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Dupilumab has recently been approved by the Food and Drug Administration for use for treatment of moderate to severe atopic dermatitis in children aged 6 to 11 years. It presents a novel treatment option with a favorable safety profile for patients who are currently reliant on immunosuppressants, including cyclosporine A, methotrexate, and mycophenolate mofetil. Particularly during the current COVID-19 pandemic, immunosuppression should be avoided to retain intrinsic antiviral immunity. Transitioning to dupilumab should be executed strategically-tapering immunosuppressants and minimizing risk of flare by overlapping with the biologic. Herein, we use results of outcome measurements from LIBERTY AD ADOL and LIBERTY AD PEDS trials of dupilumab in adolescents aged 12 to 18 years and children aged 6 to 11 years, respectively, to propose a schematic for an 8-week transition between medications.

Background/aim 18 kDa Translocator protein (TSPO) is a mitochondrial protein up-regulated in colorectal carcinoma (CRC). Our purpose was to develop a TSPO-targeted doxorubicin prodrug (Dox-TSPO) which can be loaded onto drug-eluting beads for transarterial chemoembolization. Furthermore, we evaluated its loading and release kinetics and effects on cell viability. Materials and methods N-Fmoc-DOX-14-O-hemiglutarate was coupled with a TSPO ligand, 6-TSPOmbb732, using classical N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate coupling to produce Dox-TSPO. Loading and elution studies were performed using DC beads™. Cell viability studies were performed using CellTiter-Glo® Luminescent Cell Viability Assay. Results Dox-TSPO was successfully synthesized and readily loaded onto and eluted from DC beads™, albeit at a slower rate than free doxorubicin. CRC cell lines expressing TSPO were 2- to 4- fold more sensitive to Dox-TSPO compared to free doxorubicin at 72 h. Conclusion Dox-TSPO is a promising candidate for targeted and directed cancer treatment of CRC liver metastases.

Clinical trials are currently underway to evaluate the benefit of dupilumab in treating allergic contact dermatitis (ACD). Dupilumab use has been reported to improve ACD reactions in some patients, but not all. Varying clinical responses to T helper 2 (TH2) inhibition challenge the classical view that ACD proceeds through a TH1-dominant pathway. Selective TH2 inhibitors, such as dupilumab, may attenuate ACD when the delayed hypersensitivity response is due to TH2-predominate activation; conversely, it may have no effect on ACD if it is elicited via TH1 or TH17 pathways. We hypothesize that allergen-specific T-cell responses and patient-specific factors both play an important role in determining which pathways are recalled in delayed hypersensitivity reactions.

To analyze tumor response, survival and safety in patients with non-resectable hepatocellular carcinoma (HCC) treated with transarterial hepatic chemoembolization using degradable starch microspheres (DSM-TACE) combined with doxorubicin who had no local interventional or systemic therapy alternative according to an interdisciplinary conference. In this retrospective study, 28 patients (23 male, 5 female, median age 67 years) with unresectable HCC, serum bilirubin levels 3 mg/dl and contraindications to Sorafenib, RFA, SIRT or cTACE were included. DSM-TACE was performed using Embocept DSM-TACE could be technically successfully performed in all 28 patients. At control imaging after three treatments, the overall rates of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were 14.3 %, 25 %, 39.3 % and 21.4 %, respectively, according to mRECIST. With regard to BCLC stages, the results were as follows (CR, PR, PD): BCLC A (n = 8): 7.1 %, 7.1 %, 10.7 %, 1.2 %; BCLC B (n = 12): 0 %, 10.7 %, 17.9 %, 14.3 %; BCLC C (n = 5): 0 %, 3.6 %, 10.7 %, 3.6 %; BCLC D (n = 3): 3.6 %, 3.6 %, 0 %, 3.6 %. According to this, DSM-TACE showed an overall good median survival of 682 days, although the patients' survival was strictly dependent on BCLC stage. DSM-TACE is a safe and promising treatment alternative for patients with unresectable HCC who are ineligible for other loco-regional therapies. · DSM-TACE is a safe treatment alternative for patients ineligible for other local or systemic treatments.. · DSM-TACE did not influence the MELD-score in our study population.. · Patients treated with DSM-TACE showed an overall good median survival of 682 days, strictly dependent on BCLC stage..· Haubold J, Reinboldt MP, Wetter A et al. DSM-TACE of HCC: Evaluation of Tumor Response in Patients Ineligible for Other Systemic or Loco-Regional Therapies. Fortschr Röntgenstr 2020; 192: 862 - 869. Die Studie wurde durchgeführt, um das Tumoransprechen, das Überleben und die Sicherheit der Behandlung durch transarterielle Chemoembolisation mit abbaubaren Stärke-Mikropartikeln in Kombination mit Doxorubicin (DSM-TACE) bei Patienten mit inoperablem hepatozellulärem Karzinom (HCC) zu analysieren. Die Patienten hatten dabei gemäß einer interdisziplinären Konferenz keine lokale oder systemische Therapiealternative. In diese retrospektive Studie wurden 28 Patienten (23 männlich, 5 weiblich, mittleres Alter 67 Jahre) mit inoperablem HCC, Serum-Bilirubinspiegel 3 mg/dl und Kontraindikationen gegen andere lokale oder systemische Therapien eingeschlossen. DSM-TACE wurde 3-mal alle 4–6 Wochen mit Embocept DSM-TACE konnte bei allen 28 Patienten technisch erfolgreich durchgeführt werden. Bei der Kontrollbildgebung nach 3 Therapien lagen die Gesamtraten für das vollständige Ansprechen (CR), das partielle Ansprechen (PR), die stabile Erkrankung (SD) und die progressive Erkrankung (PD) laut mRECIST bei 14,3 %, 25 %, 39,3 % bzw. 21,4 %. In Bezug auf die BCLC-Stufen ergaben sich folgende Ergebnisse (CR, PR, PD): BCLC A (n = 8): 7,1 %, 7,1 %, 10,7 %, 1,2 %; BCLC B (n = 12): 0 %, 10,7 %, 17,9 %, 14,3 %; BCLC C (n = 5): 0 %, 3,6 %, 10,7 %, 3,6 %; BCLC D (n = 3): 3,6 %, 3,6 %, 0 %, 3,6 %. Dementsprechend zeigte die DSM-TACE ein insgesamt gutes medianes Überleben von 682 Tagen, wobei das Überleben der Patienten streng vom BCLC-Stadium abhängig war. DSM-TACE ist eine sichere und vielversprechende Behandlungsalternative für Patienten mit einem inoperablen HCC, die für andere lokale und systemische Therapien nicht geeignet sind. · DSM-TACE ist eine sichere Behandlungsalternative für Patienten mit einem HCC, die für andere lokale und systemische Therapien nicht geeignet sind.. · DSM-TACE hatte in unserer Studienpopulation keinen Einfluss auf den MELD-Score.. · Die mit DSM-TACE behandelten Patienten zeigten ein insgesamt gutes medianes Überleben von 682 Tagen, das strikt vom BCLC-Stadium abhängig war..

