Hiroshi Imaoka

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

BACKGROUND AND STUDY AIM Malignancy 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. PATIENTS AND METHODS A 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. RESULTS Intratumoral 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. CONCLUSIONS Grading 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.

A Japanese case of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa. Here we present a case of EE in a 69-year-old Japanese man, who presented with abdominal pain, appetite loss, and a history of bronchial asthma. Laboratory findings included peripheral eosinophilia and an increased serum immunoglobulin E level. Computed tomography showed diffuse severe thickening of the esophageal wall, and a barium esophagogram revealed a small caliber of the middle and lower portion of the esophagus, without normal peristaltic contractions. Endoscopy of the esophagus showed a pale mucosa, with adherent whitish exudates resembling fungal infection, and prominent ring-like contractions. Histologic examination of a biopsy specimen revealed marked eosinophil infiltration into the esophageal mucosa. Endoscopic ultrasonography (EUS) demonstrated marked circumferential thickening of the esophageal submucosal layer, and an esophageal manometry study showed a high percentage of ineffective esophageal peristalsis and high-amplitude esophageal body contractions. EUS findings showed no change even after oral corticosteroid therapy, although the histological findings were improved. This is thought to be the first documented Japanese case of EE. EE should be considered in the differential diagnosis in cases of esophageal motility disturbance, even if the patients do not complain of dysphagia.

endoscopic ultrasonography-guided biliary drainage： Who,when, which, and how？

Both endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (EUS-CDS) and EUS-guided hepaticogastrostomy (EUS-HGS) are relatively well established as alternatives to percutaneous transhepatic biliary drainage (PTBD). Both EUS-CDS and EUS-HGS have high technical and clinical success rates (more than 90%) in high-volume centers. Complications for both procedures remain high at 10%-30%. Procedures performed by endoscopists who have done fewer than 20 cases sometimes result in severe or fatal complications. When learning EUS-guided biliary drainage (EUS-BD), we recommend a mentors supervision during at least the first 20 cases. For inoperable malignant lower biliary obstruction, a skillful endoscopist should perform EUS-BD before EUS-guided rendezvous technique (EUS-RV) and PTBD. We should be select EUS-BD for patients having altered anatomy from malignant tumors before balloon-enteroscope-assisted endoscopic retrograde cholangiopancreatography, EUS-RV, and PTBD. If both EUS-CDS and EUS-HGS are available, we should select EUS-CDS, according to published data. EUS-BD will potentially become a first-line biliary drainage procedure in the near future.

Rare pancreatic neoplasms : the utility of endoscopic ultrasound-guided fine-needle aspiration-a large single center study

BackgroundTumors other than ductal adenocarcinomas constitute 10%–15% of all pancreatic tumors. We describe the performance and pitfalls of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosis of these rare pancreatic tumors and their characteristic cytopathological features.MethodsThe records of 455 pancreatic fine-needle aspiration procedures done between March 1997 and August 2006 at Aichi Cancer Center, Nagoya, Japan, were reviewed. Besides cytology, aspirated material was routinely submitted in formalin for cell-block analysis. The reference standard for final diagnosis was surgical pathology from resected specimens.ResultsTwenty-eight rare (nonductal adenocarcinomas) pancreatic tumors were identified. Overall, EUS-FNA with the results of cytology, cell-block processing, and immunohistochemistry could correctly diagnose the type of neoplasm in 19 (67.9%) cases. EUS-FNA could distinguish benign from malignant rare tumors with a sensitivity of 69.2%, a specificity of 100%, positive predictive value of 100%, negative predictive value of 79.0%, and accuracy of 85.7%. None of three malignant pancreatic endocrine neoplasms could be diagnosed as malignant. An adequate core tissue sample could be obtained in 21 cases (75.0%) and provide a histopathological diagnosis in 19 (67.9%) cases. EUS-FNA could change the presumptive diagnosis in 11 (39.3%) cases. Specific immunochemical studies were useful adjuncts to the diagnosis. No major or minor complication was noted in any patient.ConclusionsPancreatic neoplasms other than ductal adenocarcinomas have diverse imaging and histopathological features. EUS-FNA is accurate and safe for their identification.

