Effectiveness of ex situ telecytology using mobile terminals for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)

Abstract

By endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), cytotechnologists obtain and prepare specimens and stain them with Diff-Quik in an endoscopic room. In most facilities, doctors specializing in cytology then diagnose them. Such doctors are dispatched to various facilities, which increases the burden on specialists and laboratories. Here, we propose EUS-FNA as a system in which a cytotechnologist upon discovery of an atypical cell at the site takes a picture of it using a smartphone with an ocular lens. The cytotechnologist then sends the image to a cytology specialist, who then diagnoses it. It was found that pancreatic ductal cancer, anaplastic pancreatic cancer, and solid pseudopapillary tumor (SPT) were all detected from images. In EUS-FNA, a simplified telecytological system using mobile terminals, was found to be effective for on-site cytological diagnosis.

Introduction

EUS-FNA is now applied to the confirmation of tumor diagnosis in the pancreaticoduodenal region, and plays a central role in the field of cytological diagnosis.^1),2) In most Japanese facilities, cytotechnologists are dispatched to endoscopic laboratories to perform EUS-FNA, stain specimens, and diagnose cells³⁾ on-site. While this system has many merits, it increases the burden on cytotechnologists and doctors specializing in cytology. At times, specialists are unable to travel to endoscopic laboratories owing to their engagements in intraoperative rapid diagnosis, conferences with other departments, and so forth. Here, we devise a simplified telecytological system with which on-site cytotechnologists and specialists can diagnose cells anywhere, anytime.

I  Subjects and Method

1.  Diseases

A total of 28 cases were included in the study as follows: 22 cases of pancreatic ductal cancer, 1 case of anaplastic pancreatic cancer, 2 cases of endocrine tumor, 1 case of acinic cell cancer, 1 case of leiomyosarcoma, and 1 case of SPT. The cases were cytologically diagnosed using mobile terminals between January 2014 and March 2016.

2.  The method we developed included picture taking with a smartphone camera, image transfer, and image diagnosis

 i. At the site, a cytotechnologist examines Diff-Quick-stained specimens microscopically in an endoscopic laboratory and takes pictures of atypical cells and cancer cells by placing the camera of an iPhone 6 on the eyepiece (Figure 1). One image is sent to the iPhone 6 of a cytology specialist by SNS. After viewing the image and diagnosing the cells, the doctor replies to the cytotechnologist by SNS. We measured the response time. When cytological diagnosis based on the image sent was not possible, pictures were retaken and resent to the doctor. When image-based cytological diagnosis failed twice, the specialist was asked to visit the site and diagnose the cells.

Figure 1 

A picture of a part that seemingly includes an atypical cell or a cancer cell is taken by placing the camera of iPhone 6 on the eyepiece

ii. We discussed the light source luminance and complexity regarding the method for taking pictures of cells with the camera of the iPhone 6.

II  Results

1. After pictures of atypical cell(s) were taken, images were sent to the doctor’s iPhone 6 within 60 s in all cases. The doctor also replied to the cytotechnologist within 60 s in all cases. In other words, these processes were completed within 2 min. The risk of erroneous transmission is reduced by using only sending and receiving addresses.

2. Diagnosis was possible with a single image in 18 cases of pancreatic ductal cancer, 1 case of anaplastic pancreatic cancer, and 1 case of SPT (Figure 2). Diagnosis was possible with two images in 3 cases of pancreatic ductal cancer (Figure 3). Owing to structural complexity, it was not always possible to correctly discern the cell form. A cytology specialist diagnosed cells at the site in 1 case of pancreatic ductal cancer, 2 cases of endocrine tumor, 1 case of acinic cell cancer, and 1 case of leiomyosarcoma (Figure 4). In all of these cases, cells were put into a cell block without conducting the on-site diagnosis for confirmation, and were diagnosed by immunohistochemical staining.

Figure 2 

Diff-Quik staining of the pancreatic ductal cancer (A), anaplastic pancreatic cancer (B), and SPT (C) diagnosed with a single image

Figure 3 

Three cases of pancreatic ductal cancer with structural complexity diagnosed with two images

Figure 4 

Pancreatic ductal cancer (A), endocrine tumor (B), acinic cell cancer (C), and leiomyosarcoma (D) diagnosed by doctors specializing in cytology at the site

3. When a picture of the cells was taken with a smartphone placed on the eyepiece of a light microscope at a light source luminance higher than that for the microscopic examination of Diff-Quik-stained specimens, good cytological images were obtained (Figure 5). In the case of cell clumps with a complex structure, it was difficult to determine the cell form. In the case of atypical cells that appear sporadically, the cell form was easy to identify (Figure 6).

Figure 5 

Bright (A), adequate (B), and dark (C), according to light source luminance

Figure 6 

In the case of cell clumps with structural complexity, it was difficult to determine the cell form, compared with atypical cells that appear sporadically

III  Discussion

The on-site application of EUS-FNA is still being debated, although on-site diagnosis provides some definite benefits. EUS-FNA allows for the confirmation of abnormal cells in the biopsy area, and can guide decisions as to the next location for testing. If a definite diagnosis is made in the initial puncture, the duration of anesthesia can be reduced. If immunostaining is required, it is possible to produce samples suitable for diseases in which cells are gathered in cell blocks. In addition to these benefits, there are cases that may be diagnosed on the basis of images taken with a smartphone. Although not applicable to all cases, when such diagnosis using this EUS-FNA system is possible, there are many benefits to the patient.

Most smartphones include a camera with a resolution of over 9 million pixels, which is quite high. In Japan, smartphones are broadly distributed and applied in various arenas.⁴⁾

After the cells were photographed, the exchange of information was completed within 2 min, demonstrating that EUS-FNA can be conducted swiftly. For some cases of pancreatic ductal cancer, anaplastic pancreatic cancer, and SPT, cytological diagnosis with a smartphone was possible, eliminating the need for a specialist to visit the laboratory. Accordingly, the method proposed in this study may alleviate the burden on cytotechnologists and cytology specialists. In some cases, however, two images were required for diagnosis, or the doctor had to visit the laboratory. Accordingly, on-site cytotechnologists play an important role in the system, and they must be careful when preparing specimens and taking pictures of atypical cells. From the cytological viewpoint, smartphone-based diagnosis is possible in cases that have characteristic cytological findings of cancer, such as mucus production, distinct nucleoli, multinuclear cells, and the formation of a pseudovessel axis.^5),6) In some cases of pancreatic ductal cancer, the number of atypical cells is small; therefore, cytotechnologists must be highly skilled to detect atypical cells in Diff-Quik-stained specimens.

In terms of methods for obtaining pictures of cells, the light source luminance should be higher than that for examination with an optical microscope, to make it easier to identify nuclear chromatin. However, it is necessary to fine-tune the camera position to avoid blurry images due to hand jiggling.

It was possible to determine the cell form of each atypical cell, including the amount of chromatin. In the case of complex cell clumps, however, cytological analysis was sometimes impossible; it is considered difficult to diagnose complex atypical cells. Sending images of atypical cells that appear sporadically is preferable. This method is considered effective for detecting pancreatic ductal cancer, anaplastic pancreatic cancer, SPT, and other tumors that show highly atypical cells.

We now consider the commercially available 0.6-power wide-angle kit used for taking the entire picture of a microscopic field of view, and a method for preventing image blurring with a dedicated mount for a smartphone, such as SNAPZOOM II.

Diagnostic imaging using smartphones can be adopted as a method for cytotechnologists. Even in the absence of a cytodiagnostician, a cytoscreener can take pictures of screened cells with a smartphone, allowing a specialist to observe them for cytoscreening. Some consider this a reasonable approach to diagnosis, while others emphasize the risks. On-site application of EUS-FNA provides many benefits to both patients and doctors, however, and the use of this system is expected to grow.

IV  Conclusions

With a simplified telecytological system connecting an on-site cytotechnologist and a doctor specializing in cytology, it is possible to conduct cytological diagnosis at low costs anywhere, anytime. This system is expected to enable the diagnosis of pancreatic ductal cancer, anaplastic pancreatic cancer, and SPT with advanced cytological findings, and reduce the burden on cytology specialists.

 

This research is approved by the ethics committee.

COI開示

本論文に関連し，開示すべきCOI 状態にある企業等はありません。

References

• 1)   Vilmann  P et al.: “Endoscopic ultrasonography with guided fine needle aspiration biopsy in pancreatic disease,” Gastrointest Endosc, 1992; 38: 172–173.
• 2)   Yamao  K et al.: “Discussion on the effectiveness of endoscopic ultrasound-guided fine-needle aspiration biopsy for digestive system diseases,” Gastroenterol Endosc, 1996; 38: 2167–2173.
• 3)   Koshikawa  T et al.: “Handling of the materials for fine-needle aspiration in EUS-FNA,” Shoukaki-Naishikyou (Gastroenterol Endosc), 2004; 16: 1281–1287.
• 4)   Laksanasopin  T et al.: “A smartphone dongle for diagnosis of infectious diseases at the point of care,” Sci Transl Med, 2015; 7: 4.
• 5)   Yoneda  M et al.: “A case of solid-pseudopapillary neoplasm of the pancreas (SPNP), in which swift cytology with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and cellblock immunostaining were effective,” J Jpn Soc Clin Cytol, 2013; 52: 158–163.
• 6)   Yoneda  M et al.: “A case of anaplastic pancreas cancer identified through preoperative diagnosis by endoscopic ultrasound-guided fine needle aspiration,” Igakukensa (Jpn J Med Technol), 2011; 60: 138–142.