GELFOAM
Report
- Report Number
- 1810189-2019-00057
- Event Type
- Injury
- Date Received
- July 10, 2019
- Report Date
- June 14, 2019
- Manufacturer
- PFIZER, INC. (DEVICE)
- Product Code
- LMF
- PMA / PMN Number
- 18-286
- Adverse Event
- Yes
- Product Problem
- Yes
- Report Source
- Manufacturer report
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
Narratives
(23OCT2019 AND 24OCT2019): AS PER THE PRODUCT COMPLAINT GROUP THE FOLLOWING WAS PROVIDED: PRODUCT DESCRIPTION: GELFOAM STERILE SPONGE SIZE 100 X 1. THERE WAS NO MALFUNCTION PRESENT. SEVERITY OF HARM WAS UNKNOWN. LOT- NUMBER: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE SITE PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER SITE. CONCLUSION: THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. NO PRODUCT QUALITY ISSUES WERE OBSERVED.
23OCT2019 AND 24OCT2019: AS PER THE PRODUCT COMPLAINT GROUP THE FOLLOWING WAS PROVIDED: PRODUCT DESCRIPTION: GELFOAM STERILE SPONGE SIZE 100 X 1. THERE WAS NO MALFUNCTION PRESENT. SEVERITY OF HARM WAS UNKNOWN. LOT- NUMBER: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE SITE PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER SITE. CONCLUSION: THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. NO PRODUCT QUALITY ISSUES WERE OBSERVED. 24OCT2019: ADDITIONAL INFORMATION FROM THE PRODUCT QUALITY COMPLAINTS GROUP. THE SEVERITY OF HARM WAS REPORTED AS S3. DEVICE MALFUNCTION WAS REASONABLY SUGGESTED.
MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS], JAUNDICE [JAUNDICE]. CASE NARRATIVE: THIS IS A LITERATURE REPORT FROM CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 2010, VOL 33 (6); PP 1168-1179 , ENTITLED, 'MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA'. THIS AUTHOR REPORTED THE SAME DRUG WITH SIMILAR EVENT FOR ELEVEN PATIENTS, AND THIS IS THE TENTH OF ELEVEN REPORTS AND REFERS TO PT. 10 IN TABLE 2, A 73-YEAR-OLD FEMALE WHO EXPERIENCED BILE DUCT STRICTURE AND JAUNDICE. IN THIS REPORT, THE AUTHORS DESCRIBE THE CLINICAL COURSE AND RISK FACTORS FOR MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TACE. MATERIALS AND METHODS: PATIENTS: BETWEEN JANUARY 2004 AND JUNE 2009, WE ENCOUNTERED 18 PATIENTS WITH MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM WITH INTRAHEPATIC BILE DUCT DILATATION DEVELOPING AFTER TACE FOR HCC AMONG 446 CONSECUTIVE PATIENTS TREATED BY TACE. WE EXCLUDED BILE DUCT INVASION OF HCC BY IMAGING FINDINGS. THERE WERE 8 MEN AND 10 WOMEN, AND THE MEAN PATIENT AGE WAS 71.9 +/- 6.6 YEARS (RANGE 58 TO 83). ALL PATIENTS HAD LIVER CIRRHOSIS. THIS WAS RELATED TO HEPATITIS C IN 13 PATIENTS AND TO HEPATITIS B IN 1 PATIENT. THE ETIOLOGY WAS UNKNOWN IN 4 PATIENTS. THE DIAGNOSIS OF HCC WAS ESTABLISHED (1) BY IMAGING FINDINGS OF COMPUTED TOMOGRAPHY (CT) AND/OR MAGNETIC RESONANCE IMAGING (MRI) (I.E., CHARACTERISTIC NODULAR ENHANCEMENT ON THE ARTERIAL-PHASE IMAGES AND WASHOUT ON THE DELAYED-PHASE IMAGES) IN ADDITION TO (2) NODULAR STAIN ON ANGIOGRAPHY AND/OR CT DURING HEPATIC ARTERIOGRAPHY (CTHA) AND (3) NODULAR PERFUSION DEFECT ON CT DURING ARTERIAL PORTOGRAPHY (CTAP). SINCE MAY 2006, CTHA AND CTAP IMAGES WERE OBTAINED USING A CONE-BEAM CT (CBCT) TECHNIQUE (XPERCT; PHILIPS MEDICAL SYSTEMS, BEST, THE NETHERLANDS). THE TREATMENT RECORDS UP TO THE INITIAL TREATMENT FOR HCC WERE RETROSPECTIVELY ANALYZED. TACE PROCEDURE: A 1.8F TIP (CARNELIAN PIXIE; TOKAI MEDICAL PRODUCTS, KASUGAI, JAPAN), 2F TIP (PROGREAT A; TERUMO, TOKYO, JAPAN) OR 2.4F TIP (MICROFERRET; COOK, BLOOMINGTON, IN) MICROCATHETER, PASSED THROUGH A 4F CATHETER, WAS USED FOR ALL TACE PROCEDURES. TO NAVIGATE THE MICROCATHETER, A 0.016- INCH GUIDEWIRE (GTWIRE; TERUMO) WAS USED. THE MICROCATHETER WAS ADVANCED INTO THE TUMOR-FEEDING BRANCH AS SELECTIVELY AS POSSIBLE TO MINIMIZE THE EMBOLIZED AREA IN EACH PATIENT. AFTER THE MICROCATHETER WAS INSERTED INTO THE TARGET BRANCH, 0.5 ML 2% LIDOCAINE (XYLOCAINE; FUJISAWA, OSAKA, JAPAN) WAS INJECTED INTRA-ARTERIALLY TO PREVENT PAIN AND VASOSPASM. FIRST, THE FOLLOWING WAS INJECTED A MIXTURE OF (1) 2 TO 10 ML IODIZED OIL (LIPIODOL; ANDRE GUERBET, AULNAYSOUS-BOIS, FRANCE), (2) CONTRAST MATERIAL, I.E., 370 MG I/ML IOPAMIDOL (IOPAMIRON 370; BAYER, OSAKA, JAPAN) OR 350 MG I/ML IOMEPROL (IOMERON 350; EZAI, TOKYO, JAPAN) EQUAL TO ONE THIRD THE QUANTITY OF IODIZED OIL, (3) ANTICANCER DRUGS, I.E., 10 TO 30 MG EPIRUBICIN (FARMORBICIN; KYOWA HAKKO, TOKYO, JAPAN), AND (4) 2 TO 6 MG MITOMYCIN C (MITOMYCIN; KYOWA HAKKO) FOLLOWED BY INJECTION OF GELATIN SPONGE PARTICLES. THE TOTAL AMOUNT OF IODIZED OIL IN A SINGLE PROCEDURE WAS DETERMINED BASED ON TUMOR SIZE (ALMOST EQUAL TO THE DIAMETER OF THE TUMOR, E.G., A 3-CM TUMOR RECEIVED 3 ML IODIZED OIL) BUT DID NOT EXCEED 10 ML IN A SINGLE TACE SESSION. UP UNTIL DECEMBER 2006, WE HAD USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES. SINCE (B)(6) 2007, WE HAVE USED COMMERCIALLY AVAILABLE 1 MM DIAMETER GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). FOR ALL PATIENTS BUT 2, THE PARTICLES WERE CRUSHED INTO APPROXIMATELY 0.5- MM PARTICLES BY PUMPING 20 TIMES USING A 3-WAY STOPCOCK AND 2 2.5-ML SYRINGES, AND THEN THE GELATIN SPONGE SLURRY WAS INJECTED TO OBSTRUCT THE TUMOR-FEEDING BRANCH. IN THE REMAINING 2 PATIENTS, WHO HAD TUMORS MEASURING 9.3 AND 10 CM IN DIAMETER, RESPECTIVELY, 1-MM DIAMETER GELATIN SPONGE PARTICLES WERE USED. GELATIN SPONGE PARTICLES WERE INJECTED UNTIL THE TUMOR-FEEDING BRANCH WAS BLOCKED AND THE TARGETED TUMOR STAIN DISAPPEARED ON ANGIOGRAPHY. IN ADDITION, STEPWISE TACE SESSIONS WERE PERFORMED AT 3-TO 10-WEEK INTERVALS TO AVOID SEVERE COMPLICATIONS, SUCH AS ABSCESS FORMATION OR TUMOR LYSIS SYNDROME. CBCT WAS PERFORMED IN 7 PATIENTS DURING THE TACE PROCEDURE. IN 3 PATIENTS, CBCT IMAGES WERE OBTAINED BY INJECTION OF CONTRAST MATERIAL THROUGH A1 (N = 2) OR IMMEDIATELY AFTER TACE OF BOTH A1 AND THE MEDIAL SEGMENTAL ARTERY (A4) (N = 1) TO CONFIRM THE EMBOLIZED AREA. FOLLOW-UP: UNENHANCED CT WAS OBTAINED AT 1 WEEK AFTER TACE IN ALL PATIENTS TO CHECK FOR IODIZED OIL DISTRIBUTION. ALL PATIENTS WERE FOLLOWED-UP, AND DYNAMIC CT WAS PERFORMED EVERY 2 TO 3 MONTHS AFTER TACE TO INVESTIGATE ANY TUMOR RECURRENCE. IF POSSIBLE, AN ADDITIONAL TACE SESSION WAS PERFORMED WHEN