Association of Preoperative Patient Frailty and Operative Stress With Postoperative Mortality.

Importance: Patients with frailty have higher risk for postoperative mortality and complications; however, most research has focused on small groups of high-risk procedures. The associations among frailty, operative stress, and mortality are poorly understood. Objective: To assess the association between frailty and mortality at varying levels of operative stress as measured by the Operative Stress Score, a novel measure created for this study. Design, Setting, and Participants: This retrospective cohort study included veterans in the Veterans Administration Surgical Quality Improvement Program from April 1, 2010, through March 31, 2014, who underwent a noncardiac surgical procedure at Veterans Health Administration Hospitals and had information available on vital status (whether the patient was alive or deceased) at 1 year postoperatively. A Delphi consensus method was used to stratify surgical procedures into 5 categories of physiologic stress. Exposures: Frailty as measured by the Risk Analysis Index and operative stress as measured by the Operative Stress Score. Main Outcomes and Measures: Postoperative mortality at 30, 90, and 180 days. Results: Of 432 828 unique patients (401 453 males [92.8%]; mean (SD) age, 61.0 [12.9] years), 36 579 (8.5%) were frail and 9113 (2.1%) were very frail. The 30-day mortality rate among patients who were frail and underwent the lowest-stress surgical procedures (eg, cystoscopy) was 1.55% (95% CI, 1.20%-1.97%) and among patients with frailty who underwent the moderate-stress surgical procedures (eg, laparoscopic cholecystectomy) was 5.13% (95% CI, 4.79%-5.48%); these rates exceeded the 1% mortality rate often used to define high-risk surgery. Among patients who were very frail, 30-day mortality rates were higher after the lowest-stress surgical procedures (10.34%; 95% CI, 7.73%-13.48%) and after the moderate-stress surgical procedures (18.74%; 95% CI, 17.72%-19.80%). For patients who were frail and very frail, mortality continued to increase at 90 and 180 days, reaching 43.00% (95% CI, 41.69%-44.32%) for very frail patients at 180 days after moderate-stress surgical procedures. Conclusions and Relevance: We developed a novel operative stress score to quantify physiologic stress for surgical procedures. Patients who were frail and very frail had high rates of postoperative mortality across all levels of the Operative Stress Score. These findings suggest that frailty screening should be applied universally because low- and moderate-stress procedures may be high risk among patients who are frail.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma With Features Mimicking Spindle Cell Lipoma.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and spindle cell lipoma are lipomatous tumors with distinct clinical, molecular, and prognostic features. Although histological and immunophenotypic features can overlap between ALT/WDL and spindle cell lipoma, the oncogenesis and clinical behavior are markedly different. In borderline cases, molecular analysis for MDM2 or CDK4 amplification can aid in distinguishing ALT/WDL from spindle cell lipoma. Although dedifferentiated liposarcoma has been reported to harbor both MDM2 amplification and loss of the RB1 region, we are not aware of a reported RB1 loss in well-differentiated ALT/WDL. In this article, we present a 69-year-old woman with a lipomatous tumor in the gluteal region that histologically, immunohistochemically, and molecularly mimicked spindle cell lipoma (with positive immunohistochemical staining for CD34 and loss of the RB1 gene region), yet harbored amplification of MDM2 and CDK4 confirmed by fluorescence in situ hybridization, supporting classification as ALT/WDL. This case strengthens the argument that in atypical clinical contexts, molecular studies for MDM2/CDK4 should be considered in tumors resembling spindle cell lipoma.

Sacroiliac stabilization for sacral metastasis: A case series.

BACKGROUND: The sacrum is a rare location for spinal metastasis. These lesions are typically large and destructive by the time of diagnosis, making treatment difficult. When indicated, surgical stabilization offers pain relief and preserves independence in patients with impending and acute pathological sacral fractures. CASE DESCRIPTION: Three consecutive patients presented with sacral metastases. After either failing radiation therapy or presenting with acute fracture and instability, the patients underwent intralesional excision, bilateral L4 to ilium fusion with instrumentation, and sacroiliac (SI) screw fixation. Pain improved after surgery, and there were no wound healing complications. Two patients could continue walking without any assistive device, while one patient required a walker. CONCLUSION: Stabilization with combined modified Galveston fixation and SI screw fixation relieves pain and allows maintenance of independence in patients with sacral metastasis.

