Development of pyothorax-associated pleural lymphoma in relation to focal cytokinemic condition and Epstein-Barr virus infection.

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.

Diagnostic criteria of Buerger's disease.

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.

Recovery of portal blood flow after percutaneous transhepatic biliary drainage in patients with obstructive jaundice.

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.

Hematologic response in patients with aplastic anemia after long-term administration of recombinant human granulocyte colony-stimulating factor and erythropoietin.

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.

A novel quantitative 'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias.

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.

Hepatic blood flow after acute biliary obstruction and drainage in conscious dogs.

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.

Effect of lipid emulsions for total parenteral nutrition on regeneration of the liver after partial hepatectomy in rats.

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.

Fibromuscular dysplasia as a cause of abdominal aortic aneurysm.

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.

Genomic instability of microsatellite repeats and its association with the evolution of chronic myelogenous leukemia.

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.

Muscle sympathetic outflow in Buerger's disease.

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: diagnosis and management.

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.

Interportal communicating branch at the hepatic bifurcation--report of two cases.

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 case of T-cell lymphoma showing multiple nodular shadows and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody].

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.

[A case of pulmonary aspergillosis by immunodiagnosis during remission induction therapy of acute myelocytic leukemia].

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.

Cholangiocellular carcinoma in the caudate lobe with intraluminal growth in the extrahepatic bile duct.

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.

Paradoxical response to cerulein on sphincter of Oddi in the patient with gastrectomy.

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.

Interventional embolization with fibrin glue for a large inferior mesenteric-caval shunt.

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.

[A case of intrahepatic cholesterol stone complicated with atrophy of the anterior superior ventral and anterior superior lateral subsegments (S8ab) of the liver].

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.

Microcirculatory characteristics in patients with Buerger's disease.

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.

Clinicopathologic studies on perineural invasion of bile duct carcinoma.

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%).