Low-grade central osteosarcoma: a difficult condition to diagnose.

Low-grade central osteosarcoma (LGCO) is a rare variant of osteosarcoma which is difficult to diagnose. If not treated appropriately, the tumour can recur with higher-grade disease. We reviewed our experience of this condition to try and identify factors that could improve both diagnosis and outcome. 18 patients out of 1540 osteosarcoma cases (over 25 years) had LGCO (1.2%). Only 11 patients (61%) were direct primary referrals. Almost 40% (7 of 18) cases were referred after treatment elsewhere when the diagnosis had not been made initially and all presented with local recurrence. Of the 11 who presented primarily, the first biopsy was diagnostic in only 6 (55%) cases. Of the remaining cases, up to three separate biopsies were required before a definitive diagnosis was made. Overall survivorship at 5 years was 90%. 17 patients were treated with limb salvage procedures, and one patient had an amputation. The diagnosis of LGCO remains challenging due to the relatively nonspecific radiological and histological findings. Since treatment of LGCO is so different to a benign lesion, accurate diagnosis is essential. Any difficult or nondiagnostic biopsies of solitary bone lesions should be referred to specialist tumour units for a second opinion.

Primary leiomyosarcoma of bone: analysis of prognosis.

Leiomyosarcoma of bone is just one of the variants of spindle cell sarcoma of bone characterised by the expression of desmin and other markers indicating a significant element of smooth muscle in the tumour, without osteoid production we have investigated the management and outcome of this rare type of primary malignant bone tumour. Method. Retrospective review of data stored on a prospective database. Results. In a database of 3364 patients with primary malignant bone sarcomas, 31 patients were identified with a primary leiomyosarcoma of bone. There were 12 males and 19 females with a mean age of 46 and tumour size of 8 cm. The most common site was the distal femur followed by the proximal tibia. Treatment was with chemotherapy and surgical resection. Seven of the patients had metastases at diagnosis. Surgery was carried out in 28 patients, 8 having amputation and 20 limb salvage. Three patients developed local recurrence, but half developed metastases. All patient disease-specific survival was 57% at five years and 44% at 10 yrs but for those without metastases was 82% and 60%, respectively. The only prognostic factors were metastases at diagnosis. Conclusion. Leiomyosarcoma of bone is a very rare primary malignant bone tumour affecting a predominantly older population. Despite the high incidence of metastases, survival is better than for other bone sarcomas for those without metastases at diagnosis.

Prognostic factors and metastatic patterns in primary myxoid/round-cell liposarcoma.

Background. This study aimed to investigate prognostic factors for patients with myxoid/round-cell liposarcoma (MRCLS), in particular the significance of the round cell component, and to identify metastatic patterns as well as possibly suggest a suitable strategy for followup. Methods. Clinical, morphologic, and follow-up data from 160 patients with MRCLS was reviewed and statistically analysed. Results. Of 130 tumours with the round cell component evaluated, 61 had no round cell component, 27 had <5% round cell component, and 42 had >5%. All patients underwent surgical excision, 15 requiring amputation. 107 patients received adjuvant radiotherapy. Local recurrence occurred in 19 patients (12%), predominantly in patients with marginal or intralesional margins and a round cell component. Overall disease specific survival was 75% at 5 years and 56% at 10 years and was related to the proportion of round cell component. Of 52 patients who developed metastases, 38 (73%) had purely extrapulmonary metastases. We could not identify any factors predicting the site of metastases developing. Conclusions. The occurrence of any round cell component is the most important adverse prognostic factor for patients with MRCLS; patients with >5% round cell component are at higher risk of local recurrence, metastasis and tumour-related death and should be considered for adjuvant radiotherapy and possibly chemotherapy. The best method of monitoring extrapulmonary metastases remains to be established.

Identification and characterization of new impurities in rivastigmine.

Rivastigmine is a drug against Alzheimer's disease, and is a non-pharmacopoeial compound. During the preparation of rivastigmine in our laboratory, two impurities were detected and identified with a simple and sensitive reversed-phase liquid chromatography coupled with electrospray-mass spectrometry. The same impurities were also observed in commercial batches. These impurities were isolated by preparative HPLC and co-injected with rivastigmine sample to confirm the retention times in HPLC. These impurities were characterized as N,N-dimethyl-3-[1-dimethylaminoethyl]phenylcarboxylate (dimethyl-rivastigmine) and N,N-diethyl-3-[1-dimethylaminoethyl]phenylcarboxamide (diethyl-rivastigmine). Structural elucidation of these impurities by spectral data (1H NMR, 13C NMR and MS) is discussed.

