LONG‐TERM OUTCOME OF ENDOSCOPIC PAPILLOTOMY FOR CHOLEDOCHOLITHIASIS WITH CHOLECYSTOLITHIASIS

Aim: To assess long‐term outcome of endoscopic papillotomy alone without subsequent cholecystectomy in patients with choledocholithiasis and cholecystolithiasis. Methods: Retrospective review of clinical records of patients treated for choledocholithiasis and cholecystolithiasis from 1976 to 2006. Of 564 patients subjected to endoscopic papillotomy and endoscopic stone extraction, 522 patients (279 men, 243 women; mean age 66.2 years) were followed up and predisposing risk factors for late complications were analyzed. Results: The mean duration of follow up was 5.6 years. Cholecystitis and recurrent choledocholithiasis occurred in 39 (7.5%) and 60 (11.5%) patients, respectively. Cholecystitis, including one severe case, resolved with conservative treatment. Recurrent choledocholithiasis was successfully treated endoscopically except in one case. Pneumobilia was found to be a significant risk factor for cholecystitis (P = 0.019) and recurrent choledocholithiasis (P = 0.013). Biliary tract cancer occurred in 16 patients; gallbladder cancer in 13 and bile duct cancer in three. Gallbladder cancer developed within 2 years after endoscopic papillotomy in seven of the 13 patients (53.8%). Conclusion: Pneumobilia was the only significant risk factor for cholecystitis and recurrent choledocholithiasis in our study population. As for the long‐term outcome, it was unclear whether endoscopic papillotomy contributed to the occurrence of biliary tract cancer.     

A lymphoma cell line resistant to 4-piperidinopiperidine was less sensitive to CPT-11

 CPT-11 is a promising new anticancer drug in which 4-piperidinopiperidine is a side-chain structure. In the present studies, we examined the role played by 4-piperidinopiperidine in the pharmacological activity of CPT-11. When T-cell lymphoma RVC cells were incubated with 4-piperidinopiperidine at concentrations higher than 50 μg/ml, the cells underwent apoptosis with a nucleosomal ladder of chromosomal DNA on agarose gels in a dose-dependent manner. We then established a cell line resistant to 4-piperidinopiperidine (4-pp-R), which was about 20-fold more resistant to 4-piperidinopiperidine than the parent RVC cells. Moreover, 4-pp-R cells showed coresistance to CPT-11. However, the growth rate and cell cycle population of 4-pp-R cells were not different from those of the parent RVC cells, and there were no differences between the two cell lines with regard to their drug transport system, CPT-11-metabolizing activity, their activity and amount of topoisomerase I, or their sensitivity to either SN-38 or etoposide, suggesting that the cytotoxicity of CPT-11 is not a consequence of the activity of its metabolite SN-38. The present studies suggested that resistance to CPT-11 is in part due to insensitivity to 4-piperidinopiperidine and its metabolites, since 4-piperidinopiperidine was cytotoxic and 4-pp-R cells were less sensitive to CPT-11. Received: 7 March 1996 / Accepted: 14 August 1996     

Impact of aortic arch stiffness on recurrence of stroke in patients with acute ischemic stroke

BACKGROUND: Aortic arch plaques are associated with increased risk of stroke recurrence. The atherosclerotic process also affects aortic stiffness. The purpose of the present study was to evaluate aortic arch stiffness by transesophageal echocardiography (TEE) and its effect on recurrence of stroke. METHODS AND RESULTS: TEE was performed in 201 patients with stroke and the aortic stiffness parameter beta was measured as an expression of the elasticity of the aortic arch wall. Patients were followed during a median follow-up period of 459 days with the endpoint as stroke recurrence. There were 21 cases of stroke recurrence (10%) during the follow-up period and the stiffness parameter beta was significantly higher in those cases (16.8+/-4.6 vs 12.5+/-3.3 [no recurrence], p<0.01). Cox multivariate hazard analysis revealed that stiffness parameter beta was the only independent predictor for stroke recurrence (hazard ratio 1.683, p<0.01). Kaplan-Meier Survival analysis revealed that stiffness parameter beta effectively risk stratified patients for stoke recurrence. Furthermore, in 3 groups based on the value of beta, the 3rd tertile had the highest stroke recurrent risk (relative risk 5.473, p<0.01). CONCLUSIONS: The value of beta in the aortic arch, assessed by TEE, may be a sensitive indicator of stroke recurrence.     

Immunohistochemical analysis of IMP3 and p53 expression in endoscopic ultrasound-guided fine needle aspiration and resected specimens of pancreatic diseases

Background

Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis.

Midkine in repair of the injured nervous system

Midkine (MK) is a growth factor with neurotrophic and neurite outgrowth activities. It was expressed in the peri-ischaemic area in the acute phase of cerebral infarction in rat brains. Astrocytes were the origin of MK in this occasion. MK has been assessed in terms of its effects on neural injury. The administration of MK into the lateral ventricle immediately prior to ischaemia prevented cell death in the hippocampal CA1 neurons degenerated by transient forebrain ischaemia in gerbils. MK administration was also beneficial in rats with neural injury, especially after kainic acid-induced seizures. Gene therapy with mouse MK cDNA using an adenovirus was effective in reducing the cerebral infarction volume and in increasing the number of neuronal precursor cells in the subventricular zone of the rat brain. MK mRNA and MK protein were found in spinal cord motor neurons of the anterior horn in both the acute phase of sciatic nerve injury and 3 weeks later. MK immunoreactivity was also found in the proximal side of a sciatic nerve-injured site in sciatic nerve axons. MK receptors were expressed in Schwann cells after injury, suggesting crosstalk between axons and Schwann cells. MK was also present in nerve terminals and influenced ACh receptor clustering during neuromuscular development in Xenopus. Thus, MK may also be involved in reinforcing and maintaining the synapse. All these findings indicate the therapeutic potential of MK for promoting repair of the nervous system after injury.

Linked Articles

This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4     

Current situation of endoscopic treatment for common bile duct stones

Background/Aims: The progression of endoscopy and devices as well as newly developed treatment methods have enabled endoscopic lithotomy. In this study, we examined to what degree is it possible to endoscopically treat patients who are diagnosed as having common bile duct stones. Methodology: Lithotomy was conducted using a backward side-viewing endoscope for patients without surgical history of upper gastrointestinal tract and patients with stomach reconstructed with Billroth-I method, using an ordinary endoscope for patients with stomach reconstructed with Billroth-II method (Bil-II) and using a double balloon endoscope for patients with difficulty in reaching the papilla or patients of Roux-en-Y anastomosis (R-Y). As for treatment methods, we selected endoscopic sphincterotomy as the first choice for papilla treatment and selected endoscopic papillary balloon dilation for patients with bleeding tendency or patients of Bil-II or R-Y. For patients with multiple stones or giant stones, lithotripsy was selected depending on judgment of the endoscopist. Results: Endoscopic complete lithotomy was successful in 97.7% (168/172). An accidental disease was observed in 2.9% (5/172). In one patient with the perforated gastrointestinal tract, a surgery was performed but others were mild. Conclusions: Common bile duct stones can be endoscopically treated safely with high rate.     

Circulating heart-type fatty acid binding protein levels predict the occurrence of appropriate shocks and cardiac death in patients with implantable cardioverter-defibrillators

BackgroundThe association between ongoing myocardial damage and outcomes in patients who have received an implantable cardioverter-defibrillator (ICD) is unclear.Methods and ResultsConsecutive patients with cardiomyopathy, who had received an ICD (n = 107, mean age 65 ± 11 years), were prospectively enrolled. Myocardial membrane injury (heart-type fatty acid binding protein [H-FABP] >4.3 ng/mL) and myofibrillar injury (troponin T >0.01 ng/mL) were defined using receiver operating characteristic curves. Patients were followed for a median of 33.6 months, to an end point of appropriate ICD shock or cardiac death. Myocardial membrane injury (45%) and myofibrillar injury (41%) were equally prevalent among patients with cardiomyopathy who had received ICDs. Appropriate ICD shocks or cardiac death occurred in 31% and 15% of patients, respectively. Multivariate Cox regression analysis showed that serum H-FABP levels >4.3 ng/mL, but not troponin T levels, were a significant independent prognostic factor for cardiac events (hazard ratio 5.502, 95% confidence interval 1.705–17.75, P = .004). Subgroup analysis revealed that measuring H-FABP levels was valuable for anticipating event-free survival among patients with ICDs who were receiving amiodarone. High H-FABP levels also predicted subsequent outcomes in patients who had received ICDs for primary or secondary prevention.ConclusionEvaluating myocardial damage using H-FABP may be a promising tool for predicting outcomes in patients with cardiomyopathy who have received ICDs.     

Anti-beta 1 adrenoreceptor antibody is frequently elevated in patients with muscular dystrophy]

Various autoantibodies had been detected in patients with dilated cardiomyopathy (DCM). Among them, anti-beta 1 adrenoreceptor antibody (ARAb) had been proven to act as agonist on beta 1 adrenoreceptor and cause DCM. Cardiomyopathy is also serious problem in progressive muscular dystrophy (PMD). Because cardiac dysfunction is quite variable even in siblings sharing identical mutations, it is highly possible that there are some modifier factors. Thus, we measured ARAb in 93 patients with PMD and 11 patients with DCM to clarify immune function for cardiac impairment of PMD. The titer was abnormally elevated in 30.1% of PMD, 72.7% of DCM and 75.0% (9/12) of PMD patients with symptomatic cardiac failure. ARAb was weakly correlated to fractional shortening, brain natriuretic peptide, noradrenalin and severity of premature ventricular contractions (Lown grade). During the study period, four patients developed cardiac failure and ARAb was increased in all these patients. In DMD, although the patients receiving both beta blocker and angiotensin converting enzyme inhibitor showed worst cardiac function, the titers were rather low compared to patients with angiotensin converting enzyme inhibitor alone. Four of five patients initiating beta blocker showed decrease of ARAb. Autoantibodies for myocardium actually exist in PMD in certain ratio as is the case with DCM. It is highly possible that immune system plays some role in cardiac impairment even in PMD. We should pay enough attention to immune system to elucidate the mechanism of cardiac dysfunction and refine strategy of cardiac treatments.