Search

High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors (GCTs) who failed to be cured by conventional chemotherapy. Hematopoietic stem cells (HSCs) collected from the peripheral blood, after appropriate pharmacologic mobilization, have largely replaced bone marrow as the principal source of HSCs in transplants. As it is currently common practice to perform tandem or multiple sequential cycles of HDCT, it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure. Moreover, the CD34+ cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment, with patients who receive > 2 × 106 CD34+ cells/kg having consistent, rapid, and sustained hematopoietic recovery. However, many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy, which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy. Therefore, alternative strategies that use novel agents in combination with traditional mobilizing regimens are required. Herein, after an overview of the mechanisms of HSCs mobilization, we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs, and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (Her2) - targeted antibody-drug conjugate that is approved for patients previously treated with trastuzumab and a taxane for Her2-positive advanced breast cancer and those who have progressed within 6 months of completion of adjuvant chemotherapy, as well as for patients with residual invasive Her2-positive disease after the completion of adjuvant chemotherapy. Peripheral neuropathy is a common adverse event; however, ocular events have also been described. With the current report we present the case of a 67-year old woman who developed transient grade 2-3 blurred vision after the first T-DM1 infusion, which was complicated with grade 2 diplopia causing vertigo after the second infusion. After extended investigation, this symptomatology was attributed to central neurotoxicity, and gradually resolved after T-DM1 discontinuation.

Background Benign bone tumors are common incidental findings in the pediatric population during radiographic evaluation. Counseling these patients requires reassurance and raises questions about the natural history of these tumors over time. The purpose of this study was to estimate the prevalence and observe the behavior of benign childhood bone tumors in an asymptomatic population. Methods A historical, longitudinal radiographic collection of healthy children was reviewed, which included comprehensive left-sided radiographs of the extremities at yearly intervals. In this study, 262 subjects with 25,555 radiographs were screened for benign bone tumors at a median age of 8 years (range, 0 to 18 years). All potential tumors were reviewed by a multidisciplinary panel, which confirmed the radiographic diagnosis of each lesion, the age at which the lesion first appeared, and the age at which it had resolved. Prevalence rates were calculated using the number of distinct subjects available for each radiographic location and age. Results Thirty-five tumors were identified in 33 subjects, including 19 nonossifying fibromas, 8 enostoses, 6 osteochondromas, and 2 enchondromas. The prevalence rate for all tumors combined increased with age and was 18.9% overall. The overall prevalence rates for specific tumor types were 7.5% for nonossifying fibromas, 5.2% for enostoses, 4.5% for osteochondromas, and 1.8% for enchondromas. Nonossifying fibromas demonstrated a bimodal distribution of prevalence, with a peak at 5 years (10.8%) and another after skeletal maturity (13.3%). The median age at the first appearance for all tumors combined was 9 years (range, 2 to 15 years), but varied by tumor type. Nonossifying fibromas often resolved (7 [37%] of 19), with further resolution possible beyond the last available radiograph. Enostoses, osteochondromas, and enchondromas persisted until the last available radiographs in all subjects. Conclusions The prevalence of benign childhood bone tumors of the extremities was 18.9% in a historical asymptomatic population. Longitudinal radiographs allowed observation of the timing of the first appearance and the potential for resolution for each tumor type. These findings provide unique evidence to answer many commonly encountered questions when counseling patients and their families on benign bone tumors. Level of evidence Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Hyaline fibromatosis syndrome (HFS) is a rare, progressive, autosomal recessive disorder that presents with connective tissue deposition of amorphous hyaline material within the musculocutaneous tissue and/or visceral organs. HFS presents clinically in infancy or early childhood and can result in severe disability and life threatening complications. Given the rarity of the disorder, the imaging characteristics of HFS are seldom described in the literature. We describe a case of a 25-year-old patient presenting with bilateral knee pain, limited range of motion in her extremities, and lower extremity weakness with detailed MR imaging demonstrating the first case of multifocal intra-articular deposition of hyaline material within several joints.

Glioblastoma multiforme is a malignant central nervous system (CNS) disease with dismal prognosis. Current treatment modalities only offer modest activity and usually of short duration, so there is an urgent need for the conduct of clinical trials exploring new treatment options and modalities. The vincristine-irinotecan-temozolomide and bevacizumab (VITb) regimen is an option of special interest, as it has produced encouraging results in young patients with various relapsed/refractory childhood and adolescence solid tumors, with an acceptable toxicity profile. With the current report, we present the case of a young male patient who was treated for GBM in second relapse at out institution, after previous surgical attempts and two radiotherapy sessions in conjunction with temozolomide and experienced a major and long-lasting response, weaned off steroids, to the VITb regimen followed by bevacizumab maintenance. The above case is discussed in the context of the existing literature regarding available evidence of synergy between the drugs used and the activity of certain components of the combination (i.e. combination of temozolomide-irinotecan ± vincristine, or bevacizumab-irinotecan in GBM) or the complete VITb regimen in other pediatric/adolescence solid tumors and the few cases reported with GBM.

Small cell carcinomas (SCCs) are poorly differentiated neuroendocrine tumors that arise predominantly in the lung and gastrointestinal tract (GIT). Neuroendocrine carcinomas can occur in a variety of extrapulmonary sites throughout the body, including breast, larynx, GIT, prostate, urinary bladder, ovary and cervix. This is a case report of a 55-year-old Asian female patient with metastatic high-grade neuroendocrine carcinoma of unknown origin that responded notably to off-label nivolumab maintenance treatment after first-line carboplatin - etoposide chemotherapy and radiation. After 2 years of nivolumab after platinum-based chemotherapy results from PET-CT showed no residual disease and we proceeded to mastectomy.

