Safety of Radioembolization in the Setting of Angiographically Apparent Arterioportal Shunting.

PURPOSE: To retrospectively analyze adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization in the setting of angiographically apparent arterioportal shunts (APSs). MATERIALS AND METHODS: Thirty-two patients with HCC underwent radioembolization with APSs from January 2011 to September 2016, totaling 34 administrations using resin (6) and glass (28) microspheres. APSs were graded angiographically as segmental (9), ipsilobar (15), contralobar (7), or main portal (2), according to portal perfusion. Tumors were categorized as solitary (9), multifocal (7), or infiltrative (16). Both unilobar (25) and bilobar (7) disease was treated. Child Pugh Score was A (22), B (10), or C (2), with a median Model for End-Stage Liver Disease (MELD)/Na-MELD of 8/8.5. Median procedure dose was 132.6 Gy. AEs were graded using Combined Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: CTCAE grade ≥3 AEs were observed in 22% of patients. Barcelona Clinic Liver Cancer (BCLC) C patients with nonsegmental shunts who received lobar administrations had a grade ≥3 AE rate of 38% compared with the remaining cohort, which was 12% (P = .076). No events were reported in patients with segmental shunts (P = .023). Imaging analysis revealed mRECIST complete response (17), partial response (13), stable disease (3), and progressive disease (1). Overall survival at 6 months and 12 months was 72% and 57%, respectively. CONCLUSIONS: Radioembolization in the setting of APS may have a higher AE profile than reported literature when BCLC-C patients with nonsegmental shunts receive lobar administrations. Segmental shunts are generally well tolerated.

Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.

Transarterial Yttrium-90 Radioembolization Treatment of Patients with Liver-Dominant Metastatic Renal Cell Carcinoma.

PURPOSE: To evaluate safety and efficacy of transarterial hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: From July 2010 to December 2014, 18 patients with liver-dominant metastatic RCC were treated with yttrium-90 glass microsphere radioembolization. Retrospective review of medical records and imaging studies was performed to evaluate toxicities, treatment response, and overall survival. The median follow-up period from radioembolization treatment was 17.8 months (range, 3-54.4 months). RESULTS: Median overall survival from RCC diagnosis was 64 months (95% confidence interval [CI], 0-144.1 months), from diagnosis of liver metastasis was 29 months (95% CI, 7.2-50.8 months), and from radioembolization treatment was 22.8 months (95% CI, 13.2-32.3 months). After treatment, 10 patients reported grade 1 clinical toxicities, and 8 patients had grade 1 or 2 biochemical toxicities. The best radiographic responses of 17 patients who underwent contrast-enhanced cross-sectional imaging showed complete response in 16 patients and partial response in 1 patient evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The last available imaging of these 17 patients demonstrated complete response in 14 patients, partial response in 1 patient, and progression of disease in 2 patients. Images of a patient who underwent noncontrast CT showed stable disease as best response and stable disease on the last available imaging evaluated by RECIST. CONCLUSIONS: Radioembolization is safe and effective and led to improved hepatic disease control and overall survival in patients with liver-dominant metastatic RCC.

Decreased bone mineral density and associated risk factors in hospital visiting people of Islamabad.

OBJECTIVE: TBesides aging there are multiple factors involved in decreasing Bone Mineral Density. Knowing the burden of the diseaseand its related factors in our population can help better treat this. Therefore, our objective was to identify subjects with low Bone Mineral Density (BMD) and its risk factors in hospital visiting people in Islamabad. METHODS: Descriptive cross sectional study was conducted atRawal Institute of Health Sciences, Islamabad in 3rd week of June, 2014. Total 300 persons including patients, attendants and hospital staff were selected.Calcaneus BMD was measured usingultrasound bone densitometer. T-score was calculated.Specific questionnaire form was filled to identify risk factors. Prevalence and prevalence ratio was calculated. RESULTS: Out of 300 study sample, 178 (59.3%) are females. Mean age of the study population is 37.34 (SD=12.93). Overall, prevalence of osteopaenia and osteoporosis in the study population is 107 (35.7%) and 5 (1.7%) respectively. Prevalence of osteopaenia is seen more in elderly subjects, females, people with low Body Mass Index (BMI), people who are usually not exposed to sunlight and who are mostly bound to houses. CONCLUSIONS: Decreased BMD is associated with increasing age, female gender, low BMI, little exposure to sun light and being restrained to homes. It is not affected by daily milk intake, parity of females, cola drinking and smoking in our part of the world.

A Case of Confounding Back Pain.

