Adjunctive Radiotherapy Research Articles

Global proteome and phosphoproteome analysis of meningiomas

Meningiomas are common brain tumours arising from meningeal tissue. Despite the majority of them displaying benign features, they can cause mild to severe morbidity. The current main therapeutic approach is complete tumour resection commonly with adjunct radiation therapy. However, tumour location can hamper complete resection and chemotherapies are ineffective. In this study we aim to elucidate dysregulated pathways in meningioma pathogenesis and identify novel molecular targets by deciphering the proteome and phosphoproteome of different grades of meningiomas. Tumour lysates were collected from grade I, II and III frozen meningioma specimens and three normal healthy human meninges. Phosphoprotein purification was performed using Qiagen® PhosphoProtein Purification Kit. Proteins were separated by SDS-PAGE followed by in-gel tryptic digestion. Extracted peptides were purified and analysed by electrospray ionization LC-MS/MS. Raw mass spectrometry files were analysed using MaxQuantTM. Expression data was validated by Western blot and functionally annotated using Ingenuity® Pathway Analysis (IPA®) and DAVID 6.8. We have quantified 3888 proteins and 3074 phosphoproteins across all grades of meningioma and normal meninges. Comparative analysis confirmed 181 proteins and 338 phosphoproteins to be commonly significantly upregulated (log2 fold-change≥1.5; p<0.05) among all grades vs. normal meninges. We have successfully validated the expression data of several upregulated proteins and phosphoproteins. Gene Ontology revealed biological processes including EFGR and VEGFR signalling to be enriched in the phosphoproteome. Grade-wise comparisons identified 667 proteins and 769 phosphoproteins to be differentially expressed (p<0.05) between grade III meningiomas compared to grade II and I. We have performed a comparative proteomic analysis across all meningioma grades and identified changes in proteomic profiles between these tumours and normal healthy meninges. We will use this data to define novel targets common to all grades and specific to a grade of meningioma for future therapies.

Basic concepts in metal work failure after metastatic spine tumour surgery.

The development of spinal implants marks a watershed in the evolution of metastatic spine tumour surgery (MSTS), which has evolved from standalone decompressive laminectomy to instrumented stabilization and decompression with reconstruction when necessary. Fusion may not be feasible after MSTS due to poor quality of graft host bed along with adjunct chemotherapy and/or radiotherapy postoperatively. With an increase in the survival of patients with spinal tumours, there is a probability of an increase in the rate of implant failure. This review aims to help establish a clear understanding of implants/constructs used in MSTS and to highlight the fundamental biomechanics of implant/construct failures. Published literature on implant failure after spine surgery and MSTS has been reviewed. The evolution of spinal implants and their role in MSTS has been briefly described. The review defines implant/construct failures using radiological parameters that are practical, feasible, and derived from historical descriptions. We have discussed common modes of implant/construct failure after MSTS to allow further understanding, interception, and prevention of catastrophic failure. Implant failure rates in MSTS are in the range of 2-8%. Variability in patterns of failure has been observed based on anatomical region and the type of constructs used. Patients with construct/implant failures may or may not be symptomatic and present either as early (<3months) or late failures (>3months). It has been noted that not all the implant failures after MSTS result in revisions. Based on the observed radiological criteria and clinical presentations, we have proposed a clinico-radiological classification for implant/construct failure after MSTS.

The role of 125I interstitial brachytherapy for inoperable parotid gland carcinoma

PurposeThe treatment of inoperable parotid gland carcinoma is challenging and controversial. The purpose of this paper was to present our experience in treating this malignancy using 125I interstitial brachytherapy. Methods and MaterialsThirteen patients with advanced carcinomas of the parotid gland were included and treated with 125I interstitial brachytherapy in Peking University School and Hospital of Stomatology from January 2003 to December 2015. All patients were treated with 125I interstitial brachytherapy as a sole modality for the primary tumor. Furthermore, all of them were treated with neck dissection with/without adjunctive external beam radiotherapy for the neck, simultaneously. The prescription dose of interstitial brachytherapy was 140–160 Gy. ResultsMedian followup was 56 months (range: 8–105 months). The 2-year and 5-year local control rates were 91.7% and 58.2%, respectively. The 2-year and 5-year overall survival rates were 100% and 61%, respectively. No cervical lymph node metastasis was observed during the followup. No interstitial brachytherapy-related severe complications occurred. Facial nerve function was preserved well. Conclusions125I interstitial brachytherapy is a feasible and effective treatment for inoperable parotid gland carcinomas without severe complications. And neck dissection with/without external beam radiotherapy is necessary for patients with cervical metastasis or at high risk of cervical metastasis.

