphoma cells by in situ hybridization. These findings suggest the possibility that EBV-transformed B cells proliferated in the focal cytokinemic condition caused by long-standing chronic inflammation of the pleura and give us a clue to the lymphoma genesis of PAPL.

Twenty patients with aplastic anemia underwent long-term administration (10 weeks) of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses from 50 to 800 micrograms/m2 per day by intravenous infusion or 50 to 100 micrograms/m2 per day by subcutaneous injection and re-combinant human erythropoietin (rhEPO) in doses ranging from 2000 to 8000 IU/m2 per day by intravenous injection three times a week for at least 4 weeks. The goal was to evaluate whether therapy ameliorated pancytopenia in these patients as well as to determine its safety. All assessable patients showed a substantial increase in absolute neutrophil count, with a recovery of myeloid components (granulocyte series) in the bone marrow, after 2 to 10 weeks of treatment. An increase > 1.5 g/dL in hemoglobin (Hb) concentration was observed in 2 patients (10%). A decrease > 50% in red cell transfusion requirement was observed in 2 patients (10%). Seven patients showed recovery of neutropenia, anemia, and platelet count. In addition, there was no serious infection before or during therapy, and side effects were mild. Of the 20 patients, 3 showed a dramatic improvement in severe anemia after 10 weeks of treatment accompanying a recovery of erythroid components in the bone marrow. They no longer require red cell transfusions and have had normal Hb concentrations and normal ferrokinetics. These results indicate that long-term administration of rhG-CSF and rhEPO may benefit some patients with aplastic anemia. Further studies will be necessary to elucidate the mechanism by which rhGCSF and rhEPO stimulate hematopoiesis and improve hematologic abnormalities in these patients.

Using an ultrasonic Doppler system, we prospectively studied the changes in portal venous flow (PVF) following percutaneous transhepatic biliary drainage (PTBD) and evaluated the correlation between PVF and liver function in 10 patients with obstructive jaundice. The patients were divided into two groups according to their rate of decrease in serum bilirubin ("b"). Group A comprised 5 patients with a "b" of less than -0.1, while group B consisted of 5 patients who did not meet this criterion. The mean PVF increased following PTBD (P < 0.01). The increase in PVF was due to an increase in the maximum velocity of the portal vein (Vmax). The rate of increase in the Vmax in group A was significantly higher than that in group B on both the 7th and 14th postdrainage days (P < 0.05). The rate of increase in the Vmax correlated significantly with the rate of decrease in the serum bilirubin concentration (P < 0.01). Based on the above findings, we conclude that measuring the Vmax by Doppler ultrasonography is useful in evaluating the liver function in patients with obstructive jaundice.

Telomerase activation is important for carcinogenesis. However, the timing and magnitude of the activation during cancer development are unknown. In this study, a new PCR-based method for measuring telomerase activity was developed and shown to be very useful for quantitative analysis of human telomerase. Using this assay, blood or bone marrow cells from healthy donors, and patients with chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) were examined as to their relative activity. Telomerase activity present in normal peripheral blood cells was generally very low. However, significant activity was detected occasionally in samples derived from younger healthy donors. Striking telomerase activation was observed at the time of the blastic crisis in CML: no samples from chronic phase cases showed significant activity, while all cases with a well established crisis showed strong activity. Most AML cases were telomerase-positive. Quantitative analyses revealed that the relative titer varied among the AML patients, from as low as found in normal cells to as high as found in cell lines. However, a tendency that the activity was higher in relapsed cases than in fresh ones was suggested. In summary, telomerase was activated during the progression of the clinical stages in leukemias. This observation suggests that shortened telomeres and increased telomerase activity might be necessary for cancer cells to undergo clonal evolution towards more malignant phenotypes in advanced stages.

Background Aims: Obstructive jaundice is a factor which effects hepatic blood flow and the relative contribution of the hepatic arterial flow and portal venous flow. In this study, and were measured in conscious dogs and the influence of biliary obstruction and drainage was investigated., Material and Methods: Hepatic arterial flow (HAF) and portal venous flow (PVF) after biliary obstruction and subsequent drainage were continuously measured in conscious dogs using implantable transit time ultrasonic flow-meters., Results: After biliary obstruction hepatic arterial flow rapidly increased compared to the pre-obstructed values(p < 0.01), while portal venous flow was significantly decreased (p < 0.01). Total hepatic blood flow was initially increased (p < 0.01) until 2 hours after obstruction. It then decreased gradually. After 2 weeks, it was less than the pre-obstructed values, but this was not significant. Biliary drainage was performed after 2 weeks. Hepatic arterial flow subsequently decreased (p < 0.01) and portal venous flow increased (p < 0.05). Blood flow did not change., Conclusion: Biliary obstruction resulted in significant changes in liver circulation. Biliary drainage facilitated recovery from these changes.

