Bench-to-bedside imaging in brain metastases: a road to precision oncology.

Radiology has seen tremendous evolution in the last few decades. At the same time, oncology has made great strides in diagnosing and treating cancer. Distant metastases of neoplasms are being encountered more often in light of longer patient survival due to better therapeutic strategies and diagnostic methods. Brain metastasis (BM) is a dismal manifestation of systemic cancer. In the present scenario, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) are playing a big role in providing molecular information about cancer. Lately, molecular imaging has emerged as a stirring arena of dynamic imaging techniques that have enabled clinicians and scientists to noninvasively visualize and understand biological processes at the cellular and molecular levels. This knowledge has impacted etiopathogenesis, detection, personalized treatment, drug development, and our understanding of carcinogenesis. This article offers insight into the molecular biology underlying brain metastasis, its pathogenesis, imaging protocols, and algorithms. It also discusses disease-specific molecular imaging features, focusing on common tumors that spread to the brain, such as lung, breast, colorectal cancer, melanoma, and renal cell carcinoma. Additionally, it covers various targeted treatment options, criteria for assessing treatment response, and the role of artificial intelligence in diagnosing, managing, and predicting prognosis for patients with brain metastases.

Clinicopathological Profile and Survival Outcomes in Patients with Localised Extremity Synovial Sarcomas.

AIMS: Synovial sarcoma is a rare but aggressive variant of soft-tissue sarcoma. Literature is sparse and reported mostly from the West. We analysed the clinical profiles and prognostic factors of extremity synovial sarcoma patients in order to study their clinical journey. MATERIALS AND METHODS: This was a retrospective analysis. All patients with extremity synovial sarcoma treated between 1992 and 2020 were included. Patients with metastases at presentation were excluded. A descriptive analysis of demographic and clinicopathological features of patients undergoing limb salvage surgery (LSS) or amputation was carried out. Overall survival and disease-free survival were calculated for the entire cohort as well as for the LSS and amputation groups. Factors prognostic for survival were identified. RESULTS: In total, 157 patients had localised extremity synovial sarcoma. Predominantly, young adults (median 31 years) and males (61%) were affected. Over 70% of patients presented after recurrence or unplanned surgeries. Sixty-seven per cent of tumours were >5 cm, 69% were deep and 23% involved bone. The limb salvage rate was 64%. In the LSS group, adjuvant radiotherapy and chemotherapy were given to 72% and 68% of patients, respectively. In the amputation group, 72% of patients received adjuvant chemotherapy. In a median follow-up of 59 months, 39.4% of patients had recurrences, the majority (61.2%) were systemic. Five-year overall survival and disease-free survival were 53.4% and 49.8%, respectively. Overall survival was 63.9% and 29.7% in the LSS and amputation groups, respectively. On multivariate analysis, tumour size, depth, omission of radiotherapy and bone invasion were found to be the adverse prognostic factors. CONCLUSION: This is one of the largest studies on extremity synovial sarcoma. Mostly males and young adults were affected. The limb salvage rate was 64%, despite most being referred after unplanned surgery. Almost 70% of patients received radiotherapy and chemotherapy. Overall survival was inferior in the amputation group. Tumour size >5 cm, depth and bone invasion were negative, whereas adjuvant radiotherapy was a positive prognostic factor for survival. Chemotherapy had no impact on survival.

Post-treatment imaging of gliomas: challenging the existing dogmas.

Gliomas are the commonest malignant central nervous system tumours in adults and imaging is the cornerstone of diagnosis, treatment, and post-treatment follow-up of these patients. With the ever-evolving treatment strategies post-treatment imaging and interpretation in glioma remains challenging, more so with the advent of anti-angiogenic drugs and immunotherapy, which can significantly alter the appearance in this setting, thus making interpretation of routine imaging findings such as contrast enhancement, oedema, and mass effect difficult to interpret. This review details the various methods of management of glioma including the upcoming novel therapies and their impact on imaging findings, with a comprehensive description of the imaging findings in conventional and advanced imaging techniques. A systematic appraisal for the existing and emerging techniques of imaging in these settings and their clinical application including various response assessment guidelines and artificial intelligence based response assessment will also be discussed.

Outcomes among preterm infants with patent ductus arteriosus: Relationship with treatment, gestational age, hemodynamic status and timing of treatment.

BACKGROUND: There remains controversy regarding the outcomes resulting from treatment versus conservative management of patent ductus arteriosus (PDA) among preterm infants. The effects of extreme prematurity, hemodynamic status of the PDA, and age at treatment remain poorly defined. STUDY DESIGN: This retrospective case-control study including infants < 1250 gm who were categorized into 3 groups: Group 1: without PDA, Group 2: with untreated PDA, and Group 3: treated PDA. Diagnosis and treatment of PDA extracted from the medical records. Demographics, clinical characteristics, and outcomes compared using chi-square and analysis of variance. Logistic regression used to estimate adjusted odds ratios. RESULTS: The study included 734 infants, with 141(19%) in Group 1, 329 (45%) in 2, and 264 (36%) in 3. Group 3 had higher incidence of bronchopulmonary dysplasia (BPD) (aOR, 2.9; 95%CI 1.7-4.8). Infant treated for hemodynamically significant PDA (HSPDA) had higher incidence of BPD (aOR, 1.9; 95%CI 1.0-3.8) and retinopathy of prematurity (ROP) (aOR, 3.4; 95%CI 1.6-6.9). There were no differences in outcome associated with treatment among≤26 weeks gestation and the age when treated. CONCLUSION: Infants with PDA who were treated had higher incidence of BPD. Among those who were treated, those with HSPDA had a higher incidence of BPD and ROP.

The long noncoding RNA MALAT1 suppresses miR-211 to confer protection from ultraviolet-mediated DNA damage in vitiligo epidermis by upregulating sirtuin 1.

BACKGROUND: The absence of melanocytes poses a challenge for long-term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I-II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same. OBJECTIVES: To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)-induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets. METHODS: Genome-wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next-generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied. RESULTS: Our study found sirtuin1 (SIRT1), an NAD-dependent deacetylase, to be a direct target of miR-211 - the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX-527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR-211 mimic led to a significant increase in γ-H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB-mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR-211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB-induced CPDs in primary keratinocytes. CONCLUSIONS: These findings establish a novel MALAT1-miR-211-SIRT1 signalling axis that potentially confers protection to the 'amelanotic' keratinocytes in vitiligo.

Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats.

OBJECTIVE: The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats. METHODS: Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology. RESULTS: DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa. CONCLUSION: The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.

Associations of cutaneous and extracutaneous infections with hidradenitis suppurativa in U.S. children and adults.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with bacterial colonization, skin-barrier disruption, immune dysregulation and treatments that can increase infection risk. OBJECTIVES: To determine whether HS is associated with cutaneous and extracutaneous infections and related outcomes. METHODS: Data from the 2002-2012 National Inpatient Sample were analysed, including a 20% sample of U.S. hospitalizations (n = 87 053 155). RESULTS: The prevalence (with 95% confidence interval) of infections was higher in adults (34·0%, 33·2-34·7% vs. 23·4%, 23·2-23·6%) and children (31·8%, 28·7-34·9% vs. 12·6% (12·1-13·1%) with vs. without HS. Inpatients with HS had higher prevalences of infections overall (excluding cellulitis and erysipelas) than those with psoriasis, but lower than those with atopic dermatitis. In multivariable logistic regression models adjusting for sociodemographics, HS was associated with 18 of 45 infections examined (adults: 16 of 45; children: six of 45), including acute infections (herpes simplex virus, herpes zoster, necrotizing fasciitis, septicaemia, bone infection, Clostridium difficile, methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Streptococcus, Pseudomonas, mycobacterial, fungal, viral), chronic infections (HIV, hepatitis B) and antibiotic-resistant infections. HS alone was associated with increased infections. Patients with comorbid cancer; HIV; cardiometabolic, autoimmune or mental health diagnoses or acne had even higher odds of infections. Inpatients with HS with vs. without serious infection had increased inpatient mortality (0·71% vs. 0·16%), mean length of stay (7·3 vs. 4·8 days) and cost of care (US$13 578 vs. $9242), with a mean annual excess 41 050 days and $71 622 339 cost of hospitalization. CONCLUSIONS: Adults and children with HS had increased acute and chronic, cutaneous, extracutaneous and systemic infections, which were associated with increased mortality and cost. What's already known about this topic? Little is known about the risk of infection in patients with hidradenitis suppurativa (HS). What does this study add? Adults and children with HS had increased cutaneous, extracutaneous and systemic infections, at even higher rates than in patients with psoriasis and atopic dermatitis. These infections were associated with increased inpatient mortality and cost. Respond to this article.

