Pylorus-preserving pancreatoduodenectomy: preoperative pancreatic function and outcome

BACKGROUND/AIMS: To investigate the effects of preoperative pancreatic function on gastric emptying, body weight, and quality of life after pylorus-preserving pancreatoduodenectomy. METHODOLOGY: Thirty-one patients who underwent pylorus-preserving pancreatoduodenectomy were divided into 2 groups according to preoperative pancreatic exocrine and endocrine function (normal vs. abnormal). Gastric emptying, body weight, and quality of life were evaluated before surgery, 1-2 months after surgery (short-term), and 6-12 months after surgery (long-term). RESULTS: Short-term body weight was significantly decreased in comparison to preoperative body weight regardless of preoperative exocrine and endocrine pancreatic function. Body weight returned to the preoperative level by 12 months after surgery in patients with normal preoperative pancreatic function but not in patients with abnormal pancreatic function. In both groups, gastric emptying was delayed at 1-2 months after surgery and then returned to the preoperative value by 12 months. Short-term quality of life did not differ from preoperative quality of life in either group, but long-term quality of life improved to beyond the preoperative level in both groups. CONCLUSIONS: Preoperative pancreatic function appears to significantly influence long-term body weight after pylorus-preserving pancreatoduodenectomy.     

In vitro selection of DNA aptamers that block toxic effects of AGE on cultured retinal pericytes

Microvessels are composed of endothelial cells and pericytes. We have previously shown that advanced glycation end products (AGE) not only inhibit DNA synthesis but also induce apoptosis in cultured retinal pericytes, thereby being involved in pericyte loss, the earliest histopathological hallmark of diabetic retinopathy. Since pericytes play a central role in the maintenance of microvascular homeostasis in the retina, blockade of the harmful effects of AGE on retinal pericytes may become a novel therapeutic strategy for the treatment of diabetic retinopathy. In this study, we selected DNA aptamers directed against AGE in vitro and then examined their cytoprotective effects on AGE-exposed retinal pericytes. We identified 15 DNA aptamers directed against AGE-human serum albumin using combinatorial chemistry techniques in vitro. Structural analysis revealed that they had bulge-loop structures with cytosine-rich sequences. All of the aptamers, but not non-binding control aptamers, were found to inhibit the AGE-induced decrease in DNA synthesis as well as apoptotic cell death in pericytes. Among the selected aptamers, the clone 9 aptamer completely blocked the toxic effects of AGE, and its dissociation constant was 1 micromol/L. These results indicate that DNA aptamers are a useful tool for inhibiting the cytotoxic effects of AGE on cultured retinal pericytes. Our study suggests that blockade of the AGE effects by DNA aptamers may lead to a novel therapeutic strategy for the treatment of diabetic retinopathy.     

Overexpressed cyclo-oxygenase-2 in the background liver is associated with the clinical course of hepatitis C virus-related cirrhosis patients after curative surgery for hepatocellular carcinoma

BACKGROUND: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. METHODS: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. RESULTS: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. CONCLUSIONS: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.     

Rupture of hepatic aneurysm complicating hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) for which hepatic arterial coil embolization was effective

A 74-year-old woman was transferred to our hospital for further examinations because of abdominal fullness and abnormal levels of serum liver/biliary enzyme persisting for 3 weeks. She had anemia and dilatation of many capillary vessels in her fingers, palms, and tongue in addition to reporting frequent incidences of nasal bleeding in herself and her family. Abdominal ultrasonography detected a cystic lesion in the right hepatic lobe, connected to a dilated tortuous hepatic artery. A low-echoic hepatic phyma was also detected in the back of the cystic lesion. Abdominal computed tomography and magnetic resonance imaging indicated that the cystic lesion was an aneurysm and the low-echoic phyma was a hematoma. Hepatic arteriography confirmed a hepatic aneurysm, tortuous dilatation of the hepatic artery, and the complication of an arteriovenous shunt in the liver. Taking all of these findings into consideration, this case was diagnosed as hereditary hemorrhagic telangiectasia (HTT) complicated by a hepatic aneurysm causing intrahepatic hematoma. To prevent re-rupture of the aneurysm, we performed a hepatic arterial coil embolization. After therapy, no blood flow to the aneurysm was detected by ultrasonic color Doppler method and the hematoma gradually diminished. There have been no reports of a case in which hepatic arterial embolization was effective for HHT-associated hepatic aneurysm causing intrahepatic hematoma. This very rare case provides important clinical information regarding abdominal vascular complications of HTT and a less invasive treatment for them.     

Successful treatment of a patient with primary Sjögren's syndrome complicated with pericarditis during pregnancy

A 35-year-old woman with primary Sj?gren's syndrome (pSS) developed fever and chest pain during pregnancy. When the dose of prednisolone was reduced, she experienced chest pain with elevated CRP and D-dimer, resulting in admission to our hospital with marked cardiomegaly and pleural effusion. Because there was no evidence of other autoimmune disorders or infection, oral prednisolone was increased to 30 mg daily with heparin, and hypercoagulopathy was carefully monitored. The patient's condition improved rapidly, and she delivered a healthy baby. This is the first case to support the beneficial effect of prednisolone in pericarditis with pSS, and illustrates its safety during pregnancy.     

Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells

Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively. We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation. In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells. Cells treated with conophylline and betacellulin-delta4 continued to grow after differentiation. Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin. Furthermore, cells treated with conophylline and betacellulin-delta4 secreted insulin in response to glucose. Likewise, conophylline and betacellulin-delta4 converted pancreatic ductal cells into insulin-producing cells. Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin. Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-delta4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice. Conophylline and betacellulin-delta4 are effective in inducing differentiation of beta cells from progenitors.     

An infant case of macroprolactinemia with transient idiopathic central precocious puberty

Macroprolactinemia was recognized more than a decade ago as a cause of hyperprolactinemia and the prevalence of macroprolactinemia is thought to be 10%-26% of patients with hyperprolactinemia. However, there are few published reports about macroprolactinemia in childhood. We report a 7-year-and-1-month-old girl with hyperprolactinemia due to macroprolactinemia with the complication of transient idiopathic central precocious puberty (ICPP). At the age of 6 years and 9 months, she was diagnosed with ICPP at another clinic, on the basis of isolated mammary development and increased height velocity with slightly advanced bone age. At that time, the unexpected finding of high PRL level was also observed. Four months later, she was referred to our clinic for persistently high PRL level. At this time, other endocrinological data showed prepubertal stage and we demonstrated macroprolactinemia and the presence of anti-PRL autoantibody. After other causes of hyperprolactinemia such as prolactinoma and stress were ruled out, we finally diagnosed her with hyperprolactinemia due to macroprolactinemia. Because most patients with macroprolactinemia are symptom-free despite hyperprolactinemia and drug therapy would not be indicated, macroprolactinemia should be suspected even in children to avoid unnecessary examinations and treatments.     

Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa

High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN.