GELFOAM
Report
- Report Number
- 1810189-2023-00085
- Event Type
- Injury
- Date Received
- April 28, 2023
- Report Date
- April 13, 2023
- Manufacturer
- PFIZER, INC. (DEVICE)
- Product Code
- LMF
- PMA / PMN Number
- 18-286
- Adverse Event
- Yes
- Product Problem
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- CH
- Reporter Occupation
- OTHER
- Health Professional
- N
Narratives
CONCLUSIONS: THE COMPLAINT FOR 'ADVERSE EVENT MD/MDCP' FOR AN UNKNOWN BATCH OF GELFOAM SPONGE WAS INVESTIGATED. THE INVESTIGATION INCLUDED REVIEWING APRRS FOR THE PRODUCT AND A MEDICAL DEVICE TREND REVIEW. THE FINAL SCOPE WAS DETERMINED TO BE ALL BATCHES OF GELFOAM MANUFACTURED BY PFIZER KALAMAZOO WITHIN THE 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO THE RECEIPT DATE OF THE COMPLAINT. A COMPLAINT SAMPLE WAS NOT RETURNED. NO RELATED QUALITY ISSUES WERE IDENTIFIED DURING THE INVESTIGATION. NO ROOT CAUSE OR CAPA WERE IDENTIFIED AS THE COMPLAINT WAS NOT CONFIRMED. NO RELATED QUALITY DEFECTS WERE IDENTIFIED THROUGH INVESTIGATION. THERE IS NO IMPACT ON MEDICAL DEVICE QUALITY, REGULATORY, VALIDATION, OR STABILITY.
EVENT VERBATIM [PREFERRED TERM] INDICATION: PARTIAL SPLENIC EMBOLIZATION [OFF LABEL USE], INDICATION: PARTIAL SPLENIC EMBOLIZATION [DEVICE USE ISSUE], SPLENIC ABSCESS [SPLENIC ABSCESS], , NARRATIVE: THIS IS A LITERATURE REPORT FOR THE FOLLOWING LITERATURE SOURCE: "CLINICAL APPLICATION OF KELP MICRO GELATION (KMG) IN PARTIAL SPLENIC EMBOLIZATION", EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2018; VOL:22, PGS:1776-1781. INTRODUCTION: HYPERSPLENISM IS A COMMON COMPLICATION OF LIVER CIRRHOSIS WITH DECOMPENSATED PORTAL HYPERTENSION. THE TRADITIONAL SPLENECTOMY HAS GREAT TRAUMA, MULTIPLE COMPLICATIONS AND HIGH MORTALITY IN THE PERIOPERATIVE PERIOD. PARTIAL SPLENIC EMBOLIZATION (PSE) IS CHARACTERIZED BY SMALL OPERATION AREA, LESS COMPLICATIONS AND THE ABILITY TO KEEP PART OF THE SPLEEN FUNCTION IN COMPARISON TO TRADITIONAL SPLENECTOMY. THEREFORE, IT HAS BEEN WIDELY APPLIED TO TREAT LEUKOPENIA AND THROMBOCYTOPENIA INDUCED BY HYPERSPLENISM. THE MAIN MATERIALS FOR EMBOLISM IN TRADITIONAL PSE INCLUDE GELFOAM PARTICLES 3-5 AND STAINLESS STEEL COIL6, IN WHICH GELFOAM PARTICLES IS MORE COMMON DUE TO ITS LOW COST AND HIGH AVAILABILITY. CLINICAL DATA SHOWED THAT SPLENIC EMBOLIZATION CAN SUBSTANTIALLY IMPROVE PERIPHERAL HEMOGRAM, THUS AMELIORATING THE HYPERSPLENISM IN EARLY STAGE. NEVERTHELESS, THE LONG-TERM EFFICACY WAS LESS SATISFACTORY. THE CURRENT STUDY WAS CONDUCTED TO COMPARE THE EFFICACY OF GELFOAM PARTICLES AND PERMANENT HISTOCOMPATIBLE KELP MICRO GELATION (KMG) (OD OF 350-560 UM) A. IN COMPARISON TO GELFOAM PARTICLES, KMG HAS AN EASY ACCESS TO SPLEEN SINUSOID AND A LONG DEGRADATION TIME IN VIVO. THEORETICALLY SPEAKING, KMG SHALL ACHIEVE A BETTER EFFICACY THAN GELFOAM PARTICLES DUE TO EXCELLENT EMBOLIZATION ABILITY. HOWEVER, THERE IS LITTLE RESEARCH ON THE APPLICATION OF KMG IN PSE. IN ADDITION, THE LITERATURE COMPARING THE LONG-TERM EFFICACY BETWEEN KMG AND GELFOAM PARTICLES IS EVEN LESS. IN THIS WORK, WE AIMED TO COMPARE AND ANALYZE THE LONG-TERM EFFICACY AND SAFETY BETWEEN KMG AND GELFOAM PARTICLES IN PSE. PATIENTS AND METHODS: PATIENTS: THE AUTHORS RETROSPECTIVELY INCLUDED 65 LIVER CIRRHOSIS PATIENTS WITH COMORBIDITY OF HYPERSPLENISM WHO WERE ADMITTED IN HOSPITAL FROM (B)(6) 2008 TO (B)(6) 2012. THERE WERE 47 MALE AND 18 FEMALE WITH AN AVERAGE AGE OF 51.43 YEARS (RANGING FROM 19 TO 80 YEARS). AMONG THE INCLUDED PATIENTS, 33 PATIENTS (25 MALES AND 8 FEMALES) WERE IN KMG-PSE GROUP, WITH AN AVERAGE AGE OF 51.06 YEARS (RANGING FROM 19 TO 80 YEARS). 