GELFOAM
Report
- Report Number
- 1810189-2019-00048
- 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
10SEP2019-A COMPLAINT HAS BEEN RECEIVED BY PFIZER WITH NO REASONABLE SUSPICION OF A MALFUNCTION; THE ASSOCIATED WORST CASE SEVERITY IS UNKNOWN. IMPACT TO THE DEVICE: POSSIBLE ADVERSE EVENT. HAZARDOUS SITUATION: UNKNOWN; HAZARD NUMBER (WORST CASE): UNKNOWN; SEVERITY (WORST CASE): UNKNOWN; P2 VALUE: H10-03 (WORST CASE) UNKNOWN. 23OCT2019 AND 24OCT2019-PRODUCT-DESCRIPTION: GELFOAM STERILE SPONGE SIZE 100 X 1. THERE WAS NO MALFUNCTION PRESENT AND SEVERITY OF HARM WAS UNKNOWN. LOT#: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE 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.
10SEP2019-A COMPLAINT HAS BEEN RECEIVED BY PFIZER WITH NO REASONABLE SUSPICION OF A MALFUNCTION; THE ASSOCIATED WORST CASE SEVERITY IS UNKNOWN. IMPACT TO THE DEVICE: POSSIBLE ADVERSE EVENT. HAZARDOUS SITUATION: UNKNOWN; HAZARD NUMBER (WORST CASE): UNKNOWN; SEVERITY (WORST CASE): UNKNOWN; P2 VALUE: H10-03 (WORST CASE) UNKNOWN. 23OCT2019 AND 24OCT2019-PRODUCT-DESCRIPTION: GELFOAM STERILE SPONGE SIZE 100 X 1. THERE WAS NO MALFUNCTION PRESENT AND SEVERITY OF HARM WAS UNKNOWN. LOT#: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE 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): NEW INFORMATION REPORTED FROM THE PRODUCT QUALITY COMPLAINTS GROUP: THE SEVERITY OF HARM WAS REPORTED AS S3. DEVICE MALFUNCTION WAS REASONABLY SUGGESTED.
A COMPLAINT HAS BEEN RECEIVED BY PFIZER WITH NO REASONABLE SUSPICION OF A MALFUNCTION; THE ASSOCIATED WORST CASE SEVERITY IS UNKNOWN. IMPACT TO THE DEVICE: POSSIBLE ADVERSE EVENT. HAZARDOUS SITUATION: UNKNOWN; HAZARD NUMBER (WORST CASE): UNKNOWN; SEVERITY (WORST CASE): UNKNOWN; P2 VALUE: H10-03 (WORST CASE) UNKNOWN.
MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS]. 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 SAME DRUG WITH SIMILAR EVENT FOR ELEVEN PATIENTS. THIS IS THE SECOND OF ELEVEN REPORTS AND REFERS TO PATIENT 2 IN TABLE 2, A 76-YEAR-OLD FEMALE WHO EXPERIENCED BILE DUCT STRICTURE. THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE CLINICAL COURSE OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC). AMONG 446 CONSECUTIVE PATIENTS WITH HCC TREATED BY TACE, MAIN BILE DUCT STRICTURE DEVELOPED IN 18 (4.0%). ALL IMAGING AND LABORATORY DATA, TREATMENT COURSE, AND OUTCOMES WERE RETROSPECTIVELY ANALYZED. ALL PATIENTS HAD 1 TO 2 TUMORS MEASURING 10 TO 100 MM IN DIAMETER (MEAN ± SD 24.5 ± 5.4 MM) NEAR THE HEPATIC HILUM FED BY THE CAUDATE ARTERIAL BRANCH (A1) AND/OR MEDIAL SEGMENTAL ARTERY (A4) OF THE LIVER. DURING THE TACE PROCEDURE THAT CAUSED BILE DUCT INJURY, A1 WAS EMBOLIZED IN 8, A4 WAS EMBOLIZED IN 5, AND BOTH WERE EMBOLIZED IN 5 PATIENTS. NINE PATIENTS (50.0%) HAD A HISTORY OF TACE IN EITHER A1 OR A4. IODIZED OIL ACCUMULATION IN THE BILE DUCT WALL WAS SEEN IN ALL PATIENTS ON COMPUTED TOMOGRAPHY OBTAINED 1 WEEK LATER. BILE DUCT DILATATION CAUSED BY MAIN BILE DUCT STRICTURE DEVELOPED IN BOTH LOBES (N = 9), IN THE RIGHT LOBE (N = 3), IN THE LEFT LOBE (N = 4), IN SEGMENT (S) 2 (N = 1), AND IN S3 (N = 1). SERUM LEVELS OF ALKALINE PHOSPHATASE AND C-GLUTAMYLTRANSPEPTIDASE INCREASED IN 13 PATIENTS. BILOMA REQUIRING DRAINAGE DEVELOPED IN 2 PATIENTS; JAUNDICE DEVELOPED IN 4 PATIENTS; AND METALLIC STENTS WERE PLACED IN 3 PATIENTS. COMPLICATIONS AFTER ADDITIONAL TACE SESSIONS, INCLUDING BILOMA (N = 3) AND/OR JAUNDICE (N = 5), OCCURRED IN 7 PATIENTS AND WERE TREATED BY ADDITIONAL INTERVENTION, INCLUDING METALLIC STENT PLACEMENT IN 2 PATIENTS. AFTER INITIAL TACE OF A1 AND/OR A4, 8 PATIENTS (44.4%), INCLUDING 5 WITH UNCONTROLLABLE JAUNDICE OR CHOLANGITIS, DIED AT 37.9 ± 34.9 MONTHS AFTER TACE, AND 10 (55.6%) HAVE SURVIVED FOR 38.4 ± 37.9 MONTHS. SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM. BILOMA AND JAUNDICE ARE SERIOUS COMPLICATIONS ASSOCIATED WITH BILE DUCT STRICTURES. 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. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. CLINICAL COURSES AND OUTCOMES: ALL PATIENTS WERE FOLLOWED-UP FOR 3 TO 129 MONTHS (MEAN 38.2 +/- 35.4) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND FOR 3 TO 72 MONTHS (MEAN 25.2 +/- 17.6) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. ELEVEN PATIENTS (61.1%) PRESENTED WITH BILE DUCT COMPLICATIONS ASSOCIATED WITH MAIN BILE DUCT STRICTURE. CHOLANGITIS DEVELOPED IN 2 PATIENTS (11.1%) AT 2 MONTHS AFTER TACE AND RESOLVED AFTER ADMINISTRATION OF ANTIBIOTICS (SULPERAZON; PFIZER, TOKYO, JAPAN). BILE DUCT DILATATION WAS IMPROVED DURING FOLLOW-UP IN THESE PATIENTS (FIG. 1). BILOMA DEVELOPED IN 4 PATIENTS (22.2%), AND PERCUTANEOUS DRAINAGE WAS PERFORMED IN 2 OF 4 PATIENTS AT 2 AND 4 MONTHS, RESPECTIVELY, AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. JAUNDICE (SERUM BILIRUBIN LEVEL 9.3 TO 14.0 MG/DL [MEAN 11.7 +/- 2.3]) DEVELOPED IN 4 PATIENTS (22.2%), INCLUDING 2 WITH A HISTORY OF BILOMA DRAINAGE, AT 5 TO 11 MONTHS (MEAN 7.3 +/- 2.9) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. THREE PATIENTS UNDERWENT PTBD. IN THE REMAINING PATIENT, BILE DUCT DRAINAGE WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. IN ANOTHER PATIENT WITHOUT JAUNDICE, PTBD WAS PERFORMED TO RELIEVE BILE DUCT DILATATION BEFORE ADDITIONAL TACE WITH BILE DUCT DILATATION FOR HCC IN THE LEFT LOBE OF THE LIVER. METALLIC STENT PLACEMENT (ZILVER 635; COOK) WAS SUBSEQUENTLY PERFORMED IN 4 PATIENTS. IN 2 PATIENTS, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO THE CBD USING EITHER A BILATERAL OR LEFT APPROACH. IN 2 PATIENTS, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CHD BY WAY OF A LEFT APPROACH. THE PTBD CATHETER WAS REMOVED AFTER STENT PLACEMENT. IN 13 PATIENTS (72.2%), INCLUDING 4 WHO UNDERWENT STENT PLACEMENT, 1 TO 5 ADDITIONAL TACE SESSIONS (MEAN 2.6 +/- 1.5) WERE PERFORMED BECAUSE OF LOCAL RECURRENCE AND/OR NEW LESIONS AT OTHER SITES. IN TOTAL, 24 TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE WERE PERFORMED IN 12 PATIENTS, AND 10 TACE SESSIONS TO THE AREA WITHOUT BILE DUCT DILATATION WERE PERFORMED IN 5 PATIENTS. COMPLICATIONS ASSOCIATED WITH ADDITIONAL TACE SESSIONS OCCURRED IN 7 OF 13 PATIENTS (53.8%). BILOMA DEVELOPED IN 3 PATIENTS. IT DEVELOPED IN 2 PATIENTS AT 2 MONTHS AFTER THE ADDITIONAL FIRST TACE SESSION TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE AND IN 1 PATIENT AT 1 MONTH AFTER 4 ADDITIONAL TACE SESSIONS TO THE STENTED LOBE. PERCUTANEOUS DRAINAGE WAS REQUIRED IN 1 PATIENT WITH PREVIOUS STENT PLACEMENT. JAUNDICE (6.5 TO 22.6 MG/DL [MEAN 12.6 +/- 6.7]) DEVELOPED IN 5 PATIENTS AT 3 TO 26 MONTHS (MEAN 15.4 +/- 19.7) AFTER THE FIRST ADDITIONAL TACE SESSION AND AT 2 WEEKS TO 5 MONTHS (MEAN 2.8 +/- 1.8) AFTER THE LAST ADDITIONAL TACE SESSION, INCLUDING 2 PATIENTS WHO HAD UNDERGONE STENT PLACEMENT. IT DEVELOPED AFTER 1 (N = 2), 3 (N = 1), AND 4 (N = 2) ADDITIONAL TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION (N = 3) OR TO THE STENTED LOBE (N = 2). ONE OF THESE PATIENTS ALSO HAD A SMALL BILOMA. ALL PATIENTS BUT 1 UNDERWENT PTBD. IN 1 PATIENT, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CBD USING A LEFT APPROACH. IN ANOTHER PATIENT, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO CBD USING A BILATERAL APPROACH (FIG. 5). THE BILE DUCT WAS OCCLUDED IN THE STENTED SEGMENT IN 2 PATIENTS WHO HAD PREVIOUSLY UNDERGONE STENT PLACEMENT. JAUNDICE DID NOT IMPROVE BECAUSE OF HEPATIC FAILURE, AND EXTERNAL DRAINAGE WAS CONTINUED UNTIL THE PATIENTS DEATH. IN THE REMAINING PATIENT, PTBD WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. CHOLANGITIS RECURRED IN 1 PATIENT AT 1 MONTH AFTER STENT PLACEMENT WITHOUT AN ADDITIONAL TACE SESSION, AND IT DID NOT IMPROVE DESPITE ADMINISTRATION OF ANTIBIOTICS. ONE PATIENT WHO HAD UNDERGONE STENT PLACEMENT TO RELIEVE BILE DUCT STRICTURE BEFORE ADDITIONAL TACE SESSIONS DID NOT DEVELOP ANY COMPLICATIONS DESPITE 4 ADDITIONAL TACE SESSIONS, INCLUDING 2 TO THE STENTED LOBE. SEVEN PATIENTS (38.9%) HAVE NOT PRESENTED ANY SYMPTOMS FOR 3 TO 68 MONTHS (MEAN 28.6 +/- 24.3) SINCE THE DEVELOPMENT OF BILE DUCT STRICTURE, AND 3 PATIENTS (16.7%) INCLUDING 2 WHO UNDERWENT METALLIC STENT PLACEMENT HAVE NOT SHOWN ANY SYMPTOMS ASSOCIATED WITH BILE DUCT STRICTURE FOR 3 TO 17 MONTHS (MEAN 9.0 +/- 7.2) SINCE THE ADDITIONAL INTERVENTION. EIGHT PATIENTS (44.4%), INCLUDING 3 WHO UNDERWENT STENT PLACEMENT (N = 5), DIED OF HEPATIC FAILURE (N = 2), UNCONTROLLABLE JAUNDICE, CHOLANGITIS, AND/OR TUMOR PROGRESSION (N = 1) AT 11 TO 119 MONTHS (MEAN 37.9 +/- 34.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND AT 11 TO 41 MONTHS (MEAN 21.3 +/- 10.4) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. TEN PATIENTS (55.6%) HAVE SURVIVED 3 TO 129 MONTHS (MEAN 38.4 +/- 37.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND 3 TO 72 MONTHS (MEAN 28.4 +/- 21.9) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. FOUR PATIENTS HAVE NOT SHOWN ANY VIABLE HCCS, BUT 6 PATIENTS HAVE VIABLE HCCS DESPITE REPEATED TACE SESSIONS. DISCUSSION: IN THE PRESENT STUDY, ALL STRICTURES WERE ALSO LOCATED AT THE CHD AND/OR THE RHD OR THE LHD. THIS MAY REFLECT THE VASCULAR SUPPLY OF THE CHD AND BILATERAL HEPATIC DUCTS FROM THE HEPATIC ARTERIAL BRANCHES, INCLUDING A1 AND A4, WHEREAS THE CBD IS MAINLY SUPPLIED BY THE BRANCHES OF THE GASTRODUODENAL ARTERY. THE POOR COLLATERAL SUPPLY TO THE CHD, COMPARED WITH A DENSER ARTERIAL NETWORK AND A RELATIVELY HIGH PROPORTION OF SUPPLY TO THE LOWER CBD, COULD EXPLAIN THE VULNERABILITY OF THE CHD TO ISCHEMIC INJURY. ALL STRICTURES WERE FOCAL AND SMOOTH, AND INTRALUMINAL COAGULA WAS FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAM. WE CONSIDER THAT THESE FINDINGS MAY BE TYPICAL IMAGE FINDINGS OF BILE DUCT INJURY BY TACE. RADIOLOGISTS SHOULD NOT MISDIAGNOSE THIS CONDITION AS BILE DUCT INVASION BY THE TUMOR. IN THE PRESENT STUDY, ALL MAIN BILE DUCT STRICTURES DEVELOPED AFTER TACE OF A1 AND/OR A4. IN ADDITION, 50% OF BILE DUCT STRICTURES DEVELOPED EVEN AFTER A SINGLE TACE SESSION OF A1 AND/OR A4, SUGGESTING THAT SELECTIVE TACE OF A1 AND/OR A4 IS A MAIN CAUSE OF BILE DUCT NECROSIS. HOWEVER, NONSELECTIVE TACE OF THE RIGHT HEPATIC ARTERY OR LEFT HEPATIC ARTERY LEVEL MAY MAINLY DAMAGE "THE PERIPHERAL BRANCHES," WHEREAS "THE CENTRAL BRANCHES," SUCH AS A1 AND A4, MAY BE SLIGHTLY DAMAGED OR OCCASIONALLY PRESERVED. REPEAT TACE SESSIONS MAY FINALLY DAMAGE THESE CENTRAL BRANCHES BECAUSE THE PERIPHERAL BRANCHES ARE SEVERELY ATTENUATED BY PREVIOUS TACE PROCEDURES, AND EMBOLIC MATERIALS FLOWS MAINLY INTO THESE CENTRAL BRANCHES. 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. WE REPORTED THAT ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS TO ACHIEVE NOT ONLY COMPLETE TUMOR NECROSIS BUT ALSO MASSIVE PERITUMORAL NECROSIS BY BLOCKAGE OF BOTH THE HEPATIC ARTERIAL AND PORTAL BLOOD FLOW. 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. IT MAY BE DIFFICULT TO PREDICT MAIN BILE DUCT INJURY BY TACE. IN 3 PATIENTS UNDERGOING SELECTIVE CBCT DURING THE TACE PROCEDURE OF A1 AND/OR A4, BILE DUCT WALL ENHANCEMENT WAS CLEARLY DEMONSTRATED. CBCT MIGHT BE USEFUL FOR PREDICTING BILE DUCT INJURY CAUSED BY TACE. WE SHOULD ALWAYS BEAR IN MIND THAT SELECTIVE TACE OF A1 AND/ OR A4 CARRIES THE RISK OF CAUSING BILE DUCT NECROSIS. THEREFORE, COMPLETE BLOCKAGE OF THESE VESSELS SHOULD BE AVOIDED, ESPECIALLY WHEN BILE DUCT ENHANCEMENT IS SEEN ON CT OR CBCT DURING ARTERIOGRAPHY THROUGH A1 OR A4. IN ADDITION, DISTAL ADVANCEMENT OF A THINNER MICROCATHETER WITH A TIP \2F INTO A1 OR A4 MAY BE USEFUL TO AVOID EMBOLIZATION OF SMALL VESSELS SUPPLYING THE MAIN BILE DUCTS BECAUSE THESE VESSELS MAY BE ESTIMATED TO ARISE FROM THE PROXIMATE PORTION OF A1 AND A4. CT OBTAINED AT 1 WEEK AFTER TACE MAY ALSO BE USEFUL TO SUGGEST MAIN BILE DUCT DAMAGE. CHANGES IN LABORATORY DATA ARE NOT SUFFICIENTLY SENSITIVE, AND ABNORMALITIES MAY BECOME APPARENT LONG AFTER DEMONSTRATION OF BILE DUCT DILATATION ON CT IN MOST PATIENTS, ALTHOUGH MARKED CHANGES SUGGEST SEVERE DAMAGE TO THE MAIN BILE DUCTS. 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. METALLIC STENT PLACEMENT MAY BE USEFUL TO MANAGE MAIN BILE DUCT STRICTURE CAUSED BY TACE BECAUSE PATIENTS WITH INOPERABLE HCC ARE NOT GOOD CANDIDATES FOR SURGICAL BILE DUCT REPAIR. HOWEVER, BILE DUCT COMPLICATIONS MAY OCCUR AT HIGH RATES AFTER ADDITIONAL TACE SESSIONS. IN ADDITION, WE SHOULD BE WELL AWARE THAT INTRAHEPATIC BILE DUCT DILATATION IS A SIGNIFICANT RISK FACTOR IN DEVELOPING BILOMA AFTER TACE. 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 (NO.2) WAS A 76-YEAR-OLD FEMALE WITH ONE TUMOR MEASURING 16 MM IN DIAMETER. SEGMENT WAS S1 AND EMBOLIZED BRANCHES WAS A1. IODIZED OIL-ACCUMULATED PORTION: COMMON HEPATIC DUCT (CHD); SITE OF BILE DUCT DILATATION: BOTH. SHRINKAGE OF GALLBLADDER: + CHANGES IN BILE DUCT DILATATION: PROGRESSED; NO. OF ADDITIONAL TACE: 1. 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 (24JUL2019): FOLLOW-UP ATTEMPTS COMPLETED. NO FURTHER INFORMATION EXPECTED. FOLLOW-UP (10SEP2019): THIS IS A FOLLOW UP REPORT, BASED ON INFORMATION RECEIVED BY PFIZER FROM PRODUCT QUALITY COMPLAINTS (PRODUCT COMPLAINT NUMBER: (B)(4) ), FOR ABSORBABLE GELATIN (GELFOAM). A COMPLAINT HAS BEEN RECEIVED BY PFIZER WITH NO REASONABLE SUSPICION OF A MALFUNCTION; THE ASSOCIATED WORST-CASE SEVERITY IS UNKNOWN. IMPACT TO THE DEVICE: POSSIBLE ADVERSE EVENT. HAZARDOUS SITUATION: UNKNOWN; HAZARD NUMBER (WORST CASE): UNKNOWN; SEVERITY (WORST CASE): UNKNOWN; P2 VALUE: H10-03 (WORST CASE) UNKNOWN. MDR ISSUED FOR THE ASSOCIATED AE CASE: (B)(4). MDR FOR OTHER CASES INVOLVING OFF-LABEL USE WERE ISSUED PREVIOUSLY THAT WERE NOT ASSOCIATED WITH THE CASES LISTED ABOVE. 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 AND SEVERITY OF HARM WAS UNKNOWN. LOT#: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE 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. COMPANY CLINICAL EVALUATION COMMENT: IN THE PRESENT STUDY, GELFOAM PARTICLES WERE CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY AND USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC), WHICH IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). PER THIS STUDY RESULT, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). 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. CONSIDERING TEMPORAL RELATIONSHIP, A POSSIBLE CONTRIBUTION ROLE OF ABSORBABLE GELATIN SPONGE TO THE ONSET OF REPORTED EVENT MAIN BILE DUCT STRICTURE CAN NOT BE COMPLETELY EXCLUDED. THE COMPANY PRODUCT QUALITY CONTROL INVESTIGATION RESULT DOES NOT SUPPORT A DEVICE ISSUE. COMMENT: IN THE PRESENT STUDY, GELFOAM PARTICLES WERE CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY AND USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC), WHICH IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). PER THIS STUDY RESULT, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). 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. CONSIDERING TEMPORAL RELATIONSHIP, A POSSIBLE CONTRIBUTION ROLE OF ABSORBABLE GELATIN SPONGE TO THE ONSET OF REPORTED EVENT MAIN BILE DUCT STRICTURE CAN NOT BE COMPLETELY EXCLUDED. THE COMPANY PRODUCT QUALITY CONTROL INVESTIGATION RESULT DOES NOT SUPPORT A DEVICE ISSUE.
EVENT VERBATIM [PREFERRED TERM] MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS]. 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 SAME DRUG WITH SIMILAR EVENT FOR ELEVEN PATIENTS. THIS IS THE SECOND OF ELEVEN REPORTS AND REFERS TO PATIENT 2 IN TABLE 2, A 76-YEAR-OLD FEMALE WHO EXPERIENCED BILE DUCT STRICTURE. THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE CLINICAL COURSE OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC). AMONG 446 CONSECUTIVE PATIENTS WITH HCC TREATED BY TACE, MAIN BILE DUCT STRICTURE DEVELOPED IN 18 (4.0%). ALL IMAGING AND LABORATORY DATA, TREATMENT COURSE, AND OUTCOMES WERE RETROSPECTIVELY ANALYZED. ALL PATIENTS HAD 1 TO 2 TUMORS MEASURING 10 TO 100 MM IN DIAMETER (MEAN ± SD 24.5 ± 5.4 MM) NEAR THE HEPATIC HILUM FED BY THE CAUDATE ARTERIAL BRANCH (A1) AND/OR MEDIAL SEGMENTAL ARTERY (A4) OF THE LIVER. DURING THE TACE PROCEDURE THAT CAUSED BILE DUCT INJURY, A1 WAS EMBOLIZED IN 8, A4 WAS EMBOLIZED IN 5, AND BOTH WERE EMBOLIZED IN 5 PATIENTS. NINE PATIENTS (50.0%) HAD A HISTORY OF TACE IN EITHER A1 OR A4. IODIZED OIL ACCUMULATION IN THE BILE DUCT WALL WAS SEEN IN ALL PATIENTS ON COMPUTED TOMOGRAPHY OBTAINED 1 WEEK LATER. BILE DUCT DILATATION CAUSED BY MAIN BILE DUCT STRICTURE DEVELOPED IN BOTH LOBES (N = 9), IN THE RIGHT LOBE (N = 3), IN THE LEFT LOBE (N = 4), IN SEGMENT (S) 2 (N = 1), AND IN S3 (N = 1). SERUM LEVELS OF ALKALINE PHOSPHATASE AND C-GLUTAMYLTRANSPEPTIDASE INCREASED IN 13 PATIENTS. BILOMA REQUIRING DRAINAGE DEVELOPED IN 2 PATIENTS; JAUNDICE DEVELOPED IN 4 PATIENTS; AND METALLIC STENTS WERE PLACED IN 3 PATIENTS. COMPLICATIONS AFTER ADDITIONAL TACE SESSIONS, INCLUDING BILOMA (N = 3) AND/OR JAUNDICE (N = 5), OCCURRED IN 7 PATIENTS AND WERE TREATED BY ADDITIONAL INTERVENTION, INCLUDING METALLIC STENT PLACEMENT IN 2 PATIENTS. AFTER INITIAL TACE OF A1 AND/OR A4, 8 PATIENTS (44.4%), INCLUDING 5 WITH UNCONTROLLABLE JAUNDICE OR CHOLANGITIS, DIED AT 37.9 ± 34.9 MONTHS AFTER TACE, AND 10 (55.6%) HAVE SURVIVED FOR 38.4 ± 37.9 MONTHS. SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM. BILOMA AND JAUNDICE ARE SERIOUS COMPLICATIONS ASSOCIATED WITH BILE DUCT STRICTURES. 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 (B)(6) 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. RESULTS: ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. CLINICAL COURSES AND OUTCOMES: ALL PATIENTS WERE FOLLOWED-UP FOR 3 TO 129 MONTHS (MEAN 38.2 +/- 35.4) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND FOR 3 TO 72 MONTHS (MEAN 25.2 +/- 17.6) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. ELEVEN PATIENTS (61.1%) PRESENTED WITH BILE DUCT COMPLICATIONS ASSOCIATED WITH MAIN BILE DUCT STRICTURE. CHOLANGITIS DEVELOPED IN 2 PATIENTS (11.1%) AT 2 MONTHS AFTER TACE AND RESOLVED AFTER ADMINISTRATION OF ANTIBIOTICS (SULPERAZON; PFIZER, TOKYO, JAPAN). BILE DUCT DILATATION WAS IMPROVED DURING FOLLOW-UP IN THESE PATIENTS (FIG. 1). BILOMA DEVELOPED IN 4 PATIENTS (22.2%), AND PERCUTANEOUS DRAINAGE WAS PERFORMED IN 2 OF 4 PATIENTS AT 2 AND 4 MONTHS, RESPECTIVELY, AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. JAUNDICE (SERUM BILIRUBIN LEVEL 9.3 TO 14.0 MG/DL [MEAN 11.7 +/- 2.3]) DEVELOPED IN 4 PATIENTS (22.2%), INCLUDING 2 WITH A HISTORY OF BILOMA DRAINAGE, AT 5 TO 11 MONTHS (MEAN 7.3 +/- 2.9) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. THREE PATIENTS UNDERWENT PTBD. IN THE REMAINING PATIENT, BILE DUCT DRAINAGE WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. IN ANOTHER PATIENT WITHOUT JAUNDICE, PTBD WAS PERFORMED TO RELIEVE BILE DUCT DILATATION BEFORE ADDITIONAL TACE WITH BILE DUCT DILATATION FOR HCC IN THE LEFT LOBE OF THE LIVER. METALLIC STENT PLACEMENT (ZILVER 635; COOK) WAS SUBSEQUENTLY PERFORMED IN 4 PATIENTS. IN 2 PATIENTS, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO THE CBD USING EITHER A BILATERAL OR LEFT APPROACH. IN 2 