Search

Background: There is no consensus on the choice of either unilateral or bilateral drainage in stent placement for patients with unresectable hilar biliary obstruction. The aim of the present study was to clarify which drainage method is superior., Methods: We retrospectively reviewed 82 patients with hilar biliary obstruction who underwent metallic stenting. These patients were divided into a unilateral drainage group (Uni group) and a bilateral drainage group (Bi group)., Results: There was no significant difference between the groups in median survival time, median stent patency period, and median complication-free survival time. The most frequent complication was stent obstruction, followed by cholangitis. Liver abscess was found at a higher frequency in the Bi group (17.6%) than in the Uni group (1.5%) (P=0.0266). There was no significant difference between the groups in the occurrence of two or more complications (P=0.247), life-threatening severe complications (P=0.0577), and stent obstruction by sludge (P=0.0912)., Conclusion: When compared with bilateral biliary drainage, unilateral biliary drainage is associated with a lower incidence of liver abscess as well as a comparable outcome of stent patency time and complication-free survival. We therefore propose that hilar biliary obstruction can be treated first by unilateral drainage with a metallic stent and by bilateral drainage only in patients who develop cholangitis in the contralateral biliary tree., (© 2010 The Authors. Digestive Endoscopy © 2010 Japan Gastroenterological Endoscopy Society.)

The prognosis of patients with pancreatic cancer is very poor because of late diagnosis and the lack of response to various therapies. Pancreatic cancer is generally resistant to chemotherapy and is highly fatal. Gemcitabine (GEM) appears to be the only effective agent for treatment of pancreatic cancer. However, a high level of inherent and acquired tumor resistance makes the clinical impact of GEM modest. Proteomic differential display analysis for GEM-sensitive human pancreatic adenocarcinoma cell line KLM1 and GEM-resistant KLM1-R cells by using two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry produced 33 protein spots. Of these, 23 were up-regulated and 10 were down-regulated in KLM1-R compared to KLM1 cells. The up-regulated proteins include acidic leucine-rich nuclear phosphoprotein 32 family member A, reticulocalbin-1, gamma-synuclein, microtubule-associated protein RP/EB family, sialic acid synthase, peptidyl-prolyl cis-trans isomerase A, far upstream element-binding protein 2 and catalase. The down-regulated proteins include far upstream element-binding protein 1, gamma-synuclein, galectin-1 and stathmin. Two spots of heat-shock protein 27 were up-regulated in KLM1-R cells. These results suggest an important complementary role for proteomics in the identification of proteins which may play a role in the poor response of pancreatic cancer to GEM.

Background: Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine: Gemzar) (GEM) appears to be the only effective anticancer drug for pancreatic cancer, but it has little impact on outcome due to a high level of inherent and acquired tumor resistance. Our previous proteomic study demonstrated that the expression of three spots of heat-shock protein 27 (HSP27) was increased in GEM-resistant pancreatic cancer cells and could play a role in determining the sensitivity of pancreatic cancer to GEM., Materials and Methods and Results: In the present study, using one-dimensional and two-dimensional Western blotting, we elucidated that these three spots of HSP27 were phosphorylated in GEM-resistant pancreatic cancer cell line, KLM1-R., Conclusion: Phosphorylated HSP27 may play an important role in the resistance to GEM, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with GEM.

We report the successful retrieval of an impacted mechanical lithotripsy basket. In a patient with two large common bile duct stones, the basket with the entrapped stone was impacted within the mid-common bile duct. We then attempted to use another mechanical lithotripter; however the central wire of the basket fractured at the handle portion. Grasping a few wires of the impacted basket with rat-tooth forceps allowed the wires of the basket to slip away from the stone. The present report describes the safe and effective use of rat-tooth forceps in the management of an impacted lithotripter basket.