Prognostic Factors in Skull Base Chordoma: A Systematic Literature Review and Meta-Analysis.

Currently, there are a lack of reviews assessing the complete range of prognostic factors in skull base chordoma (SBC). This study aimed to systematically review the published literature on prognostic factors in SBC and establish pooled hazard ratios (HRs) of such factors. MEDLINE and Embase searches (inception to April 4, 2017) were conducted. Two reviewers independently selected papers involving SBC prognostic factors, and studied them for methodologic quality and valuable factors. Pooled HRs and 95% confidence intervals (CIs) were calculated. The main end points determined were progression-free survival (PFS) and overall survival (OS). Twenty-two studies with 1754 subjects were included in this systematic review. However, only 18 of the studies provided sufficient data for quantitative synthesis. Preoperative visual deficit (pooled HR, 2.77; 95% CI, 1.57-4.89 for PFS), older patient age (pooled HR, 1.03; 95% CI, 1.1-1.05 for PFS; pooled HR, 1.03; 95% CI, 1.2-1.04 for OS), and nontotal or intralesional tumor resection (pooled HR, 2.01; 95% CI, 1.54-2.62 for PFS; pooled HR, 5.16; 95% CI, 2.27-11.70 for OS) were negative predictors of survival outcomes. However, adjunctive radiotherapy (pooled HR, 0.30; 95% CI, 0.16-0.56) and chondroid chordoma type (pooled HR, 0.5; 95% CI, 0.36-0.69) portended a favorable PFS. In addition, several prognostic biomarkers were promising. This study demonstrated that several clinicopathologic or molecular parameters are associated with survival up to tumor progression or mortality in SBC patients. However, further methodologically high-quality reports are still required to clarify the effects of these factors.

A new case of Giant Cell ‘Reparative’ Granuloma of the temporal bone related to trauma

Abstract Giant Cell Reparative Granuloma (GCRG) is an uncommon benign non-neoplastic lesion that most commonly affects the mandible and maxilla. Only sporadic cases involving the skull base have been reported. The etiology of GCRG is uncertain but may be related to trauma. The origin of ‘reparative’ in the name comes from these lesions appearing after bone trauma. We present a new case of GCRG in the temporal bone of possible posttraumatic origin. To distinguish this type of lesions from true giant cell tumours of bone, from brown tumours, from inflammatory lesions or metastatic lesions, histologic examination is required. The true giant cell tumours of bone are the most important to diagnose as these are generally considered to have a prognosis that is worse than GCRG and require adjunctive radiotherapy in addition to surgical excision.

Impact of optic canal decompression on visual outcome in subtotal resected skull base meningiomas.

Visual impairment (VI) due to neoplastic infiltration of the optic canal (OC) is frequently seen in skull base meningiomas representing a significant restriction in patients` quality of life. However, the delicate anatomy of this region often prevents gross total tumor resection. The aim of the present study was to evaluate the impact of intradural OC decompression and postoperative oncological procedure on preservation of visual acuity in subtotal resected skull base meningiomas. A retrospective analysis of 31 consecutive patients (19 females, 12 males; mean age 53 [range 18-78]), treated in our institution between 01/2011- 09/2014 was performed. Patients` charts were analyzed with special respect to operative procedure, postoperative treatment and procedural impact on late visual function. Most patients (74.2%) had VI prior to surgery. A pterional craniotomy (97%) facilitated subtotal tumor removal in 71% of the patients with no intraoperative and a low rate (6.4%) of postoperative complications. Adjunctive radiotherapy was performed in 19.3% of the patients. Preoperative visual acuity was preserved or improved in 92% of the patients. Substantial tumor regrowth occurred in only 11.2% of the patients. Intradural decompression of the OC stabilizes visual function in subtotally resected skull base meningiomas. Moreover, adjuvant radiotherapy seems to further benefit visual outcome which has to be evaluated in further prospective studies.

