- Email: [email protected]
Drs. Deipolyi et al respond:
Volume 26
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Number 8
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August
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2015
transarterial chemoembolization, it was the result of an effort to evaluate the exact effect of transarterial chemoembolization on overall survival. When these patients’ data were not censored at the date of subsequent curative treatment, the treatment effect of transarterial chemoembolization was overestimated based on the strength of the favorable outcomes in the aforementioned patient population. Actually, 18 of 21 patients whose data were censored because of subsequent curative treatment after initial transarterial chemoembolization were without clinically presumed portal hypertension at baseline. Yun Bin Lee, MD Jin Wook Chung, MD, PhD Yoon Jun Kim, MD, PhD Department of Internal Medicine and Liver Research Institute Seoul National University College of Medicine Seoul and Department of Internal Medicine CHA Bundang Medical Center CHA University Seongnam, Republic of Korea (Y.B.L.) Department of Radiology Seoul National University College of Medicine Seoul, Republic of Korea (J.W.C.) Department of Internal Medicine and Liver Research Institute Seoul National University College of Medicine Seoul, Republic of Korea (Y.J.K.)
REFERENCES 1. Lee YB, Lee DH, Cho Y, et al. Comparison of transarterial chemoembolization and hepatic resection for large solitary hepatocellular carcinoma: a propensity score analysis. J Vasc Interv Radiol 2015; 26:651–659. 2. Chen MS, Li JQ, Zheng Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006; 243:321–328.
Re: Safety and Efficacy of 70–150 lm and 100–300 lm Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma From: JianFei Tu, MD Zhongzhi Jia, MD Guomin Jiang, MD Department of Radiology and Interventional Radiology (J.T.) Li Shui Central Hospital Li Shui; and Department of Interventional Radiology (Z.J., G.J.) No. 2 People’s Hospital of Changzhou Nanjing Medical University Xing Long Road 29 Chang zhou, Jiangsu, China 213003
1251
Editor: We read with great interest the recently published article by Deipolyi et al entitled “Safety and Efficacy of 70–150 μm and 100–300 μm Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma” (1). The authors reported that patients in group 2 were readmitted more often within 1 month for hepatobiliary adverse events (P o .0001). They define hepatobiliary adverse events as new biliary dilatation on imaging, cholecystitis, new portal vein thrombosis, severe right upper quadrant pain, or evidence of worsening liver failure (gastrointestinal hemorrhage, encephalopathy, severe ascites) requiring additional physician visits, prolonged hospital stay, or additional intervention. We would like to elaborate on the definition of hepatobiliary adverse events. According to the literature (2,3), hepatobiliary adverse events associated with hepatic chemoembolization include hepatic failure, liver abscess, biloma, cholecystitis, and biliary strictures. However, portal vein thrombosis, severe right upper quadrant pain, gastrointestinal hemorrhage, and ascites are not hepatobiliary adverse events, which may have biased the results. In addition, complication rates of hepatic chemoembolization are dependent on operator experience and the clinical condition of the patient (4). In figure 2 in the article (1), the cystic artery was embolized with drugeluting beads, which were delivered by the right hepatic artery. The patient experienced severe right upper quadrant pain and was diagnosed with acute cholecystitis on computed tomography. This acute cholecystitis can be avoided by superselective catheterization and delivery of the chemotherapeutic agents to the target tumor. This may also have biased the results.
REFERENCES 1. Deipolyi AR, Oklu R, Al-Ansari S, Zhu AX, Goyal L, Ganguli S. Safety and efficacy of 70–150 mm and 100–300 mm drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2015; 26:516–522. 2. Clark T. Complications of hepatic chemoembolization. Semin Interv Radiol 2006; 23:119–125. 3. Poggi G, Pozzi E, Riccardi A, et al. Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver. Anticancer Res 2010; 30:5159–5164. 4. Angle JF, Siddiqi NH, Wallace MJ, et al. Quality improvement guidelines for percutaneous transcatheter embolization: Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 2010; 21:1479–1486.
Drs. Deipolyi et al respond: We thank Tu et al for their letter concerning our definition of hepatobiliary adverse events. The authors question whether portal vein thrombosis, severe right upper quadrant pain, gastrointestinal hemorrhage, and ascites
None of the authors have identified a conflict of interest.