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the treatment of patients with pancreaticobiliary disorders, but endoscopic therapy is very difficult to carry out in patients with a Roux-en-Y anastomosis. We herein present the results of ERCP for patients with a Roux-en-Y anastomosis using a double-balloon endoscope. Six patients (six men with a mean age of 69 years) who had undergone prior gastric resection with Roux-en-Y reconstruction were enrolled in the present study and underwent ERCP and associated procedures. ERCP was carried out with a double balloon endoscope, which has one balloon attached to the tip of the endoscope and another attached to the distal end of the soft overtube. In all patients, entering the Y loop was successfully accomplished, and the papilla of Vater was also reached in all cases (100%). Cannulation was successful in four patients (66.7%). The final diagnosis was choledocholithiasis in two patients, biliary fistula in one patient and pancreatic cancer in one patient. A needle-knife precut papillotomy was carried out after placement of a bile duct stent in two patients, and injection of N-butyl-2-cyanoacrylate into a biliary fistula was carried out in one patient. None of the patients suffered from any complications. A double balloon endoscope is therefore considered to be useful for carrying out ERCP and associated procedures in patients with a Roux-en-Y anastomosis.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) and associated procedures are difficult to perform in patients with a Roux-en-Y reconstruction. Therefore, at present, at many institutions, ERCP is not generally performed for those with a Roux-en-Y anastomosis., Methods: However, double-balloon endoscopes (DBEs) have dramatically changed this situation., Results: The use of a DBE enables an endoscopic approach into the deeply situated small intestine, which has been difficult with a conventional endoscope. Therefore, ERCP for patients with a Roux-en-Y anastomosis has been attempted using a DBE, and good results have been reported., Conclusion: The development of DBEs has created the possibility of performing ERCP for patients with Roux-en-Y reconstruction in whom an endoscopic approach has conventionally been believed to be difficult.

Pancreatic cancer is one of the most highly fatal cancers and is generally resistant to chemotherapy. Currently, gemcitabine appears to be the only effective agent for its treatment and is the preferred first-line therapy. However, the clinical impact of gemcitabine remains modest due to a high level of inherent and acquired tumor resistance. We investigated protein expression in gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines by proteomics. Tumor cell proteins were separated by two-dimensional gel electrophoresis, then the protein spots that showed increased or decreased expression in gemcitabine-sensitive cell lines were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Western blotting. Nine out of ten proteins showing differential expression in gemcitabine-resistant and -sensitive cell lines were identified, confirming an increase in heat shock protein 27 (HSP27) and a decrease in nucleophosmin (NPM) in the resistant lines. These results suggest that HSP27 and NPM may play a role in the poor response of pancreatic cancer to gemcitabine.

Pancreatic cancer remains a devastating disease and >96% of patients with pancreatic cancer do not survive for more than 5 years. Gemcitabine (2'-deoxy-2'-difluoro-deoxycytidine: Gemzar) appears to be the only clinically effective drug for pancreatic cancer, but it has little impact on outcome. Proteomic analysis of gemcitabine-sensitive cells (KLM1) and resistant pancreatic cells (KLM1-R) was performed to identify target proteins of the gemcitabine. We found seven proteins, HSP27, peroxiredoxin 2, endoplasmic reticulum protein ERp29 precursor, 6-phosphogluconolactonase, triosphospate isomerase, alpha enolase, and nucleophosmine that could play a role in determining the sensitivity of pancreatic cancer to gemcitabine. We knocked down HSP27 in KLM1-R and the sensitivity to gemcitabine was restored. In addition, increased HSP27 expression in tumor specimens was related to higher resistibility to gemcitabine in patients of pancreatic cancer. HSP27 may play an important role in the resistibility to gemcitabine, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with gemcitabine.

The prognosis of patients with pancreatic cancer is very poor because of late diagnosis and the lack of response to various therapies. We tried to identify proteins that might be available for early diagnosis and effective therapies by proteomic profiling of pancreatic cancer tissues. Pancreatic cancerous and paired non-cancerous tissues obtained from surgical resections or autopsies of 10 patients were analyzed by two-dimensional gel electrophoresis. The differential display showed 11 spots whose expression was increased in cancerous tissues compared with the paired non-cancerous tissues. The liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) system identified the spots as alpha-enolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase, transgelin, calmodulin, superoxide dismutase(Mn) mitochondrial precursor, glutathione S-transferase P, cyclophilin A, protein disulfide isomerase A3 precursor, and apolipoprotein A-I precursor. Two of the 11 spots were detected as GAPDH. We noticed that 4 of 11 spots were enzymes involved in glycolytic pathway. Increased glycolysis in cancer cells has been regarded as the effect of intratumoral hypoxia and is possibly associated with tumor invasion, metastasis or resistance to therapies. These glycolytic proteins and transgelin, were confirmed by Western blotting and immunohistochemistry.

Background: Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety., Methods: A total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33-85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up., Results: The final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred., Conclusions: EUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.

