bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant human activated FVII as prophylaxis in surgical treatment of cancer patient with acquired hemophilia A.
Authors: La Verde Giacinto , Ferrari Antonella , Ziparo Vincenzo , Naso Virginia , Bianchi Maria Paola , Antolino Giusy , Saltarelli Francesca , Monarca Bruno , Resci Federica , De Benedittis Daniela , Moscetti Alessandro 
Published: March 2020

e17006 Background: Acquired hemophilia A is caused by the development of factor (F)VIII autoantibodies and results in more serious haemorrhagic symptoms than in congenital severe HA. About 50% of cases, not identified as idiopathic, are related to autoimmune diseases, viral infections, pregnancy and also neoplasms. To treat bleeds recombinant factor VIIa and activated prothrombin complex concentrate are equally efficacious while immunosuppression with steroids alone or combined with cytotoxic agents should be started as soon as the diagnosis is made. Methods: In February 2010 a woman of 58 years with acquired hemophilia A, previously treated in 1978 with cyclophosphamide and steroids without clinical benefits, was admitted to the Hematology Department of Sant’Andrea Hospital in Rome for a recent episode of spontaneous massive enterorrhagia. The diagnostic exams revealed a colorectal carcinoma (moderately differentiated G3) associated with papillary urothelial neoplasia with low malignant potential. A coagulation panel showed an aPTT ratio of 3.75 (normal range 0.8-1.2), INR 1.03 (normal range 0.9-1.2), fibrinogen 327 mg/dL (normal range 238-500), FVIII activity level of 3% (normal reference 50-150%) and FVIII inhibitor titer > 100 Bethesda Units. Results: The patient was treated with left hemicolectomy and removal of the bladder lesion associated with chemotherapy XELOX (oxaliplatin 130 mg/sm day 1 q21, capecitabine 1000 mg/sm orally day 1-14 q21). From day -1 to day +15 post surgery, the patient was treated with intravenous recombinant human activated FVII at standard dose (NovoSeven®, 90 mcg/kg every 4 hours). Our treatment avoided both intra and post-operative surgical bleeding complications, while not changing the titer of the inhibitor nor by normalizing the aPTT ratio. Actually the patient is in good clinical conditions with no further hemorrhagic episodes, although the FVIII inhibitor titer still remains high. Conclusions: We have described this case to emphasize that the presence of acquired hemophilia A in cancer patients, thanks to its specific prophylactic treatment, cannot be a limit in performing routine diagnostic and therapeutic procedures, especially surgical ones.
Adherence and persistence to second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia.
Authors: Trivedi Digisha , Amin Shahla , Zhu Ling , Joo Sam , Kawabata Hugh , Darkow Theodore , Hebden Tony 
Published: March 2020

e17009 Background: Some studies have demonstrated the correlation between adherence and persistence to therapy and the effectiveness of that therapy, thereby reinforcing the need to optimize both as a core treatment strategy. Because available data are limited, we examined real world adherence and persistence to the 2nd generation tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). Methods: An observational retrospective study was conducted using pooled Invision Data Mart and Pharmetrics claims data. Adult CML patients with at least two prescriptions for a 2nd generation TKI between July 1, 2006 and December 31, 2010 were identified and followed for a maximum of 6 months from their index date (first observed prescription date). Dasatinib and nilotinib patients with prior imatinib use in 6 month pre-index period were classified as second-line and those with no prior use as first-line patients. Adherence to treatment was defined by the medication possession ratio (MPR) and persistence as the proportion of patients refilling prescriptions within 1.5 times the days supply during the follow-up period. Results: Of the 276 CML patients identified, 179 received dasatinib (n=50 first-line; n=129 second-line) and 97 received nilotinib (n=27 first-line; n=70 second-line). Patient characteristics were similar across treatment groups. Proportions with MPR ≥85% were 64% and 75% for first- and second-line dasatinib and 48% and 61% for first- and second-line nilotinib. Persistence rates were 36% and 47% for first- and second-line dasatinib and 26% and 39% for first- and second-line nilotinib. Conclusions: In both first- and second-line use, dasatinib was associated with higher adherence and persistence than the corresponding nilotinib-treated group. The reason for the difference between these TKIs is not known and will require further study.
Primary ovarian granulocytic sarcoma: A case report and literature review.
Authors: Njoh Roland Fokwen 
Published: March 2020

