Susumu Hijioka

Prospective clinical study of EUS-guided choledochoduodenostomy for malignant lower biliary tract obstruction.

OBJECTIVES:Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has recently been reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) in cases of biliary obstruction, when endoscopic biliary drainage (EBD) is unsuccessful. However, prospective studies of EUS-CDS have not yet been performed. We conducted a prospective study to evaluate the safety, feasibility, and efficacy of EUS-CDS in patients with malignant lower biliary tract obstruction.METHODS:A prospective study to confirm the safety of EUS-CDS was carried out in 6 patients, followed by a trial to evaluate the feasibility and efficacy of EUS-CDS in 12 additional patients. We placed a plastic stent from the duodenal bulb into the extrahepatic bile duct under EUS guidance using an oblique viewing echoendoscope, needle knife, guidewire, and biliary dilators.RESULTS:The site of extrahepatic bile duct puncture was the common hepatic duct in 15 patients and the common bile duct in 3 patients. Mean diameter of the punctured extrahepatic bile ducts was 10u2009mm (range: 6–20u2009mm). Technical and functional success rates were 94% (17/18) and 100% (17/17), respectively. Median procedure time was 30u2009min (range: 10–52u2009min). Median duration to first oral intake after the procedure was 1 day (range: 1–3 days). Early complications were encountered in three (17%) patients, including focal peritonitis in two patients and hemobilia in one patient. During the follow-up period (median: 163 days; range: 46–484 days), 12 stent occlusion events were observed in nine patients. Re-intervention with exchange of the occluded stent was successful in 8 of 12 (66%) times. Severe early and late complications were not encountered in any patients in this study. Median duration of stent patency by Kaplan–Meier analysis was 272 days.CONCLUSIONS:EUS-CDS is safe, feasible, and effective as an alternative to PTBD and EBD in cases of malignant distal biliary tract obstruction. Prospective randomized studies are needed to compare the safety and efficacy of various kinds of endoscopic devices used in EUS-CDS and to compare EUS-CDS with PTBD or EBD.

Evaluation of Ki-67 index in EUS–FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors

BACKGROUND AND STUDY AIMnMalignancy in pancreatic neuroendocrine tumors (PNETs) is graded by assessing the resected specimens according to the World Health Organization (WHO) 2010 criteria. The feasibility of such grading using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens remains unclear. The aim of this study was to ascertain the optimal method of measuring the Ki-67 index in EUS-FNA specimens, using resected specimens as the criterion standard.nnnPATIENTS AND METHODSnA total of 58 consecutive patients diagnosed with PNETs between March 1998 and May 2011 were included. The study measured intratumoral Ki-67 index heterogeneity, concordance rates of PNET grading by EUS-FNA with grade of the resected tumor, optimal method of measuring the Ki-67 index in EUS-FNA specimens, and survival analysis based on EUS-FNA specimen grading.nnnRESULTSnIntratumoral dispersion of Ki-67 index in resected specimens was 0.033 for Grade 1 and 0.782 for Grade 2 tumors (P<0.001). Concordance rates for WHO classification between EUS-FNA and resected specimens were 74.0% using the mean Ki-67 index in EUS-FNA specimens and 77.8% using the highest Ki-67 index. The concordance rate rose to 90% when EUS-FNA samples with less than 2000 tumor cells were excluded (26% of EUS-FNA cases). The Kaplan-Meier survival curves were significantly stratified by the EUS-FNA grading of PNETs with 5-year survival rates of 100%, 58.3%, and 0%, for Grade 1, Grade 2, and neuroendocrine carcinoma (NEC) tumors, respectively.nnnCONCLUSIONSnGrading of PNETs by the highest Ki-67 index in EUS-FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy.

Prospective clinical study of endoscopic ultrasound-guided choledochoduodenostomy with direct metallic stent placement using a forward-viewing echoendoscope.

A prospective clinical study was conducted to evaluate the safety, feasibility, and efficacy of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) with direct metallic stent placement using a prototype forward-viewing echoendoscope. The indication for EUS - CDS in this study was lower biliary obstruction only, and not failed endoscopic biliary drainage, because the aim was to evaluate EUS - CDS for first-line biliary drainage therapy. The technical and functional success rates were 94 % (17 /18) and 94 % (16 /17), respectively. Early complications (focal peritonitis) were encountered in two patients (11 %). No patients developed late complications. EUS - CDS with direct metallic stent placement using a forward-viewing echoendoscope was generally feasible and effective for malignant distal biliary tract obstruction. The forward-viewing echoendoscope was useful, especially for deploying the metallic stent.

Diagnostic ability and factors affecting accuracy of endoscopic ultrasound-guided fine needle aspiration for pancreatic solid lesions: Japanese large single center experience.

BackgroundSeveral studies have investigated the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic lesions, but they have included only limited patient populations. This study aimed to clarify the diagnostic accuracy of EUS-FNA in a large number of pancreatic lesions, and to describe the factors that influence it.MethodsFrom March 1997 to May 2010, 944 consecutive patients who had undergone EUS-FNA for pancreatic solid lesions were evaluated retrospectively. Factors affecting EUS-FNA accuracy were then analyzed.ResultsA total of 996 solid pancreatic lesions were sampled by EUS-FNA. The overall sampling adequacy and diagnostic accuracy of these lesions were 99.3xa0% (989/996) and 91.8xa0% (918/996), respectively. The sensitivity and specificity for differentiating malignant from benign lesions were 91.5xa0% (793/867) and 97.7xa0% (126/129), respectively. The diagnostic performance was significantly higher when both cytological and cell-block examinations were carried out than with only cytological examination. In multivariate analysis, final diagnosis, location of lesion, lesion size, availability of on-site cytopathological evaluation, and experience of EUS-FNA procedure were independent factors affecting the accuracy of EUS-FNA. On-site cytopathological evaluation and lesion size were found to be the most weighted factors affecting diagnostic accuracy.ConclusionsEUS-FNA for pancreatic solid lesions yielded a high accuracy and low complication rate. Both cytological and cell-block preparations and on-site cytopathological evaluation contributed to improve the accuracy. The diagnostic ability of EUS-FNA was less for smaller lesions, and repeated procedures may be needed if malignancy is suspected.

EUS-Guided Biliary Drainage.

Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.

Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas

BackgroundThe WHO classified pancreatic neuroendocrine neoplasms in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to the Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs.MethodsWe retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated NEC (WDNEC) and poorly differentiated NEC (PDNEC). The latter was further subdivided into large-cell and small-cell subtypes.ResultsThe median Ki67 LI was 69.1xa0% (range 40–95xa0%). Eleven WHO-NECs were subclassified into 4 WDNECs and 7 PDNECs. The latter was further separated into 3 large-cell and 4 small-cell subtypes. Comparisons of WDNEC vs. PDNEC revealed the following traits: hypervascularity on CT, 50xa0% (2/4) vs. 0xa0% (0/7) (Pxa0=xa00.109); median Ki67 LI, 46.3xa0% (40–53xa0%) vs. 85xa0% (54–95xa0%) (Pxa0=xa00.001); Rb immunopositivity, 100xa0% (4/4) vs. 14xa0% (1/7) (Pxa0=xa00.015); KRAS mutations, 0xa0% (0/4) vs. 86xa0% (6/7) (Pxa0=xa00.015); response rates to platinum-based chemotherapy, 0xa0% (0/2) vs. 100xa0% (4/4) (Pxa0=xa00.067), and median survival, 227 vs. 186xa0days (Pxa0=xa00.227).ConclusionsThe WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing profiles of Ki67 LI, Rb immunopositivity and KRAS mutation, and distinct response to chemotherapy. Further studies for the reevaluation of the current WHO 2010 classification are warranted.

Can EUS-guided FNA distinguish between gallbladder cancer and xanthogranulomatous cholecystitis?

BACKGROUNDnEUS-guided FNA (EUS-FNA) is a useful modality for sampling various targets, but its applicability to gallbladder (GB) mass lesions is limited.nnnOBJECTIVEnTo determine the usefulness of EUS-FNA for diagnosing GB mass lesions.nnnDESIGNnSingle-center, retrospective, case-series study.nnnSETTINGnTertiary-care referral center.nnnPATIENTSnThis study involved 15 consecutive patients who underwent EUS-FNA of GB mass lesions. We punctured GB masses in patients with suspected xanthogranulomatous cholecystitis to distinguish them from malignancy, and in patients with unresectable GB carcinoma for pathological confirmation. The final diagnosis was based on surgical histopathological results or follow-up outcome.nnnINTERVENTIONSnEUS-FNA.nnnMAIN OUTCOME MEASUREMENTSnEvaluation of EUS-FNA sampling adequacy rate and diagnostic yield.nnnRESULTSnXanthogranulomatous cholecystitis was suspected in 6 of the 15 patients. EUS-FNA revealed foam cells (n = 3), inflammatory cells (n = 1, proven by cholecystectomy), and GB carcinoma (n = 1), and the amount of the aspirate was insufficient in one case (xanthogranulomatous cholecystitis was later proven by extended hepatectomy). The mean follow-up period of the patients with xanthogranulomatous cholecystitis was 1177 days. Adenocarcinoma was confirmed by EUS-FNA in 8 of the 9 patients with suspected unresectable GB carcinoma, and the FNA was inconclusive in one. All 10 patients with GB carcinoma underwent chemotherapy. The overall sampling adequacy was 86.6%. The accuracy of EUS-FNA for detecting malignancy and for the final diagnosis was 93.3% (95% CI, 62.4%-99.9%) and 80% (95% CI, 54%-93.7%), respectively.nnnLIMITATIONSnA small patient cohort and a retrospective design with potential selection bias.nnnCONCLUSIONSnMalignant GB mass lesions can be safely and accurately differentiated by EUS-FNA. Thus, patients with xanthogranulomatous cholecystitis can avoid undue extensive surgery.

Current concept of endoscopic ultrasound-guided fine needle aspiration for pancreatic cancer.

Endoscopic ultrasound (EUS) provides detailed, high-resolution images of the pancreas. However, whether a lesion is malignant or benign cannot be diagnosed solely from its imaging features on EUS. The introduction of EUS-guided fine needle aspiration (EUS-FNA) offers the possibility to obtain a cytological or histological diagnosis of pancreatic lesions with a high sensitivity and specificity. Although the clinical utility of EUS-FNA for pancreatic diseases is widely accepted, the indication for preoperative tissue diagnosis of pancreatic lesions suspected to be malignant is still controversial. This review highlights the diagnostic potential of EUS-FNA, as well as its current indications and contraindications, complications, and techniques.

Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma

Cholangiocarcinoma has been reported in workers exposed to chlorinated organic solvents and has consequently been classified as an occupational disease (occupational cholangiocarcinoma) by the Japanese Ministry of Health, Labour and Welfare. This study aimed to identify the characteristics of nine workers newly diagnosed with occupational cholangiocarcinoma.

Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms.

BackgroundMultiple studies have investigated sampling adequacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic neuroendocrine neoplasms (pNENs). However, none have described the diagnostic performance of EUS-FNA for pNENs, or the influencing factors. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA, with post-operative pathological diagnosis as the gold standard, and factors predictive of inadequate EUS sampling.MethodsFrom 1998 to 2014, a total of 698 patients underwent pancreatic resection and 1455 patients underwent EUS-FNA sampling for pancreatic lesions. A total of 410 cases underwent both surgical resection and preceding EUS-FNA. Of these, 60 cases (49 true pNEN, nine non-diagnostic, two misdiagnoses) were included. We studied diagnostic performance of EUS-FNA and factors that were associated with failed diagnosis.ResultsOf the 60 cases, EUS-FNA yield was 49 true-positive cases, two misdiagnoses, and nine non-diagnostic cases (including six suggestive cases). Sensitivity, specificity, and accuracy were 84.5, 99.4, and 97.3xa0%, respectively; including the six suggestive cases, diagnostic values were 94.8xa0% sensitivity (55/58), 99.4xa0% specificity (350/352), and 98.7xa0% accuracy (405/410). In multivariate analysis, sampling adequacy rates were significantly lower when lesions were located in the pancreatic head [odds ratio (OR)xa0=xa010.0] and in tumor-rich stromal fibrosis (ORxa0=xa010.45). Tumor size, needle type, tumor grading, presence of cystic component, and time period were not significant factors.ConclusionsEUS-FNA offers high accuracy for pNEN. However, location of the tumor in the pancreatic head and presence of rich stromal fibrosis negatively impacts sampling adequacy.