Papers by Waldo Concepcion
Cureus, 2018
Here we describe the case of a 10-year-old boy with a history of chronic hepatitis B who was diag... more Here we describe the case of a 10-year-old boy with a history of chronic hepatitis B who was diagnosed with hepatocellular carcinoma (HCC) with a large central hepatic mass and metastatic disease in a celiac lymph node. His tumor was unresectable, due to location and lack of clear margins, and he could not receive chemotherapy due to elevated bilirubin. He was treated with stereotactic body radiotherapy (SBRT) to the primary site and involved nodal region. After completing radiotherapy, his total bilirubin level fell below 1.0 mg/dL, allowing him to begin systemic therapy with cisplatin and doxorubicin. At three months after SBRT, his bilirubin was 0.1 mg/dL, alpha-fetoprotein (AFP) was 88 ng/mL, and imaging demonstrated a decrease in tumor size (total volume 28.7 cc), with no evidence of local or distant disease progression. He then developed distant disease within the liver, but his disease remained controlled at the primary site and nodes that had been treated with SBRT. He under...
Biomedicines, 2020
The antigen-specific apoptotic DNA immunotherapeutic, ADi-100, is designed to suppress type 1 dia... more The antigen-specific apoptotic DNA immunotherapeutic, ADi-100, is designed to suppress type 1 diabetes and consists of two DNA plasmids encoding genetic sequences of the apoptosis-inducing molecule, BAX, and the secreted form of the autoantigen, glutamic acid decarboxylase 65, that is CpG hyper-methylated to avoid inflammatory signaling (msGAD55). Upon a four-day treatment with ADi-100 of young female non-obese diabetic (NOD) mice, the frequency of various tolerogenic dendritic cell populations increased in draining lymph nodes; these cells lost the capacity to stimulate glutamic acid decarboxylase (GAD)-specific CD4+ T lymphocytes and were associated with the previously demonstrated enhancement of GAD-specific regulatory T cells. The efficacy of two ADi-100 formulations containing different proportions of BAX and msGAD55, 1:4 (10/40 µg) and 1:2 (17/33 µg), was evaluated in mildly hyperglycemic pre-diabetic NOD female mice. Both formulations suppressed the incidence of diabetes by 8...
Molecular Genetics and Metabolism, 2020
We attest that we have received and archived written consent for participation/publication from a... more We attest that we have received and archived written consent for participation/publication from all individuals whose data is included in this study IRB Approval: Patients 1 and 2 are enrolled under COMIRB (Colorado Multiple Institutional Review Board) research protocol 16-0146
Molecular Therapy - Methods & Clinical Development, 2020
Acute kidney injury (AKI) is characterized by a sudden failure of renal function, but despite inc... more Acute kidney injury (AKI) is characterized by a sudden failure of renal function, but despite increasing worldwide prevalence, current treatments are largely supportive, with no curative therapies. Mesenchymal stromal cell (MSC) therapy has been shown to have a promising regenerative effect in AKI but is limited by the ability of cells to home to damaged tissue. Pulsed focused ultrasound (pFUS), wherein target tissues are sonicated by short bursts of sound waves, has been reported to enhance MSC homing by upregulating local homing signals. However, the exact mechanism by which pFUS enhances MSC therapy remains insufficiently explored. In this study, we studied the effect of bone marrow-derived MSCs (BM-MSCs), in conjunction with pFUS, in a mouse model of cisplatin-induced AKI. Here, BM-MSCs improved kidney function, reduced histological markers of kidney injury, decreased inflammation and apoptosis, and promoted cellular proliferation. Surprisingly, whereas pFUS did not upregulate local cytokine expression or improve BM-MSC homing, it did potentiate the effect of MSC treatment in AKI. Further analysis linked this effect to the upregulation of heat shock protein (HSP)20/ HSP40 and subsequent phosphatidylinositol 3-kinase (PI3K)/ Akt signaling. In summary, our results suggest that pFUS and BM-MSCs have independent as well as synergistic therapeutic effects in the context of AKI.
BACKGROUND The widespread use of smartphones helps individuals to self-report their subjective ph... more BACKGROUND The widespread use of smartphones helps individuals to self-report their subjective physical and emotional states, as well as to report states they perceive from significant acquaintances around them. OBJECTIVE The objective of this study was to evaluate feasibility and human factors influencing the acceptance and reliability of ‘Peer-ceived Momentary Assessment (PeerMA)’ research method where smartphones are leveraged to enable an estimate of the individual’s state e.g., stress duration based on his/her designated peers (friends, family members). METHODS We have recruited 13 participants to self-report their perceived levels of stress, fatigue, and anxiety multiple times a day using Ecological Momentary Assessment (EMA) along 4 weeks. The participants invited a total of 20 peers (e.g., friends, relatives) to assess the same outcomes as they perceived them projected by the participant using the PeerMA method. RESULTS Preliminary results show that, using PeerMA, 55% of pee...
Oncotarget, 2019
The development of chemotherapy drug resistance remains a significant barrier for effective thera... more The development of chemotherapy drug resistance remains a significant barrier for effective therapy in several cancers including breast cancer. Bone marrowderived mesenchymal stem cells (BMMSCs) have previously been shown to influence tumor progression and the development of chemoresistance. In the present study, we showed that when GFP labelled BMMSCs and RFP labelled HCC1806 cells are injected together in vivo, they create tumors which contain a new hybrid cell that has characteristics of both BMMSCs and HCC1806 cells. By labelling these cells prior to their injection, we were then able to isolate new hybrid cell from harvested tumors using FACS (DP-HCC1806:BMMSCs). Interestingly, when DP-HCC1806:BMMSCs were then injected into the mammary fat pad of NOD/SCID mice, they produced xenograft tumors which were smaller in size, and exhibited resistance to chemotherapy drugs (i.e. doxorubicin and 5-fluorouracil), when compared tumors from HCC1806 cells alone. This chemoresistance was shown to associated with an increased expression of tetraspanins (CD9, CD81) and drug resistance proteins (BCRP, MDR1). Subsequent siRNA-mediated knockdown of BMMSC-CD9 in DP-HCC1806:BMMSCs resulted in an attenuation of doxorubicin and 5-fluorouracil chemoresistance associated with decreased BCRP and serum cytokine expression (CCL5, CCR5, CXCR12). Our findings suggest that within the tumor microenvironment, CD9 is responsible for the crosstalk between BMMSCs and HCC1806 breast cancer cells (via CCL5, CCR5, and CXCR12) which contributes to chemoresistance. Hence, BMMSC-CD9 may serve as an important therapeutic target for the treatment of breast cancer.
Open Forum Infectious Diseases, 2018
Background. The empiric initial antibiotic regimen (IAR) for treatment of febrile neutropenia (FN... more Background. The empiric initial antibiotic regimen (IAR) for treatment of febrile neutropenia (FN) relies on a knowledge of epidemiology and susceptibility patterns of bacterial bloodstream infections (BSI), especially in high-risk patient populations, i.e., those receiving chemotherapy for hematologic malignancies (HM) or undergoing hematopoietic stem cell transplant (HCT). As the last US national survey of BSI epidemiology in cancer patients was published in 2003, we sought to update these data focusing exclusively on high-risk patients with attention to IARs used and their concordance with susceptibilities of isolated bloodstream pathogens. Methods. A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with BSI during first FN after cytotoxic chemotherapy or HCT. Concordance between antibiotic and BSI was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with IAR used, for single organism bacteremias only. Results. Among 294 FN bacteremic episodes (93 HCT), there were 336 bacterial pathogens (48.5% Gram negative [GN] 46.5% Gram positive [GP] and 6% anaerobes), with 88% monomicrobial episodes. E. coli and viridans group Streptococci (VGS) were the most commonly isolated GN and GP, respectively, each accounting for nearly 25% of total organisms identified. IARs included cefepime 61%, piperacillin-tazobactam 24%, and meropenem 8%. Isolates were nonsusceptible to the IAR in 38/227 (17%) of FN episodes. Antibiotic mismatch was more likely to occur with a non-VGS GP (37%) vs. GN (13%) or VGS (2%) P < 0.001. Conclusion. This is the first US national survey of high-risk BSI in FN. Although mismatch between BSI and IAR occurs in 17% of FN bacteremia episodes, this is driven primarily by non-VGS GP isolates such as CoNS and MRSA. Currently used IARs, comprised primarily of cefepime and piperacillin-tazobactam, generally provide reliable coverage for GN isolates across the United States (87%) but careful tracking of this rate is essential to identify further erosion of coverage in the current era of antimicrobial resistance.
Emerging Infectious Diseases, 2017
MSM-associated outbreak lineage characterized by reduced azithromycin susceptibility and circulat... more MSM-associated outbreak lineage characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions (4). The introduction of this MSM-associated S. flexneri 3a lineage into Taiwan in 2015 illustrates that the pathogen can spread rapidly across continents, possibly through intensified sexual networks among MSM (2,8). We recommend continued surveillance for antimicrobial resistance genes in S. flexneri to inform clinical management of shigellosis among MSM and public health interventions where needed, including appropriate antimicrobial drug stewardship.