e17011 Background: Granulocytic sarcoma, also known as myeloid sarcoma, myeloblastoma, and Chloroma are extramedullary manifestation of malignant myeloid precursor cells. Its occurrence as a primary ovarian tumor is a rare entity. Methods: A 49 y/o female presented to the clinic with right lower quadrant abdominal pain that had been present for 6 months. Eventually, a CT scan was obtained that showed a 6.5 cm mixed solid and cystic mass on the right adnexa that was felt to represent malignancy. Her history was positive for residing near a car-spraying garage. She was taken to the operating room and underwent a robotically assisted laparoscopic BSO, laparotomy, omentectomy, lymph node dissection and tumor debulking. Findings at surgery included a normal left ovary, adherent right ovary, normal omentum, nodular epiploicae, and tumor encasing the iliac vessels. Final pathology report of tumor cells showed granulocytic sarcoma with flow cytometry positive for CD 33 and CD 34. Bone marrow biopsy and peripheral blood flow cytometry was negative for leukemia. She subsequently underwent chemo-induction with cytarabine, idurubicin, and prednisone. Results: A PUBMED, MEDLINE/OVID database search revealed only three previously reported cases of primary ovarian granulocytic sarcoma without concurrent or subsequent hematological manifestation. Conclusions: Granulocytic sarcoma most frequently precedes or occurs in the setting of acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). The typical sites of isolated granulocytic sarcoma include bone, periosteum, soft tissues, and lymph nodes, and less commonly the orbit, intestine, mediastinum, epidural region, uterus, and ovary. In patients presenting with primary ovarian granulocytic sarcoma, the final diagnosis is obtained after tissue examination and often comes as a surprise to providers. Granulocytic sarcoma should therefore be included in the differential diagnosis of patients with isolated ovarian tumor.
Occult hepatitis B and occult hepatitis C viremia in patients with hematologic malignancies.
Authors: Torres Harrys A. , Mahale Parag , Kontoyiannis Dimitrios P , F. Blaine Hollinger F. Blaine 
Published: March 2020

e17016 Background: Occult Hepatitis B (OHB)and Hepatitis C (OHC) in patients with hematological malignancies (HM) are understudied, mainly because biopsies to identify these viruses in the liver are often not performed due to an associated risk of complications (e.g., bleeding). We describe our retrospective experience of patients with HM tested for OHB and OHC. Methods: Between 09/09 and 11/10, 18 unselected consecutive patients with an abnormal liver panel were tested for both OHB and OHC which was defined as detectable viremia in the absence of HBsAg and anti-HCV, respectively. Severe liver dysfunction was defined as ALT >10 times the upper limit of normal (>560 IU/L) and/or a total bilirubin >6 mg/dL. Plasma samples were tested for HBV DNA and HCV RNA by using real-time PCR (Cobas Taqman HBV and HCV Tests-Roche Molecular Systems). Results: Most patients (12 or 67%) had leukemia, followed by lymphoma (5 patients or 28%). Two patients (11%) had OHB, and none had OHC.The 2 patients with OHB were born in areas with an intermediate to high prevalence of HBV; both had only low grade viremia (<29 IU/mL). At the time HBV DNA testing was performed, peak ALT levels in these 2 patients were 843 IU/L and 6,047 IU/L compared to a median peak ALT of 302 IU/L (range, 84-1,320 IU/L) among those without OHB (P=0.03). Severe liver dysfunction occurred in the 2 (100%) patients with OHB compared to 6 (38%) of the non-OHB cases (P=0.1). Durations of ALT elevation were 12 and 17 days in patients with OHB, compared to a median duration of 13 days (range, 5-73 days) in non-OHB patients. Co-infections were identified in 1 patient with OHB and in 10 (63%) without OHB. The 2 patients with OHB and 8 (50%) patients without OHB died within 6 months after HBV DNA testing. Conclusions: Although our data are limited, in a group of cancer patients in whom a liver biopsy is not available, detection of HBV DNA or HCV RNA in serum in the absence of HBsAg or anti-HCV identifies a subset of patients with occult viral hepatitis, a phenomenon of unclear clinical significance.
Systematic literature review of processes and challenges in establishing accurate diagnosis of hematologic malignancies.
Authors: Oberthur Johnson Laura , Zarotsky Victoria , Teitelbaum April H. 
Published: March 2020

