Non-irradiated Tissue Research Articles

The usefulness of a pectoralis major myocutaneous flap in preventing salivary fistulae after salvage total laryngectomy

Salvage laryngectomy in patients treated with organ preservation protocols is associated with high rates of postoperative complications. The use of non-irradiated tissue flaps in pharyngeal reconstruction could reduce the incidence of these complications.Objective: This study aims to evaluate the usefulness of the pectoralis major myocutaneous flap in preventing salivary fistulae during the postoperative period of salvage total laryngectomy (TL).Materials and Method: This retrospective study enrolled 31 patients operated between April of 2006 and May of 2011. All patients had advanced cancer at the time of the salvage procedure and had been treated with chemoradiotherapy or radiotherapy alone. Pharyngeal reconstruction was performed using pectoralis major myocutaneous flap in 19 cases (61%); primary wound closure occurred in 12 patients (39%).Results: Salivary fistulae occurred in 16% of the patients who received the flap and in 58% of the patients with primary closure of the pharynx (p < 0.02). No statistically significant differences were noted between the groups with respect to the mean time for fistula formation, reintroduction of an oral diet, or use of a nasoenteric tube for feeding.Conclusion: The pectoralis major myocutaneous flap was found to reduce the incidence of salivary fistulae in salvage laryngectomy procedures.

Gamma Radiation Sterilization Reduces the High-cycle Fatigue Life of Allograft Bone.

Sterilization by gamma radiation impairs the mechanical properties of bone allografts. Previous work related to radiation-induced embrittlement of bone tissue has been limited mostly to monotonic testing which does not necessarily predict the high-cycle fatigue life of allografts in vivo. We designed a custom rotating-bending fatigue device to answer the following questions: (1) Does gamma radiation sterilization affect the high-cycle fatigue behavior of cortical bone; and (2) how does the fatigue life change with cyclic stress level? The high-cycle fatigue behavior of human cortical bone specimens was examined at stress levels related to physiologic levels using a custom-designed rotating-bending fatigue device. Test specimens were distributed among two treatment groups (n = 6/group); control and irradiated. Samples were tested until failure at stress levels of 25, 35, and 45 MPa. At 25 MPa, 83% of control samples survived 30 million cycles (run-out) whereas 83% of irradiated samples survived only 0.5 million cycles. At 35 MPa, irradiated samples showed an approximately 19-fold reduction in fatigue life compared with control samples (12.2 × 10(6) ± 12.3 × 10(6) versus 6.38 × 10(5) ± 6.81 × 10(5); p = 0.046), and in the case of 45 MPa, this reduction was approximately 17.5-fold (7.31 × 10(5) ± 6.39 × 10(5) versus 4.17 × 10(4) ± 1.91 × 10(4); p = 0.025). Equations to estimate high-cycle fatigue life of irradiated and control cortical bone allograft at a certain stress level were derived. Gamma radiation sterilization severely impairs the high cycle fatigue life of structural allograft bone tissues, more so than the decline that has been reported for monotonic mechanical properties. Therefore, clinicians need to be conservative in the expectation of the fatigue life of structural allograft bone tissues. Methods to preserve the fatigue strength of nonirradiated allograft bone tissue are needed. As opposed to what monotonic tests might suggest, the cyclic fatigue life of radiation-sterilized structural allografts is likely severely compromised relative to the nonirradiated condition and therefore should be taken into consideration. Methods to reduce the effect of irradiation or to recover structural allograft bone tissue fatigue strength are important to pursue.

An expression analysis of markers of radiation-induced skin fibrosis and angiogenesis in wound healing disorders of the head and neck.

BackgroundRadiation-induced fibrosis (RIF) is one of the severe long-term side effects of radiation therapy (RT) with a crucial impact on the development of postoperative wound healing disorders (WHD). The grades of fibrosis vary between mild to severe depending on individual radiosensitivity. In this study, we have investigated the molecular pathways that influence RIF and have correlated data from immunohistochemistry (IHC) for von –Willebrand Factor (vWF) and from Real-Time Polymerase Chain Reaction (RT-PCR) concerning markers such as Transforming Growth Factor (TGF)-β1, and vWF, with clinical data concerning the occurrence of WHD during follow-up.MethodsExpression profiles of the genes encoding TGF-β1, vWF, and α-procollagen (PC) were analyzed, by RT-PCR, in specimens from patients with (n = 20; 25.6 %) and without (n = 58; 74.4 %) a history of previous RT to the head and neck. Moreover, IHC against vWF was performed. Clinical data on the occurrence of cervical WHDs were analyzed and correlated.ResultsA statistically significant increase in the expression profiles of α-PC and TGF-β1 was observed in previously irradiated skin samples (occurrence of RT >91 days preoperatively). vWF showed a statistically significant increase in non-irradiated tissue. Moreover, analysis of expression profiles in patients with and without WHDs during follow-up was performed. IHC showed a reduced amount of vessels and structural changes in epidermal tissue post-RT.ConclusionsThe expression of markers of fibrosis and angiogenesis was analyzed in order to gain insight into molecular pathways that account for structural changes in irradiated skin and that eventually lead to WHDs. The results are congruent with reports from the literature and are a possible starting point for further research, as anti-TGF-β1 treatment, for example, could represent new therapeutic opportunities in the management of previously irradiated patients.

18FDG PET-CT standardized uptake value for the prediction of radiation pneumonitis in patients with lung cancer receiving radiotherapy.

The present study aimed to determine if the standardized uptake value (SUV) determined with 18F-FDG PET-CT can be used to predict radiation pneumonitis (RP) in lung cancer patients who receive radiotherapy. A total of 40 patients with non-small cell lung cancer received 18F-FDG PET-CT examinations prior to and following radiotherapy. The average SUV of lung tissue prior to and following radiation were measured at differing radiation doses. SUV differences between patients with and without RP, and the SUV ratio of the irradiated lung tissues compared with that of non-irradiated lung tissues (L/B) were compared. There were no differences in the mean SUV between the RP and no RP groups prior to radiotherapy. There were also no significant differences in the mean SUV of lung tissue within groups or between the no RP and RP groups with radiation doses of <5 Gy, 5 to ≤14.9 Gy and 15 to ≤34.9 Gy (all P>0.05) following radiotherapy. There were, however, statistically significant differences in the mean SUV of lung tissue within groups or between the no RP and RP groups with doses of ≥60 Gy prior to therapy and 35 to ≤59.9 Gy and ≥60 Gy following therapy (all P<0.05). When the L/B ratio was ≥3, the incidence of RP was 50%, and when the L/B ratio was ≥2.5 the incidence was 40.7%. When the L/B ratio was <2, there were no cases of RP. In conclusion, the present study indicates that 18F-FDG PET-CT can be used to predict RP by L/B ratio.

Transcriptional profiling of radiation damage and preventive treatments in a 3-dimensional (3D) human cell culture model of oral mucositis.

Cancer patients who receive radiation are often afflicted by oral mucositis, a debilitating disease, characterized by mouth sores and difficulty in swallowing. Oftentimes, cancer patients afflicted with mucositis must stop life-saving therapies. Thus it is very important to prevent mucositis before it develops. Using a validated organotypic model of human oral mucosa, a 3-dimensional cell culture model of human oral keratinocytes, it has been shown that a mixture (NAC–QYD) of N-acetyl cysteine (NAC) and a traditional Chinese medicine, Qingre Liyan decoction (QYD), prevented radiation damage (Lambros et al., 2014). Here we provide detailed methods and analysis of microarray data for non-irradiated and irradiated human oral mucosal tissue with and without pretreatment with NAC, QYD and NAC-QYD. The microarray data been deposited in Gene Expression Omnibus (GEO): GSE62397. These data can be used to further elucidate the mechanisms of irradiation damage in oral mucosa and its prevention.

