Characteristics of metachronous multiple early gastric cancers after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) of early gastric cancer is a minimally invasive procedure. The incidence and characteristics of metachronous multiple gastric cancers were investigated in a retrospective study in patients with early gastric cancer after EMR treatment. PATIENTS AND METHODS: A total of 143 patients with early gastric cancer who had undergone EMR treatment were periodically followed up with endoscopic examinations for 24 months or longer. RESULTS: The median period of endoscopic follow-up was 57 months (range 24 - 157 months). None of the patients died of gastric cancer, and there were no treatment-related deaths. Five patients died of other diseases. Of 20 patients (14 %) with metachronous multiple gastric cancers, 15 were treated by EMR. One patient with differentiated submucosal cancer and four with undifferentiated cancers underwent surgery. Sixteen patients (11 %) had synchronous multiple early gastric cancer lesions within 1 year of the initial EMR. About half of the multiple lesions were located in the same third of the stomach as the primary lesion, and most lesions were similar in macroscopic type to the primary lesions. Most multiple lesions were of the differentiated type. CONCLUSIONS: Annual endoscopic examinations can preserve the whole stomach in most patients with early gastric cancer after successful EMR.

A phase I study of S-1 combined with weekly cisplatin for metastatic gastric cancer in an outpatient setting.

A dose-escalation study was conducted for patients with metastatic gastric cancer to determine the recommended dose of weekly intravenous (i.v.) cisplatin combined with a fixed dose of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, on an outpatient basis. Secondary endpoints were to define the toxicity profile and to determine tumour responses. S-1 was fixed at a dose of 70 mg/m(2)/day and was administered for 2 weeks followed by a 1-week rest. Three dose levels of cisplatin (10, 15 and 20 mg/m(2)) were studied. Cisplatin was infused over 30 min on days 1 and 8. 20 patients were enrolled. No dose-limiting toxicities (DLTs) were recorded during the administration of cisplatin up to 20 mg/m(2), except for grade 3 diarrhoea and stomatitis in one patient at dose level 3. No grade 4 adverse events occurred. However, grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in 7 of 13 patients at dose level 3 within the first two treatment cycles. This was determined to be the maximum acceptable level that would not negate the advantages observed with use of an oral drug such as S-1. An objective tumour response was seen at all dose levels, and the overall response rate in the 18 patients evaluated was 61%. A higher response rate of 78% was observed in 9 patients who had received no prior chemotherapy. Oral S-1 with weekly cisplatin is a feasible and promising combination regimen that is appropriate for an outpatient setting. A randomised phase II study comparing this combination with S-1 alone in chemo-nai;ve patients is warranted.

Expression of Nov, CYR61 and CTGF genes in human hepatocellular carcinoma.

CCN family genes, Nov, CYR61 and CTGF, are immediate-early genes expressed in fibroblasts following growth stimuli. Aberrant expression of Nov has been found in human Wilms' tumor, and suggested to be involved in tumorigenesis. The aim of our experiments is to examine the expression of CCN family genes in human hepatocellular carcinomas (HCCs) and find the correlation of these gene expressions with clinicopathological parameters. A pair of tumor and surrounding non-tumor tissues were obtained from 23 patients with HCC and six with metastatic liver tumor. Total cellular RNA isolated from tissues was analyzed for the presence of mRNA of CCN family genes by the reverse-transcription polymerase chain reaction. Nov, CYR61 and CTGF mRNA were identified in 17 (73.9%), 17 (73.9%), six (26.1%) tumors, and in nine (39.1%), 16 (69.6%), one (4.3%) surrounding non-tumor tissues of 23 patients with HCC. No significant difference was found in clinicopathological parameters between cases with HCC negative and positive for these gene expressions. The prevalence of Nov and CTGF expression in HCC is significantly higher than those in surrounding non-tumor. The same tendency was found in metastatic tumors. These results suggest that Nov and CTGF is associated with the development of tumors in the liver.

Churg-Strauss Syndrome with pleural involvement.

A 51-year-old Japanese man with Churg-Strauss Syndrome (CSS) diagnosed by pleural biopsy is described. He was hospitalized because of high fever and bilateral knee, elbow and shoulder joint pain. Chest roentgenogram and chest computed tomography (CT) scan revealed bilateral massive pleural effusion. Pleural biopsy revealed eosinophilic infiltration and necrotizing granulomas. He was treated with oral prednisolone and his symptoms improved. This is the first report of CSS diagnosed by pleural biopsy.

Kinetics of expression of connective tissue growth factor gene during liver regeneration after partial hepatectomy and D-galactosamine-induced liver injury in rats.

Connective tissue growth factor (CTGF) is up-regulated by TGF-beta1 during wound healing. The present study examined the expression of CTGF during regeneration after 70% partial hepatectomy (PH) or d-galactosamine (GalN)-injured liver in rats. CTGF, TGF-beta1, and type I collagen mRNAs were semiquantified by a ribonuclease protection assay. After PH, TGF-beta1 and type I collagen were increased at 2-6 h and at 12-48 h. CTGF increased at 6 h and returned to the control level thereafter. The ribonuclease protection assay of cultured hepatic stellate cells (HSC) and in situ hybridization suggest that the cells express CTGF along sinusoid might be HSCs. After GalN administration, CTGF increased at 2-96 h with a shoulder peak at 6-12 h followed by a main peak at 24 h. TGF-beta1 and type I collagen were up-regulated with kinetics similar to those of CTGF. The different kinetics between PH and GalN regenerations indicate that regulation of CTGF in the two processes is different. Higher TGF-beta1 expression after inflammatory/necrotic process in the GalN regeneration may caused the prolonged CTGF expression.

Pulmonary lymphangiomyomatosis (LAM) developing chylothorax.

We describe a case of pulmonary lymphangiomyomatosis (LAM) with chylothorax that developed in a 46-year-old Japanese woman. This patient exhibited clinical symptoms of dyspnea and chest X-ray showed right pleural effusion. Thoracocentesis demonstrated chylous effusion. Chest computed tomography (CT) scan revealed multiple cystic lesions. Subsequent thoracoscopy revealed the chylorrhea from swelled vessels on the diaphragm. The clinical diagnosis, based on histological examinations with biopsy specimens obtained by thoracoscopy, was pulmonary LAM. Although the hormone therapy was not effective, chylous effusion was improved by the pleurodesis. Pulmonary LAM developing chylothorax is rare in Japan.

Active intestinal tuberculosis with esophageal candidiasis due to idiopathic CD4(+) T-lymphocytopenia in an elderly woman.

We describe a case of intestinal tuberculosis and esophageal candidiasis in an 85-year-old Japanese woman with idiopathic CD4+ T-lymphocytopenia (ICL). The patient exhibited clinical symptoms of odynophagia, bloody diarrhea, and high fever. Physical examination on admission showed a poor nutritional status. Endoscopic examination of the upper digestive tract revealed the esophageal mucosa to be covered with yellowish-white plaque-like lesions. Colonoscopic examination revealed multiple annular ulcerations with bleeding. She was diagnosed with intestinal tuberculosis by polymerase chain reaction (PCR) and fecal culture. Her CD4+ T-lymphocyte count was 178/mm3 and no evidence of human immunodeficiency virus (HIV) infection was found. She was successfully treated with fluconazole and antituberculosis drugs. This case emphasizes the importance of opportunistic infections in elderly patients with predisposing conditions such as ICL.

Benign gastric ulcer associated with Canidida infection in a healthy adult.

A case of benign gastric ulcer associated with Candida infection in a healthy adult is reported. The patient was a 46-year-old man complaining of epigastralgia. Endoscopic examination of the upper digestive tract revealed an elevated lesion with ulceration having an unclear border and thick exudates. The clinical diagnosis based on endoscopic findings was a benign gastric ulcer; however, biopsy was performed to distinguish it from malignant lymphoma. Histological examination of biopsy samples obtained from the base and the edge of the ulcer revealed numerous Candida. Therefore, the patient was diagnosed with Candida-infected gastric ulcer. The ulcer resolved after the administration of antiulcer drugs for 2 months. Predisposing factors for fungal infection were excluded. These observations suggest that Candida-infected gastric ulcer should be suspected in patients with a gastric submucosal tumor-like lesion with a thick, yellowish-white coated ulcer of unclear border on its summit, and this lesion should be distinguished from malignant diseases.

Serum carnitine concentrations in patients with idiopathic hypertrophic cardiomyopathy: relationship with impaired myocardial fatty acid metabolism.

