EPICEL (CULTURED EPIDERMAL AUTOGRAFTS) GRAFT
Report
- Report Number
- 1226230-2011-00003
- Event Type
- Other
- Date Received
- May 6, 2011
- Date of Event
- March 1, 1994
- Report Date
- April 25, 2011
- Manufacturer
- GENZYME BIOSURGERY (CAMBRIDGE)
- Product Code
- MGR
- PMA / PMN Number
- HDE 990002
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- MA, US
- Reporter Occupation
- PHYSICIAN
Narratives
EVALUATION SUMMARY: ON (B)(4) 2011, ADDITIONAL INFORMATION WAS RECEIVED IN THE FORM OF QA RESULTS WITHOUT A LOT NUMBER . THE PRODUCT LOT NUMBER WAS NOT PROVIDED, THEREFORE A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR CONFORMANCE TO SPECIFICATIONS PRIOR TO RELEASE. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT. GENZYME WILL CONTINUE TO MONITOR COMPLAINTS. MANUFACTURER'S COMMENT: THE BENEFIT-RISK RELATIONSHIP OF EPICEL IS NOT AFFECTED BY THIS REPORT.
REPORT SOURCE LITERATURE DESCRIPTION: JOURNAL: PLASTIC AND RECONSTRUCTIVE SURGERY, OCTOBER 2004. AUTHOR: DR. CHRISTOPH THEOPOLD. TITLE: GRAFT SITE MALIGNANCY FOLLOWING TREATMENT OF FULL-THICKNESS BURN WITH CULTURED EPIDERMAL AUTOGRAFT. YEAR: 2004. JOURNAL: PLASTIC AND RECONSTRUCTIVE SURGERY. GLOBAL OPEN 3 7 (08/10/2015): E460. AUTHOR: DR. MANSHER SINGH. TITLE: INVASIVE SQUAMOUS CELL CARCINOMA IN FULL-THICKNESS BURN WOUNDS AFTER TREATMENT WITH CULTURED EPITHELIAL AUTOGRAFTS. VOLUME: 3(7), YEAR: 2015.
ADDITIONAL INFORMATION WAS RECEIVED ON (B)(6) 2012 FROM THE PHYSICIAN. THE PHYSICIAN CONFIRMED THAT CEA WAS A GENZYME PRODUCT (EPICEL) AND UPDATED THE PATIENT INITIALS TO (B)(6). THE PHYSICIAN REPORTED THAT THE PATIENT IS DOING FINE. AS OF THE DATE OF RECEIPT OF THIS REPORT, THE PHYSICIAN WAS UNABLE TO PROVIDE THE LOT NUMBER INFORMATION. REPORT SOURCE: JOURNAL: IDEAS AND INNOVATIONS. AUTHOR: CHRISTOPH THEOPOLD, M.B.B.S., M.A., M.R.C.S.ED, DANIELA HOELLER, DR. MED., PATRIK VELANDER, M.B.B.CH, B.A.O., A.F.R.C.S.I., ROBERT DEMLING M.D., PHD, AND ELOF ERIKSSON, M.D., PHD. TITLE: GRAFT SITE MALIGNANCY FOLLOWING TREATMENT OF FULL-THICKNESS BURN WITH CULTURED EPIDERMAL AUTOGRAFT. YEAR: 2003. THE PRODUCT LOT NUMBER WAS NOT PROVIDED THEREFORE; A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR CONFORMANCE TO SPECIFICATIONS PRIOR TO RELEASE. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT. GENZYME WILL CONTINUE TO MONITOR COMPLAINTS.
REPORT SOURCE LITERATURE DESCRIPTION: JOURNAL: IDEAS AND INNOVATIONS, AUTHOR: CHRISTOPH THEOPOLD, M.B.B.S., M.A., M.R.C.S.ED., DANIELA HOELLER, DR. MED., PATRIK VELANDER, M.B.B.CH., B.A.O., A.F.R.C.S.I., ROBERT DEMLING, M.D., PH.D., AND ELOF ERIKSSON, M.D., PH.D. TITLE: GRAFT SITE MALIGNANCY FOLLOWING TREATMENT OF FULL-THICKNESS BURN WITH CULTURED EPIDERMAL AUTOGRAFT. YEAR: 2003. ADD'L INFO RECEIVED ON FEBRUARY 23, 2012 FROM THE AUTHOR AND TREATING PHYSICIAN PROVIDED THE FOLLOWING. THE PT WAS A 32 Y/O WHITE MALE, PREVIOUSLY HEALTHY, WITH NO PAST MEDICAL HISTORY AND TYPE II-III SKIN TYPE WHO WAS HOSPITALIZED ON (B)(6) 1989 AFTER BEING INVOLVED IN AN EXPLOSION WHILE WORKING IN A MANHOLE RESULTING IN 95% TOTAL BODY SURFACE AREA (TBSA) THIRD DEGREE BURNS. THE PT DID NOT APPEAR TO HAVE MUCH OF AN INHALATION INJURY ON ADMISSION. MEDICATIONS ON ADMISSION INCLUDED COMPAZINE PERCOCET, BENADRYL, HALCION, ATIVAN, DICLOXACILLIN, INDERAL AND MULTIVITAMIN. THE PT WAS ADMITTED TO THE BURN INTENSIVE CARE UNIT (ICU) WHERE HIS WOUNDS WERE TREATED WITH SILVADEINE. DURING THE SEVEN MONTH HOSPITALIZATION, THE PT UNDERWENT MULTIPLE DEBRIDEMENTS. AFTER DEBRIDEMENT THE BURNED SKIN AREAS WERE FIRST COVERED WITH BIOBRANE AND THEN REPLACED WITH SPLIT-THICKNESS SKIN GRAFTS FROM THE PT'S FEET. WHILE ALLOWING HIS FEET TO HEAL THE PT WAS THEN COVERED WITH CADAVER DONOR SKIN. SMALL AMOUNTS OF SKIN WERE OBTAINED AND GROWN IN CULTURED MEDIA TO PRODUCE EPICEL THAT WAS ALSO PLACED OVER HIS BODY. AREAS WHERE EPICEL WAS PLACED WERE NOT PROVIDED ALTHOUGH ONE OPERATIVE NOTE STATED THAT LOWER EXTREMITY GRAFTING WAS DONE WITH CULTURED EPITHELIAL AUTOGRAPHS. OVER TIME THE PT WAS GRAFT WITH SPLIT THICKNESS SKIN GRAFTS FROM HIS FEET AS THEY WOULD HEAL AND HE REUSED EACH TIME. WHILE HOSPITALIZED THE PT REMAINED THERMODYNAMICALLY STABLE BUT DID DEVELOP EPISODES OF PNEUMONIA TREATED WITH INTRAVENOUS ANTIBIOTICS, AS WELL AS DEVELOPING URINARY TRACT INFECTIONS. AS THE WOUNDS WERE HEALING THE PT WAS TREATED WITH (B)(6) TO GRAFTED AREAS AND GENTAMICIN O TO ALL OPEN AREAS. THE PT WAS ALSO RECEIVING DICLOXACICLIN ORALLY FOR A SMALL SUPERFICIAL WOUND INFECTION (LOCATION NOT PROVIDED) AND TO COVER THE PERIOPERATIVE PLASTIC SURGERY PROCEDURES. EVAL SUMMARY: THE PRODUCT LOT NUMBER WAS NOT PROVIDED THEREFORE, A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR CONFORMANCE TO SPECS PRIOR TO RELEASE. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT GENZYME WILL CONTINUE TO MONITOR COMPLAINTS. ON (B)(6) 1990, THE PT UNDERWENT PENILE CONTRACTURE RELEASE AND SPLIT THICKNESS SKIN GRAFTING TO THE EYELIDS. A CORNEAL BURN WAS ALSO NOTED WITH PLANS FOR A CORNEAL TRANSPLANT. ON (B)(6) 1990, THE PT WAS DISCHARGED TO A REHABILITATION FACILITY. ON (B)(6) 1994, PT WAS HOSPITALIZED FOR TREATMENT OF SEVERAL, SMALL LEFT LOWER EXTREMITY ULCERS THAT HAD BEEN OOZING SEROSANGUINEOUS FLUID. AT THIS TIME, PHYSICAL EXAMINATION OF THE LEFT LOWER EXTREMITY NOTED MULTIPLE ULCERATED LESIONS THAT WERE COVERED WITH WET TO DRY DRESSINGS. THE PT UNDERWENT DEBRIDEMENT, AS WELL AS SPLIT THICKNESS SKIN GRAFTING, OF THE LEFT LOWER EXTREMITY ULCERS. DURING THIS TIME, THE PT WAS TREATED PERIOPERATIVELY AND PROPHYLACTICALLY THROUGHOUT HIS HOSPITALIZATION WITH VARIOUS ANTIBIOTICS INCLUDING VANCOMYCIN, CEFTAZIDIME, AND CLINDAMYCIN. THE PT DID WELL DURING THE HOSPITALIZATION, THE GRAFTS REMAINED INTACT AND HEALED WELL AND ON (B)(6) 1994, THE PT WAS DISCHARGED TO HOME ON DICLOXACILLIN. ON (B)(6) 1994, THE PT WAS HOSPITALIZED FOR THE DEVELOPMENT OF SKIN ULCERATIONS ON THE RIGHT LATERAL KNEE AND LEFT LOWER LEG. THE ULCERATIVE AREAS OCCURRED AFTER MINOR TRAUMA (BUMPING A CAR BUMPER AND HIT WITH A BASEBALL IN THE LOWER EXTREMITY.) PHYSICAL EXAMINATION AT THE TIME OF HOSPITALIZATION NOTED THE LEFT LATERAL KNEE WITH AN OPEN WOULD APPROX 6X7 CM WITH ERYTHEMA SURROUNDING THE EDGES AND SERIOUS DRAINAGE AT THE NECROTIC BASE; RIGHT LATERAL KNEE WITH AN OPEN WOUND APPROX 6X4 CM WITH A NECROTIC BASE, NO ERYTHEMA BUT WITH SEROUS DRAINAGE AND UNEVEN EDGES TO THE WOUND, RIGHT ANTEROLATERAL KNEE WITH A 3X3 CM OPEN WOUND; RIGHT MEDIAL THIGH WITH A 3X3 CM OPEN WOULD WITH A NECROTIC BASE. THE PT UNDERWENT WOULD DEBRIDEMENT AND POSTOPERATIVELY WAS PLACED ON INTRAVENOUS (IV) VANCOMYCIN AND CEFTAZ GIVEN WOUND CULTURE RESULTS RETURNED (B)(6) FOR (B)(6) AND PSEUDOMONAS. ON OCTOBER 24, 1994, THE PT UNDERWENT SPLIT THICKNESS SKIN GRAFTING FROM THE DONOR SITE OF THE LEFT FOREARM TO THE RIGHT AND LEFT LOWER EXTREMITY WOUNDS. CULTURE OF THE WOUND SPECIMENS CONTINUED TO GROW (B)(6) AND PSEUDOMONAS; THEREFORE, IV GENTAMICIN WAS ADDED TO THE ANTIBIOTIC REGIMEN. THE PT RECEIVED A 7 DAY COURSE OF IV GENTAMICIN AND 14 DAY COURSE OF VANCOMYCIN AND CEFTAZ. THE PT WAS DISCHARGED ON (B)(6) 1994 ON KEFLEX AND AT THAT TIME THE GRAFT SITES WERE NOTED TO BE HEALING WELL, ALTHOUGH THE RIGHT MEDIAL THIGH GRAFT SITE WAS SOMEWHAT CRUSTY IN NATURE. ON (B)(6) 1997, THE PT WAS HOSPITALIZED FOR ULCERATIVE SKIN BREAKDOWN AND ON THIS DAY UNDERWENT DEBRIDEMENT OF THE RIGHT AND LEFT LEG ULCERS AND ON (B)(6) 1997 UNDERWENT SPLIT THICKNESS SKIN GRAFTING FOR THE LEFT ARM TO THE LEGS. PT WAS DISCHARGED TO HOME WITH SERVICES ON (B)(6) 1997 AND DISCHARGE MEDICATIONS INCLUDED TOBRAMYCIN IV. VANCOMYCIN IV AND LAC-HYDRIN 12%. DOCUMENTATION OF SURGICAL PROCEDURES AND/OR PATHOLOGY REPORTS PROVIDED FROM THE YEARS 2002 UNTIL 2008 NOTED THAT MULTIPLE AREAS OF THE LOWER EXTREMITIES WERE BIOPSIED OVER THESE YEARS WITH BIOPSY RESULTS REVEALING SQUAMOUS CELL CARCINOMA (SCC) INCLUDING VERRUCOUS SQUAMOUS CARCINOMA AND INVASIVE WELL-DIFFERENTIATED SCC. ON (B)(6) 2011, THE PT UNDERWENT DEBRIDEMENT OF SIX CHRONIC ULCERS IN THE LOWER EXTREMITIES. POSTOPERATIVE DIAGNOSIS FOR ALL LESIONS WAS NOTED AS "CHRONIC ULCER" WITH NO INDICATION OF MALIGNANCY. ON (B)(6) 2011, THE PT UNDERWENT DEBRIDEMENT AND SPLIT SKIN GRAFTING TO 6 OPEN WOUNDS ON THE LEFT LOWER EXTREMITY AND 2 OPEN WOUNDS ON THE RIGHT LOWER EXTREMITY. THE SITE WHERE THE SKIN GRAFT WERE HARVESTED WAS FROM THE LEFT FOREARM. AS OF (B)(6) 2012, THE TREATING PHYSICIAN INDICATED THAT THE PT WAS "DOING WELL". THE INTENSITIES FOR THE EVENTS OF "WOUND INFECTION, PNEUMONIA, URINE TRACT INFECTION, CORNEAL BURN AND SKIN CONTRACTURE OF THE PENIS" WERE NOT PROVIDED. THE RELATIONSHIP BETWEEN EPICEL AND THE EVENTS OF "WOUND INFECTIONS, PNEUMONIA, URINE TRACT INFECTION, CORNEAL BURN AND SKIN CONTRACTURE OF THE PENIS" WERE NOT PROVIDED BY THE REPORTING PHYSICIAN.
THE PATHOLOGY REPORTS, REGARDING THE PATIENT'S PATHOLOGY SLIDES, WERE REVIEWED BY AN INDEPENDENT PATHOLOGIST WITH THE PATHOLOGISTS REPORT RECEIVED ON (B)(6) 2012. THE PATHOLOGIST DESCRIBED THE FOLLOWING. FIVE PATHOLOGY REPORTS RANGING IN DATES FROM (B)(6) 2002 UNTIL (B)(6) 2003 WERE RECEIVED. EACH WAS OF AN EXCISION OR BIOPSY OF A SQUAMOUS CELL CARCINOMA OF THE LEFT LEG THE FIRST OF (B)(6) 2002 FROM THE LEFT KNEE DEBRIDEMENT WAS A SQUAMOUS CELL CARCINOMA DESCRIBED WELL DIFFERENTIATED AND VERRUCOUS (BIOPSY ONLY). THE SECOND FROM THE LEFT THIGH EXCISION OF (B)(6) 2003 WAS 7 MM IN THICKNESS, AND WAS DESCRIBED AS WELL DIFFERENTIATED. THE THIRD SPECIMEN LEFT ANTERIOR LATERAL THIGH RE-EXCISION OF (B)(6) 2003 WAS DESCRIBED AS WELL DIFFERENTIATED AND MEASURED 2.5 MM IN THICKNESS. THE FOURTH OF (B)(6) 2003 LEFT LEG, EXCISION WAS DESCRIBED AS WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMA MEASURING 3.5 MM IN THICKNESS, MARGINS INVOLVED. THE FIFTH OF (B)(6) 2003, LEFT LOWER LEG, EXCISION WAS DESCRIBED AS A WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMA 3.7 MM IN THICKNESS ADEQUATELY EXCISED. EVALUATION SUMMARY: THE PRODUCT LOT NUMBER WAS NOT PROVIDED THEREFORE; A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR CONFORMANCE TO SPECIFICATIONS PRIOR TO RELEASE. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT. GENZYME WILL CONTINUE TO MONITOR COMPLAINTS.
ADDITIONAL INFORMATION: SQUAMOUS CELL CARCINOMA [SQUAMOUS CELL CARCINOMA]. SKIN ULCERATION [SKIN ULCER]. WOUND INFECTIONS [WOUND INFECTION]. CASE DESCRIPTION: NARRATIVE LITERATURE REPORT WAS RECEIVED ON 04/25/2011 FROM A PHYSICIAN REGARDING A (B)(6) YEAR OLD MALE PATIENT, INITIALS NOT PROVIDED WHO EXPERIENCED SQUAMOUS CELL CARCINOMA AFTER RECEIVING EPICXEL. THIS REPORT IS FROM A LITERATURE ARTICLE TITLED "GRAFT SITE MALIGNANCY FOLLOWING TREATMENT OF FULL-THICKNESS BURN WITH CULTURED EPIDERMAL AUTOGRAFT". THEOPOLD, C., D HOELLER, P. VELANDER, R DEMLING, AND E. ERICKSSON, IDEAS AND INNOVATIONS, 2003. THE PATIENT WAS INVOLVED IN A GAS EXPLOSION AND SUSTAINED 95 PERCENT BURNS. DURING THE PATIENT'S STAY IN THE INTENSIVE CARE UNIT, THE BURNT SKIN WAS WIDELY EXCISED DOWN TO THE FASCIA OR THE SUB-CUTANEOUS FAT. MAJORITY OF THE PATIENT'S BODY (CHEST, ABDOMEN, FACE, AND UPPER AND LOWER EXTREMITIES ANTERIORLY AND POSTERIORLY) WAS COVERED WITH CULTURED EPIDERMAL AUTOGRAFTS (CEA). THE LOWER EXTREMITIES HAD TO BE GRAFTED THREE TIMES IN VARIOUS PLACES FOR THE GRAFTS TO TAKE. THE PATIENT WAS DISCHARGED FROM THE HOSPITAL SIX MONTHS AFTER THE INITIAL INJURY. BUT AFTER THAT, THE PATIENT HAD TO BE RE-GRAFTED NUMEROUS TIMES DUE TO ULCERATION OF THE LOWER EXTREMITIES WHICH HAD BEEN GRAFTED BY THE CEA. ON 21 DIFFERENT OCCASIONS, THE ULCERATED AREAS HAD TO BE DEBRIDED AND WERE COVERED WITH SKIN GRAFTS FROM THE FOREARM. THIRTEEN YEARS AND SIX MONTHS AFTER THE INITIAL INJURY, THE PATIENT DEVELOPED VERRUCOUS SQUAMOUS CELL CARCINOMA. FIVE MONTHS LATER, THE PATIENT DEVELOPED A LESION ON HIS LEFT ANTERIOR THIGH. PATHOLOGICAL EXAMINATION REVEALED WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMA. THIS AREA WAS EXCISED AND GRAFTED WITH SPLIT-THICKNESS SKIN FROM THE LEFT FOREARM. TWO MONTHS LATER, TWO NEW LESIONS DEVELOPED ON THE LEFT ANTERIOR THIGH CLOSE TO BUT DISTINCT FROM THE PREVIOUSLY EXCISED AREA. THESE WERE BOTH WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMAS THAT WERE EXCISED DOWN TO THE FASCIA. THESE AREAS WERE SUBSEQUENTLY GRAFTED WITH SPLIT-THICKNESS SKIN. A FIFTH LESION GREW JUST DISTAL TO THE LEFT FIBULAR HEAD. PATHOLOGICAL EXAMINATION REVEALED SQUAMOUS CELL CARCINOMA THAT WAS EXCISED TO CLEAR MARGINS AND GRAFTED WITH SPLIT-THICKNESS SKIN. ALL THE LESIONS DEVELOPED IN THE BURNT AREAS THAT WERE COVERED WITH THE CEA IN THE FIRST THREE MONTHS AFTER THE BURN. THE PATIENT IS STILL UNDER CLOSE SUPERVISION. THERE IS NO EVIDENCE OF LOCAL RECURRENCE OR DISTANT METASTASIS IN THE PATIENT. FOR OTHER EVENTS REPORTED BY THE REPORTER, PLEASE REFER TO MANUFACTURER CONTROL NUMBER (B)(4). ON (B)(6) 2011, ADDITIONAL INFORMATION WAS RECEIVED IN THE FORM OF QA RESULTS WITHOUT A LOT NUMBER. THE PRODUCT LOT NUMBER WAS NOT PROVIDED THEREFORE, A BATCH RECORD REVIEW IS NOT POSSIBLE. IT IS THE REQUIREMENT TO REVIEW ALL FINISHED BATCH RECORDS FOR CONFORMANCE TO SPECIFICATIONS PRIOR TO RELEASE. DATA IS PERIODICALLY PRESENTED AND REVIEWED BY INDIVIDUALS RESPONSIBLE FOR ASSURING PRODUCT QUALITY. THIS REVIEW HAS NOT INDICATED TRENDS THAT COULD BE ASSOCIATED WITH ANY PRODUCT COMPLAINT. GENZYME WILL CONTINUE TO MONITOR COMPLAINTS. ADDITIONAL INFORMATION WAS RECEIVED ON 01/30/2012 FROM THE PHYSICIAN. THE PHYSICIAN CONFIRMED THAT CEA WAS A GENZYME PRODUCT (EPICEL) AND UPDATED THE PATIENT INITIALS TO (B)(6). THE PHYSICIAN REPORTED THAT THE PATIENT IS DOING FINE. AS OF THE