The role of perceived patient injustice on pain related and functional outcomes in orthopaedic patients; a systematic review.

Introduction: Higher levels of perceived patient injustice has been associated with higher levels of pain and poor functional outcomes in patients with chronic musculoskeletal pain. We wanted to investigate if there was any evidence of this association in patients who underwent orthopaedic surgery. Materials and methods: A systematic search of the literature was performed independently by two researchers on the electronic databases of MEDLINE, EMBASE, Google Scholar, Web of Science, and the Cochrane Database of Systematic Reviews and data extracted in accordance with PRISMA guidelines for systematic reviews. Outcomes of interest were pain, pain intensity, pain interference, opiate use, disability, physical function, return to work, quality of life, depression, anxiety, post-traumatic stress, social functioning and quality of life. Results: Five studies were identified for qualitative analysis involving elective and trauma orthopaedic patients. All studies identified a positive correlation between higher levels of perceived injustice and depression, pain intensity and interference as well as reduced function and higher levels of disability. Conclusions: Higher levels of perceived patient injustice is associated with worse pain and functional outcomes in patients who undergo orthopaedic surgery in the traumatic and elective setting. Further research is warranted to further elucidate this association and identify potential therapeutic interventions.

Liposarcoma: a soft tissue tumor with many presentations.

Liposarcoma is an uncommon connective tissue tumor arising from lipoblast cells. The lesion is located in body soft parts and rarely arises from the bones. The tumors are variable in presentation ranging from benign well-differentiated tumors to myxoid and round cell-dedifferentiated and pleomorphic forms which can present with metastases. The lesions are most often treated by surgical resection. Chemotherapy and radiation may be added to the treatment of the more malignant variants with some success.

Pleomorphic spindle cell sarcoma (PSCS) formerly known as malignant fibrous histiocytoma (MFH): a complex malignant soft-tissue tumor.

A presentation defining the nature, characteristics, causation, treatment and outcome of patients with lesions formerly known as malignant fibrous histiocytoma and now as pleomorphic spindle cell sarcoma is clearly a very difficult subject. Many authors do not believe that the tumor exists and instead describe them as forms of fibrosarcomas, fibromyxoid lesions, dedifferentiated chondrosarcomas or even leiomyosarcomas. The reasons for this confusion are presumably related to the fact that the malignant pleomorphic spindle cell sarcoma does not seem to be a distinct type of lesion with specific histologic and genetic characteristics. Instead, the tumor has at least four separate histologic variations and no specific gene signature and in fact does not seem to be either familial or ethnic in presentation. In view of the fact that the tumor was traditionally the most frequently encountered malignant soft-tissue neoplasm, the world of orthopedic oncology is clearly distressed by the problems that these patients have and is joined by the radiation oncologists and chemotherapists in seeking new solutions.

Thromboembolic Events Associated with Thalidomide and Multimodality Therapy for Soft Tissue Sarcomas: Results of RTOG 0330.

Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to add thalidomide (THAL) to MAID chemoradiation for intermediate/high grade soft tissue sarcomas (STSs) and to preoperative radiation (XRT) for low-grade STS. Methods. Primary/locally recurrent extremity/trunk STS: ≥8 cm, intermediate/high grade (cohort A): >5 cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients. Results. 22 primary STS patients (cohort A/B 15/7). Cohort A/B: median age of 49/47 years; median tumor size 12.8/10 cm. 100% preoperative THAL/XRT and surgical resection. Three cycles of MAID were delivered in 93% cohort A. Positive margins: 27% cohort A/29% cohort B. Adjuvant THAL: 60% cohort A/57% cohort B. Grade 3/4 venous thromboembolic (VTE) events: 40% cohort A (1 catheter thrombus and 5 DVT or PE) versus 0% cohort B. RTOG 0330 closed early due to cohort A VTE risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514 with neoadjuvant MAID/XRT.

Do patients with chronic low back pain have an altered level and/or pattern of physical activity compared to healthy individuals? A systematic review of the literature.