LOCAL RECURRENCE OR NEWLY DEVELOPED LESIONS WERE DEMONSTRATED AT OTHER SITES. MRI (N = 11), ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) (N = 8), OR PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE (PTBD) (N = 6) WAS PERFORMED WHEN MAIN BILE DUCT STRICTURE WITH BILE DUCT DILATATION WAS DEMONSTRATED ON FOLLOW-UP CT. LABORATORY DATA INCLUDING SERUM BILIRUBIN (NORMAL RANGE 0.2 TO 1.0 MG/DL), ALKALINE PHOSHATASE (ALP; NORMAL RANGE 104 TO 338 U/L), AND C-GLUTAMYLTRANSPEPTIDASE (C-GTP; NORMAL RANGE 16 TO 73 U/L) WERE EXAMINED IN ALL PATIENTS 1 DAY BEFORE TACE, 1 WEEK AFTER TACE, AND EVERY 1 TO 3 MONTHS AFTER TACE. DEGREES OF INCREASED ALP LEVEL WERE DIVIDED INTO 3 GRADES: SLIGHT (150 U/L), MODERATE (151 TO 300 U/L), AND MARKED (301 U/L). DEGREES OF INCREASED C-GTP LEVEL WERE ALSO DIVIDED INTO 3 GRADES: SLIGHT (100 U/L), MODERATE (101 TO 200 U/ L), AND MARKED (201 U/L). DATA ANALYSIS: ALL IMAGING RESULTS (ARTERIOGRAMS, CBCT, CT, MRI, CHOLANGIOGRAMS), LABORATORY DATA, TREATMENT COURSES, AND OUTCOMES WERE RETROSPECTIVELY EVALUATED IN EACH PATIENT. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. TUMORS: ELEVEN PATIENTS HAD A SINGLE TUMOR, AND 7 PATIENTS HAD 1 TO 3 TUMORS. ALL PATIENTS BUT 1 HAD A TUMORS IN S1 AND/OR S4. EMBOLIZED BRANCHES: ALL PATIENTS UNDERWENT TACE OF A1 AND/OR A4 DURING THE TACE PROCEDURE JUST BEFORE DEVELOPMENT OF BILE DUCT STRICTURE. SERIAL CT FINDINGS: MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AND INTRAHEPATIC BILE DUCT DILATATION DEVELOPED IN ALL PATIENTS. EXCEPT FOR 1 PATIENT, THE SITE OF BILE DUCT STRICTURE CORRESPONDED WITH THE PORTION SHOWING IODIZED OIL ACCUMULATION ON CT OBTAINED AT 1 WEEK AFTER TACE. IN ALL PATIENTS, THE OCCLUDED OR STENOTIC SEGMENT WAS RELATIVELY SHORT AND SMOOTH ON CHOLANGIOGRAPHY OBTAINED BY MRI, ERCP, AND/OR PTBD. THE GRADES OF INCREASE IN ALP AND C-GTP WERE WELL CORRELATED. JAUNDICE DEVELOPED IN 1 PATIENT WITH A SLIGHT INCREASE, IN 2 PATIENTS WITH A MODERATE INCREASE, AND IN 3 PATIENTS WITH A MARKED INCREASE. DISCUSSION: IN THE PRESENT STUDY, GELATIN SPONGE PARTICLES APPROXIMATELY 0.5 TO 1 MM IN DIAMETER CAUSED BILE DUCT INJURY, ALTHOUGH THERE WAS A POSSIBILITY OF CONTAMINATION BY SMALL FRAGMENTS <250 UM. WE SPECULATE THAT SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF DEVELOPING BILE DUCT STRICTURE REGARDLESS OF THE SIZE OF GELATIN SPONGE PARTICLES. THE INCIDENCE OF MAIN BILE DUCT NECROSIS BY SELECTIVE TACE OF A1 AND/OR A4 WAS APPROXIMATELY 6% IN THE PRESENT STUDY. THIS INCIDENCE MAY HAVE BEEN INFLUENCED BY THE MAGNITUDE OF TACE, THE POSITION OF THE CATHETER TIP, THE PATTERNS OF ARTERIAL SUPPLY OF THE MAIN BILE DUCT, AND THE DAMAGE TO THE PERIBILIARY PLEXUS AND COLLATERALS BY PREVIOUS TACE SESSIONS. IN ADDITION, THE PRESENCE OF MULTIPLE BRANCHES OF A1 AND A4 MAY SALVAGE BILE DUCT ISCHEMIA BY ACTING AS COLLATERAL CIRCULATION. WE SPECULATE THAT THE USE OF SMALLER PARTICLES MAY NOT SIGNIFICANTLY INCREASE THE INCIDENCE OF MAIN BILE DUCT STRICTURE, EXCEPT WHEN THESE ARE SELECTIVELY INJECTED INTO A1 AND/OR A4. DURING SELECTIVE TACE OF A1 AND/OR A4, INJECTION OF EMBOLIC MATERIALS WITH SLIGHT FORCE MAY INCREASE THE RISK OF BILE DUCT NECROSIS BECAUSE EMBOLIC MATERIALS MAY FLOW INTO THE VASCULAR PLEXUS AROUND THE MAIN BILE DUCTS DIRECTLY OR INDIRECTLY THROUGH ANASTOMOSIS. WE SPECULATE THAT EMBOLIC MATERIALS INJECTED FROM A1 OR A4 MAY ALSO FLOW INTO THE CYSTIC ARTERY THROUGH THE ANASTOMOSIS, AND THUS SHRINKAGE OF THE GALLBLADDER MAY OCCUR; THIS WAS OBSERVED IN 22% OF PATIENTS IN THE PRESENT STUDY. IN THE PRESENT STUDY, WE TREATED 6 PATIENTS USING METALLIC STENTS. CHOLANGITIS AND JAUNDICE RECURRED IN 3 PATIENTS AFTER STENT PLACEMENT, INCLUDING 2 WHO UNDERWENT REPEATED TACE SESSIONS TO THE STENTED SEGMENT. IN ADDITION, A LARGE BILOMA DEVELOPED IN 1 PATIENT AFTER AN ADDITIONAL TACE SESSION PERFORMED AFTER STENT PLACEMENT. IN CONCLUSION, SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF CAUSING MAIN BILE DUCT STRICTURE AT THE HEPATIC HILIUM REGARDLESS OF THE NUMBER OF TACE SESSIONS AND THE PARTICLE SIZE OF THE EMBOLIC MATERIAL. AS PER TABLE 2: 'SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE,' THIS PATIENT (CASE NUMBER (B)(4)) WAS A 73-YEAR-OLD FEMALE WITH TUMOR DIAMETER OF 16 MM. SEGMENT WAS S4. EMBOLIZED BRANCHES WERE A1, A4, ETC. ANASTOMOSED BRANCHES WERE A1-A1. HER PREVIOUS EMBOLIZED BRANCHES (NO. OF TIMES) REPORTED AS: A4 (1), THE IODIZED OIL-ACCUMULATED PORTION WAS CHD. SITE OF BILE DUCT DILATATION: LEFT. NO SHRINKAGE OF GALLBLADDER WAS REPORTED. CHANGES IN BILE DUCT DILATATION: PROGRESSED. NO COMPLICATIONS WERE REPORTED. THE NUMBER OF ADDITIONAL TACE WAS 3. COMPLICATIONS AFTER ADDITIONAL TACE INCLUDED JAUNDICE IN WHICH PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE AND STENT PLACEMENT WAS PERFORMED. FOLLOW-UP (01JUL2019): THIS IS A FOLLOW-UP REPORT BASED ON THE RECEIPT OF THE QUERY RESPONSE FROM THE AUTHOR; THE CASE HAS BEEN UPDATED TO INCLUDE ADDITIONAL INFORMATION IDENTIFIED IN THE QUERY RESPONSE FROM AUTHOR. IN TABLE 2, GELFOAM PARTICLES WERE USED IN NO. 1-11 PATIENTS AND GELPART PARTICLES WERE USED IN NO. 12-18 PATIENTS. FOLLOW-UP (23OCT2019 AND 24OCT2019): THIS IS A FOLLOW-UP REPORT FROM THE PRODUCT COMPLAINT GROUP. PRODUCT DESCRIPTION: GELFOAM STERILE SPONGE SIZE 100 X 1. THERE WAS NO MALFUNCTION PRESENT. SEVERITY OF HARM WAS UNKNOWN. LOT- NUMBER: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE SITE PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER SITE. CONCLUSION: THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. NO PRODUCT QUALITY ISSUES WERE OBSERVED. NO FOLLOW-UP ATTEMPTS ARE NEEDED. NO FURTHER INFORMATION IS EXPECTED., COMMENT: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE WERE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE TACE COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. IN THE PRESENT STUDY, GELFOAM PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY COULD HAVE MADE FRAGMENTS SIZE UNSTABLE WHICH COULD BE PART OF REASON TO THE OCCURRENCE OF THE COMPLICATIONS. PFIZER PRODUCT QUALITY CONTROL INVESTIGATION CONCLUDED THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. NO PRODUCT QUALITY ISSUES WERE OBSERVED.
