|
1
|
Franzén B, Auer G, Lewensohn R. Minimally invasive biopsy-based diagnostics in support of precision cancer medicine. Mol Oncol 2024; 18:2612-2628. [PMID: 38519839 PMCID: PMC11547246 DOI: 10.1002/1878-0261.13640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/31/2024] [Accepted: 03/14/2024] [Indexed: 03/25/2024] Open
Abstract
Precision cancer medicine (PCM) to support the treatment of solid tumors requires minimally invasive diagnostics. Here, we describe the development of fine-needle aspiration biopsy-based (FNA) molecular cytology which will be increasingly important in diagnostics and adaptive treatment. We provide support for FNA-based molecular cytology having a significant potential to replace core needle biopsy (CNB) as a patient-friendly potent technique for tumor sampling for various tumor types. This is not only because CNB is a more traumatic procedure and may be associated with more complications compared to FNA-based sampling, but also due to the recently developed molecular methods used with FNA. Recent studies show that image-guided FNA in combination with ultrasensitive molecular methods also offers opportunities for characterization of the tumor microenvironment which can aid therapeutic decisions. Here we provide arguments for an increased implementation of molecular FNA-based sampling as a patient-friendly diagnostic method, which may, due to its repeatability, facilitate regular sampling that is needed during different treatment lines, to provide tumor information, supporting treatment decisions, shortening lead times in healthcare, and benefit healthcare economics.
Collapse
Affiliation(s)
- Bo Franzén
- Department of Oncology‐PathologyKarolinska InstitutetStockholmSweden
- Cancer Centre Karolinska (CCK) FoundationKarolinska University HospitalStockholmSweden
| | - Gert Auer
- Department of Oncology‐PathologyKarolinska InstitutetStockholmSweden
| | - Rolf Lewensohn
- Department of Oncology‐PathologyKarolinska InstitutetStockholmSweden
- Theme Cancer, Medical Unit Head and Neck, Lung, and Skin Tumors, Thoracic Oncology CenterKarolinska University HospitalStockholmSweden
| |
Collapse
|
|
2
|
Ware J, Shea D, Lim JY, Malakian A, Armstrong R, Pethig R, Ibsen S. Collection of serum albumin aggregate nanoparticles from human plasma by dielectrophoresis. Electrophoresis 2024; 45:1748-1763. [PMID: 39081085 PMCID: PMC11695576 DOI: 10.1002/elps.202400046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 10/17/2024]
Abstract
Dielectrophoresis (DEP) is a fast and reliable nanoparticle recovery method that utilizes nonuniform electric fields to manipulate particles based on their material composition and size, enabling recovery of biologically-derived nanoparticles from plasma for diagnostic applications. When applying DEP to undiluted human plasma, collection of endogenous albumin proteins was observed at electric field gradients much lower than predicted by theory to collect molecular proteins. To understand this collection, nanoparticle tracking analysis of bovine serum albumin (BSA) dissolved in 0.5× phosphate-buffered saline was performed and showed that albumin spontaneously formed aggregate nanoparticles with a mean diameter of 237 nm. These aggregates experienced a dielectrophoretic force as a function of aggregate radius rather than the diameter of individual protein molecules which contributed to their collection. In high conductance buffer (6.8 mS/cm), DEP was able to move these aggregates into regions of high electric field gradient, and in lower conductance buffer (0.68 mS/cm), these aggregates could be moved into high or low gradient regions depending on the applied frequency. Disruption of BSA aggregates using a nonionic detergent significantly decreased the particle diameter, resulting in decreased dielectrophoretic collection of albumin which increased the collection consistency of particles of interest. These results provide techniques to manipulate albumin aggregates via DEP, which impacts collection of diagnostic biomarkers.
Collapse
Affiliation(s)
- Jason Ware
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
- Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97201, USA
| | - Delaney Shea
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
- Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97201, USA
| | - Jeong Youn Lim
- Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
| | - Anna Malakian
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
| | - Randall Armstrong
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
| | - Ronald Pethig
- Institute for Integrated Micro and Nano Systems, School of Engineering & Electronics, The University of Edinburgh, Edinburgh EH9 3JF, UK
| | - Stuart Ibsen
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97201, USA
- Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97201, USA
| |
Collapse
|
|
3
|
Maruo M, Ikeura T, Takaori A, Ikeda M, Nakamaru K, Ito T, Masuda M, Mitsuyama T, Nakayama S, Shimatani M, Takaoka M, Shibata N, Boku S, Yasuda T, Miyazaki H, Matsumura K, Yamaki S, Hashimoto D, Satoi S, Naganuma M. Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma. Pancreatology 2024; 24:787-795. [PMID: 38871559 DOI: 10.1016/j.pan.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 05/20/2024] [Accepted: 06/02/2024] [Indexed: 06/15/2024]
Abstract
OBJECTIVES This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.
Collapse
Affiliation(s)
- Motonobu Maruo
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
| | - Ayaka Takaori
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masatoshi Ikeda
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Koh Nakamaru
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Takashi Ito
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masataka Masuda
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Toshiyuki Mitsuyama
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Shinji Nakayama
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masaaki Shimatani
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Makoto Takaoka
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Nobuhiro Shibata
- Cancer Treatment Center, Kansai Medical University, Osaka, Japan
| | - Shogen Boku
- Cancer Treatment Center, Kansai Medical University, Osaka, Japan
| | - Tomoyo Yasuda
- Cancer Treatment Center, Kansai Medical University, Osaka, Japan
| | | | | | - So Yamaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | | | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Makoto Naganuma
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| |
Collapse
|
|
4
|
Yang X, Liu ZM, Zhou X, Yang F, Ma WZ, Sun XZ, Sun SY, Ge N. Methods to increase the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: An updated review. World J Gastrointest Endosc 2024; 16:117-125. [PMID: 38577648 PMCID: PMC10989249 DOI: 10.4253/wjge.v16.i3.117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 12/30/2023] [Accepted: 01/27/2024] [Indexed: 03/14/2024] Open
Abstract
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.
Collapse
Affiliation(s)
- Xin Yang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Zi-Ming Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Xue Zhou
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Fan Yang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Wen-Zhuang Ma
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Xin-Zhu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Si-Yu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Nan Ge
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| |
Collapse
|
|
5
|
Kitano M, Minaga K, Hatamaru K, Ashida R. Clinical dilemma of endoscopic ultrasound-guided fine needle aspiration for resectable pancreatic body and tail cancer. Dig Endosc 2022; 34:307-316. [PMID: 34437750 DOI: 10.1111/den.14120] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 08/10/2021] [Accepted: 08/25/2021] [Indexed: 12/31/2022]
Abstract
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a first-line procedure for definitive tissue diagnosis of pancreatic cancer because of its high accuracy and low complication rate. The overall sensitivity of EUS-FNA for the diagnosis of pancreatic cancer is approximately 90%; however, its diagnostic ability for small lesions (<10 mm) remains limited. Although EUS-FNA is a relatively safe procedure, with an overall morbidity of ≤2%, it should be noted that needle tract seeding (NTS) can occur after EUS-FNA, which may affect the patient prognosis negatively. In patients with resected pancreatic tumors, preoperative EUS-FNA is not associated with an increased risk of postoperative recurrence. However, NTS after EUS-FNA for resectable pancreatic body and tail cancer has been highlighted recently, particularly by Japanese endoscopists. Thus, the use of preoperative EUS-FNA for the diagnosis of resectable pancreatic body and tail cancer has become a clinical dilemma that challenges gastroenterologists and must be carefully considered on a case-by-case basis by weighing the benefits and risks. This review summarizes the pros and cons of performing EUS-FNA in patients with resectable pancreatic body and tail cancer and provides valuable insight for gastroenterologists treating pancreatic cancer.
Collapse
Affiliation(s)
- Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Kosuke Minaga
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Keiichi Hatamaru
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Reiko Ashida
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
| |
Collapse
|
|
6
|
Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: a diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle aspiration. BMC Gastroenterol 2021; 21:382. [PMID: 34663214 PMCID: PMC8524976 DOI: 10.1186/s12876-021-01955-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 10/05/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND A pathological diagnosis of pancreatic cancer should be performed as much as possible to determine the appropriate treatment strategy, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified. AIMS To evaluate the diagnostic ability of EUS-FNA and its effect on the preoperative diagnosis, surgical outcome, and prognosis of pancreatic cancer. METHODS Between January 2005 and June 2017, 293 patients who underwent surgical resection for pancreatic cancer were retrospectively evaluated. The outcomes of interest were the diagnostic ability of EUS-FNA and its influence on the surgical results and prognosis. RESULTS The diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than that of endoscopic retrograde cholangiopancreatography (ERCP) (45.5%) (p < 0.001). The adverse event rate in ERCP was 10.2%, which was significantly higher than EUS-FNA (1.3%) (p = 0.001). Patients were divided into FNA group (N = 160) and non-FNA group (N = 133) for each preoperative diagnostic method. In the study of surgical curability R0 between the two groups, there was no significant difference in FNA group (65.0% [104/160]) and non-FNA group (64.7% [86/133], p = 1.000). In the prognostic study, 256 patients with curative R0 or R1 had a recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in the non-FNA group. Moreover peritoneal dissemination occurred in 34.3% (24/70) in the FNA group and in 21.9% (16/73) in the non-FNA group, neither of which showed a significant difference. The median survival times of the FNA and non-FNA groups were 955 days and 799 days, respectively, and there was no significant difference between the two groups (log-rank p = 0.735). In the Cox proportional hazards model, factors influencing prognosis, staging, curability, and adjuvant chemotherapy were the dominant factors, but the preoperative diagnostic method (EUS-FNA) itself was not. CONCLUSIONS EUS-FNA is a safe procedure with a high diagnostic ability for the preoperative examination of pancreatic cancer. It was considered the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.
