Large Tumor Burden Research Articles

Vasculogenic mimicry is a prognostic factor for postoperative survival in patients with glioblastoma

A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.

Performance Status Enhances the Selection of Treatment for Patients with Hepatocellular Carcinoma Within the Milan Criteria

Performance status (PS) is closely linked with survival in patients with hepatocellular carcinoma (HCC). We investigated its impact on treatment strategy for small HCC(s). A total of 360 and 362 HCC patients within the Milan criteria undergoing surgical resection (SR) and radiofrequency ablation (RFA), respectively, were prospectively enrolled. Patients were classified into PS 0 (n=558) and PS ≥1 (n=164) groups. Propensity score analysis was performed, and 168 and 35 matched pairs were selected from patients with PS 0 and ≥1, respectively. The SR group was younger and had a higher male-to-female ratio, higher prevalence of hepatitis B, lower prevalence of hepatitis C, better PS, better liver functional reserve, and larger tumor burden than the RFA group (all p<0.05). Among patients with PS 0, the SR group was consistently younger, less cirrhotic, and had larger tumor burden (all p<0.05). The long-term survival was comparable between SR and RFA group in patients with PS 0. After propensity score matching, SR provided significantly better long-term survival than RFA for patients within the Milan criteria classified as PS 0 (p=0.016); the Cox proportional hazards model showed consistent results. There was no significant difference of overall survival between the SR and RFA group in patients with PS ≥1 before or after propensity score matching (both p>0.05). For HCC patients within the Milan criteria and classified as PS 0, SR provides a better long-term survival compared with RFA. Performance status may enhance treatment selection and stratify the risk of survival in these patients.

Performance status in patients with hepatocellular carcinoma: Determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system

Performance status is included in the Barcelona Clinic Liver Cancer (BCLC) system for hepatocellular carcinoma (HCC). Few studies specifically evaluated the role of performance status in patients with HCC. This study investigated its distribution, determinants, and prognostic impact, aiming to improve the performance of the BCLC system. A total of 2,381 HCC patients were enrolled. Performance status was determined according to the Eastern Cooperative Oncology Group scale. The prognostic ability of the original and three modified BCLC systems in HCC patients was compared by the Akaike information criterion (AIC). There were 60, 17, 11, 8, and 4% of patients who were classified as performance status 0, 1, 2, 3, and 4, respectively. A worse performance status significantly correlated with age, alcoholism, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, and prothrombin time prolongation (all P < 0.001). Larger tumor burden, poorer residual liver function, more frequent vascular invasion, and diabetes mellitus were also observed in patients with worse performance status (all P < 0.001). Patients with poorer performance status more often received best supportive care (P < 0.001). In the Cox proportional hazards model, performance status was an independent prognostic predictor and the long-term survival tended to be worse in patients with progressively poor performance status (all P < 0.05). Reassigning patients with performance status 0 or 1 to stage B provided the lowest AIC among the four BCLC-based staging systems. Performance status is strongly associated with both tumoral and cirrhotic factors and accurately predicts long-term survival in HCC patients. Modification of the BCLC system based on performance status may further enhance its prognostic ability in patients with early to advanced cancer stage.

Neuroendocrine tumor presenting as metastatic carcinoid and later as insulinoma: a rare metamorphosis

We describe a very rare case of a neuroendocrine tumor, which initially presented as metastatic carcinoid with lesions in the liver and bones. Diagnosis was made by an elevated blood serotonin level and 24 hour urine 5HIAA. Liver biopsy confirmed the presence of a well differentiated neuroendocrine tumor (NET) staining positive for Chromogranin and negative for insulin. Two years after the initial diagnosis, the patient started to experience neuroglycopenic symptoms. Insulin and C-peptide levels were markedly elevated along with severe and recurrent hypoglycemic episodes. Due to extremely high insulin secretion from a large tumor burden, the patient’s clinical condition rapidly deteriorated in spite of maximal medical treatment. Shortly after the diagnosis of metastatic Insulinoma with unknown primary was made, the patient developed multiple organ system failure which limited invasive diagnostic techniques for localization. It appears that this patient’s neuroendocrine tumor had undergone a partial or complete change in its humoral function from a carcinoid or indolent neuroendcorine tumor to an Insulinoma or that the tumor started to co-secrete insulin along with serotonin. Less likely, he may have developed a separate tumor in the pancreas which was unable to be visualized by conventional imaging. Excess secretion of both Serotonin and Insulin from a single tumor is extremely rare and very few cases have been reported in the literature where a gastroenteopancreatic NET was found to secrete both insulin and serotonin.

Feasibility of Robotic Laparoendoscopic Single-Site Partial Nephrectomy for Renal Tumors >4 cm

BackgroundLaparoendoscopic single-site (LESS) urologic procedures have gained significant interest worldwide in an attempt to further reduce morbidity and minimize scarring associated with conventional laparoscopic surgery. The robotic technology has overcome some of the limitations of manual single-incision surgery relating to lack of triangulation, instrument collision, and surgical exposure. There are no data on robotic LESS partial nephrectomy (PN) for renal tumors >4cm. ObjectivesTo evaluate the feasibility of robotic LESS PN for renal tumors >4cm. Design, setting, and participantsData from 67 consecutive patients who underwent robotic LESS PN were collected between May 2009 to January 2011. Outcome measurements and statistical analysisPatients were stratified into two groups: 20 patients with renal tumors >4cm (group 1) and 47 patients with renal tumors ≤4cm (group 2). Perioperative data were recorded and comparisons between the two groups were analyzed using the Mann-Whitney U test for continuous variables and Fisher exact test for categorical variables. Results and limitationsNo statistically significant differences were found between the two groups in demographic information, operative complications, pathologic characteristics, mean decline in estimated glomerular filtration rate, estimated blood loss, operative times, conversion rate, or positive surgical margins. However, group 1 had a higher mean nephrometry score (p<0.01), longer warm ischemia time (p=0.007), and longer length of stay (p=0.046). Its retrospective design and being conducted at a single center were the main limitations of this study. ConclusionsThis study demonstrated the feasibility and safety of robotic LESS PN for tumors >4cm. Patients with tumors >4cm had a statistically significant, higher mean nephrometry score, longer warm ischemia time, and longer length of stay, but there was no increased risk of adverse outcomes. A long-term study is needed to confirm the durable renal preservation and oncologic outcomes for patients with larger tumor burden.

Discrimination of an Early Unfavorable Risk Group Has Significant Impact On Treatment Outcome in Early-Stage Hodgkin Lymphoma: An Analysis of International Staging Definitions and Risk Factors

AbstractAbstract 54 Background:In early-stage Hodgkin Lymphoma (HL), treatment according to the early favorable or unfavorable subgroup is mostly guided by a staging system including the presence of certain risk factors. However, risk factors have grown historically, they differ between the various study groups worldwide, and some experts do not recognize the necessity for an early unfavorable group at all. To shed more light on this ongoing controversy, we analyzed the impact of risk factors used in different international staging systems on treatment outcome in early-stage HL. Methods:In 1,173 qualified early-stage patients that were treated homogenously with 4 cycles of ABVD followed by involved-field radiotherapy within the GHSG trials HD10 and HD11, the impact of three international staging systems (GHSG, EORTC, NCCN) in discriminating early favorable and unfavorable treatment groups for progression free survival (PFS) and overall survival (OS) was assessed. Risk factors from the three definitions were tested for sensitivity and specificity for HL-related failure within 2.5 years, including only patients observed for at least 2.5 years (N=1,107). Univariate analyses of the respective single risk factors and of other known candidate risk factors as well as multivariate analyses were carried out using logistic regression, in order to evaluate the relevance and interaction of single factors. Results:Median observation time was 80 months. Overall, 8% of early-stage patients had HL-related failure within 2.5 years. All three staging systems selected an unfavorable “high risk” group out of early-stage patients of comparable size (55%, 54%, and 56% of patients with the GHSG, EORTC, and NCCN system, respectively) with significant impact on PFS and OS. For example, with the GHSG system, PFS was 95.8% and 86.4% for the early favorable and unfavorable group at five years, with a significant difference of −9.4% (Figure 1).Sensitivity for HL-related failure was high for all systems (84%, 79%, and 83%, respectively); however, there were high rates of false-positive results (1-specifity 54%, 53%, and 55%, respectively). Univariately, most analyzed factors had a relevant impact on the event rate. In multivariate analyses, the GHSG-system had 4/4, the EORTC-system 2/4, and the NCCN-system 3/5 independently significant risk factors. In general, models of high sensitivity included risk factors indicating large tumor burden and high tumor activity. Most risk factors for tumor-specific endpoints such as HL-related failure and PFS were also predictive for OS. Conclusions:For the first time, the relevance of selecting an unfavorable risk group out of early-stage patients was proven in a large cohort of HL patients without treatment bias, with significant impact on PFS and OS. Thus, discriminating early favorable and unfavorable patients with HL by the identified risk factors is important in the modern combined modality treatment era and strongly recommended. [Display omitted] Disclosures:Engert:Millenium The Takeda Oncology Company: Honoraria. Borchmann:Millenium The Takeda Oncology Company: Research Funding; Takeda Pharma GmbH: Travel Grants, Travel Grants Other.

Impact of the Conditioning Chemotherapy On Outcomes in Adoptive T Cell Therapy: Results From a Phase I Clinical Trial of Autologous CD19-Targeted T Cells for Patients with Relapsed CLL

AbstractAbstract 1797Patient T cells may be genetically modified to express chimeric antigen receptors (CARs) targeted to antigens expressed on tumor cells. We have previously reported initial results from a phase I clinical trial treating patients with chemotherapy refractory chronic lymphocytic leukemia (CLL) with autologous T cells modified to express the 19–28z CAR targeted to the CD19 antigen expressed on most B cell malignancies (Brentjens RJ, Rivière I et al., Blood, 2011;118(18):4817-28). In the previous reported cohorts of 8 patients, CAR-modified T cells were infused in the setting of rapidly progressive and chemotherapy refractory disease. Although prior conditioning therapy with cyclophosphamide enhanced in vivo persistence of the modified T cells, all patients had cyclophosphamide-resistant disease and none experienced objective remissions or significant hematologic recovery. We hypothesized that suboptimal clinical response observed in the study was because of a large tumor burden at the time of T cell infusion and refractoriness to conditioning therapy. On the basis of these findings, we have modified the protocol to allow prior cytoreductive therapy and conditioning with chemotherapeutic agents based on predicted chemosensitivity.Since these protocol modifications, two patients have been treated. Both had relapsed disease with unfavorable disease phenotype following previous treatments with various chemotherapy and biologic regimens. Of the two patients treated to date, one achieved partial remission (PR) and the other attained minimal residual disease (MRD)-negative complete remission (CR) according to standard international criteria. The first patient experienced reduction in peripheral lymphocytosis and obtained stable disease with persistent anemia and thrombocytopenia after two cycles of bendamustine and rituximab (BR). Following the bendamustine conditioning and modified T cell infusion, PR was achieved with complete hematologic recovery, lasting for more than 8 months at the time of this report. The second patient achieved PR following two cycles of BR and subsequently attained MRD-negative CR with concomitant development of B cell aplasia after receiving the bendamustine conditioning and CAR-modified T cells. At the time of this report, the response has been sustained for more than 5 months. Notably, this patient has long-term persistence of the CAR-modified T cells, detected at 12 weeks following the T cell infusion. No significant toxicities were observed in the two patients, except for fevers lasting 3–4 days and transient grade 2 hypoxia. While the number of treated patients on the revised protocol is too small to draw a definitive conclusion, our findings of a significant improvement in the degree and depth of response with the bendamustine conditioning compared to our previous cohorts of cyclophosphamide-refractory CLL who received cyclophosphamide as their conditioning suggest a potentially greater effect of conditioning regimens through tumor burden reduction than the induction of a supportive cytokine response or lymphocyte depletion. In light of these initial observations, the role of the conditioning chemotherapy regimen given prior to adoptive T cell therapy needs to be carefully evaluated since not all regimens may ultimately be equally effective with respect to clinical outcomes. Disclosures:Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Gastric Adenocarcinoma with Acute Tumor Lysis Syndrome: An Unusual Association

Purpose: Acute Tumor Lysis Syndrome (ATLS) is the constellation of symptoms, signs and abnormal laboratory findings caused by disintegration of tumor cells and subsequent release of their content in to blood. ATLS is primarily seen in cancers of blood but it has also been noted in solid tumors. Here we describe a very rare case of ATLS in a patient with gastric adenocarcinoma. A 51-year-old man came to our emergency room with complaint of generalized weakness, severe nausea and vomiting for 2 days. He also complained of decreased urination. He was diagnosed with infiltrating adenocarcinoma of stomach about 9 months ago. Since then, patient was receiving chemotherapy with cisplatin, docetaxel and 5-fluorouracil. His last chemotherapy was about 2 months before this admission. Physical examination was reveled mild epigastric tenderness and sluggish bowel sounds. Pertinent laboratory findings are summarized in the table. Gastric outlet obstruction was ruled out by history and physical examination. These laboratory findings were highly suggestive of ATLS. Treatment with aggressive intravenous hydration and allopurinol was started. A CT scan of abdomen revealed multiple enlarged mesenteric lymph nodes, gastric and colonic wall thickening, and multiple metastatic lesions in liver and adrenals which were suggestive large tumor burden. Patient was started on renal replacement therapy and after 2 hemodialysis sessions, patient's renal functions began to improve. Later patient responded well to symptomatic treatment with improvement in her general condition and complete resolution of electrolyte imbalance in 8 days. Association of gastric carcinoma and ATLS is very rare. This case illustrates the need for increased vigilance for ATLS even in solid tumors. An accurate diagnosis of ATLS is very essential in solid tumors as mortality in these patients is about 35% (1). We suggest that ATLS should be suspected in patients with acute renal failure accompanied by hyperuricemia.Table: Laboratory findings at the time of admission

A dedicated automated injection system for dynamic contrast‐enhanced MRI experiments in mice

To develop a reproducible small-animal dynamic contrast-enhanced (DCE) MRI set-up for mice through which volumes <100 μL can be accurately and safely injected and to test this set-up by means of DCE measurements in resting muscle and tumor tissue. The contrast agent (CA) injection system comprised 2 MR-compatible syringe pumps placed 50 cm from the 7T magnet bore where the fringe field is approximately 40 mT. Microbore tubing and T-connector, close to the injection site, minimized dead volume (<10 μL). For DCE-MRI measurements in 8 CB-17 SCID mice with 1500-2500 mm(3) large orthotopic neuroblastoma, a bolus of 10-fold-diluted Gd-DTPA CA solution (0.1 mmol/kg) was delivered (5 μL/s), followed by a 50-μL saline flush. Retro-orbital injections were given instead of tail vein injections, because the peripheral vasculature was reduced because of large tumor burden. The CA injection was successful in 19 of 24 experiments. Optical assessment showed minimal dispersion of ink-colored CA bolus. Mean (± SD) pharmacokinetic parameters retrieved from DCE-MRI examinations in resting muscle (K(trans) = 0.038 ± 0.025 min(-1), k(ep) = 0.66 ± 0.48 min(-1), v(e) = 0.060 ± 0.014, v(p) = 0.033 ± 0.021) and tumor (K(trans) = 0.082 ± 0.071 min(-1), k(ep) = 0.82 ± 0.80 min(-1), v(e) = 0.121 ± 0.075, v(p) = 0.093 ± 0.051) agreed with those reported previously. We successfully designed and implemented a DCE-MRI set-up system with short injection lines and low dead volume. The system can be used at any field strength with the syringe pumps placed at a sufficiently low fringe field (<40 mT).

Chemoembolization and Radioembolization for Metastatic Disease to the Liver: Available Data and Future Studies

Hepatic metastatic disease includes tumors from colorectal, neuroendocrine, breast, melanocytes, kidney, and other primary sites. Tumor characteristic, liver function, and performance status are factors that need to be considered while deciding on treatment. Surgery offers the most optimal therapeutic option for such patients. However, due to the diffuse nature of disease and large tumor burden, a majority of the patients are not operable. Moreover, because the morbidity and mortality is associated with hepatic metastatic disease, it is intuitive to investigate and develop treatment options that target the tumor locally, thereby minimizing systemic toxicities. Transarterial locoregional therapies, such as chemoembolization and radioembolization, have been widely investigated during the past decade for the treatment of hepatic metastatic disease and have generated encouraging outcomes in term of survival, response, and quality of life. Moreover, these options are applicable in many clinical scenarios, because they are less limited by tumor characteristics. Currently, a large number of trials are investigating the combination of locoregional and systemic therapies, and the results are expected to benefit the treating physicians and patients alike.

Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) refers to the constellation of deranged metabolic state, characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and/or azotemia, secondary to rapid breakdown of tumor cells. It is a life threatening emergency that typically follows administration of chemotherapy or may be spontaneous. Malignancies which have a large tumor burden, rapid turnover, as well as speedy breakdown following chemotherapy are susceptible. Acute lymphoblastic leukemia and non-Hodgkins lymphoma (particularly Burkitt's lymphoma) are typically predisposed. TLS is best managed by early anticipation and preventive measures than the complicated task of treating an established TLS. Vigorous intravenous hydration is the cornerstone of prevention as well as treatment. Rasburicase has revolutionized the management. It is available in India for past 1 1/2 y, although the cost is a limiting factor. Children with acute leukemia in developing countries may reach health facility late, with severe anemia and hyperleukocytosis. Exchange transfusion may have to be restored to in such patients to simultaneously correct anemia and hyperleukocytosis and enable safe administration of fluids. Dialysis may be required when the metabolic 'trash' overwhelms the renal excretion, resulting in renal failure. Chemotherapeutic drugs are often administered in a phased manner in susceptible patients, in an attempt to prevent precipitous lysis of tumor cells. Presentation and management of TLS in relevance to the pediatric emergency room is outlined.

P-0081 Patients Undergoing Transrterial Chemoembolisation (TACE) at a UK Centre: the Effect of ‘High-Risk’ Criteria on Response to Treatment and Survival

IntroductionHepatocellular is the third most common cause of cancer deaths worldwide and its incidence is increasing in the western world. In the treatment of non-resectable hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) has been shown to give a survival benefit over supportive therapy alone. However most trials have excluded patients deemed to be ‘high risk’ due to factors such as age, poor liver function and large tumour burden. Historically these criteria have then been used to select patients for treatment with TACE. In this centre it has been practice to treat some of these patients deemed to be a high risk, and this study reports our results, in particular the safety of using TACE in a higher risk population. Methods105 patients with a histological diagnosis of HCC had their first treatment with TACE at our centre between 2003 and 2008. We collected data on age (>70) liver function and signs of decompensation (bilirubin over 40, albumin under 30, presence of ascites), and tumour burden (calculated using both maximum tumour size and number of lesions). Treatment response was assessed using tumour size on CT scan. The data was collected over a 5 year period from 2003 to 2008, and the final follow up point was August 2009. The primary endpoint was overall survival and the secondary endpoint was treatment response. We conducted univariate analysis of the relationship between both endpoints and known risk factors, as previously specified. Survival analyses were performed using the Kaplan-Meier method, and conducted using the statistical software ‘R’. The log-rank test was used to assess statistical significance of survival data, and a p value of <0.05 was considered significant, with all tests being two-sided. ResultsThe median age of participants was 64 and median bilirubin was 16 umol/L. Median overall survival was 8.9 months. Overall survival and response to treatment (measured by CT scan) were independent of risk factors (age, bilirubin, albumin, ascites and tumour burden). Response to treatment on CT scan (good vs. partial/poor/progressive disease) was associated with improved overall survival (p=0.004); the group with a ‘good’ CT response had a median survival of 15.25 months, while all other response categories had a median survival of 7.43 months. ConclusionIn our cohort of patients, those that met ‘high risk’ criteria appear not to have worse outcomes, in terms of both CT response and overall survival, than ‘normal risk’ patients. A larger study which also includes patients having subsequent procedures is needed to further investigate this, and is currently in progress. In this study, CT response has been shown to have a significant association with survival, and suggests that maximising response in terms of tumour shrinkage may have a beneficial effect on mortality.

Cardiac, Hemorrhagic, and Coagulopathic Oncologic Emergencies

Cardiac, Hemorrhagic, and Coagulopathic Oncologic Emergencies

Abstract 5105: Genetic alterations of the metastatic lesions in ovarian carcinoma

Abstract Background: Ovarian cancer is the most deadly gynecological cancer. The high rate of mortality is due to the large tumor burden with extensive metastatic lesion of the abdominal cavity. There are few studies on genetic alterations and their consequences in peritoneal metastatic tumors when compared to their matched ovarian primary tumors. Our hypothesis is that differences between the metastatic and primary lesions might be the cause of residual disease and, most importantly may have a role in post-chemotherapeutic recurrences. Methods: We conducted integrated genomics analysis on matched primary and metastatic tumors from 9 patients. In the papers presented here we analyze genome-wide Copy Number Variations (CNVs) using SNP Arrays targeting peritoneal metastasis differences, Gene expression differences using Microarrays also targeting peritoneal metastasis differences, and for some patients, Single Nucleotide Polymorphisms (SNPs) in genes through Exome sequencing. Results: Here we show that CNVs vary significantly between primary and metastatic tumors and include genes that have been considered potential chemotherapeutic targets based on primary tumor only data. Gene expression differences, while minor, showed highly statistically significant enrichment of genes in ovarian cancer critical pathways. In agreement with findings in other cancers, exome sequencing data revealed very few SNP differences of which most metastasis enriched SNPs were present at very low levels in the primary tumor. The results presented here should allow better design of therapies to target residual ovarian cancer disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5105. doi:1538-7445.AM2012-5105

Prevention of Tumor Lysis Syndrome in an Outpatient Setting

The prevention and identification of hyperuricemia are critical components in the management of tumor lysis syndrome (TLS), which is common in acute leukemias, large cell lymphomas, bulky tumors, large tumor burdens, and other cancers with high proliferation rates. Such cancers are very receptive to cytotoxic therapy because of increased mitotic rates. Lysis of their tumor cells results in metabolic abnormalities because of the release of their intracellular products. TLS is an oncologic emergency that could lead to renal failure and death; therefore, early identification of high-risk patients is vital for successful treatment outcomes. Treatment modalities include the use of allopurinol and hydration while implementing evidence-based practices for the prevention of TLS in the outpatient clinical center.

Oncologic Emergencies

Oncologic Emergencies

Gender Bias in Skin Cancer: Role of Catalase Revealed

Sullivan et al. describe their finding that lower skin catalase activity in male as compared with female mice may be responsible for the increased skin carcinogenesis observed in UVB radiation-exposed male mice. This adds to the growing literature that points toward a gender bias in the pathogenesis of skin cancer. Delineating the events between UV exposure and carcinogenesis in relation to skin's antioxidant activity will provide insight into disease progression, prognosis, and responses to therapy. If substantiated with further studies in humans, this information may aid in designing gender-specific preventive measures aimed at reversing immune suppression through targeting the altered redox status in UV-exposed individuals.

IL‐10 Contributes to the Suppressive Function of Tumour‐Associated Myeloid Cells and Enhances Myeloid Cell Accumulation in Tumours

Studies have revealed that tumour-associated myeloid cells (TAMC) are one of the major sources of IL-10 in tumour-bearing mice. However, the significance of TAMC-derived IL-10 in tumour immunity is poorly understood. Here, we show that IL-10 blockade or IL-10 deficiency reduces the capacity of TAMC in suppressing the proliferation of P1A-specific CD8 T cells. In the spleen, IL-10-deficient and wild-type (WT) mice bearing large tumour burdens have similar TAMC populations. The tumours from IL-10-deficient mice, however, have reduced numbers of TAMC compared with tumours from their WT counterparts. IL-10⁻/⁻ RAG-2⁻/⁻ mice also had reduced numbers of TAMC compared with tumours from IL-10⁺/⁺ RAG-2⁻/⁻ mice; therefore, the reduction in TAMC in IL-10-deficient tumours was not because of adaptive immune response in tumours. Adoptively transferred tumour antigen-specific CD8 T cells expanded more efficiently within tumours in IL-10⁻/⁻ RAG-2⁻/⁻ mice than in tumours from IL-10⁺/⁺ RAG-2⁻/⁻ mice. Cytotoxic T lymphocyte adoptive transfer therapy prevented tumour evasion in IL-10⁻/⁻ RAG-2⁻/⁻ mice more efficiently than in IL-10⁺/⁺ RAG-2⁻/⁻ mice. Thus, IL-10 enhances the accumulation of myeloid cells in tumours, and TAMC-derived IL-10 suppresses the activation and expansion of tumour antigen-specific T cells.

Hepatic Epithelioid Hemangioendothelioma: Is Hepatitis C Viral Infection an Etiologic Factor?

Introduction: Hepatic Epithelioid Hemangioendothelioma (HEHE) is an infrequent vascular tumor of endothelial cell origin. There is no clearly established risk factor for its development. It behaves as a lowgrade malignant vascular tumor with slow progressive phenotype. Liver transplantation should be considered the first-line of therapy given the large tumor burden and favorable long-term outcome. Case: We report a 48-year-old Caucasian female who complained of abdominal pain and weight loss. She has a history of hepatitis C viral infection that was treated with interferon and ribavirin and subsequently became RNA-negative on repeated follow-up testing pre-transplant. Her work-up revealed multiple confluent infiltrating bilobar liver masses diagnosed as HEHE (biopsy-proven) and cirrhosis. She underwent a successful liver transplant and is tumor-free without evidence of recurrent HCV infection 22 months post-transplant. Conclusion: Liver transplant provides remarkable long-term survival for HEHE/HCV cirrhotic patient considering the large tumor burden and lack of evidence of recurrent tumor and/or HCV infection.Figure: [CT of the Abdomen]Figure: [Photomicrograph of HEHE in Hep C cirrhosis]

Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy.

Ascites may develop in patients with hepatocellular carcinoma (HCC) with coexisting liver cirrhosis. Few studies had specifically evaluated the role of ascites in HCC. This study investigated its prevalence, associated factors, prognostic impact, and staging strategy in a large HCC patient cohort. A total of 2,203 HCC patients were analyzed. The grading of ascites was according to the European Association for the Study of Liver. The prognostic ability of the Cancer of the liver Italian Program (CLIP), Barcelona Clinic Liver Cancer, Japan Integrated Scoring system, and Taipei Integrated Scoring system in HCC patients with ascites was compared using the Akaike information criterion (AIC). Ascites was present in 498 (23%) patients at diagnosis. Grades 1, 2, and 3 ascites were found in 13, 5, and 5% of the patients, respectively. The severity of ascites significantly correlated with hyperbilirubinemia, hypoalbuminemia, hyponatremia, prothrombin time (PT) prolongation, and renal insufficiency (all p<0.001). Large tumor burden and more frequent vascular invasion were often observed in patients with more severe ascites (both p<0.001). In the Cox proportional hazard model, ascites was identified as an independent prognostic predictor with 80-94% increased risk of mortality (p<0.001). Among HCC patients with ascites, the CLIP system had the lowest AIC value. Ascites is often seen in HCC patients and is associated with both tumoral and cirrhosis factors and decreased long-term survival. The CLIP staging system is a more feasible prognostic model for HCC patients with ascites. The optimal treatment strategy for these patients remains to be investigated.