Even experienced endoscopists have 90% success in achieving deep biliary cannulation with standard methods. Biliary cannulation may become difficult in 10%-15% of patients with biliary obstruction and pre- cut (access...Even experienced endoscopists have 90% success in achieving deep biliary cannulation with standard methods. Biliary cannulation may become difficult in 10%-15% of patients with biliary obstruction and pre- cut (access) sphincterotomy is frequently chosen as a rescue treatment in these cases. Generally, precut sphincterotomy ensures a rate of 90%-100% success- ful deep biliary cannulation. The precut technique has been performed as either a fistulotomy with a needle knife sphincterotome or as a transpapillary septotomy with a standard sphincterotome. Both methods have similar efficacy and complication rates when adminis- tered to the proper patient. Although precut sphincter- otomy ensures over 90% success of biliary cannula- tion, it has been characterized as an independent risk factor for pancreatitis. The complications of the precut technique are not limited to pancreatitis. Two more important ones, bleeding and perforation, are also re- ported in some publications as being observed more commonly than during standard sphincterotomy. It is also reported that precut sphincterotomy increases morbidity when performed in patients without dilata- tion of their biliary tract. Nevertheless, precut sphinc- terotomy is a good alternative as a rescue method in the setting of a failed standard cannulation method. This paper discusses the technical details, timing, ef- ficacy and potential complications of precut sphincter- otomy.展开更多
Cholangiocarcinoma(CC) is a devastating cancer aris-ing from biliary epithelia.Unfortunately,the incidence of this disease is increasing in Western countries.These tumors progress insidiously,and liver failure,biliary...Cholangiocarcinoma(CC) is a devastating cancer aris-ing from biliary epithelia.Unfortunately,the incidence of this disease is increasing in Western countries.These tumors progress insidiously,and liver failure,biliary sepsis,malnutrition and cancer cachexia are general modes of death associated with this disease.To date,no established therapy for advanced dis-ease has been established or validated.However,our knowledge in tumor biology is increasing dramatically and new drugs are under investigation for treatment of this notorious tumor.In clinical practice,there are better diagnostic tools in use to facilitate an earlier diagnosis of CC,at least in those patients with known risk factors.CC is resectable for cure in only a small percentage of patients.Preoperative staging for vas-cular and biliary extension of CC is very important in this tumor.Laparoscopy and recently endosonography seem to protect against unnecessary laparotomies in these patients.During the last 15 years,aggressive surgical approaches,including combined liver resec-tions and vascular reconstructive surgical expertise,have improved survival in patients with CC.Surgery is contraindicated in CC cases having primary sclerosing cholangitis(PSC).Although CC was previously consid-ered a contraindication to liver transplantation,new cautious protocols,including neo-adjuvant chemora-diation therapies and staging procedures before the transplantation,have made it possible to achieve long-term survival after liver transplantation in this disease.New ablative therapies with photodynamic therapy,intraductal high-intensity ultrasonography and chemo-therapy-impregnated plastic biliary endoprosthesis are important steps in the palliative management of extra-hepatic CCs.Radiofrequency and chemo-embolization methods are also applicable for intra-hepatic CCs as palliative modes of treatment.We need more prospec-tive randomized controlled trials to evaluate the role of the new emerging therapies for CC patients.展开更多
AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 ch...AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. RESULTS: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time-and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUSION: Proteosome inhibition induces ERdysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma.展开更多
AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 &...AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.展开更多
Lipoma within an inverted Meckel's diverticulum presen- ting with hemorrhage and partial intestinal obstruction is an exceptional clinical entity. We report a case of 47-year-old male with a history of recurrent e...Lipoma within an inverted Meckel's diverticulum presen- ting with hemorrhage and partial intestinal obstruction is an exceptional clinical entity. We report a case of 47-year-old male with a history of recurrent episodes of partial intestinal obstruction and melena due to a subserosal lipoma located in the base of an inverted Meckel's diverticulum. According to our knowledge, this is the first case of a lipoma within a Meckel's diverticulum giving rise to this clinical scenario without the existence of heterotrophic gastric or pancreatic tissues.展开更多