EVENT VERBATIM [PREFERRED TERM] MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS], JAUNDICE [JAUNDICE], CASE NARRATIVE: THIS IS A LITERATURE REPORT FROM CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 2010, VOL 33 (6); PP 1168-1179, ENTITLED, 'MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA'. THIS AUTHOR REPORTED THE SAME DRUG WITH SIMILAR EVENT FOR ELEVEN PATIENTS, AND THIS IS THE TENTH OF ELEVEN REPORTS AND REFERS TO PT. 10 IN TABLE 2, A 73-YEAR-OLD FEMALE WHO EXPERIENCED BILE DUCT STRICTURE AND JAUNDICE. IN THIS REPORT, THE AUTHORS DESCRIBE THE CLINICAL COURSE AND RISK FACTORS FOR MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TACE. MATERIALS AND METHODS: PATIENTS: BETWEEN (B)(6) 2004 AND (B)(6) 2009, WE ENCOUNTERED 18 PATIENTS WITH MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM WITH INTRAHEPATIC BILE DUCT DILATATION DEVELOPING AFTER TACE FOR HCC AMONG 446 CONSECUTIVE PATIENTS TREATED BY TACE. WE EXCLUDED BILE DUCT INVASION OF HCC BY IMAGING FINDINGS. THERE WERE 8 MEN AND 10 WOMEN, AND THE MEAN PATIENT AGE WAS 71.9 +/- 6.6 YEARS (RANGE 58 TO 83). ALL PATIENTS HAD LIVER CIRRHOSIS. THIS WAS RELATED TO HEPATITIS C IN 13 PATIENTS AND TO HEPATITIS B IN 1 PATIENT. THE ETIOLOGY WAS UNKNOWN IN 4 PATIENTS. THE DIAGNOSIS OF HCC WAS ESTABLISHED (1) BY IMAGING FINDINGS OF COMPUTED TOMOGRAPHY (CT) AND/OR MAGNETIC RESONANCE IMAGING (MRI) (I.E., CHARACTERISTIC NODULAR ENHANCEMENT ON THE ARTERIAL-PHASE IMAGES AND WASHOUT ON THE DELAYED-PHASE IMAGES) IN ADDITION TO (2) NODULAR STAIN ON ANGIOGRAPHY AND/OR CT DURING HEPATIC ARTERIOGRAPHY (CTHA) AND (3) NODULAR PERFUSION DEFECT ON CT DURING ARTERIAL PORTOGRAPHY (CTAP). SINCE (B)(6) 2006, CTHA AND CTAP IMAGES WERE OBTAINED USING A CONE-BEAM CT (CBCT) TECHNIQUE (XPERCT; PHILIPS MEDICAL SYSTEMS, BEST, THE NETHERLANDS). THE TREATMENT RECORDS UP TO THE INITIAL TREATMENT FOR HCC WERE RETROSPECTIVELY ANALYZED. TACE PROCEDURE: A 1.8F TIP (CARNELIAN PIXIE; TOKAI MEDICAL PRODUCTS, KASUGAI, JAPAN), 2F TIP (PROGREAT A; TERUMO, TOKYO, JAPAN) OR 2.4F TIP (MICROFERRET; COOK, BLOOMINGTON, IN) MICROCATHETER, PASSED THROUGH A 4F CATHETER, WAS USED FOR ALL TACE PROCEDURES. TO NAVIGATE THE MICROCATHETER, A 0.016- INCH GUIDEWIRE (GTWIRE; TERUMO) WAS USED. THE MICROCATHETER WAS ADVANCED INTO THE TUMOR-FEEDING BRANCH AS SELECTIVELY AS POSSIBLE TO MINIMIZE THE EMBOLIZED AREA IN EACH PATIENT. AFTER THE MICROCATHETER WAS INSERTED INTO THE TARGET BRANCH, 0.5 ML 2% LIDOCAINE (XYLOCAINE; FUJISAWA, OSAKA, JAPAN) WAS INJECTED INTRA-ARTERIALLY TO PREVENT PAIN AND VASOSPASM. FIRST, THE FOLLOWING WAS INJECTED A MIXTURE OF (1) 2 TO 10 ML IODIZED OIL (LIPIODOL; (B)(4), AULNAYSOUS-BOIS, FRANCE), (2) CONTRAST MATERIAL, I.E., 370 MG I/ML IOPAMIDOL (IOPAMIRON 370; BAYER, OSAKA, JAPAN) OR 350 MG I/ML IOMEPROL (IOMERON 350; EZAI, TOKYO, JAPAN) EQUAL TO ONE THIRD THE QUANTITY OF IODIZED OIL, (3) ANTI-CANCER DRUGS, I.E., 10 TO 30 MG EPIRUBICIN (FARMORBICIN; KYOWA HAKKO, TOKYO, JAPAN), AND (4) 2 TO 6 MG MITOMYCIN C (MITOMYCIN; KYOWA HAKKO) FOLLOWED BY INJECTION OF GELATIN SPONGE PARTICLES. THE TOTAL AMOUNT OF IODIZED OIL IN A SINGLE PROCEDURE WAS DETERMINED BASED ON TUMOR SIZE (ALMOST EQUAL TO THE DIAMETER OF THE TUMOR, E.G., A 3-CM TUMOR RECEIVED 3 ML IODIZED OIL) BUT DID NOT EXCEED 10 ML IN A SINGLE TACE SESSION. UP UNTIL DECEMBER 2006, WE HAD USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES. SINCE JANUARY 2007, WE HAVE USED COMMERCIALLY AVAILABLE 1 MM DIAMETER GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). FOR ALL PATIENTS BUT 2, THE PARTICLES WERE CRUSHED INTO APPROXIMATELY 0.5- MM PARTICLES BY PUMPING 20 TIMES USING A 3-WAY STOPCOCK AND 2 2.5-ML SYRINGES, AND THEN THE GELATIN SPONGE SLURRY WAS INJECTED TO OBSTRUCT THE TUMOR-FEEDING BRANCH. IN THE REMAINING 2 PATIENTS, WHO HAD TUMORS MEASURING 9.3 AND 10 CM IN DIAMETER, RESPECTIVELY, 1-MM DIAMETER GELATIN SPONGE PARTICLES WERE USED. GELATIN SPONGE PARTICLES WERE INJECTED UNTIL THE TUMOR-FEEDING BRANCH WAS BLOCKED AND THE TARGETED TUMOR STAIN DISAPPEARED ON ANGIOGRAPHY. IN ADDITION, STEPWISE TACE SESSIONS WERE PERFORMED AT 3-TO 10-WEEK INTERVALS TO AVOID SEVERE COMPLICATIONS, SUCH AS ABSCESS FORMATION OR TUMOR LYSIS SYNDROME. CBCT WAS PERFORMED IN 7 PATIENTS DURING THE TACE PROCEDURE. IN 3 PATIENTS, CBCT IMAGES WERE OBTAINED BY INJECTION OF CONTRAST MATERIAL THROUGH A1 (N = 2) OR IMMEDIATELY AFTER TACE OF BOTH A1 AND THE MEDIAL SEGMENTAL ARTERY (A4) (N = 1) TO CONFIRM THE EMBOLIZED AREA. FOLLOW-UP: UNENHANCED CT WAS OBTAINED AT 1 WEEK AFTER TACE IN ALL PATIENTS TO CHECK FOR IODIZED OIL DISTRIBUTION. ALL PATIENTS WERE FOLLOWED-UP, AND DYNAMIC CT WAS PERFORMED EVERY 2 TO 3 MONTHS AFTER TACE TO INVESTIGATE ANY TUMOR RECURRENCE. IF POSSIBLE, AN ADDITIONAL TACE SESSION WAS PERFORMED WHEN LOCAL RECURRENCE OR NEWLY DEVELOPED LESIONS WERE DEMONSTRATED AT OTHER SITES. MRI (N = 11), ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) (N = 8), OR PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE (PTBD) (N = 6) WAS PERFORMED WHEN MAIN BILE DUCT STRICTURE WITH BILE DUCT DILATATION WAS DEMONSTRATED ON FOLLOW-UP CT. LABORATORY DATA INCLUDING SERUM BILIRUBIN (NORMAL RANGE 0.2 TO 1.0 MG/DL), ALKALINE PHOSPHATASE (ALP; NORMAL RANGE 104 TO 338 U/L), AND C-GLUTAMYLTRANSPEPTIDASE (C-GTP; NORMAL RANGE 16 TO 73 U/L) WERE EXAMINED IN ALL PATIENTS 1 DAY BEFORE TACE, 1 WEEK AFTER TACE, AND EVERY 1 TO 3 MONTHS AFTER TACE. DEGREES OF INCREASED ALP LEVEL WERE DIVIDED INTO 3 GRADES: SLIGHT (150 U/L), MODERATE (151 TO 300 U/L), AND MARKED (301 U/L). DEGREES OF INCREASED C-GTP LEVEL WERE ALSO DIVIDED INTO 3 GRADES: SLIGHT (100 U/L), MODERATE (101 TO 200 U/ L), AND MARKED (201 U/L). DATA ANALYSIS: ALL IMAGING RESULTS (ARTERIOGRAMS, CBCT, CT, MRI, CHOLANGIOGRAMS), LABORATORY DATA, TREATMENT COURSES, AND OUTCOMES WERE RETROSPECTIVELY EVALUATED IN EACH PATIENT. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. TUMORS: ELEVEN PATIENTS HAD A SINGLE TUMOR, AND 7 PATIENTS HAD 1 TO 3 TUMORS. ALL PATIENTS BUT 1 HAD A TUMORS IN S1 AND/OR S4. EMBOLIZED BRANCHES: ALL PATIENTS UNDERWENT TACE OF A1 AND/OR A4 DURING THE TACE PROCEDURE JUST BEFORE DEVELOPMENT OF BILE DUCT STRICTURE. SERIAL CT FINDINGS: MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AND INTRAHEPATIC BILE DUCT DILATATION DEVELOPED IN ALL PATIENTS. EXCEPT FOR 1 PATIENT, THE SITE OF BILE DUCT STRICTURE CORRESPONDED WITH THE PORTION SHOWING IODIZED OIL ACCUMULATION ON CT OBTAINED AT 1 WEEK AFTER TACE. IN ALL PATIENTS, THE OCCLUDED OR STENOTIC SEGMENT WAS RELATIVELY SHORT AND SMOOTH ON CHOLANGIOGRAPHY OBTAINED BY MRI, ERCP, AND/OR PTBD. THE GRADES OF INCREASE IN ALP AND C-GTP WERE WELL CORRELATED. JAUNDICE DEVELOPED IN 1 PATIENT WITH A SLIGHT INCREASE, IN 2 PATIENTS WITH A MODERATE INCREASE, AND IN 3 PATIENTS WITH A MARKED INCREASE. DISCUSSION: IN THE PRESENT STUDY, GELATIN SPONGE PARTICLES APPROXIMATELY 0.5 TO 1 MM IN DIAMETER CAUSED BILE DUCT INJURY, ALTHOUGH THERE WAS A POSSIBILITY OF CONTAMINATION BY SMALL FRAGMENTS <250 UM. WE SPECULATE THAT SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF DEVELOPING BILE DUCT STRICTURE REGARDLESS OF THE SIZE OF GELATIN SPONGE PARTICLES. THE INCIDENCE OF MAIN BILE DUCT NECROSIS BY SELECTIVE TACE OF A1 AND/OR A4 WAS APPROXIMATELY 6% IN THE PRESENT STUDY. THIS INCIDENCE MAY HAVE BEEN INFLUENCED BY THE MAGNITUDE OF TACE, THE POSITION OF THE CATHETER TIP, THE PATTERNS