Takuya Ishikawa - Academia.edu (original) (raw)

Papers by Takuya Ishikawa

Research Square (Research Square), Mar 31, 2022

This study aimed to evaluate the feasibility and e cacy of Endoscopic ultrasound elastography-gui... more This study aimed to evaluate the feasibility and e cacy of Endoscopic ultrasound elastography-guided ne needle biopsy (EUS-EG-FNB) for the diagnosis of pancreatic mass lesions. Methods EUS-EG images were classi ed into heterogeneous and homogeneous groups. For the heterogeneous group, EUS-FNB was separately performed in both hard areas and soft areas. Only samples obtained during the rst two passes (hard/soft areas) were used to compare the diagnostic accuracy as well as the quality and quantity of the specimens. We investigated the association of EUS-EG ndings using strain histogram analysis with the histological ndings. Results Fifty-ve patients were enrolled including 25 patients with heterogeneous group. The homogeneous group had signi cantly lower mean strain value (hard) lesions. The adequate sampling rates from hard and soft areas were 88% and 92%, respectively (P=0.6374). Comparison of the diagnostic accuracy and the quality and quantity of the histological core between hard and soft areas showed no signi cant differences. In pancreatic adenocarcinoma cases, the proportion of brous stroma in the core tissue was signi cantly correlated with the elasticity of the region. (R2=0.1226: P=0.0022) Conclusion EUS-EG may re ect tissue composition in pancreatic tumors, however, EUS-EG did not affect either the quality and quantity of the tissues obtained.

Digestive Endoscopy, Dec 28, 2020

Background Ampullary adenomas are rare and potentially malignant. Surgery was the standard treatm... more Background Ampullary adenomas are rare and potentially malignant. Surgery was the standard treatment but endoscopic papillectomy (EP) is a possible alternative. Aim We retrospectively evaluated the principal clinical outcomes of EP in all patients referred to our unit also dividing sporadic ampullary adenoma (SAA) from familial adenomatous polyposis (FAP)-associated adenomas. Methods All consecutive patients who underwent endoscopic papillectomy because of ampullary adenoma were considered. The primary outcome was the technical success of EP. Secondary outcomes included the number of procedures, the adverse event rate, the recurrence rate, the concordance of histology pre-and post-EP, and the evaluation of factors related to technical success. Results Between January 2001 and December 2015, sixty-two patients were included (21 FAP and 41 SAA). Technical success was achieved in 75.8% and was different in the two groups (FAP 95.2%, SAA 65.8%, p 0.025). Intraductal invasion was negatively associated with technical success (41.7% vs. 84.0%; p 0.005). The intestinal subtype was predictive of success (79.7% vs. 0%; p 0.012) as well as en bloc resection (90.3% vs. 61.3%; p 0.016). Adverse events were reported in 14 patients (22.6%). Conclusions EP is an effective and safe procedure and is a viable alternative to surgery. Trial Registration ClinicalTrials.gov Identifier: NCT03494543

Gastrointestinal Endoscopy, Apr 1, 2008

undergone for unresectable pancreatic carcinoma, because of difficulty of obtaining an adequate m... more undergone for unresectable pancreatic carcinoma, because of difficulty of obtaining an adequate material. EUS-FNA enabled to obtain the pancreatic tissue safely, however the biopsy spesiemens were extremely a little. The aim of this study was to establish chemosensitivity test using the biopsy speciemen obtained by EUS-FNA and to predict of the response with gemcitabine for unresectable pancreatic carcinoma. Patients and method: Chemosensitivity testing by ATP assay was performed with fresh speciemens obtained by EUS-FNA of primary tumor from 22 patients with unresectable pancreatic carcinoma. Chemosensitivity (treated/control ratio: T/C) was calculated as the percentage of quantity of ATP of a tumor treated with gemcitabine and of a control. T/C was divided into two groups at 60%. Ten patients with initial treatment were treated by gemcitabine and followed prospectively. Patients were treated with gemcitabine 1000 mg/m 2 intravenously over 30 minutes administered on days 1, 8 and 15 every 28 days. Response was examined after 2 cycle completion according to RECIST. Results: Chemosensitivity test succeeded with 17 of 22 patients (77.3%). In 10 patients followed prospectively, 6 patients were T/C S 60% and 4 patients were T/C ! 60%. Two patients were SD and 4 patients were PD in T/C S 60%, whereas all patients were SD in T/C ! 60% (p Z 0.035). Regarding with progression free survival (PFS), median of PFS was 60 days in T/C S 60%, whereas 246 days in T/C ! 60% (p Z 0.0186). Median survival was 170 days in T/C S60%, whereas 3 of 4 patients were alive in T/C ! 60%. Conclusion: Chemosensitivity test usuig biopsy speciemens obtained from EUS-FNA is feasible. From the result of this prospective study, it is possible to predict of the response of the gemcitabine. Application of order made treatment may be possible for the patients with unresectable pancreatic carcinoma.