32 CASES (22 MALES AND 10 FEMALES) WERE INCLUDED IN GELFOAM-PSE GROUP, WITH AN AVERAGE AGE OF 51.88 +- 9.84 YEARS (RANGING FROM 29 TO 74 YEARS). ACCORDING TO CHILD-PUGH CRITERIA, THERE ARE 24 CASES IN GRADE A, 32 CASES IN GRADE B AND 9 CASES IN GRADE C. ALL ELIGIBLE PATIENTS RECEIVED CT OR MR EXAMINATION/LABORATORY EXAMINATION AND WERE DIAGNOSED WITH LIVER CIRRHOSIS COMPLICATED WITH HYPERSPLENISM. NO SIGNIFICANT DIFFERENCE WAS OBSERVED IN AGE, SEX, LIVER FUNCTION GRADE, PREOPERATIONAL PERIPHERAL BLOOD CELL NUMBERS AND EMBOLIZATION DEGREE BETWEEN THE TWO GROUPS (ALL P>0.05), IMPLYING THAT THE PATIENTS IN THE TWO GROUPS WERE COMPARABLE. BASELINE CHARACTERISTICS OF PATIENTS WERE SHOWN IN TABLE I. THIS INVESTIGATION WAS APPROVED BY THE ETHICS COMMITTEE OF THE HOSPITAL. SIGNED WRITTEN INFORMED CONSENT WAS OBTAINED FROM ALL PARTICIPANTS BEFORE THE STUDY. INCLUSION AND EXCLUSION CRITERIA: THE INCLUSION CRITERIA ARE AS FOLLOWS: LIVER CIRRHOSIS, SPLEEN ENLARGEMENT, WITH COMORBIDITIES OF THROMBOCYTOPENIA AND LEUKOPENIA, WHITE BLOOD CELL (WBC) NO MORE THAN 60 X 109/L AND/OR WBC NO MORE THAN 3 X109/L. THE EXCLUSION CRITERIA INCLUDE: (1) PATIENTS WITH SEVERE INFECTION, SEPTICOPYEMIA, OR WITH COMORBIDITIES OF SPONTANEOUS PERITONITIS WHICH MAY RESULT IN SPLENIC ABSCESS; (2) PROTHROMBIN TIME SHORTER THAN 70% OF THAT IN NORMAL PEOPLE; (3) PATIENTS WITH MEGALOSPLENIA, SEVERE JAUNDICE OR SEROPERITONEUM AND (4) PATIENTS HAD OTHER ADVANCED DISEASES. PATIENTS MEETING ABOVE CRITERIA WERE INCLUDED IN THE STUDY AND GROUPED IN TO KMG-PSE GROUP AND GELFOAM-PSE GROUP ACCORDING TO THEIR EMBOLIZATION MATERIALS. PROCESS OF PSE ALL PROCESSES WERE CONDUCTED IN ASEPTIC CONDITION AND ALL PATIENTS WERE SUBJECTED TO LOCAL ANESTHESIA. THE OPERATIONS WERE AS FOLLOWS: 5F SHEATH WERE INSERTED THROUGH FEMORAL ARTERY PUNCTURE. UNDER THE GUIDANCE OF GUIDE WIRE, THE CATHETER WAS LED TO THE COELIAC TRUNK ARTERY FOR RADIOGRAPHY. AFTER THE OPENING OF THE SPLENIC ARTERY WAS DETERMINED, THE SUPER SELECTIVE CATHETER WAS INSERTED, THROUGH WHICH THE MICRO-CATHETER AND SUPPER SELECTIVE CATHETER WERE LED TO THE ARTERIAL BRANCHES OF INTERMEDIATE AND LOWER PART OF THE SPLEEN, AVOIDING ANY OTHER POSSIBLE BLOOD SUPPLY BRANCHES. GELFOAM PARTICLES (50-500 UM) OR KMG (300-500 UM) PRE-SOAKED IN SOLUTION OF GENTAMICIN (80,000 U) WITH NORMAL SALINE WAS USED FOR EMBOLIZATION OF SPLEEN UNDER MONITORING. DURING THE EMBOLIZATION, POLYSOMNOGRAPHY WAS CONDUCTED TO ASSESS THE EMBOLIZATION DEGREE TILL THE EMBOLIZATION REACHED 40-70% OF THE WHOLE SPLEEN. FOR PATIENTS WITH BIGGER SPLEEN, THE EMBOLIZATION MAY SLIGHTLY BE DECREASED (30-40%). THE EMBOLIZATION WAS ASSESSED BY OPERATOR AND EXPERIENCE DSA TECHNICIANS (FIGURES 1 AND 2). THE FINAL EMBOLIZATION WAS DETERMINED BY CT AFTER 2 WEEKS OF PSE. THE POST-OPERATIONAL TREATMENT INCLUDED ANALGESIA AND TEMPERATURE COOLING. FOLLOW-UP: ALL PATIENTS WERE NOT ALLOWED TO DISCHARGE FROM HOSPITAL UNTIL THE COMPLICATIONS OF EMBOLIZATION AND SEVERE POST-OPERATIONAL COMPLICATIONS WERE DISAPPEARED. AFTER PATIENTS WERE DISCHARGED, FOLLOW-UP WAS CONDUCTED BY OUTPATIENT DEPARTMENT. THE ROUTINE EXAMINATIONS FOR PERIPHERAL BLOOD INCLUDE ITEMS FOR WBC, BLOOD PLATELET (PLT) AND RED BLOOD CELL (RBC). PATIENTS WERE EXAMINED BEFORE OPERATION, AND AT 7 D, 15 D AND 1 MONTH AFTER OPERATION; THEREAFTER, ONCE EVERY THREE MONTHS TILL THE 3RD YEAR. THE COMPLICATIONS DURING FOLLOW-UP WERE CHECKED AND RECORDED. ALL PATIENTS WERE SUBJECTED TO CT OR MR 2 WEEKS AFTER PSE TO REASSESS THE EMBOLIZATION, BY COMPARING WITH THE PREOPERATIONAL CT IMAGES. THE EMBOLIZATION WAS DETERMINED BY CALCULATION BY WORKING STATION. EVERY SIX MONTHS AFTER OPERATION, PATIENTS ARE REQUIRED FOR CT/MR EXAMINATION. STATISTICAL ANALYSIS: THE COMPARISONS BETWEEN TWO GROUPS WERE CONDUCTED USING T-TEST OR X2-TEST. THE COMPARISONS BETWEEN PREOPERATIONAL AND POST-OPERATIONAL PARAMETERS WERE ANALYZED USING PAIRWISE T-TEST. DATA WERE PROCESSED USING STATISTICAL PRODUCT AND SERVICE SOLUTIONS 18.0 SOFTWARE (SPSS INC., CHICAGO, IL, USA). P<0.05 WAS CONSIDERED AS STATISTICALLY SIGNIFICANT. RESULTS: LONG-TERM FOLLOW-UP: A TOTAL OF 65 PATIENTS SUCCESSFULLY RECEIVED PSE. THE FOAM USED IN PATIENTS IN GELFOAM-PSE GROUP WAS 2 CMX 6 CM AND THE PARTICLE USED IN PATIENTS IN KMG GROUP WAS NO MORE THAN 1.0 G KMG (HALF BOTTLE). DURING THE FOLLOW-UP, 5 CASES