We studied the effects of lipid emulsions for total parenteral nutrition (TPN) on hepatic regeneration after partial hepatectomy in rats. Daily energy intake was maintained at 1172 kJ.kg-1.day-1 while the percentage of nonprotein energy sources was changed. Animals were divided into four groups: lipid-free, 10%-lipid, 20%-lipid, and 40%-lipid. TPN was continued for up to 1 wk. The content of proteins, the ratio of proteins to triglycerides, and the yield of mitochondrial protein in the remnant liver 7 days after partial hepatectomy were larger in animals receiving TPN with lipids than in those receiving lipid-free TPN, whereas the amounts of triglycerides and cholesterol in the liver of the latter animals were larger. The degree of fatty infiltration of the hepatic lobule was most distinct in the lipid-free group. Furthermore, activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase in the serum tended to be higher in the lipid-free group. Phosphorylating ability of mitochondria in the regenerating liver 7 days after partial hepatectomy was not different among the four groups; however, the highest value for the respiratory control index was obtained in the 40%-lipid group. The application of a lipid emulsion to TPN is useful for hepatic regeneration after partial hepatectomy; however, the ideal concentration of lipids in TPN awaits further investigation.

A 53-year-old woman presented with abdominal discomfort and was diagnosed using ultrasonography to have an abdominal aortic aneurysm. Aortography revealed a saccular aneurysm 4 cm in diameter of the infrarenal aorta with a 'string of beads' appearance. The renal and other visceral arteries appeared to be normal. Resection and graft replacement was performed because of the possibility of rupture. Histological examination of the specimen revealed the most common type of fibromuscular dysplasia, namely medial fibroplasia. Fibromuscular dysplasia should be considered as a potential cause of abdominal aortic aneurysm in female patients with no atherosclerosis risk factors.

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor-suppressor genes. Investigation of genomic instability of microsatellites has indicated a new mechanism for human carcinogenesis in hereditary nonpolyposis colorectal cancer and sporadic cancer and this instability has been shown to be related to inherited predisposition to cancer. This study was conducted to determine whether such microsatellite instability is associated with the evolution of chronic myelogenous leukemia (CML) to the blast crisis. Nineteen CML patients clinically progressing from the chronic phase to accelerated phase or blast crisis and 20 other patients in the CML chronic phase were studied. By polymerase chain reaction assay, DNAs for genomic instability in five separate microsatellites in chromosome arms 5q (Mfd27), 17p (Mfd41), 18q (DCC), 3p (CI3-9), and 8p (LPL) were examined. Differences in unrelated microsatellites of chronic and blastic phase DNAs in 14 of 19 patients (73.7%) were demonstrated. Somatic instability in five microsatellites, Mfd27, Mfd41, DCC, CI3-9, and LPL, was detected in 2 of 19 (10.5%), 8 of 19 (42.1%), 11 of 19 (57.9%), 4 of 17 (23.5%), and 4 of 17 (23.5%) cases. In 10 of 19 cases (52.6%), genetic instability in at least two of five microsatellites was observed and was categorized as replication error (RER+) phenotype. CML evolution cases with myeloid, lymphoid, and mixed phenotypes and the blast crisis and accelerated phase showed somatic instability in a number of microsatellites. No alterations in leukemic cells at the chronic phase could be detected in any microsatellites. These data indicate instability of microsatellites (RER+) but not familial predisposition to possibly be a late genetic event in the evolution of CML to blast crisis. In the microsatellite of the DCC gene, complicated alterations in band patterns caused by instability as well as loss of heterozygosity (LOH) were observed in 13 of 19 cases (68.4%): instability in 9 cases, instability plus LOH in 2 cases, and only LOH in 2 cases. These highly frequent alterations in microsatellites, including instability and LOH, suggesting that secondary events due possibly to loss of fidelity in replication and repair machinery may be significantly associated with CML evolution.

One of the pathophysiological features in Buerger's disease, i.e. thromboangiitis obliterans (TAO), contains a sympathetic contribution which relates to vasospastic phenomenon. The purpose of this study is to clarify sympathetic mechanisms in TAO. Muscle sympathetic nerve activity (MSA) was recorded using a microneurographic technique in patients suffering from TAO. The cold pressor test (by immersing the hand of the subject into ice cold water) was used as a test to examine the sympathetic responsiveness to local cold stimulus. The basal level of the MSA in the TAO group was lower than that in the control group (control group vs. TAO group: 39.8 +/- 12.8 bursts/min vs. 26.1 +/- 12.1 bursts/min in burst rate, P < 0.05, 61.8 +/- 8.3 bursts/100 heart beats vs. 39.5 +/- 22.3 bursts/100 heartbeats in burst incidence, P < 0.05). The responsiveness of MSA to the cold pressor test in the TAO group was higher than that in the control group (TAO group vs. control group: 385 +/- 191% total MSA vs. 198 +/- 156% total MSA, P < 0.05). We directly demonstrated higher responsiveness of MSA to the local cold stimulus in patients with TAO. This hyperresponsive MSA might contribute to the pathophysiologic feature in TAO.