Gastrointestinal Endoscopy, Apr 1, 2009

Endoscopic ultrasound, 2019

Pancreatology, Oct 1, 2021

Purpose: The purpose of the study was to retrospectively analyze whether double-echo gradient-ech... more Purpose: The purpose of the study was to retrospectively analyze whether double-echo gradient-echo (GRE) chemical shift imaging (CSI) can differentiate between pancreatic metastases from clear cell renal cell carcinoma (PM-ccRCC) and pancreatic neuroendocrine tumor (pNET). Methods: Institutional review board approval and informed consent were waived. CSI, T2WI, DWI, and DCE magnetic resonance imaging (MRI) were performed in patients with PM-ccRCC and pNET. Eleven patients with PM-ccRCC and 24 patients with pNET were enrolled into this retrospective study. The signal intensity was measured in the pancreatic tumor and spleen on in-phase and opposed-phase images. The signal intensity index (SII) and tumor-to-spleen ratio (TSR) in PM-ccRCC and pNET were calculated and compared. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of SII and TSR in the differentiation between PM-ccRCC and pNET. Results: The SII between PM-ccRCC and pNET (20.3% ± 16.8% vs.-3.2% ± 11.4%) was significantly different (P < 0.001), as was the TSR (-19.2% ± 16.6% vs. 6.0% ± 13.8%) (P < 0.001). The area under the ROC curve was 0.917 for the SII and 0.902 for the TSR. Additionally, an SII threshold value of 8.1% permitted the differentiation of PM-ccRCC from pNET with a sensitivity of 90.9%, a specificity of 91.7%, a positive predictive value of 90.1%, a negative predictive value of 91.7%, and an accuracy of 91.4%. A TSR cutoff value of-4.7% enabled the differentiation of the two groups with a sensitivity of 79.2%, a specificity of 90.9%, a positive predictive value of 90.9%, a negative predictive value of 79.2% and an accuracy of 82.9%. Conclusion: Double-echo GRE chemical shift MR imaging can accurately differentiate between PM-ccRCC and pNET.

Oncogene, Apr 13, 2022

Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their pr... more Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we showed that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, nonnatural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.

Research Square (Research Square), Jun 7, 2023

Background Pancreatic cancers (PCs) are often detected late, limiting patient prognosis. Early de... more Background Pancreatic cancers (PCs) are often detected late, limiting patient prognosis. Early detection and accurate diagnosis, especially for small PCs, are thus crucial. This study investigated the use of endoscopic ultrasound elastography (EUS-EG) and contrast-enhanced harmonic EUS (CH-EUS) in diagnosing PCs of 10 mm or less. Methods This retrospective study at Nagoya University Hospital included 11 patients with pathologically con rmed PCs less than 10 mm. The patients underwent EUS with EUS-EG and/or CH-EUS between May 2005 and January 2022. The performance of these techniques and the interobserver variability was evaluated, with subsequent histopathological comparison. Survival outcomes were estimated using Kaplan-Meier survival analysis. Results The patients were predominantly male (63.6%) with a median age of 69 years and median tumor diameter of 9 mm. The EUS-EG showed excellent interobserver concordance (k-coe cient 0.815), with 80% of lesions classi ed as stiff. CH-EUS revealed a PC pattern that became hypovascular within 40 seconds during 1 minute of continuous observation in 63.6% of cases, with good to excellent interobserver concordance. Survival rates were 77.1% and 64.3% at 3 and 5 years, respectively. Differences in enhancement patterns on CH-EUS were observed based on histological type, differentiation, and tumor stage. Conclusions EUS-EG and CH-EUS demonstrated good concordance among observers and could distinguish stiffness and vascular patterns in small PCs. These techniques may aid early detection and accurate diagnosis of PCs less than 10 mm. Further larger prospective studies are needed to con rm these ndings. Trial registration This study was retrospectively registered in the ethics committee of Nagoya University Hospital (Approval number: 2015 − 0316, date of approval: December 8th, 2015).

Clinical Journal of Gastroenterology, Apr 2, 2019

Ultrasonographic imaging techniques have been rapidly developing. The new transesophageal echocar... more Ultrasonographic imaging techniques have been rapidly developing. The new transesophageal echocardiography (TEE) system made it possible to obtain the real-time three-dimensional (3D) image of the cardiac system through the esophagus, that can be applied to the field of gastroenterology. We herein present a case of 72-year-old woman who was referred for evaluation of an incidentally found cystic lesion in the tail of the pancreas. The real-time 3D imaging with TEE probe clearly demonstrated the internal features of the cyst consistent with MCN, which helped narrow down the differential diagnosis. The patient was proceeded with distal pancreatectomy and a definite diagnosis of MCN was confirmed with the histopathological findings of the resected specimen associated with ovarian-type stroma. This is the first report which showed the real-time 3D image of MCN in the pancreas obtained with TEE. Further investigation is warranted to determine the clinical relevance of 3D ultrasonographic techniques used to evaluate the pancreatic cystic lesions.