PET imaging of DNA damage using (89)Zr-labelled anti-γH2AX-TAT immunoconjugates.

The efficacy of most anticancer treatments, including radiotherapy, depends on an ability to cause DNA double-strand breaks (DSBs). Very early during the DNA damage signalling process, the histone isoform H2AX is phosphorylated to form γH2AX. With the aim of positron emission tomography (PET) imaging of DSBs, we synthesized a (89)Zr-labelled anti-γH2AX antibody, modified with the cell-penetrating peptide, TAT, which includes a nuclear localization sequence. (89)Zr-anti-γH2AX-TAT was synthesized using EDC/NHS chemistry for TAT peptide linkage. Desferrioxamine conjugation allowed labelling with (89)Zr. Uptake and retention of (89)Zr-anti-γH2AX-TAT was evaluated in the breast adenocarcinoma cell line MDA-MB-468 in vitro or as xenografts in athymic mice. External beam irradiation was used to induce DSBs and expression of γH2AX. Since (89)Zr emits ionizing radiation, detailed radiobiological measurements were included to ensure (89)Zr-anti-γH2AX-TAT itself does not cause any additional DSBs. Uptake of (89)Zr-anti-γH2AX-TAT was similar to previous results using (111)In-anti-γH2AX-TAT. Retention of (89)Zr-anti-γH2AX-TAT was eightfold higher at 1 h post irradiation, in cells expressing γH2AX, compared to non-irradiated cells or to non-specific IgG control. PET imaging of mice showed higher uptake of (89)Zr-anti-γH2AX-TAT in irradiated xenografts, compared to non-irradiated or non-specific controls (12.1 ± 1.6 vs 5.2 ± 1.9 and 5.1 ± 0.8%ID/g, respectively; p < 0.0001). The mean absorbed dose to the nucleus of cells taking up (89)Zr-anti-γH2AX-TAT was twofold lower compared to (111)In-anti-γH2AX-TAT. Additional exposure of neither irradiated nor non-irradiated cells nor tissues to (89)Zr-anti-γH2AX-TAT resulted in any significant changes in the number of observable DNA DSBs, γH2AX foci or clonogenic survival. (89)Zr-anti-γH2AX-TAT allows PET imaging of DNA DSBs in a tumour xenograft mouse model.

Abstract 556: Targeted Screening Reveals microRNAs of Therapeutic Interest in Radiotherapy-Induced Vascular Disease

Radiotherapy is an established therapeutic method in many different cancer types. The success of modern cancer treatment raises a new problem, namely radiotherapy-induced vascular disease (vRTx) or vasculopathy, which typically emerges in irradiated areas of the heart, neck and brain and manifests itself as coronary disease, heart failure or carotid stenosis. A chronic inflammatory response likely underlies vRTx. Like in atherosclerosis, complex biological processes such as vascular cell proliferation, remodeling, oxidative stress, and tumor growth factor β (TGF-β)-regulated nuclear factor kappa B (NF-κB) activation are involved. These processes are tightly regulated by a multitude of factors, which separately are difficult to influence. A set of miRNAs known to orchestrate these processes in other disease contexts likely also play a role in vRTx, and might be modifiable in order to treat or prevent RTx-induced vascular disease. We selected miR-29b, miR-125a, miR-126, miR-143, miR-145, miR-146a, miR-155, miR-221, miR-222, and miR-503 and determined their potential contribution to vRTx. Utilizing unique biobank material from microvascular free tissue transfer reconstructions, where irradiated (R) vascular tissue (branches from external carotid arteries and internal jugular veins) can be compared with non-irradiated control tissue (NR) within the same patient (n=10), we could precisely determine which miRNAs become deregulated after irradiation. Currently we are using a mouse model of local irradiation for further analysis and assessment of miRNA modulation effects. Apoe -/- mice are irradiated in the mediastinal area; control littermates were sham irradiated. We checked the expression of the 10 pre-selected miRNAs in R vs. NR vascular tissue (ascending and thoracic aorta). Of the 10 miRNAs, three (miR-29b up-; miR-143, miR-145 downregulated) were significantly differentially regulated between R and NR human arteries. miR-146a trended upward, but not significantly. Ongoing studies are aimed at histological analysis of mouse R vs. NR tissue, functional modulation of deregulated miRNAs in vivo to assess vRTx outcome, and in vitro assessment of miRNA expression differences in different human vascular cell lines exposed to radiation.

