Pi-Jung Hsiao

Significant correlations between severe fatty liver and risk factors for metabolic syndrome

Background and Aim:  It is known that ultrasonography (US) cannot differentiate between non‐alcoholic fatty liver disease (NAFLD) and steatohepatitis. However, US can accurately estimate the severity of the steatosis. The clinical significance of severe hepatic fatty change by US has not been explored. The aim of this study was to investigate the relationship between the severity of the fatty liver, classified by US, and the degree of metabolic disorders with insulin resistance.

The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients

Studies have shown an association between diabetes and cancer in Western countries; but this, as well as the influence of associated metabolic factors, must be confirmed by a prospective study in other population groups. This study aimed to investigate whether the strong association of cancer and diabetes is independent from the influence of hypertension, dyslipidemia, and gout in the Taiwanese population. A total of 985,815 study subjects were identified from the National Health Insurance in 1997 and followed up from 1998 to 2009. The demographic characteristics between patients with diabetes and cancer, including age, sex, hypertension, dyslipidemia, and gout, were analyzed using the χ(2) test. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risks of cancer. A total of 104,343 diabetic patients were followed up from 1998 to 2009. After adjusting for sex, age, hypertension, dyslipidemia, and gout, the incidences of cancer at any site and in the liver, colon, lungs, and prostate in diabetic patients were independently higher, with risk ratios of 1.56 (95% confidence interval [CI], 1.43-1.71), 1.67 (95% CI, 1.39-2.01), 1.75 (95% CI, 1.49-2.06), 1.54 (95% CI, 1.26-1.88), and 1.56 (95% CI, 1.19-2.04), respectively. Only breast cancer did not show any clinical significance. There was an increased incidence of cancer at any site in the diabetic patients compared with nondiabetic subjects. The most common cancers were liver, colon, lung, breast, and prostate cancer; and except for breast cancer, their incidences increased independently of hypertension, dyslipidemia, and gout in patients with diabetes.

Neuronal and endothelial nitric oxide synthase expression in outer medulla of streptozotocin-induced diabetic rat kidney.

Aims/hypothesis. Several investigations have shown that the renal medulla has a greater capacity to generate nitric oxide than the renal cortex. To further evaluate the changes of nitric oxide synthesis in the kidney, particularly in the outer medulla, in disorders involving fluid and electrolyte imbalances, we sought to determine renal nitric oxide synthase expression in the diabetic rats. Methods. We determined renal nitric oxide synthase mRNA and urinary nitrite/nitrate excretion in 12 normal and 12 streptozotocin-induced diabetic rats by reverse transcription-polymerase chain reaction with Southern blot hybridization and with Griess reaction, respectively. Nitric oxide synthase immunoreactivity was detected by immunohistochemistry in four normal and four diabetic rats. Results. Neuronal and endothelial nitric oxide synthase mRNA were 3.5-fold and 1.8-fold increased in the outer medulla of 12 diabetic rats with no difference found in the cortex and inner medulla when compared with 12 normal rats. Urinary nitrite/nitrate excretion was significantly increased from the first week after diabetic induction. In normal rats, immunohistochemical studies showed positive neuronal and endothelial nitric oxide synthase immunostaining in almost all segments of renal tubules. Diabetic rats had the greatest enhancement of immunostaining for neuronal and endothelial nitric oxide synthase in the proximal straight tubule and medullary thick ascending limb. Conclusion/interpretation. Our results indicate that increases in neuronal and endothelial nitric oxide synthase synthesis in the kidney, particularly in the outer medulla, possibly play an important part in the adaptation of renal function to hyperglycaemia and hyperosmolality in diabetes. [Diabetologia (2000) 43: 649–659]

Significant association of ABCG5 604Q and ABCG8 D19H polymorphisms with gallstone disease

Adenosine triphosphate‐binding cassette (ABC) transporters ABCG5 and ABCG8 are sterol export pumps regulating biliary cholesterol excretion. The formation of gallstones, supersaturated with cholesterol in bile, is determined by genetic and environmental factors. The interaction of susceptible gene polymorphisms with age, sex and body mass index in gallstone disease is unclear.

Anatomical Variations of Recurrent Laryngeal Nerve During Thyroid Surgery: How to Identify and Handle the Variations With Intraoperative Neuromonitoring

Recurrent laryngeal nerve (RLN) palsy is the most common and serious complication after thyroid surgery. Visual identification of the RLN during thyroid surgery has been shown to be associated with lower rates of palsy, and although it has been recommended as the gold standard for RLN treatment, it does not guarantee success against postoperative vocal cord paralysis. Anatomical variations of the RLN, such as extra‐laryngeal branches, distorted RLN, intertwining between branches of the RLN and inferior thyroid artery, and non‐recurrent laryngeal nerve, can be a potential cause of nerve injury due to visual misidentification. Therefore, intraoperative verification of functional and anatomical RLN integrity is a prerequisite for a safe thyroid operation. In this article, we review the literature and demonstrate how to identify and handle the anatomical variations of the RLN with the application of intraoperative neuromonitoring in the form of high resolution photography, which can be informative for thyroid surgeons. Anatomical variations of the RLN cannot be predicted preoperatively and might be associated with higher rates of RLN injury. The RLN injury caused by visual misidentification can be rare if the nerve is definitely identified early with intraoperative neuromonitoring.

