The Usefulness of Incorporating Non-pathomorphological

1. The Usefulness of Incorporating Non-pathomorphological Data Recorded in the Hospital Information System into the Pathology Report Form and a Standardized Method of Viewing Digital Pathology Images Keizo Furuya, Toshiharu Maeda, Takanori Kikuchi Department of Pathology and Radiology, Ehime Prefectural Central Hospital 　　　　古谷敬三 Oct. 25, 2010 Pathology Vision 2010 (San Diego)

2. Hospital information system of Ehime Prefectural Central Hospital (2010) (2013)

3. Constitution 1. Background 2. Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

4. Changes in the filed of pathology over the past several decades Pathologists have confined themselves within a static microscopic world. On the other hand, medical fields other than pathology, including imaging diagnosis and molecular and genomic medicine, have developed remarkably. The work of clinicians is comprehensive and dynamic because of constant changes in patient states.

5. Medical record description by POMR (problem oriented medical record) First medical examination 1. Data base 1) Patient information: patient profile, chief complaint, history of present illness, past history, family history, social history, system review, etc. 2) Physical examination findings: general status (external appearance, mental state, skin condition) specific status 3) Test findings 2. Problem list：disease name, signs and symptoms, patient’s condition or findings, etc. 1) #1 title, #2 title, #3 title--- 2) Distinguish active title from inactive title 3. Initial plan 1) Diagnostic plan: to select the diagnostic tests and plan a schedule for enforcement, e.g. urine tests, blood tests, blood biochemistry tests, immunoserum tests, chest and abdominal plain X-rays, ECG, urine culture and blood culture tests and abdominal US etc 2) Therapeutic plan 3) Education plan Second medical examination or since the second day after admission 4. Progress note 1) Narrative note S: subjective data (patient complaint) O: objective data (physical findings and test findings）： A: assessment (each problem is analyzed on the basis of the information available about the disease and a hypothesis is established on what happens and why) P: plan (make plans to prove the correctness of the hypothesis and describe it) Imaging examinations (CT scan, MRI scan, etc.) and pathological examination 2) Flow chart Record at discharge 5. Discharge summary Provide a brief description, so it is understood easily by all who read it.

6. Clinicians As for the daily duties, clinicians collect all kinds of clinical information and summarize important data in progress notes to see patients. Radiologists Imaging diagnosis in radiology has converted from screen-film to digital monitor diagnosis. Radiologists read digital images by “Paging” as they give clinical signs and symptoms, and laboratory data in mind. Pathologists Why do pathologists not move out from their static narrow minded patho- morphological world and include factors other than pathomorphological findings into pathological diagnosis reports at least from the standpoint of medical education?

7. “FDG PET-positive lung cancers with a high SUV have been considered to represent a more malignant disease process, resulting in a significantly worse survival rate.” Park CM, Goo FM, Lee HF, et al. Tumors in the tracheobronchial tree: CT and FDG PET features. RadioGraphics 2009; 29(1): 55-71. Downey RJ, Akhurt T, Gonen M, et al. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection. J Clin Oncol 2004; 22: 3255-3260. “---most pheochromocytomas accumulate FDG, uptake is found in a greater percentage of malignant than benign pheochromo- cytomas, and FDG PET is especially useful in defining the distribution of those ---.” Blake MA, Cronin CG, Broland GW. Adrenal imaging. JR 2010; 194:1450-1459 FDG, METO (11C-metomidate: a marker of 11-beta-hydroxylase), FETO, MIBG (metaiodobenzylguanidine), HED (11C-hydroxyephedorine), F-DOPA

8. Constitution 1. Background 2. Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

9. [Aim] To examine the usefulness of incorporating non-pathomorphological data recorded in the HIS (hospital information system) into the pathology report form and the applicability of a standardized method for viewing digital pathology images.

10. Constitution 1. Background 2.Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

11. [Materials and Methods 3a] Information was acquired from the HIS, including the electronic patient record and findings of radiology, pathology, and laboratory tests. The pathology report form has the “diagnosis” and “findings” sections, as before, but arestructured like research papers.

12. Structured pathology report in the environment of HIS One case is considered as one research paper Diagnosis (abstract including the clinician’s requirements) Findings: 1) Handling of specimens (materials and methods) 2) Patho(morpho)logical description (results) Incorporation of non-pathomorphological data such as radiological data (glucose uptake in PET-CT scans), results of laboratory tests (tumor markers), etc, with the date of each test. 3) Comment (discussion) Incorporation of substantial comments by utilizing our medical library containing research papers on the cases in our hospital.