Collapse
|
|
7
|
Automatic Segmentation of Pancreatic Tumors Using Deep Learning on a Video Image of Contrast-Enhanced Endoscopic Ultrasound. J Clin Med 2021; 10:jcm10163589. [PMID: 34441883 PMCID: PMC8397137 DOI: 10.3390/jcm10163589] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Background: Contrast-enhanced endoscopic ultrasound (CE-EUS) is useful for the differentiation of pancreatic tumors. Using deep learning for the segmentation and classification of pancreatic tumors might further improve the diagnostic capability of CE-EUS. Aims: The aim of this study was to evaluate the capability of deep learning for the automatic segmentation of pancreatic tumors on CE-EUS video images and possible factors affecting the automatic segmentation. Methods: This retrospective study included 100 patients who underwent CE-EUS for pancreatic tumors. The CE-EUS video images were converted from the originals to 90-s segments with six frames per second. Manual segmentation of pancreatic tumors from B-mode images was performed as ground truth. Automatic segmentation was performed using U-Net with 100 epochs and was evaluated with 4-fold cross-validation. The degree of respiratory movement (RM) and tumor boundary (TB) were divided into 3-degree intervals in each patient and evaluated as possible factors affecting the segmentation. The concordance rate was calculated using the intersection over union (IoU). Results: The median IoU of all cases was 0.77. The median IoUs in TB-1 (clear around), TB-2, and TB-3 (unclear more than half) were 0.80, 0.76, and 0.69, respectively. The IoU for TB-1 was significantly higher than that of TB-3 (p < 0.01). However, there was no significant difference between the degrees of RM. Conclusions: Automatic segmentation of pancreatic tumors using U-Net on CE-EUS video images showed a decent concordance rate. The concordance rate was lowered by an unclear TB but was not affected by RM.
Collapse
|
|
8
|
Fujita A, Ryozawa S, Tanisaka Y, Ogawa T, Suzuki M, Katsuda H, Tashima T, Araki R, Mizuide M. Evaluation of endoscopic ultrasound-guided fine-needle biopsy for preoperative pancreatic solid lesions. Scand J Gastroenterol 2021; 56:188-192. [PMID: 33295211 DOI: 10.1080/00365521.2020.1857828] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Obtaining an accurate preoperative diagnosis is crucial. This study aimed to evaluate the diagnostic accuracy and utility of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for preoperative pancreatic solid lesions. MATERIALS AND METHODS We retrospectively assessed all patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB to evaluate solid pancreatic lesions preoperatively at our center between July 2013 and June 2020. We enrolled 71 patients who underwent EUS-FNA using a 22 G conventional needle (FNA group) and 34 patients who underwent EUS-FNB using a 22 G Franseen needle (FNB group). Overall, 105 patients were analyzed. We employed propensity-matched analysis and adjusted the confounders. RESULTS No procedural adverse events were encountered. Both groups showed no significant differences in the procedure time, technical success rate, and rate of operator changes from trainee to expert. Regarding diagnostic accuracy, the FNB group (88.2%; 30/34) was higher but not significantly different from the FNA group (85.3%; 29/34) (p > .99). Furthermore, the FNB group (median 2, IQR;2-3) had a significantly lower number of punctures than the FNA group (median 3, IQR; 2-4) (p = .01). CONCLUSIONS The FNB needle provides higher diagnostic accuracy and requires significantly fewer punctures than conventional needles even at facilities with no available rapid on-site evaluation. Thus, using the FNB needle can be useful for preoperative pancreatic solid lesions.
Collapse
Affiliation(s)
- Akashi Fujita
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Shomei Ryozawa
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Yuki Tanisaka
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Tomoya Ogawa
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Masahiro Suzuki
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Hiromune Katsuda
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Tomoaki Tashima
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Ryuichiro Araki
- Community Health Science Center, Saitama Medical University, Saitama, Japan
| | - Masafumi Mizuide
- Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan
| |
Collapse
|