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1 저작자표시 - 비영리 - 변경금지. 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할수없습니다. 변경금지. 귀하는이저작물을개작, 변형또는가공할수없습니다. 귀하는, 이저작물의재이용이나배포의경우, 이저작물에적용된이용허락조건을명확하게나타내어야합니다. 저작권자로부터별도의허가를받으면이러한조건들은적용되지않습니다. 저작권법에따른이용자의권리는위의내용에의하여영향을받지않습니다. 이것은이용허락규약 (Legal Code) 을이해하기쉽게요약한것입니다. Disclaimer

2 외과학석사학위논문 담관내유두상종양의형태학적, 해부학적분류에따른임상병리학적 특성 Clinicopathologic significance of morphological and anatomical classifications of intraductal papillary neoplasm of the bile duct 7 년 월 서울대학교대학원 의학과외과학전공 김재리

3 담관내유두상종양의형태학적, 해부학적분류에따른임상병리학적 특성 지도교수장진영 이논문을외과학석사학위논문으로제출함 6 년 월 서울대학교대학원 의학과외과학전공 김재리 김재리의석사학위논문을인준함 6 년 월 위원장 ( 인 ) 부위원장 ( 인 ) 위원 ( 인 )

4 Clinicopathologic significance of morphological and anatomical classifications of intraductal papillary neoplasm of the bile duct by Jae Ri Kim (Directed by Jin-Young Jang, M.D., Ph.D.) A Thesis Submitted to the Department of Surgery in Partial Fulfillment of the Requirements for the Degree of Master of Science in Medicine at Seoul National University Graduate School October, 6 Approved by thesis committee P rofessor P rofessor P rofessor Chairman Vice Chairman

5 Abstract Clinicopathologic significance of morphological and anatomical classifications of intraductal papillary neoplasm of the bile duct Jae Ri Kim Department of Medicine, Surgery The Graduate School Seoul National University Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease among bile duct cancers. Although the clinicopathologic characteristics of IPNB are steadily being elucidated, its morphologic classification has not been well studied. Therefore, we compared several classifications to support the proper management of IPNB and to predict the prognosis. Methods: Between 3 and 6, patients with IPNB who underwent surgery at Seoul National University Hospital were included in the analysis. After reexamination of all the pathology slides by a specialized biliary and pancreas pathologist, various morphological and anatomical classifications were compared with the clinicopathologic characteristics of

6 IPNB. Results: The patient mean age was 65.9 years, and the male to female ratio was.7:. R resection was achieved in 93.7% (n=5) of the patients. Among the histologic cell types of IPNB, most patients had the intestinal type (n=53; 48.6%) and pancreatobiliary type (n=33; 3.3%). After validation of the previously known classifications which were published by Japan Biliary Association (JBA) and Kim from Samsung Medical Center (SMC) with our patient cohort, we confirmed that there was no significant difference according to the clinicopathologic features of IPNB. Even a simple anatomic classification based on location of lesion (Extrahepatic, Intrahepatic, Diffuse type) showed similar differences according to the clinicopathologic features of IPNB. Patients with a positive resection margin had a significantly poor 5-year overall survival rate. (75.9% vs. 5.7%, p=.4) With univariate and multivariate analyses, positive resection margin and perineural invasion were important risk factors for survival. Conclusion: Although radiologic characteristics have not yet been widely studied, the preoperative classification of IPNB based on a preoperative imaging study is important in determining the optimal extent of the surgical operation and in predicting the prognosis based on the clinicopathologic features. When verifying the morphological classifications, we found that a simple anatomical classification based on the location of the main lesion was sufficient to predict the clinicopathologic features of IPNB, as compared to the previously known complex morphological classifications. keywords : Intraductal papillary neoplasm of bile duct, IPNB, morphologic subtypes, morphologic classification Student Number : 5-978

7 목 차. Introduction Materials & Methods Results Discussion References < 표목차 > Table Table Table Table < 그림목차 > Figure Figure Figure Figure Figure Figure Figure

8 I. Introduction Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease entity with a previously reported prevalence of 4% 5% among bile duct cancers (-3). Ambiguous terms, such as biliary papilloma, biliary papillomatosis and mucin-producing bile duct tumors, have been used in the past. However, the World Health Organization (WHO; fourth edition, ) has classified IPNB as dilated intrahepatic bile ducts (IHD) filled with a noninvasive papillary or villous biliary neoplasm covering delicate fibrovascular stalks (4). Many previous reports have considered IPNB as a counterpart of intraductal papillary mucinous neoplasm of the pancreas (IPMN); both arise in the ductal structures and have a mass with a predominantly papillary pattern (5-7). Although the clinicopathologic features of IPNB have been widely studied and compared with those of IPMN, its radiologic characteristics have not yet been clearly standardized. Based on the differential involvement of the pancreatic ductal system, IPMN is classified as main duct, branch duct and mixed types that are perfectly correlated to the histologic subtype and prognosis (8). Although some radiologic features of IPNB (including diffuse or segmental ductal dilatation and having the appearance of an intraductal growing mass) have been identified, few studies have explored the association between the morphological subtype and the histologic cell type of IPNB (9, ) Consequently, the aims of this study were to identify the morphologic and anatomical characteristics of IPNB as well as its clinicopathologic features, to validate the previously reported morphologic classifications using our patient cohort and to select the optimal classification as a guide for the proper treatment of patients with IPNB.

9 II. Materials and Methods. Patient selection We collected the data of patients from Seoul National University Hospital who underwent surgical resection of IPNB between January 3 and October 6. Patients who did not have available preoperative images or postoperative pathologic slides were excluded. This study was approved by our institutional review board (IRB No. C ).. Interpretation of pathologic diagnosis and histologic cell type of IPNB All slides were retrospectively reviewed and confirmed as IPNB by a specialized biliary-pancreas pathologist (K.B.L). We excluded patients with biliary mucinous cystic neoplasms or other cystic tumors. The pathologic grades of the tumors were classified as low- to high-grade dysplasia, carcinoma in situ and invasive cancer according to the fourth edition of the WHO classification (4). The histologic cell types of IPNB were divided into four groups: the gastric type (GT), consisting of columnar cells with abundant mucin and clear cytoplasm (Figure -a); the intestinal type (IT), consisting of stratified columnar cells with goblet cells (Figure -b); the pancreatobiliary type (PT), consisting of columnar cells with eosinophilic cytoplasm and a round nucleus (Figure -c); and the oncocytic type (OT) reported as a variant of PT, consisting of abundant eosinophilic cytoplasm and a round nucleus (Figure -d).

10 (A) (B) (C) (D) Figure. Previously known four cell types of IPNB : (A) Gastric type, (B) Intestinal type, (C) Pancreatobiliary type, (D) Oncocytic type. 3

11 3. Classification systems based on the morphology and anatomical locations of the main lesion We validated the classification by the Japan Biliary Association (JBA) which was a morphologic classification based on the dilatation of the bile duct and cystic formation () as follows: a localized duct-ectatic type, which has an intraductal mass and distal dilatation of the bile duct; a generalized duct-ectatic type, which has entire bile duct dilatation with an intraductal mass; a cystic type which involves cystic formation with a mass; and a mixed type which involves cystic formation with dilatation of the bile duct. (Figure ) Figure. Classification by the Japan Biliary Association (JBA) 4

12 Additionally, we attempted to validate the classification by Kim, which was another morphological classification based on the dilatation of the bile duct and the presence of an intraductal mass or stricture (9) as follows: Type, diffuse duct ectasia with a grossly visible papillary mass; Type, diffuse duct ectasia without a mass; Type 3, intraductal mass with localized duct dilatation; Type 4, intraductal cast-like lesions; and Type 5, proximal duct dilatation with stricture-like lesions. (Figure 3) We added an unclassified type to identify the cystic form of tumor because the classification by Kim did not include the cystic type of IPNB. Figure 3. Classification by Kim (Samsung Medical Center [SMC]) 5

13 4. Comparison of the classifications based on the morphology and anatomical location of the main lesion In this study, we assigned our patient cohorts based on the classifications by the JBA and Kim. Moreover, to compare the usefulness of these classifications, we tried to classify them as extrahepatic and intrahepatic lesions based on the anatomical structures (classification based on location). For this additional simple classification, we divided our patients into three types as follows: Extrahepatic type for the st confluence of the bile duct, in which the main lesions were confined to the common bile duct (CBD) and common hepatic duct (CHD); Intrahepatic type for beyond the st confluence of the IHD, and Diffuse type for main lesions that were located over a wide range of intrahepatic and extrahepatic bile ducts. Furthermore, we divided the Intrahepatic type into two subgroups, namely the cystic form and duct-ectatic form, to clarify the differences according to the morphological types. By comparing these three classifications, we examined whether the previously reported morphological classifications were verified by our simple classification based on location. 5. Statistical analysis All statistical analyses were performed using IBM SPSS version 9. software (IBM Corp., Somers, NY, USA). Nominal variables were compared using the chi-square test or Fisher s exact test, and continuous variables were compared using the Student t test or analysis of variance. For binary variables, a logistic regression model was used to find significant predictors and estimate their odds ratios. Two-sided p values of.5 were considered as being statistically significant. Survival was analyzed using the Kaplan-Meier method and compared using the log rank test. 6

14 III. Results. Overall clinicopathologic characteristics Table details the patients clinicopathologic characteristics. Mean age was 65.9 years and the male to female ratio was.7:. Among the various operations, liver resection (45.5%) and pancreaticoduodenectomy (PD, 3.%) were majority. The median follow-up period was 4.8 months; (.7%) patients had recurred tumors during the follow-up period. Among the four histologic cell types of IPNB, patients with the intestinal type were the most common (IT; n=53; 48.6%) which was followed by the PT (n=33; 3.3%), GT (n=8; 6.5%) and OT (n=5; 4.6%). Most of the patients had invasive cancer (n=; 9.%) which was consisted of tumor confined to the bile duct (n=74; 66.%) and tumor beyond the bile duct (n=37; 33.%). Seven patients (6.3%) showed a positive resection margin on the final pathologic reports and only six (8.%) had lymph node metastasis. 7

15 Table. Clinicopathologic characteristics of patients cohort Clinical characteristics (N=) Pathologic characteristics (N=) Age 65.9 ± 8.5 Size 3.7 ±. Sex (M:F) 7 : 4 Cell type IHD stone 9 (8.%) Gastric 8 (6.5%) CS infection 5 (3.4%) Intestinal 53 (48.6%) Preop CA 9-9 (Median, Range) 8.5 (.~6.) Pancreatobiliary 33 (3.3%) Operation name Oncocytic 5 (4.6%) Hilar resection 4 (.5%) Histologic grade Right liver resection 7 (4.%) Dysplasia 3 (.7%) Left liver resection 37 (33.%) CIS 7 (6.3%) PPPD / Whipple 6 (3.%) Invasive cancer (9.%) Other operation 8 (7.%) Depth of invasion Operation type Confined to BD 74 (66.%) Hepatobiliary resection 68 (6.7%) Beyond BD 37 (33.%) Bile duct resection 8 (6.%) Resection margin Pancreatoduodenectomy 6 (3.%) Over HGD (.7%) Recur (.7%) cancer 7 (6.3%) Median follow-up (Range, month) 4.8 (.3 ~6.9) Lymph node metastasis 6 (8.%) Angiolymphatic invasion (.9%) Vascular invasion (9.5%) Perineural invasion 4 (5.4%) IHD, intrahepatic bile duct; CS, clonorchis sinensis; CA 9-9, cancer antigen 9-9; PPPD, pylorus-preserving pancreaticoduodenectomy; CIS, carcinoma in situ; BD, bile duct; HGD, high grade dysplasia 8

16 . Radiologic characteristics according to the various morphological and anatomical classifications based on the preoperative computed tomography (CT) scans We applied the various morphological and anatomical classifications to the preoperative CT images of our patients (Table ). The types of operations were well separated by all three classifications. With the classification by the JBA, patients with the generalized duct-ectatic type tended to undergo PD while those with the other types tended to undergo hepatic resection. Moreover, with the classification by Kim, only the generalized duct dilatation with mass type had a high proportion of PD. The simple classification based on location, which focused on the level of the main lesions, showed much clear distributions than those of the other two classifications; The Extrahepatic type tended to be removed by PD or bile duct resection (BDR) and Intrahepatic type by liver resection. Moreover, in the classification based on location, patients with diffuse type IPNB had higher rates of multiple tumors and positive resection margin (Extrahepatic and Intrahepatic type vs. Diffuse type; multiple tumor,.% and 3.8%, respectively, vs. 56.5% [p<.]; positive resection margin, 6.7% and.%, respectively, vs. 7.4% [p=.]). Additionally, there was an observed trend between the distribution of cell types and this classification. The Extrahepatic type had a higher rate of IT; the Intrahepatic type had an equally high proportion of IT and PT; the Diffuse type had a higher proportion of GT. 9

17 Table. Clinicopathologic characteristics according to the morphological and anatomical classifications Case Age>65 Sex (M:F) CA9-9 >37 OP type HBR BDR PD Beyond BD LN metastas is Positive RM Multipli city Grade I (%) 5 (46) 9 (56) Classification by the JBA II (%) 49 (44) 36 (74) III (%) 9 (8) 5 (56) IV (%) () (5) p.79 I (%) 55 (49) 36 (66) Classification by Kim (SMC) II (%) 3 (3) 3 () III (%) 39 (34) (58) IV (%) () (5) V (%) 5 (5) 5 () uncl assif ied 9 (8) 4 (44) p.39 Classification based on location Extrah epatic (%) 48 (4) 3 (7) Intrah epatic (%) 48 (4) 4 (55) Diffuse (%) 33:9 9: 7: :.734 3:5 : 7: : 3: 7:.39 7:8 3:4 3: (46) 43 (83) (4) 7 (4) 4 (8) (4) (4) () 8 (49) 5 (3) 5 (3) 9 (39) (43) 5 () 5 () 3 (7) (5) 8 (89) () () () () () 4 (44) () () () () () () ().6 8 (49) (5) 3 (35) (3) (5) (3) (33) 3 (3) (3) 5 <. <. < (7) 4 (6) 6 (47) (36) 5 () 5 (9) 3 (4) 3 () () () (33) () () () 36 (95) (5.3) () (3) (6) (3) (9) () () () () () () 4 (8) () () (4) () () () 8 (89) () () () () () 4 (44) <. 4 (9) 5 (33) 6 (58) 3 (9) 5 () 3 (7) () 43 (98) () () 3 (3) () () 4 (3) (65) 9 (39) (9) (9) () (5) (7) 4 (7) 3 (57) p <..857 Cell type Dysp lasia / CIS Canc er 3 (6) 49 (94) () 49 () () 9 () () () () () (3) (5) () () () () (4) () () (97) (5) (8) () (98) (98) (96) Recur GT IT PT OT 9 (7) (39) (4) (4) 3 (6) 7 (5) 33 (69) 7 (5) () 8 (6) () () 4 (44) () () () (5) (5) () (5).64 9 (7) 34 (63) (9) () 7 (3) () (67) (33) () () 7 (8) 3 (34) 6 (4) (5) 4 () () (5) (5) () () () 3 (6) (4) () () () () 3 (33) () ().9 4 (9) 3 (7) 9 () () 4 (9) 6 (4) 7 (39) 7 (39) 4 (9) 5 () 8 (36) 6 (7) 3 (3) (5) 3 (3).858 HBR, hepatobiliary resection; BDR, bile duct resection; PD, pancreaticoduodenectomy; BD, bile duct; LN, lymph node; RM, resection margin; CIS, carcinoma in situ; GT, gastric type; IT, intestinal type; PT, pancreatobiliary type; OT, oncocytic type

18 For the classification by the JBA, we further categorized the cystic and duct-ectatic forms. Only the Intrahepatic type IPNB was classified into these two subgroups because this additional classification was only effective for intrahepatic lesions. (Table 3) For the cell types according to this additional classification, a relatively high proportion of IT and PT were observed in the duct-ectatic type and cystic type, respectively. This was the same tendency observed in the classification by the JBA.

19 Table 3. Additional classification of Intrahepatic type IPNB (Cystic, duct-ectatic type) Extrahepatic (%) Intrahepatic (%) Cystic Duct-ectatic Diffuse (%) p Case 48 (4.7) (8.9) 34 (3.4) (8.6) Age>65 3 (7.) 5 (5.) 9 (55.9) 5 (65.).46 Sex (M:F) 7:8 8: : 3:.65 CA9-9>37 5 (33.3) (.) (35.3) 9 (39.).43 OP HBR 4 (8.9) 9 (9.) 34 (.) (9.3) <. BDR 5 (33.3) (.) (.) (8.7) PD 6 (57.8) (.) (.) (.) Beyond BD 3 (8.9) (.) (3.4) (5.).65 LN metastasis 5 (.9) (.) (.) (6.7).55 Positive RM 3 (6.7) (.) (.) 4 (7.4).5 Grade Dysplasia 3 (5.8) (.) (.9) (.).94 CIS/Cancer 49 (94.) (.) 33 (97.) (.) Cell type GT 9 (7.3) (.) 4 (.8) (.). IT (38.5) (.) 5 (44.) (5.) PT (4.4) 4 (4.) 3 (38.) (5.) OT (3.8) (.) (5.9) (.) HBR, hepatobiliary resection; BDR, bile duct resection; PD, pancreaticoduodenectomy; BD, bile duct; LN, lymph node; RM, resection margin; CIS, carcinoma in situ; GT, gastric type; IT, intestinal type; PT, pancreatobiliary type; OT, oncocytic type

20 3. Survival analysis The 5-year overall survival rate of all the patients was 7.3%: % for the dysplasia group and 7.% for the invasive cancer group (Figure 4). Survival curves did not show any differences between the four histologic cell types (Figure 5). In addition, there were no differences in the survival curves according to the three classifications based on the JBA, Kim and the location (Figure 6a-c). Patients with a positive resection margin had a 5-year survival rate of 5.7% compared with 75.9% in patients with a negative resection margin. (p=.4; Figure 7a) Additionally, patients with lymph node metastasis showed a lower survival rate than those with no lymph node metastasis with marginal significance (p=.9; Figure 7b). Figure 4. Overall survival of patients with IPNB : compared as cancer and dysplasia 3

21 Figure 5. Overall survival curves according to the four cell types of IPNB (A) 4

22 (B) (C) Figure 6. Overall survival according to the radiologic classifications : (A) Classification by the Japan Biliary Association (JBA), (B) Classification by Kim (SMC), (C) Classification based on location 5

23 (A) (B) Figure 7. Overall survival with significant differences : (A) Overall survival according to presence of positive resection margin, (B) Overall survival according to presence of lymph node metastasis 6

24 4. Risk factors for survival Table 4 shows the univariate and multivariate analyses. Positive resection margin and perineural invasion were found to be the important risk factors in both the univariate and multivariate analyses. Moreover, lymph node metastasis was one of the risk factor with marginal significance in the univariate analysis. Table 4. Univariate and multivariate analysis Univariate analysis OR (95% C.I) P Multivariate analysis EXP 95% C.I. P (B) Age (.674~4.674).4 CA (.85~5.47).5 positive RM 5.3 (.48~4.55) ~ Grade depth beyond the bile duct Cancer+CIS / Dysplasia.33 (.8~.459) (.674~4.).67 node metastasis 4.54 (.75~.99).83 cell type location of the main lesion angiolymphatic invasion vascular invasion IT+GT / Others Extrahepatic+ Diffuse/Others.7 (.477~3.55).67.6 (.635~4.33) (.46~3.4) (.695~.483).75 perineural invasion.6 (3.355~43.345) < ~46.94 <. RM. resection margin; CIS, carcinoma in situ; IT, intestinal type; GT, gastric type 7

25 IV. Discussion Since, reports of IPNB as a papillary growing mass with bile duct dilatation existing as a possible counterpart to IPMN of the pancreas have been steadily increasing (7, ). Several similarities and differences between IPNB and IPMN have been proposed to clarify the clinicopathologic characteristics and to find a new disease category that includes both tumor types (3, 4). Similar to IPMN of the pancreas, IPNB is known as a papillary tumor originating from the ductal system and mucin production. However, one-third of IPNBs have a macroscopic mucin-hypersecreting mass; they are quite different to IPMN in which most cases exhibit mucin hypersecretion (6). Many patients with IPNB have preoperative jaundice and elevation of tumor markers (carcinoembryonic antigen and cancer antigen 9-9) relative to those with IPMN in which symptom presentation and elevation of tumor markers are not so common (5). These two diseases are often divided into four histologic cell types (gastric, intestinal, pancreatobiliary and oncocytic types) (6). The predominant forms of IPNB are IT and PT; the predominant forms of IPMN of the pancreas are IT (main duct type) and GT (branch duct type) (5, 7). The published literature has mainly focused on the clinicopathologic features of IPNB, and information is limited regarding its preoperative radiologic characteristics (8, 9). IPNB is a surgical disease which has a better long-term prognosis than other types of bile duct tumors after resection (3, ). Therefore, an accurate preoperative diagnosis that can predict the prognosis is important. In the present study, we classified the preoperative computed tomography images into various types according to the level of the main abnormal lesions, including the intraductal mass, stricture, and wall thickening. Previously-suggested classifications have commonly focused on ductal 8

26 dilatation of IPNB. Kubota et al. from the JBA suggested a new classification system based on the segment of ductal dilatation (, ). The problem with this classification is a limited evaluation of the stricture site and wall thickening. In addition, the proportion of the duct-ectatic type is much higher than those of cystic type tumors. Kim et al. proposed another morphological classification which also focused on the segment with ductal dilatation and the presence of an intraductal mass (9). This classification system has some problems; a subgroup of cystic formation is not considered, and the system is quite complicated to use in clinical settings. Although these two classification systems divided IPNB in terms of ductal dilatation commonly done in previous studies, the characteristics of each subgroup were not significantly different and could not accurately predict survival (). Most patients in our study cohort had a specific point lesion regardless of the extent of dilatation (intraductal mass of 9.9%; wall thickening or stricture of 4.3%). Therefore, we applied a simple anatomical division taking into considering the level of these specific lesions from a surgeon s point of view because, in most of the cases, the range of surgical resection was determined by considering the location of these main lesions, not the extent of the ductal dilatation. The boundary of the Extrahepatic type and Intrahepatic type was the st confluence. This classification was very simple and intuitive making it easy to determine which type of surgical operation to perform. When the mass was classified as an Extrahepatic type, the operation tended to be BDR or PD, and when the mass was an Intrahepatic type, the operation tended to be a liver resection. Moreover, Diffuse type IPNB has a significantly higher proportion of multiple masses on the preoperative CT images. Therefore, in the Diffuse type, the proportion of hepatobiliary resection was higher than that for the other types of resection; thus, extension of the operation 9

27 should be considered. The classification based on location showed a simple and clear correlation between clinicopathological characteristics and types of surgical resection compared with the classifications by the JBA and Kim. When comparing the histologic cell types, all the classifications had some common tendencies; tumors associated with EHD dilatation had a higher rate of IT, and tumors with cystic formation had a higher rate of PT. With the classification based on location, the Extrahepatic type had a larger proportion of IT, and the Intrahepatic type tumors had double peak rates of IT and PT. Furthermore, the proportion of IT and PT was relatively high in the duct-ectatic form and cystic form, respectively. This correlation could be a new finding of IPNB because in IPMN of the pancreas, the rate of patients with IT is higher for the main duct type, and the rate of patients with GT and PT is higher for the branch duct type (8). None of these three morphological and anatomical classifications showed any significant differences regarding the survival analysis; in addition, the four histologic cell types did not affect the overall survival of the patients. This trend was also reported in a previous study on IPMN of the pancreas; neither overall nor disease-specific survival was affected by histologic subtypes (7). Only patients with a positive resection margin had a significantly lower overall survival than those with a negative margin. Several reports have suggested that the presence of invasive components in the surgical margin was associated with poor survival (-3). With the guidance of this simple anatomical classification, surgeons could make decisions to define the optimal extent of the resection with a sufficient resection margin. We gathered a homogenous IPNB cohort from a single center over a long period, and the data were confirmed with a strict review by a specialized

28 pathologist with extensive experience. Our study has several limitations. First, it was retrospective in design and has a comparatively small sample size. Second, the information from patients who underwent an operation in the past was not sufficient for a full evaluation, especially information on lymph node dissection, pathologic grade, and gross patterns. A validation study involving a larger population and prospectively collected data will be necessary in the future to support our findings. In conclusion, previously-reported classifications by the JBA and Kim, which mainly focus on the extent of ductal dilatation, did not predict the clinicopathological characteristics, types of surgical treatment and survival of patients with IPNB. Simple anatomical classification that considers the location and extent of the main lesions (intraductal mass, stricture, and wall thickening) was sufficient to predict the clinicopathologic features of IPNB.

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32 요약 ( 국문초록 ) 담관내유두상종양의형태학적, 해부학적분류에따른임상병리학적특성 배경 : 담관내유두상종양은담관종양중에서비교적드문질환이며잘알려져있지않다. 비록최근들어점차적으로담관내유두상종양의임상병리학적특징이밝혀지고있기는하지만, 영상학적특징은아직연구된바가적다. 따라서, 담관내유두상종양환자의수술전영상을토대로기존의형태학적분류를비교, 분석하여종양의예후나치료방침을예측하는데도움이되는지확인하고자한다. 방법 : 3년부터 6년까지, 명환자가서울대학교병원에서담관내유두상종양으로수술을받았으며이연구에포함되었다. 다년간의경험을가진췌담도전담병리전문의가모든환자의슬라이드를다시검사하여병리학적으로분류한뒤, 수술전 CT에근거하여기존의형태학적분류를적용하여환자군을구분하였다. 또한이러한기존의분류를검증하기위해, 병변의위치를간외 / 간내 / 미만형으로간단히구분하여기존의분류와어떠한차이를보이는지도같이비교하였다. 결과 : 환자의평균나이는 65.9세였으며남자와여자의비율은.7 대 이었다. R 수술을받은환자는 5명 (93.7%) 이었으며, 병리학적세포분류에따라장형 (53 명, 48.6%), 췌담도형 (33명, 3.3%) 이가장많았다. 기존의 JBA 분류나 Kim에의한분류를환자군에적용해서구분해보았을때각아형간의임상병리학적특징이명확히구분되지는않았다. 또한병변의위치만으로간단히간외 / 간내 / 미만형으로구분하였을때에도, 기존의복잡한분류와비슷한임상병리학적특징의차이를보였다. 절제면에종양이남아있었던환자의경우유의하게 5년생존율이좋지않았으며 (75.9% vs. 5.7%, p=.4) 단변량및다변량분석에서절제면양성과신경주위침윤이생존에유의한영향을미치는인자로나타났다. 결론 : 비록담관내유두상종양에대한영상학적분류는많이연구된바가없지만, 5

33 수술전영상을토대로형태학적아형을분류하는것은적절한수술범위를결정하거나환자예후를예측하는데에있어매우중요하다. 기존에보고되었던일본담도협회나 Kim에의한분류를이용하여형태학적분류를검증해보았을때, 이전에알려진복잡한분류와비교하여주병변의위치에기초한간단한해부학적분류로도담관내유두상종양의특징을예측하는데에충분하다는것을발견하였다. 주요어 : 담관내유두상종양, 형태학적아형, 영상학적분류체계 Student Number :