Interventional Cytopathology and Cancer in Peru: How to Act During COVID-19?

Interventional cytopathology and cancer in Peru: how to act during COVID-19?

Milagros Abad-Licham1,2,3a , Juan Astigueta1,4b , Caddie Laberiano Fernández5,6c , Himelda Chávez Torres7,8d , Grisnery Maquera Torres9, Edwin Figueroa10e and Ricardo Bardales11

1School of Medicine, Antenor Orrego Private University, Trujillo 13007, Peru 2Pathological Oncology Department, Northern Regional Institute of Neoplastic Diseases, Trujillo 13600, Peru 3Centre of Excellence in Pathological Oncology, Trujillo 13007, Peru 4Department of Uro-Oncology, Northern Regional Institute of Neoplastic Diseases, Trujillo 13600, Peru 5Arias Stella Institute of Pathology and Molecular Biology, Lima 15000, Peru 6Peruvian University of Applied Sciences, Lima 15000, Peru 7Cytology service, Edgardo Rebagliati Martins National Hospital, Lima 15000, Peru 8National University of San Marcos, Lima 15000, Peru 9Functional Cytopathology Unit, National Institute of Neoplastic Diseases, Lima 15000, Peru 10Head and Neck Department, Northern Regional Institute of Neoplastic Diseases, Trujillo 13600, Peru 11Precision Pathology, CA 95826, USA ahttps://orcid.org/0000-0002-3530-6937 bhttps://orcid.org/0000-0001-5984-3270 chttps://orcid.org/0000-0003-4513-6123 dhttps://orcid.org/0000-0003-4519-4745 ehttps://orcid.org/0000-0001-6203-3068

Abstract Communication Short

The worldwide health crisis due to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has affected all healthcare systems. Low- and middle-income countries have needed to establish health strategies to combat the pandemic, many of which have collaterally affected the diagnosis and treatment of other illnesses. One of these other illnesses is cancer, which in Peru represents the primary cause of mortality. In recent decades, interventional cytopathology with fine-needle biopsy techniques has emerged as a minimally invasive, rapid, economical and effective procedure for diagnosing and Correspondence to: Milagros Abad-Licham staging cancer. However, in the current health context, it is confronted by the challenge Email: [email protected] of continuing to function in spite of the pandemic. This article reviews the existing lit- ecancer 2020, 14:1152 erature on interventional cytopathology, the risk of infection from SARS-CoV-2 and bio- https://doi.org/10.3332/ecancer.2020.1152 safety and provides recommendations for carrying out said procedures for the benefit of Published: 07/12/2020 the patient and the safety of healthcare staff. Received: 18/08/2020

Keywords: fine-needle biopsy, cancer, COVID-19, biosafety Publication costs for this article were supported by ecancer (UK Charity number 1176307). Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access Introduction article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/3.0), which Cancer is a serious public health problem worldwide, and, in Peru, represents the primary permits unrestricted use, distribution, and cause of mortality [1]. The associated disability caused by cancer and the high social cost reproduction in any medium, provided the original constitutes a challenge for our debilitated healthcare system, which must also overcome work is properly cited.

