Long-term outcome and prognostic factors of patients with hilar cholangiocarcinoma

AIM: To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS: Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995–2005. Of the 96 patients, 20 were initially treated with surgery (n = 2 R0 / n = 18 R1). In non-operated patients, data analysis was performed retrospectively. RESULTS: Among the 96 patients, 76 were treated with endoscopic transpapillary (ERC, n = 45) and/or percutaneous transhepatic biliary drainage (PTBD, n = 31). The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 ± 296 d. The mean survival time of patients with initial bilirubin levels > 10 mg/dL was significantly lower (P < 0.001) than patients with bilirubin levels < 10 mg/dL. The mean survival time of patients with Bismuth stage Ⅱ (n = 8), Ⅲ (n = 28) and Ⅳ (n = 40) was 496 ± 300 d, 441 ± 385 d and 274 ± 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant beneficial effect on the mean survival time (ERC vs PTBD, P = 0.806). CONCLUSION: Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated.

Diagnostic approaches for cholangiocarcinoma

Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are associated with poor prognosis. Despite new diagnostic approaches, the definite diagnosis of this malignancy continues to be challenging. Cholangiocarcinomas often grow longitudinally along the bile duct rather than in a radial direction. Thus, large tumor masses are frequently absent and imaging techniques, including ultrasound, CT, and MRI have only limited sensitivity. Tissue collection during endoscopic (ERCP) and/or percutaneous transhepatic (PTC) procedures are usually used to confirm a definitive diagnosis of cholangiocarcinoma. However, forceps biopsy and brush cytology provide positive results for malignancy in about only 50% of patients. Percutaneous and peroral cholangioscopy using fiber-optic techniques were therefore developed for direct visualization of the biliary tree, yielding additional information about endoscopic appearance and tumor extension, as well as a guided biopsy acquistion. Finally, endoscopic ultrasonography (EUS) complements endoscopic and percutaneous approaches and may provide a tissue diagnosis of tumors in the biliary region through fine-needle aspiration. In the future, new techniques allowing for early detection, including molecular markers, should be developed to improve the diagnostic sensitivity in this increasing tumor entity.

In vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens of acute cholangitis

AIM: To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS: In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction (n = 7), benign biliary stricture (n = 16), and malignant biliary stricture (n = 42) were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS: Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species (26/63), E.coli (13/63) and Klebsiella species (8/63). A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifloxacin.CONCLUSION: Enterococcus species , E.coli and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.

Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma

AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.

Endoscopic stent therapy in patients with chronic pancreatitis:A 5-year follow-up study

AIM:This study analyzed clinical long-term outcomes after endoscopic therapy,including the incidence and treatment of relapse. METHODS:This study included 19 consecutive patients(12 male,7 female,median age 54 years)with obstructive chronic pancreatitis who were admitted to the 2nd Medical Department of the Technical University of Munich.All patients presented severe chronic pancreatitis(stageⅢ°)according to the Cambridge classification.The majority of the patients suffered intermittent pain attacks.6 of 19 patients had strictures of the pancreatic duct;13 of 19 patients had strictures and stones.The first endoscopic retrograde pancreatography(ERP)included an endoscopic sphincterotomy, dilatation of the pancreatic duct,and stent placement.The first control ERP was performed 4 wk after the initial intervention,and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological conditions.Clinical follow-up was performed annually to document the course of pain and the management of relapse.The course of pain was assessed by a pain scale from 0 to 10.The date and choice of the therapeutic procedure were documented in case of relapse. RESULTS:Initial endoscopic intervention was successfully completed in 17 of 19 patients.All 17 patients reported partial or complete pain relief after endoscopic intervention.Endoscopic therapy failed in 2 patients. Both patients were excluded from further analysis.One failed patient underwent surgery,and the other patient was treated conservatively with pain medication.Seventeen of 19 patients were followed after the successful completion of endoscopic stent therapy.Three of 17 patients were lost to follow-up.One patient was not avail-able for interviews after the 1st year of follow-up.Two patients died during the 3rd year of follow-up.In both patients chronic pancreatitis was excluded as the cause of death.One patient died of myocardial infarction, and one patient succumbed to pneumonia.All three patients were excluded from follow-up analysis.Followup was successfully completed in 14 of 17 patients.4 patients at time point 3,2 patients at time point 4,3 patients at time point 5 and 2 patients at time point 6 and time point 7 used continuous pain medication after endoscopic therapy.No relapse occurred in 57%(8/14) of patients.All 8 patients exhibited significantly reduced or no pain complaints during the 5-year follow-up.Seven of 8 patients were completely pain free 5 years after endoscopic therapy.Only 1 patient reported continuous moderate pain.In contrast,7 relapses occurred in 6 of the 14 patients.Two relapses were observed during the 1st year,2 relapses occurred during the 2nd year,one relapse was observed during the 3rd year,one relapse occurred during the 4th year,and one relapse occurred during the 5th follow-up year.Four of these six patients received conservative treatment with endoscopic therapy or analgesics.Relapse was conservatively treated using repeated stent therapy in 2 patients.Analgesic treatment was successful in the other 2 patients. CONCLUSION:57%of patients exhibited long-term benefits after endoscopic therapy.Therefore,endoscopic therapy should be the treatment of choice in patients being inoperable or refusing surgical treatment.

Management of occluded self-expanding biliary metal stents in malignant biliary disease

Background: Occlusion of self-expanding metal stents(SEMS) in malignant biliary obstruction occurs in up to 40% of patients. This study aimed to compare the different techniques to resolve stent occlusion in our collective of patients.Methods: Patients with malignant biliary obstruction and occlusion of biliary metal stent at a tertiary referral endoscopic center were retrospectively identified between April 1, 1994 and May 31, 2014. The clinical records were further analyzed regarding the characteristics of patients, malignant strictures, SEMS,management strategies, stent patency, subsequent interventions, survival time and case charges.Results: A total of 108 patients with biliary metal stent occlusion were identified. Seventy-nine of these patients were eligible for further analysis. Favored management was plastic stent insertion in 73.4% patients. Second SEMS were inserted in 12.7% patients. Percutaneous transhepatic biliary drainage and mechanical cleansing were conducted in a minority of patients. Further analysis showed no statistically significant difference in median overall secondary stent patency(88 vs. 143 days, P = 0.069), median survival time(95 vs. 192 days, P = 0.116), median subsequent intervention rate(53.4% vs. 40.0%, P = 0.501)and median case charge(€5145 vs. €3473, P = 0.803) for the treatment with a second metal stent insertion compared to plastic stent insertion. In patients with survival time of more than three months,significantly more patients treated with plastic stents needed re-interventions than patients treated with second SEMS(93.3% vs. 57.1%, P = 0.037).Conclusions: In malignant biliary strictures, both plastic and metal stent insertions are feasible strategies for the treatment of occluded SEMS. Our data suggest that in palliative biliary stenting, patients especially those with longer expected survival might benefit from second SEMS insertion. Careful patient selection is important to ensure a proper decision for either management strategy.

A new peroral mother-baby endoscope system for biliary tract disorders

AIM: To investigate a new mother-baby system, consisting of a peroral cholangioscope and a duodenoscope in patients regarding its feasibility. METHODS: In the study period from January 2007 to February 2010, 76 consecutive patients(33 men, 43 women; mean age 63 years old) were included in this pilot series. Endoluminal images and biopsies were obtained from 55 patients with indeterminate strictures, while 21 patients had fixed filling defects. The diagnostic accuracy of peroral cholangioscopy(POCS) in the visualization of strictures and tissue sampling was evaluated, and therapeutic success was monitored. Followup was performed over at least 9 mo. RESULTS: A total of 55 patients had indeterminate strictures. Using the criteria "circular stenosis" and "irregular surface or margins", POCS correctly described 27 out of 28 malignant biliary strictures and 25 out of 27 benign lesions(sensitivity, 96.4%; specificity, 92.6%, diagnostic accuracy 94.5%). Visually targeted forceps biopsies were performed in 55 patients. Tissue sampling during POCS revealed malignancy in 18 of 28 cases(sensitivity: 64.3%). In 21 patients with fixed filling defects, 10 patients with bile duct stones were successfully treated with conventional stone removal. Nine patients with difficult stones(5 giant stones and 4 intrahepatic stones) were treated with visually guided laser lithotripsy. Two patients in the group with unclear fixed filling defects had bile duct adenoma or papillary tumors and were surgically treated. CONCLUSION: The new 95 cm POCS allows for accurate discrimination of strictures and fixed filling defects in the biliary tree, provides improved sensitivity of endoscopically guided biopsies and permits therapeutic approaches for difficult intrahepatic stones.

向“烧杯”说再见——按比例放大对于优化混合流程和配料流程更具优势

化学工业中的产品研发和工艺研发经常都是在“烧杯”中进行的。该方法的问题在于：从实验室获得的知识和经验几乎无法转化到实际的生产流程中。本文将向您介绍按照缩小比例的方法利用实验室设备对混合流程和配料流程进行优化改进的优势。

超声波在硬脆材料磨削中的应用

大量的过程工艺研究表明,磨削硬脆材质工件比较有效的方法是使用超声波技术支持。在侧切面旋磨运动中轴向使用超声波会明显降低过程力度,而过程力度的降低可以提高走刀速度,从而提高单位时间切削量,提高生产率。

Simulating Spiraling Bubble Movement in the EL Approach

Simulating the detailed movement of a rising bubble can be challenging, especially when it comes to bubble path instabilities. A solution based on the Euler Lagrange (EL) approach is presented, where the bubbles show oscillating shape and/or instable paths while computational cost are at a far lower level than in DNS. The model calculates direction, shape and rotation of the bubbles. A lateral force based on rotation and direction is modeled to finally create typical instable path lines. This is embedded in an EL simulation, which can resolve bubble size distribution, mass transfer and chemical reactions. A parameter study was used to choose appropriate model constants for a mean bubble size of 3 mm. To ensure realistic solution, validation against experimental data of single rising bubbles and bubble swarms are presented. References with 2D and also 3D analysis are taken into account to compare simulative data in terms of typical geometrical parameters and average field values.