DATE OF RECEIPT OF THIS REPORT, THE PHYSICIAN WAS UNABLE TO PROVIDE THE LOT NUMBER INFORMATION. ADDITIONAL INFORMATION RECEIVED ON 02/23/2012 FROM THE AUTHOR AND TREATING PHYSICIAN PROVIDED THE FOLLOWING: THE PATIENT WAS A (B)(6) YEAR OLD WHITE MALE, PREVIOUSLY HEALTHY, WITH NO PAST MEDICAL HISTORY AND TYPE II-III SKIN TYPE WHO WAS HOSPITALIZED ON (B)(6) 1989 AFTER BEING INVOLVED IN AN EXPLOSION WHILE WORKING IN A MANHOLE RESULTING IN 95 PERCENT TOTAL BODY SURFACE AREA (TBSA) THIRD DEGREE BURNS. THE PATIENT DID NOT APPEAR TO HAVE MUCH OF AN INHALATION INJURY ON ADMISSION. MEDICATIONS ON ADMISSION INCLUDED COMPAZINE, PERCOCET, BENADRYL, HALCION, ATIVAN, DICLOXACILLIN, INDERAL AND MULTIVITAMIN. THE PATIENT WAS ADMITTED TO THE BURN INTENSIVE CARE UNIT (ICU) WHERE HIS WOUNDS WERE TREATED WITH SILVADENE. DURING THE SEVEN MONTH HOSPITALIZATION THE PATIENT UNDERWENT MULTIPLE DEBRIDEMENTS. AFTER DEBRIDEMENT THE BURNED SKIN AREAS WERE FIRST COVERED WITH BIOBRANE AND THEN REPLACED WITH SPLIT THICKNESS SKIN GRAFTS FROM THE PATIENT'S FEET. WHILE ALLOWING HIS FEET TO HEAL THE PATIENT WAS THEN COVERED WITH CADAVER DONOR SKIN. SMALL AMOUNTS OF SKIN WERE OBTAINED AND GROWN IN CULTURED MEDIA TO PRODUCE EPICEL THAT WAS ALSO PLACED OVER HIS BODY. AREAS WHERE EPICEL WAS PLACED WERE NOT PROVIDED ALTHOUGH ONE OPERATIVE NOTE STATED THAT LOWER EXTREMITY GRAFTING WAS DONE WITH CULTURED EPITHELIAL AUTOGRAPHS. OVER TIME THE PATIENT WAS GRAFTED WITH SPLIT THICKNESS SKIN GRAFTS FROM HIS FEET AS THEY WOULD HEAL AND BE REUSED EACH TIME. WHILE HOSPITALIZED THE PATIENT REMAINED THERMODYNAMICALLY STABLE BUT DID DEVELOP EPISODES OF PNEUMONIA TREATED WITH INTRAVENOUS ANTIBIOTICS, AS WELL AS DEVELOPING URINARY TRACT INFECTIONS. AS THE WOUNDS WERE HEALING THE PATIENT WAS TREATED WITH EUCERIN TO GRAFTED AREAS AND GENTAMICIN O TO ALL OPEN AREAS. THE PATIENT WAS ALSO RECEIVING DICLOXACILLIN ORALLY FOR A SMALL SUPERFICIAL WOUND INFECTION (LOCATION NOT PROVIDED) AND TO COVER THE PERIOPERATIVE PLASTIC SURGERY PROCEDURES. ON 03/13/1990, THE PATIENT UNDERWENT PENILE CONTRACTURE RELEASE AND SPLIT THICKNESS SKIN GRAFTING TO THE EYELIDS. A CORNEAL BURN WAS ALSO NOTED WITH PLANS FOR A CORNEAL TRANSPLANT. ON 03/26/1990 THE PATIENT WAS DISCHARGED TO A REHABILITATION FACILITY. ON 03/01/1994, PATIENT WAS HOSPITALIZED FOR TREATMENT OF SEVERAL, SMALL LEFT LOWER EXTREMITY ULCERS THAT HAD BEEN OOZING SEROSANGUINEOUS FLUID. AT THIS TIME, PHYSICAL EXAMINATION OF THE LEFT LOWER EXTREMITY NOTED MULTIPLE ULCERATED LESIONS THAT WERE COVERED WITH WET TO DRY DRESSINGS. THE PATIENT UNDERWENT DEBRIDEMENT, AS WELL AS SPLIT THICKNESS SKIN GRAFTING, OF THE LEFT LOWER EXTREMITY ULCERS. DURING THIS TIME THE PATIENT WAS TREATED PERIOPERATIVELY AND PROPHYLACTICALLY THROUGHOUT HIS HOSPITALIZATION WITH VARIOUS ANTIBIOTICS INCLUDING VANCOMYCIN, CEFTAZIDIME, AND CLINDAMYCIN. THE PATIENT DID WELL DURING THE HOSPITALIZATION, THE GRAFTS REMAINED INTACT AND HEALED WELL AND ON 03/17/1994, THE PATIENT WAS DISCHARGED TO HOME ON DICLOXACILLIN. ON 10/19/1994, THE PATIENT WAS HOSPITALIZED FOR THE DEVELOPMENT OF SKIN ULCERATIONS ON THE RIGHT LATERAL KNEE AND LEFT LOWER LEG. THE ULCERATIVE AREAS OCCURRED AFTER MINOR TRAUMA (BUMPING A CAR BUMPER AND HIT WITH A BASEBALL IN THE LOWER EXTREMITY). PHYSICAL EXAMINATION AT THE TIME OF HOSPITALIZATION NOTED THE LEFT LATERAL KNEE WITH AN OPEN WOUND APPROXIMATELY 6X7 CM WITH ERYTHEMA SURROUNDING THE EDGES AND SERIOUS DRAINAGE AT THE NECROTIC BASE, RIGHT LATERAL KNEE WITH AN OPEN WOUND APPROXIMATELY 6X7 CM WITH ERYTHEMA SURROUNDING THE EDGES AND SERIOUS DRAINAGE AT THE NECROTIC BASE, RIGHT LATERAL KNEE WITH AN OPEN WOUND APPROXIMATELY 6X4 CM WITH AN NECROTIC BASE, NO ERYTHEMA BUT WITH SERIOUS DRAINAGE AND UNEVEN EDGES TO THE WOUND, RIGHT ANTEROLATERAL KNEE WITH A 3X3 CM OPEN WOUND; RIGHT MEDIAL THIGH WITH A 3X3 CM OPEN WOUND WITH A NECROTIC BASE. THE PATIENT UNDERWENT WOUND DEBRIDEMENT AND POSTOPERATIVELY WAS PLACED ON INTRAVENOUS (IV) VANCOMYCIN AND CEFTAZ GIVEN WOUND CULTURE RESULTS RETURNED POSITIVE FOR MEZLOCILLIN-RESISTANT STAPH AUREUS AND PSEUDOMONAS. ON 10/24/1994, THE PATIENT UNDERWENT SPLIT THICKNESS SKIN GRAFTING FROM THE DONOR SITE OF THE LEFT FOREARM TO THE RIGHT AND LEFT LOWER EXTREMITY WOUNDS. CULTURE OF THE WOUND SPECIMENS CONTINUED TO GROW (B)(6) AND PSEUDOMONAS, THEREFORE, IV GENTAMICIN WAS ADDED TO THE ANTIBIOTIC REGIMEN. THE PATIENT RECEIVED A 7 DAY COURSE OF IV GENTAMICIN AND 14-DAY COURSE OF VANCOMYCIN AND CEFTAZ. THE PATIENT WAS DISCHARGED ON 11/04/1994 ON KEFLEX AND AT THAT TIME THE GRAFT SITES WERE NOTED TO BE HEALING WELL, ALTHOUGH THE RIGHT MEDIAL THIGH GRAFT SITE WAS SOMEWHAT CRUSTY IN NATURE. ON 01/21/1997, THE PATIENT WAS HOSPITALIZED FOR ULCERATIVE SKIN BREAKDOWN AND ON THIS DAY UNDERWENT DEBRIDEMENT OF THE RIGHT AND LEFT LEG ULCER'S AND ON 01/24/1997 UNDERWENT SPLIT THICKNESS SKIN GRAFTING FROM THE LEFT ARM TO THE LEGS. PATIENT WAS DISCHARGED TO HOME WITH SERVICES ON 01/28/1997 AND DISCHARGE MEDICATIONS INCLUDED TOBRAMYCIN IV, VANCOMYCIN IV AND LAC-HYDRIN 12 PERCENT. DOCUMENTATION OF SURGICAL PROCEDURES AND/OR PATHOLOGY REPORTS PROVIDED FROM THE YEARS 2002 UNTIL 2008 NOTED THAT MULTIPLE AREAS OF THE LOWER EXTREMITIES WERE BIOPSIED OVER THESE YEARS WITH BIOPSY RESULTS REVEALING SQUAMOUS CELL CARCINOMA (SCC) INCLUDING VERRUCOUS SQUAMOUS CARCINOMA AND INVASIVE WELL-DIFFERENTIATED SCC. ON 11/17/2011, THE PATIENT UNDERWENT DEBRIDEMENT OF SIX CHRONIC ULCERS IN THE LOWER EXTREMITIES. POSTOPERATIVE DIAGNOSIS FOR ALL LESIONS WAS NOTED AS CHRONIC ULCER WITH NO INDICATION OF MALIGNANCY. ON 12/09/2011 THE PATIENT UNDERWENT DEBRIDEMENT AND SPLIT SKIN GRAFTING TO 6 OPEN WOUNDS ON THE LEFT LOWER EXTREMITY AND 2 OPEN WOUNDS ON THE RIGHT LOWER EXTREMITY. THE SITE WHERE THE SKIN GRAFTS WERE HARVESTED WAS FROM THE LEFT FOREARM. AS OF 02/23/2012, THE TREATING PHYSICIAN INDICATED THAT THE PATIENT WAS DOING WELL. THE INTENSITIES FOR THE EVENT OF "WOUND INFECTIONS, PNEUMONIA, URINE TRACT INFECTION, CORNEAL BURN AND SKIN CONTRACTURE OF THE PENIS" WERE NOT PROVIDED. THE RELATIONSHIP BETWEEN EPICEL AND THE EVENTS OF "WOUND INFECTIONS, PNEUMONIA, URINE TRACT INFECTION, CORNEAL BURN AND SKIN CONTRACTURE OF THE PENIS" WERE NOT PROVIDED BY THE REPORTING PHYSICIAN. THE PATHOLOGY REPORTS, REGARDING THE PATIENT'S PATHOLOGY SLIDES, WERE REVIEWED BY AN INDEPENDENT PATHOLOGIST WITH THE PATHOLOGIST'S REPORT RECEIVED ON 04/30/2012. THE PATHOLOGIST DESCRIBED THE FOLLOWING. FIVE PATHOLOGY REPORTS RANGING IN DATES FROM 12/02/2002 UNTIL 10/21/2003 WERE RECEIVED EACH WAS OF AN EXCISION OR BIOPSY OF A SQUAMOUS CELL CARCINOMA OF THE LEFT LEG. THE FIRST OF 12/12/2002 FROM THE LEFT KNEE DEBRIDEMENT WAS A SQUAMOUS CELL CARCINOMA DESCRIBED WELL DIFFERENTIATED AND VERRUCOUS (BIOPSY ONLY). THE SECOND FROM THE LEFT THIGH EXCISION OF 04/10/2003 WAS 7 MM IN THICKNESS, AND WAS DESCRIBED AS WELL DIFFERENTIATED. THE THIRD SPECIMEN LEFT ANTERIOR LATERAL THIGH RE-EXCISION OF 08/13/2003 WAS DESCRIBED AS WELL DIFFERENTIATED AND MEASURED 2.5 MM IN THICKNESS. THE FOURTH OF 09/30/2003 LEFT LEG, EXCISION WAS DESCRIBED AS WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMA MEASURING 3.5MM IN THICKNESS, MARGINS INVOLVED. THE FIFTH OF 10/21/2003 LEFT LOWER LEG, EXCISION WAS DESCRIBED AS A WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMA 3.7 MM IN THICKNESS ADEQUATELY EXCISED. FOLLOW-UP INFORMATION RECEIVED ON 08/31/2015. THIS LITERATURE REPORT WAS RECEIVED FROM LITERATURE ARTICLE TITLED "INVASIVE SQUAMOUS CELL CARCINOMA IN FULL-THICKNESS BURN WOUNDS AFTER TREATMENT WITH CULTURED EPITHELIAL AUTOGRAFTS: SINGH, MANSHER 1, NUUTLIA, KRISTO 1; CHAUHAN, ANUPAM SINGH 1; ERIKSSON, ELOF 1 1 DIVISION OF PLASTIC SURGERY, BRIGHAM AND WOMEN'S HOSPITAL, BOSTON, MASS, MASS JOURNAL PLASTIC AND RECONSTRUCTIVE SURGERY. GLOBAL OPENS 3.7 (08/10/2015) E460 ON 08/31/2015, CONCERNING (B)(6) YEAR OLD MALE WHO EXPERIENCED SQUAMOUS CELL CARCINOMA AFTER EPICEL IMPLANTATION. THE ARTICLE REPORTED 8 ADDITIONAL SQUAMOUS CELL CARCINOMAS (SCCS) IN THE PATIENT'S LOWER EXTREMITIES OVER THE PAST 9 YEARS (OCTOBER 2005 TO APRIL 2015). THE PATIENT DEVELOPED MULTIPLE (ABOUT 95) EXOPHYTIC, HYPERKERATOTIC AND ULCERATED LESIONS DURING THIS TIME PERIOD WHICH INCLUDED LEFT LATERAL KNEE (3.5 X 3) ON 10/03/2013, LEFT POPLITEAL FOSSA (4 X 3) ON 05/08/2014, LEFT POSTERIOR THIGH (2.3 X 2) 03/19/2015. FOR MULTIPLE SCCS, EXCISIONAL BIOPSIES WERE DONE FOR ALL OF THESE LESIONS. EIGHT OF THEM WERE FOUND TO BE INVASIVE SCC. NONE OF THESE LESIONS WERE CONTIGUOUS TO EACH OTHER. NEGATIVE MARGIN WAS CONFIRMED IN ALL THESE PATHOLOGY SPECIMENS AFTER THE DEFINITIVE SURGERY. THERE WAS NO EVIDENCE OF METASTASIS OR LYMPH NODE INVOLVEMENT. LATEST SCC WAS EXCISED IN MARCH 2015. MULTIPLE OTHER SPECIMENS ALSO DEMONSTRATED EXTENSIVE HYPERPLASIA WITH CELLULAR ATYPIA BUT DID NOT REVEAL CARCINOMA. THE RESECTED AREA WAS COVERED WITH A SPLIT-THICKNESS SKIN GRAFT FROM THE LEFT FOREARM SINCE THAT WAS THE ONLY AREA WITH ORIGINAL SKIN PRESERVED FROM THE BURN INJURY. THE PATIENT CONTINUED TO BE CLOSELY MONITORED WITH REGULAR FOLLOW-UP CLINIC VISITS. IN VITRO EXPANSION OF KERATINOCYTES INTO SHEETS SUITABLE FOR AUTOGRAFTING INVOLVED SERIAL SUBCULTURE IN THE PRESENCE OF LETHALLY IRRADIATED 3T3 FIBROBLASTS, EPIDERMAL GROWTH FACTOR AND CHOLERA TOXIN OR ISOPROTERENOL. USE OF MITOGENIC STIMULATORS, SUCH AS EPIDERMAL GROWTH FACTOR OR CHOLERA TOXIN, MAY CONTRIBUTE TO MALIGNANT TRANSFORMATION OF THE GRAFTED EPITHELIUM. ADDITION OF CHOLERA TOXIN OR ISOPROTERENOL TO THE CULTURE MEDIUM CAUSES IRREVERSIBLE ACTIVATION OF ADENYL CYCLASE WITH INCREASE CELLULAR LEVELS OF CYCLIC ADENOSINE MONOPHOSPHATE. ALTHOUGH THIS RESULTS IN MARKEDLY INCREASED RATE OF GROWTH OF KERATINOCYTES IN VITRO, IT CAN ALSO HAVE A MITOGENIC EFFECT ON THE REGENERATED EPITHELIUM. THERE WAS A LIMITED EVIDENCE, BUT BASED ON THE REPORTS OF MULTIPLE SCCS IN THE PATIENT IN THE AREAS GRAFTED WITH CEAS AND NOT OUTSIDE OF THESE AREAS, IT WAS RECOMMENDED TO MONITOR SUCH PATIENTS CLOSELY AND A LOW THRESHOLD FOR EXCISIONAL BIOPSIES FOR ANY SUSPICIOUS LESIONS. IT WAS CONCLUDED THAT THE PATIENT REMAINED FREE OF RECURRENCES OF METASTATIC DISEASE. THE REPORTER CAUSALITY FOR EVENTS WERE NOT PROVIDED.
SQUAMOUS CELL CARCINOMA [SQUAMOUS CELL CARCINOMA]. SKIN ULCERATION [SKIN ULCER]. CASE DESCRIPTION: LITERATURE REPORT WAS RECEIVED ON (B)(4) 2011, FROM A PHYSICIAN REGARDING A (B)(6) MALE PATIENT, INITIALS NOT PROVIDED WHO EXPERIENCED SQUAMOUS CELL CARCINOMA AFTER RECEIVING EPICEL. THIS REPORT IS FROM A LITERATURE ARTICLE TITLED "GRAFT SITE MALIGNANCY FOLLOWING TREATMENT OF FULL-THICKNESS BURN WITH CULTURED EPIDERMAL AUTOGRAFT." THEOPOLD, C., D. HOELLER, P. VELANDER, R. DEMLING, AND E. ERIKSSON. IDEAS AND INNOVATIONS. 2003. THE PATIENT WAS INVOLVED IN A GAS EXPLOSION AND SUSTAINED 95% BURNS. DURING THE PATIENT'S STAY IN THE INTENSIVE CARE UNIT, THE BURNT SKIN WAS WIDELY EXCISED DOWN TO THE FASCIA OR THE SUB-CUTANEOUS FAT. MAJORITY OF THE PATIENT'S BODY (CHEST, ABDOMEN, FACE, AND UPPER AND LOWER EXTREMITIES ANTERIORLY AND POSTERIORLY) WAS COVERED WITH CULTURED EPIDERMAL AUTOGRAFTS (CEA). THE LOWER EXTREMITIES HAD TO BE GRAFTED THREE TIMES IN VARIOUS PLACES FOR THE GRAFTS TO TAKE. THE PATIENT WAS DISCHARGED FROM THE HOSPITAL (B)(6) MONTHS AFTER THE INITIAL INJURY. BUT AFTER THAT, THE PATIENT HAD TO BE RE-GRAFTED NUMEROUS TIMES DUE TO ULCERATION OF THE LOWER EXTREMITIES WHICH HAD BEEN GRAFTED BY THE CEA. ON 21 DIFFERENT OCCASIONS, THE ULCERATED AREAS HAD TO BE DEBRIDED AND WERE COVERED WITH SKIN GRAFTS FROM THE FOREARM. THIRTEEN YEARS AND SIX MONTHS AFTER THE INITIAL INJURY, THE PATIENT DEVELOPED VERRUCOUS SQUAMOUS CELL CARCINOMA. FIVE MONTHS LATER, THE PATIENT DEVELOPED A LESION ON HIS LEFT ANTERIOR THIGH. PATHOLOGICAL EXAMINATION REVEALED WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMA. THIS AREA WAS EXCISED AND GRAFTED WITH SPLIT-THICKNESS SKIN FROM THE LEFT FOREARM. TWO MONTHS LATER, TWO NEW LESIONS DEVELOPED ON THE LEFT ANTERIOR THIGH, CLOSE TO BUT DISTINCT FROM THE PREVIOUSLY EXCISED AREA. THESE WERE BOTH WELL DIFFERENTIATED SQUAMOUS CELL CARCINOMAS THAT WERE EXCISED DOWN TO THE FASCIA. THESE AREAS WERE SUBSEQUENTLY GRAFTED WITH SPLIT-THICKNESS SKIN. A FIFTH LESION GREW JUST DISTAL TO THE LEFT FIBULAR HEAD. PATHOLOGICAL EXAMINATION REVEALED SQUAMOUS CELL CARCINOMA THAT WAS EXCISED TO CLEAR MARGINS AND GRAFTED WITH SPLIT-THICKNESS SKIN. ALL THE LESIONS DEVELOPED IN THE BURNT AREAS THAT WERE COVERED WITH THE CEA IN THE FIRST THREE MONTHS AFTER THE BURN. THE PATIENT IS STILL UNDER CLOSE SUPERVISION. THERE IS NO EVIDENCE OF LOCAL RECURRENCE OR DISTANT METASTASIS IN THE PATIENT. FOR OTHER EVENTS REPORTED BY THE REPORTER, PLEASE REFER TO (B)(4).
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 1 | EPICEL (CULTURED EPIDERMAL AUTOGRAFTS) GRAFT | CULTURED EPIDERMAL AUTOGRAFTS | MGR | GENZYME BIOSURGERY (CAMBRIDGE) | UNK | UNK |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 34 YR | Other| R |