Prevalence and clinical relevance of serum anti-p53 antibodies in patients with cholangiocarcinoma

Cholangiocarcinoma (CCA) constitutes carcinoma of the bile duct found at a high prevalence in northeastern Thailand. In the present study, we examined the sera of altogether 82 Thai CCA patients for the presence of anti-p53 antibodies in order to investigate a role of the tumor suppressor gene, p53 in the carcinogenesis. Our results revealed anti-p53 antibodies in 7.3% of the cases tested, which conforms to the prevalence rate of p53 gene mutation recently reported at 5% among Thai patients. With limited number of the patients, anti-p53 antibodies were rapidly detected more frequently among patients with peripheral tumors than those with central tumors. However, further studies is required to establish significance and prognostic value of the antibodies in the context of CCA.     

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.     

Result of endoscopic biliary drainage in hilar cholangiocarcinoma

Patients with hilar obstruction usually require bilateral biliary drainage. The prognosis of patients who fail bilateral biliary drainage after contrast injection into both intrahepatic ducts is poor due to a high infection rate in the undrained segments. The incidence of post-endoscopic retrograde cholangiopancreatography cholangitis in those with successful bilateral biliary drainage was less, but still significant. Incomplete subsegmental intrahepatic duct drainage is suggested to be responsible for post-biliary drainage cholangitis in cases of advanced hilar tumors. This study was undertaken to determine the incidence of post-endoscopic retrograde cholangiopancreatography cholangitis, jaundice resolution, and stent clogging in different types of malignant biliary obstruction after biliary drainage. From our endoscopic retrograde cholangiopancreatography database, there were 63 patients who underwent endoscopic biliary drainage between September 2000 and November 2001, for malignant biliary obstruction. Sixty-one endoscopic retrograde cholangiopancreatographies had biliary drainage performed (2 patients who failed biliary drainage were excluded). We divided our patients into 3 groups: Group 1 = Bismuth I, Group 2 = Bismuth II, and Group 3 = Bismuth III and IV. All but 2 Group 1 patients had successful biliary endoprosthesis (plastic [n = 13], metallic [n = 12], failed [n = 2]) placement into an extrahepatic duct. All patients from Group 2 (n = 10) and 20 patients from Group 3 (n = 26) had successful bilateral biliary drainage. Unilateral biliary drainage was performed in 6 patients from Group 3, each with a plastic endoprosthesis. The incidence of post-biliary drainage cholangitis (new onset of fever >38.5 degrees C with leukocytosis), jaundice resolution (normal bilirubin level), and the duration of endoprosthesis patency were compared among the 3 groups. The incidences of post-endoscopic retrograde cholangiopancreatography cholangitis, jaundice resolution, and the duration of endoprosthesis patency were: Group 1 (4%, 96%, and 87.2 days, respectively), Group 2 (10%, 100%, and 69.1 days, respectively) and Group 3 (57.7%, 73.1%, and 41.3 days, respectively). Of those patients who did not undergo surgery, patients from Group 3 required endoprosthesis exchange sooner than others. The outcome of biliary drainage in patients with advanced hilar tumors (Bismuth III or IV) was poorer than hilar tumor at earlier stages (Bismuth I or II).     

Success rate and cannulation time between precut sphincterotomy and double-guidewire technique in truly difficult biliary cannulation

Background and Aim: Precut sphincterotomy (PS) is usually indicated in failed standard biliary cannulation (BC). PS requires experienced endoscopists, and contains significant risk. Double‐guidewire (DG) cannulation seems to be easier, and might be useful after failed standard BC. We aimed to compare cannulation time, success rate, and complication rates between the two techniques. Methods: Patients who failed standard BC within 10 min by the expert were defined as truly difficult BC and randomized into both groups. In the DG group, the first guidewire was left in the pancreatic duct, and then a catheter, pre‐inserted with another guidewire, was used for the BC. In the PS group, a fistulotomy technique was used. Results: From June 2008 to October 2009, 534 patients underwent endoscopic retrograde cholangiopancreatography. Forty‐four patients (8.2%) who failed standard BC were randomized into the DG group (n = 23) and the PS group (n = 21). Median cannulation times and success rates in the DG and PS groups were 172 versus 394 s (P < 0.001), and 73.9% versus 80.9% (P = 0.724), respectively. The pancreatitis rate and serum amylase at 24 h in the DG and PS groups were 21.7% versus 14.3% (P = 0.701) and 937 versus 195 mg/dL (P = 0.020), respectively. Two from each group developed mild bleeding. No perforation occurred. Conclusion: In truly difficult BC, the DG technique requires a significant shorter duration for BC, with a comparable success rate to the PS technique. The post‐procedure serum amylase level in the DG group was significantly higher, and there was a trend of more pancreatitis.     

Papillon-Lefevre syndrome: a case report

We report the first diagnosed case of Papillon-Lefevre syndrome in Thailand. The patient is the youngest child of consanguinous parents, and she has had symmetrical hyperkeratotic plaques on both plantar surfaces since birth with a history of chronic gingivitis, periodontitis, and premature loss of primary dentition. The histologic study revealed compact hyperkeratosis with epidermal acanthosis. Radiologic studies of the skull were normal. The radiographic panoramic view of the oral cavity revealed generalized severe vertical and horizontal alveolar bone loss. The immunologic analysis of polymorphonuclear leukocyte phagocytic function by nitrobluetetrazolium test (NBT test) showed decreasing response to latex stimulation. Serum parathyroid hormone, calcium, phosphate, and alkaline phosphatase levels were within normal limits. The skin lesions were temporary relieved with topical keratolytic agents. The oral lesions were improved by the extraction of hopeless teeth and conventional periodontal treatments.     

Sex hormones modulate distant organ injury in both a trauma/hemorrhagic shock model and a burn model

BACKGROUND: Emerging data suggest a gender dimorphism in resistance and susceptibility to distant organ injury after mechanical and thermal trauma. The aim of this study was to determine the role that testosterone and estradiol play in modulating resistance or susceptibility to distant organ injury, and whether their effects were associated with differences in the production of nitric oxide. METHODS: Adult male, female, castrated male, and ovariectomized female Sprague-Dawley rats were given intraperitoneal pentobarbital sodium anesthesia and subjected to trauma/sham shock or trauma/hemorrhagic shock (T/HS). A second set of animals were subjected to a 40% total body surface area, third-degree burn or sham burn. At 3 hours after resuscitation, plasma levels of nitrite/nitrate were measured, and the extent of lung injury (permeability to Evans Blue dye and neutrophil sequestration by myeloperoxidase) and intestinal injury (morphology) were determined. RESULTS: Proestrus females showed resistance to lung and gut injury after both T/HS and burns, and had low levels of nitrite/nitrate production. This resistance to injury was abrogated by ovariectomy with an associated increase in nitric oxide production. Males showed increased lung and gut injury after both T/HS and burns associated with increased production of nitrite/nitrate. Castration decreased susceptibility to both lung and gut injury, and decreased production of nitrite/nitrate. A correlation was noted between intestinal and lung injury, and both intestinal and lung injury correlated with plasma nitrite/nitrate levels. CONCLUSIONS: Male sex hormones potentiate, while female hormones reduce T/HS and burn-induced lung and gut injury. Production of nitric oxide is associated with increased lung and gut injury after T/HS and burns.