e17017 Background: Multiple tests are often needed to ensure accurate differential diagnosis (DDX) of hematologic malignancies, particularly for rare/complex conditions. Integration of morphology, immunophenotype, cytogenetic, and molecular results present challenges but is critical to determine prognostic parameters and treatment (tx) decisions. Methods: Systematic literature search was performed (PubMed/MedLine, EMBASE, Cochrane Library) for US-based articles in last 10 yrs regarding DDX of myelodysplastic syndrome, myeloproliferative neoplasm, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma. Results: 35 articles were identified that addressed methods (n=27) and/or accuracy/timing (n=15) of establishing a diagnosis. Diagnostic (dx) ability improved with use of systematic processes/algorithms (ALG), comparative techniques, and harmonization/central review; few ALG were comprehensive. Updates/revisions of disease-specific dx criteria could result in dx change. Accuracy improved with experienced clinicians (disease-specific knowledge), specialized pathologists (vs. generalists), tissue sample type/quality, and ancillary test availability. A pathologist’s dx ability was related to experience with rare/complex histological subtypes. Dx accuracy was often complicated by inconsistent/overlapping clinical presentation and lack of standardized terminology or reproducible results across facilities. Delays were attributed to lack of dx experience and patient’s health insurance type. Impact of dx delay on clinical outcomes was largely not addressed. Conclusions: With shift from morphologic- to genetic/molecular-based approaches, determination of tests done in parallel/reflexively often requires expert input. Impact of delayed dx on clinical outcomes is lacking. Standardized dx processes/ALG, along with access to expert hematopathologist review and interpretation of test results, may lead to earlier and improved dx accuracy and appropriate/timely tx initiation, thereby avoiding consequences of erroneous dx, especially of benign conditions initially dx as malignant.
Leptomeningeal disease as a manifestation of CLL.
Authors: Zaidi Aisha Salman , Burton Eric Christopher , Lotia Mitesh 
Published: March 2020

e17019 Background: Chronic Lymphocytic Leukemia is a lymphoproliferative disorder which can have variable course from being indolent to aggressive. Reported annual incidence of Chronic Lymphocytic Leukemia is 3:100000. The most common manifestation is Lymphadenopathy and Leptomeningeal involvement is very rare with only a few reported cases in literature. Methods: This is an observational case report. Results: We report a case of 57 year old White male who presented with CNS disease as his first manifestation of CLL. He reported a 6 week history of cognitive decline with inability to perform complex tasks, difficulty with calculations, word finding trouble, progressive clumsiness of right arm and leg and a weight loss. MRi revealed Left sided Leptomeningeal enhancement. As part of his work up; patient received LP, PET scans, Infectious and autoimmune studies and eventually brain biopsy which initially showed Lymphocytic predominance.On further review by NIH immunohistochemical stains for CD5, CD20 and CD23 were positive on the leptomeningeal and parenchymal lymphocytes. His bone marrow showed CLL involvement both morphologically and immunophenotypically by means of flow cytometric analysis. He was started on treatment with High dose methotrexate and Rituximab and showed remarkable improvement in his cognitive function by the completion of his second cycle. His bone marrow repeat biopsy showed complete remission and no involvement of lymphoma. Conclusions: CLL is an indolent disease and direct CNS invasion is extremely rare. Our case becomes unique in terms of its presentation. It highlights the importance of timely diagnosis and management of leptomeningeal disease in CLL can lead to resolution of neurologic symptoms.
Baby-step chemotherapy as a way to deliver chemotherapy in poor PS small cell lung cancer.
Authors: Noronha Vanita , Patil Vijay , Joshi Amit , Muddu Vamshi , Prabhash Kumar 
Published: March 2020