PATIENTS, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CHD BY WAY OF A LEFT APPROACH. THE PTBD CATHETER WAS REMOVED AFTER STENT PLACEMENT. IN 13 PATIENTS (72.2%), INCLUDING 4 WHO UNDERWENT STENT PLACEMENT, 1 TO 5 ADDITIONAL TACE SESSIONS (MEAN 2.6 +/- 1.5) WERE PERFORMED BECAUSE OF LOCAL RECURRENCE AND/OR NEW LESIONS AT OTHER SITES. IN TOTAL, 24 TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE WERE PERFORMED IN 12 PATIENTS, AND 10 TACE SESSIONS TO THE AREA WITHOUT BILE DUCT DILATATION WERE PERFORMED IN 5 PATIENTS. COMPLICATIONS ASSOCIATED WITH ADDITIONAL TACE SESSIONS OCCURRED IN 7 OF 13 PATIENTS (53.8%). BILOMA DEVELOPED IN 3 PATIENTS. IT DEVELOPED IN 2 PATIENTS AT 2 MONTHS AFTER THE ADDITIONAL FIRST TACE SESSION TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE AND IN 1 PATIENT AT 1 MONTH AFTER 4 ADDITIONAL TACE SESSIONS TO THE STENTED LOBE. PERCUTANEOUS DRAINAGE WAS REQUIRED IN 1 PATIENT WITH PREVIOUS STENT PLACEMENT. JAUNDICE (6.5 TO 22.6 MG/DL [MEAN 12.6 +/- 6.7]) DEVELOPED IN 5 PATIENTS AT 3 TO 26 MONTHS (MEAN 15.4 +/- 19.7) AFTER THE FIRST ADDITIONAL TACE SESSION AND AT 2 WEEKS TO 5 MONTHS (MEAN 2.8 +/- 1.8) AFTER THE LAST ADDITIONAL TACE SESSION, INCLUDING 2 PATIENTS WHO HAD UNDERGONE STENT PLACEMENT. IT DEVELOPED AFTER 1 (N = 2), 3 (N = 1), AND 4 (N = 2) ADDITIONAL TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION (N = 3) OR TO THE STENTED LOBE (N = 2). ONE OF THESE PATIENTS ALSO HAD A SMALL BILOMA. ALL PATIENTS BUT 1 UNDERWENT PTBD. IN 1 PATIENT, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CBD USING A LEFT APPROACH. IN ANOTHER PATIENT, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO CBD USING A BILATERAL APPROACH (FIG. 5). THE BILE DUCT WAS OCCLUDED IN THE STENTED SEGMENT IN 2 PATIENTS WHO HAD PREVIOUSLY UNDERGONE STENT PLACEMENT. JAUNDICE DID NOT IMPROVE BECAUSE OF HEPATIC FAILURE, AND EXTERNAL DRAINAGE WAS CONTINUED UNTIL THE PATIENTS DEATH. IN THE REMAINING PATIENT, PTBD WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. CHOLANGITIS RECURRED IN 1 PATIENT AT 1 MONTH AFTER STENT PLACEMENT WITHOUT AN ADDITIONAL TACE SESSION, AND IT DID NOT IMPROVE DESPITE ADMINISTRATION OF ANTIBIOTICS. ONE PATIENT WHO HAD UNDERGONE STENT PLACEMENT TO RELIEVE BILE DUCT STRICTURE BEFORE ADDITIONAL TACE SESSIONS DID NOT DEVELOP ANY COMPLICATIONS DESPITE 4 ADDITIONAL TACE SESSIONS, INCLUDING 2 TO THE STENTED LOBE. SEVEN PATIENTS (38.9%) HAVE NOT PRESENTED ANY SYMPTOMS FOR 3 TO 68 MONTHS (MEAN 28.6 +/- 24.3) SINCE THE DEVELOPMENT OF BILE DUCT STRICTURE, AND 3 PATIENTS (16.7%) INCLUDING 2 WHO UNDERWENT METALLIC STENT PLACEMENT HAVE NOT SHOWN ANY SYMPTOMS ASSOCIATED WITH BILE DUCT STRICTURE FOR 3 TO 17 MONTHS (MEAN 9.0 +/- 7.2) SINCE THE ADDITIONAL INTERVENTION. EIGHT PATIENTS (44.4%), INCLUDING 3 WHO UNDERWENT STENT PLACEMENT (N = 5), DIED OF HEPATIC FAILURE (N = 2), UNCONTROLLABLE JAUNDICE, CHOLANGITIS, AND/OR TUMOR PROGRESSION (N = 1) AT 11 TO 119 MONTHS (MEAN 37.9 +/- 34.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND AT 11 TO 41 MONTHS (MEAN 21.3 +/- 10.4) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. TEN PATIENTS (55.6%) HAVE SURVIVED 3 TO 129 MONTHS (MEAN 38.4 +/- 37.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND 3 TO 72 MONTHS (MEAN 28.4 +/- 21.9) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. FOUR PATIENTS HAVE NOT SHOWN ANY VIABLE HCCS, BUT 6 PATIENTS HAVE VIABLE HCCS DESPITE REPEATED TACE SESSIONS. DISCUSSION: IN THE PRESENT STUDY, ALL STRICTURES WERE ALSO LOCATED AT THE CHD AND/OR THE RHD OR THE LHD. THIS MAY REFLECT THE VASCULAR SUPPLY OF THE CHD AND BILATERAL HEPATIC DUCTS FROM THE HEPATIC ARTERIAL BRANCHES, INCLUDING A1 AND A4, WHEREAS THE CBD IS MAINLY SUPPLIED BY THE BRANCHES OF THE GASTRODUODENAL ARTERY. THE POOR COLLATERAL SUPPLY TO THE CHD, COMPARED WITH A DENSER ARTERIAL NETWORK AND A RELATIVELY HIGH PROPORTION OF SUPPLY TO THE LOWER CBD, COULD EXPLAIN THE VULNERABILITY OF THE CHD TO ISCHEMIC INJURY. ALL STRICTURES WERE FOCAL AND SMOOTH, AND INTRALUMINAL COAGULA WAS FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAM. WE CONSIDER THAT THESE FINDINGS MAY BE TYPICAL IMAGE FINDINGS OF BILE DUCT INJURY BY TACE. RADIOLOGISTS SHOULD NOT MISDIAGNOSE THIS CONDITION AS BILE DUCT INVASION BY THE TUMOR. IN THE PRESENT STUDY, ALL MAIN BILE DUCT STRICTURES DEVELOPED AFTER TACE OF A1 AND/OR A4. IN ADDITION, 50% OF BILE DUCT STRICTURES DEVELOPED EVEN AFTER A SINGLE TACE SESSION OF A1 AND/OR A4, SUGGESTING THAT SELECTIVE TACE OF A1 AND/OR A4 IS A MAIN CAUSE OF BILE DUCT NECROSIS. HOWEVER, NONSELECTIVE TACE OF THE RIGHT HEPATIC ARTERY OR LEFT HEPATIC ARTERY LEVEL MAY MAINLY DAMAGE "THE PERIPHERAL BRANCHES," WHEREAS "THE CENTRAL BRANCHES," SUCH AS A1 AND A4, MAY BE SLIGHTLY DAMAGED OR OCCASIONALLY PRESERVED. REPEAT TACE SESSIONS MAY FINALLY DAMAGE THESE CENTRAL BRANCHES BECAUSE THE PERIPHERAL BRANCHES ARE SEVERELY ATTENUATED BY PREVIOUS TACE PROCEDURES, AND EMBOLIC MATERIALS FLOWS MAINLY INTO THESE CENTRAL BRANCHES. 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. WE REPORTED THAT ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS TO ACHIEVE NOT ONLY COMPLETE TUMOR NECROSIS BUT ALSO MASSIVE PERITUMORAL NECROSIS BY BLOCKAGE OF BOTH THE HEPATIC ARTERIAL AND PORTAL BLOOD FLOW. 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. IT MAY BE DIFFICULT TO PREDICT MAIN BILE DUCT INJURY BY TACE. IN 3 PATIENTS UNDERGOING SELECTIVE CBCT DURING THE TACE PROCEDURE OF A1 AND/OR A4, BILE DUCT WALL ENHANCEMENT WAS CLEARLY DEMONSTRATED. CBCT MIGHT BE USEFUL FOR PREDICTING BILE DUCT INJURY CAUSED BY TACE. WE SHOULD ALWAYS BEAR IN MIND THAT SELECTIVE TACE OF A1 AND/ OR A4 CARRIES THE RISK OF CAUSING BILE DUCT NECROSIS. THEREFORE, COMPLETE BLOCKAGE OF THESE VESSELS SHOULD BE AVOIDED, ESPECIALLY WHEN BILE DUCT ENHANCEMENT IS SEEN ON CT OR CBCT DURING ARTERIOGRAPHY THROUGH A1 OR A4. IN ADDITION, DISTAL ADVANCEMENT OF A THINNER MICROCATHETER WITH A TIP \2F INTO A1 OR A4 MAY BE USEFUL TO AVOID EMBOLIZATION OF SMALL VESSELS SUPPLYING THE MAIN BILE DUCTS BECAUSE THESE VESSELS MAY BE ESTIMATED TO ARISE FROM THE PROXIMATE PORTION OF A1 AND A4. CT OBTAINED AT 1 WEEK AFTER TACE MAY ALSO BE USEFUL TO SUGGEST MAIN BILE DUCT DAMAGE. CHANGES IN LABORATORY DATA ARE NOT SUFFICIENTLY SENSITIVE, AND ABNORMALITIES MAY BECOME APPARENT LONG AFTER DEMONSTRATION OF BILE DUCT DILATATION ON CT IN MOST PATIENTS, ALTHOUGH MARKED CHANGES SUGGEST SEVERE DAMAGE TO THE MAIN BILE DUCTS. 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. METALLIC STENT PLACEMENT MAY BE USEFUL TO MANAGE MAIN BILE DUCT STRICTURE CAUSED BY TACE BECAUSE PATIENTS WITH INOPERABLE HCC ARE NOT GOOD CANDIDATES FOR SURGICAL BILE DUCT REPAIR. HOWEVER, BILE DUCT COMPLICATIONS MAY OCCUR AT HIGH RATES AFTER ADDITIONAL TACE SESSIONS. IN ADDITION, WE SHOULD BE WELL AWARE THAT INTRAHEPATIC BILE DUCT DILATATION IS A SIGNIFICANT RISK FACTOR IN DEVELOPING BILOMA AFTER TACE. 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 (NO.2) WAS A 76-YEAR-OLD FEMALE WITH ONE TUMOR MEASURING 16 MM IN DIAMETER. SEGMENT WAS S1 AND EMBOLIZED BRANCHES WAS A1. IODIZED OIL-ACCUMULATED PORTION: COMMON HEPATIC DUCT (CHD); SITE OF BILE DUCT DILATATION: BOTH. SHRINKAGE OF GALLBLADDER: + CHANGES IN BILE DUCT DILATATION: PROGRESSED; NO. OF ADDITIONAL TACE: 1. 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 (24JUL2019): FOLLOW-UP ATTEMPTS COMPLETED. NO FURTHER INFORMATION EXPECTED. FOLLOW-UP (10SEP2019): THIS IS A FOLLOW UP REPORT, BASED ON INFORMATION RECEIVED BY PFIZER FROM PRODUCT QUALITY COMPLAINTS (PRODUCT COMPLAINT NUMBER: 4189498), FOR ABSORBABLE GELATIN (GELFOAM). A COMPLAINT HAS BEEN RECEIVED BY PFIZER WITH NO REASONABLE SUSPICION OF A MALFUNCTION; THE ASSOCIATED WORST-CASE SEVERITY IS UNKNOWN. IMPACT TO THE DEVICE: POSSIBLE ADVERSE EVENT. HAZARDOUS SITUATION: UNKNOWN; HAZARD NUMBER (WORST CASE): UNKNOWN; SEVERITY (WORST CASE): UNKNOWN; P2 VALUE: H10-03 (WORST CASE) UNKNOWN. MDR ISSUED FOR THE ASSOCIATED AE CASE: (B)(4). MDR FOR OTHER CASES INVOLVING OFF-LABEL USE WERE ISSUED PREVIOUSLY THAT WERE NOT ASSOCIATED WITH THE CASES LISTED ABOVE. 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 AND SEVERITY OF HARM WAS UNKNOWN. LOT#: UNKNOWN. ROOT CAUSE: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE 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. NO FOLLOW-UP ATTEMPTS ARE NEEDED. NO FURTHER INFORMATION IS EXPECTED. COMPANY CLINICAL EVALUATION COMMENT: IN THE PRESENT STUDY, GELFOAM PARTICLES WERE CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY AND USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC), WHICH IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). PER THIS STUDY RESULT, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). 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. CONSIDERING TEMPORAL RELATIONSHIP, A POSSIBLE CONTRIBUTION ROLE OF ABSORBABLE GELATIN SPONGE TO THE ONSET OF REPORTED EVENT MAIN BILE DUCT STRICTURE CAN NOT BE COMPLETELY EXCLUDED., COMMENT: IN THE PRESENT STUDY, GELFOAM PARTICLES WERE CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY AND USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC), WHICH IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). PER THIS STUDY RESULT, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). 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. CONSIDERING TEMPORAL RELATIONSHIP, A POSSIBLE CONTRIBUTION ROLE OF ABSORBABLE GELATIN SPONGE TO THE ONSET OF REPORTED EVENT MAIN BILE DUCT STRICTURE CAN NOT BE COMPLETELY EXCLUDED.