OF ARTERIAL SUPPLY OF THE MAIN BILE DUCT, AND THE DAMAGE TO THE PERIBILIARY PLEXUS AND COLLATERALS BY PREVIOUS TACE SESSIONS. IN ADDITION, THE PRESENCE OF MULTIPLE BRANCHES OF A1 AND A4 MAY SALVAGE BILE DUCT ISCHEMIA BY ACTING AS COLLATERAL CIRCULATION. WE SPECULATE THAT THE USE OF SMALLER PARTICLES MAY NOT SIGNIFICANTLY INCREASE THE INCIDENCE OF MAIN BILE DUCT STRICTURE, EXCEPT WHEN THESE ARE SELECTIVELY INJECTED INTO A1 AND/OR A4. DURING SELECTIVE TACE OF A1 AND/OR A4, INJECTION OF EMBOLIC MATERIALS WITH SLIGHT FORCE MAY INCREASE THE RISK OF BILE DUCT NECROSIS BECAUSE EMBOLIC MATERIALS MAY FLOW INTO THE VASCULAR PLEXUS AROUND THE MAIN BILE DUCTS DIRECTLY OR INDIRECTLY THROUGH ANASTOMOSIS. WE SPECULATE THAT EMBOLIC MATERIALS INJECTED FROM A1 OR A4 MAY ALSO FLOW INTO THE CYSTIC ARTERY THROUGH THE ANASTOMOSIS, AND THUS SHRINKAGE OF THE GALLBLADDER MAY OCCUR; THIS WAS OBSERVED IN 22% OF PATIENTS IN THE PRESENT STUDY. IN THE PRESENT STUDY, WE TREATED 6 PATIENTS USING METALLIC STENTS. CHOLANGITIS AND JAUNDICE RECURRED IN 3 PATIENTS AFTER STENT PLACEMENT, INCLUDING 2 WHO UNDERWENT REPEATED TACE SESSIONS TO THE STENTED SEGMENT. IN ADDITION, A LARGE BILOMA DEVELOPED IN 1 PATIENT AFTER AN ADDITIONAL TACE SESSION PERFORMED AFTER STENT PLACEMENT. IN CONCLUSION, SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF CAUSING MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM REGARDLESS OF THE NUMBER OF TACE SESSIONS AND THE PARTICLE SIZE OF THE EMBOLIC MATERIAL. AS PER TABLE 2: 'SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE,' THIS PATIENT (CASE NUMBER 10) WAS A 73-YEAR-OLD FEMALE WITH TUMOR DIAMETER OF 16 MM. SEGMENT WAS S4. EMBOLIZED BRANCHES WERE A1, A4, ETC. ANASTOMOSED BRANCHES WERE A1-A1. HER PREVIOUS EMBOLIZED BRANCHES (NO. OF TIMES) REPORTED AS: A4 (1), THE IODIZED OIL-ACCUMULATED PORTION WAS CHD. SITE OF BILE DUCT DILATATION: LEFT. NO SHRINKAGE OF GALLBLADDER WAS REPORTED. CHANGES IN BILE DUCT DILATATION: PROGRESSED. NO COMPLICATIONS WERE REPORTED. THE NUMBER OF ADDITIONAL TACE WAS 3. COMPLICATIONS AFTER ADDITIONAL TACE INCLUDED JAUNDICE IN WHICH PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE AND STENT PLACEMENT WAS PERFORMED. FOLLOW-UP (01JUL2019): THIS IS A FOLLOW-UP REPORT BASED ON THE RECEIPT OF THE QUERY RESPONSE FROM THE AUTHOR; THE CASE HAS BEEN UPDATED TO INCLUDE ADDITIONAL INFORMATION IDENTIFIED IN THE QUERY RESPONSE FROM AUTHOR. IN TABLE 2, GELFOAM PARTICLES WERE USED IN NO. 1-11 PATIENTS AND GELPART PARTICLES WERE USED IN NO. 12-18 PATIENTS. FOLLOW-UP (23OCT2019 AND 24OCT2019): THIS IS A FOLLOW-UP REPORT FROM THE PRODUCT COMPLAINT GROUP. PRODUCT DESCRIPTION: GELFOAM STERILE SPONGE SIZE 100 X 1. THERE WAS NO MALFUNCTION PRESENT. SEVERITY OF HARM WAS UNKNOWN. LOT- NUMBER: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE SITE PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER SITE. CONCLUSION: THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. NO PRODUCT QUALITY ISSUES WERE OBSERVED. FOLLOW-UP (24OCT2019): THIS IS A FOLLOW-UP REPORT FROM PRODUCT QUALITY COMPLAINTS GROUP. THE SEVERITY OF HARM WAS REPORTED AS S3. DEVICE MALFUNCTION WAS REASONABLY SUGGESTED. COMPANY CLINICAL EVALUATION COMMENT: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE WERE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE TACE COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. IN THE PRESENT STUDY, GELFOAM PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY COULD HAVE MADE FRAGMENTS SIZE UNSTABLE WHICH COULD BE PART OF REASON TO THE OCCURRENCE OF THE COMPLICATIONS. A FOLLOW-UP REPORT FROM PRODUCT QUALITY COMPLAINTS GROUP REVEALED, THE SEVERITY OF HARM WAS REPORTED AS S3 AND DEVICE MALFUNCTION WAS REASONABLY SUGGESTED NOTED. NO FOLLOW-UP ATTEMPTS ARE NEEDED. NO FURTHER INFORMATION IS EXPECTED., COMMENT: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE WERE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE TACE COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. IN THE PRESENT STUDY, GELFOAM PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY COULD HAVE MADE FRAGMENTS SIZE UNSTABLE WHICH COULD BE PART OF REASON TO THE OCCURRENCE OF THE COMPLICATIONS. A FOLLOW-UP REPORT FROM PRODUCT QUALITY COMPLAINTS GROUP REVEALED, THE SEVERITY OF HARM WAS REPORTED AS S3 AND DEVICE MALFUNCTION WAS REASONABLY SUGGESTED NOTED. COMPANY CONDUCTED PRODUCT QUALITY CONTROL INVESTIGATION AND NO PRODUCT QUALITY ISSUES WERE OBSERVED.
MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS], JAUNDICE [JAUNDICE]. CASE DESCRIPTION: THIS IS A LITERATURE REPORT FROM THE CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 2010, VOL 33 (6); PP 1168-1179 , ENTITLED, 'MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA.' THIS AUTHOR REPORTED SIMILAR EVENT FOR EIGHTEEN PATIENTS. THIS IS THE TENTH OF EIGHTEEN REPORTS AND REFERS TO PT. 10, A 73-YEAR-OLD FEMALE WHO EXPERIENCED BILE DUCT STRICTURE AND JAUNDICE. IN THIS REPORT, WE DESCRIBE THE CLINICAL COURSE AND RISK FACTORS FOR MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TACE. MATERIALS AND METHODS: PATIENTS: BETWEEN JANUARY 2004 AND JUNE 2009, WE ENCOUNTERED 18 PATIENTS WITH MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM WITH INTRAHEPATIC BILE DUCT DILATATION DEVELOPING AFTER TACE FOR HCC AMONG 446 CONSECUTIVE PATIENTS TREATED BY TACE. WE EXCLUDED BILE DUCT INVASION OF HCC BY IMAGING FINDINGS. THERE WERE 8 MEN AND 10 WOMEN, AND THE MEAN PATIENT AGE WAS 71.9 +/- 6.6 YEARS (RANGE 58 TO 83). ALL PATIENTS HAD LIVER CIRRHOSIS. THIS WAS RELATED TO HEPATITIS C IN 13 PATIENTS AND TO HEPATITIS B IN 1 PATIENT. THE ETIOLOGY WAS UNKNOWN IN 4 PATIENTS. THE DIAGNOSIS OF HCC WAS ESTABLISHED (1) BY IMAGING FINDINGS OF COMPUTED TOMOGRAPHY (CT) AND/OR MAGNETIC RESONANCE IMAGING (MRI) (I.E., CHARACTERISTIC NODULAR ENHANCEMENT ON THE ARTERIAL-PHASE IMAGES AND WASHOUT ON THE DELAYED-PHASE IMAGES) IN ADDITION TO (2) NODULAR STAIN ON ANGIOGRAPHY AND/OR CT DURING HEPATIC ARTERIOGRAPHY (CTHA) AND (3) NODULAR PERFUSION DEFECT ON CT DURING ARTERIAL PORTOGRAPHY (CTAP). SINCE MAY 2006, CTHA AND CTAP IMAGES WERE OBTAINED USING A CONE-BEAM CT (CBCT) TECHNIQUE (XPERCT; PHILIPS MEDICAL SYSTEMS, BEST, THE NETHERLANDS). THE TREATMENT RECORDS UP TO THE INITIAL TREATMENT FOR HCC WERE RETROSPECTIVELY ANALYZED. TACE PROCEDURE: A 1.8F TIP (CARNELIAN PIXIE; TOKAI MEDICAL PRODUCTS, KASUGAI, JAPAN), 2F TIP (PROGREAT A; TERUMO, TOKYO, JAPAN) OR 2.4F TIP (MICROFERRET; COOK, BLOOMINGTON, IN) MICROCATHETER, PASSED THROUGH A 4F CATHETER, WAS USED FOR ALL TACE PROCEDURES. TO NAVIGATE THE MICROCATHETER, A 0.016- INCH GUIDEWIRE (GTWIRE; TERUMO) WAS USED. THE MICROCATHETER WAS ADVANCED INTO THE TUMOR-FEEDING BRANCH AS SELECTIVELY AS POSSIBLE TO MINIMIZE THE EMBOLIZED AREA IN EACH PATIENT. AFTER THE MICROCATHETER WAS INSERTED INTO THE TARGET BRANCH, 0.5 ML 2% LIDOCAINE (XYLOCAINE; FUJISAWA, OSAKA, JAPAN) WAS INJECTED INTRA-ARTERIALLY TO PREVENT PAIN AND VASOSPASM. FIRST, THE FOLLOWING WAS INJECTED A MIXTURE OF (1) 2 TO 10 ML IODIZED OIL (LIPIODOL; ANDRE GUERBET, AULNAYSOUS-BOIS, FRANCE), (2) CONTRAST MATERIAL, I.E., 370 MG I/ML IOPAMIDOL (IOPAMIRON 370; BAYER, OSAKA, JAPAN) OR 350 MG I/ML IOMEPROL (IOMERON 350; EZAI, TOKYO, JAPAN) EQUAL TO ONE THIRD THE QUANTITY OF IODIZED OIL, (3) ANTICANCER DRUGS, I.E., 10 TO 30 MG EPIRUBICIN (FARMORBICIN; KYOWA HAKKO, TOKYO, JAPAN), AND (4) 2 TO 6 MG MITOMYCIN C (MITOMYCIN; KYOWA HAKKO) FOLLOWED BY INJECTION OF GELATIN SPONGE PARTICLES. THE TOTAL AMOUNT OF IODIZED OIL IN A SINGLE PROCEDURE WAS DETERMINED BASED ON TUMOR SIZE (ALMOST EQUAL TO THE DIAMETER OF THE TUMOR, E.G., A 3-CM TUMOR RECEIVED 3 ML IODIZED OIL) BUT DID NOT EXCEED 10 ML IN A SINGLE TACE SESSION. UP UNTIL DECEMBER 2006, WE HAD USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES. SINCE JANUARY 2007, WE HAVE USED COMMERCIALLY AVAILABLE 1 MM DIAMETER GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). FOR ALL PATIENTS BUT 2, THE PARTICLES WERE CRUSHED INTO APPROXIMATELY 0.5- MM PARTICLES BY PUMPING 20 TIMES USING A 3-WAY STOPCOCK AND 2 2.5-ML SYRINGES, AND THEN THE GELATIN SPONGE SLURRY WAS INJECTED TO OBSTRUCT THE TUMOR-FEEDING BRANCH. IN THE REMAINING 2 PATIENTS, WHO HAD TUMORS MEASURING 9.3 AND 10 CM IN DIAMETER, RESPECTIVELY, 1-MM DIAMETER GELATIN SPONGE PARTICLES WERE USED. GELATIN SPONGE PARTICLES WERE INJECTED UNTIL THE TUMOR-FEEDING BRANCH WAS BLOCKED AND THE TARGETED TUMOR STAIN DISAPPEARED ON ANGIOGRAPHY. IN ADDITION, STEPWISE TACE SESSIONS WERE PERFORMED AT 3-TO 10-WEEK INTERVALS TO AVOID SEVERE COMPLICATIONS, SUCH AS ABSCESS FORMATION OR TUMOR LYSIS SYNDROME. CBCT WAS PERFORMED IN 7 PATIENTS DURING THE TACE PROCEDURE. IN 3 PATIENTS, CBCT IMAGES WERE OBTAINED BY INJECTION OF CONTRAST MATERIAL THROUGH A1 (N = 2) OR IMMEDIATELY AFTER TACE OF BOTH A1 AND THE MEDIAL SEGMENTAL ARTERY (A4) (N = 1) TO CONFIRM THE EMBOLIZED AREA. FOLLOW-UP: UNENHANCED CT WAS OBTAINED AT 1 WEEK AFTER TACE IN ALL PATIENTS TO CHECK FOR IODIZED OIL DISTRIBUTION. ALL PATIENTS WERE FOLLOWED-UP, AND DYNAMIC CT WAS PERFORMED EVERY 2 TO 3 MONTHS AFTER TACE TO INVESTIGATE ANY TUMOR RECURRENCE. IF POSSIBLE, AN ADDITIONAL TACE SESSION WAS PERFORMED WHEN LOCAL RECURRENCE OR NEWLY DEVELOPED LESIONS WERE DEMONSTRATED AT OTHER SITES. MRI (N= 11), ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) (N = 8), OR PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE (PTBD) (N =6) WAS PERFORMED WHEN MAIN BILE DUCT STRICTURE WITH BILE DUCT DILATATION WAS DEMONSTRATED ON FOLLOWUP CT. LABORATORY DATA INCLUDING SERUM BILIRUBIN (NORMAL RANGE 0.2 TO 1.0 MG/DL), ALKALINE PHOSHATASE (ALP; NORMAL RANGE 104 TO 338 U/L), AND C-GLUTAMYLTRANSPEPTIDASE (C-GTP; NORMAL RANGE 16 TO 73 U/L) WERE EXAMINED IN ALL PATIENTS 1 DAY BEFORE TACE, 1 WEEK AFTER TACE, AND EVERY 1 TO 3 MONTHS AFTER TACE. DEGREES OF INCREASED ALP LEVEL WERE DIVIDED INTO 3 GRADES: SLIGHT (150 U/L), MODERATE (151 TO 300 U/L), AND MARKED (301 U/L). DEGREES OF INCREASED C-GTP LEVEL WERE ALSO DIVIDED INTO 3 GRADES: SLIGHT (100 U/L), MODERATE (101 TO 200 U/ L), AND MARKED (201 U/L). DATA ANALYSIS: ALL IMAGING RESULTS (ARTERIOGRAMS, CBCT, CT, MRI, CHOLANGIOGRAMS), LABORATORY DATA, TREATMENT COURSES, AND OUTCOMES WERE RETROSPECTIVELY EVALUATED IN EACH PATIENT. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. TUMORS: ELEVEN PATIENTS HAD A SINGLE TUMOR, AND 7 PATIENTS HAD 1 TO 3 TUMORS. ALL PATIENTS BUT 1 HAD A TUMORS IN S1 AND/OR S4. EMBOLIZED BRANCHES: ALL PATIENTS UNDERWENT TACE OF A1 AND/OR A4 DURING THE TACE PROCEDURE JUST BEFORE DEVELOPMENT OF BILE DUCT STRICTURE. . SERIAL CT FINDINGS: MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AND INTRAHEPATIC BILE DUCT DILATATION DEVELOPED IN ALL PATIENTS. EXCEPT FOR 1 PATIENT, THE SITE OF BILE DUCT STRICTURE CORRESPONDED WITH THE PORTION SHOWING IODIZED OIL ACCUMULATION ON CT OBTAINED AT 1 WEEK AFTER TACE. IN ALL PATIENTS, THE OCCLUDED OR STENOTIC SEGMENT WAS RELATIVELY SHORT AND SMOOTH ON CHOLANGIOGRAPHY OBTAINED BY MRI, ERCP, AND/OR PTBD . THE GRADES OF INCREASE IN ALP AND C-GTP WERE WELL CORRELATED. JAUNDICE DEVELOPED IN 1 PATIENT WITH A SLIGHT INCREASE, IN 2 PATIENTS WITH A MODERATE INCREASE, AND IN 3 PATIENTS WITH A MARKED INCREASE. DISCUSSION: IN THE PRESENT STUDY, GELATIN SPONGE PARTICLES APPROXIMATELY 0.5 TO 1 MM IN DIAMETER CAUSED BILE DUCT INJURY, ALTHOUGH THERE WAS A POSSIBILITY OF CONTAMINATION BY SMALL FRAGMENTS <250 UM. WE SPECULATE THAT SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF DEVELOPING BILE DUCT STRICTURE REGARDLESS OF THE SIZE OF GELATIN SPONGE PARTICLES. THE INCIDENCE OF MAIN BILE DUCT NECROSIS BY SELECTIVE TACE OF A1 AND/OR A4 WAS APPROXIMATELY 6% IN THE PRESENT STUDY. THIS INCIDENCE MAY HAVE BEEN INFLUENCED BY THE MAGNITUDE OF TACE, THE POSITION OF THE CATHETER TIP, THE PATTERNS OF ARTERIAL SUPPLY OF THE MAIN BILE DUCT, AND THE DAMAGE TO THE PERIBILIARY PLEXUS AND COLLATERALS BY PREVIOUS TACE SESSIONS. IN ADDITION, THE PRESENCE OF MULTIPLE BRANCHES OF A1 AND A4 MAY SALVAGE BILE DUCT ISCHEMIA BY ACTING AS COLLATERAL CIRCULATION. WE SPECULATE THAT THE USE OF SMALLER PARTICLES MAY NOT SIGNIFICANTLY INCREASE THE INCIDENCE OF MAIN BILE DUCT STRICTURE, EXCEPT WHEN THESE ARE SELECTIVELY INJECTED INTO A1 AND/OR A4. DURING SELECTIVE TACE OF A1 AND/OR A4, INJECTION OF EMBOLIC MATERIALS WITH SLIGHT FORCE MAY INCREASE THE RISK OF BILE DUCT NECROSIS BECAUSE EMBOLIC MATERIALS MAY FLOW INTO THE VASCULAR PLEXUS AROUND THE MAIN BILE DUCTS DIRECTLY OR INDIRECTLY THROUGH ANASTOMOSIS. WE SPECULATE THAT EMBOLIC MATERIALS INJECTED FROM A1 OR A4 MAY ALSO FLOW INTO THE CYSTIC ARTERY THROUGH THE ANASTOMOSIS, AND THUS SHRINKAGE OF THE GALLBLADDER MAY OCCUR; THIS WAS OBSERVED IN 22% OF PATIENTS IN THE PRESENT STUDY. IN THE PRESENT STUDY, WE TREATED 6 PATIENTS USING METALLIC STENTS. CHOLANGITIS AND JAUNDICE RECURRED IN 3 PATIENTS AFTER STENT PLACEMENT, INCLUDING 2 WHO UNDERWENT REPEATED TACE SESSIONS TO THE STENTED SEGMENT. IN ADDITION, A LARGE BILOMA DEVELOPED IN 1 PATIENT AFTER AN ADDITIONAL TACE SESSION PERFORMED AFTER STENT PLACEMENT. IN CONCLUSION, SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF CAUSING MAIN BILE DUCT STRICTURE AT THE HEPATIC HILIUM REGARDLESS OF THE NUMBER OF TACE SESSIONS AND THE PARTICLE SIZE OF THE EMBOLIC MATERIAL. AS PER TABLE 2: 'SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE,' THIS PATIENT (CASE NUMBER 10) WAS A 73-YEAR-OLD FEMALE WITH TUMOR DIAMETER OF 16 MM. SEGMENT WAS S4. EMBOLIZED BRANCHES WERE A1, A4, ETC. ANASTOMOSED BRANCHES WERE A1-A1. HER PREVIOUS EMBOLIZED BRANCHES (NO. OF TIMES) REPORTED AS: A4 (1), THE IODIZED OIL-ACCUMULATED PORTION WAS CHD. SITE OF BILE DUCT DILATATION: LEFT. NO SHRINKAGE OF GALLBLADDER WAS REPORTED. CHANGES IN BILE DUCT DILATATION: PROGRESSED. NO COMPLICATIONS WERE REPORTED. THE NUMBER OF ADDITIONAL TACE WAS 3. COMPLICATIONS AFTER ADDITIONAL TACE INCLUDED JAUNDICE IN WHICH PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE AND STENT PLACEMENT WAS PERFORMED. PFIZER IS A MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN IN THE COUNTRY OF INCIDENCE. THIS MAY BE A DUPLICATE REPORT IF ANOTHER MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN HAS SUBMITTED THE SAME REPORT TO THE REGULATORY AUTHORITIES. COMPANY CLINICAL EVALUATION COMMENT: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE ARE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE OPERATION COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. THE SIZE OF GELATIN SPONGE PARTICLES COULD BE PART OF REASON TO THE OCCURRENCE OF THE EVENTS. IT IS UNKNOWN WHETHER THIS PATIENT USED GELATIN SPONGE (GELFOAM; (B)(6) ) OR GELATIN SPONGE PARTICLES (GELPART; (B)(6) , JAPAN). THIS CASE WILL BE REASSESSED SHOULD ADDITIONAL INFORMATION BECOME AVAILABLE. 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.