The mental health burden in acne vulgaris and rosacea: an analysis of the US National Inpatient Sample.

BACKGROUND: Little is known about the mental health (MH) hospitalization among patients with acne and rosacea. AIMS: To determine the MH disorders and cost burden associated with acne and rosacea. METHODS: Data were examined from the 2002-2012 US National Inpatient Sample, comprising a sample of ~20% of all US paediatric and adult hospitalizations (n = 87 053 155 admissions). RESULTS: A diagnosis of ≥ 1 MH disorder was much more common among all inpatients with vs. those without a diagnosis of acne (43.7% vs. 20.0%, respectively) and rosacea (35.1% vs. 20.0%, respectively). In multivariable logistic regression models controlling for sex, age, race/ethnicity and insurance status, acne (adjusted OR = 13.02; 95% CI 11.75-14.42) and rosacea (adjusted OR = 1.70; 95% CI 1.56-1.95) were associated with significantly higher odds of a primary admission for an MH disorder (13 and 8, respectively, of 15 MH disorders examined). Both acne and rosacea were associated with higher risk of mood, anxiety, impulse control and personality disorders, and with > $2 million of excess mean annual costs of hospitalization for MH disorders in the USA. CONCLUSION: In this study, inpatients with acne or rosacea had increased odds of comorbid MH disorders. In particular, there was an increased number of hospital admissions secondary to a primary MH disorder with coexistent acne/rosacea. MH comorbidities were associated with considerable excess costs among inpatients with acne or rosacea.

Role of extra oral monofocal distractor device in the correction of the facial asymmetry, sleep apnoea, and quality of life associated with TMJ ankylosis.

OBJECTIVES: The purpose of this study is to evaluate the role of primary osteo-distraction prior to ankylosis release in patients, diagnosed with sleep apnoea, facial asymmetry, and reduced quality of life secondary to temporomandibular joint (TMJ) ankylosis. METHODS: Ten patients in the age group of 13-40 years with TMJ ankylosis underwent primary osteo-distraction for mandibular advancement. They were evaluated pre- and post-operatively using radiographs, various questionnaires, and subjective evaluation of facial asymmetry, sleep apnoea, and quality of life (QOL). RESULTS: All the ten patients showed significant improvement in their sleep apnoea symptoms with a mean of 6.20 ± 1.39 (P < 0.05). The mean advancement of the mandible in all the ten patients (both bilateral and unilateral ankylosis) was 15.8 mm (P < 0.05). The quality of life showed marked improvement from very poor to very satisfactory (P < 0.001). CONCLUSION: Primary mandibular distraction is an effective method of correction of facial asymmetry, sleep apnoea, and quality of life in patients with TMJ ankylosis.

Maternal magnesium therapy, neonatal serum magnesium concentration and immediate neonatal outcomes.

OBJECTIVE: The fetus is exposed to magnesium administered to the pregnant mother. However, there is controversy regarding magnesium-related neonatal adverse outcomes, largely driven by a limited understanding of the factors that influence neonatal serum magnesium concentrations and associated outcomes. The objective of this study was to examine the relationship between antenatal maternal magnesium dose and serum concentrations, neonatal serum magnesium concentration and immediate neonatal outcomes. STUDY DESIGN: A retrospective study was conducted at a community-based teaching hospital. Neonatal serum magnesium concentrations within 48 h of birth were used to stratify magnesium-exposed neonates into three groups: group 1: <2.5 mg dl-1, group 2: ⩾2.5 to <4.5 mg dl-1, and group 3:⩾4.5 mg dl-1. Immediate neonatal outcomes were compared between the three groups. Total maternal magnesium dose and serum magnesium concentrations before the delivery were correlated with neonatal serum magnesium concentrations and outcomes. RESULTS: Of the 304 mother-baby dyads between 24 and 34 weeks gestation, 237 received antenatal magnesium. Neonatal serum magnesium concentration was 3.14±0.83 mg dl-1 in exposed and 1.96±0.42 mg dl-1 in unexposed neonates (P<0.001). Compared with group 2, neonates had higher odds of grade 3 or 4 intraventricular hemorrhage in group 1 (adjusted odds ratio (AOR) 5.95 (95% confidence interval (CI) 1.05 to 33.66)) and group 3 (AOR 8.42 (95% CI 1.35 to 52.54)). Group 3 neonates also had increased odds of periventricular leukomalacia (AOR: 5.37 (95% CI 1.02 to 28.28) compared with group 2 neonates. Predictors of neonatal serum magnesium concentrations included maternal magnesium dose (r=0.66, P<0.0001), duration of therapy (r=0.70, P<0.0001) and serum concentration (r=0.72, P<0.001). CONCLUSION: The between-group differences highlight that there is a therapeutic range of neonatal serum magnesium concentrations for neuroprotective effects of antenatal magnesium sulfate, while concentrations outside of this range may be associated with adverse neonatal outcomes. Further studies are needed to determine the optimal dose and duration of maternal magnesium to minimize adverse neonatal outcomes.

Biomechanical investigation of the effect of extracorporeal irradiation on resected human bone.

Extra Corporeal irradiation and Reimplantation Therapy (ECRT) is an established biological reconstruction technique of limb salvage surgery for malignant bone tumor. Several studies have focused on clinical outcome of the procedure, but biomechanical changes post ECRT procedure are not well established. The present study investigates changes in strength, deformation, and composition of cortical bone obtained post en block resection from five patients suffering from ECRT, and the results are verified against age-match control specimen from cadaver. For pre-irradiated sample, average indentation modulus varied from 11.1GPa to 15.8GPa, and hardness from 0.36GPa to 0.48GPa. Post 50Gy irradiation, we observed an overall increase in deformation, viscous response, and energy dissipation across all samples, together with reduction in indentation modulus and hardness. These changes in strength and deformation were found to be consistent with compositional investigations via Raman spectroscopy, where mineralization and amount of calcium content was found to be decreased. The study thus quantifies the effect of extra corporeal irradiation on bone mechanical and compositional response, which in turn can provide clinicians much needed insight into the mechanism of bone healing and repair post ECRT to guide follow-up care and recovery.

Comparison of cardiovascular responses after injection of lidocaine with either clonidine or adrenaline: a two-year comparative analysis.

Our aim was to evaluate the efficacy of clonidine with lidocaine as a local anaesthetic agent for inferior alveolar mandibular nerve blocks for dental extraction. We studied 200 patients who required extraction of mandibular teeth and divided them into two groups of 100 each, the first of which was given lidocaine and adrenaline (12.5µg/ml) and the second lidocaine and clonidine (15µg/ml). Cardiovascular vascular variables (blood pressure, heart rate, and mean arterial pressure) were assessed before, during, and after extraction, and postoperative pain was measured on a visual analogue scale. There was a significant reduction in systolic blood pressure (p=0.0001) and heart rate (p=0.000) after injection of clonidine. However, they both increased after injections of lidocaine plus adrenaline, and there was a significant reduction in pain at four hours postoperatively with clonidine (p=0.000). Our results showed that anaesthesia with lidocaine and clonidine decreases systolic blood pressure and heart rate 10minutes after injection for extraction of lower mandibular teeth. We suggest that patients who have local anaesthetic with lidocaine and clonidine are at minimal cardiovascular risk and there is no difference in the onset of anaesthesia.

Prognosticating metastatic osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate and delayed metastasectomy: a single center experience of 102 patients.

PURPOSE: Data on prognostic factors in patients with metastatic osteosarcoma treated with uniform chemotherapy protocol are lacking. The objective of this study was to analyze demographic data, treatment outcome and prognostic factors for patients with metastatic osteosarcoma at our center treated with a uniform chemotherapy protocol without high dose methotrexate. METHODS: This is a single-institutional data review of patients treated between June 2003 and December 2012 with neoadjuvant chemotherapy, local site surgery followed by adjuvant chemotherapy and metastasectomy at completion of adjuvant chemotherapy. RESULTS: 102 patients of metastatic osteosarcoma were treated with a median age of 18 years (range 8-48 years), male to female ratio of 3.3:1 and median symptom duration of 4 months. EFS and OS at 5 years were 12.7 ± 0.1 and 28.1 ± 0.1 %, respectively. On multivariate analysis, elevated serum alkaline phosphatase (p < 0.001) and number of metastasis >3 (p = 0.04) were predictive of lower EFS, whereas elevated serum alkaline phosphatase (p = 0.01), number of metastasis >3 (p = 0.05), and margin positivity (p < 0.001) were predictive of lower OS. CONCLUSIONS: This is the largest data on metastatic osteosarcoma treated with a uniform chemotherapy protocol without high dose methotrexate. The data showed prognostic factors similar to what have been observed previously such as elevated serum alkaline phosphatase and >3 metastatic lesions in lung predicting inferior outcome. Notably our survival was comparable to data from other studies despite our practice of delaying metastasectomy to completion of chemotherapy rather than performing the same along with local site surgery.

Developing a prognostic model for localized Ewing sarcoma family of tumors: A single institutional experience of 224 cases treated with uniform chemotherapy protocol.

BACKGROUND: Data on patients with localized Ewing sarcoma family of tumors (ESFT) who have received a uniform chemotherapy protocol are minimal. METHODS: This is a single institutional review of patients with ESFT treated between June 2003 and November 2011. RESULTS: 224/374 (60%) patients with ESFT presented with localized disease; median age was 15 years (range: 0.1-55). Ninety-nine patients underwent surgery of which 50 received adjuvant radiotherapy; 80 patients received radical radiotherapy following neoadjuvant chemotherapy. At median follow-up of 40.2 months (range: 1.3-129), 5-year EFS, OS, and local-control-rate, were 36.8 ± 3.6%, 52.4 ± 4.3%, and 63 ± 4.3%, respectively. In multivariate analysis, tumor diameter > 8 cm (P = 0.03), symptom duration > 4 months (P = 0.04), and WBC > 11 × 10(9) /L (P = 0.003) predicted inferior EFS; spine/abdomino-pelvic primary (P = 0.009) and WBC > 11 × 10(9) /L (P = 0.003) predicted inferior OS. Tumor size > 8 cm (P = 0.03) and radical radiotherapy as local treatment (P = 0.01) predicted inferior local-control-rate. CONCLUSION: Prognostic hazard models for EFS and OS based on significant prognostic factors suggested that patients with combination of ESFT of spine/abdomino-pelvic region and baseline WBC > 11 × 10(9) /L had inferior OS (hazard ratio 4.44, P < 0.001) while patients with combination of ESFT with symptom duration > 4 months, tumor diameter > 8 m and baseline WBC > 11 × 10(9) /L had inferior EFS (hazard ratio 3.89, P = 0.002).

Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center.

BACKGROUND: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. PATIENTS AND METHODS: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan-Meir product limit method and compared across groups using the log-rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. RESULTS: Median age at diagnosis was 55 years (range: 21-81 years). 57.4% (n = 58) of patients were male, 22% (n = 22) had performance status (PS) of <2 at diagnosis and 89% received first-line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1-year OS was 57% (95% confidence interval [CI]: 46-66%) and 47% (95% CI: 35-57%), respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. CONCLUSION: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe.

Hypoalbuminaemia is an independent predictor of poor outcome in metastatic Ewing's sarcoma family of tumours: a single institutional experience of 150 cases treated with uniform chemotherapy protocol.

AIMS: Data on metastatic Ewing's sarcoma family of tumours (ESFT) with uniform chemotherapy protocol are minimal. MATERIALS AND METHODS: This was a single institutional patient review of patients treated between June 2003 and November 2011 and evaluated on an intent-to-treat analysis. All patients received uniform chemotherapy: neoadjuvant chemotherapy (NACT), surgery and/or radiotherapy as local treatment followed by adjuvant chemotherapy. Local treatment was offered if the patient achieved a complete response and/or a partial response at both the primary and the metastatic site. RESULTS: In total, 150/374 (40%) ESFT patients were metastatic, with a median age of 15 years (range: 2-50); a tumour diameter of 10 cm (range: 1.8-26). Most common metastatic sites were lung only (53; 35%), bone only (35; 23%) and combined bone/lung (25; 17%). Twenty patients underwent surgery; 55 patients received radical radiotherapy after NACT. After a median follow-up of 26.1 months (range: 1.6-101.6), 5 year event-free survival (EFS), overall survival and local control rate (LCR) were 9.1 ± 3.3%, 16.9 ± 5.2% and 31.8 ± 7.9%, respectively. Univariate analysis showed serum albumin ≤3.4 g/dl (P < 0.001) to predict inferior EFS. Tumour size >8 cm (P = 0.05), haemoglobin ≤10 g/dl (P = 0.04), hypoalbuminaemia (P = 0.003) and radical radiotherapy as local treatment (P = 0.03) predicted inferior overall survival. No factor significantly predicted LCR, although age ≤15 years (P = 0.08) and radical radiotherapy as local treatment (P = 0.09) had a trend towards inferior LCR. Hypoalbuminaemia was the only prognostic factor to predict EFS on multivariate analysis. CONCLUSION: This was the largest study of metastatic ESFT from Asia and identified a unique prognostic factor. In view of dismal prognosis with conventional chemotherapy in metastatic ESFT with hypoalbuminaemia, palliative intent therapy may be a potential therapeutic alternative for this subgroup of patients, especially in resource-challenged situations.

Role of extracorporeal irradiation in malignant bone tumors.

AIMS AND OBJECTIVES: Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. MATERIALS AND METHODS: From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. CONCLUSION: Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.

Intralesional autologous mesenchymal stem cells in management of osteonecrosis of femur: a preliminary study.

BACKGROUND: Management of early stages of osteonecrosis aims to prevent the collapse of the femoral head by attempts at restoring the vascularity of femoral head. Bone marrow-derived mononuclear cells with their angiogenic and osteogenic properties appear to have the potential to halt the disease process when injected intralesionally following core decompression. MATERIALS AND METHODS: Forty patients (60 hips) with stage I, II or III (ARCO system) osteonecrosis of femoral head were treated by either core decompression and isolated mononuclear cells (group A) or core decompression and unprocessed bone marrow injection (group B). The patients were followed up clinically and radiologically for a minimum of 2 years. The functional outcome was assessed in terms of Harris hip score, and disease progression was assessed radiologically by comparing the preoperative and follow-up MRI at the end of 2 years. RESULTS: On 2-year follow-up, there was considerable improvement in the hip function as measured by the Harris hip score in both the groups (p = 0.031). On MRI, there was a decrease in the size of the lesion in group A (p = 0.03). Three of 30 hips (10.0 %) in group B required total hip replacement. CONCLUSIONS: Implantation of autologous bone marrow stem cells in avascular necrosis of femoral head is a safe and effective procedure and has better outcome than bone marrow for early stage of avascular necrosis of femoral head.