The mucocele of the appendix is an uncommon disorder which is often asymptomatic but sometimes causes acute appendicitis-like symptoms. Sometimes, patients with mucocele can present with confusing symptoms. Preoperati...The mucocele of the appendix is an uncommon disorder which is often asymptomatic but sometimes causes acute appendicitis-like symptoms. Sometimes, patients with mucocele can present with confusing symptoms. Preoperative suspicion and diagnosis of appendiceal mucocele are important. Ultrasonography and computed tomography are useful tools for the diagnosis of appendiceal mucocele. It may be also recognised by colonoscopy as a smooth submucosal lesion of the cecum. Optima management of the mucocele could be achieved through accurate preoperative diagnosis. Preoperative diagnosis is a major component for minimizing intra-operative and post-operative complications. We herein report five cases and discuss the diagnostic methods and surgical treatment.展开更多
There is an ongoing discussion on how to diagnose a hyperechogenic pancreas and what is the clinical significance of diffusely hyperechogenic pancreas. Computerized tomography and magnetic resonance imaging are the mo...There is an ongoing discussion on how to diagnose a hyperechogenic pancreas and what is the clinical significance of diffusely hyperechogenic pancreas. Computerized tomography and magnetic resonance imaging are the more appropriate methods to diagnose pancreatic hyperechogenicity when compared with transcutaneous or endoscopic ultrasound examination. More importantly, pancreatic hyperechogenicity may not be a certain indicator of pancreatic fat infiltration. Even if it is true, we do not know the clinical significances of pancreatic fat accumulation. Some suggested that excess fat in the pancreas is associated with chronic pancreatitis. However, several histological studies on human alcoholic chronic pancreatitis did not prove the presence of fatty pancreas in such cases. Thus, except for aging, it is very rare to have truly steatotic pancreas in the absence of certain human diseases.展开更多
Prolonged cholestasis is a very rare complication of endoscopic retrograde cholangiography (ERC). Only few cases with this complication are reported in the English literature. We report persisting cholestatic jaundice...Prolonged cholestasis is a very rare complication of endoscopic retrograde cholangiography (ERC). Only few cases with this complication are reported in the English literature. We report persisting cholestatic jaundice in a 73-year old man after successful therapeutic ERC for choledocholithiasis. Serologic tests for viral and autoimmune hepatitis were all negative. A second-look ERC was normal also. He denied any medication except for prophylaxis given intravenous 1 g ceftriaxon prior to the ERC procedure. After an unsuccessful trial with ursodeoxycholic acid and cholestyramine for 2 wk, this case was efficiently treated with corticosteroids and plasmapheresis. His cholestatic enzymes became normal and intense pruritis quickly resolved after this treatment which lasted during his follow- up period. We discussed the possible mechanisms and treatment alternatives of intrahepatic cholestasis associated with the ERC procedure.展开更多
Self expanding metalic stent(SEMS) application can cause serious problems up to one third of the patients and some studies reported negative effect of SEMSs on survival in patients with malignancy. The SEMS type espec...Self expanding metalic stent(SEMS) application can cause serious problems up to one third of the patients and some studies reported negative effect of SEMSs on survival in patients with malignancy. The SEMS type especially the rigid one like Wall-stent rather than more flexible type Ultraflex was also reported to have bad impact on the risk of perforation we believe that stent based management protocol for patients with non-perforating left sided obstructing colorectal cancer is a complex method that needs qualified medical and technical team.展开更多
文摘Even experienced endoscopists have 90% success in achieving deep biliary cannulation with standard methods. Biliary cannulation may become difficult in 10%-15% of patients with biliary obstruction and pre- cut (access) sphincterotomy is frequently chosen as a rescue treatment in these cases. Generally, precut sphincterotomy ensures a rate of 90%-100% success- ful deep biliary cannulation. The precut technique has been performed as either a fistulotomy with a needle knife sphincterotome or as a transpapillary septotomy with a standard sphincterotome. Both methods have similar efficacy and complication rates when adminis- tered to the proper patient. Although precut sphincter- otomy ensures over 90% success of biliary cannula- tion, it has been characterized as an independent risk factor for pancreatitis. The complications of the precut technique are not limited to pancreatitis. Two more important ones, bleeding and perforation, are also re- ported in some publications as being observed more commonly than during standard sphincterotomy. It is also reported that precut sphincterotomy increases morbidity when performed in patients without dilata- tion of their biliary tract. Nevertheless, precut sphinc- terotomy is a good alternative as a rescue method in the setting of a failed standard cannulation method. This paper discusses the technical details, timing, ef- ficacy and potential complications of precut sphincter- otomy.
