The vestibulocochlear bases for wartime posttraumatic stress disorder manifestations.

Preliminary findings based on earlier retrospective studies of 229 wartime head injuries managed by the Walter Reed Army Medical Center (WRAMC)/National Naval Medical Center (NNMC) Neurosurgery Service during the period 2003-08 detected a threefold rise in Posttraumatic Stress Disorder (PTSD) manifestations (10.45%) among Traumatic Brain Injuries (TBI) having concomitant vestibulocochlear injuries compared to 3% for the TBI group without vestibulo-cochlear damage (VCD), prompting the authors to undertake a more focused study of the vestibulo-auditory pathway in explaining the development of posttraumatic stress disorder manifestations among the mostly Blast-exposed head-injured. The subsequent historical review of PTSD pathophysiology studies, the evidence for an expanded vestibular system and of a dominant vestibular system, the vascular vulnerability of the vestibular nerves in stress states as well as the period of cortical imprinting has led to the formation of a coherent hypotheses utilizing the vestibulocochlear pathway in understanding the development of PTSD manifestations. Neuroimaging and neurophysiologic tests to further validate the vestibulocochlear concept on the development of PTSD manifestations are proposed.

Functional outcomes after treatment of aggressive tumors in the distal radius.

We aimed to determine whether wide excision and radiocarpal arthrodesis in patients with aggressive tumors of the distal radius resulted in more significant functional deficit than joint salvage procedures. We compared functional outcomes, surgical complications, and local tumor relapse in 33 consecutive patients. Fourteen patients initially had joint-sparing procedures, whereas 19 underwent wide resection and arthrodesis. At minimum final followup of 18 months (mean, 96 months; range, 18-204 months), local tumor relapse occurred in five of 14 patients after joint salvage versus zero of 19 after arthrodesis. Two of five patients with tumor recurrence retained their native joints, whereas three underwent resection and arthrodesis. Six of 19 patients had complications, including one nonunion, for which we performed additional surgery after arthrodesis. All patients remained disease-free at followup and none developed metastases. Disabilities of the Arm, Shoulder and Hand score, Toronto Extremity Salvage Score, and Musculoskeletal Tumor Society scores all indicated more disability after arthrodesis. Persistent pain, radiographic wrist arthritis, and weaker grip strength was seen in some patients following joint salvage. Whenever possible, joint preservation is preferable for the result of better extremity function, but weaker grip, higher local tumor relapse, and late arthritis remain concerns.

The influence of anatomic location on functional outcome in lower-extremity soft-tissue sarcoma.

BACKGROUND: The purpose of this study was to explore the relationship between the anatomical location of lower-extremity soft-tissue sarcoma and functional outcome. METHODS: Function was evaluated with the Musculoskeletal Tumor Society (MSTS 1993) score and Toronto Extremity Salvage Score (TESS); 207 patients (median age, 54 years) were eligible. The median maximum tumor diameter was 8.0 cm; 58 tumors were superficial and 149 were deep. Nine locations based on anatomical compartments were defined: 6 tumors were in the groin/femoral triangle; 8, the buttock; 52, the anterior thigh; 22, the medial thigh; 20, the posterior thigh; 10, the popliteal fossa; 13, the posterior calf; 11, the anterolateral leg; and 7, the foot or ankle. RESULTS: Treatment of superficial tumors did not lead to significant changes in MSTS score (mean, 90.6% preoperatively vs. 93.0% postoperatively; P =.566) or TESS (mean, 86.4% preoperatively vs. 90.9% postoperatively; P =.059). Treatment of deep tumors lead to significant reductions in MSTS score and TESS (mean MSTS, 86.9% preoperatively vs. 83.0% postoperatively; P =.001; and mean TESS, 83.0% preoperatively vs. 79.4% postoperatively; P =.015). Anatomical location was not a significant predictor of aggregated MSTS and TESS evaluations. Exploratory analysis showed variation in MSTS pain and gait handicap or limp items and TESS dressing, sitting, bending, and bathing items by anatomical location. CONCLUSIONS: The treatment of superficial tumors does not lead to significant changes in MSTS score or TESS. Anatomical location is not a significant predictor of aggregated MSTS and TESS evaluations. However, there is variation in MSTS and TESS item scores across anatomical locations.