e17500 Background: Majority of patients with SCLC present with advanced stage and poor ECOG performance status. Hence delivery of adequate dose of chemotherapy is compromised. We hypothesized that initial low-dose chemotherapy might improve PS and enable administration of standard-dose chemotherapy, thus extending benefit of chemotherapy to otherwise ineligible patients. Methods: 30 patients with ECOG performance status 2-4 received low-dose chemotherapy consisting of either single agent carboplatin at AUC 2 or an abbreviated course of platinum-etoposide. Patients whose PS improved got full-dose chemotherapy with the standard regimen of platinum-etoposide. Demographic details, toxicity, time to progression and overall survival were analyzed. Univariate and multivariate analysis was performed to determine factors associated with TTP and OS. Results: Median age was 58 years with male predominance. The PS was IV in 9, III in 20 and II in 1 patient. Extensive-stage and limited-stage disease was seen in 24 and 6 patients respectively.15 patients received single-agent carboplatin, 10 patients abbreviated cisplatin-etoposide, 1 patient each cyclophosphamide and cisplatin-etoposide and 3 patients refused chemotherapy. Major grade 3-4 toxicity was mucositis in 1, loose motions in 1 and hyponatremia in 4 patients. There was no grade 3- 4 haematological toxicity. The median number of dose-reduced cycles was 1 and 3 patients received more than 2 cycles. 22 patients were eligible and willing for full-dose chemotherapy. The median time to start of full-dose chemotherapy was 11.5 days (4-26 days). The median number of cycles of standard-dose chemotherapy was 5 (1-6) with 16 completing planned schedule. Grade 3-4 toxicity was neutropenia in 50%, febrile neutropenia in 25%, loose motions in 25% and hyponatremia in 40%. The overall TTP and OS was 182 days and 263 days respectively. Presence of SIADH (p = 0.02) and completion of standard treatment (p = 0.001) had a positive impact on TTP while completion of treatment (p = 0.01) and normal LDH (p = 0.03) had a positive impact on OS. Conclusions: Low-dose chemotherapy is well-tolerated and might help in extending the benefit of standard-dose chemotherapy to otherwise ineligible patients.
Stage III non-small cell lung cancer: Who passes the threshold?
Authors: Palka Magda , Ruiz-Valdepeñas Andrea , Doger de Speville Bernard Gaston , Ibeas Patricia , Perez Callejo David , Almagro Elena , Huelves Miriam , Mendez Miriam , Maximiano Constanza , Provencio-Pulla Mariano 
Published: March 2020

e17502 Background: Objective: The objective of the study is to indentify the patients diagnosed of stage III non-small cell lung cancer (NSCLC) in Puerta de Hierro Madrid Hospital (Spain) between 2000 and 2008, who had longer overall survival rates (more than 24 months) and longer time to progression after completing initial treatment. Methods: We revised all cases of NSLC seen in our hospital, and of those, selected 147, the ones diagnosed, treated and followed completely in our hospital. We reviewed the age at diagnosis, initial staging, modalities of treatment received in each case, time to progression, site of development of metastasis, time to relapse and overall survival. The time of monitoring was from date of diagnosis until death date or, until transferral to palliative care clinics. Results: We revised 966 histories of patients, of which 147 were diagnosed stage III, treated and followed in our hospital. Most common hystological type were Epidermoid Carcinomas (54.3% versus 21.7% of adenocarcinomas), and were diagnosed at older ages. 45.6% underwent surgery, most of them (41.2%) were treated before with neoadyuvant chemo or radiotherapy, with a median survival of 32.4 months, with an overall survival interval very wide, from 20 days until more than 8 years. Among these patients were the ones who survived more than 24 moths after diagnosis, and those had Ps 0 -1 at diagnosis, less comorbidities and had the same proportion of stage IIIA and IIIB stages. 53% of patients were only treated with cisplatin-based chemotherapy or radiotherapy at 60Gy, and in these cases, the median overall survival was shorter: 9.5 months Conclusions: In our study, neoadyuvant therapies and the protocols used are the most accepted in international guidelines. The patients who underwent chemotherapy and surgery lived much more and they had better Performance Status at diagnosis, so we can conclude that chemotherapy and surgery, if possible, are a good treatment option with longer global survival. Definitive chemotherapy and radiotherapy should be better reserved for those patients who are not candidates for surgery.
Impact of asbestos exposure on survival and treatment of patients with malignant mesothelioma.
Authors: Bourgouin Patrick P , Blais Normand , Tehfe Mustapha , Florescu Marie 
Published: March 2020