Reappraisal of the characteristics of glucose abnormalities in patients with chronic hepatitis C infection.

OBJECTIVES: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection.METHODS: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results.RESULTS: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70–4.56, P < 0.001).CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.

Intraoperative neuromonitoring for early localization and identification of recurrent laryngeal nerve during thyroid surgery.

Early and definite identification of the recurrent laryngeal nerve (RLN) is an important step to avoid inadvertent nerve injury during complicated thyroid operations. This study aimed to determine the feasibility of routine use of intraoperative neuromonitoring (IONM) to localize and identify the RLN at an early stage of thyroid surgery. This prospective study enrolled 220 consecutive patients (333 RLNs at risk) who underwent thyroid operations with application of IONM. The RLN was localized and identified routinely with a nerve stimulator after opening the space between the thyroid and carotid sheath. The success rates of early RLN localization and identification were evaluated. The current for localization and the amplitude of evoked laryngeal electromyographic signals were also recorded and analyzed. All RLNs, including 87 (26%) nerves that were regarded as difficult to identify, were successfully localized and identified. The stimulation level for RLN localization was 2mA in 315 nerves (95%) and 3mA in the other 18 nerves (5%). The signal obtained from RLN localization (amplitude = 932 ±436μV) showed a clear and reliable laryngeal electromyographic response that was similar to that from direct vagus (amplitude=811±389μV) or RLN stimulation (amplitude=1132±472μV). The palsy rate was 0.6% and no permanent palsy occurred. RLN injury is rare if the nerve is definitely identified early in the thyroid operation. The conclusion of this study is that IONM is a reliable tool for early RLN localization and identification, even in complicated thyroid operations.

Does extensive dissection of recurrent laryngeal nerve during thyroid operation increase the risk of nerve injury? Evidence from the application of intraoperative neuromonitoring

PURPOSE Extensive dissection of recurrent laryngeal nerve (RLN) is inevitable in some complicated thyroid operations. The study aimed to determine whether extensive dissection of RLN increases the risk of nerve injury. METHOD Three hundred thirty-one patients (506 nerves at risk) who underwent thyroid operations with intraoperative neuromonitoring were included. The study chiefly focused on the 101 RLNs on which extensive nerve dissection from the thoracic inlet to the entry of larynx was performed and for which the nerve exposure was longer than 5 cm. Electromyographic (EMG) signals were obtained from the RLN and vagus nerve before and after complete RLN dissection, and these were defined as R(1), V(1) and R(2), V(2) signals, respectively. The RLN palsy rates and the change of EMG signals were evaluated and analyzed. RESULTS Among 101 nerves with extensive dissection, 13 nerves were due to the operation for recurrent goiter; 41 nerves, for large goiter with substernal extension; and 47 nerves, for thyroid cancer with paratracheal nodal metastasis. No permanent palsy occurred, but 2 nerves experienced loss of EMG signal after complete RLN dissection from a large recurrent goiter and developed temporary palsy. The palsy rates were 2% (2/101) in the extensive dissection group and 2.5% (10/405) in the nonextensive dissection group (P = .77). Among 99 nerves with normal vocal function after operation, none experienced weakened signal after complete RLN dissection, and the mean amplitudes of R(2) and V(2) signals were not significantly different from those of R(1) and V(1) signals (R(2) vs R(1); 1038 vs 1030 μV; P = .74; V(2) vs V(1); 824 vs 816 μV; P = .75). CONCLUSIONS The results of this study suggest that careful surgical dissection is well tolerated by the RLN.

Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

BackgroundPioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY). Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression.ResultsOur results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration.ConclusionThe attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease.

Detecting and identifying nonrecurrent laryngeal nerve with the application of intraoperative neuromonitoring during thyroid and parathyroid operation

PURPOSE The nonrecurrent laryngeal nerve (NRLN) is a rare anatomical variant but associated with high risk of nerve injury during thyroid and parathyroid operations. Therefore, intraoperative detection and verification of NRLN are necessary. METHOD A total of 390 consecutive patients who underwent thyroid and parathyroid operations (310 RLNs dissected on the right side and 293 nerves on the left side) were enrolled. Electrically evoked electromyography was recorded from the vocalis muscles via an endotracheal tube with glottis surface recording electrodes. At an early stage of operation, vagal nerve was routinely stimulated at the level of inferior thyroid pole to ensure normal path of RLN. If there is a negative response from lower position but positive response from upper vagal stimulation, it indicates the occurrence of a NRLN, and we localize its separation point and path. RESULTS Four right NRLNs (1.3%) without preoperative recognition were successfully detected at an early stage of operation. Three patients were operated on for thyroid disease, one for parathyroid adenoma and all were associated with right aberrant subclavian artery. All NRLNs were localized and identified precisely with intraoperative neuromonitoring. Functional integrity of all nerves was confirmed by the intraoperative neuromonitoring and postoperative laryngeal examination. CONCLUSIONS Vagal stimulation at the early stage of operation is a simple, useful, and reliable procedure to detect and identify the NRLN.