Gastrointestinal Endoscopy, Apr 1, 2011

with pancreatic cancer. HENT1 expression was measured as either positive or negative for hENT1, o... more with pancreatic cancer. HENT1 expression was measured as either positive or negative for hENT1, or as a composite cytology score (0-300) using a combination of: hENT1 intensity (0-3) x percentage of cells with hENT1(1-100)). Two cohorts of patients were analyzed. Cohort 1 represents a group of locally advanced pancreatic cancer who were defined as having a treatment response based on RECIST criteria, drop in CA19-9, or surgical downstaging. Cohort II is a historical control of patients who did not respond to treatment. hENT1 cytologic expression was compared for both groups using Chi Square analysis and student T test. Results: 15 patient pancreatic cancer EUS-FNA samples were analyzed for hENT1 protein expression. Pancreatic cancer cytologic hENT1 expression was positive in 4 of 6 patients from Cohort 1 vs. 2 of 9 patients from Cohort 2. The mean (ϩ/Ϫ SEM) cytology hENT1 composite scores for Cohort 1 vs 2 were 26.67 ϩ/Ϫ12.02 vs. 16.67ϩ/Ϫ13.33, pϭ0.6. Conclusions. Pancreatic cancer cytologic hENT1 expression assay using limited EUS-FNA samples is feasible. In this limited series, higher hENT1 expression in cytologic samples, obtained by EUS, may be a marker for treatment response in patients with locally advanced pancreatic cancer and may help guide treatment options. Further validation of this EUS-FNA based predictive assay in a prospective clinical trial is warranted.

Scientific Reports, Oct 5, 2022

This study aimed to evaluate the feasibility and efficacy of Endoscopic ultrasound elastographygu... more This study aimed to evaluate the feasibility and efficacy of Endoscopic ultrasound elastographyguided fine needle biopsy (EUS-EG-FNB) for the diagnosis of pancreatic mass lesions. EUS-EG images were classified into heterogeneous and homogeneous groups. For the heterogeneous group, EUS-FNB was separately performed in both hard areas and soft areas. Only samples obtained during the first two passes (hard/soft areas) were used to compare the diagnostic accuracy as well as the quality and quantity of the specimens. We investigated the association of EUS-EG findings using strain histogram analysis with the histological findings. Fifty-five patients were enrolled including 25 patients with heterogeneous group. The homogeneous group had significantly lower mean strain value (hard) lesions. The adequate sampling rates from hard and soft areas were 88 and 92%, respectively (P = 0.6374). Comparison of the diagnostic accuracy and the quality and quantity of the histological core between hard and soft areas showed no significant differences. In pancreatic adenocarcinoma cases, the proportion of fibrous stroma in the core tissue was significantly correlated with the elasticity of the region. (R 2 = 0.1226: P = 0.0022) EUS-EG may reflect tissue composition in pancreatic tumors, however, EUS-EG did not affect either the quality and quantity of the tissues obtained.

Journal of Medical Ultrasonics, Jun 19, 2019

Purpose Pancreatic fibrosis or fibrosing reactions have been reported in intraductal papillary-mu... more Purpose Pancreatic fibrosis or fibrosing reactions have been reported in intraductal papillary-mucinous neoplasm (IPMN) patients. We assessed whether a higher elastic modulus (EM) measured using shear wave elastography (SW-EG) correlated with the existence of branch-duct (BD) IPMN. Methods In total, 183 normal pancreas (NP) and 123 BD-IPMN cases were enrolled. First, we assessed the difference in pancreatic EM (PEM) at different sites (head or tail side of the cyst). Second, a comparison was done between the median PEM of the NP and the BD-IPMN cases. Receiver-operating characteristic analysis was performed to determine the BD-IPMN diagnostic capabilities. Finally, in patients whose cyst was not visualized, the test-positive rate was determined. Results No significant difference was seen between the cyst head side PEM (4.61 kPa) and the tail side PEM (5.35 kPa) (P = 0.471). Among these cases matched by age, 73 were selected each from NP and BD-IPMN cases (median age 65 years). The median PEM of the BD-IPMN cases (5.18 kPa) was significantly higher than that of the NP cases (3.17 kPa) (P < 0.001). When the cutoff value was set at 4.75 kPa, the sensitivity, specificity, PPV, NPV, and accuracy were 75.3%, 64.4%, 72.3%, 67.9%, and 69.9%, respectively. The cutoff value of 4.75 kPa helped for the indirect selection of BD-IPMN patients (10/17, 58.8%) whose cyst was not detected on B-mode ultrasonography. Conclusion SW-EG measurement of the underlying pancreatic parenchyma may correlate with the presence of BD-IPMN.