e17507 Background: Malignant mesothelioma is a rare pleural cancer heavily correlated to asbestos exposure. However, the number of mesotheliomas without any known exposure to asbestos is surely increasing. The impact of asbestos exposure on patient survival and response to standard treatment is unknown. We retrospectively analyzed 49 consecutive patients diagnosed with malignant mesothelioma using an unselected SARDO database at Notre-Dame Hospital from 2006 to 2009. Methods: Patients were sorted into 2 groups based on reported asbestos exposure status, mostly on patient’s working exposure. Demographic and treatment data were collected and analyzed with Kaplan-Meier survival plots and log-rank tests. Results: The median survival was 22.6 months for the entire 49 patients, overall survival at 1 year 86.4% and at 2 years 47.3%. Median survival of exposed patients (n = 20) was 22.6 months and that of non-exposed patients (n = 29) was 59.5 months. However, survival was not significantly different between the 2 groups (p = 0.450), despite there was no treatment difference in between 2 cohorts. Most patients were men (n = 42) and women (n=7) generally belonged to the non-exposed group. 3 patients had surgical treatment (pleurectomy with either pneumonectomy or lobectomy), but their survival was not statistically superior (p = 0.091) despite a clear trend. Patients younger than 65 years did not have better survival. Conclusions: Although asbestos exposure clearly increases the risk of mesothelioma, it does not seem to have an impact on the overall survival of patients with malignant mesothelioma neither on the efficiency of their treatment. However, a reliable serum biomarker of asbestos exposure would probably be necessary to make sure patients with no working exposure have really no exposure in other circumstances to asbestos.
Association of second primary malignancies with past and family history of malignancy in patients with small cell lung cancer.
Authors: Kirita Keisuke , Goto Koichi , Umemura Shigeki , Yoh Kiyotaka , Niho Seiji , Ohmatsu Hironobu , Nagai Kanji , Ohe Yuichiro 
Published: March 2020

e17526 Background: Based on recent development in the treatment for small cell lung cancer (SCLC) such as chemotherapy and radiotherapy, long-term survivors are frequently observed. Meanwhile, etoposide and radiotherapy, which are key treatments for SCLC, are also known as methods to set up late complication including carcinogenicity. There have been few reports of second primary malignancies (SPM) in patients with SCLC, and risk factor for SPM has not become evident other than smoking continuation. Methods: From July 1992 to December 2009, 900 patients with SCLC were treated in National Cancer Center Hospital East. Medical records of all patients were retrospectively reviewed, and the incidence and risk factor for SPM were investigated. Results: Demographics of all patients with SCLC were as follows: Male/Female, 738/162; median age, 66 years (range 22-87); smoking pack-year (PY) <30/30≤, 155/745; Limited/Extensive, 468/432. Median follow up time was 4.5 years. Three and 5-year overall survival rate were 16.4% and 11.6%, respectively. Twenty-seven patients (3.0%) developed SPM, 15 patients (54%) of whom died due to SPM. Thoracic cancer occupied 52% of them (lung, 11; trachea, 1; esophagus, 4; breast, 1). Three and 5-year cumulative incidence rate (CIR) of SPM were 2.5% and 11.8%. Although there was no significant risk factor for SPM, the groups having past history of malignant disease and heavy smoker (PY ≥30) tended to develop SPM (p=0.11and 0.07). Using etoposide containing regimen and thoracic irradiation were not significant risk factors for the incidence of SPM (p=0.84 and 0.24). Neither serum level of CEA, NSE nor ProGRP were risk factors of incidence of SPM (p=0.51, 0.09 and 0.21). Within over 2-year survivors, there was a significant correlation between family history of cancer within first-degree relatives and CIR of SPM (p<0.01). Conclusions: Five years CIR of SPM was 11.6%, and secondary thoracic cancer accounted for large portion of them. It was concluded that cumulative smoking amount, past history of malignant disease, and positive family history of cancer within first-degree relatives were risk factors for SPM.