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U.S. Department of Health and Human Services

MAUDE Adverse Event Report: GENZYME BIOSURGERY (CAMBRIDGE) EPICEL (CULTURED EPIDERMAL AUTOGRAFTS) GRAFT

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GENZYME BIOSURGERY (CAMBRIDGE) EPICEL (CULTURED EPIDERMAL AUTOGRAFTS) GRAFT Back to Search Results
Lot Number E80079
Device Problem Device Operates Differently Than Expected (2913)
Patient Problems Tissue Damage (2104); Injury (2348); Cancer (3262)
Event Date 01/01/2010
Event Type  Death  
Manufacturer Narrative

Mfr's comment: the benefit-risk relationship of epicel is not affected by this report.

 
Event Description

Squamous cell carcinoma [squamous cell carcinoma]. Case description: epigastric spontaneous report was received on 04/21/2011 from a physician via a company rep regarding an (b)(6) y/o male pt (when he received epicel), initials (b)(6), with skin injury. The pt has been diagnosed with squamous cell carcinoma after receiving epicel grafts (lot number e80079). On april 21, 2011 and april 22, 2011, the following was reported. The pt's medical history is significant for an initial skin injury in 1990. In (b)(6) of 1998, the pt received the initial epicel graft. The pt also received "cultured epithelial autograft" at a later date, but the specific date of the second graft was not provided. The pt has not been diagnosed with "squamous cell carcinoma. " the date of diagnosis was not available. The reporting physician assessed the relationship between epicel and the event of squamous cell carcinoma to be related. The outcome of the pt was not provided. On april 25, 2011, add'l info was provided by the hcp: the hcp stated that the pt has a history of 99% burns. The hcp clarified that the pt received not two but three epicel grafts in (b)(6) 1998 respectively). The pt was (b)(6) years old when he received the epicel grafts and is currently (b)(6) years old. The hcp stated that the pt is experiencing squamous cell carcinoma in two locations namely, the abdomen and the left knee. The hcp stated that in his opinion, this is a very aggressive form of carcinoma. The pt has undergone two re-section surgeries for the carcinoma. The hcp stated that he was unable to provide any causality for this event in regards to epicel with the info available to him at this point. Also, the hcp stated that investigation is being done currently to assess and map the successful locations of the epicel grafts on the pt. Further is expected from the hcp. On may 3, 2011, f/u info was received from the hcp. The hcp provided more details regarding the pt. This (b)(6) year old child sustained a 99% flame burn. In (b)(6) of 1990, the pt underwent biopsy of unburned tissue which was subsequently sent to genzyme for expansion of his cells to form cea. The pt underwent the initial placement of the cea on (b)(6) 1998 followed by a second application on (b)(6), 1998 and a third application on (b)(6) 1998. The pt presented to the hospital on (b)(6) 2010 with a very large, well differentiated squamous cell carcinoma over the left abdominal wall. He underwent resection of the lesion and coverage with skin grafts. Three months later, the pt developed a local recurrence which penetrated the abdominal cavity. The pt underwent full thickness section of this lesion as well as the lesions over the left chest wall region with positive margins superiorly. The pt then underwent resection of the left five, six, eight and nine cartilaginous portion of his ribs in order to achieve tumor free margins. The pt was subsequently covered with his own autografts from his scalp meshed 2. 1 and a vac drainage was then used to cover his wounds. The defect in the abdominal wall measured approx 16x16 centimeters. Once the margins were negative of tumor, the abdominal defect was closed with strattice. The hcp stated that the vac system was changed once every four to five days, and the strattice was actually revascularized. The pt was then noted to have an add'l nodule within the medial aspect of the wound. This was biopsied and it revealed a recurrence of the squamous cell carcinoma. A ct scan showed a mass in the legs as well as in the epigastric region. At the time of this report, the outcome of the pt was not known.

 
Manufacturer Narrative

Evaluation summary: the qa investigation results were received on june 17, 2011. Qa performed a thorough review of the lot batch records and testing results and found them to be in good order. The patient lot (e80079) was processed and tested according to standard operating procedures and met all release specifications.

 
Manufacturer Narrative

On july 5, 2011, the hcp reported that the pt was treated with 2. 0 mg/kg of insulin-like growth factor (igf-1) and insulin-like growth factor binding proteins (igfbp-3) for six days between (b)(6) 1998. The hcp considered this piece of info to be circumstantial in relation to the event, but worthy of note. Evaluation summary: the qa investigation results were received on june 17, 2011. Quality assurance performed a thorough review of the lot batch records and testing results and found them to be in good order. The patient lot (e80079) was processed and tested according to standard operating procedures and met all release specifications.

 
Manufacturer Narrative

Evaluation summary: the sterility and environmental monitoring results were received on june 5, 2011. All sterility results for the production of epicel lot e80079 were negative for contamination.

