Hideki Kamada

Comparison of partially covered nitinol stents with partially covered stainless stents as a historical control in a multicenter study of distal malignant biliary obstruction: the WATCH study

BACKGROUND Covered self-expandable metal stents (CSEMSs) were developed to prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs. OBJECTIVE To evaluate a new, commercially available CSEMS with flared ends and low axial force compared with a commercially available CSEMS without the anti-migration system and high axial force. DESIGN Multicenter, prospective study with a historical cohort. SETTING Twenty Japanese referral centers. PATIENTS This study involved patients with unresectable distal malignant biliary obstruction. INTERVENTION Placement of a new, commercially available, partially covered SEMS. MAIN OUTCOME MEASUREMENTS Recurrent biliary obstruction rate, time to recurrent biliary obstruction, stent-related complications, survival. RESULTS Between April 2009 and March 2010, 141 patients underwent partially covered nitinol stent placement, and between May 2001 and January 2007, 138 patients underwent placement of partially covered stainless stents as a historical control. The silicone cover of the partially covered nitinol stents prevented tumor ingrowth. There were no significant differences in survival (229 vs 219 days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P = .385) between partially covered nitinol stents and partially covered stainless stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to recurrent biliary obstruction was significantly longer (373 vs 285 days; P = .007) with partially covered nitinol stents. Stent removal was successful in 26 of 27 patients (96%). LIMITATIONS Nonrandomized, controlled trial. CONCLUSION Partially covered nitinol stents with an anti-migration system and less axial force demonstrated longer time to recurrent biliary obstruction with no tumor ingrowth and less stent migration.

Utility of pancreatic duct brushing for diagnosis of pancreatic carcinoma

BackgroundThe aim of this study was to evaluate the usefulness of pancreatic duct brushing for diagnosis of pancreatic carcinoma.MethodsBrush cytology was attempted in 58 patients suspected of having pancreatic malignancy because of stricture of the main pancreatic duct, confirmed by endoscopic retrograde cholangiopancreatography. Thirty-eight patients were finally diagnosed by an operation or the clinical course as having pancreatic carcinoma, and the remaining 20 patients as having chronic pancreatitis. The usefulness of brush cytology for diagnosis of pancreatic carcinoma was estimated. We interpreted failures of pancreatic duct brushing to be false negatives when the lesion was malignant.ResultsIn 48 of 58 patients (82.8%), brushing was successfully performed and satisfactory specimens were obtained. Brush cytology was positive in 25 of 38 patients with pancreatic carcinoma (sensitivity 65.8%) and negative in all patients without malignancy (specificity 100%). Overall accuracy was 76.4%. During 2001–2005, the number of back-and-forth motions of the brush was increased to more than 30 times. The sensitivity significantly improved from 43.8% in 1997–2000 to 81.8% in 2001–2005 (P < 0.05). The increased success rate of brushing by improvement of skill in manipulating the guidewire and increased number of cells smeared on glass slides by increased back-and-forth motion of the brush may account for this improvement over time. Moreover, the sensitivity in 2001–2005 was 85.7% if failures of brushing with pancreatic carcinoma are excluded. No major complications occurred, except for two patients with a moderate grade of acute pancreatitis.ConclusionsAlthough further studies with a large number of patients are needed, our results suggest that with recent improvements of the brushing technique, pancreatic duct brushing is a useful and safe method for the differential diagnosis of malignancy from benign diseases of the pancreas.

Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma

Carcinoma of the ampulla of Vater is uncommon. This study aimed to clarify predictors of survival for ampullary adenocarcinoma and to identify characteristics of its two major pathological subtypes.

Usefulness of single and repetitive percutaneous transhepatic gallbladder aspiration for the treatment of acute cholecystitis

BackgroundThe aim of this study was to evaluate the safety and usefulness of single and repetitive percutaneous transhepatic gallbladder aspiration (PTGBA) for the treatment of acute cholecystitis.MethodsPTGBA was performed in patients with acute cholecystitis who showed no improvement after treatment with broad-spectrum antibiotics. PTGBA was carried out at bedside. When the bile was too thick to be aspirated through a 21-gauge needle, an 18-gauge needle was used. Aspiration of the gallbladder contents and injection of antibiotics into the gallbladder were performed without the placement of a drainage catheter. When improvement was not observed after the first attempt, PTGBA was repeated.ResultsSingle PTGBA achieved improvement in 32 of 45 patients. In 11 of the remaining 13 patients, the second PTGBA was effective. In the remaining two patients, repetitive PTGBA was not carried out because of advanced cancer. In two of 45 patients, 18-gauge needles were necessary for PTGBA because of the high viscosity of the bile. PTGBA was carried out in three patients with blockage of the cystic duct by a stent, and it was effective in all three. Two patients whose conditions improved with a single PTGBA experienced a recurrence at 4 and 31 months, respectively, after PTGBA. No other severe complications related to PTGBA were observed in any patients.ConclusionsFor the treatment of acute cholecystitis that does not react to conservative therapies, PTGBA is a safe, simple, and effective treatment modality that can be performed at bedside without any severe complications.

Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest

Cholangiocarcinoma is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Galectin-9 (Gal-9) is a tandem-repeat-type galectin that has recently been shown to exert antiproliferative effects on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human cholangiocarcinoma cells in vitro as well as the microRNAs (miRNAs) associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of cholangiocarcinoma cell lines in vitro and the growth of human cholangiocarcinoma cell xenografts in nude mice. Our data further revealed that Gal-9 increased caspase‑cleaved keratin 18 (CCK18) levels, and the expression of cytochrome c increased in Gal-9-treated cholangiocarcinoma cell lines. These data suggested that Gal-9 induced cholangiocarcinoma cell apoptosis via the intrinsic apoptosis pathway mediated by caspase-dependent or -independent pathways. In addition, Gal-9 reduced the phosphorylation of the epidermal growth factor receptor (EGFR), insulin-like growth factor and insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor receptor and fibroblast growth factor receptor 3 (FGFR3). These findings suggest that Gal-9 can be a candidate of therapeutic target in the treatment of cholangiocarcinoma.