Background: Comparative genomic hybridization (CGH) analysis of pancreatic cancer has been done exclusively for surgical and autopsy specimens, because of the difficulty of tissue sampling without surgery. To overcome this difficulty, we applied CGH technology to cells obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)., Methods: In the present study, we performed EUS-FNA for 17 patients with pancreatic cancer before surgery. Tumor cells were selected by microdissection. DNA was extracted from the cells and amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Then CGH was carried out., Results: In the 15 patients with tubular adenocarcinoma, the most common loci of gains (including amplification) were 5p, 8q, and 20q (60% of the patients); and 1q, 7p, and 12p (27%). The most frequent losses were 17p (73%); 9p, 18q, and 19p (47%); and 8p (33%). These findings were similar to our previously reported data. Both of the patients with acinar cell carcinoma showed gains of 2q and 5p, and losses of 1p, 9p, 9q, 11p, 11q, 14q, 17p, 17q, and 18q., Conclusions: The results of this study suggest that comprehensive genetic analysis is possible for EUS-FNA biopsy specimens, with a combination of microdissection and DOP-PCR. This analytical strategy will enable us to evaluate the biological characteristics of pancreatic cancer before treatment.

Background/aims: Histological typing of gastric cancer is important for determining the treatment strategy and predicting the prognosis. We compared the histological types obtained by endoscopic forceps biopsy with the finally determined histological types of surgically resected specimens to investigate the reliability of histologically typing gastric cancer by biopsy., Methodology: Agreement between the biopsy typing and the final histological typing based on the predominant histology of the resected tumor was studied in 115 consecutive gastric cancers., Results: The overall agreement rate of histological typing of gastric cancer was 75.7%. In patients with early gastric cancer, the agreement rate was a high 82.5% and the final histological type was usually predicted. In patients with advanced gastric cancer, the agreement rate was 72.0%, which was significantly lower than for early gastric cancer (p<0.05). The agreement rate for advanced differentiated cancer was also significantly lower than that for early cancer (63.6% vs. 90.0%) (p<0.05)., Conclusions: The reliability of using histological typing by biopsy to set the indications for endoscopic treatment and for preoperative prediction of the prognosis is expected to be good for differentiated early gastric cancer, but it might not be adequate for advanced cancer or undifferentiated cancer.

Lymph node metastasis is a major prognostic factor in human cancer. Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in several human solid tumors. However, the clinical significance of VEGF-C has remained unknown in gallbladder carcinoma. Paraffin-embedded tumor specimens of 52 surgically resected gallbladder cancers were immunohistochemically stained for VEGF-C, VEGF, and CD34. The correlations among VEGF-C expression, VEGF expression, microvessel density (MVD), clinicopathologic features, and clinical outcomes were statistically analyzed. Thirty-three (63%) of the 52 gallbladder cancers were highly positive for VEGF-C protein by immunohistochemistry. VEGF-C expression was significantly correlated with lymphatic vessel involvement, lymph node metastasis, and worse outcomes after operation (p<0.001, p<0.001, p<0.001, respectively), but not with MVD. By the Cox regression model, lymphatic vessel involvement emerged as an independent prognostic parameter. These results suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and lymph node metastasis in human gallbladder cancer.

Background: A new mechanical puncture-echoendoscope was evaluated by comparing it with conventional linear and radial echoendoscopes. The new instrument has a 300 degrees image field parallel to the axis of the echoendoscope, which could potentially improve accuracy and facilitate assessment of suspected pancreatic lesions before needle puncture., Methods: Twenty consecutive patients with suspected pancreatic lesions were evaluated endosonographically, including fine needle aspiration (FNA). The initial assessment was performed by random selection of either the new instrument or the standard linear echoendoscope. After completing the assessment including FNA, the procedure with FNA was repeated with the other puncture echoendoscope. The findings with these 2 instruments were compared to those with the conventional radial scanning echoendoscope., Results: FNA was performed in 17 patients with pancreatic head lesions. In 3 patients without a visible pancreatic mass lymph, nodes greater than 10 mm in diameter were aspirated. The ability to image the needle, number of punctures, and material obtained were comparable for both puncture echoendoscopes. There were no significant differences with regard to time required for FNA with both puncture echoendoscopes or in the assessment of surrounding structures with all 3 instruments. The results of cytopathologic evaluation of material obtained by FNA were similar in 15 cases. The new instrument could not be passed into the esophagus in 1 patient because of an esophageal stricture., Conclusions: The performance of the new mechanical puncture echoendoscope was satisfactory for assessment and FNA of pancreatic lesions. The additional use of the conventional radial scanning echoendoscope provided no advantage with regard to any parameter assessed.