 
Manufacturer Narrative

Clarification: narrative from (b)(6) 2011 notes the words "epigastric m" at the beginning of the narrative that were written in error. On (b)(6) 2011, follow-up information was received from the reporting physician during a phone conversation with a company physician. The hcp reported that the patient expired on (b)(6) 2011. The patient had noticed a growth on his abdomen for about six months that appeared to be growing larger. The patient decided to go to his physician in early 2010. A biopsy was taken and it showed squamous cell carcinoma (scc). The patient then went to the reporting physician and was under his care. The reporting physician described three features of the scc that were of concern to him. First, he reported that in this patient, the scc was multicentric in its presentation, appearing in the abdomen, the foot (not previously reported), and the knee he stated that this was unusual in post burn scc which is usually with a single focus. Second, the timing of the scc post burn. According to the hcp when scc does appear, its usually twenty plus years post burn and graft. In this case, it was twelve years post burn and was much more accelerated and sooner than expected. Third was the histopathology of this scc in that it was extremely aggressive and atypical in features, including altered p53. The hcp had questions regarding the use of cholera toxin and epidermal growth factor (egf) in the creation of the cea.

 
Manufacturer Narrative

On august 30, 2011, additional information was received from the hcp via the company representative. The patient's date of birth was provided. The patient was admitted to the hospital on (b)(6) 1998. The correct date of the patient's death is (b)(6) 2011 and not (b)(6) 2011 as previously reported. Evaluation summary: the qa investigation results were received on june 17, 2011. Quality assurance performed a thorough review of the lot batch records and testing results and found them to be in good order. The patient lot (e80079) was processed and tested according to standard operating procedures and met all release specifications.

 
Manufacturer Narrative

Additional information received on february 8, 2012 from the treating hcp provided the following: patient was a (b)(6) male who sustained 99% tbs area burns on (b)(6) 1998 and was hospitalized on that same day with third degree burns over his entire body except for part of his scalp, the lower back and the dorsal-lateral surface of the left foot. During hospitalization, the patient underwent excision of his burn wounds, was covered with allograft and skin biopsies from unburned tissue of the left foot were sent to the manufacturer for development of cea. The patient underwent three operations for cea application to the following areas. On (b)(6) 1998: entire body except for hands, sole of feet, back and buttocks (b)(6) 1998: meshed cadaver skin dressing on top of cultured autograph on legs. On (b)(6) 1998: chest, right and left groin, left arm, left anterior flank, posterior neck, chest and right side of trunk. On (b)(6) 1998 - both legs, left anterior flank, left antecubital fossa, right anterior axilla, left side of neck and face. Postoperatively, from the last cea treatment, the patient developed pseudomonas pneumonia requiring intubation for more than a week. From (b)(6) 1998 the patient was hospitalized for surgical release of scar contractures to the right knee and lower lip. In (b)(6) 2000, the patient had a few small open areas of skin treated with an application of integra on (b)(6) 2000. In (b)(6) 2000, the patient was admitted with right flank pain, diagnosed with right kidney stones and treated with percutaneous nephrostomy and lithotomy. From (b)(6) 2001 through (b)(6) 2007, the pt underwent multiple scar release procedures. The patient underwent a total of 23 admissions and 33 operations at the institution where he was initially hospitalized for his burns with the last date seen as (b)(6) 2008. The patient then moved to another state and was lost to f/u. In (b)(6) 2010, the patient was seen, at a hospital where he had moved, for chronic wounds on his left flank and left knee. At this time biopsies were performed (location not provided) that revealed squamous cell carcinoma (scc). On (b)(6) 2010, the patient was again seen at the hospital where he was initially treated for his burns, and biopsies were obtained from multiple regions of the left flank and multiple regions of the left knee wounds. All 11 biopsy specimens revealed "well-differentiated squamous cell carcinoma". The treating hcp noted that the flank region required 3 cea applications. Mri and ct scan of the abdomen were negative for any intra-abdominal involvement, but mri of the left knee and popliteal fossa noted enlarged popliteal lymph nodes. On (b)(6) 2010, 3 biopsies of recurrent ulcers of the abdomen were positive for invasive scc and a biopsy of the knee showed ulcer with granulation tissue, but no tumor. On (b)(6) 2010, the patient underwent excision of the flank wound (27x19 cm), knee wound (12x9 cm), biopsy of an open wound of the left foot (5x3 5 cm) and a left popliteal node dissection. The left foot biopsy revealed scc with negative margins and the node dissection was negative for metastatic tumor. Multiple specimens from the abdomen were positive for "invasive squamous cell carcinoma" with one specimen noting "invasive squamous cell carcinoma extending to the deep margin of the excision". Specimen from the knee noted "well-differentiated tumor extending focally to the deep margin, on the medial side of the superior pole. " on june (b)(6) 2010, the patient underwent re-excision of the knee with negative margins along with negative margins of the mid and lateral abdominal wall specimens. All wounds were covered with allograft followed by autograft. On (b)(6) 201 1, the patient developed a local recurrence of the abdomen that penetrated the abdominal cavity. Biopsy results from the skin and abdominal wall and upper abdomen revealed differentiated keratinizing scc extending into muscle and adipose tissue and present in two foci at the deep surgical margin. The patient underwent en bloc resection of the abdominal wall that included the greater curvature of the stomach, a partial omentectomy and the falciform ligament. There was no intra-peritoneal seeding of tumor noted at this time. Subsequently, there was resection of the left 5th, 6th, 8th and 9th cartilaginous portions of the ribs in order to achieve tumor free margins. The patient was covered with his own autographs from his scalp meshed 2:1 and a vac drainage was use to cover the abdominal wounds. The margins of the abdominal wound were negative for tumor at which time the abdominal wall defect, measuring approximately 16x 16 cm, was closed with strattice (porcine skin). As the strattice was revascularizing it was noted that new nodules had developed within the medial aspect of the wound. On (b)(6) 2011, 3 biopsies of these nodules, from the abdomen, all revealed "infiltrating well differentiated squamous cell carcinoma". A ct scan showed a mass in the leg and epigastric region. The patient and family declined further treatment and the patient subsequently developed an enterocutaneous fistula and died of sepsis on (b)(6) 2011. Evaluation summary: the qa investigation results were received on june 17, 2011. Quality assurance performed a thorough review of the lot batch records and testing results and found them to be in good order. The patient lot (e80079) was processed and tested according to standard operating procedures and met all release specifications.

 
Manufacturer Narrative

Review of the patient's pathology slides by an independent pathologist were received on (b)(6) 2012 and results noted as follows. The pathology findings showed a well differentiated squamous cell carcinoma, initially confined to the skin. The tumor recurred and attempts were made to excise it with wide margins. The patient developed multiple local recurrences, followed by metastatic disease. The patient succumbed to widespread carcinomatosis. The squamous cell carcinomas occurring in the initial biopsies were compared to the subsequent recurrences and metastases. Although minor differences were observed, the squamous cell carcinomas, in general all had similar features. There was evidence of extensive keratinization with the formation of squamous pearls and keratocysts. In some foci, the tumor showed an extensive infiltrating pattern. Secondary changes such as necrosis and glycogen accumulation were common. Evaluation summary: the qa investigation results were received on june 17, 2011. Quality assurance performed a thorough review of the lot batch records and testing results and found them to be in good order. The patient lot (e80079) was processed and tested according to standard operating procedures and met all release specifications.

 
Manufacturer Narrative

Follow up information was received on october 15, 2012 in form of a literature abstract. Finnerty c, mccauley r, hawkins d, hemdon d, genomic alterations in cultured epithelial autograft (cea) associated with the development of squamous cell carcinoma. Journal of tissue engineering and regenerative medicine 2012; 6 (suppl. 1): 94. It was reported that new squamous cell carcinoma developed after receiving cea coverage. The clonal amplification of cells selected for rapid and aggressive growth, grafted onto the patient with chronic systemic inflammation had raised concern that it might have introduced genetic alterations which now resulted in malignancy. Evaluation summary: the qa investigation results were received on june 17, 2011. Quality assurance performed a thorough review of the lot batch records and testing results and found them to be in good order. The patient lot (e80079) was processed and tested according to standard operating procedures and met all release specifications.

 
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Brand NameEPICEL (CULTURED EPIDERMAL AUTOGRAFTS) GRAFT
Type of DeviceCULTURED EPIDERMAL AUTOGRAFTS
Manufacturer (Section D)
GENZYME BIOSURGERY (CAMBRIDGE)
cambridge MA
Manufacturer (Section G)
GENZYME BIOSURGERY (CAMBRIDGE)
64 sidney street
cambridge MA 02139
Manufacturer Contact
jill robinson, ph, mba
675 west kendall street
cambridge, MA 02142
6177689000
MDR Report Key2094110
MDR Text Key64670374
Report Number1226230-2011-00002
Device Sequence Number1
Product Code OCE
Combination Product (Y/N)N
Reporter Country CodeUS
PMA/PMN NumberHDE 990002
Number of Events Reported1
Summary Report (Y/N)N
Report Source Manufacturer
Source Type HEALTH PROFESSIONAL
Reporter Occupation
Type of Report Initial,Followup,Followup,Followup,Followup
Report Date 04/21/2011
1 Device Was Involved in the Event
1 Patient Was Involved in the Event
Date FDA Received01/12/2017
Is This An Adverse Event Report? Yes
Is This A Product Problem Report? Yes
Device Operator NO INFORMATION
Device LOT NumberE80079
Was Device Available For Evaluation? No
Is The Reporter A Health Professional? Yes
Was the Report Sent to FDA? No
Event Location No Information
Date Manufacturer Received05/03/2011
Was Device Evaluated By Manufacturer? Device Not Returned To Manufacturer
Is The Device Single Use? Yes
Is this a Reprocessed and Reused Single-Use Device?
Type of Device Usage Initial

Patient TREATMENT DATA
Date Received: 01/12/2017 Patient Sequence Number: 1
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