Comparison of the clinical impact of endoscopic ultrasound-guided choledochoduodenostomy and hepaticogastrostomy for bile duct obstruction with duodenal obstruction

BACKGROUND AND STUDY AIM To date, only a few reports with small numbers of patients have described double stenting (biliary and duodenal), in particular endoscopic ultrasound (EUS)-guided biliary drainage, for patients with obstructive jaundice. In addition, no reports have sought to determine which EUS-guided biliary drainage route has better outcomes. The aim of the current study was to investigate adverse events and stent patency in patients who underwent EUS-guided biliary drainage and duodenal stenting. PATIENTS AND METHODS Patients who were admitted to the Osaka Medical College with obstructive jaundice caused by lower biliary obstruction and duodenal obstruction due to malignant tumor between June 2012 and April 2014 were retrospectively enrolled in the study. RESULTS A total of 39 patients were enrolled in the study; 13 underwent EUS-guided choledochoduodenostomy (EUS-CDS), and 26 underwent EUS-guided hepaticogastrostomy (EUS-HGS). Adjusted analyses for covariates using propensity scores showed that the EUS-HGS group had significantly longer stent patency than the EUS-CDS group (duodenal stent patency: median 113 vs. 34 days; hazard ratio [HR] 0.415, 95 % confidence interval [CI] 0.175 - 0.984; P = 0.046; biliary stent patency: median 133 vs. 37 days; HR 0.391, 95 %CI 0.156 - 0.981; P = 0.045). On logistic regression analysis, only EUS-CDS was associated with adverse events, in particular reflux cholangitis (OR 10.285, 95 %CI 1.686 - 62.733; P = 0.012). CONCLUSION In cases of obstructive jaundice with duodenal obstruction, EUS-HGS may be better than EUS-CDS, with longer stent patency and fewer adverse events.

Clinical course of gastrointestinal stromal tumor diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract. However, little is known about the clinical presentation of GIST, especially small lesions. The purpose of the present study was to clarify the efficacy of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for the diagnosis of GIST and to determine its clinical course.

Clinical characteristics of adenosquamous carcinoma of the pancreas: a matched case-control study.

Objectives Adenosquamous carcinoma of the pancreas (ASC) is a variant of pancreatic ductal adenocarcinoma (PDAC), but the prognosis remains unclear. The purpose of this study was to clarify the prognosis of ASC using a matched case-control design. Methods We evaluated clinical characteristics of ASC treated between 2001 and 2011 in our institution. As controls, PDAC cases matched with ASC cases for sex, age, pretreatment Eastern Cooperative Oncology Group performance status, location, initial therapy and American Joint Committee on Cancer TNM staging for pancreatic cancer were also evaluated. Results Of the 914 cases of pancreatic neoplasm, 28 cases (3.06%) of ASC were identified, and 56 cases of PDAC were matched as controls. Median overall survival (OS) was significantly worse for ASC (8.38 months) than for PDAC (15.75 months; hazard ratio [HR], 1.94; 95% confidence interval, 1.07–3.51; P = 0.026). Of the 22 unresected cases, median OS was again significantly worse for ASC (4.67 months) than for PDAC (12.36 months; HR, 2.39; 95% confidence interval, 1.27–4.51; P = 0.007). Conclusion These results demonstrate that ASC is more aggressive than PDAC.

Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients

We investigated peptide cocktail vaccine OCV‐C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single‐arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28‐day treatment cycle, patients received weekly subcutaneous injection of OCV‐C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8 and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease‐free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide‐specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months [95% confidence interval (CI), 11.1–20.6] and the DFS rate at 18 months was 34.6% (95% CI, 18.3–51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8–82.5). The administration of OCV‐C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A‐specific CTL responses and without (p = 0.027), and between patients with KIF20A expression and without (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A‐specific CTL responses. OCV‐C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer.

Evaluation of Modified Glasgow Prognostic Score for Pancreatic Cancer: A Retrospective Cohort Study.

Objectives The modified Glasgow prognostic score (mGPS) is known to be useful in determining the prognosis of cancers. However, the utility of mGPS for pancreatic cancer (PC) has been examined based primarily on a surgical series of early-stage cancers. The purpose of this study was to examine the utility of mGPS for PC of all stages using a retrospective cohort design. Methods We conducted a retrospective cohort study using data from a computerized database. A total of 807 patients with pathologically confirmed PC were analyzed (mGPS-0, n = 620; mGPS-1, n = 153; mGPS-2, n = 34). Results Median overall survival (OS) was significantly worse for the mGPS-1 group than for the mGPS-0 group (5.8 vs 15.8 months, respectively) but was comparable between the mGPS-2 and mGPS-1 groups (4.8 vs 5.8 months, respectively). After adjustment, both mGPS-1 and mGPS-2 were independent predictive factors of OS (mGPS-1: hazard ratio, 1.772; 95% confidence interval, 1.417–2.215; mGPS-2: hazard ratio, 2.033; 95% confidence interval, 1.284–3.219). Subgroup analysis showed that OS was significantly worse in the mGPS-1 and mGPS-2 groups than in the mGPS-0 group for all except the following 2 subgroups: localized disease and curative resection. Conclusions The present results show that the mGPS is an independent prognostic factor in patients with PC, especially for advanced-stage disease.