文摘Cholangiocarcinoma(CC) is a devastating cancer aris-ing from biliary epithelia.Unfortunately,the incidence of this disease is increasing in Western countries.These tumors progress insidiously,and liver failure,biliary sepsis,malnutrition and cancer cachexia are general modes of death associated with this disease.To date,no established therapy for advanced dis-ease has been established or validated.However,our knowledge in tumor biology is increasing dramatically and new drugs are under investigation for treatment of this notorious tumor.In clinical practice,there are better diagnostic tools in use to facilitate an earlier diagnosis of CC,at least in those patients with known risk factors.CC is resectable for cure in only a small percentage of patients.Preoperative staging for vas-cular and biliary extension of CC is very important in this tumor.Laparoscopy and recently endosonography seem to protect against unnecessary laparotomies in these patients.During the last 15 years,aggressive surgical approaches,including combined liver resec-tions and vascular reconstructive surgical expertise,have improved survival in patients with CC.Surgery is contraindicated in CC cases having primary sclerosing cholangitis(PSC).Although CC was previously consid-ered a contraindication to liver transplantation,new cautious protocols,including neo-adjuvant chemora-diation therapies and staging procedures before the transplantation,have made it possible to achieve long-term survival after liver transplantation in this disease.New ablative therapies with photodynamic therapy,intraductal high-intensity ultrasonography and chemo-therapy-impregnated plastic biliary endoprosthesis are important steps in the palliative management of extra-hepatic CCs.Radiofrequency and chemo-embolization methods are also applicable for intra-hepatic CCs as palliative modes of treatment.We need more prospec-tive randomized controlled trials to evaluate the role of the new emerging therapies for CC patients.
基金NIH grants DK63947 (to GJG)the Mayo and Palumbo Foundations
文摘AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. RESULTS: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time-and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUSION: Proteosome inhibition induces ERdysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma.
文摘AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.
文摘Lipoma within an inverted Meckel's diverticulum presen- ting with hemorrhage and partial intestinal obstruction is an exceptional clinical entity. We report a case of 47-year-old male with a history of recurrent episodes of partial intestinal obstruction and melena due to a subserosal lipoma located in the base of an inverted Meckel's diverticulum. According to our knowledge, this is the first case of a lipoma within a Meckel's diverticulum giving rise to this clinical scenario without the existence of heterotrophic gastric or pancreatic tissues.
文摘The mucocele of the appendix is an uncommon disorder which is often asymptomatic but sometimes causes acute appendicitis-like symptoms. Sometimes, patients with mucocele can present with confusing symptoms. Preoperative suspicion and diagnosis of appendiceal mucocele are important. Ultrasonography and computed tomography are useful tools for the diagnosis of appendiceal mucocele. It may be also recognised by colonoscopy as a smooth submucosal lesion of the cecum. Optima management of the mucocele could be achieved through accurate preoperative diagnosis. Preoperative diagnosis is a major component for minimizing intra-operative and post-operative complications. We herein report five cases and discuss the diagnostic methods and surgical treatment.
文摘There is an ongoing discussion on how to diagnose a hyperechogenic pancreas and what is the clinical significance of diffusely hyperechogenic pancreas. Computerized tomography and magnetic resonance imaging are the more appropriate methods to diagnose pancreatic hyperechogenicity when compared with transcutaneous or endoscopic ultrasound examination. More importantly, pancreatic hyperechogenicity may not be a certain indicator of pancreatic fat infiltration. Even if it is true, we do not know the clinical significances of pancreatic fat accumulation. Some suggested that excess fat in the pancreas is associated with chronic pancreatitis. However, several histological studies on human alcoholic chronic pancreatitis did not prove the presence of fatty pancreas in such cases. Thus, except for aging, it is very rare to have truly steatotic pancreas in the absence of certain human diseases.
文摘Prolonged cholestasis is a very rare complication of endoscopic retrograde cholangiography (ERC). Only few cases with this complication are reported in the English literature. We report persisting cholestatic jaundice in a 73-year old man after successful therapeutic ERC for choledocholithiasis. Serologic tests for viral and autoimmune hepatitis were all negative. A second-look ERC was normal also. He denied any medication except for prophylaxis given intravenous 1 g ceftriaxon prior to the ERC procedure. After an unsuccessful trial with ursodeoxycholic acid and cholestyramine for 2 wk, this case was efficiently treated with corticosteroids and plasmapheresis. His cholestatic enzymes became normal and intense pruritis quickly resolved after this treatment which lasted during his follow- up period. We discussed the possible mechanisms and treatment alternatives of intrahepatic cholestasis associated with the ERC procedure.
文摘Self expanding metalic stent(SEMS) application can cause serious problems up to one third of the patients and some studies reported negative effect of SEMSs on survival in patients with malignancy. The SEMS type especially the rigid one like Wall-stent rather than more flexible type Ultraflex was also reported to have bad impact on the risk of perforation we believe that stent based management protocol for patients with non-perforating left sided obstructing colorectal cancer is a complex method that needs qualified medical and technical team.