None of the authors have identified a conflict of interest.
http://dx.doi.org/10.1016/j.jvir.2015.04.027
http://dx.doi.org/10.1016/j.jvir.2015.05.016
1252
’
Letters to the Editor
should be grouped as hepatobiliary adverse events, and whether such grouping biased the results of our study (1). They also comment that inadvertent cystic artery embolization could have introduced further bias. During our analysis of the data, we grouped these complications as hepatobiliary adverse events separately from other adverse events to isolate the effect that different sizes of drug-eluting beads (DEBs) may have had on the liver parenchyma and its function. This isolated these events from other adverse events related to general procedural elements such as contrast agent reactions and arteriotomy complications. The authors cite two references defining adverse events after transarterial chemoembolization (2,3). One article (2) categorizes adverse events as hepatic or extrahepatic, similar to the reporting standards of the Society of Interventional Radiology (4). The second article (3) describes complications ranging from vascular access site injuries to sepsis; hepatobiliary complications are not separately defined, even though variceal bleeding is mentioned as resulting from increased portal pressures observed after chemoembolization (3). Increased portal pressures have been demonstrated experimentally and likely relate to arterioportal shunting of chemoembolization agents (5). Consequently, gastrointestinal bleeding and severe right upper quadrant pain after chemoembolization have been previously documented, and the risk is increased in patients with preexisting liver failure or portal vein obstruction (6). Ascites and portal vein thrombosis have been cited as hepatobiliary complications (7,8). Therefore, our definition of hepatobiliary adverse events is supported by the literature. More importantly, this definition was consistent for both groups during our analysis so as to minimize bias. The procedural methods, operators, and assessment of adverse events were identical between groups, aside from the incorporation of 70–150-mm DEBs into one group. Therefore, nontarget embolization to the cystic artery is expected to have occurred in equal frequency in both groups. In our experience in performing lobar chemoembolization, cholecystitis requiring intervention was not evident when using the 100–300-mm DEBs. Therefore, careful avoidance of the cystic artery was not routinely performed, which is supported by published literature. For example, among 70 conventional chemoembolization procedures in one study (9), 18 involved nontarget
Deipolyi et al
’
JVIR
embolization to the gallbladder and none resulted in cholecystitis, even though there was a nonsignificant increase in postembolization syndrome after gallbladder embolization. Given our findings of cholecystitis in the setting of 70–150-mm DEB chemoembolization (1), one would certainly argue that nontarget embolization to the gallbladder should be carefully avoided when using smaller DEBs. Amy R. Deipolyi, MD, PhD Rahmi Oklu, MD, PhD Shehab Al-Ansari, MD Suvranu Ganguli, MD Division of Vascular & Interventional Radiology Department of Radiology New York University Medical Center New York, New York (A.R.D.) Section of Interventional Radiology Department of Radiology Massachusetts General Hospital Harvard Medical School Boston, Massachusetts (R.O., S.A.-A., S.G.)
REFERENCES 1. Deipolyi AR, Oklu R, Al-Ansari S, Zhu AX, Goyal L, Ganguli S. Safety and efficacy of 70-150 mm and 100-300 mm drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2015; 26:516–522. 2. Poggi G, Pozzi E, Riccardi A, et al. Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver. Anticancer Res 2010; 30:5159–5164. 3. Clark TW. Complications of hepatic chemoembolization. Semin Intervent Radiol 2006; 23:119–125. 4. Brown DB, Gould JE, Gervais DA, et al. Transcatheter therapy for hepatic malignancy: standardization of terminology and reporting criteria. J Vasc Interv Radiol 2009; 20:S425–S434. 5. Kan Z, Sato M, Ivancev K, et al. Distribution and effect of iodized poppyseed oil in the liver after hepatic artery embolization: experimental study in several animal species. Radiology 1993; 186:861–866. 6. Chung JW, Park JH, Han JK, et al. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996; 198:33–40. 7. Goin JE, Salem R, Carr BI, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol 2005; 16:205–213. 8. Osmundson EC, Wu Y, Luxton G, Bazan JG, Koong AC, Chang DT. Predictors of Toxicity Associated With Stereotactic Body Radiation Therapy to the Central Hepatobiliary Tract. Int J Radiat Oncol Biol Phys 2015; 91:986–994. 9. Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol 2001; 12:321–326.
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Number 8
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August
’
2015
transarterial chemoembolization, it was the result of an effort to evaluate the exact effect of transarterial chemoembolization on overall survival. When these patients’ data were not censored at the date of subsequent curative treatment, the treatment effect of transarterial chemoembolization was overestimated based on the strength of the favorable outcomes in the aforementioned patient population. Actually, 18 of 21 patients whose data were censored because of subsequent curative treatment after initial transarterial chemoembolization were without clinically presumed portal hypertension at baseline. Yun Bin Lee, MD Jin Wook Chung, MD, PhD Yoon Jun Kim, MD, PhD Department of Internal Medicine and Liver Research Institute Seoul National University College of Medicine Seoul and Department of Internal Medicine CHA Bundang Medical Center CHA University Seongnam, Republic of Korea (Y.B.L.) Department of Radiology Seoul National University College of Medicine Seoul, Republic of Korea (J.W.C.) Department of Internal Medicine and Liver Research Institute Seoul National University College of Medicine Seoul, Republic of Korea (Y.J.K.)
REFERENCES 1. Lee YB, Lee DH, Cho Y, et al. Comparison of transarterial chemoembolization and hepatic resection for large solitary hepatocellular carcinoma: a propensity score analysis. J Vasc Interv Radiol 2015; 26:651–659. 2. Chen MS, Li JQ, Zheng Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006; 243:321–328.
Re: Safety and Efficacy of 70–150 lm and 100–300 lm Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma From: JianFei Tu, MD Zhongzhi Jia, MD Guomin Jiang, MD Department of Radiology and Interventional Radiology (J.T.) Li Shui Central Hospital Li Shui; and Department of Interventional Radiology (Z.J., G.J.) No. 2 People’s Hospital of Changzhou Nanjing Medical University Xing Long Road 29 Chang zhou, Jiangsu, China 213003
1251
Editor: We read with great interest the recently published article by Deipolyi et al entitled “Safety and Efficacy of 70–150 μm and 100–300 μm Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma” (1). The authors reported that patients in group 2 were readmitted more often within 1 month for hepatobiliary adverse events (P o .0001). They define hepatobiliary adverse events as new biliary dilatation on imaging, cholecystitis, new portal vein thrombosis, severe right upper quadrant pain, or evidence of worsening liver failure (gastrointestinal hemorrhage, encephalopathy, severe ascites) requiring additional physician visits, prolonged hospital stay, or additional intervention. We would like to elaborate on the definition of hepatobiliary adverse events. According to the literature (2,3), hepatobiliary adverse events associated with hepatic chemoembolization include hepatic failure, liver abscess, biloma, cholecystitis, and biliary strictures. However, portal vein thrombosis, severe right upper quadrant pain, gastrointestinal hemorrhage, and ascites are not hepatobiliary adverse events, which may have biased the results. In addition, complication rates of hepatic chemoembolization are dependent on operator experience and the clinical condition of the patient (4). In figure 2 in the article (1), the cystic artery was embolized with drugeluting beads, which were delivered by the right hepatic artery. The patient experienced severe right upper quadrant pain and was diagnosed with acute cholecystitis on computed tomography. This acute cholecystitis can be avoided by superselective catheterization and delivery of the chemotherapeutic agents to the target tumor. This may also have biased the results.
REFERENCES 1. Deipolyi AR, Oklu R, Al-Ansari S, Zhu AX, Goyal L, Ganguli S. Safety and efficacy of 70–150 mm and 100–300 mm drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2015; 26:516–522. 2. Clark T. Complications of hepatic chemoembolization. Semin Interv Radiol 2006; 23:119–125. 3. Poggi G, Pozzi E, Riccardi A, et al. Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver. Anticancer Res 2010; 30:5159–5164. 4. Angle JF, Siddiqi NH, Wallace MJ, et al. Quality improvement guidelines for percutaneous transcatheter embolization: Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 2010; 21:1479–1486.
Drs. Deipolyi et al respond: We thank Tu et al for their letter concerning our definition of hepatobiliary adverse events. The authors question whether portal vein thrombosis, severe right upper quadrant pain, gastrointestinal hemorrhage, and ascites
None of the authors have identified a conflict of interest.
None of the authors have identified a conflict of interest.
http://dx.doi.org/10.1016/j.jvir.2015.04.027
http://dx.doi.org/10.1016/j.jvir.2015.05.016
1252
’
Letters to the Editor
should be grouped as hepatobiliary adverse events, and whether such grouping biased the results of our study (1). They also comment that inadvertent cystic artery embolization could have introduced further bias. During our analysis of the data, we grouped these complications as hepatobiliary adverse events separately from other adverse events to isolate the effect that different sizes of drug-eluting beads (DEBs) may have had on the liver parenchyma and its function. This isolated these events from other adverse events related to general procedural elements such as contrast agent reactions and arteriotomy complications. The authors cite two references defining adverse events after transarterial chemoembolization (2,3). One article (2) categorizes adverse events as hepatic or extrahepatic, similar to the reporting standards of the Society of Interventional Radiology (4). The second article (3) describes complications ranging from vascular access site injuries to sepsis; hepatobiliary complications are not separately defined, even though variceal bleeding is mentioned as resulting from increased portal pressures observed after chemoembolization (3). Increased portal pressures have been demonstrated experimentally and likely relate to arterioportal shunting of chemoembolization agents (5). Consequently, gastrointestinal bleeding and severe right upper quadrant pain after chemoembolization have been previously documented, and the risk is increased in patients with preexisting liver failure or portal vein obstruction (6). Ascites and portal vein thrombosis have been cited as hepatobiliary complications (7,8). Therefore, our definition of hepatobiliary adverse events is supported by the literature. More importantly, this definition was consistent for both groups during our analysis so as to minimize bias. The procedural methods, operators, and assessment of adverse events were identical between groups, aside from the incorporation of 70–150-mm DEBs into one group. Therefore, nontarget embolization to the cystic artery is expected to have occurred in equal frequency in both groups. In our experience in performing lobar chemoembolization, cholecystitis requiring intervention was not evident when using the 100–300-mm DEBs. Therefore, careful avoidance of the cystic artery was not routinely performed, which is supported by published literature. For example, among 70 conventional chemoembolization procedures in one study (9), 18 involved nontarget
Deipolyi et al
’
JVIR
embolization to the gallbladder and none resulted in cholecystitis, even though there was a nonsignificant increase in postembolization syndrome after gallbladder embolization. Given our findings of cholecystitis in the setting of 70–150-mm DEB chemoembolization (1), one would certainly argue that nontarget embolization to the gallbladder should be carefully avoided when using smaller DEBs. Amy R. Deipolyi, MD, PhD Rahmi Oklu, MD, PhD Shehab Al-Ansari, MD Suvranu Ganguli, MD Division of Vascular & Interventional Radiology Department of Radiology New York University Medical Center New York, New York (A.R.D.) Section of Interventional Radiology Department of Radiology Massachusetts General Hospital Harvard Medical School Boston, Massachusetts (R.O., S.A.-A., S.G.)
REFERENCES 1. Deipolyi AR, Oklu R, Al-Ansari S, Zhu AX, Goyal L, Ganguli S. Safety and efficacy of 70-150 mm and 100-300 mm drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2015; 26:516–522. 2. Poggi G, Pozzi E, Riccardi A, et al. Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver. Anticancer Res 2010; 30:5159–5164. 3. Clark TW. Complications of hepatic chemoembolization. Semin Intervent Radiol 2006; 23:119–125. 4. Brown DB, Gould JE, Gervais DA, et al. Transcatheter therapy for hepatic malignancy: standardization of terminology and reporting criteria. J Vasc Interv Radiol 2009; 20:S425–S434. 5. Kan Z, Sato M, Ivancev K, et al. Distribution and effect of iodized poppyseed oil in the liver after hepatic artery embolization: experimental study in several animal species. Radiology 1993; 186:861–866. 6. Chung JW, Park JH, Han JK, et al. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996; 198:33–40. 7. Goin JE, Salem R, Carr BI, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol 2005; 16:205–213. 8. Osmundson EC, Wu Y, Luxton G, Bazan JG, Koong AC, Chang DT. Predictors of Toxicity Associated With Stereotactic Body Radiation Therapy to the Central Hepatobiliary Tract. Int J Radiat Oncol Biol Phys 2015; 91:986–994. 9. Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol 2001; 12:321–326.