EVENT VERBATIM [PREFERRED TERM] MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS] , . 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. THIS IS THE SECOND OF ELEVEN REPORTS. ABSTRACT THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE CLINICAL COURSE OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC). AMONG 446 CONSECUTIVE PATIENTS WITH HCC TREATED BY TACE, MAIN BILE DUCT STRICTURE DEVELOPED IN 18 (4.0%). ALL IMAGING AND LABORATORY DATA, TREATMENT COURSE, AND OUTCOMES WERE RETROSPECTIVELY ANALYZED. ALL PATIENTS HAD 1 TO 2 TUMORS MEASURING 10 TO 100 MM IN DIAMETER (MEAN ± SD 24.5 ± 5.4 MM) NEAR THE HEPATIC HILUM FED BY THE CAUDATE ARTERIAL BRANCH (A1) AND/OR MEDIAL SEGMENTAL ARTERY (A4) OF THE LIVER. DURING THE TACE PROCEDURE THAT CAUSED BILE DUCT INJURY, A1 WAS EMBOLIZED IN 8, A4 WAS EMBOLIZED IN 5, AND BOTH WERE EMBOLIZED IN 5 PATIENTS. NINE PATIENTS (50.0%) HAD A HISTORY OF TACE IN EITHER A1 OR A4. IODIZED OIL ACCUMULATION IN THE BILE DUCT WALL WAS SEEN IN ALL PATIENTS ON COMPUTED TOMOGRAPHY OBTAINED 1 WEEK LATER. BILE DUCT DILATATION CAUSED BY MAIN BILE DUCT STRICTURE DEVELOPED IN BOTH LOBES (N = 9), IN THE RIGHT LOBE (N = 3), IN THE LEFT LOBE (N = 4), IN SEGMENT (S) 2 (N = 1), AND IN S3 (N = 1). SERUM LEVELS OF ALKALINE PHOSPHATASE AND C-GLUTAMYLTRANSPEPTIDASE INCREASED IN 13 PATIENTS. BILOMA REQUIRING DRAINAGE DEVELOPED IN 2 PATIENTS; JAUNDICE DEVELOPED IN 4 PATIENTS; AND METALLIC STENTS WERE PLACED IN 3 PATIENTS. COMPLICATIONS AFTER ADDITIONAL TACE SESSIONS, INCLUDING BILOMA (N = 3) AND/OR JAUNDICE (N = 5), OCCURRED IN 7 PATIENTS AND WERE TREATED BY ADDITIONAL INTERVENTION, INCLUDING METALLIC STENT PLACEMENT IN 2 PATIENTS. AFTER INITIAL TACE OF A1 AND/OR A4, 8 PATIENTS (44.4%), INCLUDING 5 WITH UNCONTROLLABLE JAUNDICE OR CHOLANGITIS, DIED AT 37.9 ± 34.9 MONTHS AFTER TACE, AND 10 (55.6%) HAVE SURVIVED FOR 38.4 ± 37.9 MONTHS. SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM. BILOMA AND JAUNDICE ARE SERIOUS COMPLICATIONS ASSOCIATED WITH BILE DUCT STRICTURES. 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 (B)(6) 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. RESULTS: THE RESULTS ARE SUMMARIZED IN TABLE 2. ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. CLINICAL COURSES AND OUTCOMES: ALL PATIENTS WERE FOLLOWED-UP FOR 3 TO 129 MONTHS (MEAN 38.2 +/- 35.4) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND FOR 3 TO 72 MONTHS (MEAN 25.2 +/- 17.6) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. ELEVEN PATIENTS (61.1%) PRESENTED WITH BILE DUCT COMPLICATIONS ASSOCIATED WITH MAIN BILE DUCT STRICTURE. CHOLANGITIS DEVELOPED IN 2 PATIENTS (11.1%) AT 2 MONTHS AFTER TACE AND RESOLVED AFTER ADMINISTRATION OF ANTIBIOTICS (SULPERAZON; PFIZER, TOKYO, JAPAN). BILE DUCT DILATATION WAS IMPROVED DURING FOLLOW-UP IN THESE PATIENTS (FIG. 1). BILOMA DEVELOPED IN 4 PATIENTS (22.2%), AND PERCUTANEOUS DRAINAGE WAS PERFORMED IN 2 OF 4 PATIENTS AT 2 AND 4 MONTHS, RESPECTIVELY, AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. JAUNDICE (SERUM BILIRUBIN LEVEL 9.3 TO 14.0 MG/DL [MEAN 11.7 +/- 2.3]) DEVELOPED IN 4 PATIENTS (22.2%), INCLUDING 2 WITH A HISTORY OF BILOMA DRAINAGE, AT 5 TO 11 MONTHS (MEAN 7.3 +/- 2.9) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. THREE PATIENTS UNDERWENT PTBD. IN THE REMAINING PATIENT, BILE DUCT DRAINAGE WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. IN ANOTHER PATIENT WITHOUT JAUNDICE, PTBD WAS PERFORMED TO RELIEVE BILE DUCT DILATATION BEFORE ADDITIONAL TACE WITH BILE DUCT DILATATION FOR HCC IN THE LEFT LOBE OF THE LIVER. METALLIC STENT PLACEMENT (ZILVER 635; COOK) WAS SUBSEQUENTLY PERFORMED IN 4 PATIENTS. IN 2 PATIENTS, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO THE CBD USING EITHER A BILATERAL OR LEFT APPROACH. IN 2 PATIENTS, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CHD BY WAY OF A LEFT APPROACH. THE PTBD CATHETER WAS REMOVED AFTER STENT PLACEMENT. IN 13 PATIENTS (72.2%), INCLUDING 4 WHO UNDERWENT STENT PLACEMENT, 1 TO 5 ADDITIONAL TACE SESSIONS (MEAN 2.6 +/- 1.5) WERE PERFORMED BECAUSE OF LOCAL RECURRENCE AND/OR NEW LESIONS AT OTHER SITES. IN TOTAL, 24 TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE WERE PERFORMED IN 12 PATIENTS, AND 10 TACE SESSIONS TO THE AREA WITHOUT BILE DUCT DILATATION WERE PERFORMED IN 5 PATIENTS. COMPLICATIONS ASSOCIATED WITH ADDITIONAL TACE SESSIONS OCCURRED IN 7 OF 13 PATIENTS (53.8%). BILOMA DEVELOPED IN 3 PATIENTS. IT DEVELOPED IN 2 PATIENTS AT 2 MONTHS AFTER THE ADDITIONAL FIRST TACE SESSION TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE AND IN 1 PATIENT AT 1 MONTH AFTER 4 ADDITIONAL TACE SESSIONS TO THE STENTED LOBE. PERCUTANEOUS DRAINAGE WAS REQUIRED IN 1 PATIENT WITH PREVIOUS STENT PLACEMENT. JAUNDICE (6.5 TO 22.6 MG/DL [MEAN 12.6 +/- 6.7]) DEVELOPED IN 5 PATIENTS AT 3 TO 26 MONTHS (MEAN 15.4 +/- 19.7) AFTER THE FIRST ADDITIONAL TACE SESSION AND AT 2 WEEKS TO 5 MONTHS (MEAN 2.8 +/- 1.8) AFTER THE LAST ADDITIONAL TACE SESSION, INCLUDING 2 PATIENTS WHO HAD UNDERGONE STENT PLACEMENT. IT DEVELOPED AFTER 1 (N = 2), 3 (N = 1), AND 4 (N = 2) ADDITIONAL TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION (N = 3) OR TO THE STENTED LOBE (N = 2). ONE OF THESE PATIENTS ALSO HAD A SMALL BILOMA. ALL PATIENTS BUT 1 UNDERWENT PTBD. IN 1 PATIENT, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CBD USING A LEFT APPROACH. IN ANOTHER PATIENT, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO CBD USING A BILATERAL APPROACH (FIG. 5). THE BILE DUCT WAS OCCLUDED IN THE STENTED SEGMENT IN 2 PATIENTS WHO HAD PREVIOUSLY UNDERGONE STENT PLACEMENT. JAUNDICE DID NOT IMPROVE BECAUSE OF HEPATIC FAILURE, AND EXTERNAL DRAINAGE WAS CONTINUED UNTIL THE PATIENTS DEATH. IN THE REMAINING PATIENT, PTBD WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. CHOLANGITIS RECURRED IN 1 PATIENT AT 1 MONTH AFTER STENT PLACEMENT WITHOUT AN ADDITIONAL TACE SESSION, AND IT DID NOT IMPROVE DESPITE ADMINISTRATION OF ANTIBIOTICS. ONE PATIENT WHO HAD UNDERGONE STENT PLACEMENT TO RELIEVE BILE DUCT STRICTURE BEFORE ADDITIONAL TACE SESSIONS DID NOT DEVELOP ANY COMPLICATIONS DESPITE 4 ADDITIONAL TACE SESSIONS, INCLUDING 2 TO THE STENTED LOBE. SEVEN PATIENTS (38.9%) HAVE NOT PRESENTED ANY SYMPTOMS FOR 3 TO 68 MONTHS (MEAN 28.6 +/- 24.3) SINCE THE DEVELOPMENT OF BILE DUCT STRICTURE, AND 3 PATIENTS (16.7%) INCLUDING 2 WHO UNDERWENT METALLIC STENT PLACEMENT HAVE NOT SHOWN ANY SYMPTOMS ASSOCIATED WITH BILE DUCT STRICTURE FOR 3 TO 17 MONTHS (MEAN 9.0 +/- 7.2) SINCE THE ADDITIONAL INTERVENTION. EIGHT PATIENTS (44.4%), INCLUDING 3 WHO UNDERWENT STENT PLACEMENT (N = 5), DIED OF HEPATIC FAILURE (N = 2), UNCONTROLLABLE JAUNDICE, CHOLANGITIS, AND/OR TUMOR PROGRESSION (N = 1) AT 11 TO 119 MONTHS (MEAN 37.9 +/- 34.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND AT 11 TO 41 MONTHS (MEAN 21.3 +/- 10.4) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. TEN PATIENTS (55.6%) HAVE SURVIVED 3 TO 129 MONTHS (MEAN 38.4 +/- 37.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND 3 TO 72 MONTHS (MEAN 28.4 +/- 21.9) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. FOUR PATIENTS HAVE NOT SHOWN ANY VIABLE HCCS, BUT 6 PATIENTS HAVE VIABLE HCCS DESPITE REPEATED TACE SESSIONS. DISCUSSION: IN THE PRESENT STUDY, ALL STRICTURES WERE ALSO LOCATED AT THE CHD AND/OR THE RHD OR THE LHD. THIS MAY REFLECT THE VASCULAR SUPPLY OF THE CHD AND BILATERAL HEPATIC DUCTS FROM THE HEPATIC ARTERIAL BRANCHES, INCLUDING A1 AND A4, WHEREAS THE CBD IS MAINLY SUPPLIED BY THE BRANCHES OF THE GASTRODUODENAL ARTERY. THE POOR COLLATERAL SUPPLY TO THE CHD, COMPARED WITH A DENSER ARTERIAL NETWORK AND A RELATIVELY HIGH PROPORTION OF SUPPLY TO THE LOWER CBD, COULD EXPLAIN THE VULNERABILITY OF THE CHD TO ISCHEMIC INJURY. ALL STRICTURES WERE FOCAL AND SMOOTH, AND INTRALUMINAL COAGULA WAS FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAM. WE CONSIDER THAT THESE FINDINGS MAY BE TYPICAL IMAGE FINDINGS OF BILE DUCT INJURY BY TACE. RADIOLOGISTS SHOULD NOT MISDIAGNOSE THIS CONDITION AS BILE DUCT INVASION BY THE TUMOR. IN THE PRESENT STUDY, ALL MAIN BILE DUCT STRICTURES DEVELOPED AFTER TACE OF A1 AND/OR A4. IN ADDITION, 50% OF BILE DUCT STRICTURES DEVELOPED EVEN AFTER A SINGLE TACE SESSION OF A1 AND/OR A4, SUGGESTING THAT SELECTIVE TACE OF A1 AND/OR A4 IS A MAIN CAUSE OF BILE DUCT NECROSIS. HOWEVER, NONSELECTIVE TACE OF THE RIGHT HEPATIC ARTERY OR LEFT HEPATIC ARTERY LEVEL MAY MAINLY DAMAGE "THE PERIPHERAL BRANCHES," WHEREAS "THE CENTRAL BRANCHES," SUCH AS A1 AND A4, MAY BE SLIGHTLY DAMAGED OR OCCASIONALLY PRESERVED. REPEAT TACE SESSIONS MAY FINALLY DAMAGE THESE CENTRAL BRANCHES BECAUSE THE PERIPHERAL BRANCHES ARE SEVERELY ATTENUATED BY PREVIOUS TACE PROCEDURES, AND EMBOLIC MATERIALS FLOWS MAINLY INTO THESE CENTRAL BRANCHES. 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. WE REPORTED THAT ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS TO ACHIEVE NOT ONLY COMPLETE TUMOR NECROSIS BUT ALSO MASSIVE PERITUMORAL NECROSIS BY BLOCKAGE OF BOTH THE HEPATIC ARTERIAL AND PORTAL BLOOD FLOW. 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. IT MAY BE DIFFICULT TO PREDICT MAIN BILE DUCT INJURY BY TACE. IN 3 PATIENTS UNDERGOING SELECTIVE CBCT DURING THE TACE PROCEDURE OF A1 AND/OR A4, BILE DUCT WALL ENHANCEMENT WAS CLEARLY DEMONSTRATED. CBCT MIGHT BE USEFUL FOR PREDICTING BILE DUCT INJURY CAUSED BY TACE. WE SHOULD ALWAYS BEAR IN MIND THAT SELECTIVE TACE OF A1 AND/ OR A4 CARRIES THE RISK OF CAUSING BILE DUCT NECROSIS. THEREFORE, COMPLETE BLOCKAGE OF THESE VESSELS SHOULD BE AVOIDED, ESPECIALLY WHEN BILE DUCT ENHANCEMENT IS SEEN ON CT OR CBCT DURING ARTERIOGRAPHY THROUGH A1 OR A4. IN ADDITION, DISTAL ADVANCEMENT OF A THINNER MICROCATHETER WITH A TIP \2F INTO A1 OR A4 MAY BE USEFUL TO AVOID EMBOLIZATION OF SMALL VESSELS SUPPLYING THE MAIN BILE DUCTS BECAUSE THESE VESSELS MAY BE ESTIMATED TO ARISE FROM THE PROXIMATE PORTION OF A1 AND A4. CT OBTAINED AT 1 WEEK AFTER TACE MAY ALSO BE USEFUL TO SUGGEST MAIN BILE DUCT DAMAGE. CHANGES IN LABORATORY DATA ARE NOT SUFFICIENTLY SENSITIVE, AND ABNORMALITIES MAY BECOME APPARENT LONG AFTER DEMONSTRATION OF BILE DUCT DILATATION ON CT IN MOST PATIENTS, ALTHOUGH MARKED CHANGES SUGGEST SEVERE DAMAGE TO THE MAIN BILE DUCTS. 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. METALLIC STENT PLACEMENT MAY BE USEFUL TO MANAGE MAIN BILE DUCT STRICTURE CAUSED BY TACE BECAUSE PATIENTS WITH INOPERABLE HCC ARE NOT GOOD CANDIDATES FOR SURGICAL BILE DUCT REPAIR. HOWEVER, BILE DUCT COMPLICATIONS MAY OCCUR AT HIGH RATES AFTER ADDITIONAL TACE SESSIONS. IN ADDITION, WE SHOULD BE WELL AWARE THAT INTRAHEPATIC BILE DUCT DILATATION IS A SIGNIFICANT RISK FACTOR IN DEVELOPING BILOMA AFTER TACE. 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. FOCAL AND SMOOTH BILE DUCT STRICTURES MAINLY AT THE CHD ARE CHARACTERISTIC FINDINGS, AND INTRALUMINAL COAGULA ARE FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAPHY. RADIOLOGISTS SHOULD WELL AWARE THIS UNCOMMON BUT SEVERE COMPLICATION OF TACE. TABLE 2: SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE PATIENT NO.2 A 76-YEAR-OLD FEMALE PATIENT HAD ONE TUMOR MEASURING 16 MM IN DIAMETER. SEGMENT WAS S1 AND EMBOLIZED BRANCHES WAS A1. IODIZED OIL-ACCUMULATED PORTION: COMMON HEPATIC DUCT (CHD); SITE OF BILE DUCT DILATATION: BOTH. SHRINKAGE OF GALLBLADDER: + CHANGES IN BILE DUCT DILATATION: PROGRESSED; NO. OF ADDITIONAL TACE: 1; 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%). 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%). 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]. 