Indolent Forms Research Articles

Rare Presentation of Nasal Mucormycosis.

Nasal mucormycosis is a rare opportunistic infection of the nasal cavity and paranasal sinuses caused by saprophytic fungi which can rapidly lead to death. It usually affects individuals with poorly controlled diabetes mellitus (especially those with ketoacidosis), solid malignancies, iron overload, extensive burns, in patients undergoing treatment with glucocorticosteroid agents and in patients with neutropenia related to haematologic malignancies. Presentation of nasal mucormycosis is always very extensive, but in some patients, it can present in chronic indolent form also. Here, we present a case of 65-year old male with a history of exposed nasal bone after nasal trauma 8months back. His diabetes was in control with oral hypoglycaemics. Debridement and local flap closure was done. Culture showed the growth of Lichtheimia corymbifera and in HPE, the fungus was seen branching at right angles. So, we conclude that the possibility of nasal mucormycosis should always be borne in mind so that early and effective treatment can be initiated on time to decrease the morbidity and mortality.

Systemic rituximab for the treatment of the indolent forms of primary cutaneous B-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry

Systemic rituximab for the treatment of the indolent forms of primary cutaneous B-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry

An analysis of waiting times in patients with thyroid cancer

BackgroundScottish guidelines suggest that following a referral with a suspicion of cancer, patients should have a diagnosis within 31 days and commence treatment within 62 days. Thyroid cancer is not included in these targets. This study investigates the timelines of management of thyroid cancer, looking at factors that affect time to treatment and diagnosis in our network. MethodsThe study was a review of a prospectively held database of patients discussed at MDT meetings between January 2016 and September 2018. Of the 153 potentially suitable thyroid cancer patients in NHS Lothian, 62 were eligible for inclusion in the study, having been referred to secondary care by their general practitioner (GP) and diagnosed with differentiated thyroid cancer (DTC). ResultsAt present only 10% and 16% of patients would meet the 62-day treatment and 31-day diagnosis targets respectively. The time to both diagnosis (p=<0.0005) and treatment (p = 0.022) is significantly improved in patients that have a diagnostic biopsy or FNA (Thy5) or a highly suggestive FNA (Thy4), compared with those that do not. There is no significant effect of GP referral type on time to diagnosis or management of thyroid cancer. With a median follow-up of 33 weeks, only one patient had died. ConclusionsThyroid cancer does not fit the classical cancer targets well. It is a relatively indolent form of cancer, with many cases diagnosed either incidentally or after undergoing treatment. It is important to balance the resource implications of providing rapid treatment with the psychological effects of the diagnosis.

Immunodeficiency-Related Lymphoid Proliferations: New Insights With Relevance to Practice.

Our understanding of risk factors and mechanisms underlying immunosuppression-related lymphoproliferative disorders continues to evolve. An increasing number of patients are living with altered immune status due to HIV, solid organ or hematopoietic stem cell transplant, treatment of autoimmune disease, or advanced age. This review covers advances in understanding, emerging trends, and revisions to diagnostic guidelines. The tumor microenvironment, including interactions between the host immune system and tumor cells, is of increasing interest in the setting of immunosuppression. While some forms of lymphoproliferative disease are associated with unique risk factors, common mechanisms are also emerging. Indolent forms, such as Epstein-Barr virus positive mucocutaneous ulcer, are important to recognize. As methods to modulate the immune system evolve, more data are needed to understand and minimize lymphoproliferative disease risk. A better understanding of individual risk factors and common mechanisms underlying immunosuppression-related lymphoproliferations will ultimately enable improved prevention and treatment of these disorders.

Abstract B101: Race is associated with receipt of guideline-concordant treatment among women with endometrioid endometrial cancer: A National Cancer Database study

Abstract Background: Among women with endometrial cancer (EC), African American women have a 93% higher likelihood of dying compared to white women. This disparity is driven, in part, by the more frequent diagnosis of late stage and non-endometrioid tumors among African American women. However, even among women diagnosed with indolent forms of EC, including early stage or endometrioid histology, African American women are more likely to die. Differential receipt of guideline-based treatment might underlie worse survival among African American women. EC treatment guidelines are based on several randomized clinical trials, which provide consistently strong evidence on treatment regimens for women with early stage, endometrioid EC. Using the National Cancer Database (NCDB), we assessed the hypothesis that among women with less aggressive forms of EC, minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we examined whether a survival benefit exists for EC patients who receive guideline-concordant treatment. Methods: We defined receipt of guideline-concordant EC treatment using the National Comprehensive Cancer Network (NCCN) guidelines, which stratify treatment decisions based on tumor characteristics. We used multivariable logistic regression models to compute odds ratios (OR) and 95% confidence intervals (CIs) for the association between race, categorized as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and Asian/Pacific Islander (API), and receipt of guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios (HRs) and 95% CIs for relationships between receipt of guideline-concordant treatment and overall survival. Results: A total of 89,976 women diagnosed with stages 1A through 3C, endometrioid EC between the years 2004 and 2014 were included, among whom, 71.5% (n=64,316) received treatment in line with NCCN guidelines. In multivariable adjusted models, NHB (OR=0.91, 95% CI=0.86 – 0.97) and Hispanic women (OR=0.93, 95% CI=0.86 – 0.99) had lower odds of receiving concordant treatment compared to NHW women. Receipt of guideline-concordant treatment did not differ between API and NHW women. During the study period, NHB women had the highest proportion of deaths (28.7%) followed by NHW (22.0%), Hispanic (16.0%), and API women (14.2%). In models adjusted for patient, clinical, and facility characteristics, women not receiving guideline-concordant care were 8% more likely to die (HR=1.08, 95% CI=1.05 – 1.12). Conclusions: Receipt of guideline-concordant treatment differed according to race, with minorities less likely than NHW women to receive guideline-directed therapy. Further, in the overall study population, overall survival was better among those receiving guideline-concordant care. Future studies should evaluate reasons underlying disparate EC treatment. Citation Format: Mara K. Kaspers, Elyse Reamer, Jhalak Dholakia, Ritu Salani, Ashley S. Felix. Race is associated with receipt of guideline-concordant treatment among women with endometrioid endometrial cancer: A National Cancer Database study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B101.

Ultra-Sensitive Detection of Prostate Cancer Biomarkers Using Electron Transfer Rate Enhancement

By 2019, one in every 5 men diagnosed with cancer carry prostate malignancy. Despite being the most frequent form of cancer among American men, prostate cancer still lacks proper diagnostic tools to identify indolent and aggressive forms. Drawbacks in current screening methods such as Prostate Specific Antigen (PSA) test and Digital Rectal Exam have led to over diagnosis and over treatment of prostate cancer, adversely affecting the patient’s quality of life. Herein, we report a simple, inexpensive electrochemical immunoarray for multiplexed detection of a panel of prostate cancer biomarkers, Prostate Specific Antigen (PSA), Vascular Endothelial Growth Factor-D (VEGF-D), Gene fusion proteins ETS related gene(ERG) and Insulin-like Growth Factor-1(IGF-1) that we have verified as providing a more accurate diagnosis of the type of prostate cancer than PSA test alone. The sensor features an array of eight screen printed carbon electrodes (diameter ~700 μm) coated with a layer of 5 nm Au nanoparticles and immobilized with antibodies to capture analytes. After sample introduction and analyte binding, a mixture of poly-horseradish peroxidase (HRP)-labeled detection antibodies are delivered, followed by hydroquinone (HQ) mediator to facilitate amperometric detection. Dual amplification by H2O2-driven oxidation of each of the 400 HRPs iron hemes in poly-HRP labels to Fe=O for amperometric reduction using electron transfer catalysis by HQ along with careful optimization of antibody levels enabled ultra-sensitive detection of the biomarkers with limits of detection (LOD) at ag mL-1 levels with up to 6 log-decades dynamic range. Immunoarray analyses of sera from patients who have undergone prostatectomy and may have very low levels of these biomarkers was explored as a possible test for recurrence of prostate cancer after surgery.

Gastrointestinal Symptoms and Coronavirus Disease 2019: A Case-Control Study From the United States

Gastrointestinal Symptoms and Coronavirus Disease 2019: A Case-Control Study From the United States

Patterns of Care and Outcomes in Verrucous Carcinoma of the Larynx Treated in the Modern Era

Verrucous carcinoma is an uncommon, relatively indolent form of laryngeal squamous cell carcinoma. Historically, surgery has been the favored approach, due to concerns of potential anaplastic transformation and secondary metastasis theoretically associated with radiotherapy. To examine national trends in the treatment of verrucous carcinoma of the larynx, we utilized the National Cancer Database (NCDB).

Skeletal Muscle Metastasis in Papillary Thyroid Microcarcinoma Evaluated by F18-FDG PET/CT.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy and is characterized by slow growth and an indolent biological behavior. Papillary thyroid microcarcinoma is the PTC with the maximum size of the tumor <1cm, considered the most indolent form of thyroid cancer. PTC is usually metastasizes in cervical lymph nodes, lungs and bones and, less commonly, in brain or liver. Skeletal muscle metastases from PTC are extremely rare, a retrospective review of the literature revealed only 13 case reports. Among them, six cases are solitary skeletal muscle metastases, and seven are multiple metastases, most of them being associated with lung lesions. It seems that PTC is prone to metastasizing to the erector spinae and thigh muscles groups with unique cases located in trapezoid, biceps, deltoid, gastrocnemius and rectus abdominis muscles. Although extremely rare, one must bear in mind the fact that muscle metastasis from PTC is possible, and that is the reason we would like to discuss the existing clinical cases and to add a unique case of solitary skeletal muscle metastasis from papillary microcarcinoma.

Recent advances in the understanding and therapeutic management of mastocytosis.

Mastocytosis is a rare disease due to the abnormal accumulation of mast cells in various tissues. Its clinical presentation is heterogeneous depending on mast cell infiltration and mediators release. In some cases, it is associated with hematological malignancies. Prognosis varies from very good with a life expectancy similar to the general population in indolent forms of the disease to a survival time of just a few months in mast cell leukemia. Although in most cases a somatic KIT D816V mutation is found in tumor mast cells, the physiopathology of the disease is not yet fully understood. Additional germline and somatic mutations may explain this heterogeneity. Treatments aim at blocking effect of mast cell mediators, reducing mast cell activation and tumor burden. New drugs mainly directed against the tyrosine kinase activity of KIT have dramatically changed the quality of life and prognosis of mast cell diseases. Present and future therapeutic strategies are discussed in this review.

Is macular lymphocytic arteritis limited to the skin? Long-term follow-up of seven patients

BackgroundMacular lymphocytic arteritis most commonly presents as hyperpigmented macules on the lower limbs. The pathogenesis of this disease is still unclear and there is an ongoing debate regarding whether it represents a new form of cutaneous vasculitis or an indolent form of cutaneous polyarteritis nodosa. ObjectiveTo describe clinical, histopathological, and laboratory findings of patients with the diagnosis of macular lymphocytic arteritis. MethodsA retrospective search was conducted by reviewing cases followed at the Vasculitis Clinic of the Dermatology Department, School of Medicine, University of São Paulo, between 2005 and 2017. Seven patients were included. ResultsAll cases were female, aged 9–46 years, and had hyperpigmented macules mainly on the legs. Three patients reported symptoms. Skin biopsies evidencing a predominantly lymphocytic infiltrate affecting arterioles at the dermal subcutaneous junction were found, as well as a typical luminal fibrin ring. None of the patients developed necrotic ulcers, neurological damage, or systemic manifestations. The follow-up ranged from 18 to 151 months, with a mean duration of 79 months. Study limitationsThis study is subject to a number of limitations: small sample of patients, besides having a retrospective and uncontrolled study design. ConclusionsTo the best of the authors’ knowledge, this series presents the longest duration of follow-up reported to date. During this period, none of the patients showed resolution of the lesions despite treatment, nor did any progress to systemic vasculitis. Similarities between clinical and skin biopsy findings support the hypothesis that macular lymphocytic arteritis is a benign, incomplete, and less aggressive form of cutaneous polyarteritis nodosa.

Efficacy and Safety of Ibrutinib in Combination with Rituximab As Frontline Treatment for Indolent Clinical Forms of Mantle Cell Lymphoma (MCL): Preliminary Results of Geltamo IMCL-2015 Phase II Trial

Background: MCL is a heterogeneous disease and the existence of indolent clinical forms is increasingly recognized although their biological ground is not fully elucidated. The aim of this study was to propose a frontline tailored treatment for indolent clinical forms with a chemo-free regimen, ibrutinib in combination with rituximab. In addition, an extensive genomic study was associated to gain biological insight into these clinical forms. Methods: This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 14 Spanish GELTAMO sites (NCT02682641). Centralized histology, PET-CT review as well as minimal residual disease (MRD) studies (qPCR and NGS in peripheral blood [PB] and bone marrow [BM]) and biological studies are conducted. A total of 50 previously untreated MCL patients with indolent clinical forms are planned to be recruited, defined by the following criteria: no symptoms attributable to MCL, ECOG 0-1, stable disease without therapy need at least for 3 months, non-blastoid variants, Ki-67 &amp;lt;30% and largest tumor diameter ≤3 cm. Both leukemic non-nodal and nodal forms were acceptable. Patients received ibrutinib 560 mg daily and a total of 8 doses of Rituximab 375 mg/m2 (4 weekly doses during first 28-day cycle, followed by day 1 of cycles 3, 5, 7 and 9). Ibrutinib could be discontinued after 2 years of treatment in case of negative MRD for at least 6 months. The primary endpoint was the rate of complete remission (CR) achieved after 12 cycles according to the Lugano criteria (Cheson, 2014). Results: Forty patients (Gender M 29/ F 11; median age 65.7 years; low-risk MIPI 22% and intermediate/high MIPI 78%) were enrolled in the study up to data cut-off on 15 MAY 2019 (Consort diagram). The median observation time for the patients before treatment was of 7.6 months (range:3-107) and median follow-up was of 19 months. Efficacy data of the first 33 patients evaluable after 12 cycles of treatment are reported here, including two patients who were discontinued before cycle 12 due to related toxicity. A total of 27 patients achieved a response with an 82% overall response rate (ORR) and 75% CR. Among CR patients with evaluable MRD (N=23), the rate of undetectable MRD achieved after 12 cycles was 87%. Only 1 patient eventually became MRD positive at cycle 24, whereas 12 remained MRD negative and accordingly, nine of them discontinued ibrutinib as per protocol whereas 3 had interrupted treatment earlier because of intolerance. At data cut-off, all responding patients maintained the response with a median follow-up of 25 months (12-35). Only one patient progressed at one year of therapy. This particular case had shown intolerance to full-dose ibrutinib, received different salvage therapies and died of progressive disease. The estimated 15 month progression-free survival was 96% (CI95%: 89-100). Four patients withdrew the study because of serious adverse events, including cutaneous rash, severe aplastic anemia, pancreatic adenocarcinoma and lumbar fractures. Twenty-one additional G3 and G4 AEs related to Ibrutinib have been recorded including hematological toxicity in 7 patients, gastro-intestinal intolerance in 4 patients, arthralgias, atrial fibrillation and asthenia in one patient each. Conclusion: In indolent clinical forms of MCL frontline ibrutinib in combination with rituximab has a high efficacy, including undetectable MRD in the majority of cases, with a predictable toxicity profile. Figure Disclosures Gine: Roche: Other: Travel expenses, Research Funding; Gilead: Other: Travel expenses, Research Funding; Janssen: Other: Travel expenses, Research Funding. Martín:Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Teva: Research Funding; Roche: Consultancy, Honoraria, Other: Travel Expenses; Servier: Honoraria, Other: Travel Expenses; iQone: Consultancy; Janssen: Honoraria, Other: Travel Expenses, Research Funding; Kiowa Kirin: Consultancy. Terol:Janssen: Consultancy, Research Funding; Astra Zeneca: Consultancy; Roche: Consultancy; Gilead: Research Funding; Abbvie: Consultancy. González-Barca:AbbVie: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Kiowa: Consultancy; Roche: Consultancy, Honoraria; Celtrion: Consultancy; Takeda: Honoraria. Lopez-Guillermo:Gilead: Consultancy, Research Funding; Janssen: Research Funding; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Splenic Marginal Zone Lymphoma: A U.S Population-Based Survival Analysis (1997-2016)

INTRODUCTION: Splenic marginal zone lymphoma (SMZL) is a rare and indolent form of NHL with no standard treatment due to scarcity of clinical trials. Watch and wait approach, single agent rituximab or with chemotherapy and splenectomy are valid treatment approaches. No population-based studies examining the impact of chemotherapy and splenectomy on survival of SMZL patients are available. Thus, we decided to compare survival outcomes by clinical factors in SMZL patients deposited in the SEER database, emphasizing in the role of splenectomy on survival outcomes. METHODS: Retrospective analysis of SMZL cases in the SEER database from 1997 to 2016.SEER collects cancer incidence and survival data from population-based cancer registries covering 34% of the U.S. population. PATIENTS: SEER database was queried for SMZL patients at all ages from 1997 to 2016. Cases without histologic confirmation or no survival data were excluded. Demographic and clinical variables (age, sex, race, ethnicity, B-symptoms, Ann-Arbor stage, DLBCL transformation, first malignancy, chemotherapy with or without rituximab, splenectomy and radiotherapy) were summarized by descriptive statistics. Logistic regression used to determine variables associated with splenectomy. Overall survival (OS) and Cancer-specific survival (CSS) were the major end-points, estimated by Kaplan-Meier method. Cox regression used to calculate Hazard Ratios. RESULTS: 2212 patients met inclusion criteria, with a median age of 68yo (25-96). Patient characteristics were a follows: males (n=1152, 52.1%); whites (n=1991, 90.0%), blacks (112, 5.1%); Non-Hispanics (n=2049, 92.6%); B-symptoms (n=461, 20.8%); first malignancy (n=1754, 79.3%); Ann-Arbor Stage I (429, 19.4%), Stage IV (n=1351, 61.1%); DLBCL transformation (n=84, 3.8%). Adjusted Odds ratio (aOR) were used to compare splenectomy versus non-splenectomy treated patients: ≥60yo (aOR 0.49;0.40-0.62), males (aOR 0.77;0.64-0.93). Median survival of all the patients was 120 months (95%CI:111-132); On univariate analysis: shorter OS was significantly associated with age ≥60(HR 3.55;2.87-4.38) and non-first malignancy(HR 1.6;1.36-1.88), while shorter CSS was significantly associated with age ≥60(HR 1.76;1.33-2.34), B-symptoms (HR 1.93;1.44-2.60), Stage IV (HR 1.62;1.15-2.28), DLBCL transformation (HR 2.27;1.55-3.33) and treatment with chemotherapy (HR 1.54;1.22-1.94). On multivariate analysis, shorter OS was significantly associated with age ≥60(HR 3.52;2.83-4.37), male sex (HR 1.15;1.00-1.33), B-symptoms (HR 1.23;1.01-1.51) and non-first malignancy (HR 1.42;1.20-1.67). Shorter CSS was significantly associated with age ≥60(HR 2.15;1.61-2.87), Hispanic ethnicity (HR 1.44;1.00-2.07), B-symptoms (HR 1.77;1.30-2.39), DLBCL transformation (HR 2.03;1.38-2.99) and treatment with chemotherapy (HR 1.38;1.07-1.77). Ann Arbor staging and splenectomy were not associated with OS or CSS. CONCLUSIONS: Older age, Hispanic ethnicity, B-symptoms, DLBCL transformation, and treatment with chemotherapy were associated with poor lymphoma-specific survival. Although, age&lt;60 and female gender were associated higher odds to undergo splenectomy, splenectomy had no impact on the risk of lymphoma-related death or OS. This retrospective study demonstrates that chemotherapy treatment (excluding rituximab) was associated with inferior outcomes in SMZL, while advanced Ann-Arbor stage was not associated with shorter survival as is observed in other indolent lymphomas that commonly present at advanced stage. Table Disclosures Alderuccio: Targeted Oncology: Honoraria; Foundation Medicine: Other: Immediate family member; Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; OncLive: Consultancy; Inovio Pharmaceuticals: Other: Immediate family member. Lossos:NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees.

Health Economic Burden and Treatment-Based Survival for Current Follicular Lymphoma Treatment Practice in Japan Using a Nationwide Retrospective Claims Database

ABSTRACT Introduction: Follicular lymphoma (FL) is an indolent form of non-Hodgkin lymphoma (NHL), which accounts for 20-30% of all NHL cases. In most patients, FL is diagnosed in advance stages, mild disease progression and long treatment period that may incur a great burden to patients and healthcare system. However, to our knowledge there is no comprehensive analysis which have been done in the real world setting in Japan. Therefore, we conducted a retrospective claim database study to elucidate the lines of treatment patterns as well as the associated healthcare resource utilization (HCRU), and 3- and 5-year overall survival (OS) among 3,593 Japanese patients with a median age of 65.0 years. Methods: This retrospective study analyzed data from the Medical Data Vision (MDV) database for patients diagnosed with FL (ICD-10: C82). The MDV database is an electronic health records-based database comprised of anonymized inpatient and outpatient data covering over 25 million patients and over 374 Japanese hospitals, approximately 22% of acute phase hospitals, including 187 cancer therapeutic facilities. Patients who received treatment during the identification period from 1 October 2008 to 31 December 2017 were selected. Patients were required to have data for at least 6 months before the first treatment date (ie, patient index date) and at least 12 months after the index date (unless they died). Costs were converted from Japanese yen to US dollars using the exchange rate based on January of each year of service. For 3- and 5-year OS, patients who had a record of death in their hospital discharge were counted as an event, otherwise they were censored at the latest of: end of patient record, end of data availability, or end of the 3- or 5- year period. Results: A total of 3,593 patients with FL met the inclusion criteria of which 51.2% was female patients. Of these 3,593 patients who met the inclusion criteria, 3,004 patients (83.6%) received rituximab-based (R) therapy as index treatment, of which 1309 (36.4%) of patients received R-CHOP. During the subsequent lines of therapies, patients received heterogeneous treatment regimens (fig 1). Overall, the average healthcare cost during follow-up period was $67,557.40 for all FL patients, ranging from $39,340 (immunotherapy, targeted therapy, or hormone therapy without R) to $ 95,095 (other R-based chemotherapy). The average number of outpatient visits during follow-up for all FL patients was 51, ranging from 44.6 to 55.1 for each treatment group. There were 3,394 (94.5%) patients who had at least one hospitalization during follow up period. Among those who had at least one hospitalization, the average number of hospitalizations was 3.8 for all FL patients, ranging from 2.5 to 4.6 for each treatment group. The average number of days of hospitalization during follow-up was 74.5 for all FL patients, ranging from 31 to 110.4 for each treatment group. 85 (2.4%) FL patients received a stem cell transplant (SCT) during follow-up at the age under 79 years, with other R-based therapies having the highest percentage (7.6%). There were 346 (9.7%) FL patients receiving radiation therapy, ranging from 8.1% (other treatment groups) to 24.1% (immunotherapy, targeted therapy, or hormone therapy without R). There were 337 deaths (9.4%) recorded within 3 years and 400 (11.1%) within 5 years of index treatment. The median Kaplan-Meier OS was not reached for most analysis groups due to the overall high survival rates. When comparing overall survival by index regimen group, chemotherapy without R consistently had worse survival, especially compared to R-based regimens (fig. 2). Conclusions: Patients with FL in Japan received diverse treatment regimens and multiple lines of therapy with relatively high survival rates. Majority of patients have received R-based therapies and have shown longer survival rates compared to those who have received chemotherapy without R. This is the first study to clarify lines of treatment patterns using retrospective claims database and treatment group-based OS in FL patients in Japan, which will give clinical insights of the landscape of daily practices and the associated real world health economic burden for patients, clinicians and healthcare providers to support their better decision makings. Disclosures Tsutsue: Celgene: Employment. Tobinai:Solasia: Honoraria; Mundi Pharma: Consultancy, Honoraria, Research Funding; Takeda Pharmaceutical: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Ono Pharmaceutical: Consultancy, Honoraria, Research Funding; Yakult: Honoraria; AbbVie: Research Funding; Meiji Seika: Honoraria; Janssen Pharmaceutical: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; HUYA Bioscience: Consultancy, Honoraria; Zenyaku Kogyo: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Eisai: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Verastem: Honoraria; Kyowa Kirin: Honoraria, Research Funding. Yi:Celgene: Consultancy. Crawford:Celgene: Consultancy.

Cerebral empyema and abscesses due to Cutibacterium acnes

IntroductionCutibacterium acnes is a commensal bacterium of the skin, frequently reported in prosthetic shoulder or spinal implant infections, but rarely in cranial and intracranial infections. MethodsWe retrospectively reviewed patients with intracranial samples positive to Cutibacterium acnes managed in the neurosurgical units of our hospital of Lyon, France, between 2008–2016. ResultsWe included 29 patients, of whom 23 had empyema (with or without abscess), 17 had cranial osteomyelitis, and six only had abscess. Prior neurosurgery was reported in 28 patients, and the remaining patient had four spontaneous abscesses. Twelve patients had polymicrobial infections, including methicillin-susceptible Staphylococcus in 11 cases. The clinical diagnosis was difficult because of indolent and delayed symptoms: a CT scan or MRI was required. Thirteen patients (52%) had material at the infection site. All patients with bone flap implant or bones from biological banks had a bone flap-associated infection. Drainage was surgically performed in 25 cases or by CT scan-guided aspiration in four cases. All patients received an adapted antibiotic therapy (from three weeks to six months). The outcome was favorable in 28 patients. Three patients relapsed during the antibiotic therapy, requiring further surgery. ConclusionCutibacterium acnes can be responsible for postoperative empyema and cerebral abscesses, with particular indolent forms, which make their diagnosis difficult. They are often polymicrobial and associated with bone flap osteomyelitis. Their outcome is favorable after drainage and adapted antibiotic therapy.

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia.

The histology-based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label-free LC-MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n=10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D-20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.

CERVICOFACIAL ACTINOMYCOSIS CAUSING PNEUMONIA AND EMPYEMA

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Actinomyces are non-spore-forming, anaerobic bacteria with variable morphology found as part of normal oral flora. Active infections are seen in patients with a history of poor dental hygiene, diabetes, alcoholism, and immunosupression. Although actinomyces is a known cause of cervicofacial and lung infections separately, we present a case of a patient diagnosed with cervicofacial actinomycosis with extension into the pleural cavity causing empyema. CASE PRESENTATION: A 38 year old male with an only known history of alcohol abuse was admitted to the hospital for evaluation of an enlarging anterior neck mass. He stated that he had intermittent chills and night sweats. The patient was complaining of no shortness of breath or chest pain. Physical exam was unremarkable other than poor dentition, a large anterior neck mass, and decreased breath sounds in the right lung base. On presentation, the patient was febrile to 102.3F with a leukocytosis of 30,000 cells/mcL.The patient was initially started on broad spectrum antibiotics. CT of the chest showed posterior and medial right sided pleural thickening, dense consolidation of posterior and medial aspects of the right upper and lower lobes, likely right sided empyema with split pleura sign, and a 10cm by 6cm phlegmonous neck mass with likely extension into the apex of the right pleural cavity.There was associated mediastinal lymphadenopathy. The patient underwent surgical incision and drainage of the neck mass. Surgical pathology revealed granulation tissue with lymphohistiocytic infiltrate and focal abscess formation. Pathology also identified actinomyces species and sulfur granules. A chest tube was placed to drain the effusion and the patient's antibiotics were switched to ampicillin/sulbactam and eventually to oral penicillin. DISCUSSION: Actinomyces are non-spore-forming, strict or facultative anaerobes with a variable cellular morphology. They are only found in normal oral flora of humans and usually only cause infections in patient with poor dentician, diabetes, chronic alcoholism, and immunosupression. There is a male predominance. Disease is usually caused by direct, not hematogenous, spread and has the capability to cross fascial planes, form multiple abscesses, fistulae, and draining sinus tracts. Infections typical present in two forms as either slow indolent none painful infections or acute suppurative infection with significant pain and symptoms. Given that our patient was relatively asymptomatic, he most likely presented with the slow indolent form and had likely been infected for weeks before his neck mass was noted. CONCLUSIONS: Actinomyces infections are a well known cause of cervicofacial infections and can spread by direct extension. We present an unusually case of a patient with cervicofacial actinomycosis that formed a direct tract to the pleural cavity causing pneumonia and emypema. Reference #1: Moturi K, Kaila V. Cervicofacial Actinomycosis and its Management. Ann Maxillofac Surg . 2018;8(2):361-364. DISCLOSURES: No relevant relationships by Cory Bolinger, source=Web Response No relevant relationships by Jeffrey Williams, source=Web Response

Clinical profile of multiple myeloma in a tertiary medical college northern Kerala, India

Introduction: Multiple myeloma is a clonal plasma cell disorder which varies its clinical course ranging from relatively indolent form to frankly aggressive neoplasia. Objectives: To study the clinical profile of Multiple myeloma. Materials and Methods: Descriptive study was conducted at a tertiary medical College in Kerala. 70 patients of Multiple myeloma was found with help of laboratory work up including urine Bence Jones with heat coagulation method. Serum albumin, calcium, uric acid was also done using standard biochemical kits. X-ray of Thoracic, Lumbar spine, Humerus, Hip region was evaluated. The frequency of variables was expressed as proportions and analysed. Results: The mean age of males was 62 and females 59 appropriately. The male/female ratio of Multiple myeloma was found to be 1.6:1. The associated neurological symptoms were root pain for 14.3% of patients. Almost 8.6% had paraparesis and 2.9% were suffering from paraplegia and 1.4% had quadriplegia, paraesthesia, buldging right eye and diplopia. Anemia was found in 87.1% and ESR was raised above 30 in 92.8% of patients. The total count more than Eleven thousand was found for 10% and less than four thousand for 1.4% of patients. Easnophilia was seen among 7.1%, 1.4% of patients had Peripheral smear >10% and Electrophoresis M band was seen in 78.6% of patients. Lytic lesions on X- Ray Skull neck were found in 62.9% and X Ray Spine were found in 1.4% of patients. Conclusion: 70 cases detected at a tertiary Medical College at Northern Kerala in a year indicate significant incidence of the disease. Professional Medical Associations should give importance to this topic and case studies of Multiple Myeloma should be included in medical conferences to raise the competence of doctors regarding the disease. Keywords: Multiple Myeloma, Northern Kerala.

Multidisciplinary Challenges in Mastocytosis and How to Address with Personalized Medicine Approaches.

Mastocytosis is a hematopoietic neoplasm defined by abnormal expansion and focal accumulation of clonal tissue mast cells in various organ-systems. The disease exhibits a complex pathology and an equally complex clinical behavior. The classification of the World Health Organization (WHO) divides mastocytosis into cutaneous forms, systemic variants, and localized mast cell tumors. In >80% of patients with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is found. Whereas patients with indolent forms of the disease have a normal or near-normal life expectancy, patients with advanced mast cell neoplasms, including aggressive SM and mast cell leukemia, have a poor prognosis with short survival times. In a majority of these patients, multiple somatic mutations and/or an associated hematologic neoplasm, such as a myeloid leukemia, may be detected. Independent of the category of mastocytosis and the serum tryptase level, patients may suffer from mediator-related symptoms and/or osteopathy. Depending on the presence of co-morbidities, the symptomatology in such patients may be mild, severe or even life-threatening. Most relevant co-morbidities in such patients are IgE-dependent allergies, psychiatric, psychological or mental problems, and vitamin D deficiency. The diagnosis and management of mastocytosis is an emerging challenge in clinical practice and requires vast knowledge, a multidisciplinary approach, and personalized medicine procedures. In this article, the current knowledge about mastocytosis is reviewed with special emphasis on the multidisciplinary aspects of the disease and related challenges in daily practice.

Flow-mediated dilation shows impaired endothelial function in patients with mastocytosis

Mastocytosis is a rare disease characterized by clonal proliferation of mast cells (MCs) in different organs. Clinical manifestations of mastocytosis are mostly due to release of mediators from MCs and, in many cases, such as urticaria, flushing, angioedema, and anaphylaxis, are an expression of the biological effects of mediators on endothelial cells. Chronic secretion of mediators in patients with mastocytosis can lead to alteration of endothelial function. We sought to investigate endothelial function in patients with mastocytosis using a noninvasive technique of flow-mediated dilation (FMD). Twenty-five adult patients with indolent and advanced forms of mastocytosis and 20 healthy control subjects were enrolled in the study. Ultrasound assessment of FMD was performed by measuring changes in the diameter of the brachial artery after 5minutes of arterial occlusion. Changes in FMD were correlated with clinical parameters and serum tryptase levels. Patients with mastocytosis had lower FMD compared with healthy control subjects (P<.001). Advanced and smoldering forms showed a lower FMD compared with indolent forms (P<.001). FMD inversely correlated with age and serum tryptase levels and directly with median arterial pressure and recurrent flushing episodes. No correlation was found between FMD and osteoporosis, recurrent anaphylaxis, presence of skin lesions, and long-term antihistamine treatment. Endothelial dysfunction, as demonstrated by FMD reduction, is detectable in patients with mastocytosis and is more severe in patients with high tryptase levels and advanced disease. Endothelial function appears to be negatively influenced by MC proliferation rather than by the severity of mediator-related symptoms.