13. Structured pathology report: surgically resected cases Case 1: 73-year-old man Chief complaint: liver tumor detected at the follow-up CT imaging after gastrectomy for gastric cancer Clinical diagnosis: liver cancer suggestive of a combined type HCC (hepatocellular carcinoma), CCC (cholangiocellular carcinoma), or metastatic carcinoma

14. Diagnosis: Liver, partial hepatectomy: hepatocellualr carcinoma, Lo S7/8, size 4.0×3.1 cm, necrosis 10%, eg+ig, fc+, fc-inf+, sf-, s+, vp+, vv-, b-, im+, p-, tw＝0.3 cm Findings: 1) Materials: The resected liver was cut into 15 slices and slices 7, 8, and 11 with the main tumor and slice 2 with a metastatic nodule were examined microscopically. 2) Findings: Grossly, the tumor is basically of the nodular type but of the partly confluent multinodular type. Microscopically, the tumor consisted of 2 different patterns of HCC: the trabecular type with a thickness of 5－10 cells and the combined trabecular and pseudoglandular types consisting of stronger cellular atypia. Hence this tumor is a moderately to poorly differentiated HCC. The tumor invades the liver surface exposed in the abdominal cavity. [(Aug. 18, 2010) AFP 33.7H, PIVKA Ⅱ2180H, DUPAN-2 ≦25, SPAN-2 13.8, CA19-9 177.8H, CEA 1.3; (Aug. 25, 2010) GLU 152H, HbA1c 6.0H; (Aug. 19, 2010) PET-CT FDG-SUVmax = 4.8 (background liver 2.2)] The tumor in segment 8 exhibits similar microscopic findings as the main tumor, so it is identified as metastatic. Liver: mild fatty change (non-B, non-C) 3) Comment: Contrast-enhanced MRI shows peripheral dominance in the early phase and a low signal in the heptatocyte phase. The DWI (diffusion- weighted image) shows a high signal. The imaging pattern and relatively high value of FDG SUVmax are not analogous to typical HCC: however, the tumor is microscopically an HCC with moderate to poorly differentiated cell components. These phenomena seem to be related to the microscopic findings of 2 different patterns of HCC and the macroscopic findings of 2 gross types.

15. Structured pathology report: ESD (endoscopic submucosal dissection) case Case 2: 63-year-old man Clinical diagnosis: Early gastric cancer Chief complaint: gastric polyp (introduced from an other hospital)

16. Diagnosis: Stomach, ESD: Early gastric cancer, type 0-Ⅰ+Ⅱa, sm1, adenocarcinoma (por1+tub1), INFβ, 3.3×3.8×1.9 cm, location = M Gre, ly2+, v0, lm- 0.3 cm, vm ± [C16.9/ICD-O 814031] Findings: 1) Materials: The size of the excised specimen was 5.0×3.9 cm2, cut along the short axis into 11 slices, and all slices were examined microscopically. 2) Findings: Grossly, the tumor is type 0-Ⅰ+Ⅱa and its size is 3.3×3.8×1.9 cm3 (see reference images). Microscopically, the tumor is an adenocarcinoma (por1+tub1) and invades into the submucosa (sm1). The vertical margin is in contact with the portion of exhibiting lymphatic permeation. The lateral margin is tumor free. [(Sep. 01, 2010) H. pylori antibody (+) 66.2 U/ml; CA19-9 3.9 U/ml; CEA 0.8 ng/ml] 3) Comment: The tumor is an adenocarcinoma of the gastric type, and foveolar hyperplasia is observed in the background. Although it is difficult to clearly differentiate between hyperplasia and neoplasia, the portion with structural atypia in the hyperplastic epithelium is a very well differentiated adenocarcinoma of the gastric type. Partial gastrectomy is recommended because of a large poorly differentiated adenocarcinoma, ly2+, and vm±.

17. Constitution 1. Background 2.Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

18. Every day clinicians observe various types of imagesincluding radiological and gross pathological images using the HIS. Hospital information system of Ehime Prefectural Central Hospital (2010)

19. 1 1 1 Reference CT and MRI images in the electronic patient record are arranged in the following order: from head to foot, left to right, and top to bottom.

20. [Materials and Methods 3b] All kinds of images including radiological, gross pathological and histopathological images are arranged to be viewed seamlessly as follows. 1) The resected gross specimens were sliced in the same planes as the radiological axial images. 2) The slices were then placed on a photography table in the same order as in the radiological images and were photographed. 3) All the gross slices and histology slides were assigned corresponding numbers and 4) the glass histology slides were digitized by virtual microscopy.

21. HCC case: Gross pathology specimen 1 1)The resected gross specimens were sliced in the same planes as the radiological axial images. 2)The slices were then placed on a photo- graphy table in the same order as in the Radiological images and were photographed.

22. Gross pathology images are arranged in the following order: from head to foot, left to right, and top to bottom. 3) All the gross slices and histology slides were assigned corresponding numbers 3 4 1

23. A gross pathology slice, unicassettes for tissue embedding, and VS 10A Slice 10 10A 4) the glass histology slides were digitized by virtual microscopy. Virtual slide : 10A

24. Gross pathology slice CT image Virtual slide All kinds of images can be viewed seamlessly.

25. A resected case of HCC: macroscopically, this case is basically nodular type, but some parts are the confluent multinodular type.

26. Figure (CT images)

27. CT imaging: Radiologists observe several hundreds of images by “paging” as shown in this movie.

28. Movie on the gross pathological images: Just like radiologists, pathologists, too, can observe gross pathological imaging by paging.

29. Movie of the gross pathological images from arbitrary direction

30. Constitution 1. Background 2.Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

31. [Materials and Methods 3c] Using the HIS, a medical library was set up containing research papers about the cases in our hospital. Lib 11 Blood vessels Lib 12 Heart Lib 13 Diseases of blood cells, lymph nodes, spleen, and thymus Lib 14 The lung Lib 15 Head and neck Lib 16 The gastrointestinal tract Incidence of lymph node metastasis in cases of early gastric carcinoma (Treatment of early gastric carcinoma by ESD) Gastric carcinoma and lymph node dissection level Risk level of GIST and FDG-PET Lib 17 Liver and biliary tract HCC and FDG-PET Lib 18 The pancreas Lib 19 The kidney Lib 20 The lower urinary tract and male genital system Lib 21 The female genital tract Lib 22 The breast Lib 23 The endocrine system Lib 24 The skin Lib 25 Bones, joints, and soft tissue tumors Lib 26 Peripheral nerve and skeletal muscle Lib 27 The central nervous system Lib 28 The eye link

32. Constitution 1. Background 2.Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

33. [Result] The inclusion of a wide range of information in the pathological report form and the use of a standardized method for viewing digital images facilitated the understanding of each case and helped easy comparison of radiological and pathological images. The incorporation of non-pathomorphological data, in connection with evidence from our library, helped improve the reliability of the comments in the pathology reports. The methods presented here facilitate the research of radiology and pathology. We show the result of HCC study obtained by the present methods.

34. HCC and glucose metabolism (FDG-PET)

35. Figure. Gross types of HCC: type 1, 2x, 2a, 2b, 3, and 4 Type 1 Type 2x Type 2a Type 2b Type 3 Type 4

36. Figure 3. Morphogenetic changes in the gross types of HCC: Relation between the 4 gross types--type 1 (replacing growth type), type 2a (macro-subnodular type), type 2b (micro-subnodular type), type 3 (confluent multinodular type), and type 4(massive type); deep color: pure form, light color: mixed form ; [% of pure form] Type 4 [57.1] 8 [40.9] Type 3 9 6 11 2 3 9 71 Type 2a [84.2] 8 2 Type 2x 9 3 [72.7] Type 1 39 Type 2b

37. Table 4 Relation between HCC gross type, size, and necrosis in HCC cases with TAE • HCC: Hepatocellular carcinoma, 2) TAE: transcatherter arterial embolization, 3) Gross • type 1: replacing growth type, 2a: macro-subnodular type, 2b: micro-subnodular type, • 3: confluent multinodular type, 4: massive type • 5) vs. 6) P=0.0009, 4) vs. 6) p=0.0059, 4) vs. 7) p=0.0059, 6) vs. 8) p=0.0092

38. Table 5 Relation between HCC gross type, DD-score, DD-G, and FDG uptake in HCC cases without TAE (same cases in Table 3) HCC: Hepatocellular carcinoma, 2) DD-score: dedifferentiation score, 3) DD- G: dedifferentiation gradient, 4) FDG: 18F-fluorodeoxyglucose, 5) FDG ratio: FDG-SUVmax of HCC per background FDG value, 6) TAE: transcatherter arterial embolization, 7) Gross type 1: replacing growth type, 2a: macro-subnodular type, 2b: micro-subnodular type, 3: confluent multinodular type, 4: massive type 8) vs. 9) p<0.001, 10) vs. 11) p=0.0004, 13) vs. 14) p=0.0071, 12) vs. 13) p=0.0305

39. Constitution 1. Background 2.Aim 3. Materials and methods 3a. Pathology report form 3b. Seamlessly viewing images 3c. Medical library 4. Result 5. Conclusion

40. Conclusion The format of the pathology report form with seamless image viewing described in this study is expected to promote deeper integration of comprehensive information in evolving HIS and contribute positively to education, research, and patient care.

41. Thank you very much for your attention ご清聴、ありがとうございました。

42. New information system in Our New Hospital (2013) to utilize accumulated data in HIS Today’s presentation: #Structured pathology report #Seamless viewing images #Medical library Lab. system 専用Data Warehouse Statistical data Search engine RIS・PACS Data optimization Data base Pathology system Case data Electronic patient record