Pediatric Blood & Cancer, 2016
Here, we present the case of a pediatric patient with newly diagnosed hepatocellular carcinoma ca... more Here, we present the case of a pediatric patient with newly diagnosed hepatocellular carcinoma causing central biliary obstruction and persistently elevated bilirubin of 3.0-4.3 mg/dl despite placement of bilateral internal-external biliary drains. The tumor was not resectable, and the patient was not a candidate for liver transplant due to nodal disease, for chemotherapy due to hyperbilirubinemia, or for local therapies aside from stereotactic body radiotherapy (SBRT). In this report, we discuss the successful use of SBRT in the management of this patient, and its role in allowing the patient to become a candidate for additional therapies.
The American Journal of Gastroenterology, 2000
mass on the greater curvature adjacent pancreas that could represent a leiomyoma. There was no ob... more mass on the greater curvature adjacent pancreas that could represent a leiomyoma. There was no obvious local invasion. EGD/EUS were performed and showed no mucosal lesions, a complex partially cystic mass measuring 5ϫ6 cm, which appeared to be located deep to the muscularis propria and not involving the gastric wall. He was referred to surgery and underwent exploratory celiotomy, partial gastrectomy and resection of the juxtagastric mass with a wedge of full thickness posterior gastric wall. All adjacent structures were unremarkable. Pathology showed organizing hematoma without necrosis, normal stomach and benign nodes. He did well post-operatively. This was an unusual case of organizing hematoma due to the absence of any significant history of precipitating factors and the presentation as an abdominal mass which resembled gastric leiomyoma on imaging studies.
Transplantation proceedings, 1993
Journal of the American College of Surgeons, 1994
Clinical transplants, 1994
A number of modifications in patient selection, operative technique, and immunosuppressive manage... more A number of modifications in patient selection, operative technique, and immunosuppressive management have greatly contributed to the success of the liver transplant program at CPMC. Graft rejection and the timely detection of EBV infection are ongoing problems in hepatic transplantation that are foci of active research in our field. To address these issues, our group is investigating the activity of cytokines and adhesion molecules using sophisticated molecular techniques, and we are developing a sensitive assay for EBV markers in blood. These and other projects currently in progress will continue when we move our liver transplant program to Stanford University Medical Center in January 1995.
The Journal of pediatrics, Jan 11, 2015
To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplanta... more To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA). A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford. Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantatio...
Surgery, 1996
This study examines factors associated with the performance of orthotopic liver transplantation (... more This study examines factors associated with the performance of orthotopic liver transplantation (OLT) without red blood cell (RBC) transfusion. Between January 1992 and December 1994, 306 primary OLTs were performed with recipients divided into two groups: group 1 patients (61 recipients, 20% of total) underwent transplantation without packed RBCs, and group 2 patients (245 recipients, 80% of cases) received a transfusion of at least 1 unit of RBCs during operation. Recipients in group 1 compared with group 2 had less advanced liver disease (20% hospitalized and 48% Child&#39;s class C versus 58% hospitalized and 73% Child&#39;s class C, p &lt; 0.01) and lower frequency of right upper quadrant surgery (13% versus 25%, p &lt; 0.05). Group 1 recipients also had significantly higher preoperative hematocrits (38% versus 33%, p &lt; 0.01), lower prothrombin times (15.4 versus 16.7 seconds, p &lt; 0.001) and partial thromboplastin times (36.9 versus 42.2 seconds, p &lt; 0.01), a greater proportion of patients transplanted by piggyback technique (87% versus 59%, p &lt; 0.001), and shorter operative times (7.9 hours versus 9.2 hours, p &lt; 0.001). Moreover, a greater percentage of patients underwent OLT without RBC transfusion in each successive year: 9% in 1992, 21% in 1993, and 31% in 1994 (p &lt; 0.001). Logistic regression analysis showed the following factors to be independent predictors of OLT without RBC transfusion. Preoperative Hct, United Network of Organ Sharing status, piggyback technique, operative time, and year of transplantation. OLT can be performed without transfusion of RBCs in recipients with less advanced liver disease, and surgical technique, along with increased experience by the transplant team, are important factors.
Journal of the American College of Surgeons, 2010
C.A. Bonham1, A. Gallo2, C.O. Esquivel3, W. Concepcion4, S. Strober5 1Sugery, Division Of Transpl... more C.A. Bonham1, A. Gallo2, C.O. Esquivel3, W. Concepcion4, S. Strober5 1Sugery, Division Of Transplantation, Stanford University, Palo Alto/UNITED STATES OF AMERICA, 2Surgery, Division Of Transplantation, Stanford University, Palo Alto/UNITED STATES OF AMERICA, 3Surgery/transplantation, Stanford University, Stanford/ CA/UNITED STATES OF AMERICA, 4, Stanford University, stanford/ UNITED STATES OF AMERICA, 5Medicine, Stanford University, Stanford/UNITED STATES OF AMERICA
Journal of Pediatric Gastroenterology and Nutrition, 2005
Digestive Diseases and Sciences, 2010
A 39-year-old Hispanic male presented with early satiety and postprandial nausea and vomiting. He... more A 39-year-old Hispanic male presented with early satiety and postprandial nausea and vomiting. He also complained of right-sided abdominal pain, increasing abdominal girth, and a 25 lb weight loss over a 2-month period. The patient reported intermittent alcohol use for 17 years (3–4 beers per week), but had quit alcohol 6 years prior. He had no significant past medical, surgical, or family history. On physical examination, he was markedly jaundiced with bitemporal wasting consistent with severe malnourishment. His abdominal examination revealed a protuberant lobular mass palpable in the right upper quadrant extending inferiorly and medially. A fluid wave was also present. Laboratory studies showed leukocytosis of 23,400/mm, aspartate aminotransferase (AST) 202 U/l, alanine aminotransferase (ALT) 153 U/l, alkaline phosphatase 997 U/l, total bilirubin 10.9 mg/dl, and international normalized ratio for prothrombin time (INR) 1.5. Hepatitis serology, mitochondrial antibody, and tuberculosis smear of paracentesis fluid were all negative. Tumor markers, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and carbohydrate antigen (CA) 19-9, were all normal. Computed tomography (CT) of the abdomen revealed multiple confluent hypodense masses, some with calcifications. The right and left lobes of the liver were extensively replaced by these masses, and the caudate lobe was markedly hypertrophied (Fig. 1). Magnetic resonance imaging (MRI) of the abdomen showed similar findings (Fig. 2). Percutaneous liver biopsy revealed infiltration of the hepatic parenchyma by an epithelioid cell population, some with intracytoplasmic lumens. These cells stained positive for CD31 and CD34, two markers for vascular endothelial differentiation. The overall histologic and immunohistochemical findings supported the diagnosis of epithelioid hemangioendothelioma. The patient deteriorated rapidly during his hospital course. He had severe pain and abdominal distention despite repeated therapeutic paracentesis. His liver function declined, with total bilirubin increasing to 28.5 mg/dl and INR increasing to 2.0. His renal function also worsened. His blood urea nitrogen reached 86 mg/dl, and creatinine 2.9 mg/dl. He had several episodes of hematemesis and melena from esophageal varices requiring transfusion of fresh frozen plasma (FFP) and emergent endoscopy. Given the rapid deterioration and the fact that no metastatic lesions were found during a bone scan, positron emission tomography (PET) CT, and CT of the thorax, the patient was listed for liver transplantation. His model for end-stage liver disease (MELD) score increased from 33 to 39 in 9 days. The patient underwent liver transplantation 44 days after admission to our hospital. The explanted liver measured 27.0 9 19.5 9 14.5 cm and weighed 2,420 g (Fig. 3). There were multiple ill-defined, fibrotic, whiteyellow-tan masses that merged with each other and involved the entire liver. Histopathologic and immunohistochemical examinations confirmed the previous diagnosis Y. I. Liu S. S. Brown A. Kamaya (&) Department of Radiology, Stanford University Medical Center, 300 Pasteur Dr., H1307, Stanford, CA 94305, USA e-mail: kamaya@stanford.edu
British Journal of Surgery, 1994
Creation of a transjugular intrahepatic portasystemic stent shunt (TIPSS) was used as a rescue tr... more Creation of a transjugular intrahepatic portasystemic stent shunt (TIPSS) was used as a rescue treatment for patients with variceal bleeding refractory to standard medical and endoscopic treatment. Over a 2-year period 242 episodes of variceal bleeding were treated and emergency shunting was performed on 20 patients with uncontrolled bleeding (Pugh grade A, one; B, seven; C, 12). The procedure was technically successful and controlled bleeding in all patients. Six patients had early rebleeding within 5 days, and further shunting was required in two. Two had late rebleeding related to shunt occlusion and had a further TIPSS procedure followed by portacaval shunting. Twelve patients died within 40 days from liver failure and sepsis, and there were two late deaths after 2 and 6 months, unrelated to bleeding. TIPSS insertion is an effective therapeutic option in patients with acute variceal bleeding refractory to medical and endoscopic treatment. However, despite control of bleeding in ...
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Papers by Waldo Concepcion