A Case of Myoepithelioma of the Nasal Cavity.

Myoepithelioma is a rare tumour of the salivary glands. Only 3 cases of myoepithelioma in the nasal cavity have been reported. A 29 year old male presented to us with epistaxis and nasal obstruction. There was a fleshy mass occupying the right middle meatus. Biopsy showed evidence of myoepithelioma and an endoscopic excision of the tumour was done. Histopathological examination of the resected tumour was consistent with myoepithelioma. Due to its rarity, the nature of the tumour is not known and regular follow-ups are needed for early detection of recurrence and malignancy.

Preoperative surgical risk stratification in osteosarcoma based on the proximity to the major vessels.

AIMS: The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. PATIENTS AND METHODS: A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. RESULTS: Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. CONCLUSION: The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024-1031.

Chondroblastoma in pelvis and extremities- a signle centre study of 177 cases.

INTRODUCTION: Chondroblastoma is a rare benign bone tumour that usually occurs in children and young adults. They are cartilaginous tumours arising in the epiphysis or apophysis of a long bone. The tumour is classified as benign, although rare cases of pulmonary metastases have been reported. The aims of this study were to describe clinical, radiographic characteristics of chondroblastoma; to analyse the local recurrence rate and complications associated with surgery. MATERIAL AND METHODS: This retrospective study included 177 patients, who had been diagnosed with a chondroblastoma in extremity between 1990 and 2015. RESULTS: The most common site was proximal tibia 20%, followed by proximal humerus 19%, proximal femur 18%, distal femur 16% and foot 15%. One patient has died of the disease and one patient is alive after being operated for lung metastases. There was local recurrence in 25/177 (14%) patients. The median time to local recurrence was 10 months (range 3-158 months). The most common site for local recurrence was proximal tibia (22.2%). The proximal femur was the location in 32/178 (18%) of the cases. 18/32 (56%) were in the greater trochanter and 14/32 (44%) in the femoral head. The mean age was lower in tumours located in femoral head when compared to the greater trochanter; 19.5 years and 13.9 years respectively (p = =0.004). Tumours located in greater trochanter were all curetted without further complications. Local recurrence was seen more often in femoral head tumours, though without statistical significance; 3/14 (21%) and none, respectively (p = =0.073). CONCLUSIONS: Chondroblastoma is a rare benign to intermediate grade bone tumour with a potential to metastasise. Femoral head chondroblastoma is rare, presenting 4.5% of all chondroblastoma cases. Around 50% of the chondroblastoma in femoral head. occur in patients with open growth plates.

GIS-based approach for optimized siting of municipal solid waste landfill.

The exponential rise in the urban population of the developing countries in the past few decades and the resulting accelerated urbanization phenomenon has brought to the fore the necessity to develop environmentally sustainable and efficient waste management systems. Sanitary landfill constitutes one of the primary methods of municipal solid waste disposal. Optimized siting decisions have gained considerable importance in order to ensure minimum damage to the various environmental sub-components as well as reduce the stigma associated with the residents living in its vicinity, thereby enhancing the overall sustainability associated with the life cycle of a landfill. This paper addresses the siting of a new landfill using a multi-criteria decision analysis (MCDA) and overlay analysis using a geographic information system (GIS). The proposed system can accommodate new information on the landfill site selection by updating its knowledge base. Several factors are considered in the siting process including geology, water supply resources, land use, sensitive sites, air quality and groundwater quality. Weightings were assigned to each criterion depending upon their relative importance and ratings in accordance with the relative magnitude of impact. The results from testing the system using different sites show the effectiveness of the system in the selection process.

Delayed diagnosis of synovial sarcoma of the foot.

Soft tissue sarcomas are relatively rare in the population, rarely encountered by the average orthopedic surgeon, and may only be seen once in a lifetime by a general practitioner. Although rare, it is a serious condition that, if diagnosed early, can result in improved prognosis. This article presents a case of a delayed diagnosis of a soft tissue sarcoma and highlights possible pitfalls and causes for such delays in hope of educating and reducing such incidences in the future.

The role of grade in local recurrence and the disease-specific survival in chondrosarcomas.

Aims: The purpose of this study was to describe the effect of histological grade on disease-specific survival in patients with chondrosarcoma. Patients and Methods: A total of 343 patients with a chondrosarcoma were included. The histological grade was assessed on the initial biopsy and on the resection specimen. Where the histology showed a mixed grade, the highest grade was taken as the definitive grade. When only small focal areas showed higher grade, the final grade was considered as both. Results: The concordance between the highest preoperative biopsy grading and the highest final grading of the resection specimen in total was only 43% (146/343). In 102 specimens (30%), a small number of cells or focal areas of higher grade were observed in contrast to the main histology. The disease-specific survival, stratified according to the predominant histological grade, showed greater variation than when stratified according to the highest grade seen in the resection specimen. Conclusion: The diagnostic biopsy in chondrosarcoma is unreliable in assessing the definitive grade and the malignant potential of the tumour. When categorizing the grade of the resection specimen, the prognosis for local recurrence and disease-specific survival should be based on the highest grade seen, even when seen in only a few cells. Cite this article: Bone Joint J 2018;100-B:662-6.

Simultaneous Determination of Impurities of Atazanavir and Ritonavir in Tablet Dosage Form by Using Reversed-Phase Ultra Performance Liquid Chromatographic Method.

A simple, rapid, selective and stability indicating reversed phase-ultra performance liquid chromatography method was developed and validated for the simultaneous quantification of process related and degradation impurities present in Atazanavir and Ritonavir tablets. The two proposed drug components and their respective impurities were separated using Acquity BEH C18 (100 mm × 2.1 mm), 1.7 µ column at a flow rate of 0.4 mL/min. Buffer used as Mobile phase-A which consists of 0.01 M monobasic potassium hydrogen phosphate adjusted the pH to 3.6 and acetonitrile is used as organic modifier (mobile phase-B). The detector wavelength of 240 nm was used for quantifying the impurities. Both the drug components along with their impurities were eluted within a runtime of 18 min. The performance of the developed method was checked by validating the method according to the requirements of International Conference on Harmonization for parameters such as specificity, precision, linearity, ruggedness, accuracy, sensitivity (limit of detection (LOD) and limit of quantitation (LOQ)) and robustness. Linearity and range were established from LOQ level to 150% level. Accuracy of the method was demonstrated from LOQ level to 150% level. The developed stability indicating method is capable for determination of impurities of Atazanavir and Ritonavir in combined tablet dosage form as well as individual dosage forms also. The reported method enables lesser solvent consumption and reduces time and cost of the analysis in quality control laboratory.

Cryopreservation of in vitro grown shoots of ginger (Zingiber officinale Rosc.).

An efficient cryopreservation technique for in vitro grown shoots of ginger (Zingiber officinale Rosc) was developed based on encapsulation dehydration, encapsulation vitrification and vitrification procedures. Pregrowth and serial preculture were needed to obtain the best regrowth for all techniques. The vitrification procedure resulted in higher regrowth (80%) when compared to encapsulation vitrification (66%) and encapsulation dehydration (41%). In the vitrification procedure shoots were: precultured in liquid Murashige-Skoog medium containing 0.3 M sucrose for 3 days; cryoprotected with a mixture of 5% DMSO and 5% glycerol for 20 min at room temperature; osmoprotected with a mixture of 2 M glycerol and 0.4 m sucrose for 20 min at 25 degrees C; before being dehydrated with a highly concentrated vitrification solution (PVS2) for 40 min at 25 degrees C. The dehydrated shoots were transferred to 2 ml cryotubes, suspended in 1 ml PVS2 and plunged directly into liquid nitrogen. In all the three cryopreservation procedures tested, shoots grew from cryopreserved shoot tips without intermediary callus formation. The genetic stability of cryopreserved ginger shoot buds were confirmed using ISSR and RAPD profiling.

Does osteofibrous dysplasia progress to adamantinoma and how should they be treated?

