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  1. Article: Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer.

    Smaglo, Brandon G

    Cancers

    2023  Volume 15, Issue 8

    Abstract: Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been ...

    Abstract Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.
    Language English
    Publishing date 2023-04-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15082377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Perineural Invasion by an Intraductal Papillary Mucinous Neoplasm of Pancreas: A Case Report of an Unusual and Unreported High-Risk Feature of Malignant Progression.

    Mahadik, Juhi D / Machado Heredia, Maria Luisa / Smaglo, Brandon G / Fisher, William E / Dhingra, Sadhna

    Annals of clinical and laboratory science

    2022  Volume 52, Issue 5, Page(s) 838–842

    Abstract: Perineural invasion is a frequent histological finding in pancreatic adenocarcinoma. However, perineural invasion by intraductal papillary mucinous neoplasm (IPMN), a precursor lesion of pancreatic adenocarcinoma, has not been reported so far. We report ... ...

    Abstract Perineural invasion is a frequent histological finding in pancreatic adenocarcinoma. However, perineural invasion by intraductal papillary mucinous neoplasm (IPMN), a precursor lesion of pancreatic adenocarcinoma, has not been reported so far. We report a unique case of perineural invasion by IPMN in a 60-year-old female who underwent pancreatoduodenectomy for high-risk features of IPMN. Histological evaluation showed increased nerve density in the connective tissue of IPMN with multiple foci of perineural invasion by IPMN. In addition, there was a discrete 2 mm focus of invasive carcinoma that did not show perineural invasion. Chemotherapy was started and the patient is disease-free at 29 months follow up. The case illustrates previously unreported neuroplastic alterations and neutrotropism in benign neoplastic component of a malignant IPMN.
    MeSH term(s) Female ; Humans ; Middle Aged ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/pathology ; Adenocarcinoma, Mucinous/pathology ; Adenocarcinoma ; Pancreatic Intraductal Neoplasms ; Pancreas/pathology ; Pancreatic Neoplasms
    Language English
    Publishing date 2022-11-08
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 193092-8
    ISSN 1550-8080 ; 0091-7370 ; 0095-8905
    ISSN (online) 1550-8080
    ISSN 0091-7370 ; 0095-8905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Trends Over Time in Recurrence Patterns and Survival Outcomes after Neoadjuvant Therapy and Surgery for Pancreatic Cancer.

    Cass, Samuel H / Tzeng, Ching-Wei D / Prakash, Laura R / Maxwell, Jessica / Snyder, Rebecca A / Kim, Michael P / Huey, Ryan W / Smaglo, Brandon G / Pant, Shubham / Koay, Eugene J / Wolff, Robert A / Lee, Jeffery E / Katz, Matthew H G / Ikoma, Naruhiko

    Annals of surgery

    2024  

    Abstract: Objective: We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).: Background: Data are limited on how modern multimodality therapy ...

    Abstract Objective: We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).
    Background: Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival.
    Methods: Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018.
    Results: The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7 mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6 mo; 3-year rate, 7%, 10%, and 20%; P < 0.005).
    Conclusions: We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 340-2
    ISSN 1528-1140 ; 0003-4932
    ISSN (online) 1528-1140
    ISSN 0003-4932
    DOI 10.1097/SLA.0000000000006269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Profile and potential of ixabepilone in the treatment of pancreatic cancer.

    Smaglo, Brandon G / Pishvaian, Michael J

    Drug design, development and therapy

    2014  Volume 8, Page(s) 923–930

    Abstract: The management of metastatic pancreatic adenocarcinoma is a challenge for medical oncologists because of both the aggressive nature of the disease and the relative paucity of effective systemic treatments with activity against this type of tumor. In the ... ...

    Abstract The management of metastatic pancreatic adenocarcinoma is a challenge for medical oncologists because of both the aggressive nature of the disease and the relative paucity of effective systemic treatments with activity against this type of tumor. In the effort to discover new agents and combinations that may augment the therapeutic arsenal available for the management of this cancer, early phase clinical trials have been performed using ixabepilone, an epothilone B analog, with promising results. Targeting the microtubule system with certain taxanes in the management of pancreatic adenocarcinoma has been validated; ixabepilone also targets the microtubule system, interfering with it in an alternate manner from the taxane mechanism. Ixabepilone has demonstrated activity in cancers that have become taxane-resistant as well as those that never had any demonstrable taxane susceptibility. The available data for the use of ixabepilone in the management of pancreatic adenocarcinoma are limited but promising. Single-arm studies have demonstrated both clinical efficacy and tolerable toxicity for the use of ixabepilone as monotherapy. The trial data available for ixabepilone used as a part of combination therapy are similar: it has been paired with chemotherapy (carboplatin, irinotecan) and biologic therapy (dasatinib, sunitinib) at the Phase I level to treat solid tumors in general, again with tolerable side effects and a suggestion of benefit. A single Phase II study has evaluated combination therapy with ixabepilone in the management of patients with pancreatic cancer, pairing it with cetuximab with clinical benefit. Although these trials are promising with regard to addition of ixabepilone to the slim armamentarium for management of pancreatic cancer, further work is still to be done. Importantly, this work bears the burden of not only validating the clinical benefit of ixabepilone, but also of determining whether this benefit is enhanced in any way by combination therapy, and where ixabepilone fits in the sequence of management for patients with metastatic pancreatic cancer.
    MeSH term(s) Adenocarcinoma/drug therapy ; Adenocarcinoma/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Drug Resistance, Neoplasm ; Epothilones/adverse effects ; Epothilones/pharmacology ; Epothilones/therapeutic use ; Humans ; Neoplasm Metastasis ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Tubulin Modulators/adverse effects ; Tubulin Modulators/pharmacology ; Tubulin Modulators/therapeutic use
    Chemical Substances Epothilones ; Tubulin Modulators ; ixabepilone (K27005NP0A)
    Language English
    Publishing date 2014-07-14
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2451346-5
    ISSN 1177-8881 ; 1177-8881
    ISSN (online) 1177-8881
    ISSN 1177-8881
    DOI 10.2147/DDDT.S52964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Utility of Established Prognostic Scoring Systems for Patients with Advanced Pancreatic Adenocarcinoma Enrolled in Immunotherapy-Based Early-Phase Clinical Trials.

    Surana, Rishi / Gonzalez, Graciela Nogueras / Rogers, Jane / Hong, David S / Yap, Timothy A / Rodon, Jordi / Naing, Aung / Wolff, Robert A / Smaglo, Brandon G / Bernstam, Funda Meric / Subbiah, Vivek / Pant, Shubham

    Journal of gastrointestinal cancer

    2023  Volume 54, Issue 4, Page(s) 1308–1315

    Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy for which multiagent chemotherapy is the mainstay of treatment resulting in limited survival and symptomatic benefit. Treatment with immune checkpoint inhibitors (ICI) has proven ...

    Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy for which multiagent chemotherapy is the mainstay of treatment resulting in limited survival and symptomatic benefit. Treatment with immune checkpoint inhibitors (ICI) has proven effective in a growing number of solid tumors but has yet to show clinical benefit in patients with PDAC. Given the growing number of ICI-based clinical trials in development for patients with PDAC and lack of clinical benefit thus far with ICI-based therapies in these patients, we sought to (1) determine the outcomes of patients with PDAC treated with ICI-based therapies as part of an early phase clinical trial, (2) validate the utility of established prognostic scoring systems, and (3) identify novel prognostic factors in an attempt to better identify patients that would benefit from enrollment onto an ICI-based early phase clinical trial.
    Methods: We conducted a single-center retrospective analysis of patients with advanced PDAC who were treated with ICI-based therapy as part of an early-phase clinical trial.
    Results: Patients were only able to stay on study for a limited time due to disease progression and/or a change in performance status and had a poor overall survival. Established prognostic scoring systems were not effective in predicting outcomes in this patient population, but factors such as pre-treatment albumin neutrophil to lymphocyte ratio (NLC) may be helpful in patient selection.
    Conclusions: This study underscores the need for larger studies to help identify patient and tumor intrinsic factors that predict response to ICI-based therapies in patients with PDAC.
    MeSH term(s) Humans ; Pancreatic Neoplasms/drug therapy ; Adenocarcinoma/drug therapy ; Prognosis ; Retrospective Studies ; Carcinoma, Pancreatic Ductal/drug therapy ; Immunotherapy/methods
    Language English
    Publishing date 2023-04-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2452514-5
    ISSN 1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
    ISSN (online) 1941-6636 ; 1559-0739
    ISSN 1941-6628 ; 1537-3649
    DOI 10.1007/s12029-023-00930-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cancer of Unknown Primary Presenting as Bone-Predominant or Lymph Node-Only Disease: A Clinicopathologic Portrait.

    Huey, Ryan W / Smaglo, Brandon G / Estrella, Jeannelyn S / Matamoros, Aurelio / Overman, Michael J / Varadhachary, Gauri R / Raghav, Kanwal P S

    The oncologist

    2021  Volume 26, Issue 4, Page(s) e650–e657

    Abstract: Background: Cancer of unknown primary (CUP) presenting as bone-predominant (BCUP) or lymph node-only disease (LNCUP) represents two clinically distinct subsets of nonvisceral CUP. These present a diagnostic challenge with a large differential of ... ...

    Abstract Background: Cancer of unknown primary (CUP) presenting as bone-predominant (BCUP) or lymph node-only disease (LNCUP) represents two clinically distinct subsets of nonvisceral CUP. These present a diagnostic challenge with a large differential of putative primary cancers and defy the "one-treatment-fits-all" approach.
    Materials and methods: We identified patients with BCUP (n = 29) and LNCUP (n = 63) using a prospectively collected CUP database and tumor registry of patients seen at MD Anderson Cancer Center between 2001 to 2017. Clinicopathological characteristics, treatments, and outcomes were abstracted. A control group of non-BCUP/LNCUP cases (n = 443) from the database was used for comparison. Kaplan-Meier method was used to estimate overall survival and compared using log-rank test.
    Results: In this cohort, 64% and 60% patients had disseminated disease at diagnosis and 39% and 23% had Culine poor-risk disease in BCUP and LNCUP, respectively. Median overall survival (OS) for BCUP was 14.5 months and for LNCUP was 32.6 months. For BCUP, gemcitabine plus platinum was the most common initial chemotherapy (54%). For LNCUP, carboplatin plus paclitaxel was the most common initial chemotherapy (38%). Radiation was given to 74% of patients with BCUP and 37% of those with LNCUP. On multivariate analysis, poor-risk Culine group (hazard ratio [HR], 1.76; p < .001) and high neutrophil-to-lymphocyte ratio (HR, 2.38, p < .001) were associated with worse OS.
    Conclusion: BCUP and LNCUP are rare subsets within CUP with varying prognosis. Poor-risk Culine group and high neutrophil-to-lymphocyte ratio are associated with poor survival. Select patients with limited metastases can have long-term survival with aggressive multimodality treatment. Careful clinicopathological review can facilitate chances of site-directed therapy.
    Implications for practice: Cancer of unknown primary (CUP) rarely presents as bone-predominant (BCUP) or lymph node-only (LNCUP) disease. This article describes a cohort of each and compares with a larger CUP cohort. Patients with BCUP have unique issues with fractures and pain, often receiving radiation. Overall survival of 14.5 months was similar to a larger CUP comparison cohort. Patients with LNCUP had improved overall survival at 32.6 months, with longer survival in patients without disseminated disease. Culine poor-risk group and neutrophil-to-lymphocyte ratio were associated with worse overall survival. Tips regarding diagnosis and management of these rare malignant subsets are provided.
    MeSH term(s) Humans ; Kaplan-Meier Estimate ; Lymph Nodes ; Neoplasms, Unknown Primary/therapy ; Paclitaxel ; Prognosis
    Chemical Substances Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2021-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1002/onco.13700
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  7. Article: Continuum of care with anti-angiogenic therapies in metastatic colorectal cancer.

    Smaglo, Brandon G / Hwang, Jimmy

    Journal of gastrointestinal oncology

    2013  Volume 4, Issue 3, Page(s) 299–307

    Abstract: Inhibition of tumor angiogenesis has emerged as an important therapeutic component in the management of metastatic colorectal cancer. Three anti-angiogenic agents are currently approved in this clinical setting: bevacizumab, ziv-aflibercept, and ... ...