Buerger's disease is characterized by peripheral arterial occlusion of the extremities in young male smokers. In true Buerger's disease lesions rarely occur in the proximal arteries. The incidence of the disease is low in Europe and the USA, but its management remains a major problem for vascular surgeons in Asia where its incidence is higher. Aetiology of the disease remains unknown, but there is a clear relationship between tobacco abuse and its occurrence or recurrence; complete cessation of smoking renders the disease benign. Despite a high incidence of digital gangrene or ulceration, a functional foot or hand can generally be preserved because of the good healing potential of the trophic lesions. Specificity of the disease is characterized by peripheral ischaemia of an inflammatory nature and with a self-limiting course. The clinical term Buerger's disease is preferred to the pathological term thromboangiitis obliterans. Diagnosis is based on knowledge of the natural history of the disease, which aids prognosis and the decision to undertake surgical or conservative management. Treatment of Buerger's disease should avoid premature, possibly unnecessary, surgery. The condition is no longer a disease of misconceptions; its diagnosis and management should be based on a clear understanding of the pathophysiology.

An interportal communicating branch was found at the hepatic bifurcation in two (2.4%) out of 83 hepatectomized cases of carcinoma of the biliary tract. The first case was a 54-year-old male with intrahepatic bile duct cancer, and the second was a 64-year-old female with gallbladder cancer. No other anatomical anomalies were found in the portal vein, hepatic artery, or biliary tract.

A 42-year-old man, born in Chiba prefecture, was admitted to our hospital because of multiple nodular shadows on chest X-ray film and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody. The pulmonary lesion was diagnosed as T-cell lymphoma by open lung biopsy. There has been only one previous report of T-cell lymphoma showing multiple nodular shadows on chest X-ray. The elevated titer of HTLV-I antibody strongly suggested that the present case was one of adult T-cell lymphoma.

The frequency of a visceral mycosis grows definitely higher with an immunocompromised host. Invasive fungal infection can be controlled by means of development of early diagnosis and antifungal therapy. In these types of cases, it is difficult to establish an antemortem diagnosis of invasive pulmonary aspergillosis and most of them were diagnosed postmortem. A patient was diagnosed as aspergillosis from the clinical and serological features. This patient underwent successful therapy during remission induction therapy of acute myelocytic leukemia (AML). A 26-year-old male was admitted to our hospital because of leukocytosis with a diagnosis of AML made by reviewing peripheral blood smears and bone marrow aspirate. After remission induction therapy, he was still febrile in spite of treatment with a broad spectrum antibiotics and empiric therapy of fluconazole. Unfortunately shadowing appeared on the chest radiograph and aspergillus antigen was detected from the serum and the sputum. Consequently, the patient who suffered from invasive pulmonary aspergillosis was diagnosed and treated with intravenous amphotericin B and flucytosine. The radiological shadow improved but AML relapsed, therefore, remission induction therapy of AML was started again but he died of sepsis caused MRSA. In the postmortem histopathological examination the lung tissues, the hyphae could not be confirmed while, in immunohistochemical examinations of the lesion at the left S8, aspergillus antigens were detected around the small necrotic lesions and in the polymorphologic giant cells. We emphasize that invasive pulmonary aspergillosis is very difficult to diagnose whereas active examinations and clinical early diagnosis may lead to more effective therapy and the prognosis.

A case of cholangiocellular carcinoma in the caudate lobe with intraluminal growth in the extrahepatic bile duct is reported. The main tumor in the caudate lobe was detected by computed tomography and angiography, and two intraluminal tumors at the hepatic hilus and at the root of the right posterior segmental duct were well demonstrated by cholangiography and percutaneous transhepatic cholangioscopy. Independent total caudate lobectomy with bile duct resection was performed. Cholangiocellular carcinoma of the liver with intraluminal growth in the extrahepatic bile duct is very rare and has not been reported in the literature. Independent caudate lobe resection requires a rather complicated technique. However, this method has the advantage of reducing to a minimum the hepatic volume to be resected, and is useful for poor-risk patients or for cases with localized carcinoma at the hepatic hilus.

Sphincter of Oddi motility was measured in 55 gallstone patients either through the sinus tract of percutaneous transhepatic biliary drainage or through the T tube. The influence of cholecystectomy and gastrectomy on the sphincter of Oddi was analyzed by comparing responses in patients with or without surgery to the administration of cerulein and the ingestion of dry egg yolk. When comparing cholecystectomized patients to nonsurgical subjects, cholecystectomy revealed no influence on the response to cerulein and feeding. Both groups showed relaxation of contraction waves after provocations. On the other hand, two thirds of the postgastrectomy patients showed an acceleration in the contractions of the sphincter of Oddi after provocations (one third showed no change), while all of the nongastrectomy group saw the disappearance of the wave after cerulein administration and 83% revealed complete suppression of the wave after feeding. It is suspected that this paradoxical response to CCK on the sphincter of Oddi is a lithogenic factor after gastrectomy.

A 61-year-old male patient with intrahepatic cholesterol stone is reported. Stones were detected in the anterior superior lateral subsegment (S8ab) of the right lobe with bile duct stenosis, the lateral anterior segment (S3) of the left lobe, and the left caudate lobe (S11). Partial hepatectomy including S8ab, S3 and S11 was performed to remove all stones. Atrophy of S8ab was diagnosed by CT, and PTP clarified the patency of the subsegmental portal vein (P8ab). This is a rare case with cholesterol intrahepatic stone with regional bile duct stenosis and subsegmental atrophy of S8ab of the liver.

