Lola Y Kwan

Cedars-Sinai Medical Center, Los Ángeles, California, United States

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Publications (10)51.06 Total impact

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    ABSTRACT: Mercaptopurine and azathioprine (AZA) are efficacious in treating IBD. 6-tioguanine (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Some IBD patients exhibit dose-limiting preferential 6-MMP production, which may lead to undesired side effects and impact efficacy. To review the outcomes of thiopurine split-dosing in patients with preferential 6-MMP metabolism. A retrospective chart review of 179 IBD patients treated at the Cedars-Sinai IBD Center with AZA or mercaptopurine was performed. Preferential 6-MMP metabolisers with 6-MMP levels greater than 7000 pmol/8 × 10(8) erythrocytes who underwent split-dosing were identified and assessed for biochemical and clinical responses to these dose modifications. A total of 20 of 179 patients met the criteria for preferential 6-MMP metabolism and underwent thiopurine split-dosing. Dividing the total daily thiopurine dose led to a reduction in 6-MMP levels (11785 vs. 5324 pmol/8 × 10(8) erythrocytes; P < 0.0001) without negatively affecting clinical disease activity or 6-TGN levels (239 vs. 216 pmol/8 × 10(8) erythrocytes; P = N.S.) and led to resolution of 6-MMP associated side effects (elevated transaminases, leucopenia and flu-like symptoms) in all but two patients. After mean follow-up of 36 months, 12 patients remained in clinical remission on split-dose mercaptopurine. Five of the remaining eight patients escalated to anti-TNF therapy, two progressed to surgery, and one switched to tioguanine therapy. Split-dose administration of mercaptopurine/AZA represents an alternative option in IBD patients with preferential 6-MMP metabolism who might otherwise require steroid exposure or escalation of therapy.
    Alimentary Pharmacology & Therapeutics 07/2012; 36(5):449-58. DOI:10.1111/j.1365-2036.2012.05206.x · 4.55 Impact Factor
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    Brian Huang · Lola Y. Kwan · David Q. Shih
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    ABSTRACT: An extraintestinal manifestation (EIM) very often occurs in ulcerative colitis (UC) patients. EIM modifies the natural course of UC and decreases the quality of life in these patients. The aim of this study was to analyze clinical and laboratory findings in UC patients with joint EIM. 319 UC patients were examined. Among them were 131 (41.1&percnt;) patients with distal UC, 102 (32.0&percnt;) suffered from left-sided UC and 86 (26.9&percnt;) had pancolitis. 95 (29.8&percnt;) UC patients had joint EIM. Arthritis correlated with extensive forms of UC and was more often determined in patients with left-sided UC and pancolitis. Arthralgia was a prevalent symptom of joint EIM in patients with distal UC. Colon microbiocenosis and the mucosal barrier in UC patients were analyzed. The cytokine status with privileged cytokine profile changes was investigated. In all UC patients, dysbiosis with a decreasing quantity of bifidobacteria, lactobacilli and �·scherichia coli was found, but an increase of facultative flora was also found. At the same time, an association of facultative flora in UC patients with arthritis was observed. In these patients, Staphylococcus, Klebsiella and Proteus were found more often in stool cultures. These associations correlated with a modification of the colonocytes’ cell receptor maturity of mucus, a condition with a decreased staining intensity by lectins. A cytokine imbalance with an increase of proinflammatory and a decrease of anti-inflammatory cytokines was found in all UC patients. The privileged cytokine profile changes in UC patients with joint EIM were analyzed. Maximal increases of IL-1 and TNF with decreases of IL-10 in plasma in patients with joint EIM were observed.
    Ulcerative Colitis - Epidemiology, Pathogenesis and Complications, 12/2011; , ISBN: 978-953-307-880-9
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    Lola Y Kwan · Stephan R Targan · David Q Shih
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    ABSTRACT: Small bowel tumors and Crohn's disease are common causes of small bowel obstruction. Early stage neoplasms can easily be mistaken for Crohn's disease. Therefore, thorough work-ups including imaging studies and endoscopic evaluation with biopsies are critical for accurate diagnosis. Here we report a case of an otherwise healthy female with progressive onset of multiple, recurrent obstructive symptoms secondary to terminal ileal narrowing who was referred for management of steroid-dependent Crohn's disease. After thorough evaluation, the diagnosis was revised to myeloid granulocytic sarcoma involving the terminal ileum. In this case, a delay in diagnosis can be detrimental for prognosis, as myeloid granulocytic sarcoma is highly predictive of underlying acute myeloid leukemia and needs urgent referral for chemotherapy and/or resection.
    World Journal of Gastroenterology 05/2011; 17(19):2446-9. DOI:10.3748/wjg.v17.i19.2446 · 2.43 Impact Factor
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    Lola Y Kwan · Uma Mahadevan
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    ABSTRACT: Women with inflammatory bowel disease have similar rates of conception to the general population unless they have had pelvic surgery. Once pregnant, regardless of disease activity, they have an increased risk of adverse pregnancy outcome and should be followed as high-risk obstetric patients. Most medications are compatible with pregnancy and lactation, as described in this article. Ideally, women should discuss their plans for pregnancy with their physician prior to conception so that risks and benefits can be reviewed, medications adjusted and healthcare maintenance updated. Once pregnant, a multidisciplinary team of gastroenterologists, obstetricians and pediatricians should help to ensure the best care for the mother and child.
    Expert Review of Clinical Immunology 07/2010; 6(4):643-57. DOI:10.1586/eci.10.35 · 3.34 Impact Factor
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    ABSTRACT: TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Neutralizing anti-mouse TL1A Ab attenuates chronic colitis in two T-cell driven murine models, suggesting that TL1A is a central modulator of gut mucosal inflammation in inflammatory bowel disease. We showed previously that TL1A is induced by immune complexes via the Fc gamma R signaling pathway. In this study, we report that multiple bacteria, including gram negative organisms (E. coli, E. coli Nissle 1917, Salmonella typhimurium), gram positive organisms (Listeria monocytogenes, Staphylococcus epidermidis), partial anaerobes (Campylobacter jejuni), and obligate anaerobes (Bacteroides thetaiotaomicron, Bifidobacterium breve, Clostridium A4) activate TL1A expression in human APC, including monocytes and monocyte-derived DC. Bacterially induced TL1A mRNA expression correlates with the detection of TL1A protein levels. TL1A induced by bacteria is mediated in part by the TLR signaling pathway and inhibited by downstream blockade of p38 MAPK and NF-kappaB activation. Microbial induction of TL1A production by human APC potentiated CD4(+) T-cell effector function by augmenting IFN-gamma production. Our findings suggest a role for TL1A in pro-inflammatory APC-T cell interactions and implicate TL1A in host responses to enteric microorganisms.
    European Journal of Immunology 11/2009; 39(11):3239-50. DOI:10.1002/eji.200839087 · 4.52 Impact Factor
  • Gastroenterology 05/2009; 136(5). DOI:10.1016/S0016-5085(09)63119-X · 13.93 Impact Factor
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    ABSTRACT: 6-Mercaptopurine and its prodrug azathioprine are effective for the treatment of inflammatory bowel disease. Thiopurine methyltransferase is important for the metabolism of thiopurines. However, there is controversy as to the clinical utility of measuring thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide levels. Our aim was to determine if thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide level monitoring would predict response to therapy with thiopurines in patients with inflammatory bowel disease. Baseline thiopurine methyltransferase enzyme activity prior to initiation of therapy with either 6-mercaptopurine or azathioprine was determined in 39 patients with inflammatory bowel disease. The association between clinical response and thiopurine methyltransferase activity and 6-thioguanine nucleotide levels singly or in combination were analysed. Seventeen of 39 patients (44%) responded to 6-mercaptopurine or azathioprine therapy. Thiopurine methyltransferase enzyme activity below the mean of 30.5 U was significantly associated with clinical response. The thiopurine methyltransferase low phenotype was associated with response in 65% vs. 29% in individuals with thiopurine methyltransferase enzyme activity above 30.5 U (p = 0.05). There was no correlation between thiopurine methyltransferase activity and 6-thioguanine nucleotide levels. The maximal 6-thioguanine nucleotide levels did not predict clinical response. When combining thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide levels, the combination of thiopurine methyltransferase low/6-thioguanine nucleotide high was associated with response in 7/7 (100%) vs. only 2/8 (25%) with the combination of thiopurine methyltransferase high/6-thioguanine nucleotide low (p=0.01). Thiopurine methyltransferase activity inversely correlated with clinical response to thiopurine treatment in inflammatory bowel disease. Thiopurine methyltransferase enzyme activity below 30.5 U combined with a post-treatment 6-thioguanine nucleotide level > 230 pmol/8 x 10(8) erythrocytes was the best predictor of response.
    Digestive and Liver Disease 06/2008; 40(6):425-32. DOI:10.1016/j.dld.2008.01.003 · 2.89 Impact Factor
  • Gastroenterology 04/2008; 134(4). DOI:10.1016/S0016-5085(08)60114-6 · 13.93 Impact Factor
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    Inflammatory Bowel Diseases 01/2007; 13(5):639-40. DOI:10.1002/ibd.20103 · 5.48 Impact Factor
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    David Q Shih · Lola Y Kwan
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    ABSTRACT: The recently published Rome III criteria reflect current understanding of functional gastrointestinal disorders. These criteria include definitions of these conditions and their pathophysiologic subtypes and offer guidelines for their management. At the 2006 Annual Scientific Meeting of the American College of Gastroenterology, a panel of experts discussed these criteria as they pertain to irritable bowel syndrome, functional dyspepsia, and chronic constipation. This article reviews the panel's findings, highlights the differences between the Rome II and III criteria, and summarizes best treatment options currently available to practitioners and their patients.

Publication Stats

102 Citations
51.06 Total Impact Points

Institutions

  • 2007–2012
    • Cedars-Sinai Medical Center
      • • Inflammatory Bowel & Immunobiology Research Institute
      • • Cedars Sinai Medical Center
      • • Department of Medicine
      Los Ángeles, California, United States
  • 2010–2011
    • University Center Rochester
      Рочестер, Minnesota, United States