DIED FROM LIVER CANCER WITHIN 2 YEARS AFTER PSE, 2 CASES RECEIVED SURGICAL RESECTION DUE TO CONSTANT PAIN IN SPLEEN, AND 2 CASES WERE LOST IN FOLLOW-UP. THE REST OF THE PATIENTS WERE FOLLOWED UP TILL THE 3RD YEAR AFTER OPERATION. COMPARISONS OF PREOPERATIONAL PERIPHERAL BLOOD CELL NUMBERS BEFORE AND AFTER OPERATION COMPARISONS OF PREOPERATIONAL PERIPHERAL BLOOD CELL NUMBERS BEFORE AND AFTER OPERATION WERE SHOWN IN TABLE II AND III. NO SIGNIFICANT DIFFERENCES WERE OBSERVED IN WBC AND PLT BETWEEN THE TWO GROUPS (P>0.05). THE WBC AND PLT MEASURED ON 2 WEEKS AFTER OPERATION AND 3 YEARS AFTER OPERATION WERE SUBSTANTIALLY HIGHER THAN THOSE MEASURED BEFORE OPERATION (P<0.001). THE WBC AND PLT MEASURED ON DIFFERENT FOLLOW-UP TIME POINTS IN KMG GROUP WERE SIGNIFICANT HIGHER THAN THOSE IN GELFOAM-PSE GROUP (P<0.05). COMPARISONS OF COMMON COMPLICATIONS AFTER SPLEEN EMBOLIZATION: THE MOST COMMON COMPLICATIONS AFTER SPLEEN EMBOLIZATION INCLUDE PAIN, FEVER, NAUSEA AND VOMITING (TABLE IV). THE COMPLICATIONS OCCURRED BETWEEN BOTH GROUPS HAD NO SIGNIFICANT DIFFERENCE (ALL P>0.05). COMPARISONS OF SEVERE COMPLICATIONS BETWEEN TWO GROUPS AFTER SPLEEN: EMBOLIZATION: 5 CASES OF SEVERE COMPLICATION WERE REPORTED IN KMG GROUP (15.2%) AND 7 CASES WERE IDENTIFIED IN GELFOAM-PSE GROUP (21.9%) AFTER PSE FOR 1 MONTH, AMONG WHICH 2 PATIENTS RECEIVED PARACENTESIS AND PROTEIN SUPPLEMENTATION DUE TO PLEURAL EFFUSION, PERITONEUM EFFUSION, DYSPNEA, ABDOMINAL DISTENSION AND ABDOMINAL PAIN; 3 PATIENTS RECEIVED ADDITIONAL THERAPY DUE TO BACTERIAL PERITONITIS; 1 PATIENT DIED FROM GASTROINTESTINAL BLEEDING (ESOPHAHEAL VARICEAL BLEEDING); 2 PATIENTS HAD CONSTANT HIGH FEVER (> 38.5°C) AND WERE CONFIRMED AS SPLENIC ABSCESS USING BLOOD CULTIVATION AND CT SCANNING (1 RECEIVED PARACENTESIS AND RECOVERED AND 1 RECEIVED SURGICAL RESECTION); 3 PATIENTS HAD PORTAL VENOUS THROMBOSIS, WHILE NO ADDITIONAL THERAPY WAS CONDUCTED (THROMBOSIS WAS DISSOLVED IN 2 CASES DURING FOLLOW UP) (TABLE V). COMPLICATION ON EMBOLIZATION AND COMPLICATION: AMONG THE 12 PATIENTS WHO HAD SEVERE COMPLICATION, THE EMBOLIZATION IN 10 PATIENTS WAS GREATER THAN 70%, AND THE REST HAD EMBOLIZATION LESS THAN 70%. AMONG THE 47 PATIENTS WHO HAD EMBOLIZATION LESS THAN 70%, SEVERE COMPLICATIONS WERE FOUND IN 2 CASES 1 MONTH AFTER OPERATION (3.7%); AMONG THE 16 PATIENTS WHO HAD EMBOLIZATION GREATER THAN 70%, SEVERE COMPLICATIONS WERE FOUND IN 10 CASES 1 MONTH AFTER OPERATION (62.5%). USING THE EMBOLIZATION OF 70% AS CUT-OFF VALUE, PATIENTS WERE GROUPED INTO LARGE EMBOLIZATION AREA (>70%) AND SMALL EMBOLIZATION AREA (NO MORE THAN 70%). THE COMPLICATIONS WERE INDICATED IN TABLE V. PATIENTS WITH LARGE EMBOLIZATION AREA HAD A SIGNIFICANTLY HIGHER COMPLICATION RATE (P<0.001). DISCUSSION: PSE HAS BEEN THE OPTIMAL STRATEGY TO DECREASE PORTAL VENOUS PRESSURE AND TO IMPROVE HYPERSPLENISM, REPLACING SURGICAL SPLEEN RESECTION. AMONG THE EMBOLIZATION AGENTS USED IN PSE, INCLUDING STAINLESS STEEL COIL, GELFOAM PARTICLES AND PVA, GELFOAM PARTICLES HAVE BEEN THE MOST COMMON USED DUE TO THEIR HIGH AVAILABILITY, LOW COST AND RELATIVELY SATISFYING SHORT-TERM EFFICACY. HOWEVER, THE LONG-TERM EFFICACY OF GELFOAM WAS LESS SATISFACTORY. THIS IS POSSIBLY CAUSED BY THE LARGE SIZE OF GELFOAM PARTICLES, WHICH MAY LEAD TO EMBOLIZATION OF SPLENIC ARTERY BRACHES AND CONSEQUENTLY RESULT IN SEVERE COMPLICATION AND UNCOMPLETE SPLEEN NECROSIS. IN COMPARISON, SODIUM ALGINATE (THE MATERIAL FOR KMG) HAS THE FOLLOW BIOLOGICAL MATERIAL WITH GOOD BIOCOMPATIBILITY; (2) COMPARED WITH PVA, IT HAS SATISFACTORY BIODEGRADABILITY, WHICH CAN BE DEGRADED INTO POLYSACCHARIDE, MANNOSE AND GLUCOSE AFTER 3 TO 6 MONTHS. IN ADDITION, IT HAS NO SIDE-EFFECT TO HUMAN BODY, AS IT IS NON-TOXIC AND CAN BE DISCHARGED WITH THE URINE; (3) IT CAN BE SPECIALLY MADE SO AS TO ADJUST EMBOLIZATION REQUIREMENTS AND CAN BE ENLARGED IN BLOOD FOR ACCURATE INSERTION IN TARGET VESSELS. GELFOAM PARTICLES CAUSE VASCULAR EMBOLIZATION PREDOMINANTLY DUE TO