EVENT VERBATIM [PREFERRED TERM] MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS] , JAUNDICE [JAUNDICE]. CASE NARRATIVE:THIS IS A LITERATURE REPORT FROM THE CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 2010, VOL 33 (6); PP 1168-1179 , ENTITLED, 'MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA.' THIS AUTHOR REPORTED SAME DRUG WITH SIMILAR EVENT FOR ELEVEN PATIENTS, AND THIS IS THE TENTH OF ELEVEN REPORTS, REFERS TO PT. 10 IN TABLE 2, A 73-YEAR-OLD FEMALE WHO EXPERIENCED BILE DUCT STRICTURE AND JAUNDICE. IN THIS REPORT, WE DESCRIBE THE CLINICAL COURSE AND RISK FACTORS FOR MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TACE. MATERIALS AND METHODS: PATIENTS: BETWEEN JANUARY 2004 AND JUNE 2009, WE ENCOUNTERED 18 PATIENTS WITH MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM WITH INTRAHEPATIC BILE DUCT DILATATION DEVELOPING AFTER TACE FOR HCC AMONG 446 CONSECUTIVE PATIENTS TREATED BY TACE. WE EXCLUDED BILE DUCT INVASION OF HCC BY IMAGING FINDINGS. THERE WERE 8 MEN AND 10 WOMEN, AND THE MEAN PATIENT AGE WAS 71.9 +/- 6.6 YEARS (RANGE 58 TO 83). ALL PATIENTS HAD LIVER CIRRHOSIS. THIS WAS RELATED TO HEPATITIS C IN 13 PATIENTS AND TO HEPATITIS B IN 1 PATIENT. THE ETIOLOGY WAS UNKNOWN IN 4 PATIENTS. THE DIAGNOSIS OF HCC WAS ESTABLISHED (1) BY IMAGING FINDINGS OF COMPUTED TOMOGRAPHY (CT) AND/OR MAGNETIC RESONANCE IMAGING (MRI) (I.E., CHARACTERISTIC NODULAR ENHANCEMENT ON THE ARTERIAL-PHASE IMAGES AND WASHOUT ON THE DELAYED-PHASE IMAGES) IN ADDITION TO (2) NODULAR STAIN ON ANGIOGRAPHY AND/OR CT DURING HEPATIC ARTERIOGRAPHY (CTHA) AND (3) NODULAR PERFUSION DEFECT ON CT DURING ARTERIAL PORTOGRAPHY (CTAP). SINCE MAY 2006, CTHA AND CTAP IMAGES WERE OBTAINED USING A CONE-BEAM CT (CBCT) TECHNIQUE (XPERCT; PHILIPS MEDICAL SYSTEMS, BEST, THE NETHERLANDS). THE TREATMENT RECORDS UP TO THE INITIAL TREATMENT FOR HCC WERE RETROSPECTIVELY ANALYZED. TACE PROCEDURE: A 1.8F TIP (CARNELIAN PIXIE; TOKAI MEDICAL PRODUCTS, KASUGAI, JAPAN), 2F TIP (PROGREAT A; TERUMO, TOKYO, JAPAN) OR 2.4F TIP (MICROFERRET; COOK, BLOOMINGTON, IN) MICROCATHETER, PASSED THROUGH A 4F CATHETER, WAS USED FOR ALL TACE PROCEDURES. TO NAVIGATE THE MICROCATHETER, A 0.016- INCH GUIDEWIRE (GTWIRE; TERUMO) WAS USED. THE MICROCATHETER WAS ADVANCED INTO THE TUMOR-FEEDING BRANCH AS SELECTIVELY AS POSSIBLE TO MINIMIZE THE EMBOLIZED AREA IN EACH PATIENT. AFTER THE MICROCATHETER WAS INSERTED INTO THE TARGET BRANCH, 0.5 ML 2% LIDOCAINE (XYLOCAINE; FUJISAWA, OSAKA, JAPAN) WAS INJECTED INTRA-ARTERIALLY TO PREVENT PAIN AND VASOSPASM. FIRST, THE FOLLOWING WAS INJECTED A MIXTURE OF (1) 2 TO 10 ML IODIZED OIL (LIPIODOL; ANDRE GUERBET, AULNAYSOUS-BOIS, FRANCE), (2) CONTRAST MATERIAL, I.E., 370 MG I/ML IOPAMIDOL (IOPAMIRON 370; BAYER, OSAKA, JAPAN) OR 350 MG I/ML IOMEPROL (IOMERON 350; EZAI, TOKYO, JAPAN) EQUAL TO ONE THIRD THE QUANTITY OF IODIZED OIL, (3) ANTICANCER DRUGS, I.E., 10 TO 30 MG EPIRUBICIN (FARMORBICIN; KYOWA HAKKO, TOKYO, JAPAN), AND (4) 2 TO 6 MG MITOMYCIN C (MITOMYCIN; KYOWA HAKKO) FOLLOWED BY INJECTION OF GELATIN SPONGE PARTICLES. THE TOTAL AMOUNT OF IODIZED OIL IN A SINGLE PROCEDURE WAS DETERMINED BASED ON TUMOR SIZE (ALMOST EQUAL TO THE DIAMETER OF THE TUMOR, E.G., A 3-CM TUMOR RECEIVED 3 ML IODIZED OIL) BUT DID NOT EXCEED 10 ML IN A SINGLE TACE SESSION. UP UNTIL DECEMBER 2006, WE HAD USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES. SINCE JANUARY 2007, WE HAVE USED COMMERCIALLY AVAILABLE 1 MM DIAMETER GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). FOR ALL PATIENTS BUT 2, THE PARTICLES WERE CRUSHED INTO APPROXIMATELY 0.5- MM PARTICLES BY PUMPING 20 TIMES USING A 3-WAY STOPCOCK AND 2 2.5-ML SYRINGES, AND THEN THE GELATIN SPONGE SLURRY WAS INJECTED TO OBSTRUCT THE TUMOR-FEEDING BRANCH. IN THE REMAINING 2 PATIENTS, WHO HAD TUMORS MEASURING 9.3 AND 10 CM IN DIAMETER, RESPECTIVELY, 1-MM DIAMETER GELATIN SPONGE PARTICLES WERE USED. GELATIN SPONGE PARTICLES WERE INJECTED UNTIL THE TUMOR-FEEDING BRANCH WAS BLOCKED AND THE TARGETED TUMOR STAIN DISAPPEARED ON ANGIOGRAPHY. IN ADDITION, STEPWISE TACE SESSIONS WERE PERFORMED AT 3-TO 10-WEEK INTERVALS TO AVOID SEVERE COMPLICATIONS, SUCH AS ABSCESS FORMATION OR TUMOR LYSIS SYNDROME. CBCT WAS PERFORMED IN 7 PATIENTS DURING THE TACE PROCEDURE. IN 3 PATIENTS, CBCT IMAGES WERE OBTAINED BY INJECTION OF CONTRAST MATERIAL THROUGH A1 (N = 2) OR IMMEDIATELY AFTER TACE OF BOTH A1 AND THE MEDIAL SEGMENTAL ARTERY (A4) (N = 1) TO CONFIRM THE EMBOLIZED AREA. FOLLOW-UP: UNENHANCED CT WAS OBTAINED AT 1 WEEK AFTER TACE IN ALL PATIENTS TO CHECK FOR IODIZED OIL DISTRIBUTION. ALL PATIENTS WERE FOLLOWED-UP, AND DYNAMIC CT WAS PERFORMED EVERY 2 TO 3 MONTHS AFTER TACE TO INVESTIGATE ANY TUMOR RECURRENCE. IF POSSIBLE, AN ADDITIONAL TACE SESSION WAS PERFORMED WHEN LOCAL RECURRENCE OR NEWLY DEVELOPED LESIONS WERE DEMONSTRATED AT OTHER SITES. MRI (N = 11), ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) (N = 8), OR PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE (PTBD) (N = 6) WAS PERFORMED WHEN MAIN BILE DUCT STRICTURE WITH BILE DUCT DILATATION WAS DEMONSTRATED ON FOLLOWUP CT. LABORATORY DATA INCLUDING SERUM BILIRUBIN (NORMAL RANGE 0.2 TO 1.0 MG/DL), ALKALINE PHOSHATASE (ALP; NORMAL RANGE 104 TO 338 U/L), AND C-GLUTAMYLTRANSPEPTIDASE (C-GTP; NORMAL RANGE 16 TO 73 U/L) WERE EXAMINED IN ALL PATIENTS 1 DAY BEFORE TACE, 1 WEEK AFTER TACE, AND EVERY 1 TO 3 MONTHS AFTER TACE. DEGREES OF INCREASED ALP LEVEL WERE DIVIDED INTO 3 GRADES: SLIGHT (150 U/L), MODERATE (151 TO 300 U/L), AND MARKED (301 U/L). DEGREES OF INCREASED C-GTP LEVEL WERE ALSO DIVIDED INTO 3 GRADES: SLIGHT (100 U/L), MODERATE (101 TO 200 U/ L), AND MARKED (201 U/L). DATA ANALYSIS: ALL IMAGING RESULTS (ARTERIOGRAMS, CBCT, CT, MRI, CHOLANGIOGRAMS), LABORATORY DATA, TREATMENT COURSES, AND OUTCOMES WERE RETROSPECTIVELY EVALUATED IN EACH PATIENT. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. TUMORS: ELEVEN PATIENTS HAD A SINGLE TUMOR, AND 7 PATIENTS HAD 1 TO 3 TUMORS. ALL PATIENTS BUT 1 HAD A TUMORS IN S1 AND/OR S4. EMBOLIZED BRANCHES: ALL PATIENTS UNDERWENT TACE OF A1 AND/OR A4 DURING THE TACE PROCEDURE JUST BEFORE DEVELOPMENT OF BILE DUCT STRICTURE. SERIAL CT FINDINGS: MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AND INTRAHEPATIC BILE DUCT DILATATION DEVELOPED IN ALL PATIENTS. EXCEPT FOR 1 PATIENT, THE SITE OF BILE DUCT STRICTURE CORRESPONDED WITH THE PORTION SHOWING IODIZED OIL ACCUMULATION ON CT OBTAINED AT 1 WEEK AFTER TACE. IN ALL PATIENTS, THE OCCLUDED OR STENOTIC SEGMENT WAS RELATIVELY SHORT AND SMOOTH ON CHOLANGIOGRAPHY OBTAINED BY MRI, ERCP, AND/OR PTBD . THE GRADES OF INCREASE IN ALP AND C-GTP WERE WELL CORRELATED. JAUNDICE DEVELOPED IN 1 PATIENT WITH A SLIGHT INCREASE, IN 2 PATIENTS WITH A MODERATE INCREASE, AND IN 3 PATIENTS WITH A MARKED INCREASE. DISCUSSION: IN THE PRESENT STUDY, GELATIN SPONGE PARTICLES APPROXIMATELY 0.5 TO 1 MM IN DIAMETER CAUSED BILE DUCT INJURY, ALTHOUGH THERE WAS A POSSIBILITY OF CONTAMINATION BY SMALL FRAGMENTS <250 UM. WE SPECULATE THAT SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF DEVELOPING BILE DUCT STRICTURE REGARDLESS OF THE SIZE OF GELATIN SPONGE PARTICLES. THE INCIDENCE OF MAIN BILE DUCT NECROSIS BY SELECTIVE TACE OF A1 AND/OR A4 WAS APPROXIMATELY 6% IN THE PRESENT STUDY. THIS INCIDENCE MAY HAVE BEEN INFLUENCED BY THE MAGNITUDE OF TACE, THE POSITION OF THE CATHETER TIP, THE PATTERNS OF ARTERIAL SUPPLY OF THE MAIN BILE DUCT, AND THE DAMAGE TO THE PERIBILIARY PLEXUS AND COLLATERALS BY PREVIOUS