Case ReportA Case of Gingival Candidiasis with Bone Destruction onGastric Cancer Patient Receiving Cytotoxic ChemotherapySeungtaek Lim,1Tae-jun Kil,2Hye Ryun Kim,3,4,5Seonhui Han,6and Sun Young Rha3,4,51Department of Internal Medicine, Konyang University Hospital, Gasuwon-dong, Seo-gu, Daejeon 302-718, Republic of Korea2Department of Oral and Maxillofacial Surgery, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu,Seoul 120-752, Republic of Korea3Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro,Seodaemun-gu, Seoul 120-752, Republic of Korea4Yonsei Cancer Center, Yonsei Cancer Research Institute, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea5Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu,Seoul 120-752, Republic of Korea6Department of Oral Pathology, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu,Seoul 120-752, Republic of KoreaCorrespondence should be addressed to Sun Young Rha; rha7655@yuhs.acReceived 20 October 2014; Revised 13 December 2014; Accepted 16 December 2014; Published 29 December 2014Academic Editor: Rafaele PalmirottaCopyright 2014 Seungtaek Lim et al. Tis is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.We herein report a case of gingival candidiasis in an advanced gastric cancer patient while receiving palliative cytotoxic chemo-therapy. A46-year-old male patient admitted to our hospital for known advanced gastric cancer with newly developed multiple livermetastases. While receiving 2ndline cytotoxic chemotherapy with5FU, leucovorin, andpaclitxel, he complainedof gingival swellingaccompanied by pain and whitish plaque. Due to lack of response to the conservative oral care, incisional biopsy of gingiva wasdone and the pathology confrmed gingival candidiasis. Although the lesion healed apparently afer two-week antifungal therapy,pain as well as bony destruction remains. By presenting this case report, we intend to emphasize the immunocompromising efectof cancer while being on systemic chemotherapy.1. IntroductionGastric cancer is the second in all causes of cancer relateddeaths worldwide with higher prevalence in East Asia [1].Te prognosis is extremely poor in patients with unresectableor metastaticgastriccancer andpalliativechemotherapyis the treatment of choice for them [2].Since the aim ofchemotherapy in this setting is to prolong the survival period[3] and to palliate symptoms,quality of life is one of theimportant issues. Terefore, chemotherapy induced toxicityshouldbewell balancedwithitsefcacy[4]. Despitethedevelopment of new generation of chemotherapeutic agentsincludingmoleculartargeteddrugswithlesstoxicity, stillthe conventional cytotoxic chemotherapeutic agents have themajor role in palliative treatment of gastric cancer. So, thecomplications from the cytotoxic chemotherapy are still ofmajor concern. Oral complications are one of the commonestsymptomatic and troublesome problems resulting in difcul-ties in eating, poor oral intake with weight loss, and poorperformance[5]. Tesubsequent nutritional impairment,inturn, hasanegativeimpact onthehost immunesys-tem, making patients vulnerable to the variable infectiousorganisms. Candida is one of the normal foras residing inthe oral cavity,but oral candidiasis rarely develops in thegingiva among those with intact immune system. In addition,gingival candidiasis has been reported almost exclusively inHIV-seropositive patients and known as a surrogate markerfor the immunocompromised status. Here we report a case ofgastric cancer patient who sufered from gingival candidiasiswhich has progressed to periodontitis resulting in permanentbony destruction. By this case report, we intend to emphasizeHindawi Publishing CorporationCase Reports in Oncological MedicineVolume 2014, Article ID 145394, 5 pageshttp://dx.doi.org/10.1155/2014/1453942 Case Reports in Oncological MedicineFigure 1: Generalized gingival swelling and redness with desquamation of necrotic tissue is observed (arrow).(a) (b)Figure 2: (a) Necrotic tissue with chronic nonspecifc infammation (H-E stain, 100). (b) PAS stain reveals candida hyphae (periodic acid-Schif stain, 200).the immune compromising efect of cancer, especially whenthey are treated with the cytotoxic chemotherapy agents.2. Case ReportA46-year-oldmalepatient was referredtoour hospitalwith complaint of epigastric discomfort for 6 months.Asendoscopy and abdominopelvic computed tomography (CT)showed advanced gastric cancer at lesser curvature, lowerbody of stomach without distant metastasis, he underwentradical subtotal gastrectomy. Te fnal pathological diagnosiswas poorly diferentiated tubular adenocarcinoma withoutvascular or lymphatic invasionwithT2N2M0, stage IIBaccording to TNM 7th edition. However, one month laterwhen he admitted for adjuvant chemotherapy, the CT scanshowed multiple liver metastases without evidence of othersite metastases or carcinomatosis. He was enrolled to ran-domized, placebo controlled phase III clinical trial exploringthe efcacy of bevacizumab in combination with capecitabineand cisplatin. Afer eleven cycles of chemotherapies, follow-up CT scan revealed further progression of liver metastasis.Since the patients performance status was Eastern Cooper-ative Oncology Group (ECOG) 1, we decided to treat himwith 2nd line palliative chemotherapy of FL-Taxol (infusionalfuorouracil with leucovorin and paclitaxel).Afer the 2nd cycles of FL-Taxol chemotherapy, he visitedoutpatientclinicforexcessiveoral painresultinginpoororal intake lasting for one week. On inspection, the gingivaswelled and whitish plaque was covered on it. Tere was afoul odor from the lesion, too. At that time, there was noevidenceofotherchemotherapyrelatedtoxicitiessuchasbone marrow suppression, diarrhea, or neuropathies. ChestX-ray was normal, and he was in afebrile status. With theimpressionof chemotherapy-inducedlocalizedgingivitis,routine oral care such as scaling, tooth brushing instructionwas done. However, since desquamationcontinuedandsymptom did not subside despite conventional oral care for 2weeks, he was referred to the oral and maxillofacial surgeon.Incisional biopsy was done to diferentiate gingival infectionor metastatic lesion (Figure 1).Te pathologic fnding revealednecrotic tissue withcandidiasis (Figure 2). Te serologic test for human immun-odefciency virus was negative, and there was no evidenceof systemic involvement of candidiasis other than gingiva.We started oral fuconazole 100 mg daily with nystatin sus-pension. When he visited outpatient clinic two weeks later,the apparent gingival lesion nearly disappeared (Figure 3).But, excessive oral pain and bony destruction still persisted.During the follow-up period, the necrotic alveolar bone wasexposed due to desquamation of the necrotized gingiva. Tenecrotic gingiva and sequestra were removed as needed.Two months later, the gingival lesion was nearly healed,but the radiographic examinations revealed severe marginalbone loss at upper andlower incisor due to destructive changeby the previous infammation (Figure 4). Loss of the attachedgingiva and marginal bone resulted in an increased mobilityCase Reports in Oncological Medicine 3(a) (b)Figure 3: An apparent improvement, with a decreased swelling and necrotic tissue, is observed afer a two-week antifungal therapy.(a) (b) (c)Figure 4: (a) Initial panoramic view (September 2, 2009). Te dotted line denotes the marginal bone level. (b), (c) Panoramic and periapicalview 2 months afer treatment (November 19, 2009). Note the marginal bone loss and the sequestrumat the lower anterior teeth area (arrow).Also note that the radices of the second right lower molar have been removed.of the overall teeth, especially the lower anterior teeth.Hence, additional visits to the dentist for dental extractionsandprosthodonticrehabilitationwererequired, but poorperformance status hindered himfromgetting further dentalcare.While the patient received dental care,with improvedgeneral condition, he resumed 3rd cycle of chemotherapy.Since CT scan afer 4 cycles FL/Taxol showed further pro-gression of liver metastasis, regimen change to FOLFOX wasdone. Afer4cyclesof FOLFOXchemotherapy, CTscanrevealed disease progression, and the patient stopped furtherchemotherapy because of poor performance. He expired dueto disease progression on 13th February, 2010 (Figure 5).3. DiscussionFor metastatic advanced gastric cancer, palliative chemother-apy is the mainstay of treatment. Since the combinationof TS-1, an oral derivative of 5-fuorouracil (5-FU), with cisplatindemonstratedoverall survival over12monthsinSPIRITtrial, 5-FU analogues with platinum agent has been generallyaccepted as standard frst line regimen for the patients withrecurrent or metastatic gastric cancer [6].Various organisms are responsible for oral infection. Inanearlier literature investigating the incidence of oral infection,the frequency rates were 9.7% for the total population [7].Almost all (93.8%) of the infections were caused by singleorganism, and only 6.2%were polymicrobial, of which 68.9%isolates were fungal. Gramnegative bacilli and Grampositivecocci were isolated from 10.7% and 9.7%, respectively. Whileseveral species of candida reside in the mouth as normalfora, opportunistic infection by them can occur when hostimmune system is compromised [8]. Among them, Candidaalbicans is causative organism for over 90% of the fungalinfections encountered in cancer patients [7].Although candida species are frequently isolated in thesubgingival tissue, gingival candidiasis rarely developed inthe individual with intact immune system [9, 10]. It occursalmostexclusivelyinHIV-seropositiveorotherimmuno-compromisedpatients andpresents as erythema of theattachedgingiva, referredtoas HIV-associatedgingivitisor linear gingival erythema [10]. Periodontitis is caused by4 Case Reports in Oncological MedicineDeath due todiseaseprogression(10.2.13)3rd line chemotherapyFOLFOX 2nd line chemotherapy5FU +leucovorin +paclitaxel 1st line chemotherapybevacizumab +capecitabine +cisplatin Livermetastasis(08.8.13)Radical totalgastrectomy(08.7.8)ECOG1Diagnosis(08.6.30)PD PDAntifungal therapyOnset of gingivalwhitish plaque (09.9.2)Gingiva biopsy(09.9.15)Tooth extraction(09.10.19)2 3 5(09.10.2012.9)(09.7.910.01) (08.8.2909.6.11)Figure 5: Summary of patient progress.the extension of infection from the gingiva to the periodon-tium and resorption of alveolar bone, resulting in looseningand loss of teeth and deep dental pain. In HIV-seropositivepatients, the risk of progression fromgingivitis to periodonti-tis is known to increase in proportion with immune functiondeterioration and