We evaluated the clinical significance of serum carnitine concentrations in determining the severity of impaired myocardial fatty acid metabolism in idiopathic hypertrophic cardiomyopathy (HCM). We studied 56 asymptomatic or mildly symptomatic patients with HCM. Serum levels of free carnitine and acylcarnitine were measured by the enzymic cycling method. Myocardial scintigraphy with (123)I-labelled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) was performed, and the images were analysed quantitatively and semi-quantitatively. Serum free carnitine levels were significantly higher in HCM patients than in normal subjects (52. 5+/-9.5 and 42.3+/-5.5 nmol/ml respectively; P<0.0001). On the other hand, serum acylcarnitine levels and acyl/free carnitine ratios were lower in HCM patients than in normal subjects (10.2+/-4.0 nmol/ml and 0.19+/-0.08, compared with 13.2+/-3.9 nmol/ml and 0.32+/-0.11 respectively; P<0.0001). Clinical characteristics were not significantly different between the patients showing high and normal free carnitine levels, although female patients with high free carnitine levels were few (P=0.02). Both quantitative and semi-quantitative analyses revealed that the severity of decreased myocardial BMIPP uptake was significantly correlated with serum free carnitine levels (quantitative analysis: r=-0.422, P<0.0012; semi-quantitative analysis: r=0.633, P<0.0001). In the presence of reduced carnitine uptake into the myocardium in HCM, there may also be reduced transport of acylcarnitines out of the myocardium into the plasma. Although inborn errors of fatty acid metabolism and carnitine deficiencies are reported to provoke secondary HCM and are associated with low serum carnitine concentrations, this study has revealed that the levels of carnitine are, in contrast, increased in idiopathic HCM. Moreover, serum carnitine concentrations are a sensitive indicator of the severity of impaired myocardial fatty acid metabolism even in asymptomatic patients with HCM.

CD36 deficiency has little influence on the pathophysiology of hypertrophic cardiomyopathy.

CD36 is homologous with myocardial long-chain fatty acid (LCFA) binding protein and has been suggested to relate to myocardial fatty acid metabolism. Myocardial scintigraphy with iodine-123 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) revealed an impairment in LCFA metabolism chiefly in the hypertrophic myocardium in hypertrophic cardiomyopathy (HCM). Recently, the incidence of CD36 deficiency has been reported to be high in HCM patients, and CD36 deficiency was proposed as an etiology of hereditary HCM. However, the pathophysiological effect of CD36 deficiency on HCM has not been fully investigated. We analysed the expression of CD36 antigens on both platelets and monocytes obtained from 82 patients with HCM using two-color flow cytometry. Among the study patients, seven patients (8.5%) demonstrated type II CD36 deficiency, whereas type I CD36 deficiency was not detected. Two of 23 patients (8.7%) with a family history of HCM and five of 59 patients (8.5%) without a family history of HCM showed type II CD36 deficiency respectively. Contrary to the previous report, three of 53 patients with asymmetric septal hypertrophy (ASH) (5.7%) and four of 29 patients without ASH (13.8%) showed CD36 deficiency. Moreover, clinical characteristics, scintigraphic findings, echocardiographic data, and hemodynamic findings disclosed no significant differences between the HCM patients showing normal CD36 expression and those with CD36 deficiency. The incidence of CD36 deficiency in HCM patients is not higher than in the general population. Therefore, CD36 deficiency is not a characteristic factor of HCM and has little influence on the pathyphysiology of HCM.

Tuberous sclerosis associated with multiple hepatic lipomatous tumors and hemorrhagic renal angiomyolipoma.

We report a case of tuberous sclerosis associated with hepatic lipomatous tumors and renal angiomyolipomas. Abdominal ultrasonography revealed a high echoic large tumor in the left kidney. A provisional diagnosis of angiomyolipomas of the kidney was made based on computed tomography. Subsequent laparotomy revealed that the extracted tumor was renal angiomyolipoma. It was also revealed that there was an association with hepatic lipomatous tumors thought to be lipomas or angiomyolipomas by liver biopsy. Nearly half of all cases of angiomyolipoma in the kidney are reported as occasional association with tuberous sclerosis complex, but lipomatous tumors in the liver are rare.

Abnormal course, abnormal flow, and systolic compression of the septal perforator associated with impaired myocardial perfusion in hypertrophic cardiomyopathy.

BACKGROUND: The septal perforators in hypertrophic cardiomyopathy (HCM) show systolic compression. The compression is thought to be related to the malpositioned septal perforators, but its relation to the development of myocardial ischemia remains controversial. METHODS: We examined echocardiographically the blood flow and course of the major septal perforator in 142 consecutive patients with HCM; of these, 94 underwent coronary angiography to assess systolic compression of the septal perforators and 110 had thallium-201 scintigraphy. We then analyzed the relation of the findings in comparison with the results in 15 patients with valvular aortic stenosis (AS). RESULTS: The major septal perforator was visualized in 82 patients with HCM and in 8 patients with AS. The visualization did not depend on the pressure gradient between the left ventricle and aorta in the HCM patients, but did in the AS patients. In AS the perforator always showed a normal course near to, and convexly toward, the right ventricle. In 71 of the 82 HCM patients, the perforator was distant from the right-sided endocardium of the ventricular septum and often convex toward the left. The greater the leftward deviation, the higher was the grade of compression. In 48 of the 82 patients with HCM and in all of the 8 patients with AS who showed the flow signal, the septal perforator showed systolic retrograde flow; in the patients with HCM there was a significant correlation (r = 0.54, P <.05) between the peak velocity and the degree of leftward deviation. Furthermore, higher degrees of the leftward deviation and higher degrees of the systolic compression of the major perforator were each associated with a higher incidence of exercise-induced defect of thallium-201. CONCLUSION: The echocardiographic, angiographic, and scintigraphic findings in HCM may be closely related to one another. We speculate that the series of abnormalities is initiated by a high intramural pressure and impedance on the septal perforators due to their deviation toward the left.

Improved survival of idiopathic dilated cardiomyopathy in the 1990s.

To analyze the recent change in the long-term survival of patients with dilated cardiomyopathy (DCM), the present study comprised consecutive 111 patients with ejection fraction <50% and left ventricular end-diastolic diameter >58 mm. who were admitted to hospital from January 1983 to December 1994. The patients were divided into 2 groups: group A who were diagnosed before 1989 and group B diagnosed after 1990. Basic characteristics at diagnosis, including age, NYHA functional class, left ventricular end-diastolic diameter and ejection fraction, were similar between these 2 groups. Calculated survival rate at 5 years was 90.0% in group B in contrast to 62.3% in group A. Event-free survival also improved in group B. In group B, beta-blockers and angiotensin converting enzyme inhibitors were more frequently used than in group A (p<0.0001) whereas digitalis and other positive inotropic agents were significantly less used. Left ventricular ejection fraction was significantly improved during the follow-up period in patients treated with beta-blockers compared with those not treated with beta-blockers. These data indicate a significant improvement in the survival of patients with dilated cardiomyopathy after 1990, which may be explained by the change of medical treatment, especially the use of beta-blockers.

Expression of the midkine gene in human hepatocellular carcinomas.

BACKGROUND/AIMS: Aberrant expression of Midkine (MK) has been found in various human carcinomas including hepatocellular carcinoma (HCC). The aim of study is to identify the incidence of MK expression in tumor and surrounding non-tumor tissues of the liver, and to find the correlation of MK expression with other tumor markers. METHODOLOGY: Liver tissues were obtained from 16 patients with HCC and 4 with metastatic liver cancer. Background diseases of the HCC patients include liver cirrhosis and chronic hepatitis of type B or C. RNA was prepared from both cancerous and surrounding non-cancerous tissues, and analyzed for the presence of MK mRNA by RT-PCR, PCR-Southern blot, and Northern blot analysis. RESULTS: MK expression was detected in 12 (75%) of 16 HCCs by PCR-Southern blot analysis, the most sensitive of the 3 methods. Three of 9 surrounding cirrhotic tissues were weakly positive for MK expression, and none of chronic hepatitis and 4 normal tissues were negative. No significant difference was found in clinical and pathological parameters between MK negative and positive cases. Among metastatic cancers, 1 of gastric origin was positive for MK expression, but 1 each of chorangiocellular, gall bladder, and gastrinoma origin was negative. CONCLUSIONS: These results suggest that MK is expressed in the majority of HCC tissues and rarely in surrounding tissues in chronic liver diseases.

Reverse redistribution of Tc-99m-tetrofosmin in exercise myocardial SPECT in patients with hypertrophic cardiomyopathy.

We examined the usefulness of Tc-99m-tetrofosmin in detecting exercise induced perfusion abnormalities in patients with hypertrophic cardiomyopathy (HCM) and to clarify time-related changes in myocardial distribution of Tc-99m-tetrofosmin after a single injection. We studied 44 consecutive patients with HCM by means of exercise/rest Tc-99m-tetrofosmin single photon emission computed tomography (SPECT). After injecting 370 MBq of Tc-99m-tetrofosmin at the peak exercise, the early SPECT imaging was performed at 30 min (EX-30) and the delayed imaging at 180 min (EX- 180). Immediately after the delayed imaging, 740 MBq of Tc-99m-tetrofosmin was injected in the resting state, and the rest SPECT imaging was performed 30 min later. Exercise-induced regional perfusion defects and/or apparent reversible left ventricular cavity dilation were identified in 26 (68.2%) of the 44 patients. When EX-30 images and EX-180 images were compared, reverse redistribution was confirmed in 36 patients (81.8%). Reverse redistribution was detected most frequently in the septal portion of the anterior wall, followed by the septal portion of the posterior wall and the septum. Exercise/rest Tc-99m-tetrofosmin myocardial imaging was a useful method for assessing myocardial perfusion abnormalities in patients with HCM. Reverse redistribution was detected very frequently on early and delayed images of exercise. We assumed that reverse redistribution may reflect a retention disorder of Tc-99m-tetrofosmin caused by some metabolic dysfunction of myocytes.

Unusual variant of left paraduodenal hernia herniated into the mesocolic fossa leading to jejunal strangulation.

Paraduodenal hernia is a rare condition in which the small bowel loops are herniated into an unusual fossa in the periduodenal area. We treated a patient with paraduodenal hernia diagnosed preoperatively. A 28-year-old woman was admitted to our hospital because of intermittent abdominal pain. Abdominal ultrasonography revealed a large tumor adjacent to the pancreas. Provisional diagnosis made according to computed tomography (CT) findings was tumor of the pancreas tail. However, on a CT scan performed after the administration of diatrizoate meglumine/diatrizoate sodium (Gastrografin, Schering, Berlin, Germany) the mass was shown as a jejunum loop located between the stomach and the pancreas body. Subsequent laparotomy revealed that the jejunum loop was herniated into an unusually large mesocolic fossa and that the hernial orifice was covered by the adhesion between the transverse and descending colons. It seemed that the small intestine within the mesocolic fossa was strangulated by this adhesion. The patient's abdominal pain resolved postoperatively. These observations suggest that paraduodenal hernia should be suspected in patients with chronic, atypical abdominal pain, regardless of the findings for small bowel obstruction.

Two cases of renal hypouricemia with nephrolithiasis.

We treated two cases of renal hypouricemia with nephrolithiasis. The serum uric acid level of the first patient was 1.5 mg/dl, and the ratio of uric acid clearance to creatinine clearance (CUA/Ccr) was 75.7%. In the benzbromarone (BZB) suppression test, CUA/Ccr was increased from 60.4% to 130.0%, but was not decreased in response to the pyrazinamide (PZA) suppression test. This patient was considered to have a presecretory reabsorptive urate transportation defect. His condition was also associated with IgA nephropathy. The serum uric acid level in the second patient was 1.0 mg/dl and CUA/Ccr was 56.0%. Neither PZA nor BZB had a significant effect on CUA/Ccr. He was considered to have a subtotal uric acid transportation defect. Both patients were incidentally found to have nephrolithiasis. The second patient had abnormal maximum tubular secretory capacity for para-aminohippurate (PAH) (TmPAH), and was found to have two kinds of proximal tubular abnormalities related to uric acid and PAH.

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis.

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynaud's phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.

A family with hereditary serum cholinesterase deficiency.

A family with serum cholinesterase (SChE) deficiency is reported. A 64-year-old woman was admitted for the excision of colon adenoma; her laboratory data revealed a markedly decreased level of SChE. SChE genes of the patient and her family members were amplified by the polymerase chain reaction (PCR) and analyzed by direct sequencing. The patient's SChE gene had a homozygous frame shift mutation, in which an extra adenine was inserted in codon 315 (ACC-->AACC), resulting in the appearance of a new stop codon in codon 322. The family study disclosed that her brother and sister had the same frame shift mutations in homozygote and heterozygote, respectively.