BACKGROUND Acute back pain is common in primary care settings (>60% lifetime prevalence). Patients can also have associated red flag signs, such as fever, spinal tenderness, and neurologic deficits, that warrant further evaluation and investigation to optimize diagnosis and treatment. CASE REPORT A 70-year-old man with a history of benign prostatic hyperplasia and hypertension sought care for midthoracic back pain. He had been recently admitted to the hospital for sepsis from a urinary tract infection (UTI) caused by multidrug-resistant (MDR) Escherichia coli. Initial treatment was conservative management with physical therapy, given the lack of red flag signs on physical examination and the likelihood that his pain was musculoskeletal, resulting from immobilization during hospitalization. At follow-up, thoracic spine radiography showed no fracture or other acute abnormalities. After persistent pain, he underwent magnetic resonance imaging, which showed T7-T8 osteomyelitis and discitis with substantial paraspinal soft tissue involvement. Computed tomography-guided biopsy showed MDR E. coli, which indicated hematogenous spread from his recent UTI. Pharmacologic treatment included intravenous ertapenem for 8 weeks, with consideration for discectomy if later indicated. This case highlights the value of maintaining a broad differential diagnosis and high alert for red flag symptoms during routine office visits with a chief concern of back pain. CONCLUSIONS A high clinical suspicion for vertebral osteomyelitis must be maintained for patients with acute back pain associated with red flag signs. Detailed assessment with appropriate investigations and close follow-up is recommended to support the diagnosis and to allow timely management to prevent complications.

Analysis of dynamic hepatobiliary contrast-enhanced MRI signal intensity after Yttrium-90 radioembolization with glass microspheres for the treatment of hepatocellular carcinoma.

PURPOSE: To analyze hepatobiliary specific contrast agent (HBA) dynamic MRI signal intensity (SI) differences between treated liver (TL) and untreated liver (UL) parenchyma in patients following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) using yttrium-90 containing glass microspheres. MATERIALS: This was a single institution retrospective study of patients with HCC treated with lobar or segmental TARE who received pre- and post-treatment HBA multiphase MRI within a 3-year period. Patients with prior locoregional therapies or multiple TAREs were excluded. SI was obtained by drawing a 2D ROI on T1-weighted non-contrast, arterial (25 s.), portal venous (60 s.), transitional (180 s.), and hepatobiliary (HB) (1200 s.) phase sequences in the (TL) angiosome and UL. HB phase signal enhancement characteristics were correlated with TARE dose thresholds (< 120 Gy, 120-190 Gy, and > 190 Gy) using the medical internal radiation dose (MIRD) methodology. RESULTS: 282 patients received TARE using glass microspheres during the study period and 58 patients who met inclusion criteria were analyzed. Median dose was 141.5 Gy MIRD [IQR 122.0, 161.5; range 100-540 Gy]). Statistically significant differences were present between treated and non-treated liver on non-contrast (- 28.0, p = 0.003), arterial (38.5, p = 0.013), and HB phases (- 95.8, p ≤ 0.001). Median follow-up time to furthest post-treatment MRI was 6 months (range 3-11 months). There was no significant SI difference on portal venous or transitional phases. HB phase SI changes in the TL compared to UL were significant at all TARE dose thresholds (p < 0.05). CONCLUSIONS: SI differences between treated and untreated liver after TARE are most significant on the HB phase and present at all evaluated dose levels at a median of 6 months after treatment. These findings support the parenchymal ablative potential for TARE and the necessity to consider liver function loss within targeted liver volumes.

Deep convolutional neural network and emotional learning based breast cancer detection using digital mammography.

Breast cancer is one of the deadly diseases among women. However, the chances of death are highly reduced if it gets diagnosed and treated at its early stage. Mammography is one of the reliable methods used by the radiologist to detect breast cancer at its initial stage. Therefore, an automatic and secure breast cancer detection system that accurately detects abnormalities not only increases the radiologist's diagnostic confidence but also provides more objective evidence. In this work, an automatic Diverse Features based Breast Cancer Detection (DFeBCD) system is proposed to classify a mammogram as normal or abnormal. Four sets of distinct feature types are used. Among them, features based on taxonomic indexes, statistical measures and local binary patterns are static. The proposed DFeBCD dynamically extracts the fourth set of features from mammogram images using a highway-network based deep convolution neural network (CNN). Two classifiers, Support Vector Machine (SVM) and Emotional Learning inspired Ensemble Classifier (ELiEC), are trained on these distinct features using a standard IRMA mammogram dataset. The reliability of the system performance is ensured by applying 5-folds cross-validation. Through experiments, we have observed that the performance of the DFeBCD system on dynamically generated features through highway network-based CNN is better than that of all the three individual sets of ad-hoc features. Furthermore, the hybridization of all four types of features improves the system's performance by nearly 2-3%. The performance of both the classifiers is comparable using the individual sets of ad-hoc features. However, the ELiEC classifier's performance is better than SVM using both hybrid and dynamic features.

Granulomatous-Lymphocytic Interstitial Lung Disease in a Patient With Common Variable Immunodeficiency.

Common variable immunodeficiency is the most common primary immunodeficiency and consists of impaired immunoglobulin production causing recurrent sinopulmonary infections. The most common cause of mortality for this disorder, however, is from the development of malignancy and autoimmune disorders. One common entity that develops is a systemic granulomatous and lymphoproliferative disorder that can cause an interstitial lung disease more formally referred to as granulomatous-lymphocytic interstitial lung disease (GL-ILD). We discuss a case of a 25-year-old woman with common variable immunodeficiency and GL-ILD and review the literature to summarize the most common radiological findings to raise the suspicion for GL-ILD on high-resolution computed tomography and delineate this from infection and other mimickers. We will also review key histopathological characteristics for diagnosis and the clinical approach and treatment options for this rare disease.

Non-surgical management of patients with intrahepatic cholangiocarcinoma in the United States, 2004-2015: an NCDB analysis.

BACKGROUND: Surgical resection is the standard of care for intrahepatic cholangiocarcinoma (ICC), but only a minority of patients are managed surgically. Other modalities, including external beam radiation (XRT), radiofrequency ablation (RFA), and radioactive implants (RIs) have been employed with significant heterogeneity of prognosis reported in the literature. The aim of this study was to evaluate the demographics of patients with ICC managed non-surgically and compare prognosis in patients managed surgically to those that underwent XRT, RFA, or RI. METHODS: All patients diagnosed with ICC from 2004 to 2015 in the National Cancer Database (NCDB) were reviewed. Patient demographics, treatments, and survival outcomes were analyzed. RESULTS: Of the 6,140 patients with ICC, 4,374 (71%) did not undergo surgery. Patients managed non-surgically were typically older, treated at community centers, more likely to have severe fibrosis or cirrhosis, and present with higher stage disease. The strongest association to receipt of XRT, RI, or RFA modalities was treatment at an academic center. Increased clinical stage was associated with decreased use of RFA; a significantly higher proportion of patients with stage IV disease were given no local therapy. RFA associated with a statistically significant survival benefit over no local therapy only in stage I disease (2.1 vs. 0.7 years, P=0.012) as well as XRT over no local therapy (1.7 vs. 0.7 years, P=0.009). No survival benefit was realized for any treatment in stage II disease. Patients with stage III disease had a survival benefit from XRT versus no local therapy (0.9 vs. 0.6 years, P=0.029) and RI over no local therapy (1.2 vs. 0.6 years, P=0.013). Patients with stage IV disease only demonstrated survival benefit from RI over no local therapy (0.9 vs. 0.3 years, P=0.014). CONCLUSIONS: The majority of patients with ICC in the United States continue to be managed non-surgically. RFA was associated with improved survival only in stage I disease. XRT was associated with improved survival in stage I & III disease, while RI was associated with improved survival in stage III and IV disease.

Angiosomal radiopathologic analysis of transarterial radioembolization for the treatment of hepatocellular carcinoma.

PURPOSE: To assess the radiopathologic correlation following Yttrium-90 transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) using variable radiodosimetry to identify imaging surrogates of histologic response. METHODS: Twelve patients with HCC underwent ablative (≥ 190 Gy) and/or non-ablative (< 190 Gy) TARE delivered in a segmental, lobar, or combined fashion as a surgical neoadjuvant or bridge to transplantation. Both targeted tumor and treatment angiosome were analyzed before and after TARE utilizing hepatocyte-specific contrast-enhanced MRI or contrast-enhanced CT. Responses were graded using EASL and mRECIST criteria. Histologic findings including percent tumor necrosis and adjacent hepatic substrate effects were correlated with imaging features. RESULTS: Complete pathologic necrosis (CPN) was observed in 7/12 tumors post-TARE. Ablative and non-ablative dosing resulted in CPN in 5/6 and 2/6 tumors, respectively. Hyperintensity on T2-weighted imaging, the absence of hepatocyte-specific gadolinium contrast uptake, and plateau or persistent enhancement kinetics in the angiosome correlated with CPN and performed similarly to EASL and mRECIST criteria in predicting CPN. CONCLUSIONS: The absence of hepatocyte-specific contrast uptake, increased signal on T2-weighted sequences, and plateau or persistent enhancement in the angiosome may represent MRI surrogates of CPN following TARE of HCC. These findings correlated with EASL and mRECIST response criteria. Further investigation is needed to determine the role of these findings as possible adjuncts to conventional imaging criteria.

Emergent presentation of Langerhans cell histiocytosis in a pediatric patient: Acute cerebellar involvement causing obstructive hydrocephalus requiring posterior fossa decompression.

Langerhans cell histiocytosis (LCH) is a disorder of the monocyte-macrophage system that can be unifocal or systemic. Here, we present a pediatric case who initially presented with osseous LCH but again presented 6 years later emergently with cerebellar symptoms, cerebellar mass and obstructive hydrocephalus. Patient underwent biopsy of the cerebellum which was path proven intracranial LCH.

Neoadjuvant transarterial radiation lobectomy for colorectal hepatic metastases: a small cohort analysis on safety, efficacy, and radiopathologic correlation.

Colorectal cancer patients have a high incidence of liver metastasis (ml-CRC). Surgical resection is the gold standard for treatment of hepatic metastasis but only a small percent of patients are traditional candidates based on disease extent and adequate size of the future liver remnant (FLR). Interventions such as portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are performed to increase FLR for operative conversion. Limitations to PVE include intrahepatic disease progression, portal vascular invasion, and utilization with concurrent chemotherapy. ALPPS is associated with a high morbidly and mortality. Radiation lobectomy (RL) with yttrium-90 (Y-90) delivers transarterial ablative brachytherapy to the future hepatectomy site which generates FLR hypertrophy similar or greater than PVE. Early results indicate that RL is safe, effective, and may offer unique benefits by providing cytoreduction of hepatic metastases which extends FLR hypertrophy time and allows FLR surveillance to gauge disease biology. A retrospective analysis of four patients with ml-CRC treated with RL prior to hepatectomy was performed to evaluate initial safety, efficacy, FLR hypertrophy, and radiopathologic correlation. Adverse events after RL and hepatectomy were evaluated. Imaging findings were analyzed for efficacy defined as FLR hypertrophy and disease control. Radiopathologic correlation was performed after histologic analysis. RL was well tolerated without major adverse events or hepatic decompensation. FLR hypertrophy ranged from 24.9% to 119% at mean follow-up of three months. The majority of complications were related to surgical instrumentation of the FLR due to upstaging at time of surgery. Hepatectomy specimen histology demonstrated complete pathologic response in 50% of patients, 50% radiopathologic concordance rate, and no significant hepatic fibrosis. Initial experience with neoadjuvant RL for ml-CRC is safe and provides both durable disease control and FLR hypertrophy with concurrent chemotherapy. A 50% complete pathologic response rate raises the possibility of definitive chemoradiation in poor surgical candidates. Prospective investigation is required.

The evaluation of physical exam findings in patients assessed for suspected burn inhalation injury.

The purpose of this investigation was to evaluate the utility of singed nasal hair (SN), carbonaceous sputum (CS), and facial burns (FB) as indicators of burn inhalation injury, when compared to the accepted standard of bronchoscopic diagnosis of inhalation injury. An institutional review board approved, retrospective review was conducted. All patients were suspected to have burn inhalation injury and subsequently underwent bronchoscopic evaluation. Data collected included: percent burn TBSA, burn injury mechanism, admission physical exam findings (SN, CS, FB), and bronchoscopy findings. Thirty-five males and twelve females met inclusion criteria (n = 47). Bronchoscopy was normal in 31 patients (66%). Data were analyzed as all patients and in subgroups according to burn TBSA and an enclosed space mechanism of injury. Physical exam findings (SN, CS, FB) were evaluated individually and in combination. Overall, the sensitivities, specificities, positive predictive values, and negative predictive values calculated were poor and inconsistent, and they did not improve within subgroup analysis or when physical findings were combined. Further statistical analysis suggested the physical findings, whether in isolation or in combination, have poor discrimination between patients that have and do not have inhalation injury (AUC < 0.7, P > .05) and poor agreement with the diagnosis made by bronchoscopy (κ < 0.4, P > .05). This remained true in the subgroup analysis as well. Our data demonstrated the findings of SN, CS, and FB are unreliable evidence for inhalation injury, even in the context of an enclosed space mechanism of injury. Thus, these physical findings are not absolute indicators for intubation and should be interpreted as one component of the history and physical.

Regulation of apoptotic effects by erythrocarpine E, a cytotoxic limonoid from Chisocheton erythrocarpus in HSC-4 human oral cancer cells.

The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC(50) value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent.