Pancreatic cancer is one of the leading causes of cancer-related mortality in western countries. Early diagnosis of pancreatic cancers plays a key role in the management by identification of patients who are surgical candidates. The advancement in the radiological imaging and interventional endoscopy (including endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography and endoscopic enteral stenting techniques) has a significant impact in the diagnostic evaluation, staging and treatment of pancreatic cancer. The multidisciplinary involvement of radiology, gastroenterology, medical oncology and surgical oncology is central to the management of patients with pancreatic cancers. This review aims to highlight the diagnostic and therapeutic role of EUS in the management of patients with pancreatic malignancy, especially pancreatic ductal adenocarcinoma.

Introduction: The blood transfusion (BT) system in Pakistan is fragmented, demand-driven, and depends on weakly regulated transfusion practices. This is primarily a big problem in smaller cities and remote rural areas. Pakistan has one of the highest hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalence worldwide, estimated around 5 & 10 million cases, respectively. There is a considerable risk that transfusion-transmissible infections (TTIs) may have contributed to the current epidemic of HBV & HCV, affecting 7.4 % of the general population, and potential risk of HIV transmission in the country. In this systematic review, we aim to identify the prevalence of TTIs among the blood donor population and associated safety challenges. Method & Material: We conducted a systematic literature search to identify studies related to TTIs and transfusion safety in Pakistan from January 1, 2010, to January 31, 2020. A search was conducted using PubMed and PakMedinet.com (largest medical database of Pakistan); initial search retrieved 981 articles, 166 met the inclusion criteria, and after review by two independent reviewers, 33 articles met the final criteria for qualitative synthesis. Results: Analysis of 33 studies showed the seroprevalence of HBV of 2.04 % (0.81% to 4.22%), HCV of 2.44% (1.29 % to 10%), HIV of 0.038% (0% to 0.18%), syphilis of 1.1% (0.11-3.01%) and malaria of 0.11% (0.05-1.20). The rate of coinfections among blood donors varied from 0.0099% to 0.35 %. The highest number of coinfections were HCV & syphilis, followed by HCV & HBV infections. The rate of TTIs was dependent on the number of donors, donor types (replacement vs. voluntary), screening techniques used, number, and type of TTIs tested. There was a lack of universal screening for common TTIs. Syphilis and malaria were tested only 38 % & 46 % of all the blood donations. The studies with a high number of replacement donors (RDs) noted a high prevalence of TTIs of 2.5 % to 12 % compared to the studies with a high number of voluntary non-remunerated donations (VNRDs) reported TTIs rates of 1.57% to 6.2 %. There was a significant difference in the prevalence of HBV & HCV in VNRDs (0.48%) compared to RDs (4.15%). The rate of VNRDs was 0.10 % to 13%. The majority of blood donations were from male donors, representing more than 70 % of all donations. The female donations varied from 0.03% to 15 % in government/public blood banks than 29 % in private sector blood banks. The HBV & HCV infections and anemia were the most common causes of blood donation deferral. The 69.5 % of donors who tested positive for TTIs in a study reported previous blood donations. The educational status of donors noted to have an association with knowledge about the risk of TTIs. Odds of having limited knowledge about TTIs (OR: 4.04, CI: 1.567-10.435, p<0.01) were greater if donors had a secondary level of education compared to those with tertiary education. 48 % of blood donors did not know about the risk of TTIs through blood transfusion. There was notification of only about 54.25 % of all donors, who tested positive for any TTIs. This was mainly due to a lack of standardized reporting and follow up systems. Conclusion: This systemic review shows a high prevalence of TTIs, especially HBV, HCV & syphilis in the blood donor population. There is a high dependency on RDs, with minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods, and limited knowledge of donors about their health. There is a lack of widespread standardized testing and follow up of patients who tested positive on initial testing. Large prospective multicenter clinical trials are required for a better understanding of the TTIs by testing and creating a follow-up system for both blood donors and recipients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

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A pseudoaneurysm of the splenic artery (SAP) is a rare entity which is associated with pancreatitis in 52% of cases. In the presence of pancreatitis, the enzymatic damage to the wall of splenic artery results in pseudoaneurysm formation. The clinical presentation is variable and ranges from asymptomatic to hemodynamic instability. The diagnosis of SAP is challenging in the presence of peripancreatic fluid collection or pseudocyst, where CT abdomen can miss small pseudoaneurysms. Angiography is a useful modality to establish a definitive diagnosis. We present a 49-year-old male with a history of recurrent pancreatitis due to alcoholism who presented with acute abdominal pain and was found to have acute pancreatitis. Abdominal CT scan showed a peripancreatic fluid collection and hyperdense lesion at the splenic hilum, which was diagnosed as SAP on angiography. A transcatheter embolization was performed with complete resolution of symptoms thereafter.

Introduction: Secondary Central Nervous System Lymphoma (SCNSL) is the spread of a lymphoma to the CNS, the primary focus of which is situated elsewhere in the body. Most commonly, it is a non-Hodgkin lymphoma which either presents as a CNS involvement due to systemic relapse or progression, or as an isolated relapse in the CNS despite systemic remission. Traditionally, it has been treated by intrathecal or systemic chemotherapy and/or WBRT (Whole-brain radiation therapy) but recently, the use of high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has shown encouraging results. We present a systematic review of literature displaying the treatment outcomes of HDT/ASCT in SCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on July 08 2020 on PubMed, Cochrane Library and Clinicaltrials.Gov by using the relevant MeSH terms of high-dose chemotherapy, autologous stem cell transplantation, CNS lymphoma, efficacy and safety. Following screening by 2 reviewers, we selected 12 published studies (n=353) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 232/353 patients eventually underwent sequential HDT+ASCT who were evaluable for treatment response out of which 190 patients had SCNSL (see table 1). Carmustine (BCNU) based HDT: BCNU based regimens have been the most extensively studied HDT among SCNSL patients (n=81). Korfel et al. in a phase 2 trial (2013, n=30) used HDT combination of BCNU, thiotepa and etoposide followed by ASCT in SCNSL patients. No patient was given whole brain radiation therapy (WBRT). The results yielded a PR of 8%, CR of 63% and 2-year OS of 63%. 1 toxicity related mortality (TRM) was noted and >grade 4 adverse effects included infection (4%) and stomatitis (13%). Ferreri et al. (2015, n=38) in a phase 2 trial use HDT with BCNU plus thiotepa on 38 patients 20 of whom underwent subsequent ASCT. The results showed CR of 100%, event free survival (EFS) of 40% ±9% and OS of 41% ±8% at 5 years with four patients suffering TRM. Thiotepa, busulfan and cyclophosphamide (TBC) based HDT: The combination based on TBC has been a popular option for SCNSL patients (n=53). In a retrospective analysis by Welch et al. (2014, n=17), TBC combination followed by sequential ASCT was studied in both primary and SCNSL patients (primary malignancy being diffuse large B-cell lymphoma) and the collective results showed complete response (CR) of 100%, PFS of 93% (95% CI: 61-99%) and OS of 93% (95% CI: 61-99%) at 3 years. In addition to the excellent efficacy response, no TRM or grade 4 toxicities were documented. Chen et al. (2015, n=12) in a phase 2 trial used HDT with rituximab and TBC (R-TBC) combination followed by ASCT rescue in 12 SCNSL patients. At 2 years, the progression free survival (PFS) was 51% (95% CI: 18-77%) and overall survival (OS) was 83% (95% CI: 48-96%). Two patients developed neurotoxicity and one TRM was recorded. Methotrexate (MTX) based HDT: MTX based combinations have also been widely used as HDT preceding ASCT in SCNSL patients (n=51). Fischer et al. (2008, n=20) studied HDT of MTX plus ifosfamide (IFO) in a retrospective analysis which showed PR of 30%, CR of 60% and median OS of 8.7 months and two TRM (due to sepsis in neutropenia) in SCNSL patients. Lee et al. (2015, n=31) in a prospective cohort study evaluated HDT with MTX based multidrug combination with ASCT in SCNSL patients which yielded a PR of 41.6%, CR of 50% and OS of 9 months (95% CI: 5-12 months). Five patients had suffered TRM. Conclusion: The combination of HDT with ASCT has yielded promising treatment outcomes both in terms of favorable efficacy rates and reduced rates of toxicity in SCNSL patients proving to be a comparable alternative to traditionally used chemo-radiation. However, the data at present is limited to few phase 2 trials with some being displayed collectively with data of primary CNS lymphoma