Michael J. Joyce

Allograft Update: The Current Status of Tissue Regulation, Procurement, Processing, and Sterilization

Allografts are commonly used during sports medicine surgical procedures in the United States, and their frequency of use is increasing. Based on surgeon reports, it is estimated that more than 60 000 allografts were used in knee surgeries by members of the American Orthopaedic Society for Sports Medicine in 2005. In the United States, there are governmental agencies and other regulatory bodies involved in the oversight of tissue banks. In 2005, the Food and Drug Administration finalized its requirements for current good tissue practice and has mandated new rules regarding the “manufacture” of allogenic tissue. In response to well-publicized infections associated with the implantation of allograft tissue, some tissue banks have developed methods to sterilize allograft tissue. Although many surgeons have significant concerns about the safety of allografts, the majority believe that sterilized allografts are safe but that the sterilization process negatively affects tissue biology and biomechanics. However, most know very little about the principles of sterilization and the proprietary processes currently used in tissue banking. This article will review the current status of allograft tissue regulation, procurement, processing, and sterilization in the United States.

Musculoskeletal allograft risks and recalls in the United States.

&NA; There have been several improvements to the US tissue banking industry over the past decade. Tissue banks had limited active government regulation until 1993, at which time the US Food and Drug Administration began regulatory oversight because of reports of disease transmission from allograft tissues. Reports in recent years of disease transmission associated with the use of allografts have further raised concerns about the safety of such implants. A retrospective review of allograft recall data was performed to analyze allograft recall by tissue type, reason, and year during the period from January 1994 to June 30, 2007. During the study period, more than 96.5% of all allograft tissues recalled were musculoskeletal. The reasons underlying recent musculoskeletal tissue recalls include insufficient or improper donor evaluation, contamination, recipient infection, and positive serologic tests. Infectious disease transmission following allograft implantation may occur if potential donors are not adequately evaluated or screened serologically during the prerecovery phase and if the implant is not sterilized before implantation.

Paraarticular osteochondroma of the knee : report of 2 cases and review of the literature

Paraarticular osteochondromas are unusual osteocartilaginous tumors that arise in the soft tissue adjacent to a joint. Their pathogenesis and classification are controversial, and worrisome histologic features make the distinction from chondrosarcoma difficult on morphologic grounds alone. Two cases of paraarticular osteochondroma of the knee arising in patients 66 and 75 years of age are reported in this study. Although the exact biologic nature of these tumors is not well characterized, limited data suggest that they will behave in benign fashion, similar to soft tissue chondromas. Paraarticular osteochondromas should be recognized to avoid unnecessarily aggressive surgical management.

Soft-tissue sarcomas: Overview of management, with a focus on surgical treatment considerations

Outcomes for patients with bone sarcomas have improved dramatically over the past 40 years, and most bone sarcomas today are treated with surgery and chemotherapy. The most common clinical findings in patients with bone sarcomas are pain and an enlarging bone mass, although pain is not generally a good indicator of malignancy. In general, any patient with a bone mass with indeterminate imaging findings should be referred to an orthopedic oncologist. Bone sarcomas are diagnosed after a biopsy, which is best performed by the surgeon who will be doing the curative resection. Postresection reconstruction of the affected limb is generally done with an allograft-prosthetic composite or a modular metallic prosthetic joint replacement device. Post- therapy follow-up at frequent and regular intervals is critical to assess for recurrence and lung metastasis.

Can MDM2 analytical tests performed on core needle biopsy be relied upon to diagnose well-differentiated liposarcoma?

Well-differentiated liposarcoma/atypical lipomatous tumor can be difficult to differentiate from benign lipomatous tumors, especially on limited biopsy material. Adjunctive tests for MDM2 (murine double minute 2) have proven useful in whole-tissue sections; however, their utility has not been determined within the increasingly popular core needle biopsy. Herein, we compare the ability of MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization (FISH) to discriminate benign lipomatous tumors from well-differentiated liposarcoma on core needle biopsies. Well-differentiated liposarcoma (n=17) and an assortment of benign lipomatous tumors (n=37), which had concurrent or previous core needle biopsies, and resection specimens were subjected to both MDM2 immunohistochemistry and MDM2 FISH on both whole-tissue sections and corresponding core needle biopsy sections. Percentage tumor cells positive for MDM2 by immunohistochemistry and an MDM2:CEP12 FISH ratio was calculated in each biopsy and resection specimen pair and the results were compared. MDM2 FISH had a higher sensitivity (100%) and specificity (100%) compared with MDM2 immunohistochemistry (65 and 89%) in core needle biopsies, respectively. In addition, MDM2 immunohistochemistry had a false-positive rate of 11%, compared to 0% with FISH. The average MDM2:CEP12 ratio was similar in the biopsy material compared with the whole-tissue sections in both well-differentiated liposarcoma and the benign lipomatous tumor group of neoplasms. Detection of MDM2 amplification by FISH is a more sensitive and specific adjunctive test than MDM2 immunohistochemistry to differentiate well-differentiated liposarcoma from various benign lipomatous tumors, especially on limited tissue samples.

Treatment of Heterotopic Ossification

Heterotopic ossification is defined as bone formation in nonosseous tissues. Heterotopic ossification usually occurs in trauma such as fractures and surgical procedures. Heterotopic ossification of the hip, for example, is the most common complication of total hip arthroplasty (THA). It can occur in as many as 53% of THA patients, and it causes postoperative disability from pain and limited range of motion (ROM) 7% of the time.1 Heterotopic ossification also is seen in neurologic disorders such as spinal cord and brain injury.

