Introduction of GB polyp

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1 Management of Gallbladder Polyp as Physician's View Sang Hyub Lee, MD, PhD Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Internal Medicine Division of Gastroenterology Introduction of GB polyp Outgrowths of the gallbladder mucosal wall Polypoid Lesion of Gallbladder Incidentally detected on ultrasonography or after cholecystectomy Epidemiology 0.01~13.8% of resected GBs % of GBs assessed by USG About 5% of GBs assessed by USG in Korea Yang HL, et al. Br J Surg 1992;79 Jørgensen T, et al. Scand J Gastroenterol 1990;25 Park JK, et al. Gut Liver 2008;2 262 분당서울대학교병원

2 제 8 회분당서울대학교병원내과연수강좌 2012 Histologic Classification of GB polyps Bang S. Korean J Gastroenterol 2009;53 Benign non-neoplastic polyp Cholesterol polyp - most common of the non-neoplastic polyps - lamina propria is infiltrated with lipid-laden foamy macrophages - about 60% of all gallbladder polyps - generally less than 10mm - often, multiple cholesterol polyps William C, et al. Gastroenterol Clin N Am 2010;39 분당서울대학교병원 263

3 Management of Gallbladder Polyp as Physician's View Adenomyomatosis - 25% of gallbladder polyp - usually localized to the gallbladder fundus mm Inflammatory polyps Benign non-neoplastic polyp - 10% of gallbladder polyps - result from granulation and fibrous tissue (secondary to chronic inflammation) - typically less than 10 mm William C, et al. Gastroenterol Clin N Am 2010;39 Adenoma Benign neoplastic polyp - 4% of gallbladder polyps mm - generally solitary - often associated with gallstones - Adenoma-to cancer progression: debate Miscellaneous neoplastic polyps leiomyomas, lipomas, neurofibromas and carcinoids less than 1% of gallbladder polyps varying sizes William C, et al. Gastroenterol Clin N Am 2010;39 Kozuka S, et al. Cancer 1982;50 Harbison J,et al. Ir Med J 1997; 분당서울대학교병원

4 제 8 회분당서울대학교병원내과연수강좌 2012 GB polyp & Symptom Generally thought not to cause any symptoms 대부분의용종은무증상 증상이있는용종 : 콜레스테롤용종또는유두상선종 전형적인담도성산통 : 용종이이탈하여담낭관폐쇄 특발성췌장염 : 총담관원위부에서췌관폐쇄 Laboratory abnormality Alkaline P Bilirubin Amylase Lipase OP DDx PUD Chronic pancreatitis GB polyp and symptom Terzi and colleagues et al 74 patients undergoing cholecystectomy for GB polyps 91% had symptoms RUQ pain, nausea, dyspepsia, and jaundice etc. Unclear association due to combined GB stones (60%) Japanese study 23% had abdominal symptoms 13% had elevated liver function tests Clue Recurrent pain DDx other causes Laboratory supportive evidence Evidence of polyp detachment Terzi C, et al. Surgery 2000;127 Ito H, et al. J Am Coll Surg 2009;208 분당서울대학교병원 265

5 Management of Gallbladder Polyp as Physician's View Risk Factors for GB polyp Positive risk factors Old age Male gender Obesity Medical conditions such as diabetes Peutz-Jeghers syndrome and Gardner syndrome Negative risk factors GB stones Consistent relationship? Jorgensen T, et al. Scand JGastroenterol 1990;25 Myers RP, et al. Can J Gastroentereol 2002;16 Wada K, et al. Dig Dis Sci 1987;32 Komorowski RA, et al. Dis Colon Rectum 1986;29 Risk Factors for GB polyp 34,669 chinese patients underwent a general check up ( ) Lin WR, et al. J Gastroenterol hepatol 2008; 분당서울대학교병원

6 제 8 회분당서울대학교병원내과연수강좌 2012 Diagnosis of GB polyps Ultrasonography Transabdominal USG (USG) Endoscopic Ultrasound Computed tomography Oral cholecystography MRI/MRCP ERCP PET USG Diagnostic accuracy of ultrasound Yang HL, et al. Br J Surg. 1992;79 Sensitivity: 90% If no stones are present, up to 99% Specificity: 94%\ 분당서울대학교병원 267