patients. There is an increased need to carry out randomized phase 3 trials exclusively on SCNSL patients to better predict the efficacy and safety profile of HDT/ASCT in these patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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Introduction: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) variant limited to the CNS with rare evidence of systemic spread. It constitutes 4% of all CNS malignancies. Owing to the impenetrable blood-brain barrier to routine chemo-immunotherapy, the efficacy of such treatment is less than optimal. The combination of chemoradiotherapy has substantial associated risk of late neurotoxicity and increased disease recurrence. High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) as rescue has been shown to be effective. We performed a systematic review of literature to explore the efficacy of HDT and ASCT in patients with PCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on May 28, 2020 on Pubmed, Cochrane Library and Clinicaltrials.Gov by using the MeSH terms related to high-dose chemotherapy, autologous transplantation and primary CNS lymphoma which yielded 561 relevant articles. Following subsequent screening by 2 reviewers, we selected 16 published trials (n=745) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 405/745 patients eventually underwent sequential HDT+ASCT the results of which are illustrated in table 1 and 2 stratified on the basis of newly diagnosed (ND) (n=641) and relapsed, refractory (RR) PCNSL patients (n=104) respectively. ND PCNSL: Among ND PCNSL patients, carmustine and thiotepa based regimens were the most widely studied HDT regimens (n= 351). Illerhaus et al. (2016, n= 81) in a phase 2 trial used HDT of intravenous (IV) combinations of rituximab, thiotepa and carmustine followed by ASCT on 73 patients which yielded partial response (PR) 13.9 %, complete response (CR) 77.2% and overall survival (OS) 81% at 36 months. 4 patients suffered transplant related mortality (TRM), mucositis (8%) and arrhythmias (2%) were the most common nonhematologic >grade 4 adverse effects. Ferreri et al. (2017) [n=122] in a phase 2 trial (n=59) used ASCT following Carmustine + Thiotepa HDT and reported 2-year OS of 71% and CR of 93% with a modest toxicity profile (infections (8%), mucositis (5%) and 2 (3%) treatment related deaths). IV thiotepa, busulfan and cyclophosphamide (TBC) combination was used as HDT / ASCT in ND PCNSL patients (n=208). Omuro et al. (2015) (n=32) used HDT with TBC followed by ASCT in 26 patients. Whole brain radiation therapy (WBRT) was not given to any patient regardless of recurrence or relapse. At 5 years, the study reported PR=11%, CR=81%, and OS=81%. In a phase 2 trial, Houillier et al. (2019, n=140) used TBC combination as HDT followed by either WBRT or ASCT (2 separate arms), 44 patients of the latter arm exhibited a CR of 38% and OS of 66% at 5 years with 5 treatment related deaths. An IV combinations of carmustine, etoposide, cytarabine and melphalan (BEAM) have also been used as HDT with ASCT in 3 phase 2 trials (n=59). Abrey et al. (2003, n=28) in a phase 2 trial used high-dose BEAM therapy followed by ASCT which yielded PR of 14%, CR of 57% and OS of 55% at 28 months. Only 1 treatment related mortality occurred. RR PCNSL: TBC combination has been the most extensively used HDT regimen for RR PCNSL patients undergoing ASCT (n=65). Soussain et al. (2008, n=43) conducted a phase 2 trial in which high-dose TBC sequentially followed by ASCT was studied in 27 RR PCNSL patients. The results showed median PFS of 41.1 months with OS of 45% at 2 years however, 3 toxicity related deaths were observed. Kasenda et al. (2017, n=39) in a phase 2 trial used high-dose combination of rituximab, carmustine and thiotepa coupled with ASCT on RR PCNSL patients which yielded PR of 15.4%, CR of 56% and median PFS of 12.4 months with an OS of 56.4% at 2 years. However, there were 4 treatment related deaths and an extensive toxicity spectrum with widespread pancytopenia (thrombocytopenia =96.9%, leukopenia =100%, anemia =65.6%) and nonhematologic infections (65.6%) observed. Conclusion: HDT followed by ASCT rescue has exhibited favorable outcomes and can be used an alternative to WBRT especially in ND PCNSL patients. Evidence is limited by mainly phase II non randomized data. Although, hematologic adverse effects due to HDT were observed on a widespread basis, transplant related mortality was however minimal. There is need to carry out prospective randomized phase III trials to access the safety and efficacy profile of HDT / ASCT for ND and RR PCNSL. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: According to the National Comprehensive Cancer Network (NCCN) 2019 guidelines on multiple myeloma (MM) treatment, three-drug regimens using bortezomib (V) and dexamethasone (d) in combination with either lenalidomide (R), (VRd) or Cyclophosphamide (C) combination (VCd) are standard first-line treatment options in newly diagnosed multiple myeloma (NDMM), regardless of transplant eligibility. However, the two combinations have not been studied head-to-head. This systemic review aims to compare the efficacy and safety outcomes of VCd versus VRd in NDMM patients. Methods: We performed a comprehensive literature search on PubMed, Cochrane Library, and ClinicalTrials.gov on July 27, 2020. We used the MeSH terms for 'multiple myeloma', 'cyclophosphamide', 'bortezomib', 'dexamethasone', 'lenalidomide', and their associated keywords. The search yielded 410 articles. Screening and data extraction were done according to PRISMA guidelines. After excluding case reports, case series, observational studies, review articles, meta-analysis, and retrospective studies, 11 phase II and III clinical trials (n=1088) were included of which three assessed VCd and eight assessed VRd in NDMM. Results: There was no trial on the direct comparison of VCd with VRd. Total 111 NDMM patients were evaluable who received VCd (Table 1). Moreover, total 977 NDMM patients were evaluable who received VRd (Table 2). VCd arm results: Reeder et al. (2009, n=33) achieved the best ORR of 88% which was largely VGPR or better (61%). Tuchman et al. (2017, n=14) reported similar results of ORR (64%) with 58% achieving VGPR or better and 7% achieving PR. Contrary to these ORR distributions, Sunami et al. (2019, n=64) reported the ORR of 80% which was largely driven by PR of 41%. Moreover, a 2-year OS of 97% and PFS of 77% which is consistent with previous results. The toxicity profile with VCd was manageable with mostly hematological adverse events. Neuropathy was significantly lower when compared to VRd. VRd arm results: NDMM patients, in a phase III trial by Durie et al. (2016, n=471) achieved ORR of 82% (PR=38%, VGPR=28%, and CR=16%) with VRd. The mPFS was 43 months and mOS was 75 months, both significantly better than control. Stadtmauer et al. (2019, n=254) results were similar as well with 3-year PFS and OS as 58% and 85% respectively. Kumar et al. (2012, n=42) had a 1-year OS of 100% and PFS of 83%. O'Donnel et al. (2018, n=50) achieved mPFS of 35 months while mOS could not be reached. Luoma et al. (2019, n=78) achieved a 3-year PFS of 52% while OS of 83%. Severe neuropathy was reported with VRd regimen. The remaining toxicity profile was mostly hematological and manageable with prompt intervention. Conclusion: The two upfront regimens of VCd and VRd show favorable efficacy and safety outcomes in NDMM patients. VRd arm achieves relatively higher rates of ORR, CR and VGPR. Cost-effectiveness and lower neuropathy incidence associated with VCd makes it favorable over VRd. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.