Francis Patterson

Treatment of advanced metastatic lesions of the acetabulum using the saddle prosthesis

Current methods of treating advanced patients with metastatic periacetabular disease are complex and result in high complication rates. The purpose of this study was to show whether the implantation of the saddle prosthesis would serve as an additional tool to help treat metastatic disease in these patients. From 1991 to 2003, 20 patients with advanced metastatic periacetabular lesions (Harrington Class III) were treated using the saddle prosthesis. Goals of surgery were a decrease in pain, functional restoration, and ambulation. The mean age was 61 years. Average length of followup was 20 months. Postoperatively, ambulation was achieved in 16 of 20 patients. There were four postoperative complications (20%) in three patients. Surgical goals were met in 18 of 20 patients. The MSTS–ISOLS emotional score was 2.9 of 5. The average total MSTS–ISOLS score was 16.6 of 30 (55%). Using the Allan scoring system consisting of analgesia, independence and ambulation, and mobility, all scores had significant improvements postoperatively. Careful surgical indications and technique should result in a stable, functional reconstruction allowing patients the ability to ambulate outside the house with a cane. Patients can expect to be emotionally satisfied with the procedure while using nonnarcotic analgesia and can expect an improved quality of life despite bone metastasis.

Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases

Abstract Purpose. The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2α), as possible markers of prognostic significance. Methods. From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases. Results. The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2α. Spearmans correlation co-efficient was 0.86 with P=0.001 (n=17). Conclusions. In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fishers exact test, P=0.02).

HER-2/neu and p53 in Osteosarcoma: An Immunohistochemical and Fluorescence In Situ Hybridization Analysis

The overexpression of HER-2/neu and p53 has been associated with poor outcome in many neoplasms. Their role in patients with osteosarcoma is unclear. We studied the expression of HER-2/neu and p53 in 22 osteosarcoma samples (from 20 patients—2 had locally recurrent disease) biopsied at the University of Medicine and Dentistry of New Jersey (UMDNJ) from 1996–2000 using both immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Fourteen patients (14 samples) presented with Stage II and 6 patients (8 samples) presented with Stage III disease. Median follow-up is two years (range one year to five years). Four of 22 (18%) samples showed focal membranous or cytoplasmic positivity for HER-2/neu and six of 22 samples (27%) showed nuclear positivity for p53 by IHC analysis. In contrast, none of 22 tested samples showed gene amplification for HER-2/neu by FISH analysis. Seven of 13 HER-2/neu and p53 negative patients (54%) are currently disease free (between one year to five years). In this sample of patients, the HER-2/neu oncogene is not overexpressed or amplified in osteosarcoma; six of 22 samples (27%) showed overexpression of p53 by IHC analysis. By FISH, none of the samples demonstrated deletion of p53. Neither HER2/neu nor p53 expression was important for the biology of osteosarcoma in this population.

Reconstruction of musculoskeletal defects following oncologic resection in 76 patients.

Between 1990 and 2002, 76 patients underwent 102 muscle flap reconstructions for extremity sarcomas. The patients had radical resection with immediate reconstruction. Reconstructions were performed by the Musculoskeletal Oncology and Plastic Surgery services. The mean age of our patients was 39.1 years. Patients were studied for a mean of 25.4 months. There were 79 pedicle flaps and 23 free flaps. Complications occurred in 23.7% of patients, including wound necroses, seromas, postoperative bleeding, postoperative infections, and flap loss. Five patients required a secondary flap procedure. The overall flap survival rate was 98%. Three patients had local recurrences. Sixteen patients (21.1%) have died of their disease. Five patients are alive with metastases. In 54 patients, Musculoskeletal Tumor Society (MSTS) functional evaluation scores averaged 27.1 (range, 12–30). In this large series of patients, we have demonstrated that, although minor complications are common, functional limbs can be salvaged following oncologic resection from the extremities.

p16 immunohistochemistry as an alternative marker to distinguish atypical lipomatous tumor from deep-seated lipoma.

Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) is a locally aggressive malignant mesenchymal neoplasm, resembling ordinary lipoma in many clinical aspects. This study investigates the value of expression of p16, an important cell cycle regulator, alone or in combination with MDM2, to distinguish the 2 entities. Fifty cases of lipomatous neoplasms, with cytogenetic results, from 45 patients were collected from the archives in Department of Pathology, University of Medicine and Dentistry of New Jersey/New Jersey Medical School during 1998 to 2006. These include 18 cases of deep-seated lipoma, 1 hibernoma, 1 lipoblastoma, and 30 cases of ALT/WDLPS. p16 was detected in 25/30 (83.3%) of ALT/WDLPS, and none (0/18) of the deep-seated lipomas (P<0.0000001, Fisher exact test). MDM2 was detected in 18/30 (60%) of ALT/WDLPS, and was negative in 0/18 of the deep-seated lipomas (P<0.0001, Fisher exact test). Combined together, 27/30 (90%) of ALT/WDLPS showed positive staining of either p16, MDM2, or both, whereas no staining was observed in all the deep-seated lipomas (P<0.0000001, Fisher exact test). The single case of hibernoma and lipoblastoma revealed p16+MDM2− phenotype. These results indicated that p16 is yet another marker which seems to be a valuable marker to differentiate ALT/WDLPS from deep-seated lipomas.

Immediate reconstruction of oncologic hemipelvectomy defects.

Background:Soft tissue and bony tumors of the pelvis are rare, but when they occur, treatment presents both an oncologic surgical and a reconstructive challenge. After reconstruction, soft tissue defects can be large and there is usually exposed bone and/or joint. A retroperitoneal abdominal wall defect may also be present. Flap mobilization is generally necessary to eliminate dead space and cover the exposed bone, viscera, and/or prosthetic orthopedic material. We performed immediate reconstruction on 11 patients after radical pelvic resections for tumor. Patients and Methods:Eleven cases of radical pelvic resection and immediate reconstruction were identified during the period from 1992 to 2002 at University Hospital, Newark, New Jersey. All patients were treated by both the orthopedic oncology and plastic surgery teams. A retrospective review of office charts and hospital records was performed. Data were gathered regarding the following: tumor type and oncologic history, extent of resection, reconstructive modality, complications, and outcome. Results:All patients underwent radical resection of pelvic masses depending on the tumor type and location. Tumor types included chondrosarcoma (6), Paget osteosarcoma (1), giant cell tumor (1), metastatic uterine carcinoma (2), and invasive squamous cell carcinoma arising in a chronic decubitus ulcer (1). The reconstructive procedures performed were the following: rectus abdominus flaps (6), gluteus maximus musculocutaneous flaps (3), and thigh fillet flaps (2). The retroperitoneal defects were repaired with primary tissue approximation of the surrounding available musculature. Additionally, Gore-Tex mesh was used in 2 cases, tensor fascia lata was used in 2 cases, and acellular dermal matrix in 1 case. Blood loss for the combined procedures ranged from 400 mL to 1400 mL. The follow-up period in this series ranged from 24 to 114 months. Complications included skin flap loss with subsequent infection (1), local cellulitis controlled with antibiotics (1), regional recurrence (2). The postoperative course was uneventful for the remainder of the cases. Conclusion:Soft tissue reconstructions after extensive pelvic resections always present as complex reconstructive problems. Reconstruction is dictated by the size of the defects and by tissue availability. The extent and type of resections vary according to tumor size and location. In our experience, local pedicled muscle-based flaps, if available, usually provide adequate tissue mass to eliminate dead space, cover the extent of the wound, and close the retroperitoneal defect. Microvascular tissue transfer is always an option but was reserved in our series for cases with no suitable local alternative.

Outcomes of a Modular Intercalary Endoprosthesis as Treatment for Segmental Defects of the Femur, Tibia, and Humerus

BackgroundResection of diaphyseal bone tumors for local tumor control and stabilization often results in an intercalary skeletal defect and presents a reconstructive challenge for orthopaedic surgeons. Although many options for reconstruction have been described, relatively few studies report on the functional outcomes and complications of patients treated with modular intercalary endoprostheses.Questions/purposesThe objectives of this study were to examine clinical outcomes after reconstruction with a modular intercalary endoprosthesis with a specific focus on (1) the rate of complication or failure; (2) differences in complication rates by anatomic site; (3) functional results as assessed by the Musculoskeletal Tumor Society System (MSTS); and (4) differences in complication rate between patients treated with cemented versus noncemented fixation.MethodsWe conducted a retrospective chart review of patients treated with a modular intercalary endoprosthesis from three musculoskeletal oncology centers from 2008 to 2013. The indication for use of this intercalary endoprosthesis was segmental bone loss from aggressive or malignant tumor with sparing of the joint above and below and deemed unsuitable for biologic reconstruction. No other implant was used for this indication during this period. During this period, 41 patients received a total of 44 intercalary implants, which included 18 (40%) humeri, 5 (11%) tibiae, and 21 (48%) femora. There were 27 (66%) men and 14 (34%) women with a mean age of 63 years (range, 18–91 years). Eight patients (20%) had primary bone tumors and 33 (80%) had metastatic lesions. Thirty-five (85%) patients were being operated on as an initial treatment and six (15%) for revision of a previous reconstruction. Twenty-nine (66%) procedures had cemented stem fixation and 15 (34%) were treated with noncemented fixation. The overall mean followup was 14 months (range, 1–51 months). Patients with primary tumors had a mean followup of 19 months (range, 4–48 months) and patients with metastatic disease had a mean followup of 11 months (range, 1–51 months). Causes of implant failure were categorized according to Henderson et al. [19] into five types as follows: Type I (soft tissue failure), Type II (aseptic loosening), Type III (structural failure), Type IV (infection), and Type V (tumor progression). At 2 years of followup, 38 (93%) of these patients were accounted for with three (7%) lost to followup. MSTS functional assessment was available for 39 of 41 patients (95%).ResultsAt latest followup of these 41 patients, 14 (34%) patients were dead of disease, two patients (5%) dead of other causes, seven (17%) are continuously disease-free, one (2%) shows no evidence of disease, and 17 (41%) are alive with disease. There were 12 (27%) nononcologic complications. Five (11%) of these were Type II failures occurring in noncemented implants between the stem and bone, and six (14%) were Type III failures occurring in cemented implants at the clamp-rod implant interface. One patient developed a deep infection (2%, Type IV failure) and underwent removal of the implant. Additionally, one patient (2%, Type V failure) was treated by amputation after local progression of his metastatic disease. Complications were more common in femoral reconstructions than in tibial or humeral reconstructions. Twelve of 21 patients (57%) with femoral reconstructions had complications versus 0% of tibial or humeral reconstructions (0 of 23; odds ratio [OR], 62; 95% confidence interval [CI], 3–1154; p < 0.0001). The mean overall MSTS score was 77%. Implants with cemented fixation (29) had higher mean MSTS scores when compared with implants with noncemented (15) fixation (84% versus 66%, p = 0.0017). The complication rate was 33% in noncemented cases and 21% in cemented cases (p = 0.39); however, Type II failure at the bone-stem interface was associated with noncemented fixation and Type III failure at the clamp-rod interface was associated with cemented fixation (OR, 143; 95% CI, 2.413–8476; p = 0.0022).ConclusionsThe results of this study indicate that this modular intercalary endoprosthesis yields equivalent results to other studies of intercalary endoprostheses in terms of MSTS scores. We found that patients treated with intercalary endoprostheses in the femur experienced more frequent complications than those treated for lesions in either the humerus or tibia and that the femoral complication rate of this endoprosthesis is higher when compared with other studies of intercalary endoprostheses for femoral reconstruction. Further studies are still needed to determine the long-term outcomes of this endoprosthesis in patients with primary tumors where longevity of the implant is of more importance than in the metastatic setting. We recommend cemented fixation for this intercalary modular endoprostheses because this provides improved MSTS scores and allows immediate return to weightbearing, which is of advantage to metastatic patients with limited lifespans.Level of EvidenceLevel III, therapeutic study.

Liquid-Based vs. Conventional Smears in Fine Needle Aspiration of Bone and Soft Tissue Tumors

OBJECTIVE To compare the accuracy of fine needle aspiration cytology of bone and soft tissue tumors utilizing ThinPrep (TP) (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) vs. conventional smears (CS). STUDY DESIGN Fine needle aspiration cytology from bone and soft tissue tumors was processed and assessed for cellularity, nuclear and cytoplasmic preservation, cellular architecture and stromal background with both the TP liquid-based smear technique and conventional methods. RESULTS An accurate diagnosis was made in 13% of TP cases as compared to 64% in CS cases. CONCLUSION CS of fine needle aspiration sample is far superior to TP in diagnosing tumors of bone and soft tissues. Preservation of cytoplasmic features and cellular architecture was superior in conventionally prepared smears.

OPERATIVE MANAGEMENT OF METASTASES TO THE PELVIS AND ACETABULUM

Bone metastases to the acetabulum and pelvis can be a devastating and debilitating problem. In certain patients, operative reconstruction of the involved hip can lead to maintenance of independence, pain control, and an increase in the overall quality of life for their remaining life span. These procedures are technically challenging and are associated with a higher complication rate than that for patients having surgery for nonneoplastic disease. They are probably best performed by surgeons with specific training and expertise in tumor surgery and acetabular reconstruction. With proper patient selection, appropriate component use, and competent surgical technique, good-to-excellent results can be obtained.

Functional outcomes after limb-salvage surgery and endoprosthetic reconstruction with an expandable prosthesis: a report of 4 cases.

OBJECTIVE To determine the functional outcomes of skeletally immature patients after replacement of the femur and tibia performed by using noninvasive expandable endoprostheses. DESIGN Case series. SETTING A hospital-based ambulatory care center. PARTICIPANTS Pediatric patients (N=4) with primary bone tumors of the distal femur and proximal tibia who underwent surgical replacement performed by using the Repiphysis noninvasive expandable endoprosthesis (Wright Medical Technology, Memphis, TN). INTERVENTIONS Wide resection of bone sarcoma and placement of expandable endoprosthesis. MAIN OUTCOME MEASURES Musculoskeletal Tumor Society (MSTS) scores were assessed at the beginning of the study and at each follow-up visit. Medical Outcomes Study 36-Item Short-Form Health Survey, Version 2 (SF-36); gait; sit-to-stand transition; and range of motion (ROM) were assessed at an average follow-up of 31.5 months. RESULTS At an average of 31.5 months postoperative, the SF-36 physical component summary scores lagged behind the national mean, whereas the mental component summary scores were satisfactory. MSTS scores indicated low levels of pain and supports use with high emotional acceptance and walking ability but persisting difficulties with function and gait. Patients also showed altered patterns of sit-to-stand transition including decreased peak vertical force in the operated limb and increased center of mass momentum in a shorter amount of time. Parts of gait functioning were found to be decreased, including gait velocity, stride length, and cadence. Some patients displayed alternate weight-bearing strategies that accompanied increased double-limb support and stance phase during walking. ROM and strength were diminished at both the hip and knee joints in the operated limb and in the nonoperated limb. CONCLUSIONS Reconstruction with a noninvasive expandable endoprosthesis produces satisfactory functional outcomes in pediatric patients with primary tumors of the bone. Patients in our study displayed some persisting physical difficulties including decreased ROM and strength and altered gait and sit-to-stand patterns, yet they maintained high levels of emotional acceptance and coping.