Eponymous Instruments in Orthopaedic Surgery.

Every day surgeons call for instruments devised by surgeon trailblazers. This article aims to give an account of commonly used eponymous instruments in orthopaedic surgery, focusing on the original intent of their designers in order to inform how we use them today. We searched PubMed, the archives of longstanding medical journals, Google, the Internet Archive, and the HathiTrust Digital Library for information regarding the inventors and the developments of 7 instruments: the Steinmann pin, Bovie electrocautery, Metzenbaum scissors, Freer elevator, Cobb periosteal elevator, Kocher clamp, and Verbrugge bone holding forceps. A combination of ingenuity, necessity, circumstance and collaboration produced the inventions of the surgical tools numbered in our review. In some cases, surgical instruments were improvements of already existing technologies. The indications and applications of the orthopaedic devices have changed little. Meanwhile, instruments originally developed for other specialties have been adapted for our use. Although some argue for a transition from eponymous to descriptive terms in medicine, there is value in recognizing those who revolutionized surgical techniques and instrumentation. Through history, we have an opportunity to be inspired and to better understand our tools.

What's Wrong With the Bone? An Overview of Metabolic and Neoplastic Bone Conditions.

The evaluation of any orthopaedic condition often begins with obtaining plain radiographs. Fortuitously, plain radiographs provide surgeons with direct information on the biologic activity and, therefore, the aggressiveness of any bone lesion. More advanced imaging modalities may fail to elucidate the problem and may even obscure the diagnosis. The accurate interpretation of the aggressiveness of a bone lesion on plain radiographs is the first step in establishing a differential diagnosis for any bone lesion and, often, may result in a correct diagnosis without the need for additional imaging studies. A thorough understanding of the radiographic classification of bone lesions will allow surgeons to accurately diagnose and manage metabolic bone disease, benign bone lesions, and malignant bone lesions.

2011 Mid-America Orthopaedic Association Dallas B. Phemister Physician in Training Award: Can musculoskeletal tumors be diagnosed with ultrasound fusion-guided biopsy?

BACKGROUND: Percutaneous biopsy for musculoskeletal tumors commonly relies on imaging adjuncts including ultrasound (US), CT, or MRI. These modalities however have disadvantages (US) or are cumbersome, not universally available, and costly (CT and MRI). US fusion is a novel technique that fuses previously obtained CT or MRI data with real-time US, which allows biopsies to be performed in an US suite. It has proven useful in various body systems but musculoskeletal applications remain scarce. Our goal is to evaluate the fusion technology and determine its ability to diagnose musculoskeletal tumors. QUESTIONS/PURPOSES: We determined whether biopsies performed via US fusion compared with CT guidance provide equivalent diagnostic yield and accuracy and allow quicker biopsy scheduling and procedure times. METHODS: Forty-seven patients were assigned to undergo either US fusion (with MR, n = 16 or CT, n = 15) or CT-guided biopsies (n = 16). We evaluated adequacy of the histologic specimen (diagnostic yield) and correlation with surgical pathology (diagnostic accuracy). We determined scheduling times and lengths of the biopsy. RESULTS: US fusion and CT-guided biopsy groups had comparable diagnostic yields (CT = 94%; US/MRI = 94%; US/CT = 93%) and accuracy (CT = 83%; US/MRI = 90%; US/CT = 100%). US fusion biopsies were faster to schedule and perform. All procedures were safe with minimal complications. CONCLUSIONS: US fusion provides a high diagnostic yield and accuracy comparable to CT-guided biopsy while performed in the convenience of an US suite. This may have resulted in the observed faster scheduling and biopsy times. LEVEL OF EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Tumors for the general orthopedist: how to save your patients and practice.

It is likely that most orthopaedic surgeons will see a patient with a benign or malignant musculoskeletal tumor sometime during their career. However, because of the rarity of these entities, many surgeons may benefit from a review of how to evaluate a patient with a bone lesion or soft-tissue mass. A logical approach is necessary in evaluating imaging studies as well as in the workup of children and adults with a possible tumor. It is important to have a good working relationship with a musculoskeletal radiologist to assist in interpreting the images. If the treatment algorithms lead to a conclusive diagnosis of a benign bone tumor, benign soft-tissue mass, or metastatic bone disease, the orthopaedic surgeon may choose to definitively treat the patient. If the workup indicates an indeterminate lesion, it may be prudent to discuss the situation with an orthopaedic oncologist or transfer the care of the patient to a physician with more specialized knowledge. A careful, logical workup is needed prior to surgery to limit risks to the patient and optimize the chances for a favorable outcome.

VEGF blockade decelerates the growth of a murine experimental osteosarcoma.

Retrovirus-mediated sFlt-1 gene modification was performed to examine the influence of VEGF in controlling the growth of an experimental osteosarcoma in mice. Human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses. Successful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size when compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ-treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue. Overall, data suggest that retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.

High VEGF with rapid growth and early metastasis in a mouse osteosarcoma model.

A murine model of osteosarcoma was developed to investigate the association between the expression of VEGF and the progression of osteosarcoma. Two human osteosarcoma cell lines with distinct VEGF expressions were introduced into proximal tibiae of immuno-deficient SCID mice, either by direct injection through the cortical bone or surgical exposing and drilling on the tibial metaphysis to seed tumor cells. Bone tumors were obvious on microCT within 4 weeks following osteosarcoma cell inoculation through surgical delivery. In contrast, direct injection without drilling often resulted in periosteal tumors. Although neoplasms were developed regardless of VEGF levels, orthotopic tumors derived from high VEGF-expressing cells were detected 2 weeks earlier on CT images than the ones from VEGF negative cells. At sacrifice, high VEGF tumors were distinctively larger in size and more frequently invaded the adjacent bone tissue. Multiple metastatic lesions were found in all the lung tissues at 8 weeks from high VEGF group, whereas only 1 of 7 VEGF negative tumors exhibited pulmonary metastasis. Overall, this model developed with the surgical tumor cell delivery results in histological and radiographic features more consistent with primary osteosarcoma. Interestingly, VEGF expression correlates with the early establishment, rapid tumor growth, and the development of pulmonary metastasis.

A unique radiation scheme for the treatment of high-grade non-metastatic soft tissue sarcoma: the detroit medical center experience.

PURPOSE: This is the initial report on the utilization of combined photon irradiation followed by a neutron boost irradiation for the initial management of patients with high-grade non-metastatic soft tissue sarcoma (STS). We present data on local control, complications, disease-free survival and overall survival in patients at high risk for local relapse. METHODS AND MATERIALS: Between 1/1/1995 and 10/31/02, twenty-three patients with high-grade non-metastatic soft tissue sarcoma were referred to the Department of Radiation Oncology at the Detroit Medical Center. These patients were referred for consultation due to surgical margin status (tumor within 3mm of surgical margin (n=11)), or gross residual disease (n=12). There were 14 males and nine females whose ages ranged from 12 to 75 at the time of diagnosis (med=44 years). The most common histology was malignant fibrous histiocytoma (n=6), followed by liposarcoma (n=5), synovial sarcoma (n=4), and angiosarcoma (n=2). Twenty-one of 23 patients also received multi-agent multi-cyclic cyto-reductive therapy. Treatment consisted of initial daily photon irradiation delivered either using twice daily fractions of 120 cGy (n=10) or once daily 200 cGy/fx (n=13).Total photon dose was 36-39.6 Gy. Neutron irradiation was initiated immediately following the photon irradiation and consisted of fraction sizes of 1.0-1.25NGy to a total dose of 6-10 NGy. The neutrons were given once daily. Follow-up is calculated from the day of last radiation treatment. RESULTS: No patient has been lost to follow-up, which has ranged from 18 to 82 months (med=36 months). To date there have been two local relapses and three patients with distant disease development without local relapse. Each of the patients with distant disease has died. The local failures occurred at 9 and 12 months. The 36-month local control is 91%. Thirtysix month disease-free survival was 78%. Overall survival at 36 months was 87%. Three patients had unusual complications consisting of delayed wound healing, and in one of these patients a fracture of the tibia has been noted. CONCLUSION: The use of this unique radiation sequence post-surgically in patients at high risk for local relapse has resulted in an exciting 36-month local control rate of 91%. The 3-year disease-free survival of 78% and overall survival rate of 87% are exciting but need to mature. The low complication rate is similar to that reported in other large institutional series that have not utilized neutrons. We continue to evaluate the role of combined photon and once-off neutron irradiation in the treatment of patients with high-grade STS that are risk for local recurrence.

The role of irradiation in the management of locally recurrent non-metastatic soft tissue sarcoma of extremity/trunkal locations.

BACKGROUND: Patients who have had initial curative intent therapy for non-metastatic soft tissue sarcoma, and who subsequently relapse at the initial site without evidence of metastatic disease, have various options regarding local treatment. The treatment options available will be determined by the extent of relapse, previous therapy rendered, and patient characteristics. We reported on a series of 31 patients treated initially with only surgery for extremity/trunkal high-grade soft tissue sarcoma and then seen for recurrence at our institution between 1980 and 1999. Local re-treatment consisted of combined modality therapy, most often aggressive surgical debulking/resection and irradiation, in an effort to reduce the need for amputation and, where anatomically allowable, to maintain a functional limb. We report our results in re-establishing local control, subsequent survival, and complication rates. METHODS: Thirty-one patients with locally recurrent, non-metastatic high-grade soft tissue sarcoma, (excluding extraabdominal desmoid) were retrospectively reviewed to determine local control, survival, and complication rates associated with the relapsed disease. All patients had multimodality re-treatment most often utilizing aggressive surgical debulking and irradiation. The irradiation consisted of either external beam alone, brachytherapy alone, or a combination of external beam and brachytherapy. Nine patients also received multi-agent, multi-cycle chemotherapy using various regimens. In addition, the impact of surgical margin at the time of re-resection (gross versus microscopic disease), radiation treatment type, total radiation dose delivered, size of relapse, histological sub-type, sex and age, were evaluated to determine if they had any impact on the re-establishment of local control and subsequent survival. RESULTS: Local control was re-established in 25 of 31 (80.6%) patients. Two additional patients with isolated local relapse after irradiation were salvaged with amputation and remain NED at last follow-up. With these patients a total of 27/31 (87%) are now with local control. At last follow-up, which ranged from 23 to 192 months, 23 of 31 (74%) remained alive. Of the eight patients who have died, four had evidence of local and distant failure. Two additional patients died of distant failure while the treated sites remained in local control and two patients, both NED, died of intracurrent processes. Follow-up for those patients who had re-established local control has ranged from 23 to 192 months (median=60.5 months). Time to local failure following re-treatment ranged between 3 and 72 months following re-treatment (median=12 months). Five patients had significant treatment related complications. Included are two patients in which amputation was required due to local recurrences. Two patients developed a soft tissue necrosis and one patient had a wound healing problem that resolved with conservative management. No statistical significance in the development of local control could be found based on surgical margin status, total dose of irradiation (greater or less than 60 Gy), size of recurrence (greater than 5 cm), histological sub-type, sex, or age (greater than 50 years). There was a trend for negative impact for those patients receiving only external beam irradiation. CONCLUSION: Selective locally recurrent, non-metastatic soft tissue sarcoma of the extremity/trunkal regions should still be considered eligible for aggressive limb-sparing therapy. Our experience suggests that a majority of patients re-establish local control following aggressive surgical resection/debulking and irradiation and this appears to be durable in its nature. The role of chemotherapy in this group of patients remains investigational. In a surprising finding, one patient re-relapsed in the re-treatment site at 72 months, thus justifying continued strict surveillance not only in the primary site but also for subsequent metastatic disease.