Clinical Journal of Gastroenterology, Mar 13, 2018

Endoscopic ultrasound is increasingly being used for evaluation of pancreatic diseases and pancre... more Endoscopic ultrasound is increasingly being used for evaluation of pancreatic diseases and pancreatic tumors. Among various pancreatic cystic lesions, cystic degeneration of pancreatic neuroendocrine neoplasm is of the challenge in making diagnosis. Although unique characteristic of each type of pancreatic cystic lesions has been proposed abundantly, typical morphology of cystic degeneration of pancreatic neuroendocrine neoplasm is still unclear. We, herein, reported a case of 66-year-old woman who was incidentally found to have a cystic lesion in the tail of pancreas upon screening transabdominal ultrasonography. A well-defined cystic lesion with rim calcification was noted on subsequent abdominal computed tomography. Endoscopic ultrasound revealed a markedly thick-wall cystic lesion containing solid nodule inside which was not enhanced following contrast-enhanced study. A mucinous cystic neoplasm was suspected and the patient was proceeded with distal pancreatectomy. A definite diagnosis of neuroendocrine neoplasm was confirmed after staining with synaptophysin and chromogranin A. We performed a meticulous review on current literatures focusing on endoscopic characteristics of pancreatic neuroendocrine neoplasms with cystic degeneration.

Gastrointestinal Endoscopy, May 1, 2017

Journal of Medical Ultrasonics, Feb 21, 2012

Purpose To investigate the utility of contrast-enhanced transabdominal ultrasonography (CEUS) in ... more Purpose To investigate the utility of contrast-enhanced transabdominal ultrasonography (CEUS) in the diagnosis of ampullary cancer (AC). Methods In 12 patients with AC, the presence of tumor enhancement, histological type, amount of connective tissue in cancer, and tumor growth pattern were evaluated. The correlation between the tumor growth pattern and enhancement shape, that between the enhancement pattern and surrounding tissue, and the presence of pancreatic infiltration were evaluated. The depth of cancer invasion was mucosa in five patients, within Oddi's sphincter in four, beyond the duodenum but not to the pancreas in two, and pancreatic invasion less than 5 mm in one. Results The tumor was enhanced in 11 patients but not in the patient with much connective tissue in the tumor. Enhancement was observed in all patients with the intraluminal papillary or mixed type, but not in those with the periductal invasive type. The enhancement shape was predominantly round or irregular in the intraluminal papillary type and predominantly serrated in the mixed type. The enhancement shape differed among the growth patterns. The normal pancreatic parenchyma around the tumor was enhanced in all patients, and pancreatic infiltration was regarded as absent when there was a continuous unenhanced area between the tumor and pancreatic parenchyma. Conclusion CEUS correlates with pathological findings of ampullary cancer.

Pancreatology, Mar 1, 2021

BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) is reported as a high-risk factor for p... more BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) is reported as a high-risk factor for pancreatic cancer (PC) that includes IPMN-derived cancers (IPMC) and the development of invasive pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMN. Since invasive IPMC and PDAC exhibit different oncological behaviors, their differentiation is clinically important. We aimed to investigate the use of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) for the differential diagnosis between invasive IPMC and PDAC. METHODS This study involved 183 consecutive patients with PC (invasive IPMC: 42, PDAC concomitant with IPMN: 9, without IPMN: 132) who underwent CEH-EUS preoperatively. While investigating the patterns, enhanced effects in the solid part of the tumor were compared with those in the surrounding pancreatic parenchyma after administration of Sonazoid® and evaluated as hyperenhanced, isoenhanced, or hypoenhanced. We retrospectively compared the enhanced pattern of CEH-EUS by using multiphasic analysis and clinicopathological factors between invasive IPMC and PDAC. RESULTS In multiphase evaluations at 20, 40 and 60 s in CEH-EUS, 75.2% (106/141) of PDACs were hypoenhanced (-) at ≥2 of the 3 time points, with significant differences from those of invasive IPMC (P < 0.001). The solid tumor diameter was significantly larger in PDAC than in invasive IPMC, and the tumor stage and preoperative serum carbohydrate antigen 19-9 level were higher. After propensity score matching of stage and solid tumor diameter, contrast enhancement patterns were significantly more persistent in invasive IPMC than in PDAC (P = 0.0013). CONCLUSIONS Multiphase evaluation using CEH-EUS is a useful method for differentiating between invasive IPMC and PDAC.

Oncology, Oct 26, 2018

Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-l... more Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. Methods: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. Results: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741–1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). Conclusion: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.