decreased number of CD4 counts [8, 11].Althoughtherehavebeenafewprevious reports ofgingival candidiasis developing in the solid cancer patient[7], our case is of interest in that gingivitis progressed intoperiodontitis resultingpermanent alveolar bonedamage.According tothe literature, the rate as well as severityof periodontal destruction is increased in proportion withthe reduction in number of functional polymorphonuclearleukocytes (PMNs) [12].Tere are emerging data indicat-ing that,to evade and compromise host immune surveil-lance, cancer cells utilize various strategies, one of which ismediated by several tumor derived soluble factors such asinterleukin-10 (IL-10), transforming growth factor (TGF), andvascular endothelial growthfactor (VEGF) [13].Moreover,while the patients sufer from poor oral intakedue to chemotherapy related complications such as nausea,vomiting, or oral mucositis, thenutritional impairmentsfurther exacerbate their immune function. Given both theoccurrence of gingival candidiasis and progression of gin-givitis to periodontitis resulting in bony destruction, we canpostulate that his immune function was deteriorated.One of the important issues to be addressed is how todetect and manage the oral mucositis and gingival candidi-asis. According to the guidelines multinational associationof supportive care in cancer/International Society of OralOncology (MASCC/ISOO) published and updated, carefuloral investigation at each patient visit and frequent use ofgargle are generally considered as the standard treatment [14].Even though the patient was treated with the oral care asprotocol, there was no improvement in the oral lesion. Twoweeks later, gingival candidiasis was confrmed by incisionbiopsy. Although antifungal therapy was initiated right aferdiagnosis, bonydestructionprogressed, whichmakesthepatient sufer excessive pain for the rest of life. In addition,economic and time cost for subsequent visit to dentist fortooth extractions and prosthodontic rehabilitation was alsoa big burden for the patient. Earlier suspicion and invasivediagnostic approach would have brought better outcomes,although there is no clear evidence at present that initiationofantifungal therapy in early phase of gingival candidiasis canprevent its progression into periodontitis and its long termsequela.Regardingthis patient presentedhere, several pointsshouldbefurtheraddressed. First, it wouldbebettertoprovideinformationwhichcanshowthebaselinedentalstatus to compare.Unfortunately,prechemotherapy dentalevaluation was not performed for this patient. Hence, it wasnot possible to precisely assess the infuence of chemotherapyonhis dental health. Second, althoughcandida specieswere identifed in the incisional biopsy and certainly mayhave contributed to the pathogenesis of periodontitis, otherperiodontopathogenic microorganisms may also have playeda role. Since no microbiological assessment (cultures/PCR)has been performed, we could not rule out the possibility ofpotential interplay of other microorganisms such as bacteriaor virus and could not fnd out which Candida subspecieswere involved, either. Given the similarity between this caseand acute necrotizing gingivitis/periodontitis, it should beconsideredas another potential diferential diagnosis. Also, asrecent evidence reports the associationbetweenbevacizumaband periodontitis [15], bevacizumab may contribute to thiscomplication.To the best of our knowledge,this is the frst case ofgingival candidiasis occurring in the solid tumor patientsreported in Korean PubMed. By this case report, we intend toemphasize the immune compromising efect of cancer, espe-cially when they are treated with the cytotoxic chemotherapyagents. Moreover, given this immunocompromising efect ofthe conventional cytotoxic chemotherapy, when apparentlycommon side efects were not treated efectively with conser-vative oral care using gargle, the rarer complications such asuncommon infection should be suspected earlier, and moreaggressive diagnostic tools including surgical biopsy shouldbe considered in the early phase of the disease to stop itsprogression.Conflict of InterestsTeauthorsdeclarethat thereisnoconfict of interestsregarding the publication of this paper.Case Reports in Oncological Medicine 5References[1]J. R. Kelley and J. M. Duggan, Gastric cancer epidemiology andrisk factors, Journal of Clinical Epidemiology, vol. 56, no. 1, pp.19, 2003.[2]Y. H. Kim, Chemotherapy for advancedgastric cancer: slowbutfurther progress, Cancer Research and Treatment, vol. 37, no. 2,pp. 7986, 2005.[3]B. Glimelius, K. Ekstr om, K. 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Eltinget al., Updatedclinical practice guidelines for the prevention and treatment ofmucositis, Cancer, vol. 109, no. 5, pp. 820831, 2007.[15]K.Ogawa,T.Ueno,K.Kato et al.,A retrospective analysisof periodontitis during bevacizumab treatment in metastaticcolorectal cancer patients,International Journal of ClinicalOncology, vol. 18, no. 6, pp. 10201024, 2013.Submit your manuscripts athttp://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientifc World JournalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational andMathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinsons DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com