Effect by Gamma Irradiation and Low-Temperature Storage on Bacteriological Profile of Edible Estuarine CrabScylla serrata

The effect of dose-dependent gamma irradiation and subsequent cold storage on bacteriological profile of tissues derived from Scylla serrata was evaluated. Irradiation at 0.5, 1.0 and 2.0 kGy significantly reduced the (P = 0.0001) total plate count (TPC) by 1.0, 2.0 and 2.5 log units, respectively. Treatments of 1.0 and 2.0 kGy irradiation reduced total coliform (TC) count below 1 most probable number (MPN)/g in the muscle and hepatopancreas and below 50 MPN/g in the gills of S. serrata. Irradiated tissues stored at −20C showed significant reduction in TPC and TC. Bacillus spp. was predominant in the tissues before and after gamma irradiation. While live crab tissues harbored both gram-positive and gram-negative bacteria in equal proportion, more than 90% of them from irradiated tissues were gram-positive. Biochemical and 16S rRNA gene-based study on generic composition of heterotrophic bacteria revealed fairly good diversity in nonirradiated tissues and the dose-dependent gamma irradiation significantly reduced their diversity concomitantly. Practical Applications The mud crab Scylla serrata in which the present study was conducted has immense market demand all over the world. The present study clearly demonstrated the possibility to utilize gamma irradiation to reduce the microbial contamination and thereby extend the shelf life of this expensive shellfish under refrigerated temperatures.

Non-Invasive Tissue Injury Monitoring Using Bioimpedance Spectroscopy

An understanding of normal tissue response is necessary for the optimization of radiation treatment in cancer therapy. Cancer cells exhibit altered local dielectric properties compared to normal cells because of the difference in shape, size and orientation. These properties are measurable as a difference in electrical conductance using electrical impedance spectroscopy. Multiple frequency bioimpedance analysis is used to measure change in electrical properties of the irradiated tissues as a function of frequency and time. From the experimental results, it is clear that the electrical properties demonstrated good detection performance. The electrical parameters of the tissues could be used to distinguish the tissue's status. Changes in electrical properties at different frequencies show, that there are differences between conductivity of non-irradiated and irradiated tissues.

Effects of Radiation Therapy on Breast Epithelial Cells in BRCA1/2 Mutation Carriers.

Women carrying BRCA1 and BRCA2 mutations have significantly elevated risk of developing breast and ovarian cancers. BRCA1-associated breast cancer likely originates from progenitors of the luminal epithelial lineage. Recent studies indicate that radiation therapy (RT) for BRCA1 cancer patients is associated with lower incidence of developing subsequent ipsilateral breast cancer. In the current study, we analyzed tumor-free breast tissue procured via prophylactic bilateral mastectomy from three BRCA1 and one BRCA2 mutation carriers, who had been previously treated with RT for unilateral breast cancers. Freshly isolated breast cells from the irradiated and nonirradiated breast tissue of the same individuals were subjected to flow cytometry, using established cell-surface markers. Two out of the three BRCA1 carriers and one BRCA2 carrier exhibited significantly diminished luminal cell population in the irradiated breast versus the nonirradiated side. There was also RT-associated reduction in the colony-forming ability of the breast epithelial cells. Our finding suggests that prior RT could result in the depletion of the luminal epithelial compartment and thus reduced incidence of BRCA1/2-associated breast cancer.