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 SECOND OF EIGHTEEN REPORTS. ABSTRACT THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE CLINICAL COURSE OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC). AMONG 446 CONSECUTIVE PATIENTS WITH HCC TREATED BY TACE, MAIN BILE DUCT STRICTURE DEVELOPED IN 18 (4.0%). ALL IMAGING AND LABORATORY DATA, TREATMENT COURSE, AND OUTCOMES WERE RETROSPECTIVELY ANALYZED. ALL PATIENTS HAD 1 TO 2 TUMORS MEASURING 10 TO 100 MM IN DIAMETER (MEAN ± SD 24.5 ± 5.4 MM) NEAR THE HEPATIC HILUM FED BY THE CAUDATE ARTERIAL BRANCH (A1) AND/OR MEDIAL SEGMENTAL ARTERY (A4) OF THE LIVER. DURING THE TACE PROCEDURE THAT CAUSED BILE DUCT INJURY, A1 WAS EMBOLIZED IN 8, A4 WAS EMBOLIZED IN 5, AND BOTH WERE EMBOLIZED IN 5 PATIENTS. NINE PATIENTS (50.0%) HAD A HISTORY OF TACE IN EITHER A1 OR A4. IODIZED OIL ACCUMULATION IN THE BILE DUCT WALL WAS SEEN IN ALL PATIENTS ON COMPUTED TOMOGRAPHY OBTAINED 1 WEEK LATER. BILE DUCT DILATATION CAUSED BY MAIN BILE DUCT STRICTURE DEVELOPED IN BOTH LOBES (N = 9), IN THE RIGHT LOBE (N = 3), IN THE LEFT LOBE (N = 4), IN SEGMENT (S) 2 (N = 1), AND IN S3 (N = 1). SERUM LEVELS OF ALKALINE PHOSPHATASE AND C-GLUTAMYLTRANSPEPTIDASE INCREASED IN 13 PATIENTS. BILOMA REQUIRING DRAINAGE DEVELOPED IN 2 PATIENTS; JAUNDICE DEVELOPED IN 4 PATIENTS; AND METALLIC STENTS WERE PLACED IN 3 PATIENTS. COMPLICATIONS AFTER ADDITIONAL TACE SESSIONS, INCLUDING BILOMA (N = 3) AND/OR JAUNDICE (N = 5), OCCURRED IN 7 PATIENTS AND WERE TREATED BY ADDITIONAL INTERVENTION, INCLUDING METALLIC STENT PLACEMENT IN 2 PATIENTS. AFTER INITIAL TACE OF A1 AND/OR A4, 8 PATIENTS (44.4%), INCLUDING 5 WITH UNCONTROLLABLE JAUNDICE OR CHOLANGITIS, DIED AT 37.9 ± 34.9 MONTHS AFTER TACE, AND 10 (55.6%) HAVE SURVIVED FOR 38.4 ± 37.9 MONTHS. SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM. BILOMA AND JAUNDICE ARE SERIOUS COMPLICATIONS ASSOCIATED WITH BILE DUCT STRICTURES. 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. RESULTS: THE RESULTS ARE SUMMARIZED IN TABLE 2. ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. CLINICAL COURSES AND OUTCOMES: ALL PATIENTS WERE FOLLOWED-UP FOR 3 TO 129 MONTHS (MEAN 38.2 +/- 35.4) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND FOR 3 TO 72 MONTHS (MEAN 25.2 +/- 17.6) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. ELEVEN PATIENTS (61.1%) PRESENTED WITH BILE DUCT COMPLICATIONS ASSOCIATED WITH MAIN BILE DUCT STRICTURE. CHOLANGITIS DEVELOPED IN 2 PATIENTS (11.1%) AT 2 MONTHS AFTER TACE AND RESOLVED AFTER ADMINISTRATION OF ANTIBIOTICS (SULPERAZON; PFIZER, TOKYO, JAPAN). BILE DUCT DILATATION WAS IMPROVED DURING FOLLOW-UP IN THESE PATIENTS (FIG. 1). BILOMA DEVELOPED IN 4 PATIENTS (22.2%), AND PERCUTANEOUS DRAINAGE WAS PERFORMED IN 2 OF 4 PATIENTS AT 2 AND 4 MONTHS, RESPECTIVELY, AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. JAUNDICE (SERUM BILIRUBIN LEVEL 9.3 TO 14.0 MG/DL [MEAN 11.7 +/- 2.3]) DEVELOPED IN 4 PATIENTS (22.2%), INCLUDING 2 WITH A HISTORY OF BILOMA DRAINAGE, AT 5 TO 11 MONTHS (MEAN 7.3 +/- 2.9) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. THREE PATIENTS UNDERWENT PTBD. IN THE REMAINING PATIENT, BILE DUCT DRAINAGE WAS NOT PERFORMED\ BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. IN ANOTHER PATIENT WITHOUT JAUNDICE, PTBD WAS PERFORMED TO RELIEVE BILE DUCT DILATATION BEFORE ADDITIONAL TACE WITH BILE DUCT DILATATION FOR HCC IN THE LEFT LOBE OF THE LIVER. METALLIC STENT PLACEMENT (ZILVER 635; COOK) WAS SUBSEQUENTLY PERFORMED IN 4 PATIENTS. IN 2 PATIENTS, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO THE CBD USING EITHER A BILATERAL OR LEFT APPROACH. IN 2 PATIENTS, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CHD BY WAY OF A LEFT APPROACH. THE PTBD CATHETER WAS REMOVED AFTER STENT PLACEMENT. IN 13 PATIENTS (72.2%), INCLUDING 4 WHO UNDERWENT STENT PLACEMENT, 1 TO 5 ADDITIONAL TACE SESSIONS (MEAN 2.6 +/- 1.5) WERE PERFORMED BECAUSE OF LOCAL RECURRENCE AND/OR NEW LESIONS AT OTHER SITES. IN TOTAL, 24 TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE WERE PERFORMED IN 12 PATIENTS, AND 10 TACE SESSIONS TO THE AREA WITHOUT BILE DUCT DILATATION WERE PERFORMED IN 5 PATIENTS. COMPLICATIONS ASSOCIATED WITH ADDITIONAL TACE SESSIONS OCCURRED IN 7 OF 13 PATIENTS (53.8%). BILOMA DEVELOPED IN 3 PATIENTS. IT DEVELOPED IN 2 PATIENTS AT 2 MONTHS AFTER THE ADDITIONAL FIRST TACE SESSION TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE AND IN 1 PATIENT AT 1 MONTH AFTER 4 ADDITIONAL TACE SESSIONS TO THE STENTED LOBE. PERCUTANEOUS DRAINAGE WAS REQUIRED IN 1 PATIENT WITH PREVIOUS STENT PLACEMENT. JAUNDICE (6.5 TO 22.6 MG/DL [MEAN 12.6 +/- 6.7]) DEVELOPED IN 5 PATIENTS AT 3 TO 26 MONTHS (MEAN 15.4 +/- 19.7) AFTER THE FIRST ADDITIONAL TACE SESSION AND AT 2 WEEKS TO 5 MONTHS (MEAN 2.8 +/- 1.8) AFTER THE LAST ADDITIONAL TACE SESSION, INCLUDING 2 PATIENTS WHO HAD UNDERGONE STENT PLACEMENT. IT DEVELOPED AFTER 1 (N = 2), 3 (N = 1), AND 4 (N = 2) ADDITIONAL TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION (N = 3) OR TO THE STENTED LOBE (N = 2). ONE OF THESE PATIENTS ALSO HAD A SMALL BILOMA. ALL PATIENTS BUT 1 UNDERWENT PTBD. IN 1 PATIENT, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CBD USING A LEFT APPROACH. IN ANOTHER PATIENT, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO CBD USING A BILATERAL APPROACH (FIG. 5). THE BILE DUCT WAS OCCLUDED IN THE STENTED SEGMENT IN 2 PATIENTS WHO HAD PREVIOUSLY UNDERGONE STENT PLACEMENT. JAUNDICE DID NOT IMPROVE BECAUSE OF HEPATIC FAILURE, AND EXTERNAL DRAINAGE WAS CONTINUED UNTIL THE PATIENTS DEATH. IN THE REMAINING PATIENT, PTBD WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. CHOLANGITIS RECURRED IN 1 PATIENT AT 1 MONTH AFTER STENT PLACEMENT WITHOUT AN ADDITIONAL TACE SESSION, AND IT DID NOT IMPROVE DESPITE ADMINISTRATION OF ANTIBIOTICS. ONE PATIENT WHO HAD UNDERGONE STENT PLACEMENT TO RELIEVE BILE DUCT STRICTURE BEFORE ADDITIONAL TACE SESSIONS DID NOT DEVELOP ANY COMPLICATIONS DESPITE 4 ADDITIONAL TACE SESSIONS, INCLUDING 2 TO THE STENTED LOBE. SEVEN PATIENTS (38.9%) HAVE NOT PRESENTED ANY SYMPTOMS FOR 3 TO 68 MONTHS (MEAN 28.6 +/- 24.3) SINCE THE DEVELOPMENT OF BILE DUCT STRICTURE, AND 3 PATIENTS (16.7%) INCLUDING 2 WHO UNDERWENT METALLIC STENT PLACEMENT HAVE NOT SHOWN ANY SYMPTOMS ASSOCIATED WITH BILE DUCT STRICTURE FOR 3 TO 17 MONTHS (MEAN 9.0 +/- 7.2) SINCE THE ADDITIONAL INTERVENTION. EIGHT PATIENTS (44.4%), INCLUDING 3 WHO UNDERWENT STENT PLACEMENT (N = 5), DIED OF HEPATIC FAILURE (N = 2), UNCONTROLLABLE JAUNDICE, CHOLANGITIS, AND/OR TUMOR PROGRESSION (N = 1) AT 11 TO 119 MONTHS (MEAN 37.9 +/- 34.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND AT 11 TO 41 MONTHS (MEAN 21.3 +/- 10.4) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. TEN PATIENTS (55.6%) HAVE SURVIVED 3 TO 129 MONTHS (MEAN 38.4 +/- 37.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND 3 TO 72 MONTHS (MEAN 28.4 +/- 21.9) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. FOUR PATIENTS HAVE NOT SHOWN ANY VIABLE HCCS, BUT 6 PATIENTS HAVE VIABLE HCCS DESPITE REPEATED TACE SESSIONS. DISCUSSION: IN THE PRESENT STUDY, ALL STRICTURES WERE ALSO LOCATED AT THE CHD AND/OR THE RHD OR THE LHD. THIS MAY REFLECT THE VASCULAR SUPPLY OF THE CHD AND BILATERAL HEPATIC DUCTS FROM THE HEPATIC ARTERIAL BRANCHES, INCLUDING A1 AND A4, WHEREAS THE CBD IS MAINLY SUPPLIED BY THE BRANCHES OF THE GASTRODUODENAL ARTERY. THE POOR COLLATERAL SUPPLY TO THE CHD, COMPARED WITH A DENSER ARTERIAL NETWORK AND A RELATIVELY HIGH PROPORTION OF SUPPLY TO THE LOWER CBD, COULD EXPLAIN THE VULNERABILITY OF THE CHD TO ISCHEMIC INJURY. ALL STRICTURES WERE FOCAL AND SMOOTH, AND INTRALUMINAL COAGULA WAS FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAM. WE CONSIDER THAT THESE FINDINGS MAY BE TYPICAL IMAGE FINDINGS OF BILE DUCT INJURY BY TACE. RADIOLOGISTS SHOULD NOT MISDIAGNOSE THIS CONDITION AS BILE DUCT INVASION BY THE TUMOR. IN THE PRESENT STUDY, ALL MAIN BILE DUCT STRICTURES DEVELOPED AFTER TACE OF A1 AND/OR A4. IN ADDITION, 50% OF BILE DUCT STRICTURES DEVELOPED EVEN AFTER A SINGLE TACE SESSION OF A1 AND/OR A4, SUGGESTING THAT SELECTIVE TACE OF A1 AND/OR A4 IS A MAIN CAUSE OF BILE DUCT NECROSIS. HOWEVER, NONSELECTIVE TACE OF THE RIGHT HEPATIC ARTERY OR LEFT HEPATIC ARTERY LEVEL MAY MAINLY DAMAGE "THE PERIPHERAL BRANCHES," WHEREAS "THE CENTRAL BRANCHES," SUCH AS A1 AND A4, MAY BE SLIGHTLY DAMAGED OR OCCASIONALLY PRESERVED. REPEAT TACE SESSIONS MAY FINALLY DAMAGE THESE CENTRAL BRANCHES BECAUSE THE PERIPHERAL BRANCHES ARE SEVERELY ATTENUATED BY PREVIOUS TACE PROCEDURES, AND EMBOLIC MATERIALS FLOWS MAINLY INTO THESE CENTRAL BRANCHES. 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. WE REPORTED THAT ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS TO ACHIEVE NOT ONLY COMPLETE TUMOR NECROSIS BUT ALSO MASSIVE PERITUMORAL NECROSIS BY BLOCKAGE OF BOTH THE HEPATIC ARTERIAL AND PORTAL BLOOD FLOW. 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. IT MAY BE DIFFICULT TO PREDICT MAIN BILE DUCT INJURY BY TACE. IN 3 PATIENTS UNDERGOING SELECTIVE CBCT DURING THE TACE PROCEDURE OF A1 AND/OR A4, BILE DUCT WALL ENHANCEMENT WAS CLEARLY DEMONSTRATED. CBCT MIGHT BE USEFUL FOR PREDICTING BILE DUCT INJURY CAUSED BY TACE. WE SHOULD ALWAYS BEAR IN MIND THAT SELECTIVE TACE OF A1 AND/ OR A4 CARRIES THE RISK OF CAUSING BILE DUCT NECROSIS. THEREFORE, COMPLETE BLOCKAGE OF THESE VESSELS SHOULD BE AVOIDED, ESPECIALLY WHEN BILE DUCT ENHANCEMENT IS SEEN ON CT OR CBCT DURING ARTERIOGRAPHY THROUGH A1 OR A4. IN ADDITION, DISTAL ADVANCEMENT OF A THINNER MICROCATHETER WITH A TIP \2F INTO A1 OR A4 MAY BE USEFUL TO AVOID EMBOLIZATION OF SMALL VESSELS SUPPLYING THE MAIN BILE DUCTS BECAUSE THESE VESSELS MAY BE ESTIMATED TO ARISE FROM THE PROXIMATE PORTION OF A1 AND A4. CT OBTAINED AT 1 WEEK AFTER TACE MAY ALSO BE USEFUL TO SUGGEST MAIN BILE DUCT DAMAGE. CHANGES IN LABORATORY DATA ARE NOT SUFFICIENTLY SENSITIVE, AND ABNORMALITIES MAY BECOME APPARENT LONG AFTER DEMONSTRATION OF BILE DUCT DILATATION ON CT IN MOST PATIENTS, ALTHOUGH MARKED CHANGES SUGGEST SEVERE DAMAGE TO THE MAIN BILE DUCTS. 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. METALLIC STENT PLACEMENT MAY BE USEFUL TO MANAGE MAIN BILE DUCT STRICTURE CAUSED BY TACE BECAUSE PATIENTS WITH INOPERABLE HCC ARE NOT GOOD CANDIDATES FOR SURGICAL BILE DUCT REPAIR. HOWEVER, BILE DUCT COMPLICATIONS MAY OCCUR AT HIGH RATES AFTER ADDITIONAL TACE SESSIONS. IN ADDITION, WE SHOULD BE WELL AWARE THAT INTRAHEPATIC BILE DUCT DILATATION IS A SIGNIFICANT RISK FACTOR IN DEVELOPING BILOMA AFTER TACE. 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. FOCAL AND SMOOTH BILE DUCT STRICTURES MAINLY AT THE CHD ARE CHARACTERISTIC FINDINGS, AND INTRALUMINAL COAGULA ARE FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAPHY. RADIOLOGISTS SHOULD WELL AWARE THIS UNCOMMON BUT SEVERE COMPLICATION OF TACE. TABLE 2: SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE A 76-YEAR-OLD FEMALE PATIENT HAD ONE TUMOR MEASURING 16 MM IN DIAMETER. SEGMENT WAS S1 AND EMBOLIZED BRANCHES WAS A1.\ IODIZED OIL-ACCUMULATED PORTION: COMMON HEPATIC DUCT (CHD); SITE OF BILE DUCT DILATATION: BOTH. SHRINKAGE OF GALLBLADDER: + CHANGES IN BILE DUCT DILATATION: PROGRESSED; NO. OF ADDITIONAL TACE: 1; 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). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM, AND ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS AND LESS BILE DUCT COMPLICATIONS. IT WAS REPORTED THAT INTRAHEPATIC AND EXTRAHEPATIC BILE DUCTS WOULD BECOME NECROTIC IF SMALL PARTICLES <250 UM WERE USED. 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. 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.
MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS] , . 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. THIS IS THE SECOND OF ELEVEN REPORTS. ABSTRACT THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE CLINICAL COURSE OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC). AMONG 446 CONSECUTIVE PATIENTS WITH HCC TREATED BY TACE, MAIN BILE DUCT STRICTURE DEVELOPED IN 18 (4.0%). ALL IMAGING AND LABORATORY DATA, TREATMENT COURSE, AND OUTCOMES WERE RETROSPECTIVELY ANALYZED. ALL PATIENTS HAD 1 TO 2 TUMORS MEASURING 10 TO 100 MM IN DIAMETER (MEAN ± SD 24.5 ± 5.4 MM) NEAR THE HEPATIC HILUM FED BY THE CAUDATE ARTERIAL BRANCH (A1) AND/OR MEDIAL SEGMENTAL ARTERY (A4) OF THE LIVER. DURING THE TACE PROCEDURE THAT CAUSED BILE DUCT INJURY, A1 WAS EMBOLIZED IN 8, A4 WAS EMBOLIZED IN 5, AND BOTH WERE EMBOLIZED IN 5 PATIENTS. NINE PATIENTS (50.0%) HAD A HISTORY OF TACE IN EITHER A1 OR A4. IODIZED OIL ACCUMULATION IN THE BILE DUCT WALL WAS SEEN IN ALL PATIENTS ON COMPUTED TOMOGRAPHY OBTAINED 1 WEEK LATER. BILE DUCT DILATATION CAUSED BY MAIN BILE DUCT STRICTURE DEVELOPED IN BOTH LOBES (N = 9), IN THE RIGHT LOBE (N = 3), IN THE LEFT LOBE (N = 4), IN SEGMENT (S) 2 (N = 1), AND IN S3 (N = 1). SERUM LEVELS OF ALKALINE PHOSPHATASE AND C-GLUTAMYLTRANSPEPTIDASE INCREASED IN 13 PATIENTS. BILOMA REQUIRING DRAINAGE DEVELOPED IN 2 PATIENTS; JAUNDICE DEVELOPED IN 4 PATIENTS; AND METALLIC STENTS WERE PLACED IN 3 PATIENTS. COMPLICATIONS AFTER ADDITIONAL TACE SESSIONS, INCLUDING BILOMA (N = 3) AND/OR JAUNDICE (N = 5), OCCURRED IN 7 PATIENTS AND WERE TREATED BY ADDITIONAL INTERVENTION, INCLUDING METALLIC STENT PLACEMENT IN 2 PATIENTS. AFTER INITIAL TACE OF A1 AND/OR A4, 8 PATIENTS (44.4%), INCLUDING 5 WITH UNCONTROLLABLE JAUNDICE OR CHOLANGITIS, DIED AT 37.9 ± 34.9 MONTHS AFTER TACE, AND 10 (55.6%) HAVE SURVIVED FOR 38.4 ± 37.9 MONTHS. SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM. BILOMA AND JAUNDICE ARE SERIOUS COMPLICATIONS ASSOCIATED WITH BILE DUCT STRICTURES. 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. RESULTS: THE RESULTS ARE SUMMARIZED IN TABLE 2. ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. CLINICAL COURSES AND OUTCOMES: ALL PATIENTS WERE FOLLOWED-UP FOR 3 TO 129 MONTHS (MEAN 38.2 +/- 35.4) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND FOR 3 TO 72 MONTHS (MEAN 25.2 +/- 17.6) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. ELEVEN PATIENTS (61.1%) PRESENTED WITH BILE DUCT COMPLICATIONS ASSOCIATED WITH MAIN BILE DUCT STRICTURE. CHOLANGITIS DEVELOPED IN 2 PATIENTS (11.1%) AT 2 MONTHS AFTER TACE AND RESOLVED AFTER ADMINISTRATION OF ANTIBIOTICS (SULPERAZON; PFIZER, TOKYO, JAPAN). BILE DUCT DILATATION WAS IMPROVED DURING FOLLOW-UP IN THESE PATIENTS (FIG. 1). BILOMA DEVELOPED IN 4 PATIENTS (22.2%), AND PERCUTANEOUS DRAINAGE WAS PERFORMED IN 2 OF 4 PATIENTS AT 2 AND 4 MONTHS, RESPECTIVELY, AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. JAUNDICE (SERUM BILIRUBIN LEVEL 9.3 TO 14.0 MG/DL [MEAN 11.7 +/- 2.3]) DEVELOPED IN 4 PATIENTS (22.2%), INCLUDING 2 WITH A HISTORY OF BILOMA DRAINAGE, AT 5 TO 11 MONTHS (MEAN 7.3 +/- 2.9) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. THREE PATIENTS UNDERWENT PTBD. IN THE REMAINING PATIENT, BILE DUCT DRAINAGE WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. IN ANOTHER PATIENT WITHOUT JAUNDICE, PTBD WAS PERFORMED TO RELIEVE BILE DUCT DILATATION BEFORE ADDITIONAL TACE WITH BILE DUCT DILATATION FOR HCC IN THE LEFT LOBE OF THE LIVER. METALLIC STENT PLACEMENT (ZILVER 635; COOK) WAS SUBSEQUENTLY PERFORMED IN 4 PATIENTS. IN 2 PATIENTS, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO THE CBD USING EITHER A BILATERAL OR LEFT APPROACH. IN 2 PATIENTS, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CHD BY WAY OF A LEFT APPROACH. THE PTBD CATHETER WAS REMOVED AFTER STENT PLACEMENT. IN 13 PATIENTS (72.2%), INCLUDING 4 WHO UNDERWENT STENT PLACEMENT, 1 TO 5 ADDITIONAL TACE SESSIONS (MEAN 2.6 +/- 1.5) WERE PERFORMED BECAUSE OF LOCAL RECURRENCE AND/OR NEW LESIONS AT OTHER SITES. IN TOTAL, 24 TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE WERE PERFORMED IN 12 PATIENTS, AND 10 TACE SESSIONS TO THE AREA WITHOUT BILE DUCT DILATATION WERE PERFORMED IN 5 PATIENTS. COMPLICATIONS ASSOCIATED WITH ADDITIONAL TACE SESSIONS OCCURRED IN 7 OF 13 PATIENTS (53.8%). BILOMA DEVELOPED IN 3 PATIENTS. IT DEVELOPED IN 2 PATIENTS AT 2 MONTHS AFTER THE ADDITIONAL FIRST TACE SESSION TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE AND IN 1 PATIENT AT 1 MONTH AFTER 4 ADDITIONAL TACE SESSIONS TO THE STENTED LOBE. PERCUTANEOUS DRAINAGE WAS REQUIRED IN 1 PATIENT WITH PREVIOUS STENT PLACEMENT. JAUNDICE (6.5 TO 22.6 MG/DL [MEAN 12.6 +/- 6.7]) DEVELOPED IN 5 PATIENTS AT 3 TO 26 MONTHS (MEAN 15.4 +/- 19.7) AFTER THE FIRST ADDITIONAL TACE SESSION AND AT 2 WEEKS TO 5 MONTHS (MEAN 2.8 +/- 1.8) AFTER THE LAST ADDITIONAL TACE SESSION, INCLUDING 2 PATIENTS WHO HAD UNDERGONE STENT PLACEMENT. IT DEVELOPED AFTER 1 (N = 2), 3 (N = 1), AND 4 (N = 2) ADDITIONAL TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION (N = 3) OR TO THE STENTED LOBE (N = 2). ONE OF THESE PATIENTS ALSO HAD A SMALL BILOMA. ALL PATIENTS BUT 1 UNDERWENT PTBD. IN 1 PATIENT, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CBD USING A LEFT APPROACH. IN ANOTHER PATIENT, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO CBD USING A BILATERAL APPROACH (FIG. 5). THE BILE DUCT WAS OCCLUDED IN THE STENTED SEGMENT IN 2 PATIENTS WHO HAD PREVIOUSLY UNDERGONE STENT PLACEMENT. JAUNDICE DID NOT IMPROVE BECAUSE OF HEPATIC FAILURE, AND EXTERNAL DRAINAGE WAS CONTINUED UNTIL THE PATIENTS DEATH. IN THE REMAINING PATIENT, PTBD WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. CHOLANGITIS RECURRED IN 1 PATIENT AT 1 MONTH AFTER STENT PLACEMENT WITHOUT AN ADDITIONAL TACE SESSION, AND IT DID NOT IMPROVE DESPITE ADMINISTRATION OF ANTIBIOTICS. ONE PATIENT WHO HAD UNDERGONE STENT PLACEMENT TO RELIEVE BILE DUCT STRICTURE BEFORE ADDITIONAL TACE SESSIONS DID NOT DEVELOP ANY COMPLICATIONS DESPITE 4 ADDITIONAL TACE SESSIONS, INCLUDING 2 TO THE STENTED LOBE. SEVEN PATIENTS (38.9%) HAVE NOT PRESENTED ANY SYMPTOMS FOR 3 TO 68 MONTHS (MEAN 28.6 +/- 24.3) SINCE THE DEVELOPMENT OF BILE DUCT STRICTURE, AND 3 PATIENTS (16.7%) INCLUDING 2 WHO UNDERWENT METALLIC STENT PLACEMENT HAVE NOT SHOWN ANY SYMPTOMS ASSOCIATED WITH BILE DUCT STRICTURE FOR 3 TO 17 MONTHS (MEAN 9.0 +/- 7.2) SINCE THE ADDITIONAL INTERVENTION. EIGHT PATIENTS (44.4%), INCLUDING 3 WHO UNDERWENT STENT PLACEMENT (N = 5), DIED OF HEPATIC FAILURE (N = 2), UNCONTROLLABLE JAUNDICE, CHOLANGITIS, AND/OR TUMOR PROGRESSION (N = 1) AT 11 TO 119 MONTHS (MEAN 37.9 +/- 34.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND AT 11 TO 41 MONTHS (MEAN 21.3 +/- 10.4) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. TEN PATIENTS (55.6%) HAVE SURVIVED 3 TO 129 MONTHS (MEAN 38.4 +/- 37.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND 3 TO 72 MONTHS (MEAN 28.4 +/- 21.9) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. FOUR PATIENTS HAVE NOT SHOWN ANY VIABLE HCCS, BUT 6 PATIENTS HAVE VIABLE HCCS DESPITE REPEATED TACE SESSIONS. DISCUSSION: IN THE PRESENT STUDY, ALL STRICTURES WERE ALSO LOCATED AT THE CHD AND/OR THE RHD OR THE LHD. THIS MAY REFLECT THE VASCULAR SUPPLY OF THE CHD AND BILATERAL HEPATIC DUCTS FROM THE HEPATIC ARTERIAL BRANCHES, INCLUDING A1 AND A4, WHEREAS THE CBD IS MAINLY SUPPLIED BY THE BRANCHES OF THE GASTRODUODENAL ARTERY. THE POOR COLLATERAL SUPPLY TO THE CHD, COMPARED WITH A DENSER ARTERIAL NETWORK AND A RELATIVELY HIGH PROPORTION OF SUPPLY TO THE LOWER CBD, COULD EXPLAIN THE VULNERABILITY OF THE CHD TO ISCHEMIC INJURY. ALL STRICTURES WERE FOCAL AND SMOOTH, AND INTRALUMINAL COAGULA WAS FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAM. WE CONSIDER THAT THESE FINDINGS MAY BE TYPICAL IMAGE FINDINGS OF BILE DUCT INJURY BY TACE. RADIOLOGISTS SHOULD NOT MISDIAGNOSE THIS CONDITION AS BILE DUCT INVASION BY THE TUMOR. IN THE PRESENT STUDY, ALL MAIN BILE DUCT STRICTURES DEVELOPED AFTER TACE OF A1 AND/OR A4. IN ADDITION, 50% OF BILE DUCT STRICTURES DEVELOPED EVEN AFTER A SINGLE TACE SESSION OF A1 AND/OR A4, SUGGESTING THAT SELECTIVE TACE OF A1 AND/OR A4 IS A MAIN CAUSE OF BILE DUCT NECROSIS. HOWEVER, NONSELECTIVE TACE OF THE RIGHT HEPATIC ARTERY OR LEFT HEPATIC ARTERY LEVEL MAY MAINLY DAMAGE "THE PERIPHERAL BRANCHES," WHEREAS "THE CENTRAL BRANCHES," SUCH AS A1 AND A4, MAY BE SLIGHTLY DAMAGED OR OCCASIONALLY PRESERVED. REPEAT TACE SESSIONS MAY FINALLY DAMAGE THESE CENTRAL BRANCHES BECAUSE THE PERIPHERAL BRANCHES ARE SEVERELY ATTENUATED BY PREVIOUS TACE PROCEDURES, AND EMBOLIC MATERIALS FLOWS MAINLY INTO THESE CENTRAL BRANCHES. 