7 Management of Gallbladder Polyp as Physician's View Diagnostic accuracy of ultrasound USG Overall US-based diagnosis of GB polyp was accurate in 82% Akyurek N, et al. HPB (Oxford). 2005;7 Diagnostic accuracy of ultrasound 23/651 patients having polyp-like gallbladder lesion followed for 9 years Overall sensitivity and specificity of US scan are 66.66%, 100% Cut off value: 10 mm on US sensitivity 100%, specificity 86.95%, PPV 50% for diagnosis of malignancy Chattopadhyay D, et al. World J Gastroenterol 2005; 분당서울대학교병원

8 제 8 회분당서울대학교병원내과연수강좌 2012 Diagnosis of GB polyps Transabdominal Ultrasonography generally considered the first of line study by no means a definitive indicator The presence of a GB polyp The malignant potential of GB polyp Endoscopic Ultrasound (EUS) Risk factor evaluation for Malignancy Potential in GB polyp Akyurek N, et al. HPB (Oxford). 2005;7 Another modalities for diagnosis of GB polyp Computed tomography diagnostic sensitivity: 72% Positron emission tomography scanning case series Oral cholecystography less sensitive and specific than ultrasound Koh T, et al. Clin Positron Imaging 2000;3 분당서울대학교병원 269

9 Management of Gallbladder Polyp as Physician's View Management of GB polyp Indication of cholecystectomy Natural course of GB polyp? Risk factor of neoplastic GB polyp? Patient s preference? Eager to receive cholecystectomy Very low surgical morbidity Laparoscopic cholecystectomy Assurance of Patients How to follow up? Optimal Follow-up 270 분당서울대학교병원

10 제 8 회분당서울대학교병원내과연수강좌 2012 Optimal Follow-up Surgery or follow-up Natural History of Gallbladder Polyps Very low prevalence of GB adenoma compared to that of GB cancer. 담낭암의발생률 >> 담낭선종의발생률 Question 담낭선종은악성화하는가? 대부분의담낭암은선종을거쳐발생하는가? 분당서울대학교병원 271

11 Management of Gallbladder Polyp as Physician's View Development of GB Cancers Two or three pathway Adenoma to carcinoma De novo carcinoma De novo without APBDU De novo with APBDU Support Adenoma-to-carcinoma progression 1.8% of Cholecystectomy Specimens: Neopalstic polyp 23.5% of Neopalstic polyp: carcinoma Lee SH, et al. Korean J Gastroenterol 2010; 분당서울대학교병원

12 제 8 회분당서울대학교병원내과연수강좌 2012 Support Adenoma-to-carcinoma progression Lee SH, et al. Korean J Gastroenterol 2010;55 Support Adenoma-to-carcinoma progression Cha BH, Lee SH, et al. World J Gastroenterol. 2011;17 분당서울대학교병원 273

13 Management of Gallbladder Polyp as Physician's View Mutations in GB neoplastic lesions Wistuba II, et al. J Hepatobiliary Pancreat Surg. 1999;6 Support Mutations in neoplastic lesions Wistuba II, et al. J Hepatobiliary Pancreat Surg. 1999;6 274 분당서울대학교병원

14 제 8 회분당서울대학교병원내과연수강좌 2012 Adenoma-to-carcinoma progression Support UK study in 2009: - Mutation of K-ras (associated with an adenoma) is never detected in carcinoma Chile study in 2006: -196 completely mapped early carcinomas did not reveal adnoma residue support two different genetic pathways Wistuba II, et al. Hum Pathol 1999;30 Roa I, et al. Cancer J Surg Oncol 2006;93 Natural History of Gallbladder Polyps Question 담낭선종은악성화하는가? Yes 대부분의담낭암은선종을거쳐발생하는가? No 분당서울대학교병원 275

15 Management of Gallbladder Polyp as Physician's View Favor benign nature Retrospective analysis by Ito and colleagues 417 patients with GB polyps detected on USG Variable follow-up duration Ito H, et al. J Am Coll Surg 2009;208 Favor benign nature Retrospectively analysis by Shinkai and colleagues 145 patients with GB polyps 2 USG F/U at least 6 months apart till cholecystectomy Shinkai H, et al. Am J Surg 1998; 분당서울대학교병원