BACKGROUND: It is commonly assumed that patients with chronic low back pain are less active than healthy individuals. There has been a recent increase in the number of studies published comparing the physical activity levels of patients with chronic low back pain and healthy individuals. OBJECTIVES: The aim of this systematic review was to determine, based on the current body of evidence, if patients with chronic low back pain have a lower level and/or altered pattern of physical activity compared with asymptomatic, healthy individuals. DATA SOURCES: The electronic databases Embase, Medline, ISI Web of Knowledge, Cinahl, Sport Discus and Nursing and Allied Health were searched from the beginning of each database until the end of December 2009. REVIEW METHODS: Studies which compared the level and/or pattern of physical activity of patients with chronic low back pain and healthy controls were included. The quality of the included studies was assessed using an assessment tool based on the Newcastle-Ottawa Scale. The scale was modified for the purposes of this study. RESULTS: Seven studies were included in the final review. Four studies recruited adult patients (18-65 years), two studies examined older adults (≥65 years) and one study recruited adolescents (<18 years). Pooled data revealed no significant difference in the overall activity level of adults or adolescents with CLBP, however there is evidence that older adults with chronic low back pain are less active than controls. The results suggest that patients exhibit an altered pattern of physical activity over the course of a day compared to controls. Major methodological limitations were identified and are discussed. CONCLUSION: There is no conclusive evidence that patients with chronic low back pain are less active than healthy individuals. Based on a limited number of studies, there is some evidence that the distribution of activities over the course of a day is different between patients with chronic low back pain and controls.

Severe acute enteritis in a multiple myeloma patient receiving bortezomib and spinal radiotherapy: case report.

Proteasome inhibitors have been reported to enhance radiosensitivity in vitro. A case of potential clinical interaction between bortezomib, a proteasome inhibitor, and spine radiation is reported. A woman undergoing palliative radiotherapy to the T12 -S2 spine with concurrent bortezomib developed unexpectedly severe, acute radiation enteritis requiring hospital admission. Clinicians are advised to consider the potential for interactions of bortezomib with radiotherapy when the two agents are used simultaneously in the clinic.

S100beta and nitric oxide product concentrations following cerebral aneurysm clipping in patients with subarachnoid haemorrhage: a pilot study.

OBJECTIVE: The objective of this investigation was to determine the efficacy of S100beta and nitric oxide product (nitrate and nitrite [NOx]) concentrations as markers of brain injury following cerebral aneurysm clipping in patients with spontaneous subarachnoid haemorrhage. METHODS: Fifteen patients with spontaneous subarachnoid haemorrhage were studied. Blood samples were obtained for estimation of serum S100beta (microg/L) and nitric oxide product (nitrate and nitrite [NOx]) (microM) concentrations immediately preoperatively (baseline) and then 10 minutes, 2, 6 and 12 hr postoperatively and daily thereafter for five days. Neurological outcome was assessed three months after surgery by the Glasgow Outcome Scale (GOS) (poor outcome, grade 1 - 3 and good outcome as grade 4 - 5). Data were analysed using the Mann-Whitney-U-test. RESULTS: S100beta concentrations were greater at two hours postoperatively compared to baseline (0.33 +/- 0.16 vs 0.25 +/- 0.04)(P = 0.02). S100beta concentrations were similar in good and poor neurological outcome groups as defined by GOS at three months. NOx concentrations were less at 12 hours postoperatively compared to baseline (9.81 +/- 3.25 vs 12.74 +/- 2.9)(P = 0.03). NOx concentrations were greater on the fourth and fifth postoperative days compared to baseline (t0) (17.22 +/- 7.9, 12.74 +/- 2.9 vs 9.81 +/- 3.25) (P < 0.05). NOx concentrations were greater in patients with a poor neurological outcome (n = 4) compared to the good outcome group (n = 11) (24.7 +/- 4.9 vs. 11.3 +/- 3.3)(P = 0.04). CONCLUSIONS: S100beta and NOx concentrations increase after cerebral aneurysm clipping in patients with spontaneous SAH. Increased nitric oxide product concentrations were associated with subsequent poor neurological outcome.

Long-term results of combined modality therapy in primary bone lymphomas.