MECHANICAL EMBOLIZATION AND THE PROMOTION OF THROMBUS FORMATION. THE TIME OF OCCLUSION OF THE TARGETING BLOOD VESSELS RANGES FROM A FEW DAYS TO A FEW MONTHS. HOWEVER, RECANALIZATION MAY OCCUR IF THE AMOUNT OF GELFOAM USED IS NOT ENOUGH OR THE OCCLUSION IS NOT ENOUGH STRONG, THEREBY RESULTING IN RECURRENCE IN THE SHORT- AND MEDIUM-TERM OF EMBOLIC CASES. IN COMPARISON, WHEN KMG IS DISSOLVED IN WATER, IT CAN FORM A VISCOUS COLLOID AND PRODUCE MACROMOLECULAR CROSS-LINKING, AND BECOME SOLIDITY. THIS IS THE MECHANISM OF ITS PERMANENT EMBOLIC EFFECT. BESIDES, THIS LONG-TERM STABILITY ALSO EFFECTIVELY REDUCES THE POSSIBILITY OF ABSORPTION IN THE DISEASED VASCULAR IN THE EARLY AND MEDIUM-TERM STAGES. CURRENTLY, THERE ARE A FEW STUDIES REPORTING THE APPLICATION OF KMG IN PSE. THEREFORE, THE AUTHORS AIMED TO COMPARE THE LONG-TERM EFFICACY OF KMG AND GELFOAM PARTICLES ON SPLEEN EMBOLIZATION AND TO DETECT WHETHER KMG WAS ABLE TO IMPROVE WBC AND PLT IN PATIENTS WHO UNDERGONE PSE. THE AUTHORS' DATA SHOWED THAT BOTH KMG AND GELFOAM PARTICLES COULD SUBSTANTIALLY IMPROVE THROMBOCYTOPENIA LEUKOPENIA IN SHORT-TERM. HOWEVER, THE EFFECTS OF KMG ARE SUPERIOR TO THAT OF GELFOAM GROUP IN SHORT- AND LONG-TERM. THE AUTHORS VERIFIED THE SAFETY OF KMG IN HYPERSPLENISM AND FOUND NO SIGNIFICANT DIFFERENCE BETWEEN GELFOAM PARTICLES AND KMG GROUPS. THE SEVERE COMPLICATIONS AFTER PSE WERE REPORTED IN OTHER STUDIES. SAKAI ET AL SHOWED AMONG THE 17 LIVER CIRRHOSIS PATIENTS WITH HYPERSPLENISM AND RECEIVED PSE USING GELFOAM PARTICLES, 2 PATIENTS HAD SEVERE COMPLICATIONS, ONE OF WHICH DIED DUE TO THE DETERIORATION OF LIVER FUNCTION AND LIVER FAILURE. VUJIC ET AL REPORTED 3 DEATHS DUE TO LIVER FAILURE, PNEUMONIA, SEPTICOPYEMIA AND ABSCESS AFTER PSE USING GELFOAM PARTICLES FOR 6 WEEKS. OTHER STUDIES USING GELFOAM PARTICLES ALSO REPORTED SEVERE COMPLICATIONS SUCH AS PLEURAL AND PERITONEUM EFFUSION, SPLEEN RUPTURE AND PORTAL VENOUS THROMBOSIS. IN ABOVE RESEARCHES, THE PATIENTS WITH GRADE C LIVER FUNCTION AND GREAT EMBOLIZATION DEGREE HAD A SIGNIFICANTLY HIGHER RISK OF SEVERE COMPLICATIONS. THIS STUDY ALSO IDENTIFIED THAT PATIENTS WITH EMBOLIZATION GREATER THAN 70% SUFFERED MORE POST-OPERATIONAL COMPLICATIONS. IN THIS REGARD, THE EMBOLIZATION SHOULD BE CONTROLLED UNDER 70% REGARDLESS OF THE EMBOLIZATION AGENTS. CONCLUSIONS: KMG CAN BE USED AS A SAFE AND EFFECTIVE EMBOLIZATION AGENT IN PSE. IT HAS SUPERIOR EFFECTS COMPARED TO GELFOAM PARTICLES IN PSE IN BOTH SHORT-TERM AND LONG-TERM. THE EMBOLIZATION AREA SHOULD BE CONTROLLED WITHIN 70%. FOLLOW-UP (06DEC2023): THIS IS A FOLLOW-UP REPORT FROM PRODUCT QUALITY COMPLAINT GROUP PROVIDING THE FOLLOWING INVESTIGATION RESULTS: CONCLUSIONS: THE COMPLAINT FOR 'ADVERSE EVENT MD/MDCP' FOR AN UNKNOWN BATCH OF GELFOAM SPONGE WAS INVESTIGATED. THE INVESTIGATION INCLUDED REVIEWING APRRS FOR THE PRODUCT AND A MEDICAL DEVICE TREND REVIEW. THE FINAL SCOPE WAS DETERMINED TO BE ALL BATCHES OF GELFOAM MANUFACTURED BY PFIZER KALAMAZOO WITHIN THE 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO THE RECEIPT DATE OF THE COMPLAINT. A COMPLAINT SAMPLE WAS NOT RETURNED. NO RELATED QUALITY ISSUES WERE IDENTIFIED DURING THE INVESTIGATION. NO ROOT CAUSE OR CAPA WERE IDENTIFIED AS THE COMPLAINT WAS NOT CONFIRMED. NO RELATED QUALITY DEFECTS WERE IDENTIFIED THROUGH INVESTIGATION. THERE IS NO IMPACT ON MEDICAL DEVICE QUALITY, REGULATORY, VALIDATION, OR STABILITY. NO FOLLOW-UP ATTEMPTS ARE POSSIBLE. NO FURTHER INFORMATION IS EXPECTED., COMMENT: BASED ON THE AVAILABLE INFORMATION, A POSSIBLE CONTRIBUTORY ROLE OF SUBJECT PRODUCT, ABSORBABLE GELATIN, CANNOT BE EXCLUDED FOR THE REPORTED EVENT OF SPLENIC ABSCESS, BASED ON TEMPORAL RELATIONSHIP AND THE KNOWN PRODUCT SAFETY PROFILE. HOWEVER, THE REPORTED EVENT MAY POSSIBLY REPRESENT A POTENTIAL COMPLICATION OF THE SURGICAL PROCEDURE OF PARTIAL SPLENIC EMBOLIZATION. THERE IS LIMITED INFORMATION PROVIDED IN THIS REPORT. THIS CASE WILL BE REASSESSED UPON RECEIPT OF FOLLOW-UP INFORMATION.