    Abstract Inhibition of tumor angiogenesis has emerged as an important therapeutic component in the management of metastatic colorectal cancer. Three anti-angiogenic agents are currently approved in this clinical setting: bevacizumab, ziv-aflibercept, and regorafenib. Bevacizumab, a monoclonal antibody that targets the angiogenesis-driving ligand vascular endothelial growth factor A (VEGF-A), is the only anti-angiogenic agent approved in first-line therapy for metastatic colorectal cancer, where it can be used in combination with intravenous 5-fluorouracil-containing chemotherapy regimens. In conjunction with second-line chemotherapies, bevacizumab also has anti-cancer activity, both for the management of metastatic colorectal cancer in patients who received it as a part of their first line therapy and for those who are naïve to it. Ziv-aflibercept also has demonstrated clinical activity in conjunction with the chemotherapeutic regimen FOLFIRI in the second line management of patients with metastatic colorectal cancer; it functions by binding VEGF-A to the vascular endothelial growth factor proteins VEGF-B and PIGF (placental growth factor). Regorafenib, which inhibits multiple tyrosine kinases, including the VEGF receptors, has proven clinical benefit in the management of patients with metastatic colorectal cancer refractory to all other therapies. For patients' whose cancers are refractory to all other therapies, there is also evidence for the use of bevacizumab with fluoropyrimidine monotherapy, but only in the bevacizumab-naïve patient subset. Presently, it is not clear if any one agent as more activity in a particular line of therapy than another, has greater efficacy when paired with a particular chemotherapy backbone, or if a particular patient subset is more likely to benefit from these agents. Given the present benefit and tolerance data, an anti-angiogenic agent should be considered in all lines of therapy in the management of metastatic colorectal cancer, with the evidence for the use of these agents in each specific line of therapy and in specific chemotherapeutic combinations driving agent selection.
    Language English
    Publishing date 2013-02-14
    Publishing country China
    Document type Journal Article
    ZDB-ID 2594644-4
    ISSN 2219-679X ; 2078-6891
    ISSN (online) 2219-679X
    ISSN 2078-6891
    DOI 10.3978/j.issn.2078-6891.2013.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Discordance of KRAS mutational status in a single colonic resection specimen in a patient with colorectal cancer: a case report and review of the literature.

    Smaglo, Brandon G / Marshall, John L

    Clinical colorectal cancer

    2013  Volume 12, Issue 3, Page(s) 214–217

    MeSH term(s) Adenocarcinoma, Mucinous/drug therapy ; Adenocarcinoma, Mucinous/genetics ; Adenocarcinoma, Mucinous/surgery ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/surgery ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Mutation/genetics ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Review Literature as Topic ; ras Proteins/genetics
    Chemical Substances KRAS protein, human ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2013-09
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2112638-0
    ISSN 1938-0674 ; 1533-0028
    ISSN (online) 1938-0674
    ISSN 1533-0028
    DOI 10.1016/j.clcc.2013.04.003
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  9. Article: Microsatellite instability in colorectal cancer.

    Smaglo, Brandon G / Marshall, John L

    Clinical advances in hematology & oncology : H&O

    2013  Volume 11, Issue 10, Page(s) 659–661

    MeSH term(s) Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; DNA, Neoplasm/genetics ; DNA, Neoplasm/metabolism ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Portraits as Topic
    Chemical Substances DNA, Neoplasm
    Language English
    Publishing date 2013-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2271951-9
    ISSN 1543-0790
    ISSN 1543-0790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Approach to the medical management of surgically resectable gastric cancer.

    Tesfaye, Anteneh / Marshall, John L / Smaglo, Brandon G

    Clinical advances in hematology & oncology : H&O

    2016  Volume 14, Issue 2, Page(s) 129–135

    Abstract: The optimal adjuvant management of patients with resectable gastric cancer remains a therapeutic challenge. Although the benefit of adjuvant therapy for these patients is clearly established, recurrence and mortality rates remain high despite such ... ...

    Abstract The optimal adjuvant management of patients with resectable gastric cancer remains a therapeutic challenge. Although the benefit of adjuvant therapy for these patients is clearly established, recurrence and mortality rates remain high despite such treatment. Moreover, surgical comorbidities and treatment toxicities result in high rates of failure to complete treatment after surgery. Two divergent approaches to adjuvant treatment have emerged as standard: postoperative chemoradiotherapy and perioperative chemotherapy. Because these approaches have never been compared directly, recommendations for adjuvant treatment require multidisciplinary discussion. During this discussion, the characteristics of the symptoms, the histology, location, and stage of the tumor, and the feasibility of the patient's completing all recommended therapy may be considered. In our own practice, we favor perioperative chemotherapy for patients with asymptomatic, proximal, higher-stage disease and adjuvant chemoradiotherapy for patients with symptomatic, distal, lower-stage disease. Herein, we summarize the available data for approaches to the adjuvant treatment of gastric cancer, with special consideration of the characteristics of the patients enrolled in the various studies. We also describe how we developed our paradigm for recommending a particular approach to adjuvant treatment for each patient.
    MeSH term(s) Chemoradiotherapy, Adjuvant ; Combined Modality Therapy ; Disease Management ; Humans ; Neoplasm Staging ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/epidemiology ; Stomach Neoplasms/etiology ; Stomach Neoplasms/surgery ; Treatment Outcome
    Language English
    Publishing date 2016-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2271951-9
    ISSN 1543-0790
    ISSN 1543-0790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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