The role of postoperative irradiation in the treatment of locally recurrent incompletely resected extra-abdominal desmoid tumors.

BACKGROUND: To define the efficacy of postoperative irradiation in patients with recurrent extra-abdominal desmoid tumors in whom surgical intervention has resulted in microscopically or grossly positive surgical margins. METHODS: A retrospective analysis was performed on all patients referred to the department of radiation oncology at the Detroit Medical Center with a diagnosis of recurrent extra-abdominal desmoid tumor. This analysis includes all patients seen from 1 January 1990 through 31 December 1999. A total of 11 patients were treated to 13 sites. Ten had microscopically positive margins and three had gross residual disease. Three patients were noted to have multifocal disease at the time of initial representation. Local control, survival, follow-up, and subsequent development of new tumors are measured from the last day of treatment with irradiation. RESULTS: Thirteen sites were treated. Seven patients had received chemotherapy/hormonal therapy prior to surgery and/or irradiation. The most commonly used drug was tamoxifen (n=6). The type of radiation delivered included external beam irradiation alone (n=3), combined external beam irradiation and brachytherapy (n=4), brachytherapy alone (n=3) and 252-Cf neutron brachytherapy alone (n=3). Follow-up has ranged from 29 to 115 months (median=76 months). Three patients have failed locally at 17, 24 and 29 months. One of these was treated for gross residual disease. No patient has died of tumor-related causes. Salvage at the failed sites was possible in twom of three with re-irradiation using external neutrons and/or aggressive surgical intervention and systemic therapy. Complications were most often noted to include decrease range in motion, especially in joint areas, and skin reactions which were normal in presentation. In one site there was development soft tissue necrosis. CONCLUSION: Based on our experience we recommend postoperative irradiation for all recurrent extra-abdominal desmoid lesions with microscopically or grossly positive surgical margins. Furthermore, patients with recurrent desmoid tumors involving the bony structures of the hand or feet are poor candidates for brachytherapy alone. For patients with extremity lesions, brachytherapy may be a reasonable treatment option provided adequate margins around the tumor bed are covered. The continued recommended use of irradiation in this group of patients is warranted.

Osteosarcoma as a second malignant neoplasm.

PURPOSE: The aim of this study is to compare primary and secondary osteosarcomas using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. METHODS: Osteosarcoma cases were identified in the SEER Cancer Incidence Public-Use Database, 1973-96 (1,511 primary and 133 secondary osteosarcomas). Secondary osteosarcomas were further classified as occurring within or outside the previously irradiated field. Comparisons among groups were performed by nominal logistic regression. Survival analyses were performed using Kaplan-Meir and proportional hazards regression. RESULTS: Secondary osteosarcomas were more likely to have a non-extremity primary site and an older age at diagnosis (>40 years) (<0.0001 for both). Secondary osteosarcoma cases continued to be more likely to have a non-extremity site when excluding those occurring within the radiation field. Five-year overall survival was 50% lower for secondary osteosarcomas for both extremity and non-extremity sites. Primary malignancies associated with secondary osteosarcomas included 14 lymphomas/leukemias, six sarcomas, 54 carcinomas, and seven other cancers. Secondary osteosarcomas occurring within a field of radiation were more likely to occur at a younger age, have a malignancy with a primary morphology other than carcinoma, a non-limb site, and a longer duration between their primary malignant neoplasms and the development of osteosarcoma. No difference in the overall survival was noted between secondary osteosarcomas occurring within an irradiated field and those that did not. CONCLUSIONS: Secondary osteosarcomas are associated with carcinomas especially in the elderly. Although a 50% decreased 5-year survival was observed for secondary osteosarcomas in this study, this might not reflect the current outcomes with more aggressive therapy.