Background To investigate the impact of insurance status on outcomes in patients with hepatocellular carcinoma (HCC). Methods Patients diagnosed with HCC in the cancer registry from 2005 to 2016 were retrospectively stratified by insurance group. Overall survival was assessed via Kaplan‐Meier curves and Cox proportional hazard models including potential confounders in multivariable analyses. Results Seven hundred and sixty‐nine patients met inclusion criteria (median age 63 years, 78.8% male, 65.9% Caucasian). 44.5% had private insurance (n = 342), 29.1% had Medicare (n = 224), and 26.4% had Medicaid (n = 203). At diagnosis, Medicaid patients had higher rates of Child‐Pugh B (32.0%) and C disease (23.6%) vs Medicare (28.6% and 9.8%) and private insurance (26.9% and 6.7%, P, Medicaid is associated with advanced liver cirrhosis at time of hepatocellular carcinoma diagnosis. Primary insurance is not an independent predictor of survival.

Image-guided locoregional therapies (LRTs) have long been a vital part of treatment regimens for hepatocellular carcinoma (HCC). Ablation, chemoembolization, and radioembolization are examples of commonly used treatment techniques for HCC. This review describes the various methods utilized to treat HCC in the field of interventional oncology and also focuses on new and novel treatment concepts being developed in the field including the use of novel immunotherapy agents and combination therapy of LRTs with immunotherapy.

Checkpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p + T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p p p

Purpose Accurate therapeutic management of the neck is a challenge in patients with supraglottic laryngeal cancer. Nodal metastasis is common at all disease stages, and treatment planning relies on clinical staging of the neck, for both surgical and non-surgical treatment. Here, we compared clinical and surgical staging results in supraglottic carcinoma patients treated with primary surgery to assess the accuracy of pre-therapeutic clinical staging and guide future treatment decisions. Methods Retrospective analysis of clinical, pathological, and oncologic outcome data of 70 patients treated with primary surgery and bilateral neck dissection for supraglottic laryngeal cancer. Patients where clinical and pathological neck staging results differed, were identified and analyzed in detail. Results On pathologic assessment, patients with early stage (pT1/2) primaries showed cervical lymph node metastases in 55% (n = 17/31) of cases, compared to 67% (n = 26/39) of patients with pT3/4 tumors. In 24% (n = 17/70) of all patients, cN status differed from pN status, resulting in an upstaging in 16% of cases (n = 11/70) and a downstaging in 9% (n = 6/70) of cases. 14% of patients with cN0 status had occult metastases (n = 5/30). As assessed by a retrospective tumor board, in case of a non-surgical treatment approach, the inaccurate clinical staging of the neck would have led to an over- or undertreatment of the neck in 20% (n = 14/70) of all patients. Conclusion Our data re-emphasize the high cervical metastasis rates of supraglottic laryngeal cancer across all stages. Inaccurate clinical staging of the neck is common and should be taken into consideration when planning treatment.

Background Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil‐to‐lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. Methods Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan–Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). Results A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low‐NLR group (, Lower baseline NLR was associated with increased overall survival in HCC. Chronic viral hepatitis serves as an effect modifier of NLR, attenuating its prognostic relevance in this hepatitis C‐predominant population.

To assess serum lactate dehydrogenase (LDH) as a pretreatment prognostic factor in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion (THC). 56 patients (48 % male, median age: 63.5 years) underwent a median of 4 THC sessions. Kaplan-Meier for median overall survival (OS) and time to hepatic progression (TTP; 95 %CI) in months and Cox proportional hazards model for uni- (UVA)multivariate analyses (MVA) for hazard ratio (HR) evaluation were calculated. The median OS was 9.4 months. The pretreatment LDH value before 1st THC was the strongest OS predictor with 19.8 months for normal (≦ 280 units per liter (U/L)), 9.7 for intermediate ( 280- 1000 U/L), and 3.84 months for high (≧ 1000 U/L) LDH. LDH significantly predicted a median TTP with 8 months, 4 months, and 1 month for normal, intermediate, and high LDH, respectively. UVA revealed intermediate (16.5) and high (77.3) LDH, bilirubin the upper limit of normal (ULN) (2.89), alkaline phosphatase 1.5 ULN (6.8), leukocytes ULN (4.2), gamma-glutamyl transferase (GGT) ULN (7), extrahepatic metastases (1.8) and liver lesions ≥ 5 cm (3.6) as significant predictors for worse OS. MVA confirmed intermediate (5) and high (27.1) LDH, bilirubin (5.7), GGT (2.9), and tumor size ≥ 5 cm (3.7) as significant independent predictors for worse OS. Patients with decreasing vs. increasing LDH 10 % between 1st and 2nd THC (median: 38 days) survived longer (14.6 vs. 4.3 months) and progressed later (7 months vs. 1 month). Elevated pretreatment serum LDH is an essential and robust OS and TTP predictor, potentially allowing for the identification of patients benefiting most from transarterial hepatic chemoperfusion.· Pretherapeutic LDH is the most reliable prognosticator for OS and TTP. · Therapy-related LDH decrease 10 % between 1st and 2nd THC had prolonged OS and TTP. · Lower Values of LDH, bilirubin, gamma-glutamyl transferase, and tumor size are independent pretherapeutic predictors for longer OS. · Extrahepatic metastases do not have an independent influence on overall survival.· Ludwig J, Haubold J, Heusner T et al. Lactate Dehydrogenase Prior to Transarterial Hepatic Chemoperfusion Predicts Survival and Time to Progression in Patients with Uveal Melanoma Liver Metastases. Fortschr Röntgenstr 2021; 193: 683 - 691.ZIEL: Beurteilung der Serum-Laktatdehydrogenase (LDH) als prätherapeutischer prognostischer Faktor bei Patienten mit Lebermetastasen eines Aderhautmelanoms, die mit der transarteriellen hepatischen Chemoperfusion (THC) behandelt wurden. 56 Patienten (48 % männlich, medianes Alter: 63,5 Jahre) erhielten im Median 4 Behandlungen. Die Kaplan-Meier-Analyse für das mediane Gesamtüberleben und die Zeit bis zur hepatischen Tumorprogression (TTP; 95 %-KI) in Monaten sowie das Cox-Proportional-Hazard-Modell für die univariate (UVA) und multivariate Analyse (MVA) zur Bewertung des Risikoquotienten (HR) wurden berechnet. Das mediane Überleben betrug 9,4 Monate. Der LDH-Wert vor der ersten Behandlung war der stärkste Prädiktor für das Überleben mit 19,8 Monaten für normale (≦ 280 Einheiten/Liter (U/L)), 9,7 Monaten für mittlere ( 280– 1000 U/L) und 3,84 Monaten für hohe (≧ 1000 U/L) LDH-Werte. Die LDH war der signifikanteste Vorhersagewert für die TTP mit 8, 4 und 1 Monaten für normale, mittlere bzw. hohe LDH-Werte. Die UVA identifizierte mittlere (16,5) und hohe (77,3) LDH-Werte, Bilirubin Obergrenze des Normalbereichs (ULN) (2,89), alkalische Phosphatase 1,5 ULN (6,8), Leukozyten ULN (4,2), Gamma-Glutamyltransferase (GGT) ULN (7), extrahepatische Metastasen (1,8) und Leberläsionen ≥ 5 cm (3,6) als signifikante Prädiktoren für ein kürzeres Überleben. Die MVA bestätigte mittlere (5,0) und hohe (27,1) LDH-Werte, Bilirubin (5,7), GGT (2,9) und eine Tumorgröße von ≥ 5 cm (3,7) als unabhängige signifikante Prädiktoren für das Überleben. Patienten mit einer LDH-Abnahme vs. einer Zunahme 10 % zwischen der ersten und zweiten Behandlung (median: 38 Tage) überlebten länger (14,6 vs. 4,3 Monate) und zeigten eine spätere Progression (7 vs. 1 Monate). Ein erhöhter prätherapeutischer LDH-Wert ist ein wesentlicher und robuster OS- und TTP-Prädiktor, der es potenziell ermöglicht die Patienten zu identifizieren, welche am meisten von der transarteriellen hepatischen Chemoperfusion profitieren.· Prätherapeutisches LDH ist der stärkste prognostische Faktor für das Überleben und die Tumorprogression. · Eine therapiebedingte LDH-Abnahme 10 % zwischen der ersten und zweiten Behandlung ist mit einem längeren OS und TTP assoziiert. · Niedrigere LDH, Bilirubin und Gamma-Glutamyl-Transferase Werte sowie kleinere Tumore sind unabhängige prätherapeutische Prädiktoren für ein längeres Gesamtüberleben. · Extrahepatische Metastasen haben keinen unabhängigen Einfluss auf das Gesamtüberleben.

While dietary triggers have been investigated in acne and other inflammatory follicular dermatoses, there is a paucity of data on diet and hidradenitis suppurativa (HS). We sought to identify exacerbating and alleviating foods in HS patients. An anonymous survey was distributed via HS Facebook support groups and in person at HS specialty clinics. Participants were asked to select all that apply from a list to indicate foods that worsen and make HS better including sweet foods, breads and pasta, red meat, chicken, fish, canned foods, fruits, vegetables, dairy, high-fat foods, I do not know, and no. Only 12.0% (n = 89/744) identified alleviating foods while 32.6% (n = 237/728) identified HS-symptom-exacerbating foods. The most commonly reported exacerbating foods were sweets (67.9%), bread/pasta/rice (51.1%), dairy (50.6%), and high-fat foods (44.2%). The most commonly reported alleviating foods included vegetables (78.7%), fruit (56.2%), chicken (51.7%), and fish (42.7%). Further studies are required to evaluate the mechanistic links between diet and HS. HS patients may benefit from receiving dietary counseling as part of a comprehensive HS management plan.

Atopic dermatitis (AD), a chronic inflammatory skin condition, negatively affects sexual health in various ways including causing physical discomfort and changes in physical appearance that can lead to low self-confidence. The chronic and debilitating nature of this disease can interfere with the sexual well-being of patients and their partners. This review describes the ways that AD affects sexual health. In addition, we review the impact that partnered relationships and physical intimacy can have on AD and provide practical recommendations for optimizing sexual health in AD patients.

Interventional oncology (IO) and oncoimmunology (OI) are fields that have significantly evolved during the last two decades and are providing new opportunities to conquer cancer with a safe and effective treatment profile. Novel IO treatments have the potential to complement OI and sensitize “cold” tumors to immunostimulatory therapies with the ultimate aim of improving patient outcomes. In this manuscript, we provide an overview of the current knowledge of the immune system in cancer, the potential for IO to modulate the immune system, and how IO and OI may synergize.

Ingredients found in facial moisturizers can impact a myriad of skin conditions, including sensitive skin syndrome and contact dermatitis. There is a paucity of evidence on the allergenic potential and marketing claims of facial moisturizers, posing challenges to clinician recommendation and consumer selection. In this study, we systematically evaluate the 100 top-selling sun protective facial moisturizers that claim to be natural, fragrance free, expert-approved, age preventing, beneficial for sensitive skin, and sun protective. Allergenic potential of these moisturizers is evaluated based on ingredients used and prices and consumer ratings are compared. Accordingly, 75 of 100 marketed at least one additional benefit. "Anti-aging" products had the highest average price ($14.99/oz) and "expert-approved" had the lowest ($5.91/oz). Consumer rating was highest for facial moisturizers that were "fragrance-free" (4.35/5.00) whereas products that were "natural" received the lowest ratings (3.49/5.00). The most prevalent allergens found in these moisturizers were ethylenediamine tetraacetic acid (EDTA), phenoxyethanol, and cetyl alcohol. "Expert-approved" products had the fewest average allergens in their ingredient lists (P=0.033), whereas products advertising "SPF" had significantly more (P

Dear Editor,Medication costs for atopic dermatitis (AD) have been persistently high in the United States, with cumulative health care spending of $29.3 billion in 2012 (1). Although some prices of ...

Purpose To compare adverse events and survival outcomes, including cancer-specific survival and overall survival (OS), in patients with T1aN0M0 renal cell carcinoma (RCC) who are undergoing partial nephrectomy (PN), radical nephrectomy (RN), thermal ablation (TA), or active surveillance (AS). Materials and Methods Through use of the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 to 2011 with at least 1 year of consecutive follow-up, a HIPAA-compliant retrospective propensity score-matched study of patients with T1aN0M0 RCC who underwent PN, RN, TA, or AS was performed. Medicare beneficiaries (n = 10 218) with T1aN0M0 RCC as first primary cancer diagnosis were included. Survival and adverse health outcomes were compared across treatment groups. Results Overall, cancer-specific survival significantly differed in the PN versus RN (P.001), AS versus TA (P = .03), and AS versus PN (P = .002) groups. There were no significant differences when TA was compared with PN or RN, with 9-year cancer-specific survival rates of 96.4% versus 96.3% (PN vs TA, P = .07) and 96.1% versus 96.0% (RN vs TA, P = .14), respectively. With the exception of cancer-specific survival in AS versus RN groups (P = .29), cancer-specific survival and OS for all AS comparisons were significantly lower. In addition, compared with the patients undergoing TA, those in the PN and RN groups had increased rates of renal, cardiovascular, and thromboembolic adverse events up to 1 year after the procedure (P.05 for all comparisons). Conclusion For T1aN0M0 RCC, TA confers cancer-specific survival and OS similar to those seen with surgical management, with significantly fewer adverse outcomes at 1 year after the procedure and similar rates of secondary cancer events compared with surgery.

Dear Editor,Atopic dermatitis (AD) is a chronic relapsing inflammatory dermatosis characterized by intense pruritus and rash. Its etiology is complex and influenced by an interplay of genetics, env...

While much research has been invested in understanding preparedness among emergency managers during natural disasters, substantially less attention has been devoted to evaluating the level of understanding and preparedness among nonemergency management employees who must direct others during natural disasters. Among those second-tier leaders are university residential housing staff, who are responsible for the safety of thousands of youth who may be far from the influence of their family. Using varimax-rotated principal components analysis, an instrument was developed for assessing the knowledge and practices of such residential housing staff at Louisiana State University, Baton Rouge, in the wake of Hurricane Isaac (2012). Relationships were derived between hurricane preparedness and general knowledge of hurricane meteorology, experience with past hurricanes, preparation and threat anxiety, duration of experience of the housing staff and in residing in Baton Rouge, whether the respondent’s primar...

// Meaghan S. Dendy 1,2 , Johannes M. Ludwig 2 and Hyun S. Kim 2,3 1 Drexel University College of Medicine, Philadelphia, PA, USA 2 Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA 3 Yale Cancer Center, Yale University, New Haven, CT, USA Correspondence to: Hyun S. Kim, email: // Keywords : colorectal cancer, liver cancer, radioembolization, Y 90 , biomarkers Received : December 28, 2016 Accepted : February 27, 2017 Published : March 08, 2017 Abstract This critical review aims to explore predictive and prognostic biomarkers of Yttrium-90 (Y 90 ) radioembolization therapy of colorectal liver metastases. A brief overview of established predictive and prognostic molecular and genetic biomarkers in colorectal cancer therapies will be discussed. A review of the literature on imaging modalities, genetic, metabolic and other molecular markers and the subsequent outcomes in post-Y 90 treatment will be presented. How these biomarkers and future biomarker research can inform locoregional treatment decisions in the clinical setting of metastatic colorectal cancer lesions of the liver will be explored. There are opportunities for personalized cancer treatment in the setting of Y 90 radioembolization. The ability to predict tumor response after Ytrium-90 radioembolization therapy can greatly impact clinical decision making and enhance treatment outcomes, therefore further research into the field is needed.

Aim: To simulate effects of the new Organ Procurement and Transplantation Network/United Network for Organ Sharing policy on the patients’ characteristics and post orthotopic liver transplantation (OLT) outcome. Materials & methods: The United Network for Organ Sharing database was used to identify patients with hepatocellular carcinoma who were listed for OLT 2002–2014. All patients (actual group) versus simulated group with new 6-month delay in assigning Model for End-Stage Liver Disease score exception and Model for End-Stage Liver Disease exception cap of 34 were compared. Results & conclusion: With the new policy, 7,745 (30.4%) of the transplanted patients would have received a delayed transplantation or not be transplanted. The simulated group also showed significantly higher mean overall survival after OLT (p

Background To investigate the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status. Methods In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan‐Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA). Results About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child‐Pugh A patients (P, The neutrophil‐to‐lymphocyte ratio (NLR) has the strongest impact as a prognostic marker in intrahepatic cholangiocarcinoma (ICC) versus the platelet‐to‐lymphocyte ratio and systemic immune‐inflammation index, and increased NLR is associated with decreased survival in ICC. The NLR has decreased prognostic utility in patients with advanced liver disease.

Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8.6 cm right upper lobe lung lesion with local invasion, adenopathy, and a malignant pericardial effusion. This lesion was biopsied and identified to be cT3N3M1b squamous cell cancer of the lung without any recognizable PD-L1 expression on tumor cells. For her metastatic NSCLC, the patient underwent two lines of conventional chemotherapy before initiation of combination immunotherapy with an anti-PD-L1 and anti-CTLA-4 antibody. Though she initially achieved a response, she thereafter progressed and developed immunotherapy resistant lymph nodal metastasis. While cervical lymph nodes could be surgically removed, another metastasis in an aortocaval area required a more sensitive therapy like thermal ablation. The aortocaval node was partially treated with a single treatment of cryotherapy and demonstrated durable complete response. Cryotherapy for checkpoint immunotherapy resistant metastasis appears to be a safe and feasible treatment for treating metastatic disease in non-small cell lung cancer. The prospect of cryotherapy adjuvancy may enable local control of metastatic disease after initial response to immune checkpoint immunotherapy and may impact on overall outcomes. CA extern

To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 (90Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus 90Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger’s and Begg’s tests. Fourteen studies comparing DEB-TACE or 90Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and 90Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to 90Y-radioembolization but direct comparison is warranted for further evaluation. • This meta-analysis shows greater 1-year survival benefit for DEB-TACE over 90 Y-radioembolization. • DEB-TACE has a favourable 2- & 3-year survival benefit trend over 90 Y-radioembolization. • No significant difference for tumour response was detected. • Direct comparison of these methods for a more robust evaluation is warranted.

To investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival.A single-center, prospective study of 44 consecutive patients (median age: 58.5 years, 29.5 % male) diagnosed with pancreatic (52.3 %) or carcinoid (47.7 %) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients' baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10 %) and low (10 %) LSF. Baseline comparisons were performed using Fisher's exact tests for categorical and Mann-Whitney U test for continuous variables. Survival was calculated using the Kaplan-Meier method. Univariate (Wilcoxon rank-sum test) and multivariate analyses (Cox Proportional Hazard Model) for risk factor analysis were performed.There was no statistically significant difference in age, gender, race, tumor properties, or previous treatments between patients with high (n = 15) and low (n = 29) LSF. The median OS was 27.4 months (95 %CI 12.73-55.23), with 4.77 months (95 %CI 2.87-26.73) for high and 42.77 months (95 %CI 18.47-59.73) for low LSF (p = 0.003). Multivariate analysis identified high LSF (p = 0.001), total serum bilirubin1.2 mg (p = 0.016), and lack of pretreatment with octreotide (p = 0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival.LSF ≥10 %, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.

Purpose To investigate baseline and early apparent diffusion coefficients (ADC) derived from diffusion-weighted imaging (DWI) as a predictor of objective response (OR) and survival in unresectable hepatocellular carcinoma (HCC) treated with doxorubicin drug-eluting bead (DEB) transcatheter arterial chemoembolization. Materials and Methods In a prospective study, 57 patients underwent DEB chemoembolization. Dynamic contrast-enhanced magnetic resonance imaging and DWI were performed at baseline and 1 and 3 months after DEB chemoembolization. OR was evaluated per modified Response Evaluation Criteria In Solid Tumors (mRECIST) and European Association for the Study of the Liver (EASL) guidelines. Baseline ADCs of tumors that showed OR at 1 and 3 months were compared with nonresponding tumor ADCs by two-sample t test and receiver operating characteristic curves. Additionally, ADC changes at 30 days were correlated with OR. Finally, Kaplan–Meier analysis was used to compare survival between patients with lesions demonstrating more restricted baseline diffusion and others. Results At 1 month, 33 patients (60%) showed OR (21 complete responses and 12 partial responses). At baseline, tumors with OR at 1 month showed significantly more restricted diffusion (0.731 × 10 −3 mm 2 /s) compared with others (1.057 × 10 −3 mm 2 /s; P = .031). No difference between response rates at 1 and 3 months according to mRECIST and EASL was observed. For an area under the curve of 0.965, the sensitivity and specificity of predicting objective tumor response at 1 month using a baseline HCC ADC of 0.83 × 10 −3 mm 2 /s were 91% and 96%, respectively. In addition, patients with lesions with a baseline ADC −3 mm 2 /s showed prolonged survival compared with others ( P Conclusions In unresectable HCC, a baseline ADC −3 mm 2 /s is a predictor of survival and treatment response at 1 and 3 months after DEB chemoembolization with high sensitivity and specificity.

Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC). Current response assessment is mainly based on: (1) changes in size, which is at times unreliable and lag behind the result of therapy; and (2) contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI) techniques, such as diffusion-weighted imaging (DWI) have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement), which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies.

Background: Biosensor imaging of redundant deviation in shifts (BIRDS) is a non-invasive MR imaging modality that maps extracellular pH (pHe) by directly detecting paramagenetically shifted non-exchangeable protons of exogeneous agents. Previously it has been used to characterize various tumors in the rat brain and to monitor the response to loco-regional treatment of liver cancer. The purpose of this study was to investigate the feasibility of utilizing pHe mapping with BIRDS to differentiate ablated and non-ablated tumors in the setting of systemic immunotherapy of murine colorectal cancer (CRC). Materials and Methods: Eight BALB/c mice (Charles River Laboratories, Wilmington, MA, USA) were implanted with bilateral flank injections of 0.5 × 106 CT26.WT colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Mice were randomly assigned into 3 treatment groups; group 1 received injections of sham antibodies (InVivoMAb IgG controls), group 2 was treated with dual anti-PD-1 and anti-CTLA-4 antibodies (Clone J43 & Clone 9D9; BioXcell, West Lebanon, NH, USA), III). Group 3 received cryoablation in combination with systemic injections of dual checkpoint inhibitors. Mapping of pHe was performed between 3-10 days after the initiation of treatment and was immediately followed by sacrifice. Results: The mean pHe of untreated, control tumors was significantly lower than the average pHe of tumors treated with immuno-thermal ablations (6.6 vs 6.96; p0.05). Conclusions: BIRDS MR quantification was feasible for imaging murine CRC model. BIRDS quantification of pHe could serve as an imaging non-invasive biomarker for metabolic changes of the tumor microenvironment in a murine CRC model with Immuno-Thermal Ablation Therapy. Significance at a GlanceTreatment GroupMean Extracellular pHSignificant DifferencesControl6.6Vs Target Ablated Tumors (p Citation Format: Ryan J. Slovak, Daniel Coman, Johannes M. Ludwig, Hyun S. Kim. Mapping the extracellular pH gradient of colorectal cancer after immuno-thermal ablation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2778.

160 Background: Checkpoint inhibitors have demonstrated significant clinical impact in colorectal cancer with deficient mismatch repair (MMR) and high microsatellite instability. However, most patients have disease with stable microsatellites and typically respond poorly to most immunotherapies. The purpose of this study was to quantify the immune responses induced by mono versus dual immune checkpoint blockade (DICB) in a MMR proficient model of colorectal cancer. Methods: A MMR proficient model of colorectal cancer was established in 30 BALB/c mice via bilateral subcutaneous flank injections of 0.5x106 CT26.WT murine colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Mice were assigned to receive either sham antibodies (InVivoMAb IgG controls), monotherapy with anti-PD-1 antibodies (Clone J43; BioXcell, West Lebanon, NH, USA), or DICB with anti-PD-1 and anti-CTLA-1 antibodies (Clone 9D9; BioXcell). Tumor growth was monitored over time and mice were sacrificed at either 7 or 14 days post-treatment. Single cell suspensions of harvested tumors and spleens were analyzed using FACS. The number of CD8+ and CD4+ T cells as well as the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3 was quantified in each sample. Results: DICB was associated with a reduction in tumor volume as compared to either mono PD-1 inhibition or control (p < 0.05). Neither monotherapy nor DICB significantly affected tumor infiltration by lymphocytes. Tumor infiltrating CD8+ T cells in the DICB treatment group demonstrated less expression of PD-1 and LAG3 compared to the control and monotherapy groups (PD-1: 1723±90.5 [Mean fluorescence intensity ± SEM] vs 2489±119.9 & 2404±117.9; p < 0.05) (LAG3: 453.8±21.58 vs 664.1±53.21 & 719.7±14.25; p < 0.05). The DICB group also showed increased expression of TIM3 (11,779±1271 vs 2832±380.9 & 4081±426.6; p < 0.05). Conclusions: These results suggest dual therapy with anti-CTLA and anti-PD-1 antibodies inhibits the growth of stable microsatellite colorectal cancer by suppressing key immunosuppressive checkpoints. Upregulation of TIM3 represents a potential escape mechanism that could be a target for future combination immunotherapies.

198 Background: Cryoablation exposes tumoral antigens capable of provoking an anti-cancer immune response. The addition of immunotherapy alongside cryoablation may synergistically promote a more robust systemic response. The purpose of this investigation was to study the growth of targeted and off-target tumors after combined cryoablation and dual immune checkpoint blockade (DICB). Methods: Sixty BALB/c mice were implanted with bilateral flank injections of 0.5 x 106 CT26.WT colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Tumor volume was measured every other day via caliper (LxW2). Mice were randomly assigned to receive either sham injections (InVivoMAb IgG controls), dual anti-PD-1 and anti-CTLA-4 (DICB) (Clone J43 & Clone 9D9; BioXcell, West Lebanon, NH, USA), or DICB plus either partial or full cryoablation of a single targeted tumor. Treatment day 0 began once tumors reached a volume of ~300mm3. Injections of antibodies were given on treatment day 0, 3, and 5. Cryoablation was performed on treatment day 2. Full ablation was achieved via two 3-minute cycles at 100% power and partial ablation was defined as a single 3 minute cycle at 70% power ablation (Visual-ICE System, Galil Medical, St. Paul MN). Animals were sacrificed at 7 and 14 days after treatment. Results: There was an average of 177.15% ± 75.22 (SD) increase in tumor volume among control animals and 14.47% ± 9.69 decrease in animals treated solely with DICB. Mice that received full ablation demonstrated an average 72.39% ± 29.21 decreased volume in the target tumors and 48.94% ± 25.97 decrease in the off-target tumors. Partially ablated mice averaged 81.21% ± 16.43 decreased volume in the target tumors and 35.87% ± 16.95 decreased volume in the off-target tumors. The mean change in volume of every group was significantly less than that of the control (p < 0.05) and there was a significantly larger reduction in volume between both the full and the partial target tumors versus the DICB group (p < 0.05). Conclusions: The addition of cryoablation to DICB resulted in a significant reduction in volume of the targeted tumors. Additionally, this combination led to larger volume reductions in off-target tumors as compared to immunotherapy alone.

Purpose Extrahepatic portal vein thrombosis (EPVT) is one major cause of portal hypertension in children. Surgical reinstallation of portal venous flow can be achieved in patients with patent intrahepatic portal venous system/Rex recess. Our study aimed to compare the ability of magnetic resonance imaging (MRI) and retrograde portography (RP) to assess patency of the intrahepatic portal venous system in children with EPVT. Methods All pediatric patients with EPVT who were examined with contrast enhanced MRI (1.5 T) and invasive RP between 2013 and 2017 were included in this retrospective study. Medical records were reviewed for demographic, biochemical and clinical data. Patency of the Rex recess as detected by MRI and RP was retrospectively reviewed. Results Sixteen children (7.6 ± 5.0 years) with EPVT were included. Sensitivity, specificity, positive and negative predictive value for the detection of patent Rex recess by MRI compared to RP were 55%, 57%, 63% and 50%. Diagnostic accuracy was 56%. Diagnostic failure of MRI compared to RP was explained by the following: I. Problems differentiating collaterals from portal venous vessels II. Incapability showing dynamic blood flow in compromised portal venous flow III. Poor spatial resolution, especially in small children. Conclusion RP is a reliable method for the visualization of the Rex recess and the intrahepatic portal venous system in children with EPVT, whereas MRI has shown to be unsuitable for the assessment of the intrahepatic portal vein in these patients. In the preoperative setup, we recommend both procedures, RP and MRI for the visualization of the intrahepatic portal venous system, and the extrahepatic vessels, respectively. Level of evidence Level III.

BACKGROUND Primary liver cancer, including Hepatoblastoma (HB) and hepatocellular carcinoma (HCC), in pediatric populations is often fatal. The outcomes are poor despite universal health care access in pediatric patients. AIM We investigated the sociodemographic factors affecting outcomes in pediatric patients with primary liver cancer. MATERIALS AND METHODS This is a large population database study of Surveillance, Epidemiology, and End Results cancer registry data from 1973 to 2011. HB and HCC were analyzed regarding age, sex, race, geographic area, and treatment-related information including survival. RESULTS In total, 998 patients, the median age at time of diagnosis was 1 year for HB [0-19; 95% confidence interval (CI), 1.5-1.9] and 14 years for HCC (0-19; 95% CI, 12.1-13.3) (P

Early visual impairments probably partially caused by impaired interactions between magnocellular (M) and parvocellular (P) pathways (M priming deficit), and disturbances of basic self-awareness or self-disorders (SDs) are core features of schizophrenia. The relationships between these features have not yet been studied. We hypothesized that the M priming was impaired in first-episode patients and that this deficit was associated with visual aspects of SDs.To investigate early visual processing in a sample of first-episode schizophrenia patients and to explore the relationships between M and P functioning and visual aspects of SDs addressed by the Examination of Anomalous Self-Experience (EASE) interview.Nine stimulating conditions were used to investigate M and P pathways and their interaction in a pattern reversal visually evoked potential (VEP) paradigm. N80 at mixed M- and P-conditions was used to investigate magnocellular priming. Generators were analyzed using source localization (Brain Electrical Source Analysis software: BESA). VEPs of nineteen first-episode schizophrenia patients were compared to those of twenty matched healthy controls by a bootstrap resample procedure. Visual aspects of SDs were analyzed through a factor analysis to separate symptom clusters of derealization phenomena. Thereafter, the associations between the main factors and the N80 component were explored using linear mixed models.Factor analyses separated two EASE factors ("distance to the world", and "intrusive world"). The N80 component was represented by a single dipole located in the occipital visual cortex. The bootstrap analysis yielded significant amplitude reductions and prolonged latencies in first-episode patients relative to controls in response to mixed M-P conditions, and normal amplitudes and latencies in response to isolated P- and M-biased stimulation. Exploratory analyses showed significant negative correlations between the N80 amplitude values at mixed M-P conditions and the EASE factor "distance to the world", i.e. relatively higher amplitudes in the patient group were associated with higher subjective perceived derealization ("distance to the world").The early VEP component N80 evoked by mixed M-P conditions is assumed to be a correlate of M priming, and showed reduced amplitudes and longer latencies in first-episode patients. It probably reflects a hypoactivation of the M-pathway. The negative association between visual SDs (derealization phenomena characterized by visual experiences of being more distant to the world), and the M priming deficit was counterintuitive. It might indicate a dysregulated activity of the M-pathway in patients with SDs. Further research is needed to better understand this preliminary finding.

Administrative data are often used to estimate state Medicaid/Children's Health Insurance Program duration of enrollment and insurance continuity, but they are generally not used to estimate participation (the fraction of eligible children enrolled) because administrative data do not include reasons for disenrollment and cannot observe eligible never-enrolled children, causing estimates of eligible unenrolled to be inaccurate. Analysts are therefore forced to either utilize survey information that is not generally linkable to administrative claims or rely on duration and continuity measures derived from administrative data and forgo estimating claims-based participation. We introduce appendectomy-based participation (ABP) to estimate statewide participation rates using claims by taking advantage of a natural experiment around statewide appendicitis admissions to improve the accuracy of participation rate estimates.We used Medicaid Analytic eXtract (MAX) for 2008-2010; and the American Community Survey for 2008-2010 from 43 states to calculate ABP, continuity ratio, duration, and participation based on the American Community Survey (ACS).In the validation study, median participation rate using ABP was 86% versus 87% for ACS-based participation estimates using logical edits and 84% without logical edits. Correlations between ABP and ACS with or without logical edits was 0.86 (P .0001). Using regression analysis, ABP alone was a significant predictor of ACS (P .0001) with or without logical edits, and adding duration and/or the continuity ratio did not significantly improve the model.Using the ABP rate derived from administrative claims (MAX) is a valid method to estimate statewide public insurance participation rates in children.

Background. Infiltrative hepatocellular carcinoma with macrovascular invasion is a relatively rare presentation and usually fatal disease. Methods. Both patients exceeded Milan and University of California-San Francisco (UCSF) criteria, and per Barcelona Clinic Liver Cancer group guidelines, they were enrolled in a prospective open-label radioembolization phase II trial that gave them optimized lobar doses of Yttrium-90 as solely the first-line therapy without concomitant or additional pharmacological or locoregional therapies. Results. Three months after radioembolization, the patients demonstrated no residual viable disease on surveillance imaging. The patients were then followed up with serial imaging for 2 years in 3-month intervals, without documenting recurrence or extrahepatic disease. Finally, both patients underwent transplantation and after more than 20 months of imaging surveillance, no locoregional or systemic recurrence have been observed. Conclusions. We present, to our knowledge, the first 2 reports of transplantation after successfully downstaging infiltrative disease with portal vein tumoral thrombosis, which traditionally poses as a relative contraindication for resection or transplantation.

Rationale and objectives To develop a human metastatic colorectal cancer (mCRC) model in a rabbit liver. Materials and methods Immunosuppression in 4 adult New Zealand White rabbits weighing 3.5 to 4.5 kg was induced with daily subcutaneous injection of 15 mg/kg Cyclosporine A (CsA). On day 3 open mini-laparotomy was performed and 0.2 ml (1.8x105 cells) suspension of HCT-116 and HT-29 human CRC cells were injected into the left and right medial lobe respectively. On day 10 the CsA dose was reduced to 10 mg/kg daily maintenance dose. Rabbits were weighed weekly, closely monitored for CsA side effects (weight loss, gingival hyperplasia and gut modification). Rabbits were sacrificed 5, 6, 7, and 8 weeks after cells injection. Liver tumors were collected for histopathology and immunohistochemical analysis. Results HT-29 Tumor growth was observed in 3 rabbits (75%). Tumors measured 3, 4 and 6 mm after 5, 6 and 8 weeks respectively. Microscopically, tumors contained hyperchromatic, pleomorphic cells that stained for monoclonal carcinoembryonic antigen (CEA), polyclonal CEA, cytokeratin 20, vascular markers (CD31, CD34), and vascular endothelial growth factor (VEGF) by immunohistochemistry, supporting involvement by the poorly differentiated HT-29 colorectal cancer cell line. No gross tumor growth or microscopic viability was observed from HCT-116 cell injection. CsA extra-hepatic manifestations included minimal gum hyperplasia and decrease in gut motility in 3 rabbits (75%), which was treated with Azithromycin 15 mg/kg and Cisapride 0.5 mg/kg every 12 hours, respectively. Conclusion We successfully developed a human metastatic colon cancer model in immunosuppressed rabbit liver using HT-29 cells.

Aim To evaluate whether radiofrequency ablation (RFA) or surgical resection (RES) has superior overall survival (OS) and disease-free survival (DFS) in patients with hepatocellular carcinoma and Child–Pugh class A liver cirrhosis. Materials and methods Meta-analysis was used to compare 1-, 3-, and 5-year OS and DFS between RFA and RES. Those studies meeting inclusion criteria and published prior to 1 June 2015 were included. The odds ratio (OR) was used as the treatment effect measure. A priori defined sensitivity analyses of study subgroups was performed. Results: Fifteen studies were included in this analysis. Subgroup analyses based on predetermined patient characteristics were performed to minimise bias. No difference in 1-year OS, 3-year OS, and 3-year DFS was found in analyses limited to studies where patients were equally eligible for both therapies. There was also not a significant difference in OS and DFS between RFA and RES when studies were limited to those with only solitary tumours or tumours Conclusion The data suggest the equivalence of RFA and RES in patients with solitary tumours

The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemo-embolization drug-eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for cancer targeting, doxorubicin (DOX), and 89yttrium (89Y) as nonradioactive surrogate for therapeutic (yttrium-90, luteti-um-177) and imaging (yttrium-86) radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2 tumor allografts were used. SW43-DOX-89Y was synthesized, loaded onto DEB (100 μL; 100–300 μm), and administered intra-arterially in six rabbits at increasing doses (0.2–1.0 mg/kg). As controls, two rabbits each received either doxorubicin IV (0.3 mg/kg) or no treatment. Consecutive serum analysis for safety and histopathological evaluation after sacrifice were performed. One-Way ANOVA incl. Bonferroni Post-Hoc test was performed to compare groups. Targeted compound synthesis, loading onto DEB, and intra-arterial administration were feasible and successful in all cases. Serum liver enzyme levels increased in a dose dependent manner within 24 h and normalized within 3 days for 0.2/0.6 mg/kg SW43-DOX-89Y loaded onto DEB. The two rabbits treated with 1 mg/kg SW43-DOX-89Y had to be euthanized after 3/24 h due to worsening general condition. Histopathological necrosis increased over time in a dose depended manner with 95–100% tumor necrosis 3–7 days post treatment (0.6 mg/kg). SW43-DOX-89Y loaded onto DEB can be formulated and safely administered at a concentration of 0.6 mg/kg. Loading with radioactive isotopes (e.g., 86yttrium/90yttrium/177lutetium) to synthesize the targeted radio-chemoembolization drug-eluting bead (TRCE-DEB) concept drug is feasible.

Apraxia is a cognitive disorder of skilled movements that characteristically affects the ability to imitate meaningless gestures, or to pantomime the use of tools. Despite substantial research, the neural underpinnings of imitation and pantomime have remained debated. An influential model states that higher motor functions are supported by different processing streams. A dorso-dorsal stream may mediate movements based on physical object properties, like reaching or grasping, whereas skilled tool use or pantomime rely on action representations stored within a ventro-dorsal stream. However, given variable results of past studies, the role of the two streams for imitation of meaningless gestures has remained uncertain, and the importance of the ventro-dorsal stream for pantomime of tool use has been questioned. To clarify the involvement of ventral and dorsal streams in imitation and pantomime, we performed voxel-based lesion-symptom mapping in a sample of 96 consecutive left-hemisphere stroke patients (mean age ± SD, 63.4 ± 14.8 years, 56 male). Patients were examined in the acute phase after ischaemic stroke (after a mean of 5.3, maximum 10 days) to avoid interference of brain reorganization with a reliable lesion-symptom mapping as best as possible. Patients were asked to imitate 20 meaningless hand and finger postures, and to pantomime the use of 14 common tools depicted as line drawings. Following the distinction between movement engrams and action semantics, pantomime errors were characterized as either movement or content errors, respectively. Whereas movement errors referred to incorrect spatio-temporal features of overall recognizable movements, content errors reflected an inability to associate tools with their prototypical actions. Both imitation and pantomime deficits were associated with lesions within the lateral occipitotemporal cortex, posterior inferior parietal lobule, posterior intraparietal sulcus and superior parietal lobule. However, the areas specifically related to the dorso-dorsal stream, i.e. posterior intraparietal sulcus and superior parietal lobule, were more strongly associated with imitation. Conversely, in contrast to imitation, pantomime deficits were associated with ventro-dorsal regions such as the supramarginal gyrus, as well as brain structures counted to the ventral stream, such as the extreme capsule. Ventral stream involvement was especially clear for content errors which were related to anterior temporal damage. However, movement errors were not consistently associated with a specific lesion location. In summary, our results indicate that imitation mainly relies on the dorso-dorsal stream for visuo-motor conversion and on-line movement control. Conversely, pantomime additionally requires ventro-dorsal and ventral streams for access to stored action engrams and retrieval of tool-action relationships.

A crucial component of regulating organismal homeostasis is maintaining proper cell number and eliminating damaged or potentially malignant cells. Apoptosis, or programed cell death, is the mechanism responsible for this equilibrium. The intrinsic apoptotic pathway is also especially important in the development and maintenance of the immune system. Apoptosis is essential for proper positive and negative selection during B- and T-cell development and for efficient contraction of expanded lymphocytes following an immune response. Tight regulation of the apoptotic pathway is critical, as excessive cell death can lead to immunodeficiency while apoptotic resistance can lead to aberrant lymphoproliferation and autoimmune disease. Dysregulation of cell death is implicated in a wide range of hematological malignancies, and targeting various components of the apoptotic machinery in these cases is an attractive chemotherapeutic strategy. A wide array of compounds has been developed with the purpose of reactivating the intrinsic apoptotic pathway. These compounds, termed BH3 mimetics are garnering considerable attention as they gain greater clinical oncologic significance. As their use expands, it will be imperative to understand the effects these compounds have on immune homeostasis. Uncovering their potential immunomodulatory activity may allow for administration of BH3 mimetics for direct tumor cell killing as well as novel therapies for a wide range of immune-based directives. This review will summarize the major proteins involved in the intrinsic apoptotic pathway and define their roles in normal immune development and disease. Clinical and preclinical BH3 mimetics are described within the context of what is currently known about their ability to affect immune function. Prospects for future antitumor immune amplification and immune modulation are then proposed.

Background: Using Pennsylvania Medicare claims from 1995 to 1996, the authors previously reported that anesthesia procedure length appears longer in blacks than whites. In a new study using a different and larger data set, the authors now examine whether body mass index (BMI), not available in Medicare claims, explains this difference. The authors also examine the relative contributions of surgical and anesthesia times. Methods: The Obesity and Surgical Outcomes Study of 47 hospitals throughout Illinois, New York, and Texas abstracted chart information including BMI on elder Medicare patients (779 blacks and 14,596 whites) undergoing hip and knee replacement and repair, colectomy, and thoracotomy between 2002 and 2006. The authors matched all black Medicare patients to comparable whites and compared procedure lengths. Results: Mean BMI in the black and white populations was 30.24 and 28.96 kg/m2, respectively (P < 0.0001). After matching on age, sex, procedure, comorbidities, hospital, and BMI, mean white BMI in the comparison group was 30.1 kg/m2 (P = 0.94). The typical matched pair difference (black–white) in anesthesia (induction to recovery room) procedure time was 7.0 min (P = 0.0019), of which 6 min reflected the surgical (cut-to-close) time difference (P = 0.0032). Within matched pairs, where the difference in procedure times was greater than 30 min between patients, blacks more commonly had longer procedure times (Odds = 1.39; P = 0.0008). Conclusions: Controlling for patient characteristics, BMI, and hospital, elder black Medicare patients experienced slightly but significantly longer procedure length than their closely matched white controls. Procedure length difference was almost completely due to surgery, not anesthesia.

The prostatitis syndrome is a frequent and complex disease. During the last 40 years the scientific perception has shifted between sometimes success and sometimes disappointment. Whereas acute prostatitis is most frequently considered an infectious disease, in only about 10% of cases with a chronic prostatitis syndrome can pathogens be identified. The bacterial spectrum is similar to that of complicated urinary tract infections with mainly Gram-negative pathogens. In some studies atypical pathogens, such as Chlamydia trachomatis and mycoplasmas, can be found in a considerable proportion. In most cases, however, a multifactorial aetiology is discussed. This has lead to a phenotyping directed multimodal treatment approach, considering the main symptoms. In prostatitis of microbial origin antibiotics, particulary fluorquinolones, are still the therapy of first choice. In the other cases multimodal treatment strategies are used considering evidence-based monotherapeutic studies. The evidence for multimodal combination treatment is still sparse.

Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively.