Increased thyroid blood flow in the hypoechoic lesions in patients with recurrent, painful Hashimoto's thyroiditis at the time of acute exacerbation

We report two cases with painful Hashimoto's thyroiditis, who developed recurrent fever and painful thyroid. Glucocorticoid treatment was transiently successful but tenderness in the thyroid gland and fever developed when glucocorticoid was tapered. One patient underwent total thyroidectomy uneventfully. As is well known, it is frequently difficult to make differential diagnosis between painful Hashimoto's thyroiditis and subacute thyroiditis particularly at the initial phase. Interestingly, color flow doppler sonography of patient 1 revealed an increased thyroid blood flow in the hypoechoic lesions at the time of acute exacerbation although the serum level of TSH was suppressed. In the other patient, thyroid blood flow was also increased mainly in the hypoechoic lesions when the serum level of TSH was moderately increased, and it disappeared completely after supplementation of prednisolone and L-T4. Since thyroid blood flow in subacute thyroiditis is always decreased, such an increased blood flow in the hypoechoic lesion may be one of clinical characteristics of painful Hashimoto's thyroiditis, and useful for differential diagnosis from subacute thyroiditis.     

Intraductal Secretin Test Is as Useful as Duodenal Secretin Test in Assessing Exocrine Pancreatic Function

We assessed the clinical usefulness of theintraductal secretin test in order to ascertain whetherit can substitute for the conventional duodenal secretintest. Duodenal juice was obtained with a triple-lumen tube and pure pancreatic juice was obtained byretrograde cannulation of the main pancreatic duct usinga duodenofiberscope. Pancreatic secretion was stimulatedby a bolus intravenous injection of secretin (100 units). The two tests showed comparableinterindividual coefficients of variation, significantlygood correlations, and comparable diagnosticefficiencies. The intraductal secretin test showed noless reproducibility than that of the duodenalsecretin test as reported in the literature. In theintraductal secretin test, secretory volume, peak flowrate, bicarbonate output, and lipase output yielded the best diagnostic efficiency, followed by amylaseoutput and maximal bicarbonate concentration. In theintraductal secretin test, a 10-min collection providedas much information as a 20-min collection. We conclude, therefore, that the 10-minintraductal secretin test is as useful as theconventional duodenal secretin test in assessingexocrine pancreatic function and that the mostdiscriminatory parameters are secretory volume, bicarbonate output, andamylase (or lipase) output.     

Efficacy of combination therapy of interferon-α with ursodeoxycholic acid in chronic hepatitis C: A randomized controlled clinical trial

The efficacy of interferon- therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon- with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon- (group A,n=40) and the other with a combination of interferon- and UDCA (group B,n=40). In both groups, human interferon- (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P=0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significantP=0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P<0.01). Although this combination therapy did not lead to a sufficiently sustained complete response, it could serve as adjuvant antiviral therapy when a suitable dosage and administration period are determined.     

Expression of cyclins D1, D2 and E correlates with proliferation of rat stellate cells in culture

BACKGROUND/AIMS: Regulation of cell cycle progression of cultured rat stellate cells was studied. METHODS: DNA synthesis was determined by the uptake of [3H]thymidine or 5-bromo-2'-deoxyuridine. Cell cycle distribution was analyzed using FACScan of cellular DNA stained with propidium iodide. Expression of cyclins and cyclin-dependent kinase 4 was evaluated by Western and Northern blotting. RESULTS: DNA synthesis of primary-cultured stellate cells was found to accelerate 48 h after plating. Cell cycle analysis revealed that more than 93% of the cells were in G0/G1 phase during the first 48 h after plating. The cell population in S phase abruptly increased to about 16% 72 h after culture and shifted to G2/M phase thereafter. The level of proteins and mRNAs for cyclins D1, D2 and E started to increase 48 h after culture with a concomitant expression of platelet-derived growth factor receptor beta, while the level of cyclin-dependent kinase 4 and its mRNA remained unchanged. On the other hand, stellate cells remained in G1 phase when they were cultured in the presence of 3-isobutyl-1-methylxanthine or dibutyryl cAMP after plating. Attenuation of the expression of cyclins D1, D2 and E and platelet-derived growth factor receptor beta, but not cyclin-dependent kinase 4 was found in stellate cells cultured with these agents. Further analysis revealed that LY294002, a selective inhibitor of phosphatidylinositol 3-kinase, suppressed DNA synthesis and cyclin D1 expression in a dose-dependent manner without affecting platelet-derived growth factor receptor beta expression. CONCLUSIONS: Induction of G1 cyclins may play crucial roles in cell cycle transition of cultured stellate cells from G1 to S. Expression of platelet-derived growth factor receptor beta and activation of phosphatidylinositol 3-kinase may be involved in the process.     

Results of internal mammary artery-coronary artery bypass surgery and the characteristics of internal mammary artery grafts

Coronary artery bypass grafting utilizing the internal mammary artery (IMA) was performed in 108 patients with an operative mortality (less than 1 month) of 0% and a hospital mortality of 1.9%. The IMA was used most often in the left anterior descending artery system in combination with saphenous vein grafts (SVG) to the right and left circumflex artery systems. Although the IMA flow was smaller than the SVG flow when measured intraoperatively by an electromagnetic flow meter, postoperative clinical, electrocardiographic, isotopic, angiographic and coronary sinus flow-metric studies all demonstrated that the IMA can respond well to myocardial blood flow demand both at rest and during exercise, resulting in excellent clinical improvements with no detectable signs of flow deficiency. In addition, no signs of ischemia were detected in any of the 15 patients with stenosis in the left main trunk treated with an IMA graft. The IMA graft appears to have a great adaptive capacity to meet increased myocardial demand. Postoperative angiography performed at an average of 3 months after surgery in 60 unselected patients demonstrated an IMA patency rate of 98% in comparison with 88% patency in SVGs to the left anterior descending artery (p less than 0.05). Not only the patency rate, but also the graft wall characteristics were much better in IMA grafts than in SVGs. Some SVGs showed marked wall irregularity as early as 3 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment

Background and aims

In two Japanese infants with neonatal cholestasis, 3-oxo-Δ⁴-steroid 5β-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ⁴ bile acids were detected in their serum and urine by gas chromatography–mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment.

Patients and methods

SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated.

Results

With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.

Conclusion

Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.     

Hepatocellular carcinoma complicated by gastrointestinal hemorrhage caused by direct tumor invasion of stomach

A 65-year-old man with multiple hepatocellular carcinoma (HCC) underwent intra-hepato-arterial chemotherapy (IHAC) through an implantable port over a period of 10 months after transcatheter arterial embolization (TAE) had been performed three times. TAE was performed twice more, and radiotherapy (total dose, 30 Gy; given over a 3-week period) was given for progressive disease in the lateral segment of the liver. Three months after the radiotherapy had finished, the patient suddenly developed melena. Diagnostic imaging revealed gastrointestinal (GI) hemorrhage from HCC invading the stomach, and total gastrectomy and lateral segmentectomy of the liver were performed because the bleeding could not be controlled. The resected specimen disclosed a centrally necrotic tumor that had invaded the lesser gastric curvature and perforated into the lumen. Pathology examination revealed that the HCC had expansively invaded the gastric mucosa, resulting in exposure in the lumen. The possible mechanisms of direct GI invasion by HCC are briefly discussed, with a review of the literature. GI bleeding secondary to involvement by HCC is rare. The enteric radiation injury seems to have been largely resposible for the GI bleeding in this patient.     

Gallstone pancreatitis: Sixteen years of clinical management

Of 1465 patients with cholelithiasis admitted from 1980 to 1995, we reviewed 49 patients (3.3%) with gallstone pancreatitis. The patients were 26 men and 23 women, with a mean age of 57.7 years and mean serum amylase level of 2195IU/l. We examined laboratory data needed to determine Ranson's score, and we examined clinical findings, including the timing and choice of treatment, site of gallstones, and the postoperative course. Thirty-five patients (72%) were classified as having mild pancreatitis, with a Ranon's score of 2 or less; 9 patients (18%) had severe pancreatitis (score of 3 or more), and the remaining 5 (10%) could not be classified. Common bile duct (CBD) stones were identified in 18 of the 49 patients with severe pancreatitis, more than two times higher than that in patients with mild pancreatitis (31%). Although 92% of the patients (45/49) recovered from pancreatitis initially with conservative, treatment, such as antibiotics and protease inhibitors; 4 of the 9 patients with severe pancreatitis (44%) required urgent treatment. After the pancreatitis settled, cholecystectomy, predominatly performed laparoscopically, and endoscopic sphincterotomy were the primary treatment procedures. The overall morbidity rate was 6% (mild pancreatitis, 6%; severe pancreatitis, 11%), with no mortality. Most mild pancreatitis and some severe gallstone pancreatitis can be treated conservatively, followed by treatment for the gallstones causing the acute pancreatitis. However, in some patients with severe pancreatitis, especially those with acute necotizing pancreatitis or suppurative cholangitis, urgent treatment is mandatory. The final treatment for gallstones should be performed after the pancreatitis is alleviated.     

Intraductal papillary adenoma: Usefulness of magnetic resonance cholangiopancreatography in the diagnosis of cystic branch-duct dilatation of the pancreas

A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice.     

Recombinant interferon-α-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study

Abstract: To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-α-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-α-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p=0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p=0.0035) and platelet count (p=0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10⁵ copies/ml and serum platelet level above 15×10⁴/μl was 71%, whereas that in patients with a serum HCV-RNA level above 10⁵ copies/ml and serum platelet level less than 15×10⁴/μl was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.