EVENT VERBATIM [PREFERRED TERM]. INDICATION: PARTIAL SPLENIC EMBOLIZATION [OFF LABEL USE], SPLENIC ABSCESS [SPLENIC ABSCESS]. NARRATIVE: THIS IS A LITERATURE REPORT FOR THE FOLLOWING LITERATURE SOURCE: "CLINICAL APPLICATION OF KELP MICRO GELATION (KMG) IN PARTIAL SPLENIC EMBOLIZATION", EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2018; VOL:22, PGS:1776-1781. INTRODUCTION: HYPERSPLENISM IS A COMMON COMPLICATION OF LIVER CIRRHOSIS WITH DECOMPENSATED PORTAL HYPERTENSION. THE TRADITIONAL SPLENECTOMY HAS GREAT TRAUMA, MULTIPLE COMPLICATIONS AND HIGH MORTALITY IN THE PERIOPERATIVE PERIOD. PARTIAL SPLENIC EMBOLIZATION (PSE) IS CHARACTERIZED BY SMALL OPERATION AREA, LESS COMPLICATIONS AND THE ABILITY TO KEEP PART OF THE SPLEEN FUNCTION IN COMPARISON TO TRADITIONAL SPLENECTOMY. THEREFORE, IT HAS BEEN WIDELY APPLIED TO TREAT LEUKOPENIA AND THROMBOCYTOPENIA INDUCED BY HYPERSPLENISM. THE MAIN MATERIALS FOR EMBOLISM IN TRADITIONAL PSE INCLUDE GELFOAM PARTICLES 3-5 AND STAINLESS STEEL COIL6, IN WHICH GELFOAM PARTICLES IS MORE COMMON DUE TO ITS LOW COST AND HIGH AVAILABILITY. CLINICAL DATA SHOWED THAT SPLENIC EMBOLIZATION CAN SUBSTANTIALLY IMPROVE PERIPHERAL HEMOGRAM, THUS AMELIORATING THE HYPERSPLENISM IN EARLY STAGE. NEVERTHELESS, THE LONG-TERM EFFICACY WAS LESS SATISFACTORY. THE CURRENT STUDY WAS CONDUCTED TO COMPARE THE EFFICACY OF GELFOAM PARTICLES AND PERMANENT HISTOCOMPATIBLE KELP MICRO GELATION (KMG) (OD OF 350-560 UM) A. IN COMPARISON TO GELFOAM PARTICLES, KMG HAS AN EASY ACCESS TO SPLEEN SINUSOID AND A LONG DEGRADATION TIME IN VIVO. THEORETICALLY SPEAKING, KMG SHALL ACHIEVE A BETTER EFFICACY THAN GELFOAM PARTICLES DUE TO EXCELLENT EMBOLIZATION ABILITY. HOWEVER, THERE IS LITTLE RESEARCH ON THE APPLICATION OF KMG IN PSE. IN ADDITION, THE LITERATURE COMPARING THE LONG-TERM EFFICACY BETWEEN KMG AND GELFOAM PARTICLES IS EVEN LESS. IN THIS WORK, WE AIMED TO COMPARE AND ANALYZE THE LONG-TERM EFFICACY AND SAFETY BETWEEN KMG AND GELFOAM PARTICLES IN PSE. PATIENTS AND METHODS: PATIENTS: THE AUTHORS RETROSPECTIVELY INCLUDED 65 LIVER CIRRHOSIS PATIENTS WITH COMORBIDITY OF HYPERSPLENISM WHO WERE ADMITTED IN HOSPITAL FROM JULY 2008 TO MAY 2012. THERE WERE 47 MALE AND 18 FEMALE WITH AN AVERAGE AGE OF 51.43 YEARS (RANGING FROM 19 TO 80 YEARS). AMONG THE INCLUDED PATIENTS, 33 PATIENTS (25 MALES AND 8 FEMALES) WERE IN KMG-PSE GROUP, WITH AN AVERAGE AGE OF 51.06 YEARS (RANGING FROM 19 TO 80 YEARS). 32 CASES (22 MALES AND 10 FEMALES) WERE INCLUDED IN GELFOAM-PSE GROUP, WITH AN AVERAGE AGE OF 51.88 +- 9.84 YEARS (RANGING FROM 29 TO 74 YEARS). ACCORDING TO CHILD-PUGH CRITERIA, THERE ARE 24 CASES IN GRADE A, 32 CASES IN GRADE B AND 9 CASES IN GRADE C. ALL ELIGIBLE PATIENTS RECEIVED CT OR MR EXAMINATION/LABORATORY EXAMINATION AND WERE DIAGNOSED WITH LIVER CIRRHOSIS COMPLICATED WITH HYPERSPLENISM. NO SIGNIFICANT DIFFERENCE WAS OBSERVED IN AGE, SEX, LIVER FUNCTION GRADE, PREOPERATIONAL PERIPHERAL BLOOD CELL NUMBERS AND EMBOLIZATION DEGREE BETWEEN THE TWO GROUPS (ALL P>0.05), IMPLYING THAT THE PATIENTS IN THE TWO GROUPS WERE COMPARABLE. BASELINE CHARACTERISTICS OF PATIENTS WERE SHOWN IN TABLE I. THIS INVESTIGATION WAS APPROVED BY THE ETHICS COMMITTEE OF THE HOSPITAL. SIGNED WRITTEN INFORMED CONSENT WAS OBTAINED FROM ALL PARTICIPANTS BEFORE THE STUDY. INCLUSION AND EXCLUSION CRITERIA: THE INCLUSION CRITERIA ARE AS FOLLOWS: LIVER CIRRHOSIS, SPLEEN ENLARGEMENT, WITH COMORBIDITIES OF THROMBOCYTOPENIA AND LEUKOPENIA, WHITE BLOOD CELL (WBC) NO MORE THAN 60 X 109/L AND/OR WBC NO MORE THAN 3 X109/L. THE EXCLUSION CRITERIA INCLUDE: (1) PATIENTS WITH SEVERE INFECTION, SEPTICOPYEMIA, OR WITH COMORBIDITIES OF SPONTANEOUS PERITONITIS WHICH MAY RESULT IN SPLENIC ABSCESS; (2) PROTHROMBIN TIME SHORTER THAN 70% OF THAT IN NORMAL PEOPLE; (3) PATIENTS WITH MEGALOSPLENIA, SEVERE JAUNDICE OR SEROPERITONEUM AND (4) PATIENTS HAD OTHER ADVANCED DISEASES. PATIENTS MEETING ABOVE CRITERIA WERE INCLUDED IN THE STUDY AND GROUPED IN TO KMG-PSE GROUP AND GELFOAM-PSE GROUP ACCORDING TO THEIR EMBOLIZATION MATERIALS. PROCESS OF PSE ALL PROCESSES WERE CONDUCTED IN ASEPTIC CONDITION AND ALL PATIENTS WERE SUBJECTED TO LOCAL ANESTHESIA. THE OPERATIONS WERE AS FOLLOWS: 5F SHEATH WERE INSERTED THROUGH FEMORAL ARTERY PUNCTURE. UNDER THE GUIDANCE OF GUIDE WIRE, THE CATHETER WAS LED TO THE COELIAC TRUNK ARTERY FOR RADIOGRAPHY. AFTER THE OPENING OF THE SPLENIC ARTERY WAS DETERMINED, THE SUPER SELECTIVE CATHETER WAS INSERTED, THROUGH WHICH THE MICRO-CATHETER AND SUPPER SELECTIVE CATHETER WERE LED TO THE ARTERIAL BRANCHES OF INTERMEDIATE AND LOWER PART OF THE SPLEEN, AVOIDING ANY OTHER POSSIBLE BLOOD SUPPLY BRANCHES. GELFOAM PARTICLES (50-500 UM) OR KMG (300-500 UM) PRE-SOAKED IN SOLUTION OF GENTAMICIN (80,000 U) WITH NORMAL SALINE WAS USED FOR EMBOLIZATION OF SPLEEN UNDER MONITORING. DURING THE EMBOLIZATION, POLYSOMNOGRAPHY WAS CONDUCTED TO ASSESS THE EMBOLIZATION DEGREE TILL THE EMBOLIZATION REACHED 40-70% OF THE WHOLE SPLEEN. FOR PATIENTS WITH BIGGER SPLEEN, THE EMBOLIZATION MAY SLIGHTLY BE DECREASED (30-40%). THE EMBOLIZATION WAS ASSESSED BY OPERATOR AND EXPERIENCE DSA TECHNICIANS (FIGURES 1 AND 2). THE FINAL EMBOLIZATION WAS DETERMINED BY CT AFTER 2 WEEKS OF PSE. THE POST-OPERATIONAL TREATMENT INCLUDED ANALGESIA AND TEMPERATURE COOLING. FOLLOW-UP: ALL PATIENTS WERE NOT ALLOWED TO DISCHARGE FROM HOSPITAL UNTIL THE COMPLICATIONS OF EMBOLIZATION AND SEVERE POST-OPERATIONAL COMPLICATIONS WERE DISAPPEARED. AFTER PATIENTS WERE DISCHARGED, FOLLOW-UP WAS CONDUCTED BY OUTPATIENT DEPARTMENT. THE ROUTINE EXAMINATIONS FOR PERIPHERAL BLOOD INCLUDE ITEMS FOR WBC, BLOOD PLATELET (PLT) AND RED BLOOD CELL (RBC). PATIENTS WERE EXAMINED BEFORE OPERATION, AND AT 7 D, 15 D AND 1 MONTH AFTER OPERATION; THEREAFTER, ONCE EVERY THREE MONTHS TILL THE 3RD YEAR. THE COMPLICATIONS DURING FOLLOW-UP WERE CHECKED AND RECORDED. ALL PATIENTS WERE SUBJECTED TO CT OR MR 2 WEEKS AFTER PSE TO REASSESS THE EMBOLIZATION, BY COMPARING WITH THE PREOPERATIONAL CT IMAGES. THE EMBOLIZATION WAS DETERMINED BY CALCULATION BY WORKING STATION. EVERY SIX MONTHS AFTER OPERATION, PATIENTS ARE REQUIRED FOR CT/MR EXAMINATION. STATISTICAL ANALYSIS: THE COMPARISONS BETWEEN TWO GROUPS WERE CONDUCTED USING T-TEST OR X2-TEST. THE COMPARISONS BETWEEN PREOPERATIONAL AND POST-OPERATIONAL PARAMETERS WERE ANALYZED USING PAIRWISE T-TEST. DATA WERE PROCESSED USING STATISTICAL PRODUCT AND SERVICE SOLUTIONS 18.0 SOFTWARE (SPSS INC., CHICAGO, IL, USA). P<0.05 WAS CONSIDERED AS STATISTICALLY SIGNIFICANT. RESULTS: LONG-TERM FOLLOW-UP: A TOTAL OF 65 PATIENTS SUCCESSFULLY RECEIVED PSE. THE FOAM USED IN PATIENTS IN GELFOAM-PSE GROUP WAS 2 CMX 6 CM AND THE PARTICLE USED IN PATIENTS IN KMG GROUP WAS NO MORE THAN 1.0 G KMG (HALF BOTTLE). DURING THE FOLLOW-UP, 5 CASES DIED FROM LIVER CANCER WITHIN 2 YEARS AFTER PSE, 2 CASES RECEIVED SURGICAL RESECTION DUE TO CONSTANT PAIN IN SPLEEN, AND 2 CASES WERE LOST IN FOLLOW-UP. THE REST OF THE PATIENTS WERE FOLLOWED UP TILL THE 3RD YEAR AFTER OPERATION. COMPARISONS OF PREOPERATIONAL PERIPHERAL BLOOD CELL NUMBERS BEFORE AND AFTER OPERATION COMPARISONS OF PREOPERATIONAL PERIPHERAL BLOOD CELL NUMBERS BEFORE AND AFTER OPERATION WERE SHOWN IN TABLE II AND III. NO SIGNIFICANT DIFFERENCES WERE OBSERVED IN WBC AND PLT BETWEEN THE TWO GROUPS (P>0.05). THE WBC AND PLT MEASURED ON 2 WEEKS AFTER OPERATION AND 3 YEARS AFTER OPERATION WERE SUBSTANTIALLY HIGHER THAN THOSE MEASURED BEFORE OPERATION (P<0.001). THE WBC AND PLT MEASURED ON DIFFERENT FOLLOW-UP TIME POINTS IN KMG GROUP WERE SIGNIFICANT HIGHER THAN THOSE IN GELFOAM-PSE GROUP (P<0.05). COMPARISONS OF COMMON COMPLICATIONS AFTER SPLEEN EMBOLIZATION: THE MOST COMMON COMPLICATIONS AFTER SPLEEN EMBOLIZATION INCLUDE PAIN, FEVER, NAUSEA AND VOMITING (TABLE IV). THE COMPLICATIONS OCCURRED BETWEEN BOTH GROUPS HAD NO SIGNIFICANT DIFFERENCE (ALL P>0.05). COMPARISONS OF SEVERE COMPLICATIONS BETWEEN TWO GROUPS AFTER SPLEEN: EMBOLIZATION: 5 CASES OF SEVERE COMPLICATION WERE REPORTED IN KMG GROUP (15.2%) AND 7 CASES WERE IDENTIFIED IN GELFOAM-PSE GROUP (21.9%) AFTER PSE FOR 1 MONTH, AMONG WHICH 2 PATIENTS RECEIVED PARACENTESIS AND PROTEIN SUPPLEMENTATION DUE TO PLEURAL EFFUSION, PERITONEUM EFFUSION, DYSPNEA, ABDOMINAL DISTENSION AND ABDOMINAL PAIN; 3 PATIENTS RECEIVED ADDITIONAL THERAPY DUE TO BACTERIAL PERITONITIS; 1 PATIENT DIED FROM GASTROINTESTINAL BLEEDING (ESOPHAHEAL VARICEAL BLEEDING); 2 PATIENTS HAD CONSTANT HIGH FEVER (> 38.5°C) AND WERE CONFIRMED AS SPLENIC ABSCESS USING BLOOD CULTIVATION AND CT SCANNING (1 RECEIVED PARACENTESIS AND RECOVERED AND 1 RECEIVED SURGICAL RESECTION); 3 PATIENTS HAD PORTAL VENOUS THROMBOSIS, WHILE NO ADDITIONAL THERAPY WAS CONDUCTED (THROMBOSIS WAS DISSOLVED IN 2 CASES DURING FOLLOW UP) (TABLE V). COMPLICATION ON EMBOLIZATION AND COMPLICATION: AMONG THE 12 PATIENTS WHO HAD SEVERE COMPLICATION, THE EMBOLIZATION IN 10 PATIENTS WAS GREATER THAN 70%, AND THE REST HAD EMBOLIZATION LESS THAN 70%. AMONG THE 47 PATIENTS WHO HAD EMBOLIZATION LESS THAN 70%, SEVERE COMPLICATIONS WERE FOUND IN 2 CASES 1 MONTH AFTER OPERATION (3.7%); AMONG THE 16 PATIENTS WHO HAD EMBOLIZATION GREATER THAN 70%, SEVERE COMPLICATIONS WERE FOUND IN 10 CASES 1 MONTH AFTER OPERATION (62.5%). USING THE EMBOLIZATION OF 70% AS CUT-OFF VALUE, PATIENTS WERE GROUPED INTO LARGE EMBOLIZATION AREA (>70%) AND SMALL EMBOLIZATION AREA (NO MORE THAN 70%). THE COMPLICATIONS WERE INDICATED IN TABLE V. PATIENTS WITH LARGE EMBOLIZATION AREA HAD A SIGNIFICANTLY HIGHER COMPLICATION RATE (P<0.001). DISCUSSION: PSE HAS BEEN THE OPTIMAL STRATEGY TO DECREASE PORTAL VENOUS PRESSURE AND TO IMPROVE HYPERSPLENISM, REPLACING SURGICAL SPLEEN RESECTION. AMONG THE EMBOLIZATION AGENTS USED IN PSE, INCLUDING STAINLESS STEEL COIL, GELFOAM PARTICLES AND PVA, GELFOAM PARTICLES HAVE BEEN THE MOST COMMON USED DUE TO THEIR HIGH AVAILABILITY, LOW COST AND RELATIVELY SATISFYING SHORT-TERM EFFICACY. HOWEVER, THE LONG-TERM EFFICACY OF GELFOAM WAS LESS SATISFACTORY. THIS IS POSSIBLY CAUSED BY THE LARGE SIZE OF GELFOAM PARTICLES, WHICH MAY LEAD TO EMBOLIZATION OF SPLENIC ARTERY BRACHES AND CONSEQUENTLY RESULT IN SEVERE COMPLICATION AND UNCOMPLETE SPLEEN NECROSIS. IN COMPARISON, SODIUM ALGINATE (THE MATERIAL FOR KMG) HAS THE FOLLOW BIOLOGICAL MATERIAL WITH GOOD BIOCOMPATIBILITY; (2) COMPARED WITH PVA, IT HAS SATISFACTORY BIODEGRADABILITY, WHICH CAN BE DEGRADED INTO POLYSACCHARIDE, MANNOSE AND GLUCOSE AFTER 3 TO 6 MONTHS. IN ADDITION, IT HAS NO SIDE-EFFECT TO HUMAN BODY, AS IT IS NON-TOXIC AND CAN BE DISCHARGED WITH THE URINE; (3) IT CAN BE SPECIALLY MADE SO AS TO ADJUST EMBOLIZATION REQUIREMENTS AND CAN BE ENLARGED IN BLOOD FOR ACCURATE INSERTION IN TARGET VESSELS. GELFOAM PARTICLES CAUSE VASCULAR EMBOLIZATION PREDOMINANTLY DUE TO MECHANICAL EMBOLIZATION AND THE PROMOTION OF THROMBUS FORMATION. THE TIME OF OCCLUSION OF THE TARGETING BLOOD VESSELS RANGES FROM A FEW DAYS TO A FEW MONTHS. HOWEVER, RECANALIZATION MAY OCCUR IF THE AMOUNT OF GELFOAM USED IS NOT ENOUGH OR THE OCCLUSION IS NOT ENOUGH STRONG, THEREBY RESULTING IN RECURRENCE IN THE SHORT- AND MEDIUM-TERM OF EMBOLIC CASES. IN COMPARISON, WHEN KMG IS DISSOLVED IN WATER, IT CAN FORM A VISCOUS COLLOID AND PRODUCE MACROMOLECULAR CROSS-LINKING, AND BECOME SOLIDITY. THIS IS THE MECHANISM OF ITS PERMANENT EMBOLIC EFFECT. BESIDES, THIS LONG-TERM STABILITY ALSO EFFECTIVELY REDUCES THE POSSIBILITY OF ABSORPTION IN THE DISEASED VASCULAR IN THE EARLY AND MEDIUM-TERM STAGES. CURRENTLY, THERE ARE A FEW STUDIES REPORTING THE APPLICATION OF KMG IN PSE. THEREFORE, THE AUTHORS AIMED TO COMPARE THE LONG-TERM EFFICACY OF KMG AND GELFOAM PARTICLES ON SPLEEN EMBOLIZATION AND TO DETECT WHETHER KMG WAS ABLE TO IMPROVE WBC AND PLT IN PATIENTS WHO UNDERGONE PSE. THE AUTHORS' DATA SHOWED THAT BOTH KMG AND GELFOAM PARTICLES COULD SUBSTANTIALLY IMPROVE THROMBOCYTOPENIA LEUKOPENIA IN SHORT-TERM. HOWEVER, THE EFFECTS OF KMG ARE SUPERIOR TO THAT OF GELFOAM GROUP IN SHORT- AND LONG-TERM. THE AUTHORS VERIFIED THE SAFETY OF KMG IN HYPERSPLENISM AND FOUND NO SIGNIFICANT DIFFERENCE BETWEEN GELFOAM PARTICLES AND KMG GROUPS. THE SEVERE COMPLICATIONS AFTER PSE WERE REPORTED IN OTHER STUDIES. SAKAI ET AL SHOWED AMONG THE 17 LIVER CIRRHOSIS PATIENTS WITH HYPERSPLENISM AND RECEIVED PSE USING GELFOAM PARTICLES, 2 PATIENTS HAD SEVERE COMPLICATIONS, ONE OF WHICH DIED DUE TO THE DETERIORATION OF LIVER FUNCTION AND LIVER FAILURE. VUJIC ET AL REPORTED 3 DEATHS DUE TO LIVER FAILURE, PNEUMONIA, SEPTICOPYEMIA AND ABSCESS AFTER PSE USING GELFOAM PARTICLES FOR 6 WEEKS. OTHER STUDIES USING GELFOAM PARTICLES ALSO REPORTED SEVERE COMPLICATIONS SUCH AS PLEURAL AND PERITONEUM EFFUSION, SPLEEN RUPTURE AND PORTAL VENOUS THROMBOSIS. IN ABOVE RESEARCHES, THE PATIENTS WITH GRADE C LIVER FUNCTION AND GREAT EMBOLIZATION DEGREE HAD A SIGNIFICANTLY HIGHER RISK OF SEVERE COMPLICATIONS. THIS STUDY ALSO IDENTIFIED THAT PATIENTS WITH EMBOLIZATION GREATER THAN 70% SUFFERED MORE POST-OPERATIONAL COMPLICATIONS. IN THIS REGARD, THE EMBOLIZATION SHOULD BE CONTROLLED UNDER 70% REGARDLESS OF THE EMBOLIZATION AGENTS. CONCLUSIONS: KMG CAN BE USED AS A SAFE AND EFFECTIVE EMBOLIZATION AGENT IN PSE. IT HAS SUPERIOR EFFECTS COMPARED TO GELFOAM PARTICLES IN PSE IN BOTH SHORT-TERM AND LONG-TERM. THE EMBOLIZATION AREA SHOULD BE CONTROLLED WITHIN 70%., COMMENT: BASED ON THE AVAILABLE INFORMATION, A POSSIBLE CONTRIBUTORY ROLE OF SUBJECT PRODUCT, ABSORBABLE GELATIN, CANNOT BE EXCLUDED FOR THE REPORTED EVENT OF SPLENIC ABSCESS, BASED ON TEMPORAL RELATIONSHIP AND THE KNOWN PRODUCT SAFETY PROFILE. HOWEVER, THE REPORTED EVENT MAY POSSIBLY REPRESENT A POTENTIAL COMPLICATION OF THE SURGICAL PROCEDURE OF PARTIAL SPLENIC EMBOLIZATION. THERE IS LIMITED INFORMATION PROVIDED IN THIS REPORT. THIS CASE WILL BE REASSESSED UPON RECEIPT OF FOLLOW-UP INFORMATION.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 476298 | GELFOAM | SPONGE, STERILE; CLASS III | LMF | PFIZER, INC. (DEVICE) |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | Unknown | Other| R |