AIMS: The aim of this study was to identify any progression between benign osteofibrous dysplasia (OFD), OFD-like adamantinoma and malignant adamantinoma, and to investigate the rates of local recurrence, metastases and survival, in order to develop treatment algorithms for each. PATIENTS AND METHODS: A single institution retrospective review of all patients presenting with OFD, OFD-like adamantinoma and adamantinoma between 1973 and 2012 was undertaken. Complete data were available for 73 patients (42 with OFD; ten with an OFD-like adamantinoma and 21 with an adamantinoma). The mean follow-up was 10.3 years (3 to 25) for OFD, 9.2 years (3.0 to 26.3) for OFD-like and 11.6 years (0.25 to 33) for adamantinoma. RESULTS: The mean age at diagnosis for OFD was 13.5 years (1 to 49), 10.5 years (6 to 28) for OFD-like and 34 years (14 to 86) for adamantinoma. A total of 24 of the 42 patients with OFD (57%) have not required any treatment and have been managed with observation. A total of 18 of the 42 patients with OFD underwent surgery, 13 with curettage and five with resection. In all, three patients developed recurrence following curettage (23%) but none following resection. All these patients were cured with further limited surgery. A total of six patients initially diagnosed with OFD were subsequently found to have OFD-like adamantinoma. Of the ten patients initially diagnosed with OFD-like adamantinoma, three (30%) were managed with observation alone and seven underwent surgery, two with curettage and five with resection. Local recurrence arose in two patients, one each after curettage and resection. No patients with either OFD or an OFD-like adamantinoma developed metastases or had progression to adamantinoma. All patients with an adamantinoma were treated by surgery, three with curettage, six with amputation and 12 with excision. In all, two of the three treated with curettage developed local recurrence, requiring further surgery. Late development of both local recurrence and metastases led to a ten year disease specific survival of 93% which had dropped to 39% by 20 years. CONCLUSION: We found no evidence of progression from OFD to adamantinoma. Conservative management with observation or curettage is often successful for patients with OFD and OFD-like adamantinoma. Resection with clear margins is required for patients with adamantinoma. Late tumour recurrence is not uncommon in adamantinoma and prolonged follow-up should be considered. Cite this article: Bone Joint J 2017;99-B:409-16.

Ewing's sarcoma masquerading as chronic osteomyelitis: a case report.

We report an unusual presentation of Ewing's sarcoma in an adult female who was treated for tuberculous chronic osteomyelitis before a diagnosis of Ewing's sarcoma was finally made. Emphasis is on the fact that these two conditions can masquerade each other with delays in diagnosis and possibility of devastating results.

Protocols for In Vitro Propagation, Conservation, Synthetic Seed Production, Microrhizome Production, and Molecular Profiling in Turmeric (Curcuma longa L.).

Turmeric is a rhizomatous herbaceous perennial but cultivated as annual, belonging to the family Zingiberaceae. It is a native of India and South East Asia. The tuberous rhizomes or underground stems of turmeric are used from antiquity as condiments, a dye and as an aromatic stimulant in several medicines. Turmeric is an important crop in India and it is used as a spice, food preservative, coloring agent, cosmetic as well as for its medicinal properties. Propagation is done vegetatively with rhizome bits as seed materials. It is plagued by rhizome rot diseases most of which are mainly spread through infected seed rhizomes. Micropropagation will help in production of disease-free seed. Sexual reproduction is rare in turmeric, making recombinant breeding very difficult. In vitro technology can thus become the preferred choice and it can be utilized for multiplication, conservation of genetic resources, generating variability, gene transfer, molecular tagging, and their utility in crop improvement.

Protocols for In Vitro Propagation, Conservation, Synthetic Seed Production, Embryo Rescue, Microrhizome Production, Molecular Profiling, and Genetic Transformation in Ginger (Zingiber officinale Roscoe.).

Ginger is a rhizomatous plant that belongs to the family Zingiberaceae. It is a herbaceous perennial but cultivated as annual, with crop duration of 7-10 months. Ginger is native to India and Tropical South Asia. The tuberous rhizomes or underground stems of ginger are used as condiment, an aromatic stimulant, and food preservative as well as in traditional medicine. Ginger is propagated vegetatively with rhizome bits as seed material. Cultivation of ginger is plagued by rhizome rot diseases, most of which are mainly spread through infected seed rhizomes. Micropropagation will help in production of disease-free planting material. Sexual reproduction is absent in ginger, making recombinant breeding very impossible. In vitro technology can thus become the preferred choice as it can be utilized for multiplication, conservation of genetic resources, generating variability, gene transfer, molecular tagging, and their utility in crop improvement of these crops.

