Description of Event or Problem · 1
EVENT VERBATIM [PREFERRED TERM] . GELATIN (GELFOAM) POWDER WAS USED AS THE EMBOLUS [OFF LABEL USE], BILE DUCT NECROSIS/EPITHELIAL NECROSIS OF THE MAIN BILE DUCT [BILE DUCT NECROSIS], , NARRATIVE: THE INITIAL CASE WAS MISSING THE FOLLOWING MINIMUM CRITERIA: NO SPECIFIC EVENTS REPORTED FOR A CERTAIN GELATIN PRODUCT. UPON RECEIPT OF FOLLOW-UP INFORMATION ON 02MAR2021, THIS CASE NOW CONTAINS ALL REQUIRED INFORMATION TO BE CONSIDERED VALID. THIS IS A LITERATURE REPORT FROM THE RADIOLOGY, 1985, VOLUME 156; PP. 331-334, ENTITLED, 'BILE DUCT NECROSIS: COMPLICATION OF TRANSCATHETER HEPATIC ARTERIAL EMBOLIZATION,' THIS AUTHOR REPORTED SIMILAR EVENTS FOR TWO PATIENTS. THIS CASE REFERS TO CASE 1, A (B)(6) YEAR-OLD MALE PATIENT. BILE DUCT NECROSIS BECAUSE OF TRANSCATHETER HEPATIC ARTERIAL EMBOLIZATION (THAE) IN TWO PATIENTS WITH HEPATOCELLULAR CARCINOMA IS REPORTED. PREOPERATIVE THAE WAS PERFORMED ON 29 PATIENTS, AND BILE DUCT NECROSIS WAS EXPERIENCED BY TWO OF THE 29 (7%). IN THESE TWO PATIENTS, GELATIN (GELFOAM) POWDER WAS USED AS THE EMBOLUS. AMONG THE 24 WHOSE EMBOLUS WAS CLEAR, FOUR WERE EMBOLIZED WITH GELATIN POWDER. THEREFORE, INCIDENCE OF BILE DUCT NECROSIS AFTER THAE WITH GELATIN POWDER WAS 50%. BECAUSE OF THE HAZARDS OF SEVERE COMPLICATIONS SUCH AS BILE DUCT NECROSIS, WE CONCLUDE THAT GELATIN POWDER SHOULD NOT BE USED EXCEPT FOR THE THAE OF NO MORE THAN ONE SEGMENT OF THE LIVER. TRANSCATHETER HEPATIC ARTERIAL EMBOLIZATION (THAE) IS COMMONLY APPLIED TO HEPATOCELLULAR CARCINOMA (HCC) AND METASTATIC TUMOR OF THE LIVER. COMPLICATIONS OF THAE SUCH AS CHOLECYSTITIS AND GALLBLADDER NECROSIS ARE COMMON AND PERIPHERAL BILE DUCT NECROSIS ARE RARE AND MAIN BILE DUCT NECROSIS HAS NEVER BEEN REPORTED. WE PERFORMED THAE ON 29 PATIENTS WITH HCC BEFORE HEPATECTOMY TO PREVENT METASTASIS AND TO REDUCE BLOOD LOSS DURING RESECTION. GELATIN POWDER (GELFOAM, UPJOHN, KALAMAZOO, MICH.) WAS USED IN FOUR PATIENTS, AND IN TWO OF THESE FOUR, EPITHELIAL NECROSIS OF THE MAIN BILE DUCT WAS FOUND FOLLOWING THAE. THESE TWO CASES ARE REPORTED. CASE 1 - A (B)(6) YEAR-OLD MAN WAS A PATIENT AT ANOTHER HOSPITAL BECAUSE OF HYPERTENSION WHEN LIVER CIRRHOSIS WAS FOUND. HE WAS REFERRED TO OUR HOSPITAL FOR HEPATECTOMY. ULTRASOUND (US) EXAMINATION REVEALED A TUMOR 3 CM IN DIAMETER IN THE LEFT LATERAL INFERIOR AREA. DURING HEPATIC ARTERIOGRAPHY PERFORMED BEFORE THAE, A TUMOR WAS SEEN IN THE LEFT LATERAL INFERIOR AREA. TRANSARTERIAL PORTOGRAPHY WAS USED TO REVEAL PATENCY OF THE INTRAHEPATIC PORTAL VENOUS BRANCHES. THE SERUM ALPHA-FETOPROTEIN (AFP) VALUE WAS 1234 NG/ML. THAE WAS PERFORMED USING GELATIN POWDER MIXED WITH 10 MG DOXORUBICIN HYDROCHLORIDE (ADRIAMYCIN, ABBOTT, NORTH CHICAGO, III.) AND MITOMYCINE. THE MIXTURE WAS INJECTED VIA THE PROPER HEPATIC ARTERY, THE BLOOD FLOW THROUGH WHICH HAD BEEN ALMOST COMPLETELY OBSTRUCTED. LAPAROTOMY WAS PERFORMED 5 MONTHS LATER FOR HEPATIC RESECTION. THE LIVER SURFACE SHOWED APPEARANCES OF MICRONODULAR LIVER CIRRHOSIS, BUT THERE WAS NO DISCOLORED REGION SUGGESTING INFARCTION. THE SEPARATION OF THE SEVERELY NECROTIC GALLBLADDER FROM ITS BED AND DISSECTION OF THE CYSTIC DUCT TOWARD THE COMMON BILE DUCT EXPOSED THE NORMAL CYSTIC DUCT WITH A LENGTH OF APPROXIMATELY 1.5 CM. FURTHER SEPARATION TOWARD THE COMMON BILE DUCT RESULTED IN SUDDEN EXTRACTION OF THE BILE DUCT FROM THE COMMON BILE DUCT WITH NO APPRECIABLE RESISTANCE. THE EXTRAHEPATIC BILE DUCT AT THE CONFLUENCE OF THE CYSTIC DUCT WAS SCLEROSED OVER 1 CM. AND MILD ENLARGEMENT OF THE OUTER DIAMETER OF THE BILE DUCT WAS OBSERVED. THE EXTRACTED STUMP OF THE CYSTIC DUCT WAS NECROTIC, AND THE INNER MUCOSA OF THE COMMON BILE DUCT WAS DARKENED AND NECROTIC. THE LEFT LATERAL INFERIOR AREA AND THE LEFT MEDIAL SEGMENT WERE RESECTED, AND A T-TUBE WAS INSERTED INTO THE COMMON BILE DUCT. THE WEIGHT OF THE RESECTED SPECIMEN WAS 340 G. HISTOPATHOLOGIC EXAMINATION OF THE SPECIMEN REVEALED THAT ONLY A SMALL PART OF THE MAIN TUMOR AND A PART OF THE DAUGHTER NODULES WERE VIABLE. RESULTS: NECROSIS OF THE EXTRAHEPATIC BILE DUCT AND/OR THE HEPATIC DUCTS WERE FOUND IN TWO PATIENTS (CASES 1 AND 2). MACROSCOPIC INFARCTION OF THE LIVER PARENCHYMA WAS FOUND IN TWO PATIENTS (CASE 2 AND A PATIENT WHO UNDERWENT THAE AND EMBOLIZATION OF THE RIGHT ANTERIOR PORTAL VENOUS BRANCHES WITH PERCUTANEOUS TRANSHEPATIC PORTAL VEIN CATHETERIZATION). DISCUSSION: IF THE DIAMETER OF THE EMBOLIC PARTICLES IS SMALL, THEIR ISCHEMIC EFFECTS ON THE TUMOR BECOME MORE EVIDENT. FOR THIS REASON, POWDER IS OFTEN FAVORED AS AN EMBOLIC SUBSTANCE. BUT WHAT PARTICLE SIZE WOULD BE SAFE TO THE LIVER AND THE BILE DUCT? (B)(6) REPORTED THAT NECROSIS AND ABSCESS OF THE LIVER AND CYSTIC CHANGES OF THE BILE DUCT DEVELOPED WITH SILICONE EMBOLIC PARTICLES OF 175 UM. AS STATED ABOVE, HOWEVER, GELATIN POWDER ALSO CONTAINS SMALLER PARTICLES (DIAMETERS LESS THAN 125 UM) AND WOULD POSSIBLY BRING ABOUT DISTURBANCES IN THE LIVER. (B)(6) REPORTED ON LIVER INFARCTION WITH GELATIN (GELFOAM) POWDER IN THAT AREA. BOTH THE EXTRAHEPATIC BILE DUCT AND THE RIGHT AND LEFT HEPATIC DUCTS HAVE MUTUAL ANASTOMOSIS AMONG THE ARTERIAL BRANCHES UNCER THE MUCOSA OF THE BILE DUCT AND RECEIVE BLOOD FROM THE PLURAL ARTERIES FROM THE CONNECTIVE TISSUE AROUND THE BILE DUCT. THEREFORE, THERE SHOULD BE NO INCIDENCE OF MAIN BILE DUCT NECROSIS AS SEEN IN THE GALLBLADDER. AS VERIFIED IN OUR CASES, HOWEVER, IT IS LIKELY THAT IF SMALL PARTICLES (LESS THAN 250 UM) ARE USED AS THE EMBOLIC MATERIALS, NOT ONLY THE INFARCTION OF LIVER PARENCHYMA BUT ALSO THE INTRA- AND EXTRAHEPATIC BILE DUCT WOULD BECOME NECROTIC. IF GELATIN POWDER IS USED AS THE EMBOLIC SUBSTANCE, THE CATHETER SHOULD BE INSERTED SELECTIVELY TO THE MORE PERIPHERAL ARTERIES RATHER THAN THE SEGMENTAL HEPATIC ARTERY. IT IS ALSO NECESSARY TO CAREFULLY PERFORM THE PROCEDURE, TAKING INTO CONSIDERATION THE SIZE OF THE PARTICLES AND THE DURA-TION OF THE TIME FOR ISCHEMIA. ADDITIONAL INFORMATION HAS BEEN REQUESTED AND WILL BE PROVIDED AS IT BECOME AVAILABLE. COMPANY CLINICAL EVALUATION COMMENT: BASED ON INFORMATION AVAILABLE, THE REPORTED SERIOUS EVENT OF BILE DUCT NECROSIS WITH OFF LABEL USE OF GELATIN (GELFOAM) POWDER USED AS THE EMBOLUS FOR TRANSCATHETER HEPATIC ARTERIAL EMBOLIZATION (THAE) IN THIS PATIENT WITH HEPATOCELLULAR CARCINOMA (HCC) WAS NOTED. THIS PATIENT UNDERWENT THAE AND EMBOLIZATION OF THE RIGHT ANTERIOR PORTAL VENOUS BRANCHES WITH PERCUTANEOUS TRANSHEPATIC PORTAL VEIN CATHETERIZATION. HOWEVER, IT IS LIKELY THAT IF SMALL PARTICLES (LESS THAN 250 UM) ARE USED AS THE EMBOLIC MATERIALS, NOT ONLY THE INFARCTION OF LIVER PARENCHYMA BUT ALSO THE INTRA- AND EXTRAHEPATIC BILE DUCT WOULD BECOME NECROTIC. IF GELATIN POWDER IS USED AS THE EMBOLIC SUBSTANCE, THE CATHETER SHOULD BE INSERTED SELECTIVELY TO THE MORE PERIPHERAL ARTERIES RATHER THAN THE SEGMENTAL HEPATIC ARTERY. IT IS ALSO NECESSARY TO CAREFULLY PERFORM THE PROCEDURE, TAKING INTO CONSIDERATION OF THE SIZE OF THE PARTICLES AND THE DURATION OF THE TIME FOR ISCHEMIA. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE., COMMENT: BASED ON INFORMATION AVAILABLE, THE REPORTED SERIOUS EVENT OF BILE DUCT NECROSIS WITH OFF LABEL USE OF GELATIN (GELFOAM) POWDER USED AS THE EMBOLUS FOR TRANSCATHETER HEPATIC ARTERIAL EMBOLIZATION (THAE) IN THIS PATIENT WITH HEPATOCELLULAR CARCINOMA (HCC) WAS NOTED. THIS PATIENT UNDERWENT THAE AND EMBOLIZATION OF THE RIGHT ANTERIOR PORTAL VENOUS BRANCHES WITH PERCUTANEOUS TRANSHEPATIC PORTAL VEIN CATHETERIZATION. HOWEVER, IT IS LIKELY THAT IF SMALL PARTICLES (LESS THAN 250 UM) ARE USED AS THE EMBOLIC MATERIALS, NOT ONLY THE INFARCTION OF LIVER PARENCHYMA BUT ALSO THE INTRA- AND EXTRAHEPATIC BILE DUCT WOULD BECOME NECROTIC. IF GELATIN POWDER IS USED AS THE EMBOLIC SUBSTANCE, THE CATHETER SHOULD BE INSERTED SELECTIVELY TO THE MORE PERIPHERAL ARTERIES RATHER THAN THE SEGMENTAL HEPATIC ARTERY. IT IS ALSO NECESSARY TO CAREFULLY PERFORM THE PROCEDURE, TAKING INTO CONSIDERATION OF THE SIZE OF THE PARTICLES AND THE DURATION OF THE TIME FOR ISCHEMIA. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.