We report an unusual case of a large inferior mesenteric-caval shunt in a 25-year-old man without cirrhosis with hypoproteinemia and hypochromic anemia. In this large shunt the direct communication was between the inferior mesenteric vein and the internal iliac vein. Hemodynamic change as a result of the shunt was thought to cause his present clinical problems and future portosystemic encephalopathy. Percutaneous transcatheter embolization of the shunt with fibrin glue was performed through the internal iliac vein, and this offered amelioration of hypoproteinemia and reduction of serum ammonia levels without any complications. An interventional radiologic approach instead of surgical ligation should be attempted for portosystemic shunts, and fibrin glue, as well as coils or a detachable balloon, is also valuable as an embolizing material.

The most characteristic pathophysiologic change in Buerger's disease or thromboangiitis obliterans (TAO) is considered the breakdown of microcirculation in the extremity, but this has not yet been proven. The purpose of this study is to examine the damage of microcirculation in TAO objectively, by means of intra-arterial injection of two kinds of radioisotope. In 7 TAO and 4 infrainguinal arteriosclerosis obliterans (ASO) patients, thallium 201 chloride (201Tl) and 99mTc macroaggregated human serum albumin (99mTc-MAA) were administered through bilateral common femoral artery injections. In the planar image of the foot, rectangular regions of interest (ROIs) were placed on the foot muscles and toes. Normalized counts of 99mTc-MAA in each ROI were divided by that of 201Tl, and the result was defined as the microcirculation damage index, based on their different kinetics. The damage index of the foot muscle was not different between ASO and TAO, but that of the toe was lower in TAO than ASO patients. Lumbar sympathectomy was performed in 5 TAO patients, but it did not improve the damage index. It is concluded that there is breakdown of the microvascular defense system from the beginning of the disease, and critical ischemia make the regional cell function deteriorate as if a precursor to a trophic lesion. Lumbar sympathectomy did not immediately improve microcirculation.

To elucidate the clinical significance of perineural invasion on bile duct cancer, a clinicopathologic study was performed on 70 resected patients with bile duct carcinoma. The overall incidence of perineural invasion in the resected specimen was 81.4%. There seemed to be no correlation between perineural invasion and site, size of the tumor, and lymph node metastasis. A significant correlation was observed, however, between macroscopic type, microscopic type, depth of invasion, and perineural invasion. Perineural invasion index (PNI) was defined as the ratio between the number of nerve fibers invaded by cancer and the total number of nerve fibers with and without cancer invasion. Perineural invasion index was significantly higher at the center compared with the proximal and distal part of the tumor (p less than 0.001). The 5-year survival rate for patients with perineural invasion was significantly lower (p less than 0.05) than that for those without perineural invasion (67% versus 32%).

The case of a mucin-producing intrahepatic cholangiocellular carcinoma in a 73 year-old-man is presented. A tumor originating in the right posterior inferior segment of the liver was found to be invading the right posterior and anterior bile ducts, and the hepatic hilus. Extensive superficial spread was observed in the entire posterior segmental bile duct extending to the hepatic hilus. Mucin produced and excreted by the tumor was retained in the common hepatic and common bile duct. The diagnosis in this case was suggested by percutaneous transhepatic aspiration of mucinous bile, and was confirmed by utilizing the techniques of ultrasonography, percutaneous transhepatic cholangiography, computed tomography and angiography. Curative surgery, which included right hepatic lobectomy with total caudate lobectomy and bile duct resection, was performed. Biliary continuity was maintained by left hepaticojejunostomy using a Roux-en-Y jejunal loop. The histological diagnosis was mucin-producing papillary adenocarcinoma originating in the right posterior inferior segment of the liver. Postoperative recovery was very good and the patient has now been enjoying a good active social life for the last 20 months with no signs of tumor recurrence. This case report discusses the unusual growth pattern of a mucin-producing intrahepatic cholangiocellular carcinoma involving the hepatic hilus, and suggests rational surgical treatment.

A 44 year-old woman with a family history of abdominal aortic aneurysm (AAA) underwent resection of an AAA. Histological examination revealed a lack of elastic fibers of the media and a diminished content of smooth muscle cells. A congenital hypoplasia of the aortic media was postulated as the etiology of this AAA. This condition may represent an aortic variety of medial defect observed in intracranial berry aneurysms, and be associated with a hereditary predisposition to AAAs.

In order to discover the effect of external biliary drainage on liver regeneration, we have produced a model system carrying cannula in the common bile duct of rat liver and examined the regeneration capacity of liver after partial hepatectomy under various conditions. Previously we have shown that hepatic cells proliferate by obstructive jaundice alone without partial hepatectomy [Terasaki et al; Jpn J Cancer Res 1991;82:170-175]. In the present study, we showed that DNA polymerase-alpha was induced by partial hepatectomy of rats suffering from obstructive jaundice and the induced level was similar to that of the normal regenerating liver. The level of DNA polymerase-alpha activity corresponded well to the liver regeneration capacity estimated by mitotic index. Contrary to our expectation, external biliary drainage for obstructive jaundice markedly suppressed the regeneration capacity of the remaining liver which was estimated by DNA polymerase-alpha activity, mitotic index and [3H]thymidine incorporation. The suppression may be due to the external biliary drainage itself because the liver regeneration of normal rats without jaundice was also suppressed by the biliary drainage. These results suggest that the external biliary drainage seriously suppresses the regeneration capacity of liver at least at the early stage of obstructive jaundice.