Utility of immunohistochemical markers in irradiated breast tissue: an analysis of the role of myoepithelial markers, p53, and Ki-67.

Radiation therapy is an important adjunct to breast-conserving surgery, but the diagnosis of recurrent/de novo carcinoma in a background of radiation atypia can be difficult, especially on small biopsies. Immunostaining for myoepithelial cell proteins is often used to assess invasion in nonirradiated breast tissue, yet these stains have not been investigated specifically in irradiated breast. We studied 29 irradiated breast resection specimens, some with carcinoma in situ (CIS, n=13) and/or invasive carcinoma (n=13). Representative blocks were stained for the myoepithelial proteins p63, smooth muscle myosin heavy chain (SMM), calponin, CK5/6, the proliferative marker Ki-67, and the tumor-suppressor p53. Nonirradiated control tissue was also stained with Ki-67 and p53 (CIS, normal, contralateral). Areas of radiation atypia/atrophy and nearly all CIS in irradiated breast tissue had abundant myoepithelial cells as evidenced by SMM, calponin, and p63 stains, with focal staining attenuation or gaps with SMM and calponin and frequently absent CK5/6 staining. As predicted, myoepithelial cell staining was absent in invasive carcinoma. p63 staining revealed postradiation myoepithelial nuclear morphologic changes. p53 staining was increased, although weak, in irradiated non-neoplastic breast (12% irradiated; 4% nonirradiated); however, irradiated CIS had less p53 staining when compared with control CIS (3% irradiated; 38% nonirradiated). As expected, Ki-67 was increased in carcinoma as compared with non-neoplastic irradiated tissue. Thus, myoepithelial immunostaining is a useful diagnostic adjunct in irradiated breast, with caveats similar to nonirradiated breast. Ki-67 may be helpful in some postradiation specimens; however, p53 staining is not reliable in this setting.

Amelioration of cardiac function and activation of anti-inflammatory vasoactive peptides expression in the rat myocardium by low level laser therapy.

Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation.

Perineal reconstruction using pedicled vertical rectus abdominis myocutaneous flap (VRAM).

The perineal wound is a major source of morbidity after abdominoperineal resection (APR) for rectal cancer, particularly after preoperative irradiation. Myocutaneous flap reconstruction is a viable alternative to primary perineal wound repair providing well-vascularized non-irradiated tissue to fill the dead space, and improve wound healing. Sixty patients with low rectal cancer receiving neoadjuvant radiotherapy were prospectively randomized to either primary perineal wound closure (Group B) or VRAM perineal reconstruction (Group A). The study was carried out in the surgical department, National Cancer Institute (NCI), Cairo University over a period of 4 years from August 2008 to July 2012. All patients were evaluated as regards incidence of perineal wound complications, abdominal wall complications, and added co-morbidity. Perineal wound complications were observed in 5 patients in group A (17.2%) and in 14 patients in group B (46.4%) (P = 0.015). There was no significant difference in the incidence of abdominal wound morbidity between both groups. Operative blood loss and time were lower in group B. The vertical rectus myocutaneous flap (VRAM) is a relatively simple and reliable technique for perineal wound reconstruction after abdominoperineal resection.

Combined anterior cruciate ligament and posterolateral reconstruction of the knee using allograft tissue in chronic knee injuries.

Combined anterior cruciate ligament (ACL) and posterolateral injury of the knee can result in significant functional instability for the affected individual. Both components of the instability must be treated to maximize the probability of success for the surgical procedure. Higher failure rates of the ACL reconstruction have been reported when the posterolateral instability has been left untreated. The purpose of this article is to describe our surgical technique, and present the results of 34 chronic combined ACL posterolateral reconstructions in 34 knees using allograft tissue, and evaluating these patient outcomes with KT 1000 knee ligament arthrometer, Lysholm, Tegner, and Hospital for Special Surgery knee ligament rating scales. In addition, observations regarding patient demographics with combined ACL posterolateral instability, postoperative range of motion loss, postinjury degenerative joint disease, infection rate, return to function, and the use of radiated and nonirradiated allograft tissues will be presented.