How many cytological examinations should be performed for the diagnosis of malignant biliary stricture via an endoscopic nasobiliary drainage tube

Background and Aim:  The sensitivity of bile cytology is recognized as being low. Repeating cytological sampling is likely to improve the sensitivity. The aim of this study is to determine the optimal number of repeated cytological sampling of bile obtained via an endoscopic nasobiliary drainage (ENBD) tube for the diagnosis of malignant biliary stricture.

Molecular Biologic Approach to the Diagnosis of Pancreatic Carcinoma Using Specimens Obtained by EUS-Guided Fine Needle Aspiration

We review the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), a rapid, safe, cost-effective, and accurate diagnostic modality for evaluating pancreatic tumors. EUS-FNA is currently used for the diagnosis and staging of pancreatic tumors. The sensitivity of EUS-FNA for pancreatic malignancy ranges from 75% to 94%, and its specificity approaches 100% in most studies. However, EUS-FNA has some limitations in the diagnosis of well-differentiated or early-stage cancers. Recent evidence suggests that molecular biological analysis using specimens obtained by EUS-FNA improves diagnostic sensitivity and specificity, especially in borderline cytological cases. It was also reported that additional information regarding patient response to chemotherapy, surgical resectability, time to metastasis, and overall survival was acquired from the genetic analysis of specimens obtained by EUS-FNA. Other studies have revealed that the analysis of KRAS, MUC, p53, p16, S100P, SMAD4, and microRNAs is helpful in making the diagnosis of pancreatic carcinoma. In this paper, we describe the present state of genetic diagnostic techniques for use with EUS-FNA samples in pancreatic diseases. We also discuss the role of molecular biological analyses for the diagnosis of pancreatic carcinoma.

The anti-diabetic drug metformin inhibits pancreatic cancer cell proliferation in vitro and in vivo: Study of the microRNAs associated with the antitumor effect of metformin.

Recent studies suggest that metformin, which is a commonly used oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis, yet the detailed mechanisms by which metformin affects various types of cancers, including pancreatic cancer, remain unknown. The aim of the present study was to evaluate the effects of metformin on human pancreatic cancer cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin. We used the human pancreatic cancer cell lines Panc1, PK1 and PK9 to study the effects of metformin on human pancreatic cancer cells. Athymic nude mice bearing xenograft tumors were treated with or without metformin. Tumor growth was recorded after 5 weeks, and the expression of cell cycle-related proteins was determined. In addition, we used miRNA microarray tips to explore the differences in the levels of miRNAs in Panc1 cells and xenograft tumors treated with metformin or without. Metformin inhibited the proliferation of Panc1, PK1 and PK9 cells in vitro. This inhibition was accompanied by a strong decrease in G1 cyclins (particularly in cyclin D1) and retinoblastoma protein (Rb) phosphorylation. In addition, metformin reduced the phosphorylation of epidermal growth factor receptor (EGFR), particularly the phosphorylation of EGFR at Tyr845, and insulin-like growth factor 1 receptor (IGF-1R) in vitro and in vivo. miRNA expression was markedly altered by the treatment with metformin in vitro and in vivo. Our results revealed that metformin inhibits human pancreatic cancer cell proliferation and tumor growth, possibly by suppressing the cell cycle-related molecules via alteration of miRNAs.

Pre-cutting using a noseless papillotome with independent lumens for contrast material and guidewire

Background:  The technical success of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) depends on selective cannulation into the bile duct. We have developed a new type of precut papillotome for selective cannulation.

Analysis of the amount of tissue sample necessary for mitotic count and Ki-67 index in gastrointestinal stromal tumor sampling

There are no established opinions concerning whether the amount of tissue affects the accuracy of histological analyses in gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the appropriate amount of tissue sample needed for mitotic count based on the risk classification of GISTs and the Ki-67 index using the following three methods: endoscopic ultrasound-guided fine-needle aspiration (FNA), a novel sampling method called tunneling bloc biopsy (TBB), and biopsy forceps followed by TBB (Bf). Forty-three samples (12 FNA, 17 TBB and 14 Bf) diagnosed as GISTs by immunohistological analysis were utilized. The major and minor axes and overlay area of one piece of specimen (OPS) from the three sampling methods were measured using digital imaging software and were analyzed comparatively regarding the acquisition of histological data. The mean major and minor axes (mm) and overlay areas (mm2) were in the order of TBB > Bf > FNA. The evaluable rates by mitotic count and Ki-67 were, respectively, 75% (9/12) and 83.3% (10/12) for FNA samples, 100% (17/17) and 100% (17/17) for TBB samples, and 100% (14/14) and 100% (14/14) for Bf samples (P>0.05). Three FNA samples were judged unevaluable due to too small specimens in overall diagnosis including mitotic count and Ki-67, calculating the cut-off value for the overlay area of OPS as 0.17 mm2. Comparing the concordance rates between the pre- and post-operative samples, TBB samples was significantly better than FNA (P<0.05). Conclusively, while the amounts of tissues obtained by TBB and Bf are unnecessary for the histological assessment of mitotic count and Ki-67 index, developments of the FNA method are needed to minimize sample error. Considering the technical aspects, as well as the size of the specimens, could help to guide therapeutic planning and improve diagnostic yield for GI subepithelial tumors.