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. WE REPORTED THAT ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS TO ACHIEVE NOT ONLY COMPLETE TUMOR NECROSIS BUT ALSO MASSIVE PERITUMORAL NECROSIS BY BLOCKAGE OF BOTH THE HEPATIC ARTERIAL AND PORTAL BLOOD FLOW. 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. IT MAY BE DIFFICULT TO PREDICT MAIN BILE DUCT INJURY BY TACE. IN 3 PATIENTS UNDERGOING SELECTIVE CBCT DURING THE TACE PROCEDURE OF A1 AND/OR A4, BILE DUCT WALL ENHANCEMENT WAS CLEARLY DEMONSTRATED. CBCT MIGHT BE USEFUL FOR PREDICTING BILE DUCT INJURY CAUSED BY TACE. WE SHOULD ALWAYS BEAR IN MIND THAT SELECTIVE TACE OF A1 AND/ OR A4 CARRIES THE RISK OF CAUSING BILE DUCT NECROSIS. THEREFORE, COMPLETE BLOCKAGE OF THESE VESSELS SHOULD BE AVOIDED, ESPECIALLY WHEN BILE DUCT ENHANCEMENT IS SEEN ON CT OR CBCT DURING ARTERIOGRAPHY THROUGH A1 OR A4. IN ADDITION, DISTAL ADVANCEMENT OF A THINNER MICROCATHETER WITH A TIP \2F INTO A1 OR A4 MAY BE USEFUL TO AVOID EMBOLIZATION OF SMALL VESSELS SUPPLYING THE MAIN BILE DUCTS BECAUSE THESE VESSELS MAY BE ESTIMATED TO ARISE FROM THE PROXIMATE PORTION OF A1 AND A4. CT OBTAINED AT 1 WEEK AFTER TACE MAY ALSO BE USEFUL TO SUGGEST MAIN BILE DUCT DAMAGE. CHANGES IN LABORATORY DATA ARE NOT SUFFICIENTLY SENSITIVE, AND ABNORMALITIES MAY BECOME APPARENT LONG AFTER DEMONSTRATION OF BILE DUCT DILATATION ON CT IN MOST PATIENTS, ALTHOUGH MARKED CHANGES SUGGEST SEVERE DAMAGE TO THE MAIN BILE DUCTS. 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. METALLIC STENT PLACEMENT MAY BE USEFUL TO MANAGE MAIN BILE DUCT STRICTURE CAUSED BY TACE BECAUSE PATIENTS WITH INOPERABLE HCC ARE NOT GOOD CANDIDATES FOR SURGICAL BILE DUCT REPAIR. HOWEVER, BILE DUCT COMPLICATIONS MAY OCCUR AT HIGH RATES AFTER ADDITIONAL TACE SESSIONS. IN ADDITION, WE SHOULD BE WELL AWARE THAT INTRAHEPATIC BILE DUCT DILATATION IS A SIGNIFICANT RISK FACTOR IN DEVELOPING BILOMA AFTER TACE. 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. FOCAL AND SMOOTH BILE DUCT STRICTURES MAINLY AT THE CHD ARE CHARACTERISTIC FINDINGS, AND INTRALUMINAL COAGULA ARE FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAPHY. RADIOLOGISTS SHOULD WELL AWARE THIS UNCOMMON BUT SEVERE COMPLICATION OF TACE. TABLE 2: SUMMARY OF 18 PATIENTS WITH MAIN BILE DUCT STRICTURE OCCURRING AFTER TACE PATIENT NO.2 A 76-YEAR-OLD FEMALE PATIENT HAD ONE TUMOR MEASURING 16 MM IN DIAMETER. SEGMENT WAS S1 AND EMBOLIZED BRANCHES WAS A1. IODIZED OIL-ACCUMULATED PORTION: COMMON HEPATIC DUCT (CHD); SITE OF BILE DUCT DILATATION: BOTH. SHRINKAGE OF GALLBLADDER: + CHANGES IN BILE DUCT DILATATION: PROGRESSED; NO. OF ADDITIONAL TACE: 1; 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 (24JUL2019): FOLLOW-UP ATTEMPTS COMPLETED. NO FURTHER INFORMATION EXPECTED. FOLLOW-UP (10SEP2019): THIS IS A FOLLOW UP REPORT, BASED ON INFORMATION RECEIVED BY PFIZER FROM PRODUCT QUALITY COMPLAINTS (PRODUCT COMPLAINT NUMBER: 4189498), FOR ABSORBABLE GELATIN (GELFOAM). A COMPLAINT HAS BEEN RECEIVED BY PFIZER WITH NO REASONABLE SUSPICION OF A MALFUNCTION; THE ASSOCIATED WORST CASE SEVERITY IS UNKNOWN. IMPACT TO THE DEVICE: POSSIBLE ADVERSE EVENT. HAZARDOUS SITUATION: UNKNOWN; HAZARD NUMBER (WORST CASE): UNKNOWN; SEVERITY (WORST CASE): UNKNOWN; P2 VALUE: H10-03 (WORST CASE) UNKNOWN. MDR ISSUED FOR THE ASSOCIATED AE CASE: 2019275884, 2019275885, 2019275886, 2019275887, 2019275888, 2019275889, 2019275890, 2019275891, 2019275892, 2019275893, 2019275894, 2019275895, 2019275896, 2019275897, 2019275898, 2019275899, 2019275900. MDR FOR OTHER CASES INVOLVING OFF-LABEL USE WERE ISSUED PREVIOUSLY THAT WERE NOT ASSOCIATED WITH THE CASES LISTED ABOVE. COMPANY CLINICAL EVALUATION COMMENT: IN THE PRESENT STUDY, GELFOAM PARTICLES WERE CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY AND USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC), WHICH IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). PER THIS STUDY RESULT, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). 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. THE COMPANY INVESTIGATION RESULT FROM PRODUCT QUALITY COMPLAINTS DOES NOT SUPPORT A DEVICE ISSUE., COMMENT: IN THE PRESENT STUDY, GELFOAM PARTICLES WERE CUT INTO APPROXIMATELY 1-MM CUBES MANUALLY AND USED IN TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC), WHICH IS OFF LABEL USE FOR GELATIN SPONGE (GELFOAM). PER THIS STUDY RESULT, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). 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. THE COMPANY INVESTIGATION RESULT FROM PRODUCT QUALITY COMPLAINTS DOES NOT SUPPORT A DEVICE ISSUE.
MAIN BILE DUCT STRICTURE OCCURRING AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION [BILE DUCT STENOSIS]. 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 SECOND OF EIGHTEEN REPORTS. ABSTRACT: THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE CLINICAL COURSE OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) FOR HEPATOCELLULAR CARCINOMA (HCC). AMONG 446 CONSECUTIVE PATIENTS WITH HCC TREATED BY TACE, MAIN BILE DUCT STRICTURE DEVELOPED IN 18 (4.0%). ALL IMAGING AND LABORATORY DATA, TREATMENT COURSE, AND OUTCOMES WERE RETROSPECTIVELY ANALYZED. ALL PATIENTS HAD 1 TO 2 TUMORS MEASURING 10 TO 100 MM IN DIAMETER (MEAN ± SD 24.5 ± 5.4 MM) NEAR THE HEPATIC HILUM FED BY THE CAUDATE ARTERIAL BRANCH (A1) AND/OR MEDIAL SEGMENTAL ARTERY (A4) OF THE LIVER. DURING THE TACE PROCEDURE THAT CAUSED BILE DUCT INJURY, A1 WAS EMBOLIZED IN 8, A4 WAS EMBOLIZED IN 5, AND BOTH WERE EMBOLIZED IN 5 PATIENTS. NINE PATIENTS (50.0%) HAD A HISTORY OF TACE IN EITHER A1 OR A4. IODIZED OIL ACCUMULATION IN THE BILE DUCT WALL WAS SEEN IN ALL PATIENTS ON COMPUTED TOMOGRAPHY OBTAINED 1 WEEK LATER. BILE DUCT DILATATION CAUSED BY MAIN BILE DUCT STRICTURE DEVELOPED IN BOTH LOBES (N = 9), IN THE RIGHT LOBE (N = 3), IN THE LEFT LOBE (N = 4), IN SEGMENT (S) 2 (N = 1), AND IN S3 (N = 1). SERUM LEVELS OF ALKALINE PHOSPHATASE AND C-GLUTAMYLTRANSPEPTIDASE INCREASED IN 13 PATIENTS. BILOMA REQUIRING DRAINAGE DEVELOPED IN 2 PATIENTS; JAUNDICE DEVELOPED IN 4 PATIENTS; AND METALLIC STENTS WERE PLACED IN 3 PATIENTS. COMPLICATIONS AFTER ADDITIONAL TACE SESSIONS, INCLUDING BILOMA (N = 3) AND/OR JAUNDICE (N = 5), OCCURRED IN 7 PATIENTS AND WERE TREATED BY ADDITIONAL INTERVENTION, INCLUDING METALLIC STENT PLACEMENT IN 2 PATIENTS. AFTER INITIAL TACE OF A1 AND/OR A4, 8 PATIENTS (44.4%), INCLUDING 5 WITH UNCONTROLLABLE JAUNDICE OR CHOLANGITIS, DIED AT 37.9 ± 34.9 MONTHS AFTER TACE, AND 10 (55.6%) HAVE SURVIVED FOR 38.4 ± 37.9 MONTHS. SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM. BILOMA AND JAUNDICE ARE SERIOUS COMPLICATIONS ASSOCIATED WITH BILE DUCT STRICTURES. 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. RESULTS: THE RESULTS ARE SUMMARIZED IN TABLE 2. ALL PATIENTS WERE FOLLOWED-UP UNTIL DEATH OR TO DATE. CLINICAL COURSES AND OUTCOMES: ALL PATIENTS WERE FOLLOWED-UP FOR 3 TO 129 MONTHS (MEAN 38.2 +/- 35.4) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND FOR 3 TO 72 MONTHS (MEAN 25.2 +/- 17.6) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. ELEVEN PATIENTS (61.1%) PRESENTED WITH BILE DUCT COMPLICATIONS ASSOCIATED WITH MAIN BILE DUCT STRICTURE. CHOLANGITIS DEVELOPED IN 2 PATIENTS (11.1%) AT 2 MONTHS AFTER TACE AND RESOLVED AFTER ADMINISTRATION OF ANTIBIOTICS (SULPERAZON; PFIZER, TOKYO, JAPAN). BILE DUCT DILATATION WAS IMPROVED DURING FOLLOW-UP IN THESE PATIENTS (FIG. 1). BILOMA DEVELOPED IN 4 PATIENTS (22.2%), AND PERCUTANEOUS DRAINAGE WAS PERFORMED IN 2 OF 4 PATIENTS AT 2 AND 4 MONTHS, RESPECTIVELY, AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. JAUNDICE (SERUM BILIRUBIN LEVEL 9.3 TO 14.0 MG/DL [MEAN 11.7 +/- 2.3]) DEVELOPED IN 4 PATIENTS (22.2%), INCLUDING 2 WITH A HISTORY OF BILOMA DRAINAGE, AT 5 TO 11 MONTHS (MEAN 7.3 +/- 2.9) AFTER THE LAST TACE BEFORE BILE DUCT DILATATION. THREE PATIENTS UNDERWENT PTBD. IN THE REMAINING PATIENT, BILE DUCT DRAINAGE WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. IN ANOTHER PATIENT WITHOUT JAUNDICE, PTBD WAS PERFORMED TO RELIEVE BILE DUCT DILATATION BEFORE ADDITIONAL TACE WITH BILE DUCT DILATATION FOR HCC IN THE LEFT LOBE OF THE LIVER. METALLIC STENT PLACEMENT (ZILVER 635; COOK) WAS SUBSEQUENTLY PERFORMED IN 4 PATIENTS. IN 2 PATIENTS, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO THE CBD USING EITHER A BILATERAL OR LEFT APPROACH. IN 2 PATIENTS, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CHD BY WAY OF A LEFT APPROACH. THE PTBD CATHETER WAS REMOVED AFTER STENT PLACEMENT. IN 13 PATIENTS (72.2%), INCLUDING 4 WHO UNDERWENT STENT PLACEMENT, 1 TO 5 ADDITIONAL TACE SESSIONS (MEAN 2.6 +/- 1.5) WERE PERFORMED BECAUSE OF LOCAL RECURRENCE AND/OR NEW LESIONS AT OTHER SITES. IN TOTAL, 