Preoperative radiotherapy is effective in the treatment of fibromatosis.

The use of preoperative radiation is well-established for soft tissue sarcoma, but its use in fibromatosis is not well-characterized. The purpose of this study was to examine the impact of preoperative radiotherapy on the local control of fibromatosis and to assess treatment-related morbidity in this setting. In particular we assessed complication rates in comparison with soft tissue sarcoma treatment. All patients with fibromatosis referred to this unit who received preoperative radiotherapy (50 Gy in 25 fractions) from 1988 to 2000 and who had at least 2 years of followup were included in this study. The rate of recurrence in this group was ascertained. Similarly constructed datasets from all patients with soft tissue sarcomas of the extremities who received preoperative radiation from 1986 to 1997 also were analyzed. The rates of complications in the two groups were compared. Fifty-eight patients were treated with preoperative radiation for fibromatosis and the median followup was 69 months. There were 11 local recurrences (19%). Major wound complications manifested in two patients (3.4%). Wound-related complications arose in 89 of 265 patients with soft tissue sarcomas (33.5%). There was a significant difference in the rate of major wound complications observed in the two groups. The use of radiotherapy before surgery is effective in the combined treatment of fibromatosis.

Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.

Instability after major tumor resection: prevention and treatment.

Instability is a significant problem after resection of musculoskeletal tumors. In this article, the authors discuss the issue of instability after resections of the pelvis, the femur, and the proximal tibia. The options for reconstruction in each area are discussed along with a review of the literature and a description of the authors' preferred approach.

Comparison of p53 mutations in patients with localized osteosarcoma and metastatic osteosarcoma.

BACKGROUND: In some malignancies, p53 mutations are associated with tumor progression. To address the role of p53 mutations in the development and progression of osteosarcoma, the authors analyzed specimens from 247 patients with primary localized osteosarcomas and 25 patients with osteosarcomas that were metastatic at the time of diagnosis. The group included 27 matched biopsy-resection specimens and 21 biopsy-metastasis paired specimens. METHODS: The authors examined the nature and location of p53 mutations (exons 4-10) by polymerase chain reaction-single-strand conformation polymorphism and confirmed mutations by direct DNA sequencing. RESULTS: The overall frequency of p53 mutations was 22% (60 of 272 specimens), with 13 of 60 mutations located in exons 4 or 10. A similar proportion of localized osteosarcomas had alterations of the p53 gene (55 of 247 specimens; 22.3%) compared with tumors from patients who had metastases at the time of diagnosis (5 of 25 specimens; 20%; P = 0.96). Patients who had p53 missense mutations were older compared with patients who had nonsense alterations or a wild type gene (P = 0.01). Examination of paired biopsy-resection and biopsy-metastasis specimens revealed that the p53 status was concordant between the biopsy and later tumor specimens in all patients. CONCLUSIONS: The p53 mutation status did not differentiate between patients who presented with a localized osteosarcoma and those who presented with metastases at the time of diagnosis. The current data indicate that p53 mutations are not late events in osteosarcoma tumor progression, because they are evident before the development of metastases. The inclusion of exons 4 and 10 increased the sensitivity of the analysis.

Periosteal chondroid tumors: radiologic evaluation with pathologic correlation.

OBJECTIVE: The purpose of this study was to determine whether the imaging features of periosteal chondroid tumors correlate with histopathology. MATERIALS AND METHODS: Twenty-two patients (nine women and 13 men; mean age, 33 years) with pathologically proven periosteal chondroid lesions were retrospectively reviewed. The imaging modalities included conventional radiography (n = 17), CT (n = 10), and MR imaging (n = 14). The images were reviewed by two osteoradiologists, with agreement by consensus. Evaluation criteria included lesion location, mineralization, and size; periosteal reaction; and cortical response. Intramedullary extension, adjacent intramedullary edema, soft-tissue edema, and intrinsic characteristics were also evaluated on MR imaging. After the evaluation, a radiologic diagnosis of chondroma or chondrosarcoma was obtained. An experienced osteopathologist who was unaware of the patient's medical history and radiologic findings reviewed all histopathology. Agreement between the radiologic and the histopathologic diagnosis was tested using the kappa analysis. Imaging features were correlated with the pathologic findings, and a statistical analysis was performed. RESULTS: Using strict pathologic criteria, we diagnosed 11 chondromas and 11 chondrosarcomas (nine, grade I; two, grade II). Moderate agreement was reached between the radiologic and the pathologic diagnosis (kappa = 0.55). The size of periosteal chondrosarcomas (range, 3-14 cm; median, 4 cm) was considerably larger than the size of the chondromas (range, 1-6.5 cm; median, 2.5 cm; p < 0.05). Other imaging features did not significantly correlate with benign versus malignant disease at pathology (all p > 0.05). CONCLUSION: A variable overlap existed in the imaging appearances of benign and malignant periosteal chondroid lesions, with size being the most reliable indicator in distinguishing the two lesions. This and the fact that histologic differentiation of the entities can be difficult, suggests that surgical wide excision may be the most appropriate procedure in treating patients with lesions greater than 3 cm.

Extraskeletal Ewing sarcoma in a 77-year-old woman.

Extraskeletal Ewing sarcoma (EES) is a rare soft tissue tumor that is morphologically indistinguishable from Ewing sarcoma of bone. It is usually found in young people, but several cases have occurred in patients older than 50 years. The differential diagnoses include other small, blue round cell tumors (SBRCTs) and other members of the Ewing family of tumors such as the primitive neuroectodermal tumor. We present a case of EES in the left inguinal region of a 77-year-old woman. The tumor was distinguished from other SBRCTs by lack of immunoreactivity for epithelial, lymphoid, vascular, neuroendocrine, neural, histiocytic, and muscle markers. Primitive neuroectodermal tumor was excluded because of the lack of neural differentiation by histologic analysis, immunohistochemistry, and electron microscopy. Extraskeletal Ewing sarcoma was confirmed by characteristic features on histologic analysis, histochemistry, immunohistochemistry, and electron microscopy and by the presence of the t(11;22)(q24;q12) fusion transcript detected by reverse transcriptase-polymerase chain reaction. This case serves to remind the reader that EES is not a tumor that occurs exclusively in young patients.

Functional evaluation in distal femoral endoprosthetic replacement for bone sarcoma.

A multicenter study of successfully treated patients (mean age, 36.7 years) with a minimum 1-year followup (average, 35.4 months) after distal femoral endoprosthetic replacement for bone sarcoma was done using the 1987 and 1993 versions of the Musculoskeletal Tumor Society, the Short Form-36, and the Toronto Extremity Salvage Score functional evaluation criteria. Fifty-six patients (28 women and 28 men) fulfilled the criteria. Thirty-one Kotz prostheses (fixed hinge, uncemented) and 25 Modular Replacement System Prostheses (rotating hinge, cemented) were used. Thirty-five patients walked without aids, 19 used a cane, and two used crutches or a walker. The Musculoskeletal Tumor Society 1987 mean score was 28.1. The Musculoskeletal Tumor Society 1993 mean score was 80.4. The Toronto Extremity Salvage Score mean was 81.6. The Short Form-36 Physical Component Score had a mean of 43.2 and Mental Component Score mean of 54.2. The two groups of implants were comparable, except for the length of bone resection. Multivariate regression analysis revealed that patient age, existence of a pathologic fracture, and type of prosthesis all significantly accounted for differences in functional outcome as measured by the Musculoskeletal Tumor Society 1993, the Toronto Extremity Salvage Score, and the Short Form-36 Physical Component Score scales. Although both implants provided satisfactory function, the Musculoskeletal Tumor Society 1993 and the Toronto Extremity Salvage Score results were significantly better with the Modular Replacement System prosthesis. The effect of possible differences among surgeons or institutions was not addressed.

Comparison of two methods of reconstruction for primary malignant tumors at the knee: a sequential cohort study.

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the complications and functional outcome associated with the use of an irradiated allograft-implant composite or a bone-ingrowth modular tumor prosthesis for replacement of the knee joint after resection of a bone sarcoma from the distal femur or proximal tibia. METHODS: Eleven patients initially received an allograft reconstruction, followed by 64 treated with a tumor prosthesis. The primary analysis concerned reconstructive failure, defined by the requirement for removal of the original construct. Functional outcome was assessed by using the 1987 Musculoskeletal Tumor Society rating system. RESULTS: Reconstructive failure occurred in 6 of 11 (55%) allograft constructs compared with 10 of 64 (16%) tumor prostheses (P = 0.009). Failures were due to infection (2 of 11 allografts versus 4 of 64 prostheses; P = 0.2) or mechanical complications (4 of 11 allograft fractures versus 5 of 64 broken prosthetic stems and 1 aseptically loose prosthesis; P = 0.03). The limb salvage rate was 95% (61 of 64) for patients with a tumor prosthesis compared with 64% (7 of 11) for those with an allograft (P = 0.007). Patients with a tumor prosthesis had a better functional outcome with a mean score of 75% compared with 57% for those with an allograft reconstruction (P = 0.006). CONCLUSIONS: This comparative study suggests that limb salvage surgery at the knee has a better and more predictable outcome with a tumor prosthesis than with an allograft-implant reconstruction.

p53 missense but not truncation mutations are associated with low levels of p21(CIP1/WAF1) mRNA expression in primary human sarcomas.

Many growth-suppressing signals converge to control the levels of the CDK inhibitor p21(CIP1/WAF1). Some human cancers exhibit low levels of expression of p21(CIP1/WAF1) and mutations in p53 have been implicated in this down-regulation. To evaluate whether the presence of p53 mutations was related to the in vivo expression of p21(CIP1/WAF1) mRNA in sarcomas we measured the p21(CIP1/WAF1) mRNA levels for a group of 71 primary bone and soft tissue tumours with known p53 status. As expected, most tumours with p53 mutations expressed low levels of p21(CIP1/WAF1)mRNA. However, we identified a group of tumours with p53 gene mutations that exhibited normal or higher levels of p21(CIP1/WAF1) mRNA. The p53 mutations in the latter group were not the common missense mutations in exons 4-9, but were predominantly nonsense mutations predicted to result in truncation of the p53 protein. The results of this study suggest that different types of p53 mutations can have different effects on the expression of downstream genes such as p21(CIP1/WAF1) in human sarcomas.

Soft tissue sarcomas involving the pelvis.

BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) of the true pelvis are rare tumors and there is little information in the literature related to pelvic STS. The purposes of this review were to understand the anatomic extension of these tumors to better plan surgical treatment and to determine the outcome of these patients. METHODS: Eighteen consecutive patients presenting between 1987 and 1995 with soft tissue sarcomas involving the true pelvis were retrospectively reviewed at minimum follow-up of 18 months. Cross-sectional imaging was reviewed for each patient to determine the anatomical location of the lesions. RESULTS: The tumors were confined to the true pelvis in 4 patients, extended to the retroperitoneum in three cases, and extended to the thigh in 11 patients. Adjuvant radiation was administered to all but 2 patients who had received radiation to the region in the past and all patients underwent surgical resection (local resection in 13 patients and hindquarter amputation in 5 patients). Surgical resection had a high rate of morbidity and complications including positive resection margins in nine individuals. Of the 18 patients, 11 died at a mean time of 15.5 (2-58) months from surgery, 4 were alive with evidence of disease at a mean time of 44.3 (18-68) months, and 3 were alive with no evidence of disease at a mean time of 57 (43-71) months. CONCLUSIONS: Soft tissue sarcoma of the pelvis is fortunately a rare disease with a high risk of local and systemic disease progression despite treatment with irradiation and surgical resection.

Changing rates of cancer. The hazards of using a single definition.

Changing cancer rates, abstracted from tumor registries, are used to make inferences about the effect of carcinogens and cancer treatments on a population-wide basis. We compared the annual age-standardized incidence rates of extremity soft tissue sarcomas from two large tumor registries using different case definitions. We identified all limb soft tissue sarcoma cases diagnosed 1973-1993 in the Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology, and End Results (SEER) databases. Two case definitions for limb soft tissue sarcoma were used based on missing data, incomplete diagnostic methods and ICD-9 codes; an upper limit estimate of the rates which included all possible cases of limb soft tissue sarcoma and a lower limit estimate of the rates which included all definite cases of limb soft tissue sarcoma (with the true rates lying in between). The upper limit OCR rates showed a statistically significant decreasing linear trend (slope = -0.021, P < 0.01). Whereas the slope of the OCR lower limit regression line showed a statistically significant increase in rates (slope = 0.01, P = 0.04). Neither the upper or lower limit SEER rates had a statistically significant linear trend (slope = 0.002, P = 0.60 and slope = 0.001, P = 0.18, respectively). Case definition affects incidence rates and changing rates of cancer. Thus the use of a single case definition along with changing coding practices may alone explain changing cancer rates.

Sciatic nerve resection in the thigh: a functional evaluation.

Patients with a soft tissue malignancy involving the sciatic nerve who present with neurologic loss generally are advised to have an amputation. Twenty patients who underwent limb-sparing procedures with complete resection of the sciatic nerve as treatment for neurofibrosarcomas (12 patients), liposarcomas (four patients), malignant fibrous histiocytomas (two patients), recurrent desmoid tumor (one patient), and epithelioid hemangioendothelioma (one patient) were reviewed retrospectively. The mean age of these nine women and 11 men at the time of surgery was 51 years (range, 28-84 years). The right sciatic nerve was affected in 12 patients. These tumors were large and high grade. A mean of 22 cm of the nerve had to be resected (range, 8-42 cm). Ten patients received preoperative radiotherapy and 16 patients had intraoperative or postoperative radiotherapy. At a mean followup of 35 months (range, 7-97 months), 14 of the 20 patients were alive. Two patients had local recurrences develop (10%), whereas 12 patients had distant metastases. The function of the 10 patients as assessed by the Toronto Extremity Salvage Score averaged 74%. Most patients indicated that walking in the house is not difficult, but walking is compromised as soon as an effort is needed. Four patients walk without a cane, four needed one cane, and two needed two canes. The patients experienced stiffness, a sense of numbness, and premature fatigue. The use of analgesics was infrequent. Generally, patients rated themselves to be mildly to moderately disabled. From this small number of patients, it is shown that a tumor involving the sciatic nerve can be treated by limb-sparing surgery, including complete nerve resection, as an alternative to hip disarticulation or hindquarter amputation because the limb salvage option provides an acceptable functional outcome.

Pathologic fractures of the proximal femur secondary to benign bone tumors.

Pathologic fractures of the proximal femur secondary to benign bone tumors often are difficult to treat because of specific anatomic features of this region and the aggressiveness of the tumors. Between 1986 and 1996, 11 patients presented with a pathologic fracture of the proximal femur secondary to a benign bone tumor. All were treated with a uniform approach consisting of biopsy, intralesional curettage, high-speed burring, and reconstruction using morselized allograft, autograft, and a fixed-angle implant. The average followup was 4 years 3 months (range, 24-114 months). One patient was lost to followup. All fractures healed, and there were no local recurrences and no cases of avascular necrosis. Functional evaluation revealed generally good results. Patients scored a mean of 32.6 on the original Musculoskeletal Tumor Society scale and 95.8 on the revised version. The average Toronto Extremity Salvage Score was 91.3. With the numbers available, there were no significant differences between the study group and population norms in the Short Form-36. These results suggest that a uniform approach based on preservation of the femoral head can be applied successfully to the treatment of these lesions with good local tumor control, fracture healing, and acceptable functional outcomes.

Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence.

We considered whether a positive margin occurring after resection of a soft-tissue sarcoma of a limb would affect the incidence of local recurrence. Patients with low-grade liposarcomas were expected to be a low-risk group as were those who had positive margins planned before surgery to preserve critical structures. Two groups, however, were expected to be at a higher risk, namely, patients who had undergone unplanned excision elsewhere with a positive margin on re-excision and those with unplanned positive margins occurring during primary resection. Of 566 patients in a prospective database, 87 with positive margins after limb-sparing surgery and adjuvant radiotherapy were grouped according to the clinical scenario by an observer blinded to the outcome. The rate of local recurrence differed significantly between the two low- (4.2% and 3.6%) and the two high-risk groups (31.6% and 37.5%). This classification therefore provides useful information about the incidence of local recurrence after positive-margin resection.