Increased p16 DNA methylation in mouse thymic lymphoma induced by irradiation.

DNA methylation is an important part of epigenetics. In this study, we examined the methylation state of two CpG islands in the promoter of the p16 gene in radiation-induced thymic lymphoma samples. The mRNA and protein levels of P16 were significantly reduced in radiation-induced thymic lymphoma tissue samples. Twenty-three CpG sites of the CpG islands in the p16 promoter region were detected, and the methylation percentages of −71, −63, −239, −29, −38, −40, −23, 46 CpG sites were significantly higher in radiation-induced thymic lymphoma tissue samples than those in matched non-irradiated thymus tissue samples. This study provides new evidence for the methylation state of p16 in the radiation-induced thymic lymphoma samples, which suggests that the methylation of these CpG sites in the p16 promoter may reduce its expression in the thymic lymphoma after irradiation.

Use of Irradiated and Non-Irradiated Allograft Tissue in Anterior Cruciate Ligament Reconstruction Surgery: A Critical Analysis Review.

Mariscalco, Michael W. MD1; Magnussen, Robert A. MD1; Kaeding, Christopher C. MD1; Hewett, Timothy E. PhD1; Flanigan, David C. MD1,a Author Information

Vascular and Nerval Damage After Intraoperative Radiation Therapy of the Liver Hilum in a Large Animal Model

ABSTRACTIt has been demonstrated that intraoperative radiotherapy is a therapeutic option for patients suffering from perihilar cholangiocarcinoma. Aim of our study was to investigate vascular and nerve damages after irradiation of the liver hilum in a pig model. Twenty-four pigs underwent central bile duct resection followed by biliodigestive anastomosis. Nine pigs underwent this surgical procedure alone (group 1). Ten pigs were treated with additional intraoperative radiation therapy (IORT) of 20Gy to the liver hilum (group 2). And five pigs received operation and IORT with 40Gy to the area of anastomosis (group 3). Six weeks after operation and treatment the animals were sacrificed and histopathological examination was performed. Histology showed no vascular or nerve damage in non-irradiated perihilar tissue. Significant changes of nerve structures occurred, as well as vascular damage in large and even more in small hilar arteries in the irradiated neighboring liver tissue. In detail for small hilar arteries: intima proliferation (p ≤ .0001), endothelial swelling (p ≤ .0001), fibrinoid arterial wall necrosis (p ≤ .0001), and arterial thrombosis (p = .0079) were detected. Venous vessels did not show significant dose dependant cell damage. Overall, 20Gy as a single dose application during operation showed similar damage to vessels and nerves compared to 40Gy. A radiation dosage of 20Gy seems to be sufficient to induce necrosis due to vascular and nerve damage in potential malignant liver tissue with acceptable damage to surrounding tissue. Perineural invaded tumor cells might be diminished due to IORT.

Involvement of free radicals in breast cancer.

Researchers have recently shown an increased interest in free radicals and their role in the tumor microenvironment. Free radicals are molecules with high instability and reactivity due to the presence of an odd number of electrons in the outermost orbit of their atoms. Free radicals include reactive oxygen and nitrogen species, which are key players in the initiation and progression of tumor cells and enhance their metastatic potential. In fact, they are now considered a hallmark of cancer.However, both reactive species may contribute to improve the outcomes of radiotherapy in cancer patients. Besides, high levels of reactive oxygen species may be indicators of genotoxic damage in non-irradiated normal tissues. The purpose of this article is to review recent research on free radicals and carcinogenesis in order to understand the pathways that contribute to tumor malignancy.This review outlines the involvement of free radicals in relevant cellular events, including their effects on genetic instability through (growth factors and tumor suppressor genes, their enhancement of mitogenic signals, and their participation in cell remodeling, proliferation, senescence, apoptosis, and autophagy processes; the possible relationship between free radicals and inflammation is also explored. This knowledge is crucial for evaluating the relevance of free radicals as therapeutic targets in cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-404) contains supplementary material, which is available to authorized users.

Autograft Versus Nonirradiated Allograft Tissue for Anterior Cruciate Ligament Reconstruction

Background: An autograft has traditionally been the gold standard for anterior cruciate ligament reconstruction (ACLR), but the use of allograft tissue has increased in recent years. While numerous studies have demonstrated that irradiated allografts are associated with increased failure rates, some report excellent results after ACLR with nonirradiated allografts. The purpose of this systematic review was to determine whether the use of nonirradiated allograft tissue is associated with poorer outcomes when compared with autografts. Hypothesis: Patients undergoing ACLR with autografts versus nonirradiated allografts will demonstrate no significant differences in graft failure risk, laxity on postoperative physical examination, or differences in patient-oriented outcome scores. Study Design: Systematic review. Methods: A systematic review was performed to identify prospective or retrospective comparative studies (evidence level 1, 2, or 3) of autografts versus nonirradiated allografts for ACLR. Outcome data included graft failure based on clinical findings and instrumented laxity, postoperative laxity on physical examination, and patient-reported outcome scores. Studies were excluded if they did not specify whether the allograft had been irradiated. Quality assessment and data extraction were performed by 2 examiners. Results: Nine studies comparing autografts and nonirradiated allografts were included. Six of the 9 studies compared bone–patellar tendon–bone (BPTB) autografts with BPTB allografts. Two studies compared hamstring tendon autografts to hamstring tendon allografts, and 1 study compared hamstring tendon autografts to tibialis anterior allografts. The mean patient age in 7 of 9 studies ranged from 24.5 to 32 years, with 1 study including only patients older than 40 years and another not reporting patient age. The mean follow-up duration was 24 to 94 months. Six of 9 studies reported clinical graft failure rates, 8 of 9 reported postoperative instrumented laxity measurements, 7 of 9 reported postoperative physical examination findings, and all studies reported patient-reported outcome scores. This review demonstrated no statistically significant difference between autografts and nonirradiated allografts in any outcome measure. Conclusion: No significant differences were found in graft failure rate, postoperative laxity, or patient-reported outcome scores when comparing ACLR with autografts to nonirradiated allografts in this systematic review. These findings apply to patients in their late 20s and early 30s. Caution is advised when considering extrapolation of these findings to younger, more active cohorts.

Anterior Cruciate Ligament Reconstruction With Autografts Compared With Non-irradiated, Non-chemically Treated Allografts

Allograft anterior cruciate ligament (ACL) reconstruction obviates donor site morbidity and may accelerate postoperative recovery. However, allograft use can lead to increased rates of surgical failure, particularly when chemical processing or irradiation is used. Few studies have rigorously evaluated the comparative outcomes of autografts and fresh-frozen allograft tissue for ACL reconstruction. We performed a PubMed search to identify and systematically evaluate outcomes of autograft and non-chemically treated non-irradiated allograft tissue in ACL reconstruction between 1980 and 2012. We included studies with Level of evidence of I to III, determinate graft treatment, a minimum of 25 patients per treatment arm, a minimum 2-year follow-up, and selected subjective and objective outcome measures. After the exclusion of 585 citations, we isolated 11 studies for further review. All patients showed improvement in clinical outcome measures and knee stability end points from injury to definitive surgical management. No statistically significant differences were detected between autografts and non-chemically processed non-irradiated allografts in Lysholm scores, International Knee Documentation Committee (IKDC) scores, Lachman examinations, pivot-shift testing, KT-1000 measurements, or failure rates. Further large-scale, well-designed studies are required to better evaluate the comparative outcomes after fresh-frozen allograft ACL reconstruction. The current study suggests that the results after autograft ACL reconstruction are comparable to those using non-chemically processed nonirradiated allograft tissue. Systematic review of Level I to III studies.