24 TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE WERE PERFORMED IN 12 PATIENTS, AND 10 TACE SESSIONS TO THE AREA WITHOUT BILE DUCT DILATATION WERE PERFORMED IN 5 PATIENTS. COMPLICATIONS ASSOCIATED WITH ADDITIONAL TACE SESSIONS OCCURRED IN 7 OF 13 PATIENTS (53.8%). BILOMA DEVELOPED IN 3 PATIENTS. IT DEVELOPED IN 2 PATIENTS AT 2 MONTHS AFTER THE ADDITIONAL FIRST TACE SESSION TO THE AREA WITH BILE DUCT DILATATION OR STENTED LOBE AND IN 1 PATIENT AT 1 MONTH AFTER 4 ADDITIONAL TACE SESSIONS TO THE STENTED LOBE. PERCUTANEOUS DRAINAGE WAS REQUIRED IN 1 PATIENT WITH PREVIOUS STENT PLACEMENT. JAUNDICE (6.5 TO 22.6 MG/DL [MEAN 12.6 +/- 6.7]) DEVELOPED IN 5 PATIENTS AT 3 TO 26 MONTHS (MEAN 15.4 +/- 19.7) AFTER THE FIRST ADDITIONAL TACE SESSION AND AT 2 WEEKS TO 5 MONTHS (MEAN 2.8 +/- 1.8) AFTER THE LAST ADDITIONAL TACE SESSION, INCLUDING 2 PATIENTS WHO HAD UNDERGONE STENT PLACEMENT. IT DEVELOPED AFTER 1 (N = 2), 3 (N = 1), AND 4 (N = 2) ADDITIONAL TACE SESSIONS TO THE AREA WITH BILE DUCT DILATATION (N = 3) OR TO THE STENTED LOBE (N = 2). ONE OF THESE PATIENTS ALSO HAD A SMALL BILOMA. ALL PATIENTS BUT 1 UNDERWENT PTBD. IN 1 PATIENT, 1 METALLIC STENT WAS PLACED FROM THE LHD TO CBD USING A LEFT APPROACH. IN ANOTHER PATIENT, 2 METALLIC STENTS WERE PLACED FROM THE BILATERAL HEPATIC DUCTS TO CBD USING A BILATERAL APPROACH (FIG. 5). THE BILE DUCT WAS OCCLUDED IN THE STENTED SEGMENT IN 2 PATIENTS WHO HAD PREVIOUSLY UNDERGONE STENT PLACEMENT. JAUNDICE DID NOT IMPROVE BECAUSE OF HEPATIC FAILURE, AND EXTERNAL DRAINAGE WAS CONTINUED UNTIL THE PATIENTS DEATH. IN THE REMAINING PATIENT, PTBD WAS NOT PERFORMED BECAUSE OF THE PATIENT'S POOR GENERAL CONDITION. CHOLANGITIS RECURRED IN 1 PATIENT AT 1 MONTH AFTER STENT PLACEMENT WITHOUT AN ADDITIONAL TACE SESSION, AND IT DID NOT IMPROVE DESPITE ADMINISTRATION OF ANTIBIOTICS. ONE PATIENT WHO HAD UNDERGONE STENT PLACEMENT TO RELIEVE BILE DUCT STRICTURE BEFORE ADDITIONAL TACE SESSIONS DID NOT DEVELOP ANY COMPLICATIONS DESPITE 4 ADDITIONAL TACE SESSIONS, INCLUDING 2 TO THE STENTED LOBE. SEVEN PATIENTS (38.9%) HAVE NOT PRESENTED ANY SYMPTOMS FOR 3 TO 68 MONTHS (MEAN 28.6 +/- 24.3) SINCE THE DEVELOPMENT OF BILE DUCT STRICTURE, AND 3 PATIENTS (16.7%) INCLUDING 2 WHO UNDERWENT METALLIC STENT PLACEMENT HAVE NOT SHOWN ANY SYMPTOMS ASSOCIATED WITH BILE DUCT STRICTURE FOR 3 TO 17 MONTHS (MEAN 9.0 +/- 7.2) SINCE THE ADDITIONAL INTERVENTION. EIGHT PATIENTS (44.4%), INCLUDING 3 WHO UNDERWENT STENT PLACEMENT (N = 5), DIED OF HEPATIC FAILURE (N = 2), UNCONTROLLABLE JAUNDICE, CHOLANGITIS, AND/OR TUMOR PROGRESSION (N = 1) AT 11 TO 119 MONTHS (MEAN 37.9 +/- 34.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND AT 11 TO 41 MONTHS (MEAN 21.3 +/- 10.4) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. TEN PATIENTS (55.6%) HAVE SURVIVED 3 TO 129 MONTHS (MEAN 38.4 +/- 37.9) AFTER THE INITIAL TACE OF A1 AND/OR A4 AND 3 TO 72 MONTHS (MEAN 28.4 +/- 21.9) AFTER THE LAST TACE SESSION BEFORE BILE DUCT DILATATION. FOUR PATIENTS HAVE NOT SHOWN ANY VIABLE HCCS, BUT 6 PATIENTS HAVE VIABLE HCCS DESPITE REPEATED TACE SESSIONS. DISCUSSION: IN THE PRESENT STUDY, ALL STRICTURES WERE ALSO LOCATED AT THE CHD AND/OR THE RHD OR THE LHD. THIS MAY REFLECT THE VASCULAR SUPPLY OF THE CHD AND BILATERAL HEPATIC DUCTS FROM THE HEPATIC ARTERIAL BRANCHES, INCLUDING A1 AND A4, WHEREAS THE CBD IS MAINLY SUPPLIED BY THE BRANCHES OF THE GASTRODUODENAL ARTERY. THE POOR COLLATERAL SUPPLY TO THE CHD, COMPARED WITH A DENSER ARTERIAL NETWORK AND A RELATIVELY HIGH PROPORTION OF SUPPLY TO THE LOWER CBD, COULD EXPLAIN THE VULNERABILITY OF THE CHD TO ISCHEMIC INJURY. ALL STRICTURES WERE FOCAL AND SMOOTH, AND INTRALUMINAL COAGULA WAS FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAM. WE CONSIDER THAT THESE FINDINGS MAY BE TYPICAL IMAGE FINDINGS OF BILE DUCT INJURY BY TACE. RADIOLOGISTS SHOULD NOT MISDIAGNOSE THIS CONDITION AS BILE DUCT INVASION BY THE TUMOR. IN THE PRESENT STUDY, ALL MAIN BILE DUCT STRICTURES DEVELOPED AFTER TACE OF A1 AND/OR A4. IN ADDITION, 50% OF BILE DUCT STRICTURES DEVELOPED EVEN AFTER A SINGLE TACE SESSION OF A1 AND/OR A4, SUGGESTING THAT SELECTIVE TACE OF A1 AND/OR A4 IS A MAIN CAUSE OF BILE DUCT NECROSIS. HOWEVER, NONSELECTIVE TACE OF THE RIGHT HEPATIC ARTERY OR LEFT HEPATIC ARTERY LEVEL MAY MAINLY DAMAGE "THE PERIPHERAL BRANCHES," WHEREAS "THE CENTRAL BRANCHES," SUCH AS A1 AND A4, MAY BE SLIGHTLY DAMAGED OR OCCASIONALLY PRESERVED. REPEAT TACE SESSIONS MAY FINALLY DAMAGE THESE CENTRAL BRANCHES BECAUSE THE PERIPHERAL BRANCHES ARE SEVERELY ATTENUATED BY PREVIOUS TACE PROCEDURES, AND EMBOLIC MATERIALS FLOWS MAINLY INTO THESE CENTRAL BRANCHES. 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. WE REPORTED THAT ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS TO ACHIEVE NOT ONLY COMPLETE TUMOR NECROSIS BUT ALSO MASSIVE PERITUMORAL NECROSIS BY BLOCKAGE OF BOTH THE HEPATIC ARTERIAL AND PORTAL BLOOD FLOW. 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. IT MAY BE DIFFICULT TO PREDICT MAIN BILE DUCT INJURY BY TACE. IN 3 PATIENTS UNDERGOING SELECTIVE CBCT DURING THE TACE PROCEDURE OF A1 AND/OR A4, BILE DUCT WALL ENHANCEMENT WAS CLEARLY DEMONSTRATED. CBCT MIGHT BE USEFUL FOR PREDICTING BILE DUCT INJURY CAUSED BY TACE. WE SHOULD ALWAYS BEAR IN MIND THAT SELECTIVE TACE OF A1 AND/ OR A4 CARRIES THE RISK OF CAUSING BILE DUCT NECROSIS. THEREFORE, COMPLETE BLOCKAGE OF THESE VESSELS SHOULD BE AVOIDED, ESPECIALLY WHEN BILE DUCT ENHANCEMENT IS SEEN ON CT OR CBCT DURING ARTERIOGRAPHY THROUGH A1 OR A4. IN ADDITION, DISTAL ADVANCEMENT OF A THINNER MICROCATHETER WITH A TIP \2F INTO A1 OR A4 MAY BE USEFUL TO AVOID EMBOLIZATION OF SMALL VESSELS SUPPLYING THE MAIN BILE DUCTS BECAUSE THESE VESSELS MAY BE ESTIMATED TO ARISE FROM THE PROXIMATE PORTION OF A1 AND A4. CT OBTAINED AT 1 WEEK AFTER TACE MAY ALSO BE USEFUL TO SUGGEST MAIN BILE DUCT DAMAGE. CHANGES IN LABORATORY DATA ARE NOT SUFFICIENTLY SENSITIVE, AND ABNORMALITIES MAY BECOME APPARENT LONG AFTER DEMONSTRATION OF BILE DUCT DILATATION ON CT IN MOST PATIENTS, ALTHOUGH MARKED CHANGES SUGGEST SEVERE DAMAGE TO THE MAIN BILE DUCTS. 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. METALLIC STENT PLACEMENT MAY BE USEFUL TO MANAGE MAIN BILE DUCT STRICTURE CAUSED BY TACE BECAUSE PATIENTS WITH INOPERABLE HCC ARE NOT GOOD CANDIDATES FOR SURGICAL BILE DUCT REPAIR. HOWEVER, BILE DUCT COMPLICATIONS MAY OCCUR AT HIGH RATES AFTER ADDITIONAL TACE SESSIONS. IN ADDITION, WE SHOULD BE WELL AWARE THAT INTRAHEPATIC BILE DUCT DILATATION IS A SIGNIFICANT RISK FACTOR IN DEVELOPING BILOMA AFTER TACE. 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. FOCAL AND SMOOTH BILE DUCT STRICTURES MAINLY AT THE CHD ARE CHARACTERISTIC FINDINGS, AND INTRALUMINAL COAGULA ARE FREQUENTLY DETECTED ON CT, MRI, AND CHOLANGIOGRAPHY. RADIOLOGISTS SHOULD WELL AWARE THIS UNCOMMON BUT SEVERE COMPLICATION OF TACE. A (B)(6) FEMALE PATIENT HAD ONE TUMOR MEASURING 16 MM IN DIAMETER. SEGMENT WAS S1 AND EMBOLIZED BRANCHES WAS A1. IODIZED OIL-ACCUMULATED PORTION: COMMON HEPATIC DUCT (CHD); SITE OF BILE DUCT DILATATION: BOTH. SHRINKAGE OF GALLBLADDER: + CHANGES IN BILE DUCT DILATATION: PROGRESSED; NO. OF ADDITIONAL TACE: 1; 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). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM, AND ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS AND LESS BILE DUCT COMPLICATIONS. IT WAS REPORTED THAT INTRAHEPATIC AND EXTRAHEPATIC BILE DUCTS WOULD BECOME NECROTIC IF SMALL PARTICLES <250 UM WERE USED. 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. 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). IN THIS STUDY, MAIN BILE DUCT STRICTURE DEVELOPED IN 18/446 (4.0%). SELECTIVE TACE OF A1 AND/OR A4 CARRIES A RISK OF MAIN BILE DUCT STRICTURE AT THE HEPATIC HILUM, AND ULTRASELECTIVE TACE HAS STRONG THERAPEUTIC EFFECTS AND LESS BILE DUCT COMPLICATIONS. IT WAS REPORTED THAT INTRAHEPATIC AND EXTRAHEPATIC BILE DUCTS WOULD BECOME NECROTIC IF SMALL PARTICLES <250 UM WERE USED. 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. 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 |
|---|---|---|---|---|---|---|---|
| 569346 | GELFOAM | SPONGE, STERILE; CLASS III | LMF | PFIZER, INC. (DEVICE) |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 76 YR | Other| R | FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| FARMORUBICIN.| IOMERON.| IOMERON.| IOMERON.| IOMERON.| IOMERON.| IOMERON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| IOPAMIRON.| LIPIODOL.| LIPIODOL.| LIPIODOL.| LIPIODOL.| LIPIODOL.| LIPIODOL.| MITOMYCIN C.| 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].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE].| XYLOCAINE [LIDOCAINE]. |