TACE SESSIONS. IN ADDITION, THE PRESENCE OF MULTIPLE BRANCHES OF A1 AND A4 MAY SALVAGE BILE DUCT ISCHEMIA BY ACTING AS COLLATERAL CIRCULATION. WE SPECULATE THAT THE USE OF SMALLER PARTICLES MAY NOT SIGNIFICANTLY INCREASE THE INCIDENCE OF MAIN BILE DUCT STRICTURE, EXCEPT WHEN THESE ARE SELECTIVELY INJECTED INTO A1 AND/OR A4. DURING SELECTIVE TACE OF A1 AND/OR A4, INJECTION OF EMBOLIC MATERIALS WITH SLIGHT FORCE MAY INCREASE THE RISK OF BILE DUCT NECROSIS BECAUSE EMBOLIC MATERIALS MAY FLOW INTO THE VASCULAR PLEXUS AROUND THE MAIN BILE DUCTS DIRECTLY OR INDIRECTLY THROUGH ANASTOMOSIS. WE SPECULATE THAT EMBOLIC MATERIALS INJECTED FROM A1 OR A4 MAY ALSO FLOW INTO THE CYSTIC ARTERY THROUGH THE ANASTOMOSIS, AND THUS SHRINKAGE OF THE GALLBLADDER MAY OCCUR; THIS WAS OBSERVED IN 22% OF PATIENTS IN THE PRESENT STUDY. IN THE PRESENT STUDY, WE TREATED 6 PATIENTS USING METALLIC STENTS. CHOLANGITIS AND JAUNDICE RECURRED IN 3 PATIENTS AFTER STENT PLACEMENT, INCLUDING 2 WHO UNDERWENT REPEATED TACE SESSIONS TO THE STENTED SEGMENT. IN ADDITION, A LARGE BILOMA DEVELOPED IN 1 PATIENT AFTER AN ADDITIONAL TACE SESSION PERFORMED AFTER STENT PLACEMENT. IN CONCLUSION, SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF CAUSING MAIN BILE DUCT STRICTURE AT THE HEPATIC HILIUM REGARDLESS OF THE NUMBER OF TACE SESSIONS AND THE PARTICLE SIZE OF THE EMBOLIC MATERIAL. AS PER TABLE 2: 'SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE,' THIS PATIENT (CASE NUMBER (B)(6)) WAS A 73-YEAR-OLD FEMALE WITH TUMOR DIAMETER OF 16 MM. SEGMENT WAS S4. EMBOLIZED BRANCHES WERE A1, A4, ETC. ANASTOMOSED BRANCHES WERE A1-A1. HER PREVIOUS EMBOLIZED BRANCHES (NO. OF TIMES) REPORTED AS: A4 (1), THE IODIZED OIL-ACCUMULATED PORTION WAS CHD. SITE OF BILE DUCT DILATATION: LEFT. NO SHRINKAGE OF GALLBLADDER WAS REPORTED. CHANGES IN BILE DUCT DILATATION: PROGRESSED. NO COMPLICATIONS WERE REPORTED. THE NUMBER OF ADDITIONAL TACE WAS 3. COMPLICATIONS AFTER ADDITIONAL TACE INCLUDED JAUNDICE IN WHICH PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE AND STENT PLACEMENT WAS PERFORMED. FOLLOW-UP (01JUL2019): THIS IS A FOLLOW-UP REPORT BASED ON THE RECEIPT OF THE QUERY RESPONSE FROM THE AUTHOR; THE CASE HAS BEEN UPDATED TO INCLUDE ADDITIONAL INFORMATION IDENTIFIED IN THE QUERY RESPONSE FROM AUTHOR. IN TABLE 2, GELFOAM PARTICLES WERE USED IN NO. 1-11 PATIENTS AND GELPART PARTICLES WERE USED IN NO. 12-18 PATIENTS. COMPANY CLINICAL EVALUATION COMMENT: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE WERE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE TACE COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. IN THE PRESENT STUDY, GELFOAM PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY COULD HAVE MADE FRAGMENTS SIZE UNSTABLE WHICH COULD BE PART OF REASON TO THE OCCURRENCE OF THE COMPLICATIONS. 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: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE WERE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE TACE COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. IN THE PRESENT STUDY, GELFOAM PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY COULD HAVE MADE FRAGMENTS SIZE UNSTABLE WHICH COULD BE PART OF REASON TO THE OCCURRENCE OF THE COMPLICATIONS. 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.
MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS], JAUNDICE [JAUNDICE]. CASE NARRATIVE: THIS IS A LITERATURE REPORT FROM THE CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 2010, VOL 33 (6); PP 1168-1179 , ENTITLED, 'MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA.' THIS AUTHOR REPORTED SIMILAR EVENT FOR EIGHTEEN PATIENTS. THIS IS THE TENTH OF EIGHTEEN REPORTS AND REFERS TO PT. 10, A (B)(6) FEMALE WHO EXPERIENCED BILE DUCT STRICTURE AND JAUNDICE. IN THIS REPORT, WE DESCRIBE THE CLINICAL COURSE AND RISK FACTORS FOR MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TACE. MATERIALS AND METHODS: PATIENTS: BETWEEN JANUARY 2004 AND JUNE 2009, WE ENCOUNTERED 18 PATIENTS WITH MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM WITH INTRAHEPATIC BILE DUCT DILATATION DEVELOPING AFTER TACE FOR HCC AMONG 446 CONSECUTIVE PATIENTS TREATED BY TACE. WE EXCLUDED BILE DUCT INVASION OF HCC BY IMAGING FINDINGS. THERE WERE 8 MEN AND 10 WOMEN, AND THE MEAN PATIENT AGE WAS 71.9 +/- 6.6 YEARS (RANGE 58 TO 83). ALL PATIENTS HAD LIVER CIRRHOSIS. THIS WAS RELATED TO HEPATITIS C IN 13 PATIENTS AND TO HEPATITIS B IN 1 PATIENT. THE ETIOLOGY WAS UNKNOWN IN 4 PATIENTS. THE DIAGNOSIS OF HCC WAS ESTABLISHED (1) BY IMAGING FINDINGS OF COMPUTED TOMOGRAPHY (CT) AND/OR MAGNETIC RESONANCE IMAGING (MRI) (I.E., CHARACTERISTIC NODULAR ENHANCEMENT ON THE ARTERIAL-PHASE IMAGES AND WASHOUT ON THE DELAYED-PHASE IMAGES) IN ADDITION TO (2) NODULAR STAIN ON ANGIOGRAPHY AND/OR CT DURING HEPATIC ARTERIOGRAPHY (CTHA) AND (3) NODULAR PERFUSION DEFECT ON CT DURING ARTERIAL PORTOGRAPHY (CTAP). SINCE MAY 2006, CTHA AND CTAP IMAGES WERE OBTAINED USING A CONE-BEAM CT (CBCT) TECHNIQUE (XPERCT; PHILIPS MEDICAL SYSTEMS, BEST, THE NETHERLANDS). THE TREATMENT RECORDS UP TO THE INITIAL TREATMENT FOR HCC WERE RETROSPECTIVELY ANALYZED. T ACE PROCEDURE: A 1.8F TIP (CARNELIAN PIXIE; TOKAI MEDICAL PRODUCTS, KASUGAI, JAPAN), 2F TIP (PROGREAT A; TERUMO, TOKYO, JAPAN) OR 2.4F TIP (MICROFERRET; COOK, BLOOMINGTON, IN) MICROCATHETER, PASSED THROUGH A 4F CATHETER, WAS USED FOR ALL TACE PROCEDURES. TO NAVIGATE THE MICROCATHETER, A 0.016- INCH GUIDEWIRE (GTWIRE; TERUMO) WAS USED. THE MICROCATHETER WAS ADVANCED INTO THE TUMOR-FEEDING BRANCH AS SELECTIVELY AS POSSIBLE TO MINIMIZE THE EMBOLIZED AREA IN EACH PATIENT. AFTER THE MICROCATHETER WAS INSERTED INTO THE TARGET BRANCH, 0.5 ML 2% LIDOCAINE (XYLOCAINE; FUJISAWA, OSAKA, JAPAN) WAS INJECTED INTRA-ARTERIALLY TO PREVENT PAIN AND VASOSPASM. FIRST, THE FOLLOWING WAS INJECTED A MIXTURE OF (1) 2 TO 10 ML IODIZED OIL (LIPIODOL; ANDRE GUERBET, AULNAYSOUS-BOIS, FRANCE), (2) CONTRAST MATERIAL, I.E., 370 MG I/ML IOPAMIDOL (IOPAMIRON 370; BAYER, OSAKA, JAPAN) OR 350 MG I/ML IOMEPROL (IOMERON 350; EZAI, TOKYO, JAPAN) EQUAL TO ONE THIRD THE QUANTITY OF IODIZED OIL, (3) ANTICANCER DRUGS, I.E., 10 TO 30 MG EPIRUBICIN (FARMORUBICIN; KYOWA HAKKO, TOKYO, JAPAN), AND (4) 2 TO 6 MG MITOMYCIN C (MITOMYCIN; KYOWA HAKKO) FOLLOWED BY INJECTION OF GELATIN SPONGE PARTICLES. THE TOTAL AMOUNT OF IODIZED OIL IN A SINGLE PROCEDURE WAS DETERMINED BASED ON TUMOR SIZE (ALMOST EQUAL TO THE DIAMETER OF THE TUMOR, E.G., A 3-CM TUMOR RECEIVED 3 ML IODIZED OIL) BUT DID NOT EXCEED 10 ML IN A SINGLE TACE SESSION. UP UNTIL DECEMBER 2006, WE HAD USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) PARTICLES CUT INTO APPROXIMATELY 1-MM CUBES. SINCE JANUARY 2007, WE HAVE USED COMMERCIALLY AVAILABLE 1 MM DIAMETER GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). FOR ALL PATIENTS BUT 2, THE PARTICLES WERE CRUSHED INTO APPROXIMATELY 0.5- MM PARTICLES BY PUMPING 20 TIMES USING A 3-WAY STOPCOCK AND 2 2.5-ML SYRINGES, AND THEN THE GELATIN SPONGE SLURRY WAS INJECTED TO OBSTRUCT THE TUMOR-FEEDING BRANCH. IN THE REMAINING 2 PATIENTS, WHO HAD TUMORS MEASURING 9.3 AND 10 CM IN DIAMETER, RESPECTIVELY, 1-MM DIAMETER GELATIN SPONGE PARTICLES WERE USED. GELATIN SPONGE PARTICLES WERE INJECTED UNTIL THE TUMOR-FEEDING BRANCH WAS BLOCKED AND THE TARGETED TUMOR STAIN DISAPPEARED ON ANGIOGRAPHY. IN ADDITION, STEPWISE TACE SESSIONS WERE PERFORMED AT 3-TO 10-WEEK INTERVALS TO AVOID SEVERE COMPLICATIONS, SUCH AS ABSCESS FORMATION OR TUMOR LYSIS SYNDROME. CBCT WAS