BACKGROUND The differences in histopathology and molecular biology between right colon cancer (RCC) and left colon cancer (LCC) were first reported in the literature by Bufill in 1990. Since then, a large number of studies have confirmed their differences in epidemiology, clinical presentation, comorbidities and biological behaviours, which may be related to the difference in prognosis and overall survival (OS) between the two groups. AIM To investigate statistically significant differences between Greek patients with LCC and RCC. METHODS The present observational study included 144 patients diagnosed with colon cancer of any stage who received chemotherapy in a Greek tertiary oncology hospital during a 2.5-year period. Clinical information, comorbidities, histopathologic characteristics and molecular biomarkers were collected from the patients’ medical records retrospectively, while administered chemotherapy regimens, targeted agents, progression-free survival (PFS) periods with first- and second-line chemotherapy and OS were recorded retroactively and prospectively. Data analysis was performed with the SPSS statistical package. RESULTS Eighty-six males and 58 females participated in the study. One hundred (69.4%) patients had a primary lesion in the left colon, and 44 (30.6%) patients had a primary lesion in the right colon. Patients with RCC were more likely to display anaemia than patients with LCC [odds ratio (OR) = 3.09], while LCC patients were more likely to develop rectal bleeding (OR = 3.37) and a feeling of incomplete evacuation (OR = 2.78) than RCC patients. Considering comorbidities, RCC patients were more likely to suffer from diabetes (OR = 3.31) and coronary artery disease (P = 0.056) than LCC patients. The mucinous differentiation rate was higher in the right-sided group than in the left-sided group (OR = 4.49), as was the number of infiltrated lymph nodes (P = 0.039), while the percentage of high-grade differentiation was higher in the group of patients with left-sided colon cancer than in RCC patients (OR = 2.78). RAS wild-type patients who received anti-epidermal growth factor receptor (EGFR): Treatment experienced greater benefit (PFS: 16.5 mo) than those who received anti-vascular endothelial growth factor treatment (PFS: 13.7 mo) (P = 0.05), while among RAS wild-type patients who received anti-EGFR treatment, LCC patients experienced greater benefit (PFS: 15.8 mo) than the RCC subgroup (PFS: 5.5 mo) in the first-line chemotherapy setting (P = 0.034). BRAF-mutant patients had shorter PFS (9.3 mo) than BRAF wild-type patients (14.5 mo) (P = 0.033). RCC patients showed a shorter tumour recurrence period (7.7 mo) than those with LCC (14.5 mo) (P < 0.001), as well as shorter (OS) (58.4 mo for RCC patients; 82.4 mo for LCC patients) (P = 0.018). CONCLUSION RCC patients present more comorbidities, worse histological and molecular characteristics and a consequently higher probability of tumour recurrence, poor response to targeted therapy and shorter OS than LCC patients.

Background An appreciable proportion of patients in need of salvage high-dose chemotherapy (HDC) and autologous peripheral blood stem cell (PBSC) transplantation (PBSCT) fail to mobilize adequate numbers of hematopoietic progenitors, and plerixafor is applied for that purpose. Limited data exist on remobilization of PBSCs in patients who have relapsed after prior HDC + PBSCT. Herein, we report on consecutive patients that had undergone successful prior single or tandem HDC for a variety of malignant neoplasms in our institution, and later required re-mobilization of PBSCs in order to support further HDC cycles. Patients and Methods Plerixafor was administered in combination with granulocyte-colony stimulating factor alone, or after mobilizing chemotherapy. Five patients, 2 B-cell non-Hodgkin lymphomas, 1 multiple myeloma, 1 germ-cell tumor, and 1 Ewing sarcoma, having relapsed after prior HDC + PBSCT, were deemed candidates for further cycle(s) of PBSC-supported HDC. Plerixafor was applied in a “just-in-time” strategy after low CD34+ numbers were measured on the first day of anticipated hematopoietic stem cell collection (non-Hodgkin lymphoma, germ-cell tumor, and Ewing sarcoma), or pre-emptively in multiple myeloma. Results Successful collection of adequate PBSCs was achieved in all patients, from 1.8 to 3.8 × 106/kg after a median of 2 (range, 1-3) leukaphereses; 4 of 5 patients underwent subsequent HDC + PBSCT and engrafted after a median of 11 days (range, 9-55 days) and 25 days (range, 17-76 days) for neutrophils and platelets, respectively. Conclusion Plerixafor proved effective to mobilize adequate numbers of PBSCs in individual patients with relapsed malignancies after prior single or tandem HDC + PBSCT. These PBSCs could establish sustained multi-lineage hematopoietic engraftment without any sequelae.

Background Patients with active cancer have a 4–sevenfold increased risk for venous thromboembolism (VTE) especially during systematic anticancer treatment. Simultaneously, surgery is an additional risk factor. Methods The Metaxas’s Hospital THromboprophylaxis program in Oncological & Surgical Patients (MeTHOS) is a prospective, phase IV, observational, non-interventional cohort study, aiming to record the thromboprophylaxis practice patterns in high-risk active cancer patients undergoing surgical and/or chemotherapy treatment. Results We are reporting results from 291 ambulatory patients (median age: 67 years, Q1–Q3: 59–73 years, 54.6% males) who received anti-neoplastic treatment and administered thromboprophylaxis. 59.8% had cardiovascular disease (mostly hypertension), 76.6% were reported as having at least one comorbidity, while 27.5% and 15.8% accumulated two and three comorbidities, respectively. 94.9% of the patients were receiving highly thrombogenic agents such as platinum-based agents, 5-FU, immunotherapy, antiangiogenics/anti-VEGF, or erythropoietin. 26.5% of the patients were initially surgically treated. In terms of anticoagulation, all patients were treated with tinzaparin (fixed dose, 10,000 Anti-Xa IU, OD). The median anticoagulation duration was 6.2 months. Six thrombotic events were observed (2.06%, 95% CI: 0.76–4.43%): 5 were DVT, and one PE. With respect to safety, 7 bleeding events occurred (2.6%, 95% CI: 1.0–5.3%); 6 of them were minor. Conclusions Thromboprophylaxis with LMWH in patients with active cancer and high thrombotic burden was safe and effective. Intermediate dose of tinzaparin seems to be an appropriate agent for cancer-associated thromboprophylaxis management. Clinical trial registration ClinicalTrials.gov: NCT04248348.

Monoclonal antibodies against programmed cell death protein 1 (PD-1) and PD-1 ligand 1 (PD-L1) are the main representatives in the field of immunotherapy and their indications are constantly increasing in medical oncology and hematology during the last decade. They are associated with long-lasting responses and an acceptable toxicity profile, although they may infrequently cause life-threatening complications requiring prolonged hospitalization or urgent interventions. With the current report, we present the case of a 75-year-old woman diagnosed with stage IV lung adenocarcinoma, who developed acute abdominal pain without preceding symptomatology while on pembrolizumab-pemetrexed maintenance treatment. A contained rupture of the appendix was found, for which she was managed conservatively. Subsequent endoscopic as well as histopathological findings from biopsies obtained via colonoscopy associated the clinical and imaging findings with grade 4 immune-mediated colitis. Interestingly, high-grade colitis is more frequent with anti-CTLA-4 agents in comparison to anti-PD-1 agents; moreover, most cases of anti-PD-1-mediated colitis present with preceding symptomatology (like diarrhea or vomiting), while cases or colonic perforation are extremely rare if ever described.

Salvage high-dose chemotherapy (HDC) and autologous hematopoietic stem cell (HSC) transplantation (ASCT) represents a potentially curative/survival extending treatment option in patients with a var...

Background One of the key steps in generating three-dimensional (3D) printed models in medicine is segmentation of radiologic imaging. The software tools used for segmentation may be automated, semi-automated, or manual which rely on differences in material density, attenuation characteristics, and/or advanced software algorithms. Spectral Detector Computed Tomography (SDCT) is a form of dual energy computed tomography that works at the detector level to generate virtual monoenergetic images (VMI) at different energies/ kilo-electron volts (keV). These VMI have varying contrast and attenuation characteristics relative to material density. The purpose of this pilot project is to explore the use of VMI in segmentation for medical 3D printing in four separate clinical scenarios. Cases were retrospectively selected based on varying complexity, value of spectral data, and across multiple clinical disciplines (Vascular, Cardiology, Oncology, and Orthopedic). Results In all four clinical cases presented, the segmentation process was qualitatively reported as easier, faster, and increased the operator’s confidence in obtaining accurate anatomy. All cases demonstrated a significant difference in the calculated Hounsfield Units between conventional and VMI data at the level of targeted segmentation anatomy. Two cases would not have been feasible for segmentation and 3D printing using conventional images only. VMI data significantly reduced conventional CT artifacts in one of the cases. Conclusion Utilization of VMI from SDCT can improve and assist the segmentation of target anatomy for medical 3D printing by enhancing material contrast and decreasing CT artifact. Electronic supplementary material The online version of this article (10.1186/s41205-019-0038-y) contains supplementary material, which is available to authorized users.

OBJECTIVE The objective of this study was to investigate the quantitative and qualitative effects of virtual monoenergetic images (VMIs) by spectral detector computed tomography (SDCT) on metal artifacts in routine examinations. METHODS Fifty-nine patients with metal artifacts (caused by pacemakers, ports, screws, or prosthetic joints) affecting muscular tissue in the chest and/or abdomen were scanned using SDCT. Attenuation values around the metallic device were compared with contralateral unaffected values, for conventional images and 80 to 200 keV VMIs. In addition, general image quality and artifact intensity were rated by 2 readers. RESULTS The VMIs significantly decreased metal artifact intensity in all patients (P < 0.05). In 39 patients (66.1%), the attenuation values of the artifact and the unaffected area on the optimal keV level were very similar (≤5 Hounsfield unit difference). Qualitative analysis showed that high VMIs significantly improved artifact intensity, with best scores at 140 keV. CONCLUSIONS High monoenergetic images of SDCT significantly reduce metal artifacts, with optimal assessment at 140 keV.

11565 Background: Accounting for >15,000 cases annually, soft tissue sarcomas (STSs) represent a large spectrum of tumors with varying histology and clinical course. However, diagnosis of STSs on MRI is challenging due to its heterogeneous imaging phenotypes, such as surrounding soft tissue edema, vascular lesion characteristics, and specific imaging signs, such as splitting of fat between muscles. The goal of this study was to evaluate the utility of radiomic feature analysis for characterizing subtle heterogeneity patterns on T2-weighted MRI to distinguish benign and malignant STSs. Methods: T2-weighted MRI of N = 176 patients with STS were retrospectively obtained from a single institution. (Table) Tumor regions were manually annotated by a radiologist. The radiomic features included textural features, e.g. gray-level co-occurrence matrix features, which quantify the correlation between textural patterns within annotated regions. Maximum relevance minimum redundancy feature selection was employed to identify top 10 radiomic features that are associated with STS malignancy. Then, the identified features were integrated to generate a radiomic risk score (RRS) via logistic regression on a 10-fold cross validation to differentiate benign and malignant STS. Multivariate analysis and the area under the receiver operating characteristic curve (AUC) were employed to evaluate the association of RRS and clinical parameters, including age, gender, and STS location, with STS malignancy. Results: Multivariate analysis illustrated that age and RRS are independent variables in predicting STS malignancy (p < 0.05). The RRS yielded AUC as 0.76 (confidence interval (CI): 0.69-0.83), age 0.71 (CI: 0.64-0.79) and the combination of the RRS and age 0.84 (CI: 0.78-0.90). Conclusions: The RRS generated by radiomic features was found to be a significant predictor of STS malignancy. Furthermore, RRS could provide complementary information to the clinical parameters in differentiating benign and malignant STSs.[Table: see text]

Glioblastoma multiforme is a malignant central nervous system (CNS) disease with dismal prognosis. Current treatment modalities only offer modest activity and usually of short duration, so there is an urgent need for the conduct of clinical trials exploring new treatment options and modalities. The vincristine-irinotecan-temozolomide and bevacizumab (VITb) regimen is an option of special interest, as it has produced encouraging results in young patients with various relapsed/refractory childhood and adolescence solid tumors, with an acceptable toxicity profile. With the current report, we present the case of a young male patient who was treated for GBM in second relapse at out institution, after previous surgical attempts and two radiotherapy sessions in conjunction with temozolomide and experienced a major and long-lasting response, weaned off steroids, to the VITb regimen followed by bevacizumab maintenance. The above case is discussed in the context of the existing literature regarding available evidence of synergy between the drugs used and the activity of certain components of the combination (i.e. combination of temozolomide-irinotecan ± vincristine, or bevacizumab-irinotecan in GBM) or the complete VITb regimen in other pediatric/adolescence solid tumors and the few cases reported with GBM.

Malignant tumors in young patients present a significant therapeutic challenge for physicians, partially due to their rarity and a relative lack of data, at least compared to adult tumors. As a result, there is an urgent need to explore new possible therapeutic regimens, either by introducing novel agents or by exploring combinations of existing agents. Vincristine, Temozolomide and Irinotecan are chemotherapeutic drugs which have emerged over the last six decades as monotherapy or as part of therapeutic regimens in various solid tumors. Combining these agents can yield strong synergistic effects, as suggested by preclinical data and results from clinical trials. Furthermore, adding novel molecules, such as anti-VEGF factor Bevacizumab to the aforementioned regimens, has shown efficacy in a limited number of trials, which are thoroughly analyzed throughout this review. Data presented throughout this paper suggest that VIT(b) regimen should be further explored in solid tumors in pediatric and adolescent patients.

Background and objectives Success rates for initial image-guided biopsy of musculoskeletal (MSK) lesions have been well documented; evidence regarding success rates for repeat biopsy following initially nondiagnostic (ND) image-guided biopsy of MSK lesions is more limited. This study evaluates the outcomes of repeat computerized tomography-guided MSK biopsies following ND biopsies using a multidisciplinary approach. Materials and methods Electronic medical record search covering a 10-year period identified patients that received two or more biopsies for an MSK tumor or tumor-like process. The decision for initial and repeat image-guided biopsy of each lesion was made following multidisciplinary MSK tumor board review. Lesion location, histopathology results, size of biopsy needle when available, and change in technique between biopsy attempts was documented. Results Repeat biopsy rate was 1.6%. 23 patients with repeat MSK biopsy were identified. A total of 17 of 23 (74%) repeat biopsy attempts were diagnostic. A total of 22 of 23 (96%) repeat biopsy attempts were clinically useful. Diagnostic repeat biopsies were described as employing one or more of five technical differences compared to the first biopsy attempt, the most common being improved targeting of the lesion itself. Conclusions A multidisciplinary approach may yield improved repeat-biopsy rates and clinical utility of repeat MSK biopsies compared to prior reports.

We report the case of a 79-year-old male with previous history of non-Hodgkin's lymphoma in remission, who presented acutely to the Accident and Emergency department with recurrent episodes of hypoglycaemia. At the time of presentation, a random glucose was low at 1.4 mmol/l, which upon correction resolved his symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 2 months to which he did not give much notice. While hospitalized, he continued having episodes of symptomatic hypoglycaemia, requiring treatment with intravenous dextrose and per os steroids. Once stable, he was discharged on oral prednisolone and dietary advice. A computed tomography scan performed during inpatient stay showed multiple deposits in the abdomen. An ultrasound guided biopsy of one of the liver deposits was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. The diagnosis of non-islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=105.9 nmol/l; IGF2:IGF1 ratio 23, Upper Level of Normal (ULN)

Juxtacortical or surface tumors of bone are neoplasms arising from or just outside the cortex, and are composed of different histologic types. Although the imaging appearances of these lesions have similarities to their intramedullary counterparts, their location alters their radiographic and MR characteristics, creating difficulties in diagnosis. Meanwhile, several non-neoplastic lesions, such as stress reaction/stress fracture and indolent infectious processes, compound the differential diagnosis. Neoplastic juxtacortical lesions of bone have been classified into five categories: cartilaginous, fibrous, lipomatous, osseous, and metastatic tumors. Our goal in part one of this review is to illustrate the characteristic radiographic, CT and MR imaging features of various juxtacortical neoplasms, including pathognomonic imaging findings that can aid in diagnosis, and to develop an appropriate differential diagnosis for surface lesions based on imaging characteristics, lesion location and patient age.

Introduction Joint bleeding resulting in synovial hypertrophy and articular cartilage damage are the hallmarks of hemophilic arthropathy. Early prophylaxis with extended half-life factor products and non-factor replacement therapies reduce joint bleeds but do not provide complete protection from development of arthropathy. MRI is the gold standard imaging technique to diagnose and monitor arthropathy in hemophilia. MRI changes that are associated with joint bleeding and development of arthropathy, however, are not sensitive enough to detect early changes in the synovial membranes after sub-clinical bleeding. Radiomics, the computerized extraction of sub-visual attributes from imaging scans can detect early changes of hemophilic arthropathy and help in more accurate characterizations of severe joint disease. The goal of this project was to develop and compare MRI radiomics with the International Prophylaxis Study Group (IPSG) score, an established MRI joint disease scale, in assessing the severity of joint disease. Methods After IRB approval, knee MRI scans of 17 hemophilia patients with a history of joint bleeding and 12 age-matched healthy controls were included in this study. Manual annotations were performed in consensus by a board-certified musculoskeletal radiologist to include the prefemoral fat, suprapatellar fat pad and bursa . To ensure that the signal intensities from different cases were in tissue-specific correspondence, a landmark-based histogram transformation was used to align MRI signal intensity distributions across all cases. 560 radiomic features capturing MRI pixels texture heterogeneity (Gabor wavelets, Laws texture, Haralick and GoLIAGe co-occurrence patterns) were subsequently extracted on all MRI slices with ROI for all the cases. Top 2 radiomic features (F 2) for differentiating between abnormal joint changes and control were selected by Minimum Redundancy Maximum Relevance (mRMR) algorithm with 100 iterations of 3-fold cross-validation. Consensus hierarchical clustering was then applied on F 2, from which two patient clusters were generated. A disease severity score was calculated based on historical lifetime bleed events in the joint, designation of target joint status, and history of surgical synovectomy. A previously described 17-point MRI IPSG score was also calculated by 2 independent reviewers. Both the IPSG score and the F 2 were then fit into a linear regression model separately as predictors whereas the disease severity score was set to be the response variable. The Akaike's Information Criteria (AIC) and the root mean square error (RMSE) were used to evaluate the model fitness and the likelihood ratio (LR) test was applied for model comparison. Results The dataset consisted of 17 males with moderate and severe hemophilia ranging in age from 10-55 years. The median disease severity score was 2 (0-11) and the median IPSG MRI Score was 2 (0-11). The top 2 radiomic features F 2, a Gabor wavelet feature and a Lawshc texture feature, yielded an AUC of 0.94 and an accuracy of 0.9 for differentiating between hemophilic joint changes and healthy control patients. Unsupervised clustering demonstrated good separation between the two classes (Fig panel A and B). The radiomic-based linear regression model (AIC: 86.67; RMSE: 2.86) was significantly better than the IPSG score-based model (AIC: 94.24; RMSE: 3.66) in joint disease severity characterizations (LR, p = 0.0083, Fig panel C). Conclusions Radiomic analysis of knee MRI in hemophilia patients with history of joint bleeding is correlated with the severity of joint disease. Our study demonstrates the feasibility of developing and utilizing a radiomics based tool to detect the severity of joint damage in a small population of knee joint hemophilic arthropathy. We plan to perform an Independent validation of the radiomics signature in a larger dataset of hemophilia joint MRI scans Figure 1 Figure 1. Disclosures Madabhushi: Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers-Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Caris: Consultancy; Aiforia: Consultancy; Philips: Research Funding; AstraZeneca: Research Funding; Boehringer-Ingelheim: Research Funding; Bristol Meyers-Squibb: Research Funding. Ahuja: Sanofi: Membership on an entity's Board of Directors or advisory committees; XaTek, Inc: Patents & Royalties; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB member .

Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after oral administration, is metabolized to its active cytotoxic compound: 5-fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a closely related fluorinated pyrimidine antagonist. In the present report, we report on two patients who were admitted to our department after being treated with oral capecitabine for colorectal carcinoma and developed symptoms and signs of acute myocardial infarction that resolved after appropriate treatment and monitoring. The above two cases are discussed in the context of fluoropyrimidine, 5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature review of relevant cases and patient series reports is presented.

Salvage high-dose chemotherapy (HDC) and autologous hematopoietic stem cell (HSC) transplantation represents a curative treatment option for patients with relapsed/refractory germ-cell tumors (GCTs). However, an appreciable proportion of these fail to mobilize adequate numbers of hematopoietic progenitors; thus, plerixafor is applied for that purpose. Limited data exist on remobilization of HSCs after previous autografting. Here, we report a unique case that had undergone successful previous tandem HDC for relapsed GCT, and 1 year later required remobilization of HSCs to support two further cycles of HDC after subsequent multiple relapses and refractoriness requiring various salvage regimens. Plerixafor in combination with granulocyte-colony stimulating factor showed its efficacy in mobilizing 6×106 CD34+/kg HSCs able to rescue two HDC cycles of carboplatin-etoposide, leading to stable hematopoietic engraftment. Plerixafor showed its potency to mobilize adequate numbers of HSCs in a patient with relapsed/refractory GCT after previous tandem HDC and autografting. The case is discussed in the context of HSC mobilization in patients who have undergone previous HDC and autografting and are deemed to have poor hematopoietic reserves, and a detailed literature review of this topic is provided.

The purpose of our study was to improve awareness and knowledge of the American College of Radiology Appropriateness Criteria (ACR-AC) among Emergency Medicine (EM) residents and to assess the long-term effectiveness of this ACR-AC lecture-based series.Ten lectures-based on the ACR-AC were given to EM residents at an academic medical center. Four of these lectures were subsequently repeated in the subsequent academic year. A prelecture quiz was given to all participants prior to each lecture and the same quiz was given after each lecture. Participants were instructed to select the most appropriate imaging study for each question. Results were analyzed with a 2-tailed paired sample t-test for the means.A total of 28 residents from three EM resident classes participated in the lecture-based series over the course of this 2-year study. In phase I of the study, there was statistically significant improvement in mean postlecture quiz scores compared to prelecture quiz scores (55.7% vs 80.5%, P0.01) for each topic, as well as within each training level, (P0.05). In phase II, the resident class of 2018 had the only statistically significant difference between prelecture and postlecture quiz scores (59% vs 94%, P0.05). EM residents further demonstrated an enduring effect at 1 year with statistically significant improvement in prelecture quiz scores during phase II compared with phase I (88% vs 50%, P0.05).This work revealed that lecture-based education on the ACR-AC, relevant to EM residents, significantly increased the participant knowledge for ordering appropriate imaging. In addition, it was evident participants retained the knowledge they acquired from these lectures during phase II 1 year later.

Metal artifacts limit the diagnostic utility of computerized tomography (CT) for implant-related complications. Dual-layer spectral detector CT imaging has been suggested for artifact reduction. Our objective was to evaluate the utility of spectral CT in artifact reduction in patients with small and large metal implants. In this prospective study, patients with metallic orthopedic implants underwent CT imaging using a prototype spectral detector CT scanner. Conventional images were generated with iterative reconstruction at 120 kVp, and virtual monochromatic images were generated at 20-keV intervals between 40 to 200 keV. Conventional and monochromatic images were compared quantitatively using signal-to-noise ratio (SNR) and artifact improvement. Qualitative analysis was performed independently by two musculoskeletal radiologists and included six image quality indicators. A total of 12 patients were scanned. In monochromatic images, as the energy level increased, the artifact size decreased progressively (p

Salvage high-dose chemotherapy (HDC) together with autologous hematopoietic stem cell (HSC) transplantation (ASCT) represents a curative treatment option for patients with relapsed/refractory germ-cell tumor. Usually, 2-3 cycles of HDC are administered with encouraging results, and a sizeable percentage of patients experience long-term survival. However, an appreciable number of patients fail to mobilize adequate numbers of HSCs, adequate to support more than one HDC cycle. There have been no data so far on remobilization of HSCs after prior autografting. We report a unique case with relapsed germ-cell tumor that had undergone the first cycle of HDC with myeloablative doses of carboplatin-etoposide, and HSCs were mobilized successfully in the early posthematopoietic engraftment period to support further cycles of HDC. Four weeks after the first ASCT, an identical second cycle of myeloablative HDC was administered and rescued successfully with the HSCs collected after engraftment following the previous HDC cycle. The present case report illustrates that HSCs can be mobilized successfully in the early postengraftment period after myeloablative doses of carboplatin-etoposide, and these cells can be applied as the sole source of hematopoietic rescue in planned sequential cycles of myeloablative HDC, leading to successful multilineage engraftment. Provided that more extensive experience is gathered in future studies in large numbers of patients, this strategy could prove helpful in patients who cannot initially collect sufficient HSC numbers, before the first autografting cycle, and are in need of sequential HDC+ASCT cycles. A detailed literature review is provided to highlight the uniqueness of the presented case.

Mucolipidosis type II (I-Cell disease) is a rare autosomal recessive lysosomal disorder, resulting from functional deficiency of lysosomal enzymes due to an impaired targeting of the enzymes to lysosomes, which leads to an abnormal cell architecture and the overflow of lysosomal enzymes into the body fluids. The life expectancy of the patients is poor, with multisystem deterioration leading to death in early childhood. According to the available reports, patients with I-cell disease do not survive beyond the first decade of life. Here, we describe and illustrate various radiological-musculoskeletal manifestations of a rare case of mucolipidosis II who has been a survivor up to now, 20 years old. The course of her disease has been complicated by early severe visual compromise due to optic nerve swelling, hearing loss and mitral valve regurgitation/stenosis, bilateral carpal tunnel, and severe growth impairment. Our case demonstrates several skeletal features of dysostosis multiplex. At the age of 20, she is wheelchair bound and her medical course is complicated by recurrent pneumonia, treated with multiple hospitalizations, antibiotics, and BiPAP. She is on outpatient palliative care, Do Not Resuscitate/Do Not Intubate (DNR/DNI) status.Mukolipidoza typu II (I komórkowa choroba) jest rzadkim zaburzeniem lizosomalnym dziedziczonym autosomalnie recesywnie, wynikającym z niedobórów funkcjonalnych enzymów lizosomalnych spowodowanych zaburzeniami. Prognoza przeżywalności pacjentów jest zła. Liczne zaburzenia prowadzą do śmierci we wczesnym dzieciństwie. W aktualnej literaturze nie znaleziono opisu pacjenta żyjącego dłużej niż 10 lat. Przedstawiamy opis pacjentki, która przeżyła 20 lat z radiologiczno-mięśniowoszkieletową postacią rzadkiego schorzenia mukolipidozy II. Przebieg schorzenia jest skomplikowany wczesnymi zaburzeniami wynikającymi z obrzęku nerwu wzrokowego, ubytku słuchu stenozą mitralną, dwustronnym kanałem nadgarstka oraz ciężkimi zaburzeniami wzrastania. Pacjentka prezentuje ciężkie zaburzenia szkieletowe dyzostozy rozsianej. W wieku 20 lat pacjentka nie chodzi (porusza się na wózku). Medyczny przebieg choroby jest wikłany nawracającymi zapalenia płuc, wymagającymi wielokrotnie hospitalizacji, leczona antybiotykami i BiPAP. Znajduje się w opiece paliatywnej w statusie DNR/DNI (nie reanimować, nie intubować).

Primary bone malignancies are characterized with anatomic imaging. However, in recent years, there has been an increased interest in PET/computed tomography scanning and PET/MRI with fludeoxyglucose F 18 for evaluating and staging musculoskeletal neoplasms. These hybrid imaging modalities have shown promise largely owing to their high sensitivity, ability to perform more thorough staging, and ability to monitor treatment response. This article reviews the current role of PET/computed tomography scanning and PET/MRI in primary malignancies of bone, with an emphasis on imaging characteristics, clinical usefulness, and current limitations.

Καθώς η τεχνολογία αναπτύσσεται ραγδαία τα διαφορετικά σύνολα ανθρώπων και μηχανών που συνιστούν τον πολύπλοκο τεχνολογικό κόσμο μας βρίσκονται αντιμέτωπα με μια ολοένα αυξανόμενη πολυπλοκότητα. Κατά συνέπεια τα προβλήματα και οι προκλήσεις δεν μπορούν να αντιμετωπιστούν αποτελεσματικά από τις παραδοσιακές μεθόδους και θεωρίες. Μολοταύτα, η θεωρία των System of Systems (SoS) εμφανίζεται ως μια εξαιρετική μέθοδος για να καλύψει τα συγκεκριμένα ερευνητικά κενά που δημιουργούνται στα συστήματα πληροφορικής και τηλεπικοινωνιών και ιδιαίτερα στα πλαίσια σχεδιασμού αποδοτικών τηλεπικοινωνιακών δικτύων, το οποίο αποτελεί και το αντικείμενο της διατριβής Πρόσφατα, παρατηρήθηκε ένα σημαντικό ερευνητικό ενδιαφέρον στο πεδίο των System of Systems. Ιδιαίτερη σημασία έχει δοθεί στη μηχανική των SoS [1]–[3] η οποία ασχολείται με την ανάπτυξη εργαλείων , μεθόδων και παροχής ολοκληρωμένων λύσεων στα σύνθετα προβλήματα των SoS. Η αρχική ιδέα των System of Systems έχει αναπτυχθεί περαιτέρω από το αρχικό πεδίο ανάπτυξης των στρατιωτικών εφαρμογών [4], [5] όπως , παγκόσμια συστήματα γεω-επισκόπησης [6] , συστήματα φροντίδας υγείας [7] συστήματα πρόληψης φωτιάς και φυσικών καταστροφών [8], [9]. Επιπλέον, τα τελευταία χρόνια , γίνεται μια σημαντική προσπάθεια για την εφαρμογή της θεωρίας των SoS στη λειτουργία και διαχείριση των επιχειρήσεων [10]–[12]. Επίσημος ορισμός , δεν έχει ακόμα επιδοθεί στην έννοια των System of Systems. Παρόλα αυτά οι πολύπλοκες αυτές οντότητες περιγράφονται από μια πληθώρα ανεπίσημων ορισμών [13], [14] ανάλογα με το πεδίο εφαρμογής και ανάπτυξης όλα αυτά τα χρόνια. Εντούτοις, για την καλύτερη κατανόηση των SoS, χρειάζεται να αποσαφηνιστούν τα επιμέρους χαρακτηριστικά της σύνθετης συστημικής οντότητας που ακολουθεί την έννοια των SoS . Ένα σύστημα συστημάτων (SoS) θα πρέπει να αποτελείται από έναν αριθμό συστημάτων, τα οποία έχουν λειτουργική και διαχειριστική ανεξαρτησία. Τα μεμονωμένα αυτά συστήματα θα πρέπει επίσης να είναι πλήρως αυτόνομα, ώστε να μπορούν να εκτελούν το σκοπό τους με αυτοτέλεια. Από την άλλη πλευρά, τα ανεξάρτητα συστήματα δύνανται να ολοκληρωθούν σε μια ανώτερη σύνθετη οντότητα με χαρακτηριστικά υπερ-συστήματος (metasystem), η οποία είναι ικανή να εκτελέσει έναν ανώτερο και πιο σύνθετο σκοπό/υπηρεσία σε σύγκριση με τους επιμέρους σκοπούς των αυτοτελών συστημάτων που το αποτελούν . Αξίζει επίσης να αναφερθεί ότι η περιγραφόμενη ολοκλήρωση των αυτόνομων συστημάτων σε υπερ-σύστημα δημιουργεί με τη σειρά της δυνατότητες πολύ παραπάνω από αυτές που μπορεί να έχει ή να παράγει κάθε επιμέρους αυτοτελές υποσύστημα. Ένα επίσης πολύ σημαντικό χαρακτηριστικό των SoS είναι η πολυπλοκότητα και ως συνέπεια αυτής η εμφάνιση δυναμικής και αναδυόμενης συμπεριφοράς. Η αυξανόμενη πολυπλοκότητα των SoS οφείλεται κυρίως στη δυνατότητα των συστατικών συστημάτων να λειτουργήσουν ανεξάρτητα. Συνεπώς, εκτός από τη συνέργεια των συστημάτων συνίσταται και ένας αντίστοιχος ανταγωνισμός για επιμέρους καθήκοντα και λειτουργίες. Ένας επίσης παράγοντας που οδηγεί στην πολυπλοκότητα είναι η αδυναμία πρόβλεψης της μελλοντικής λειτουργίας του System of Systems , καθώς αναπτύσσεται σε ιδιαίτερα αβέβαιο περιβάλλον. Τέλος, ένα SoS, είναι μια δυναμική οντότητα , καθώς προστίθενται συνεχώς καινούργια συστήματα, ενώ παράλληλα υπάρχοντα συστήματα καταργούνται ή αντικαθίστανται. Είναι επίσης άξιο αναφοράς το γεγονός ότι ένα System of Systems δεν έχει τελική μορφή. Επομένως , η έννοια της βασικής και στοχευόμενης αρχιτεκτονικής είναι πλημμελής, καθώς τα υποσυστήματα εξελίσσονται και μεταβάλλονται συνεχώς με σκοπό τη βέλτιστη αρχιτεκτονική στις εκάστοτε ιδιαίτερες συνθήκες. Επομένως, προκύπτει ότι η σχεδίαση και η ανάπτυξη των SoS είναι μια προσπάθεια πολυπλοκότερη από τη διαχείριση και δημιουργία ενός απλού αυτόνομου συστήματος. Πιο συγκεκριμένα ,στο πρώτο κεφάλαιο της διατριβής εισάγονται οι σχετικές έννοιες , αναλύεται το θεωρητικό υπόβαθρο, τα βασικά ερωτήματα και οι συνεισφορές της εργασίας στο σχετικό τομέα των ICT. Στο δεύτερο κεφάλαιο, εξετάζεται η ανάλυση αξιοπιστίας στα τηλεπικοινωνιακά δίκτυα μέσα στη θεωρία των SoS. Το προτεινόμενο πλαίσιο, είναι ένας συνδυασμός αναλυτικών και μαθηματικών μεθόδων αξιοπιστίας σε συνδυασμό με κατευθυνόμενους γράφους. Έχουν επίσης ενσωματωθεί μέθοδοι ευαισθησίας με σκοπό να αξιολογηθεί ποσοτικά ο αντίκτυπος των άγνωστων κινδύνων και γεγονότων. Στο τρίτο κεφάλαιο , μελετώνται προβλήματα σύνθετης βελτιστοποίησης με τη βοήθεια εξελικτικών αλγορίθμων στις τεχνολογίες τηλεπικοινωνιών και πληροφορικής. Ο σκοπός είναι να δημιουργηθεί ένα τρόπον τινά αυτοματοποιημένο σύστημα αποφάσεων με προβολή δέσμης ενεργειών. Ως πιλότος χρησιμοποιήθηκε ένα FTTH δίκτυο, με τα πλέον πρόσφατα δεδομένα τιμολόγησης και διείσδυσης στην αγορά εργασίας. Στο τέταρτο κεφάλαιο, παρουσιάζεται μια σε βάθος ανάλυση ενός πληροφοριακού συστήματος (IS) ακολουθώντας ξανά τη δομική ανάλυση των SoS, με την εισαγωγή του ανθρώπινου παράγοντα σε επιχειρησιακό περιβάλλον. Στο τελευταίο κεφάλαιο, συνοψίζονται τα κύρια σημεία της διατριβής μαζί με τα εργαλεία και τις μεθοδολογίες που αναπτύχτηκαν, όπως επίσης και η δυνατότητα εφαρμογής & τροφοδότησης θεμάτων μελλοντικής έρευνας. Ένα πλαίσιο με τα υπάρχοντα στοιχεία της διατριβής για τον υπολογισμό ρίσκου σε πραγματικό χρόνο παρουσιάζεται στα συστήματα έξυπνων πόλεων. As technology rapidly evolves, the different sets of people and machines are becoming increasingly complex. Thus, their problems and challenges cannot be addressed by the traditional systems’ theories and methods. However, System of Systems approach is presented as a candidate to fulfill the resultant gap. This Ph.D. Thesis discusses the System of Systems (SoS) concept adjustment into information and communication technology (ICT) relative fields. Recently, a significant interest was observed in the field of System of Systems. Particular attention has been paid on System of Systems Engineering[1]–[3] which deals with the development of tools, methods and solutions to the challenges of System of Systems. The System of Systems concept is extended to several scientific areas from defense systems [4], [5], global earth observation systems[6] , health care systems [7] to fire and disasters monitoring systems[8], [9]. Moreover in the last years, there has been a strong effort to implement System of Systems Engineering in the operation of enterprises [10]–[12]. A formal definition has not yet been given to the System of Systems concept. Such entities can be described by a plethora of unofficial definitions[13], [14] that have been proposed in the past. However, for better understanding a SoS, one needs to clarify the characteristics that should be included in it. A System of Systems should consist of a number of operationally and managerially independent systems. The individual systems should be autonomous; that is to perform a standalone operation. On the other hand, the independent systems should be integrated in a higher level system (metasystem) to perform a mission/purpose for which each member plays an integral role. It should be noticed that the above collaboration should lead to capabilities beyond which any of the constituent member (sub) systems is independently capable of producing. Another main feature of System of Systems is that it is complex and as such exhibits a dynamic and emergent behavior. The increased complexity of System of Systems is mainly due to the capability of the constituent systems to operate independently. Hence, apart from co-operating, the systems could also compete for subtasks. Another factor leading to the complexity is the inability to predict the operation of a System of Systems since the latter is usually occurred in uncertain environments. Finally, the System of Systems is a dynamic entity, as new systems are added and current systems are replaced or removed. It is worth noting that a System of Systems does not have a defined final state. Hence, the concept of target architecture is meaningless since these systems are evolving, and thus constantly changing. Therefore, it is deduced that the design and development of System of Systems is a task far more complicated than creating a standalone system. In particular the first chapter of this thesis is presenting the key points covered from this work along with various details which in total describing the achieved contributions in the relative field of ICT. The second chapter is covering the Reliability analysis in Telecommunications networks using the SoS concept. More specific a FTTC network was used as a pilot in the context analysis formulated into SoS. The methodology is using a combination from reliability analyses and Probabilistic techniques coupled with sensitivity analysis, in order to encapsulate also the unknown risk. Third chapter discusses the adjustment of SoS concept over a telecom investment problem. An optimization study is revealed together with selectivity over strategies. An FTTH network was used, with the most updated data for pricing and market penetration. Main Purpose was to present all the useful information, which was revealed from the SoS optimization process. The fourth chapter goes into an in-depth analysis of an information system (IS) following again the SoS structural analysis. Human factor is involved and its proper analysis enhances reliability overall of the pilot study.. Last chapter is presenting the SoS concept adjustment into the newer Smart Cities research field. IBM relative work is presented and the applications of the current Thesis findings are outlined. A real time risk analysis is presented using experience, tools and methods that were gained from the Ph.D. Thesis research effort.

Introduction Bone and soft tissue sarcomas are rare and heterogeneous tumor entities; more than 50 histologic subtypes of these exist. Soft tissue sarcomas account for 0.7% and 6.5% of all adult and childhood malignancies, respectively, and primary bone cancer comprises 0.2% of all malignancies. Established treatment protocols for sarcoma are multimodal and complex and include surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiation therapy. Most recently, targeted therapy has been introduced in the clinical setting and is being tested in a variety of trials. Metastatic disease occurs in up to 60% of patients with sarcoma who have been treated initially with curative intention, and the lung is the most common site of metastasis in most histologic subtypes of sarcoma. Improved outcomes may be attainable with earlier detection of metastatic disease and with accurate detection of local recurrence following therapy.

e19527 Background: Skeletal MRI plays an integral role in diagnosing Multiple Myeloma and, in many cases, dictates need for treatment. While axial skeleton MRI is performed with established clinical utility, appendicular MRI is performed sparingly with utility not fully ascertained. We aim to assess the utility of appendicular MRI while establishing clinical factors which may predict outcomes. Methods: 107 appendicular skeleton MRIs were included for retrospective analysis over 15 years. No statistically significant age or gender related variability was noted. Variables including patient age, diagnosis, disease stage/activity, indication, transplant status, MRI result, treatment course, and survival were analyzed via Likelihood Ratio Chi-Square test or logistic regression. Results: Patient age, disease stage, presence of active marrow disease, history of relapse, and presence of axial or appendicular osseous disease were found to have a statistically significant correlation with MRI result. Disease stage and presence of active hematologic disease correlated with post MRI management alterations. Additionally, presence of active hematologic disease at time of MRI demonstrated a correlation with post MRI management strategy. Furthermore, MRI result was a predictor of downstream development of additional skeletal lesions. Interestingly, MRI result was not a predictor of survival. Conclusions: Several parameters may be used to determine a clinical pre-test probability of appendicular disease at the time of MRI. In addition, these clinical parameters and MRI results correlate with trends in subsequent patient treatment strategies. [Table: see text]

The aim of this study was to assess systemic immunological responses in non-small-cell lung cancer (NSCLC) patients with stage III/IV disease during treatment with paclitaxel–ifosfamide–cisplatin (TIP) chemotherapy. Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (HD) (n = 20) and chemotherapy-naive NSCLC patients treated with TIP (n = 32) were tested for production of IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10, IL-12 and IL-2 upon polyclonal stimulation with anti-CD3 mAb. They were further assessed over a treatment period of twelve weeks (i.e., four treatment cycles). PBMCs from NSCLC patients produced higher IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 levels, whereas IL-2 exhibited lower values compared to HD (p

Objective: To identify changes in peripheral immune responses in patients with metastatic colorectal cancer (mCRC) treated with irinotecan/5-fluorouracil/leucovorin (IFL) alone or in combination with cetuximab (C-IFL). Methods: Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (n = 20) and patients with mCRC receiving treatment with either IFL (n = 30) or C-IFL (n = 30) were tested for cytokine production upon polyclonal stimulation with anti-CD3 monoclonal antibody, T cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR) and T regulatory cell (Treg) frequency. The respective results were evaluated over two treatment cycles and further assessed in relation to response to treatment. Results: PBMCs prior to treatment exhibited significantly lower production of IL-2, IFN-γ, IL-12 and IL-18 cytokines and lower auto-MLR responses, whereas Treg frequency, IL-4, IL-10 cytokines were increased compared to healthy donors. During treatment, IL-2, IFN-γ, IL-12, IL-18 and auto-MLR responses increased, while Treg frequency and IL-10 secretion decreased significantly compared to the baseline. Responders to treatment exhibited a significantly higher increase in IL-2, IFN-γ, IL-12 and IL-18 production and auto-MLR responses, and higher decrease in IL-4, IL-10 secretion and Treg frequency. Among all patient subgroups analysed, responders to C-IFL demonstrated significantly higher increase in auto-MLR responses, IL-12 and IL-18 secretion and higher decrease in Treg frequency. Conclusion: The disturbed immune parameters observed in patients with mCRC at presentation can be significantly improved during treatment with IFL and this effect can be potentiated by the addition of cetuximab. Monitoring of the peripheral immune system function could be used as surrogate marker in predicting treatment-related outcome.

The purpose of this study was to investigate how the use of multi-modal rigid image registration integrated within a standard picture archiving and communication system affects the efficiency of a radiologist while performing routine interpretations of cases including prior examinations. Six radiologists were recruited to read a set of cases (either 16 neuroradiology or 14 musculoskeletal cases) during two crossover reading sessions. Each radiologist read each case twice, one time with synchronized navigation, which enables spatial synchronization across examinations from different study dates, and one time without. Efficiency was evaluated based upon time to read a case and amount of scrolling while browsing a case using Wilcoxon signed rank test. Significant improvements in efficiency were found considering either all radiologists simultaneously, the two sections separately and the majority of individual radiologists for time to read and for amount of scrolling. The relative improvement for each individual radiologist ranged from 4 to 32% for time to read and from 14 to 38% for amount of scrolling. Image registration providing synchronized navigation across examinations from different study dates provides a tool that enables radiologists to work more efficiently while reading cases with one or more prior examinations.

Diffusion-weighted imaging (DWI) is an established diagnostic tool with regards to the central nervous system (CNS) and research into its application in the musculoskeletal system has been growing. It has been shown that DWI has utility in differentiating vertebral compression fractures from malignant ones, assessing partial and complete tears of the anterior cruciate ligament (ACL), monitoring tumor response to therapy, and characterization of soft-tissue and bone tumors. DWI is however less useful in differentiating malignant vs. infectious processes. As of yet, no definitive qualitative or quantitative properties have been established due to reasons ranging from variability in acquisition protocols to overlapping imaging characteristics. Even with these limitations, DWI can still provide clinically useful information, increasing diagnostic accuracy and improving patient management when magnetic resonance imaging (MRI) findings are inconclusive. The purpose of this article is to summarize recent research into DWI applications in the musculoskeletal system.

The expression of various angiogenic factors was assessed in tumour samples of patients with stage III non-small-cell lung cancer (NSCLC) and further evaluated in terms of response to induction paclitaxel-ifosfamide-cisplatin chemotherapy. Freshly isolated lung tumour specimens obtained by bronchoscopy from 70 stage IIIA NSCLC chemotherapy-naive patients were sampled and analysed for vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3. Microvessel density was assessed through evaluating the angiogenic markers CD34 and CD105. Immunostaining scores were calculated by multiplying the percentage of labeled cells by the intensity of staining for each examined parameter. The overall mean immunostaining score value from all NSCLC samples was 7.83, 5.56 and 15.86 for VEGFR-1, VEGFR-2 and VEGFR-3, respectively. The overall mean value of the endothelial antigen CD34 was 16.29, whereas the expression of the CD105 antigen in endothelial cells yielded a multivariate distribution. Patients who responded to chemotherapy expressed significantly higher VEGFR-1 and VEGFR-3 mean values compared with non-responders (P

High-dose chemotherapy and hematopoietic stem cell support remains a valuable treatment option for the rare patient population with relapsed Wilms' tumor. Here we report the case of a 22-year-old male patient treated with two cycles of high-dose chemotherapy at relapse after nephrectomy and adjuvant chemotherapy; the first cycle with melphalan--etoposide--carboplatin and the second with a novel preparative regimen incorporating high-dose topotecan (topotecan--cyclophosphamide--melphalan). A detailed discussion and literature review pertaining to that case is provided.

Background Bevacizumab, a monoclonal antibody (mAb) targeting vascular endothelial growth factor (VEGF), has produced promising results when combined with chemotherapy in the treatment of advanced colorectal cancer (CRC). The aim of the present study was to define the immunological profile of metastatic CRC patients at baseline and following chemotherapy with either irinotecan/5-fluorouracil/leucovorin (IFL) alone or IFL in combination with.bevacizumab (B-IFL). Methods Peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HD) (n = 20) and patients (n = 40) were tested for T-cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and cytokine production following stimulation with anti-CD3 mAb. Results,PBMCs obtained from CRC patients prior to treatment exhibited lower auto-MLR responses and low production of IL-2, IFN-γ, IL-12 and IL-18 cytokines, whereas IL-4 and IL-10 cytokines were increased as compared to HD (p < 0.001, for all parameters) following in vitro stimulation with anti-CD3 mAb. During treatment, and in particular in week 12 of evaluation, IL-2 (p < 0.001 for both IFL and B-IFL groups), IFN-γ (p < 0.001 for IFL and p = 0.001 for B-IFL), IL-12 (p < 0.001 for both IFL and B-IFL) and IL-18 (p < 0.001 for both IFL and B-IFL) production, as well as auto-MLR responses increased (p < 0.001 for both IFL and B-IFL), whereas IL-4 (p < 0.001 for IFL and p = 0.001 for B-IFL) and IL-10 [p < 0.001 for IFL and p = 0.067 (non-significant) for B-IFL] production decreased over baseline in the two treatment groups, yet their respective values never reached those of HD. Moreover, IL-2, IFN-γ production, and auto-MLR were higher in the B-IFL over the IFL treatment group (p < 0.001, p < 0.04, p < 0.001, respectively). Conclusion Our study demonstrates that the abnormal immune parameters observed in metastatic CRC patients at presentation can substantially improve during treatment with either IFL or B-IFL. The immune parameters examined can provide a sensitive and valuable tool for monitoring immune function in CRC patients, and could be applied as surrogate markers predicting treatment-related outcome.

Purpose Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer. Patients and methods Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections. Results Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression. Conclusions The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence.

Objective. This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain. Patients. Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol. Outcome Measures. Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response. Results. All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group. Conclusions. Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.