Osteosarcoma of the pelvis.

AIMS: Osteosarcoma of the pelvis is a particularly difficult tumour to treat as it often presents late, may be of considerable size and/or associated with metastases when it presents, and is frequently chondroid in origin and resistant to chemotherapy. The aim of this study was to review our experience of managing this group of patients and to identify features predictive of a poor outcome. PATIENTS AND METHODS: Between 1983 and 2014, 121 patients, (74 females and 47 males) were treated at a single hospital: 74 (61.2%) patients had a primary osteosarcoma and 47 (38.8%) had an osteosarcoma which was secondary either to Paget's disease (22; 18.2%) or to previous pelvic irradiation (25; 20.7%). The mean age of those with a primary osteosarcoma was 29.3 years (nine to 76) and their mean follow-up 2.9 years (0 to 29). The mean age of those with a secondary sarcoma was 61.9 years (15 to 85) and their mean follow-up was one year (0 to 14). A total of 22 patients with a primary sarcoma (52.4%) and 20 of those with a secondary sarcoma (47.6%) had metastases at the time of presentation. RESULTS: The disease-specific survival at five years for all patients was 27.2%. For those without metastases at the time of diagnosis, the five-year survival was 32.7%. Factors associated with a poor outcome were metastases at diagnosis and secondary tumours. In primary osteosarcoma, sacral location, surgical margin and a diameter > 10 cm were associated with a poor outcome. CONCLUSION: In this, the largest single series of patients with an osteosarcoma of the pelvis treated in a single hospital, those with secondary tumours and those with metastases at presentation had a particularly poor outcome. For those with a primary sarcoma, sacral location, an intralesional margin and a diameter of > 10 cm were poor prognostic indicators.

Ewing's sarcoma: only patients with 100% of necrosis after chemotherapy should be classified as having a good response.

AIMS: The purpose of this study was to review a large cohort of patients and further assess the correlation between the histological response to chemotherapy in patients with Ewing's sarcoma with the overall (OS) and event-free survival (EFS). PATIENTS AND METHODS: All patients treated for Ewing's sarcoma between 1980 and 2012 were reviewed. Of these, 293 patients without metastases at the time of diagnosis and treated with chemotherapy and surgery were included. Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. RESULTS: The mean age at diagnosis was 16 years (1 to 62) and the mean follow-up was 9.1 years (six months to 32.6 years). The OS and EFS for the series were 75% and 65% at five years. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years, respectively) (p < 0.001). There were no significant differences in survival between patients treated between 1980 and 1989 compared with those treated between 1990 and 1999, and those treated between 2000 and 2012 (p = 0.55). CONCLUSION: Only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumour in the surgical specimen. Cite this article: Bone Joint J 2016;98-B:1138-44.

Resectable extra-pleural and extra-meningeal solitary fibrous tumours: A multi-centre prognostic study.

BACKGROUND: Extra-pleural and extra-meningeal solitary fibrous tumour (SFT) is a rare sarcoma histotype curable with surgery in the majority of patients. The behaviour of these tumours ranges from indolent/very low grade to malignant/high grade but it is still not possible to accurately predict prognosis after surgery. We have investigated a multi-centre series to stratify the risk of recurrence to patients with SFTs. METHODS: We retrospectively analysed the data from 243 patients who underwent surgery (2002-2011) at four sarcoma referral centres. RESULTS: Upon univariate analysis, hypercellularity, atypia, necrosis, high mitotic rate (ie >4 mitoses/10 HPF) were associated with both disease-free and overall survival. Surgical margins were a significant prognostic factor for disease-free (P = 0.007) but not for overall survival. Unexpectedly, larger tumour size was associated with a better prognosis (P = 0.038) and fewer recurrences (P = 0.024). Upon multivariable analysis, high mitotic rate (hazard ratio, HR = 2.85, P = 0.002), cellular atypia (HR = 1.62, P = 0.015) and hypercellularity (HR = 1.82, P = 0.031) were significantly associated with recurrences. A SFT recurrence score has been provided to stratify risk of recurrence. CONCLUSION: This study provides a prognostic model to stratify risk of recurrence in patients with resectable SFTs. This allows clinician to decide on an optimal follow-up strategy and to select patients that may benefit from adjuvant treatments.