PERFORMED IN 7 PATIENTS DURING THE TACE PROCEDURE. IN 3 PATIENTS, CBCT IMAGES WERE OBTAINED BY INJECTION OF CONTRAST MATERIAL THROUGH A1 (N = 2) OR IMMEDIATELY AFTER TACE OF BOTH A1 AND THE MEDIAL SEGMENTAL ARTERY (A4) (N = 1) TO CONFIRM THE EMBOLIZED AREA. FOLLOW-UP: UNENHANCED CT WAS OBTAINED AT 1 WEEK AFTER TACE IN ALL PATIENTS TO CHECK FOR IODIZED OIL DISTRIBUTION. ALL PATIENTS WERE FOLLOWED-UP, AND DYNAMIC CT WAS PERFORMED EVERY 2 TO 3 MONTHS AFTER TACE TO INVESTIGATE ANY TUMOR RECURRENCE. IF POSSIBLE, AN ADDITIONAL TACE SESSION WAS PERFORMED WHEN LOCAL RECURRENCE OR NEWLY DEVELOPED LESIONS WERE DEMONSTRATED AT OTHER SITES. MRI (N = 11), ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) (N = 8), OR PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE (PTBD) (N = 6) WAS PERFORMED WHEN MAIN BILE DUCT STRICTURE WITH BILE DUCT DILATATION WAS DEMONSTRATED ON FOLLOWUP CT. LABORATORY DATA INCLUDING SERUM BILIRUBIN (NORMAL RANGE 0.2 TO 1.0 MG/DL), ALKALINE PHOSPHATASE (ALP; NORMAL RANGE 104 TO 338 U/L), AND C-GLUTAMYLTRANSPEPTIDASE (C-GTP; NORMAL RANGE 16 TO 73 U/L) WERE EXAMINED IN ALL PATIENTS 1 DAY BEFORE TACE, 1 WEEK AFTER TACE, AND EVERY 1 TO 3 MONTHS AFTER TACE. DEGREES OF INCREASED ALP LEVEL WERE DIVIDED INTO 3 GRADES: SLIGHT (150 U/L), MODERATE (151 TO 300 U/L), AND MARKED (301 U/L). DEGREES OF INCREASED C-GTP LEVEL WERE ALSO DIVIDED INTO 3 GRADES: SLIGHT (100 U/L), MODERATE (101 TO 200 U/ L), AND MARKED (201 U/L). DATA ANALYSIS: ALL IMAGING RESULTS (ARTERIOGRAMS, CBCT, CT, MRI, CHOLANGIOGRAMS), LABORATORY DATA, TREATMENT COURSES, AND OUTCOMES WERE RETROSPECTIVELY EVALUATED IN EACH PATIENT. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. TUMORS: ELEVEN PATIENTS HAD A SINGLE TUMOR, AND 7 PATIENTS HAD 1 TO 3 TUMORS. ALL PATIENTS BUT 1 HAD A TUMORS IN S1 AND/OR S4. EMBOLIZED BRANCHES: ALL PATIENTS UNDERWENT TACE OF A1 AND/OR A4 DURING THE TACE PROCEDURE JUST BEFORE DEVELOPMENT OF BILE DUCT STRICTURE. . SERIAL CT FINDINGS: MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AND INTRAHEPATIC BILE DUCT DILATATION DEVELOPED IN ALL PATIENTS. EXCEPT FOR 1 PATIENT, THE SITE OF BILE DUCT STRICTURE CORRESPONDED WITH THE PORTION SHOWING IODIZED OIL ACCUMULATION ON CT OBTAINED AT 1 WEEK AFTER TACE. IN ALL PATIENTS, THE OCCLUDED OR STENOTIC SEGMENT WAS RELATIVELY SHORT AND SMOOTH ON CHOLANGIOGRAPHY OBTAINED BY MRI, ERCP, AND/OR PTBD . THE GRADES OF INCREASE IN ALP AND C-GTP WERE WELL CORRELATED. JAUNDICE DEVELOPED IN 1 PATIENT WITH A SLIGHT INCREASE, IN 2 PATIENTS WITH A MODERATE INCREASE, AND IN 3 PATIENTS WITH A MARKED INCREASE. DISCUSSION: IN THE PRESENT STUDY, GELATIN SPONGE PARTICLES APPROXIMATELY 0.5 TO 1 MM IN DIAMETER CAUSED BILE DUCT INJURY, ALTHOUGH THERE WAS A POSSIBILITY OF CONTAMINATION BY SMALL FRAGMENTS <250 UM. WE SPECULATE THAT SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF DEVELOPING BILE DUCT STRICTURE REGARDLESS OF THE SIZE OF GELATIN SPONGE PARTICLES. THE INCIDENCE OF MAIN BILE DUCT NECROSIS BY SELECTIVE TACE OF A1 AND/OR A4 WAS APPROXIMATELY 6% IN THE PRESENT STUDY. THIS INCIDENCE MAY HAVE BEEN INFLUENCED BY THE MAGNITUDE OF TACE, THE POSITION OF THE CATHETER TIP, THE PATTERNS OF ARTERIAL SUPPLY OF THE MAIN BILE DUCT, AND THE DAMAGE TO THE PERIBILIARY PLEXUS AND COLLATERALS BY PREVIOUS TACE SESSIONS. IN ADDITION, THE PRESENCE OF MULTIPLE BRANCHES OF A1 AND A4 MAY SALVAGE BILE DUCT ISCHEMIA BY ACTING AS COLLATERAL CIRCULATION. WE SPECULATE THAT THE USE OF SMALLER PARTICLES MAY NOT SIGNIFICANTLY INCREASE THE INCIDENCE OF MAIN BILE DUCT STRICTURE, EXCEPT WHEN THESE ARE SELECTIVELY INJECTED INTO A1 AND/OR A4. DURING SELECTIVE TACE OF A1 AND/OR A4, INJECTION OF EMBOLIC MATERIALS WITH SLIGHT FORCE MAY INCREASE THE RISK OF BILE DUCT NECROSIS BECAUSE EMBOLIC MATERIALS MAY FLOW INTO THE VASCULAR PLEXUS AROUND THE MAIN BILE DUCTS DIRECTLY OR INDIRECTLY THROUGH ANASTOMOSIS. WE SPECULATE THAT EMBOLIC MATERIALS INJECTED FROM A1 OR A4 MAY ALSO FLOW INTO THE CYSTIC ARTERY THROUGH THE ANASTOMOSIS, AND THUS SHRINKAGE OF THE GALLBLADDER MAY OCCUR; THIS WAS OBSERVED IN 22% OF PATIENTS IN THE PRESENT STUDY. IN THE PRESENT STUDY, WE TREATED 6 PATIENTS USING METALLIC STENTS. CHOLANGITIS AND JAUNDICE RECURRED IN 3 PATIENTS AFTER STENT PLACEMENT, INCLUDING 2 WHO UNDERWENT REPEATED TACE SESSIONS TO THE STENTED SEGMENT. IN ADDITION, A LARGE BILOMA DEVELOPED IN 1 PATIENT AFTER AN ADDITIONAL TACE SESSION PERFORMED AFTER STENT PLACEMENT. IN CONCLUSION, SELECTIVE TACE OF A1 AND/OR A4 PRESENTS A RISK OF CAUSING MAIN BILE DUCT STRICTURE AT THE HEPATIC HILIUM REGARDLESS OF THE NUMBER OF TACE SESSIONS AND THE PARTICLE SIZE OF THE EMBOLIC MATERIAL. THIS PATIENT (CASE NUMBER 10) WAS A (B)(6) FEMALE WITH TUMOR DIAMETER OF 16 MM. SEGMENT WAS S4. EMBOLIZED BRANCHES WERE A1, A4, ETC. ANASTOMOSED BRANCHES WERE A1-A1. HER PREVIOUS EMBOLIZED BRANCHES (NO. OF TIMES) REPORTED AS: A4 (1), THE IODIZED OIL-ACCUMULATED PORTION WAS CHD. SITE OF BILE DUCT DILATATION: LEFT. NO SHRINKAGE OF GALLBLADDER WAS REPORTED. CHANGES IN BILE DUCT DILATATION: PROGRESSED. NO COMPLICATIONS WERE REPORTED. THE NUMBER OF ADDITIONAL TACE WAS 3. COMPLICATIONS AFTER ADDITIONAL TACE INCLUDED JAUNDICE IN WHICH PERCUTANEOUS TRANSHEPATIC BILIARY DRAINAGE AND STENT PLACEMENT WAS PERFORMED. PFIZER IS A MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN IN THE COUNTRY OF INCIDENCE. THIS MAY BE A DUPLICATE REPORT IF ANOTHER MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN HAS SUBMITTED THE SAME REPORT TO THE REGULATORY AUTHORITIES. COMPANY CLINICAL EVALUATION COMMENT: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE ARE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE OPERATION COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. THE SIZE OF GELATIN SPONGE PARTICLES COULD BE PART OF REASON TO THE OCCURRENCE OF THE EVENTS. IT IS UNKNOWN WHETHER THIS PATIENT USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) OR GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). THIS CASE WILL BE REASSESSED SHOULD ADDITIONAL INFORMATION BECOME AVAILABLE. 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: GELATIN SPONGE PARTICLES USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC) IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). THE REPORTED MAIN BILE DUCT STRICTURE WITH JAUNDICE ARE ASSOCIATED WITH THE GELATIN SPONGE OFF LABEL USE. THERE ARE MULTIPLE FACTORS IMPACTED THE INCIDENCE OF THE OPERATION COMPLICATIONS, ESPECIALLY THE OPERATION TECHNIQUE, THE SELECTIVE TACE OF A1 AND/OR A4 RATHER THAN ULTRASELECTIVE TACE. THE SIZE OF GELATIN SPONGE PARTICLES COULD BE PART OF REASON TO THE OCCURRENCE OF THE EVENTS. IT IS UNKNOWN WHETHER THIS PATIENT USED GELATIN SPONGE (GELFOAM; UPJOHN, KALAMAZOO, MI) OR GELATIN SPONGE PARTICLES (GELPART; NIPPON KAYAKU, TOKYO, JAPAN). THIS CASE WILL BE REASSESSED SHOULD ADDITIONAL INFORMATION BECOME AVAILABLE. 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.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 569343 | GELFOAM | SPONGE, STERILE; CLASS III | LMF | PFIZER, INC. (DEVICE) |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 73 YR | Other| R | FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| IOMERON.| IOMERON.| IOMERON.| IOMERON.| IOMERON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| LIPIODOL.| LIPIODOL.| LIPIODOL.| LIPIODOL.| LIPIODOL.| MITOMYCIN C.| MITOMYCIN C.| MITOMYCIN C.| MITOMYCIN C.| MITOMYCIN C.| XYLOCAINE [LIDOCAINE]| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE]. |