The use of allograft bone in spine surgery: is it safe?

BACKGROUND CONTEXT Allograft bone is commonly used in various spinal surgeries. The large amount of recalled allograft tissue, particularly in recent years, has increased concerns regarding the safety of allograft bone for spinal surgery. An analysis of allograft recall and its safety in spinal surgery has not been reported previously. PURPOSE To determine 1) the number and types of allograft recall and the reasons for recall, 2) the types of disease transmission to spine patients, and 3) assess the safety of allograft bone in spinal surgery. STUDY DESIGN/SETTING Retrospective review. METHODS A retrospective review of all Food and Drug Administration (FDA) data from 1994 to June 2007 was reviewed to determine the amount and types of recalled allograft tissue. The literature and data from the Center for Disease Control were reviewed to determine the number and types of disease transmissions from allograft bone that have occurred to spine surgery patients during the study period. RESULTS There were 59,476 musculoskeletal allograft tissue specimens recalled by FDA during the study period, which accounts for 96.5% of all allograft tissue recalled in the United States. Improper donor evaluation, contamination, and recipient infections are the main reasons for allograft recall. There has been one case of human immunodeficiency virus infection transmission to a spine surgery patient in 1988. This is the only reported case of viral transmission. There are no reports of bacterial disease transmission from the use of allograft bone to spine surgery patients. CONCLUSIONS The precise number of allografts used in spine surgery annually and the precise incidence of disease transmission to spine surgery patients linked to the use of allograft tissue is unknown. Musculoskeletal allograft tissue accounts for the majority of recalled tissue by FDA. Despite the large number of allograft recalls in this country, there is only one documented case in the literature of disease transmission to a spine surgery patient. There appears to be no overt risk associated with the use of allograft bone in spine surgery. However, as discussed in this article, there are certain aspects regarding the use of allograft bone that should be considered.

Complex prosthetic joint infections due to carbapenemase-producing Klebsiella pneumoniae: a unique challenge in the era of untreatable infections

SUMMARY Objectives Limited clinical experience exists regarding the management of prosthetic joint infection (PJI) due to multidrug-resistant (MDR) Gram-negative organisms. We review three cases of carbapenem-resistant Klebsiella pneumoniae (CRKP) complicating PJI. Methods This was a retrospective study of all patients at a tertiary care institution with CRKP complicating PJI between January 2007 and December 2010. Demographic data, procedures, organisms involved, length of stay, antibiotic treatments, and outcomes were collected. Antimicrobial susceptibility testing was performed on CRKP isolates, and the mechanism of resistance was ascertained by PCR. Results This analysis demonstrated that: (1) the CRKP possessed blaKPC and were difficult to eradicate (persistent) in PJI; (2) multiple surgeries and antibiotic courses were undertaken and patients required a prolonged length of stay; (3) resistance to colistin and amikacin emerged on therapy; (4) the same strain of CRKP may be responsible for relapse of infection; (5) significant morbidity and mortality resulted. Conclusions These cases highlight the opportunistic and chronic nature of CRKP in PJIs and the need for aggressive medical and surgical treatment. Further investigations of the management of CRKP PJI and new drug therapies for infections due to MDR Gram-negative organisms are urgently needed.

Decubital Ischemic Fasciitis: Clinical, Pathologic, and MRI Features of Pseudosarcoma

OBJECTIVE The purpose of this report is to describe clinical, pathologic, and MRI findings on decubital ischemic fasciitis, which is a rare soft-tissue tumor sarcoma simulator. CONCLUSION Decubital ischemic fasciitis is a reactive, nonneoplastic lesion typically seen in older debilitated patients at pressure points. Because this lesion simulates soft-tissue sarcoma, both clinically and histologically, it is important to recognize the MRI features and limit misdiagnosis of sarcoma.

Imaging findings, prevalence and outcome of de novo and secondary malignant fibrous histiocytoma of bone

ObjectiveTo evaluate the radiographic and magnetic resonance (MR) imaging features of primary and secondary malignant fibrous histiocytoma in bone and determine the demographics, prevalence and outcome of patients with this tumor.Materials and methodsA retrospective search of files from two institutions identified 28 patients with malignant fibrous histiocytoma (MFH) of bone. Microscope slides were reviewed to confirm diagnosis and identify any pre-existing lesions. Medical records were reviewed with respect to patients’ demographic characteristics and outcomes.ResultsRadiographic features demonstrated an aggressive osteolytic lesion with a permeative pattern of bone destruction. Periosteal reaction was seen in three of 13 lesions. T1-weighted images (T1WIs) demonstrated signal intensity iso- to slightly hyperintense to muscle. T2-weighted images (T2WIs) demonstrated mildly higher signal intensity than that of muscle. The 5-year survival rate was 53%. The tumor arose secondarily in pre-existing lesions in 43% of patients. Metastases occurred in 46% of patients during the course of the disease, with pulmonary and osseous metastases being the most common.ConclusionSecondary MFH of bone was slightly less common than primary MFH and had a prognosis similar to that of primary MFH of bone. MR imaging showed variable and somewhat unusual low to intermediate T2 signal characteristics for a radiographically malignant osteolytic lesion.