16 제 8 회분당서울대학교병원내과연수강좌 2012 Favor benign nature gallbladder polyps less than 10 mm do not need to be removed simply because they grow Shin SR, et al. J Clin Gastroenterol 2009;43 Favor benign nature prospective follow-up 56 patients with small GB polyp( <10 mm) over 5 years with annual US No any clinical symptoms developed No changes in polyp morphology Colecchia A, et al. Am J Gastroenterol 2009;104 분당서울대학교병원 277

17 Management of Gallbladder Polyp as Physician's View Favor malignant nature Retrospective analysis by Park and colleagues 1558 patients with gallbladder polyps over an average of 37 months Cumulative detection rate of neoplastic polyps: 1.7% at 1 year 2.8% at 5 years 4% at 8 years Park JY, et al. J Gastroenterol Hepatol 2009;24 Risk factors for Malignancy Potential in GB polyp Retrospectively analysis from the MayoClinic 137patients with preoperative USG Subsequent cholecystectomy Yang HL, et al. Br J Surg 1992; 분당서울대학교병원

18 제 8 회분당서울대학교병원내과연수강좌 2012 Risk factors for Malignancy Potential in GB polyp Terzi C, et al. Surgery 2000; 127 Risk factors for Malignancy Potential in GB polyp Shinkai H, et al. Am J Surg 1998;175 분당서울대학교병원 279

19 Management of Gallbladder Polyp as Physician's View Risk factors for Malignancy Potential in GB polyp Age over 60 Sessile morphology Size of 10 mm Kwon W, et al. J Korean Med Sci 2009;24 Risk factors for Malignancy Potential in GB polyp Frequency of malignant polyps according to number of risk factors Kwon W, et al. J Korean Med Sci 2009; 분당서울대학교병원

20 제 8 회분당서울대학교병원내과연수강좌 2012 Risk factors for Malignancy Potential in GB polyp Cha BH, Lee SH, et al. World J Gastroenterol. 2011;17 Risk factors for Malignancy Potential in GB polyp Cha BH, Lee SH, et al. World J Gastroenterol. 2011;17 분당서울대학교병원 281

21 Management of Gallbladder Polyp as Physician's View Risk factors for Malignancy Potential in GB polyp Sensitivity: 81%, Specificity: 86%, Accuracy: 83.7% Choi WB, et al. Gastrointest endosc 2000; 52 Risk factors for Malignancy Potential in GB polyp 88 surgical cases of gallbladder polyps less than 20mm in diameter Sensitivity: 90%, Specificity: 89% in predicting neoplastic polyps Cho JH, et al. Gastrointest Endosc 2009; 분당서울대학교병원

22 제 8 회분당서울대학교병원내과연수강좌 2012 Leung UC, et al. ANZ J Surg 2007; patients with gallbladder polyps 37 months cut-off point of 10mm: sensitivity and specificity of predicting neoplastic polyps were 54.5% and 94.1% 46% of the neoplastic polyps were less than 10 mm at the time of diagnosis / even small polyps warrant close follow-up Park JY, et al. J Gastroenterol Hepatol 2009;24 분당서울대학교병원 283

23 Management of Gallbladder Polyp as Physician's View Malignancy potential according to size High incidence of neoplasm Cholesterol polyp (50%) Neoplasm (100%) Low incidence of neoplasm (37%) (6%) mm Shinkai H, et al. Am J Surg 1998;175 Retrospective study from Mayo Clinic Zielinski MD, et al. J Gastrointest Surg 2009; 분당서울대학교병원

24 제 8 회분당서울대학교병원내과연수강좌 mm rule for follow-up of GB polyp 7.4% of polyps less than 1cm were neoplastic. polyp size greater than 6mm was a significant risk factor for malignancy. Zielinski MD, et al. J Gastrointest Surg 2009;13 Favor benign nature Less than 6mm on US: No neoplastic lesions Ito H, et al. J Am Coll Surg 2009;208 분당서울대학교병원 285

25 Management of Gallbladder Polyp as Physician's View Risk factors for Malignancy Potential in GB polyp Larger size Older age Increase in Size Sessile lesion Association of Gallstones DM High EUS score Hypoechoic foci in EUS Considerations for Cholecystectomy of GB polyp Clinical Practice Guideline Development Committee, Korean Association of HBP Surgery. Korean Journal of HBP Surgery 2010; 분당서울대학교병원

26 제 8 회분당서울대학교병원내과연수강좌 2012 Optimal Follow-up Asymptomatic, 6 mm 6 ~10mm, risk factor evaluation : Age, morphology, gallstones, DM, EUS finding Optimal Follow-up 분당서울대학교병원 287

27 Management of Gallbladder Polyp as Physician's View USG Accuracy of diagnostic modality 23/651 patients having polyp-like gallbladder lesion followed for 9 years Overall sensitivity and specificity of US scan are 66.66%, 100% Cut off value: 10 mm on US sensitivity 100%, specificity 86.95%, PPV 50% for diagnosis of malignancy Chattopadhyay D, et al. World J Gastroenterol 2005;11 USG Accuracy of diagnostic modality Overall US-based diagnosis of GB polyp was inaccurate in 82% Akyurek N, et al. HPB (Oxford). 2005;7: 분당서울대학교병원

28 제 8 회분당서울대학교병원내과연수강좌 2012 Accuracy of diagnostic modality Total 194 patients with small polypoid lesions Underwent both ultrasonography and EUS Followed up with US alone or with EUS for years EUS Accuracy of EUS: 97%, of abdominal ultrasound: 76% Sugiyama M, et al. Gut. 2000;46 EUS Accuracy of diagnostic modality Total 194 patients with small polypoid lesions Underwent both ultrasonography and EUS Followed up with US alone or with EUS for years Sugiyama M, et al. Gut. 2000;46 분당서울대학교병원 289

29 Management of Gallbladder Polyp as Physician's View Accuracy of diagnostic modality 98 surgical cases of gallbladder polyps less than 20 mm in diameter EUS Cheon YK, et al. World J Gastroenterol 2009;15 HRUSG-EUS Accuracy of diagnostic modality 144 patients with more than 1cm-sized GB polyp, underwent surgery Jang JY, et al. Ann Surg 2009; 분당서울대학교병원

30 제 8 회분당서울대학교병원내과연수강좌 2012 Optimal follow-up modality Consideration besides diagnostic accuracy Cost-effectiveness Easy availability Invasiveness Radiation exposure Ultrasound (HR USG) is recommanded by experts Park JY, et al. J Gastroenterol Hepatol. 2009;24 Noone TC, et al. Maqn Reson Imaging. 2004;22 Optimal Follow-up After initial w/u with USG and ESU, USG (HR USG) is recommended for F/U 분당서울대학교병원 291

31 Management of Gallbladder Polyp as Physician's View Optimal Follow-up Natural History of GB polyp Retrospective analysis by Park and colleagues 1558 patients with gallbladder polyps over an average of 37 months Cumulative detection rate of neoplastic polyps: 1.7% at 1 year 2.8% at 5 years 4% at 8 years Park JY, et al. J Gastroenterol Hepatol 2009; 분당서울대학교병원

32 제 8 회분당서울대학교병원내과연수강좌 2012 Average age of Dysplasia cancer sequence 1,326 patients (201 dysplasias and 1,125 cancers) dysplasia: 51.9 years early cancer: 56.8 years advanced carcinoma: 62.9 years metastasis: 63.1 years 80% of invasive gallbladder cancers present areas adjacent to the CIS and epithelial dysplasia period (dysplasia advanced carcinoma) : theoretically 10 years RoaI, et al. J Surg Oncol. 2006;93 Adenoma-to-carcinoma progression Cha BH, Lee SH, et al. World J Gastroenterol. 2011;17 분당서울대학교병원 293

33 Management of Gallbladder Polyp as Physician's View 72 GB polyp patients monitored with US till cholecystectomy 16 GB cancer detected among them 5/16 patients 1.5 ~ 4 fold increase in maximum diameter during 4 to 12 months of follow -up 4-6month interval follow-up Kubota K, et al. Surgery 1995; patients with gallbladder polyps detected by US Prospective F/U for 6 years Every 6 monthly with US 24mm gallbladder cancer detected Less than 6months F/U Moriguchi H, et al. Gut 1996; 분당서울대학교병원

34 제 8 회분당서울대학교병원내과연수강좌 2012 Optimal Follow-up Interval: every 6-12 months Duration: more than 10 years Proposed F/U Strategy for GB Polyps GB polyp Symptomatic Asymptomatic > 10mm 6 ~ 10mm < 6mm EUS (HRUSG) Yes High risk for malignancy potential No Cholecystectomy Old age GB stone Sessile polyp DṂ. f/u USG q 6-12 month for >10 years 분당서울대학교병원 295