PURPOSE: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35-66.5). All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only. RESULTS: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015). CMT was associated with improved DFS (p = 0.0008) and OS p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4-228). CONCLUSION: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones.

A staff dialogue on aggressive palliative treatment demanded by a terminally ill patient: psychosocial issues faced by patients, their families, and caregivers.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members. In this article, the case presentation and verbatim dialogue from the rounds are discussed with an emphasis on staff psychosocial issues. The case presented was of a 32-year-old man, who developed small cell osteosarcoma and was treated at MGH. He died after undergoing multiple courses of relatively ineffective chemotherapy. The case is made all the more poignant because of the pleasures, hopes and stresses of having a child late in the course of his illness. Staff identified closely, both with him and his family, and their concern for him brought joy and meaning to their work, yet this complicated their ability to deal with his impending death. They felt that his unwillingness to admit defeat prevented them from saying goodbye to someone whom they loved and admired. Despite this, staff recognized that, ultimately, the patient's emotional needs and wishes had to be respected as a first priority and that constructive closure can be worked toward, if not achieved. In such situations, it is vital to have a colleague support system and a forum for discussion of such issues in order to defuse distress and reassure staff that they are doing all that can be done as professionals and caregivers.

Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B.

BACKGROUND: In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro-5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS: Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS: Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. CONCLUSIONS: The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.

Prognostic factors for local control of sarcomas of the soft tissues managed by radiation and surgery.

During the past decade, local control of primary sarcomas of the extremities by radiation and conservative surgery has supplanted more radical compartmental resections or amputations. Reviews of others and our published data show that the probability of achieving local control is highly dependent on achieving negative surgical margins. Other factors, such as pathological grade and size, histopathology, and concomitant chemotherapy may also affect local control, to a much lesser extent, although these are strongly correlated with the likelihood of distant metastatic disease. Appreciation of the importance of these different prognostic factors has been fundamental to the development of the current rationale for sarcoma management.

Dihydro-5-azacytidine in malignant mesothelioma. A phase II trial demonstrating activity accompanied by cardiac toxicity. Cancer and Leukemia Group B.

BACKGROUND: Malignant mesothelioma is a disease that is refractory to chemotherapy. Therefore, the objective of this multi-institutional, cooperative group Phase II trial was to determine the efficacy of dihydro-5-azacytidine (DHAC), a pyrimidine analogue, in the treatment of malignant mesothelioma. METHODS: Forty-one patients with histologically confirmed malignant mesothelioma received 120-hour continuous infusions of DHAC (1,500 mg/m2/day every 21 days) until maximal response, intolerable toxicity, or disease progression. RESULTS: One patient had a complete response, two had objective partial responses, and four had regression of evaluable disease. The overall response rate was 17%. The one complete responder remains without disease progression at 6 years. Chest pain and nausea were the most common toxicities. Supraventricular tachycardia and pericardial effusion occurred in 20% and 15% of patients, respectively. In most patients, gastrointestinal effects were manageable. There was no significant hematologic toxicity. CONCLUSIONS: In malignant mesothelioma, a disease that is refractory to chemotherapy, dihydro-5-azacytidine has definite antitumor activity. Its modest hematologic toxicity profile favors its use in combination with other agents. Caution regarding cardiac arrhythmias and pericardial effusion is necessary.

Evaluation of case reports of aplastic anemia among patients treated with felbamate.

PURPOSE: Felbamate (FBM) is a new antiepileptic drug (AED) that is often effective in seizure disorders refractory to other treatments; its use has been greatly restricted after cases of aplastic anemia were reported. To elucidate the putative association between FBM and aplastic anemia, we made a detailed evaluation of the first 31 reports. METHODS: Hematologic review according to the criteria of the International Agranulocytosis and Aplastic Anemia Study (IAAAS) confirmed 23 cases (74%) as aplastic anemia; FBM was judged to be the only plausible cause for three; confounding (mostly by other drugs) was considered possible, but FBM remained the most likely cause for 11; and there was at least one other plausible cause for 9. RESULTS: Using a denominator from sales data of 110,000 persons exposed and a numerator of the cases for which FBM was considered the only plausible cause, we established a lower limit of incidence of 27 cases of aplastic anemia per million users as compared with the general population rate of 2.0 per million per year. With all confirmed cases used as the numerator, the upper limit of incidence was 209 per million. The 'most probable" incidence was estimated to be 127 per million. CONCLUSIONS: Intensive, systematic investigation can maximize the utility of case reports for assessing risks of newly released drugs. The present evaluation confirmed an association between FBM and aplastic anemia; however, confounding was significant for most cases and there was a tenfold range in the "best case" and "worst case" incidence estimates among users.

Compositional changes in vertebral bone marrow during treatment for acute leukemia: assessment with quantitative chemical shift imaging.

A modified Dixon chemical shift imaging technique was used to quantify longitudinal changes in bone marrow that occur during induction chemotherapy in patients with acute leukemia. Results were correlated with those of bone marrow biopsy. Forty-seven quantitative images were obtained with a 0.6-T whole body imager in a total of 11 patients over the course of treatment. Quantitative measures of fat fractions and water and fat component T1 and T2 relaxation times were determined, as well as average relaxation times. Imaging results showed sequential increases in fat fractions among responding patients (n = 9), consistent with biopsy-confirmed clinical remission. In the two patients who later relapsed, sharp decreases in fat fractions were noted. In the two patients who failed to regenerate normal marrow, unchanging, low fat fractions were seen. Water component T1 values reflected posttherapeutic changes in the hematopoietic elements. Quantitative chemical shift imaging proved useful in assessing treatment response in acute leukemia during early bone marrow regeneration and, later, in ascertaining remission or relapse.

Primary lymphoma of bone. A B-cell neoplasm with a high frequency of multilobated cells.

Primary lymphoma of bone is an uncommon neoplasm that can be difficult to diagnose and subclassify. Only in a few cases has the immunophenotype been determined with monoclonal antibodies. We evaluated the histological features and immunophenotype of 12 cases of primary lymphoma of bone. The patients ranged in age from 16 to 80 years (mean, 41 years) with a male:female ratio of 1:1. The sites involved included femur (three cases), humerus (two cases), tibia (three cases), pelvis (two cases), ulna (one case), and scapula (one case). All cases were diffuse large-cell lymphomas: nine large-cleaved (eight with multilobated cells), two large-cell not otherwise specified, and one immunoblastic. Sclerosis was noted in six cases. Immunohistochemical studies on frozen-tissue sections demonstrated staining with the following antibodies: 11 of 11 with CD45, 12 of 12 with CD20, eight of 12 with monotypic immunoglobulin (six IgG, two IgM, seven kappa, one lambda). Tumor cells were negative for T-cell markers in each case. Ten patients are alive and well 0.5-4.5 years (median, 1.5 years) following treatment with radiation or chemotherapy. Two patients had recurrence at another site 0.75 years and 4 years after the initial diagnosis, respectively. Primary bone lymphoma is a B-lineage large-cell lymphoma with an unusually high incidence of large-cleaved and multilobated cells. The frequency of IgG heavy chain expression suggests a post-germinal center stage of differentiation. Frozen section immunohistologic studies are useful in the diagnosis of this tumor. Aggressive therapy has resulted in a favorable outcome in most cases.

Immunohistologic features predict clinical behavior of orbital and conjunctival lymphoid infiltrates.

The natural history of lymphoid infiltrates of the orbit and conjunctiva is poorly understood. To determine if immunohistologic features could predict clinical outcome, these features were evaluated in 61 patients with orbital and conjunctival lymphoid infiltrates, including 44 patients with lesions localized to one or both orbits or conjunctivae. Using histologic criteria, 20 infiltrates were classified as malignant lymphoma (cytologically atypical), 14 cases were classified as benign (follicular hyperplasia or inflammatory pseudotumor), and 27 infiltrates (44%) were dense infiltrates of small lymphocytes without cytologic atypia, which could not be confidently classified as benign or malignant (histologically indeterminate). Based on expression of monotypic immunoglobulin, 20 of these cases were reclassified as small lymphocytic lymphoma. For all cases, monotypic immunoglobulin expression correlated with reduced survival (P less than .05) and increased likelihood of dissemination (P less than .001). Monotypic immunoglobulin expression also correlated with increased risk of dissemination for all histologically indeterminate (small lymphocytic) infiltrates (P less than .05). Separate analysis of the localized infiltrates showed that monotypic immunoglobulin expression significantly correlated with an increased likelihood of dissemination for all 44 cases (P less than .005) and for the 22 histologically indeterminate lesions (P = .06). For the localized small lymphocytic infiltrates, monotypic immunoglobulin expression conferred a 50% risk of dissemination. In contrast, no patients with polytypic small lymphocytic infiltrates have disseminated, although one lesion locally recurred 30 months later as lymphoma. Thus, monotypic immunoglobulin expression significantly correlates with reduced patient survival and increased risk of dissemination by orbital and conjunctival lymphoid infiltrates. Monotypic small lymphocytic infiltrates without cytologic atypia behave as do low grade B-cell malignant lymphomas with a significant risk of dissemination and an indolent clinical course. The relationship of polytypic small lymphocytic infiltrates to lymphoma remains to be determined.

Ewing's sarcoma: surgical resection as a prognostic factor.

A retrospective review of 46 cases of Ewing's (43) and extraosseous Ewing's (3) sarcoma was performed to examine for prognostic factors. Follow-up ranged from 27 to 135 months with a mean of 77.6 months, 86% greater than 36 months. Nine (20%) patients presented with distant metastases, 98% received multiagent chemotherapy, and 98% received radiation therapy. Overall actuarial survival and local control at 5 years were .52 +/- .08 and .78 +/- .07, respectively. The freedom from relapse or treatment related mortality at 5 years was .46 +/- .08. In 12 (26%) patients, surgical resection of the involved bone or soft tissue was part of the initial treatment plan. Ninety-two percent (11/12) of these patients also received radiation therapy. In addition to surgical resection, tumor size (less than 500 cc vs. greater than or equal to 500 cc), primary site (central vs. other), and stage were also analyzed for prognostic significance, and where appropriate, were included in Cox multivariate analyses. Considering all patients, the 5-year actuarial survival was .92 +/- .08 vs. .37 +/- .09 for patients receiving and not receiving surgical resection, respectively (p = .001 by logrank, p = .02 by Cox). To make the groups more comparable, 8 patients with local failure and 5 patients with non-evaluable primary sites were excluded. After these exclusions, the presence or absence of surgical resection had decreased significance: .92 +/- .08 vs. .59 +/- .11, respectively; p = .01 by logrank, p = .07 by Cox. Only primary site remained statistically significant: .86 +/- .08 for noncentral sites vs. .38 +/- .16 for central sites, p less than .0002 by logrank, p = .0004 by Cox. Surgical resection when added to local irradiation has prognostic significance in this retrospective review. The reason for this is not clear, but may be related to a decrease in local failure after resection.

Treatment of the patient with stage M0 soft tissue sarcoma.

During the period 1971 to 1985, 220 patients with soft tissue sarcoma of the extremities, torso, and head-neck region were managed by radiation and resectional surgery at the Massachusetts General Hospital (MGH). Actuarial 5-year local control and disease-free survival rates were 86% and 70%, respectively. The success rate improved during this time period. Namely, the local control rates for 1971 to 1975, 1976 to 1980, and 1981 to 1985 were 81%, 81%, and 94%, respectively. For the same time periods, the 5-year disease-free survival rates were 64%, 70%, and 76%. One hundred thirty-one patients were treated with postoperative radiation, and 89 with preoperative radiation. In the most recent 5-year period, the local control rates were 91% and 97% for the two groups (number of patients being 50 and 57 in the post- and preoperative groups, respectively). Treatment by preoperative radiation appears to have a major advantage for patients with very large sarcomas, ie, greater than 15 cm in maximum dimension. None of our patients with local control of grade 1 sarcoma have developed distant metastasis (DM). In contrast, among patients with grade 2 or 3 sarcomas, there is a relentless and progressive increase in the frequency of DM with size of the primary lesion, namely, 6% at less than or equal to 2.5 cm, congruent to 60% at 15 to 20 cm, and congruent to 80% at greater than 20 cm.