A case of aneurysm of the extracranial internal carotid artery (ICA) caused by fibromuscular dysplasia (FMD) is reported. The patient also had an aneurysm of the contralateral intracranial ICA, but the renal arteries were normal. A review of the literature shows extracranial ICA aneurysms to be uncommon, with only 3% caused by FMD. The surgical management of such difficult lesions at the base of the skull is discussed.

Calmodulin has been identified in parathyroid cells and is thought to play an important role in the production or secretion of parathyroid hormone. However, a detailed investigation of calmodulin-binding proteins in parathyroid glands has not been conducted. In this study, we attempted to determine the presence of calmodulin-binding protein in human parathyroid adenoma by affinity chromatography. The eluted protein from a calmodulin-coupled Sepharose 4B column with EGTA was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis which revealed a major protein band of Mr 50,000. A Ca2+/calmodulin-dependent protein kinase activity was detected at the protein peak using dephosphorylated casein as a substrate. The 50 kDa band was identified as calcium/calmodulin-dependent protein kinase II (CaM-kinase II) by immunoblotting. The substrate specificity, pH dependency and affinity for calmodulin of this enzyme were identical to those of CaM-kinase II from rat brain. Also, the kinase activity was sensitive to KN-62, a specific inhibitor of CaM-kinase II. In total, 0.48 mg of this kinase was purified from 3 g human parathyroid adenoma.

We describe a 54-year-old asymptomatic male with carcinoma of the hepatic hilus. Elevated serum transaminases were detected during the annual medical examination. The diagnosis was confirmed by ultrasonography (US), computed tomography (CT), percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP). Curative surgery, which included right hepatic lobectomy with total caudate lobectomy, was performed. The resected specimen revealed a localized tumor in the right anterosuperior dorsal intrahepatic bile duct branch. The histological diagnosis was moderately differentiated tubular adenocarcinoma. The patient's postoperative recovery was smooth and he has remained in good health for 15 months after surgery without any signs of recurrence. This case report discusses the early diagnosis and rational surgical treatment for carcinoma of the hepatic hilus.

Diagnostic value of the cholangiography was studied for carcinoma of the biliary tract involving the hepatic hilus, and special attention was paid on the cholangiogram of the bile duct branches (B1) of the caudate lobe. Cholangiograms of B1 were compared with pathologic findings in 42 (27 bile duct carcinomas, 15 gallbladder carcinomas) of 43 cases of biliary tract carcinomas. Sixty-four of B1 in the 42 cases could be studied radiologically and histopathologically. The findings of the root of B1 were classified into 4 groups: group A, not stenotic; group B, short segmental stenosis; group C, long segmental stenosis and group D, poorly imaged. Carcinoma invasion was found in 6 of 18 of group B, and in 9 of 16 of group C. Carcinoma was confirmed near the root of B1 in the remaining 7 of the 16 group C. Carcinoma invasion was found in 20 of 21 of group D, and invasion was suspected in the remaining one. Carcinomas were found in the root of B1 in all cases of poorly imaged or long segmental stenosis of B1, and in 33% of short segmental stenosis of B1. Therefore caudate lobe resection should be performed for carcinoma of the biliary tract involving the hepatic hilus.

Although Buerger's disease is known to be closely related to smoking, no objective analysis of the smoke-associated problems has been performed. In this study, cotinine, the major metabolite of nicotine, was used as a sensitive marker to measure levels of active smoking and the exposure of nonsmokers to tobacco smoke because it has a relatively long half-life and because cotinine levels can be determined by noninvasive means in urine. According to urinary cotinine levels, 40 patients with Buerger's disease were classified as (1) smokers: those with urinary cotinine levels above 50 ng/mg creatinine; (2) passive smokers: those with levels between 10 and 50 ng/mg creatinine; and (3) nonsmokers who did not experience noticeable passive smoking: those with levels below 10 ng/mg creatinine. There were 10 smokers, 9 passive smokers, and 21 nonsmokers. The course of the disease, after the initial treatment at our hospital, was studied retrospectively. Seven of the 10 smokers, none of the 9 passive smokers, and 4 of the 21 nonsmokers experienced aggravation of the disease. Of the four nonsmokers who experienced aggravation, three had still been smokers and one had been exposed to tobacco smoke in the workplace at the time of relapse. There was a significant difference in the aggravation rate between the smokers' group and the other two groups. Among the smokers, the seven patients whose conditions worsened showed significantly higher cotinine levels than the three remaining patients who were in the stage of remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-nine patients with advanced carcinoma of the bile duct or gallbladder underwent combined portal vein and liver resection. Segmental excision of the portal vein was performed in 16 cases and wedge resection of the vessel wall in 13. The operative mortality rate was 17 per cent. The median survival for the 24 patients who left hospital was 19.8 months. Actuarial survival rates at 1, 3 and 5 years for all 29 patients were 48 per cent, 29 per cent, and 6 per cent respectively, whereas the median survival for 46 patients with unresectable carcinoma was 3 months and the 1 and 3-year actuarial survival rates were 13 per cent and zero respectively. This difference in survival times between patients undergoing hepatectomy with portal vein resection and those with unresectable carcinoma were statistically significant (P less than 0.01). Combined portal vein and liver resection is recommended as a reasonable surgical approach in selected patients with advanced carcinoma of the biliary tract.

Twenty-four patients with advanced carcinoma of the gallbladder and/or the bile duct underwent hepatopancreatoduodenectomy, that is, en bloc hepatic resection with pancreatoduodenectomy. They included 14 cases of gallbladder carcinoma, nine cases of bile duct carcinoma, and one case of double cancer of the gallbladder and the bile duct. Eleven kinds of hepatic lobectomy or segmentectomy with pancreatoduodenectomy were carried out, and the caudate lobe was also removed en bloc from 17 patients with carcinoma involving the hepatic hilus. Combined resection of the portal vein was performed in 11 patients, of the inferior vena cava in 2, and of the colon in 5, patients. Forty-four postoperative complications occurred in 22 patients (91.7%). The operative mortality rate was 12.5% (3/24). The median survival and the 2-year survival rate were 7.0 months and 17.9% for all 24 patients, including 3 operative deaths, or 11.0 months and 20.4% for 21 patients surviving hepatopancreatoduodenectomy, and 12.4 months and 20.8% for all 14 patients with gallbladder carcinoma, and 5.2 months and 14.8% for all 9 patients with bile duct carcinoma. The longest survivor died of recurrent tumors at 5 years and 7 months. Hepatopancreatoduodenectomy offered not only an unexpectedly long survival period, but also unexpected morbidity in some cases.

We reviewed 60 cases of biliary carcinoma with hilar bile duct stenosis which had received percutaneous transhepatic cholangio-drainage (PTCD). Of the 60 cases, nine were complicated with acute cholangitis (AC) and three with segmental acute obstructive suppurative cholangitis (S-AOSC). The incidence of cholangitis was 20%. Six patients with AC and three with S-AOSC underwent hepatic resection for carcinoma. As to preoperative management for cholangitis in these 9 cases, conservative chemotherapy was effective in only 2 cases, and additional PTCD or segmental introduction of the drainage catheter under PTCS were useful in 5 cases. The remaining 2 cases with S-AOSC needed urgent hepatic resection including suppurative hepatic segments after various interventional treatments. No significant difference was found in resectability, morbidity and mortality between the cholangitis group and non-cholangitis group. In conclusion, it is emphasized that postoperative outcome of biliary carcinoma with cholangitis will be improved by adequate PTCD and/or urgent hepatic resection.

To study the pathogenesis of chronic venous insufficiency (CVI), photoplethysmography and strain-gauge plethysmography were simultaneously performed in 84 patients. Of the 128 limbs studied, 24 were normal, 64 had primary varicose veins and 40 had post-thrombotic syndrome. Venography was also performed in all patients. The results of this study indicate that reflux in the superficial veins is the main pathophysiology involved in the development of CVI, though incompetence of the perforators and deep veins plays some role. In post-thrombotic syndrome, however, CVI is mainly a sequel of deep venous incompetence, the condition being complicated by incompetent perforators and superficial venous reflux.

Obstructive jaundice, produced by ligating the common bile duct, induced a transient DNA replication followed by cell proliferation in rat liver. At 48 h after the operation, DNA polymerase alpha activity started to increase and reached its maximum level (more than twice the control) at day 4. At day 7, the enzyme level had decreased to the control level. Pulse-labeling experiment using radioactive thymidine showed that the rate of DNA synthesis increased approximately 2.5-fold in the same pattern as that of DNA polymerase alpha. The mitotic index in hepatocytes also increased 10-fold at day 4 and then decreased. The proliferation of liver cells induced by obstructive jaundice mimics the regeneration of partially hepatectomized liver, although the response was slightly delayed and the proliferation was transient.

Laser-assisted anastomosis of medium-size vessels can be performed with satisfactory short-term patency. This study was undertaken to evaluate patency and structural integrity up to 1 year. An argon laser was used to make bilateral femoral arteriovenous anastomoses in 12 dogs compared to conventional suture method in another 8 dogs. These anastomoses were evaluated for patency and aneurysm formation at 1 hour; 1, 2, 4, and 8 weeks; and 12 months after surgery. All anastomotic sites were patent and without aneurysmal change or luminal narrowing at all harvesting intervals. Histologic examination revealed that within 1 month laser anastomotic sites were almost completely healed and without intimal hyperplasia. In suture anastomoses, foreign-body reaction remained evident up to 1 year. Use of the argon laser for medium size vessel anastomoses resulted in excellent patency without aneurysm formation or intimal hyperplasia even in the long term. These data suggest promising clinical applications.

Sodium-dependent amino acid transport of methylaminoisobutyric acid (MeAIB) in a human myelogenous leukemic cell line K562 was inhibited by 30 nM etoposide (VP-16). Cell growth in suspension was almost completely suppressed by 30 nM VP-16 after 72 h. Colony formation by K562 cells markedly decreased after 24 h in a culture medium containing 30 nM VP-16, whereas MeAIB transport was inhibited after 72 h. K562 cell proliferation was restored in drug-free medium after recovery from 72-h culture with 30 nM VP-16. Colony formation and MeAIB transport were restored to pretreatment levels after 1-2 weeks. Thus, two conclusions may be drawn. (1) MeAIB transport may be correlated with cellular growth and (2) the effects of VP-16 on MeAIB transport were partially reversible.

From January 1976 through December 1988 we encountered ninety nine cases of intrahepatic stones. Eight of them were complicated with postoperative bile duct strictures which were formed on cholangiojejunostomy in 5 cases, cholangioduodenostomy, hepatic hilum and common hepatic duct in 1 case, respectively. Six cases of them are anastomotic strictures. The stones were mainly composed of bilirubin calcium. We guessed that the bile duct stricture resulted from cholangiojejunostomy without Roux-en-Y in 1 case and anastomotic insufficiency in 5 cases. Intrahepatic stones were removed by percutaneous transhepatic cholangioscopy (PTCS), and the treatment for the stricture was cholangiojejunostomy in 1 case and the dilatation by PTCS in 5 cases, including 3 endoprostheses by pig-tail silicone catheter and 2 internal-external biliary drainage. Two patients who did not undergo cholangioscopic dilatation died of sepsis due to cholangitis. Three of 5 patients who underwent endoscopic dilatation by PTCS could return to social life without recurrence of gallstones. In other two cases an endoprosthetic catheter was removed by PTCS because of dislodgement or obstruction of the catheter after confirming anastomotic strictures had improved. Authors recommended that PTCS should be applied for postoperative bile duct stricture complicated with intrahepatic stone.

A case of resected intrahepatic bile duct cancer with hilar bile duct and portal vein invasion is presented. Percutaneous transhepatic biliary drainage was performed to alleviate jaundice and evaluate the biliary system. Intraductal tumor extension was determined, and an accurate histological diagnosis was made in biopsy material obtained under percutaneous transhepatic cholangioscopy. Preoperative surgical planning was carried out on the basis of an evaluation of the findings of ultrasonography, computed tomography, arteriography, portography and percutaneous transhepatic cholangioscopy. Curative surgery, which included right hepatic lobectomy with total caudate lobectomy and combined resection and reconstruction of the portal vein, was performed. Bilioenteric continuity was re-established by a Roux-en-Y jejunal loop. The histological diagnosis was moderately differentiated tubular adenocarcinoma originated in the right posterior branch of the intrahepatic bile duct. Postoperative recovery was very good, and the patient has now been enjoying a good active social life for the past three years with no signs of tumor recurrence. This case report discusses the accurate diagnosis and rational surgical treatment for intrahepatic bile duct carcinoma with hilar invasion.

From 1979 through 1989, surgical resection was performed in 55 of 66 patients with carcinoma of the hepatic hilus after improving jaundice by percutaneous transhepatic biliary drainage (PTBD). Selective cholangiography through PTBD was done to define precisely the anatomical location--extent of the obstructing lesion in each segmental hepatic duct. Percutaneous transhepatic cholangioscopy was performed through the sinus tract of PTBD after replacing the drainage catheter with a 15 French catheter for superselective cholangiography and biopsy to make the definitive diagnosis of the histological extent of the tumor and any variation of each segmental hepatic duct that joins the hepatic hilus. In 46 (69.7%) of 66 patients, curative resection was possible. Forty-five of these underwent various types of hepatic segmentectomy with caudate lobectomy for a morbidity rate of 41.3% and an operative mortality rate of 6.4%. Fourteen (31.1%) advanced cases underwent combined resection of the portal vein together with hepatectomy. Microscopic tumor involvement in the caudate branches was confirmed in 44 of 45 patients who underwent caudate lobe resection. The 3-year survival rate for all 43 patients surviving the curative excision was 55.1% and the 5-year survival rate was 40.5%. All 11 patients who had an unresectable advanced tumor died within 9 months. Curative resection should be designed according to the preoperative findings of the extent of cancer in each segmental duct, and caudate lobe resection should be performed together with the smallest necessary hepatic segmentectomy possible.

Bile duct carcinoma, which produces clinically recognizable mucus, was defined as "mucus producing bile duct carcinoma", and clinicopathological study was carried out in 7 cases of bile duct carcinoma suitable for the definition. All the tumors arose from the intrahepatic bile duct. There were no tumors arising from the extrahepatic bile duct. Superficially spreading mucosal infiltration of carcinoma was recognized in 6 cases out of 7, and accordingly distinct cholangiography after draining mucus through percutaneous transhepatic cholangio-drainage (PTCD) and percutaneous transhepatic cholangioscopy (PTCS) were indispensable for accurate diagnosis of the extent of carcinoma. The prognosis of patients with mucus producing bile duct carcinoma were almost satisfactory if rational operation had been performed according to accurate diagnosis. On the other hand, since mucus producing bile duct carcinoma frequently has a cystic lesion, the relation to biliary cystadenocarcinoma may become a subject of question. We advocate that biliary cystadenocarcinoma should be included in mucus producing bile duct carcinoma since biliary cystadenocarcinoma originally arises from the intrahepatic bile duct and very rarely from the extrahepatic bile duct. But now the concept of biliary cystadenocarcinoma is equivocal and further investigations will be requested.

Seven cases of hepato-biliary and pancreatic malignancies that underwent partial resection of the inferior vena cava) were reviewed. Histological findings of inferior venca cava involvement were direct invasion in 5 cases, tumor thrombus in 1 case, and adhesion in 1 case. Correct preoperative diagnosis of inferior vena cava involvement was made in only 2 cases. A retrospective study on enhanced CT revealed that irregular deformity of the inferior vena cava had suggested inferior vena cava involvement. Total occlusion of the inferior vena cava was employed temporarily for inferior vena cava resection in 3 cases. A saphenous vein graft was used for reconstruction in 2 cases. Complications due to inferior vena cava resection are, as yet, unknown. One patient is alive, without recurrence, 24 months after the operation. One case underwent re-resection of liver metastasis, and is alive 17 months after the operation. Although advanced hepato-biliary and pancreatic malignancies involving inferior vena cava have been regarded as having a poor prognosis, an aggressive surgical approach may be applicable in some cases.

Paraaortic lymph nodes dissection was performed routinely in 28 patients with advanced gallbladder cancer who underwent curative or relative non-curative resection. In 10 patients out of 28 (36%), metastasis was found in the dissected paraaortic nodes. The incidence of paraaortic lymph nodes metastasis was 50% when the gallbladder serosa or adjacent organs were involved by cancer. If routine paraaortic lymph nodes dissection had not been carried out, the operation would be regarded as curative in 4 patients out of 10 with paraaortic lymph nodes metastasis. The incidence of paraaortic lymph nodes metastasis was twice higher than that of the mesenteric root and the metastatic route was possibly derived directly from the retroportal and/or retropancreactic nodes. Therefore, we emphasize that the paraaortic nodes should be regarded as the nodes between the 2nd group such as the retroportal or retropancreatic nodes and the 3rd group including the nodes of mesenteric root. In spite of positive paraaortic nodes, mean survival time of the patients without other non-curative factors was 26 months and the longest survival was 42 months. It seems that paraaortic nodes dissection has palliative effects to prolong the survival period of those patients. Paraaortic lymph nodes dissection should be employed in radical operative procedures for advanced gallbladder cancer.

Effects of acute portal hypertension on systemic hemodynamics after hepatectomy were evaluated by portal venous stenosis (PVS) model in dogs. In protocol 1, portal hypertension of about twice portal venous pressure (PVP) decreased cardiac output (CO) and left atrial pressure (LAP) by 24.5% (p less than 0.01) and 1.0 mm Hg (p less than 0.01), respectively. In protocol 2, stepwise PVS demonstrated that CO change (%) and LAP change (mm Hg) were inversely proportional to PVP change (r = -0.937 and -0.883, respectively). The ratio of CO change to LAP change with stepwise PVS was comparable to that obtained by repeated hemorrhage in protocol 3. The present study shows that low CO with portal hypertension is caused by a reduction of venous return to the heart.

During the past thirteen and a half years, 222 cases of iliofemoral venous occlusion were treated. Diagnosis was based mainly on clinical symptoms and phlebography. Surgery, injury, malignancy and heavy muscular exercise were the chief etiologic factors of this disease. As therapeutic maneuvres: (1) thrombectomy, (2) Palma's operation, (3) conservative procedures, (4) extirpation of a tumor, and (5) removal of secondary varicose veins were performed. Long-term results of treatment were reviewed. Thrombectomy and Palma's operation obtained good results in 59% and in 42% of cases respectively, while conservative procedures showed a favorable outcome in 36% of cases where followed. Results of thrombectomy were statistically better than those of conservative procedures (p less than 0.05).

This article reports a case of an infrarenal abdominal aortic aneurysm complicated with chronic disseminated intravascular coagulopathy (DIC). The patient was a 68-year-old man; bleeding of 20 months' duration was reported. Physical examination indicated a pulsating mass in the abdomen. The diagnosis of DIC was made on the basis of standard coagulation studies. Indium 111-labeled platelet scintigraphy demonstrated an increased accumulation of radioactivity over the aneurysm. After preoperative control of the bleeding tendency was obtained by continuous intravenous infusion of gabexate mesilate (FOY), the aneurysm was successfully replaced with a prosthetic graft. Gabexate mesilate therapy is useful for DIC as is heparin therapy. If surgical intervention is required for an abdominal aortic aneurysm with concomitant DIC, preoperative control of bleeding with gabexate mesilate or heparin is recommended to lessen operative bleeding.

The effect of intrajejunal infusion of pancreatic juice on basal pancreatic secretion was studied in patients who had received pancreatoduodenectomy for pancreatic, biliary, or duodenal malignancy. Pure pancreatic juice was obtained through a drainage tube inserted into the main pancreatic duct. There was little fibrosis in the pancreatic remnant and daily pancreatic juice output was more than 200 ml. After intraluminal infusion of pancreatic juice, water, protein, bicarbonate, and enzyme outputs were decreased significantly by about 30%. Intraluminal trypsin also reduced pancreatic secretion. Trypsin inhibitor (aprotinin) suppressed the significant decrease caused by autopancreatic juice or trypsin solution. We conclude that basal pancreatic secretion in humans is under negative feedback control by intestinal pancreatic juice or tryptic activity.