Chirurgische Methoden in der Behandlung des Aderhautmelanoms

Significant advancements have been made in the last decades in the treatment of uveal melanoma. Radiation therapy can achieve, depending on the method, local tumour control in up to 98% of cases. Surgical modalities have been implemented in the ocular therapy for uveal melanoma either to treat/prevent radiation complications, such as so-called toxic tumour syndrome, or to primarily treat the tumour with or without adjunctive radiotherapy. These include endoresection and transscleral resection for melanomas of the choroid/ciliary body or irido-trabeculo-cyclectomy for melanomas of the iris-ciliary body. Furthermore, tumour biopsy is playing a progressively more important role in the diagnosis, treatment and follow-up planning of melanoma cases. This paper focuses on the background, the surgical technique as well as the results and complications of tumour excisional and biopsy surgery.

Aryepiglottic lymphoma in a 19‐year‐old Paint gelding treated with excision and adjunctive radiotherapy

SummaryThis case report describes the diagnosis and treatment of an aryepiglottic tumour in a 19‐year‐old Paint gelding. Diagnostic work‐up included physical examination, endoscopic evaluation of the upper airway, and histopathology of the mass following removal. Treatment consisted of surgical excision of the aryepiglottic mass under endoscopic guidance followed by a 100 Gy dose of radiation delivered with strontium‐90 plesiotherapy to the surgical bed at 72 h post‐operatively. The radiation applicator was passed through the left nostril and the application area was confirmed via endoscopic evaluation. Histopathology, including immunohistochemistry, confirmed that the aryepiglottic tumour was T cell lymphoma. Recheck examination, including physical examination and upper airway endoscopy, was performed 1, 3 and 6 months following treatment and local recurrence was not observed. Local control with minimal morbidity can be achieved with surgical excision of equine lymphoma followed by strontium‐90 plesiotherapy.

Comprehensive genomic profiling of parathyroid carcinoma.

6088 Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy, which can cause life-threatening hypercalcemia. Initial surgery is often noncurative, and adjunctive radiotherapy and previous chemotherapies have not been shown to be effective. Previous studies identified recurring mutations in CDC73 and PRUNE2in a limited number of patients. We queried whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 13 consecutive cases of relapsed/metastatic PC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 672x for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Total of 13 specimens were identified from 7 male and 6 female patients. The mean age of the patients in this study was 54 years (range 38 to 76 years). All (100%) cases were Stage IV at the time of CGP. Tumor mutation burden was generally low - median mutation load per mega base was 1.8. There were 58 total GA (4.5 GA/sample) and 10 CRGA (0.8 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (31%) and CDC73 (31%). MEN1 mutations were identified in 23% of cases. Frequent alterations in genes controlling cell cycle progression at G1 including CDKN1B, CDKN2A, CDKN2B and CDKN2C were identified (30%). The most frequent CRGA involved PTEN (23%), NF1 (23%) and KDR (15%). No alterations in BRAF or RETwere identified. A patient with KDR mutation treated with cabozantinib experienced &gt; 50% drop in PTH level and radiographic partial response in 3 months. Conclusions: CGP identified previously unreported TP53 mutations in PCs and potentially actionable genomic alterations including PTEN, NF1 and KDR. Clinical benefit and response observed in a patient treated with VEGFR targeted therapy suggest that patients with this rare tumor may be candidates for targeted therapies.

Adjuvant therapies utilization pattern and survival outcomes in high-grade head and neck soft tissue sarcoma; a population based study

PurposeHead and neck soft tissue sarcoma (HNSTS) is a distinct entity within the soft tissue sarcoma group and the evidence supporting treatment options for this disease is poorly defined. Using the National Cancer Database, this study aims to reveal adjuvant therapy utilization patterns and their outcomes. MaterialsHNSTS patients constituted 6.5% of all sarcoma patients and the analysis was limited to non-metastatic patients who underwent resection between 2004 and 2012. Chi-square test assessed the distribution of demographic, tumor and treatment variables in the treatment subgroups. Kaplan-Meier method estimated overall survival and proportional hazards model estimated survival hazard ratios for prognostic factors including age, comorbidity, gender, race, size, grade, margin status, histology, chemotherapy administration and radiotherapy technique/dose. ResultsThe cohort included 2493 patients with a median age of 62years. Adjuvant therapies were more frequently delivered in high-grade, large tumors and with positive surgical margins. Limiting the analysis to 788 high-grade HNSTS patients, adjunctive radiotherapy improved 5-year survival from 44% (95% confidence interval (CI): 38–50) to 49% (CI: 43–55); reducing mortality hazards ratio by 24% (p<0.001). On multivariate analysis, older age, positive surgical margins and large tumor size were significant predictors of poor survival. These findings were consistent after propensity score analysis. ConclusionOur analysis suggests that adjuvant radiotherapy is associated with improved survival in high-grade HNSTS. Higher dose and precise technique did not accentuate this benefit; however, further studies are needed to refine the treatment strategies, including the role of chemotherapy in the management of this rare disease.

The Response to Chemo Radiation Therapy in Unresectable Glioblastoma Multiforme Patients in Relation to MGMT Promoter Methylation Status: A Study from a Single Saudi Center

Background: The optimal therapy for Glioblastoma Multiforme (GBM) constitutes of maximal safe resection followed by adjunctive concurrent radiation and chemotherapy with Temozolomide (TMZ). However, in certain cases safe maximal resection is not practically amenable. The methylation of the MGMT promoter is being used as a prognostic and predictive factor for the GBM response to TMZ therapy. In the present study, we aimed to measure the outcome of GBM Saudi patients who underwent tumor biopsy followed by radiation therapy with or without chemotherapy based on the MGMT promoter methylation status. Methods: The methylation-specific PCR assay was used to study the methylation status of the MGMT promoter in 77 formalin-fixed paraffin-embedded tissues of high grade glioblastoma. Results: MGMT promoter methylation was detected in 48 samples (62%). Interestingly, significant difference (p=0.0073) was found in overall survival between patients treated with surgery, radiotherapy and temozolomide and those treated with surgery and radiotherapy only, irrespective of MGMT promoter status. The survival rate for patients with MGMT methylated tumor was significantly different favoring the plus temozolomide group (p=0.0107). However, for the patients with MGMT unmethylated tumor, there was no significant difference (p=0.1453) between the two groups. Using the Cox proportional-hazards model, the methylation status of the MGMT promoter emerged as a significant (p=0.0234) clinically relevant predictor of benefit from temozolomide. Conclusion: Here, we have demonstrated that MGMT methylation has significantly improved the survival rate in Saudi patients with unresectable GBM who received concomitant radiation therapy and TMZ. However, MGMT methylation status did not impact the response to radiation therapy.

Breast cancer screening-opportunistic use of registry and linked screening data for local evaluation.

Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more common prognostic and treatment measures and survivals to gain evidence of screening effects among patients attending 4 local hospitals for treatment. To compare prognostic, treatment, and survival measures by screening history to determine whether expected screening effects are occurring. Employing routine clinical registry and linked screening data to investigate associations of screening history with these measures, using unadjusted and adjusted analyses. Screened women had a 10-year survival from breast cancer of 92%, compared with 78% for unscreened women; and 79% of screened surgical cases had breast conserving surgery compared with 64% in unscreened women. Unadjusted analyses indicated that recently screened cases had earlier tumor node metastasis stages, smaller diameters, less nodal involvement, better tumor differentiation, more oestrogen and progesterone receptor positive lesions, more hormone therapy, and less chemotherapy. Radiotherapy tended to be more common in screening participants. More frequent use of adjunctive radiotherapy applied when breast conserving surgery was used. Results confirm the screening effects expected from the scientific literature and demonstrate the value of opportunistic use of available registry and linked screening data for indicating to local health administrations, practitioners, and consumers whether local screening services are having the effects expected.

Management of Primary Acquired Melanosis, Nevus, and Conjunctival Melanoma.

The management of conjunctival melanoma is difficult because of the rarity of the disease, confusing terminology, high rates of local tumor recurrence, controversies regarding treatment, a poor evidence base, unreliable prognostication, and significant mortality rates. The medical literature was reviewed, focusing on treatment and management options for conjunctival melanoma. Recent trends and developments were summarized with respect to terminology, local treatment, histology, genetic analysis, prognostication, and systemic treatment, highlighting the scope for research and possible improvements in patient care. Histopathological diagnostic terminology for primary acquired melanosis is being superseded by more explicit terminology, thus differentiating hypermelanosis from conjunctival melanocytic intraepithelial neoplasia. Topical chemotherapy and increased use of adjunctive radiotherapy have helped improve rates of local tumor control. Use of exenteration has become rare. Regional and systemic metastases are common in patients with nonbulbar conjunctival melanoma, although long-term survivors with metastases are growing in number. Prognostication is mainly based on tumor size and location, but histological and genetic data into multivariate analyses will soon be incorporated. The role of sentinel lymph-node biopsy continues to be controversial. Chemotherapy for metastatic disease is being superseded by targeted therapy based on genetic abnormalities such as BRAF mutations. The management of conjunctival melanoma requires expert care from an experienced, multidisciplinary team. The goal of therapy is to provide good local tumor control with minimal morbidity, high-quality pathology, and adequate psychological support. Maximizing patient enrollment in multicenter clinical trials is likely to strengthen evidence-based decision-making.

Use of Botox (OnabotulinumtoxinA) for the Treatment of Parotid Sialocele and Fistula After Extirpation of Buccal Squamous Cell Carcinoma With Immediate Reconstruction Using Microvascular Free Flap: A Report of 3 Cases

Buccal squamous cell carcinoma is an aggressive form of oral carcinoma with a high recurrence rate. Injury to the parotid duct is often unavoidable when surgically treating buccal squamous cell carcinoma because of the intimate anatomic relation among the buccal mucosa, Stensen duct, and parotid gland. It is often difficult to achieve negative margins and preserve the integrity of the parotid duct. Sialocele formation is a frequent and untoward complication owing to extravasation of saliva into the surgical defect, which delays healing, creates fistulas, and produces painful facial swelling. Currently, no consensus exists regarding the management of a parotid sialocele. Multiple investigators have described different modalities of treatment, such as repeated percutaneous needle aspiration, pressure dressings, antisialagogue therapy, radiotherapy, botulinum toxin, and surgical techniques, including duct repair, diversion, ligation, drain placement, and parotidectomy. With approval from the institutional review board of the University of Texas Health Sciences Center at Houston, 3 cases of parotid sialocele and nonhealing fistulas successfully treated with Botox (onabotulinumtoxinA) after tumor extirpation, neck dissection, and reconstruction with a microvascular free flap are presented. At the University of Texas Health Sciences Center at Houston, the radiation oncologist prefers not to start adjunctive radiation treatment with a nonhealing wound or a drain in the field of radiation. Ideally, a standard timing of adjuvant radiotherapy is 6 to 8weeks after surgery and 60cGy should be completed before 7months. With the use of Botox, the nonhealing wound resolved and the drain was removed at least 2weeks before the initiation of adjunctive radiotherapy, thus minimizing the delay in adjuvant treatment.

Clinical Outcome of Parotidectomy with Reconstruction: Experience of a Regional Head and Neck Cancer Unit.

Background:Salivary gland pathologies represent a histologically diverse group of benign and malignant neoplasms. Currently, World Health Organization recognizes 13 benign and 24 malignant variants of all salivary gland neoplasms. Surgery continues to remain the main-stay for treatment of parotid gland neoplasms. The aim of this study was to document our experiences of the patients treated for parotid tumors and find out if any compelling variable predicted the relative clinical outcomes.Materials and Methods:This was a retrospective study, from records of parotidectomies performed at the operating theatre by the head and neck cancer division of the study institution between 2010 and 2013. Eligibility for study inclusion included cases with benign or malignant parotid neoplasms requiring surgical management with or without adjunct radiotherapy. The predictors of postoperative complications, overall survival (OS), and disease-free survival (DFS) were analyzed.Results:A total of 20 patients underwent parotidectomy. The mean age was 42 years. Tumors were located on the left parotid in 13 cases (65%) and the right parotid in 7 cases (35%). The surgical procedures comprised 16 superficial parotidectomies, 1 total parotidectomy, and 3 radical parotidectomy (inclusive of facial nerve sacrifice) and 2 neck dissections levels II–V. The reconstructive procedures were 2 facial nerve branch cable grafts, 1 end-to-end facial-facial nerve branch anastomoses, and 2 facial re-animation surgeries (temporalis muscle suspensions). A total of five cases (33.3%) had postoperative complications. 2 variables (length of surgery and neck dissection) were found to have an impact on postoperative complications that were statistically significant. Additionally, length of surgery was a significant predictor on the 2 years OS and DFS.Conclusion:The result of this study showed good clinical outcome, especially in the benign cases. The comprehensive clinical outcome of the malignant cases could not be objectively assessed, as the OS and DFS were 50% at 2-years follow-up. It is our submission that a larger sample size is utilized in subsequent studies and quality of life evaluation is included in the methodology.

Epithelioid myxofibrosarcoma: a clinicopathologic analysis of 10 cases

To investigate clinicopathologic features, pathologic diagnosis, differential diagnosis and biological behavior of epitheioid myxofibrosarcoma (EMFS). The clinical and pathological data of 10 cases were collected, and microscopic examination and immunostains were performed along with a review of the literatures. There were 5 males and 5 females with age ranging from 53 to 74 years, and the mean and median age was 63.6 and 62.5 years, respectively. Six cases developed in the extremities, including upper limbs (n=3) and lower limbs (n=3). Three developed in the trunk and 1 case in the mesentery of sigmoid colon. Tumor size ranged from 4.2 to 7.0 cm (mean, 5.3 cm). Most patients presented with painless masses with duration of 1 to 24 months (mean, 8 months). All 10 patients were treated by surgery, with adjunctive chemotherapy and/or radiotherapy in 4 patients and interventional therapy in 1 patient. Histologically, 8 cases were high grade and 2 were intermediate grade. Like the conventional myxofibrosarcomas, all primary tumors presented a multinodular growth pattern consisting of hypocellular myxoid and hypercellular areas. Prominent curvilinear vessels and pseudolipoblasts were observed in the hypocellular myxoid areas. Besides the spindled neoplastic cells, all tumors were characterized by a variable proportion of epithelioid cells with vesicular nuclei, prominent nucleoli and moderate to abundant eosinophilic cytoplasm. They were arranged singly or in small clusters in the myxoid areas, and in compact sheets in the solid areas. The epithelioid component comprised 30% to 90% of the tumors. In addition, areas with resemblance to undifferentiated pleomorphic sarcoma were also noted, especially in the recurrent tumors. Immunohistochemically, tumor cells showed diffuse staining of vimentin in 6 tested cases with focal expression of smooth muscle actin and epithelial membrane antigen in 1 case each. Ki-67 index ranged from 30% to 80% (mean, 58%). Follow-up data (range, 2 to 74 months; mean, 23 months) were available in 10 cases: 4 patients were alive with unresectable or recurrent disease and 6 patients were alive with no evidence of disease. Five patients experienced local recurrence and 2 cases developed metastasis. The median interval to recurrence/metastasis was 7 months (mean, 9 months). The presence of epithelioid cells in a myxofibrosarcomatous background portends an aggressive clinical behavior.EMFS should be differentiated from other myxoid sarcomas with epithelioid morphology.

Clinical Presentation and Long-Term Outcome of Patients With Ectopic Acth Syndrome Due to Bronchial Carcinoid Tumors: A One-Center Experience

To describe the diagnostic features and long-term outcome of patients with bronchial carcinoid tumors with ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), treated in our department. We studied 10 cases with EAS and histologically confirmed bronchial carcinoid tumors, diagnosed from 1992 until 2006. Diagnosis was based upon blood, urine, radiologic, and interventional tests. Disease status at the time of the last follow-up was the primary outcome measure. Clinical manifestations included Cushingoid features (100%), psychiatric symptoms (90%), hypertension (70%), diabetes/impaired glucose tolerance (40%), osteoporosis (10%), and hypokalemia (10%). The average time from the onset of symptoms until diagnosis was 14.2 ± 17.0 months. None of the patients exhibited a positive cortisol or ACTH response to corticotropin-releasing hormone (CRH) test, and none showed a positive gradient on bilateral inferior petrosal sinus sampling (BIPSS). All tumors were identified by computed tomography and by octreotide scintigraphy in 8 patients. All patients underwent surgical resection of the tumor, and 2 patients had adjuvant radiation therapy. The mean follow-up was 126.6 ± 63.3 months. At latest follow-up, 8 patients were in remission and 2 had recurrence of the EAS; both had a multifocal tumor. The 2 patients submitted to adjuvant radiation therapy were in remission at their latest follow-up, despite local invasion and lymph node metastases. CRH test and BIPSS are the most useful methods in diagnosing EAS. For localization, repeated imaging studies are necessary. Surgical treatment is effective in most cases. Adjunctive radiotherapy may be useful in patients with lymph node metastases. Patients with multifocal disease should be monitored for potential recurrence.

Cerebral tumefactive demyelinating lesions.

Tumefactive demyelinating lesions (TDLs), are a rare demyelinating pathological disease in the central neurological system, which have been proven to be a diagnostic dilemma to neurosurgeons. The clinical presentation and radiographic appearance of these lesions often results in their misdiagnosis as intracranial tumors, such as gliomas, which leads to unnecessary surgical resection and adjunct radiation. In the present study, the clinical and radiographic features of 14 patients with cerebral TDLs who underwent surgical treatment between January 2004 and January 2009 were reviewed and analyzed. The surgical methods used included biopsy and resection, while steroid therapy was indicated when TDLs were confirmed by histopathological analysis. The patients were followed-up and the outcomes were evaluated using the Karnofsky performance scale (KPS). The main clinical presentations included: Hemiplegia (8 cases), increased intracranial pressure (4 cases) and seizures (general in 1 case; partial in 3 cases). On magnetic resonance imaging scans, 12/14 TDL cases demonstrated an isolated local subcortical mass and 6/14 cases (42.9%) demonstrated enhancing veins coursing undistorted through the lesion. The postoperative complications included: Hemiplegia (2 cases) and mortality (1 case). A total of 9 cases underwent microsurgical total resection, and 5 cases received stereotactic biopsy that was followed with high-dose methylprednisolone therapy. The follow-up study demonstrated that 2 cases presented recurrence with multiple sclerosis and the KPS scores for 13/14 patients (92.9%) were ≥80. In conclusion, the clinical and radiographic features of TDLs may help to establish the correct diagnosis prior to surgery, in order to avoid unnecessary resection or adjunctive therapy. Using steroid therapy, the majority of patients with TDLs appeared to achieve satisfactory prognosis.

Multiple spinal metastases from a well-differentiated liposarcoma of the iliac wing: a case report.

A case report. To report an unusual case of multiple spinal metastases from an undiagnosed well-differentiated liposarcoma (WDLPS) of the iliac wing and to stress the need of a meticulous clinical examination and further screening of patients with chronic and asymptomatic bony lesions. University of medicine of Monastir, Department of neurological surgery, Fattouma Bourguiba University Hospital, Monastir, Tunisia and University of Medicine of Tunis EL Manar, Department of neurological surgery, Tunisian National Institute of Neurology, Tunis, Tunisia. A 39-year-old man presented with signs of spinal cord compression for the past 2 weeks. His medical history was consistent for an asymptomatic right iliac wing mass that appeared 3 years ago and for which he has not consulted. Magnetic resonance imaging revealed multiple bony lesions of the thoraco-lumbar spine associated with a 6-cm right paravertebral mass at the T4 level extending posteriorly through the intervertebral foramina to the spinal canal causing major spinal cord compression. An emergent T2-T6 laminectomy allowed for a complete resection of the epidural mass. Pathological examination confirmed the diagnosis of well-differentiated liposarcoma. Adjunctive radiation therapy was administered. The patient's neurological status improved remarkably under an intensive care and rehabilitation program. He was ambulatory without assistance in the second postoperative week. The case reported in this paper represents a genuine example of the possible metastatic potential of WDLPSs of the bone and underscores the importance of examining patients thoroughly, especially when they have chronic and asymptomatic lesions.

Feasible study of MRgFUS of early breast cancer - report of completion of BC006 in Japan

Among applications of MRgFUS such as uterine fibroid, breast cancer (BC), metastatice bone tumor, prostate, and the brain, the breast is prsently the only organ where complete local control of breast cancer is aimed. Immediately after completion of excision study (BC003, 2002-2003), one-arm prospective follow-up study to evaluate MRgFUS followed by adjunct radiation therapy (BC004) has been running wiht no local and systemic recurrences among 67 cases at Breastopia Namba Hospital in Japan. We report completion of excision study (BC006), the goal of which is, similar to BC003, prospective, non-randomized, single-arm, multiinternational study, and is to develop data to evaluate the safety and effectiveness of the Exablate 2000™ (InSightec, Israel) in the ablation of breast cancer by histopathological evaluation of MRI-guidance and the effect of FUS. A prospective randomized 2-arm study of MRgFUS+radiation therapy (RT) and breast conserving surgery + RT will start September, 2014.