ecancer 2020, 14:1152; www.ecancer.org; DOI: https://doi.org/10.3332/ecancer.2020.1152 1 patient, butalsofor thecare andhealthof laboratory staff. guarantee correctin thearea functioning of interventional cytopathology sothat oncology cytodiagnosis isprioritisedfor thebenefit of the Consciousof theimportance of continuing diagnostic with work, inthisarticle,therecommendations madeintheliterature are analysed to including interventional cytopathologists, are inahigh-riskgroup outbreaks ofprecariousnessand the thismagnitude foregoingthe inlow- andmiddle-income countries. In thiscontext, laboratory staff, symptoms,limited availability of personal protective equipment(PPE), inadequate healthcare service infrastructure to confront infectious systemsaround the world [10].Healthcare professionals have ahigh risk of infection dueto contact infectedwith people with or without pathology laboratory faces agreat challenge:during thepandemiccausedby functioning SARS-CoV-2, which hasbrought down healthcare In spite of its virtues and the growing interest ininterventional cytopathology evidenced inseveral national publications [6–9], today’s cyto- [5, 6]. and economicaltechnique complications,minimal with it requires though adequate training incytopathology andthenecessary equipment has setas agoal reduction the of advanced cancerpopulation inits [2–4]. This includesinterventional cytopathology asaneffective, simple tors, several of which are related to low socioeconomiclevels [2].In thiscontext, Peru hasestablishedstrategies to control thediseaseand geographicand cultural barriers, population growthand migration andtheassociated changes intheprevalence of anddistribution riskfac ecancer 2020, 14:1152; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1152 block, immunocytochemistry, genetic study andflow cytometry, amongothers [13,19]. immediatelymust befixed in96%alcohol for subsequent anddefinitive staining. The sampleobtained canalsobeusedto prepare acell greatestthe torisk due generation the of aerosolspossibility andthe of infection [12].Once thesamplehasbeenspread ontheslides,they the helpofwith asyringe onto amicroscope slide[14,15,18].For of thepurposes biosafety within thecurrent pandemic,thislaststep holds Indifficult. both variations(FNA obtainedsample the andFNC), remains intheneedle, with theexception of thecysts, to thenbeejected FNAare andFNC techniquesout carried needle a fine with reduceswhich thepresence of haematic matter, which often makes diagnosis response to treatment andeven asascreening test [5,6]. [7]. To date, interventionalcytopathology hasbeenadopted inother for institutions early diagnosisinoncology, staging,evaluation of the of NeoplasticDiseases, predominantly using needles. 27and25G This experiment constituted thefirstnational publication onthismatter and subsequently for other neoplasms.Four years later, Bardales and Abad implemented FNA intheNorthern andFNC Regional Institute oncology space,National in2007,the Institute of NeoplasticDiseases includedthediagnosticprotocol inLima for headandnecktumours approachthyroid glandtumours [17]. [16]. In Peru,startedit formally ofdecade final inthe centurylast the with Columbie, Somocurcio and collaborators routinely usingFNA to fromDudgeon andPatrickUnitedin the Kingdom,Martin and Ellis intheUnited States andZajdela, Zajicek andFranzen intheNetherlands other,each improving their validity [14,15].Interventionalcytopathology traces itshistory to Arabic medicine, with previous contributions needle capillarybiopsy (FNC) technique.Both have ahighdegree of accuracy diagnostic andinsomecasesare usedtogether to complement diagnosis. There are two variantsneedle aspirationtechnique:fine on the biopsy, (FNA) and biopsy aspiration,without alsoknown asthefine oron palpablemasses identified masses by ultrasound,a finecalibreusing needle(fine needle) to obtain thesampleandissueacytological Interventionalcytopathology isabranchof anatomical pathology in which thecytopathologistminimallycarries out invasive procedures Interventional cytopathology Results anddiscussion cussed and wrote therecommendations. safety’, inbothEnglish andSpanish. The bibliographicsearch was by carriedout theauthors, who, in virtual form, selected, analysed, dis- A literature review wason PubMed,out carried SCOPUSand LILACS, usingtheterms ‘fineneedlebiopsy’, ‘cancer’, ‘COVID-19’ and‘bio- Methodology Theof diffusion procedure this to other andtheprovinces inLima hospitals crept forward slowly. In the [10–13]. 2 -

Short Communication ecancer 2020, 14:1152; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1152 virus incytologyhas forced samples usto adoptbiosafety strict measures, starting the with workers andtheir Considering duties. that the The arrival of COVID-19in our country andthe world haschanged themanner in which we actand work. The potential presence of the Laboratory staff as adiagnosticprocedure isreinforced. for results,enabling earlier therapeuticinterventions reduces the number of unnecessary surgeries, inmany caseseliminating theneedfor intraoperative biopsies,andshortens the waiting time utility and advantages outweigh therisks,it will have to beperformed under optimal biosafety conditions [24]. The evidence shows that it In thecurrentcontext,health focusesthe discussion procedureon risksthe posesto thecytopathologist. In casesof necessity, and when its sample processing israpid, andasecond samplecanbetaken shouldthefirst prove insufficient [26]. explained tothat them itisfast, safe, largely painless,outpatient, minimally traumatic andessentially complications.without Furthermore, preparatory exams, surgery, instruments,equipment special or nursing staff); thepatient usually easily agrees to theprocedure when itis are reinforced inthecontext ofas, forsuch thepandemic, example: speedinschedulingtheprocedure; low or minimalcosts (no needfor The technique has demonstrated its in virtues as summarised analysis andgenetic studiesincrease thediagnostic value of thetechnique [7,15,19]. definitivecontextclinical diagnosis,supported inthe imaging andauxiliarywith Flow studies. cytometry, immunocytochemistry, molecular surgical procedure andtheradicality of same.In summary, itisafundamental pillar for makingmanagement decisions.It canalsoprovide a also instaging,evaluatingbut recurrence, progression andmonitoring of thedisease,as well astheuseof diagnosticcytology inplanninga Interventional cytopathology hasanimportant role incancer, not only inthediagnosisof patients with palpableandnon-palpabletumours, Role of intervention inoncology decisions sonal protection andcorrect processing of thespecimen The eliminationoftime SARS-CoV-2 the RNA ofsamples inthe infected patients remains partially unknown, hence theimportance of per secretions andanyobtained specimen a fineneedle,rubbingorwith coming from asuspected or confirmed COVID-19 patient [12,24,25]. are thosefrom therespiratory tract,nasopharyngealas sputum, such swabs, broncho-alveolar lavages, pleural fluid,as well asconjunctival Regardingsource the of andtheirsamples the level of virulence, thesehave beenclassifiedashighandlow risk.Sources considered highrisk sneezing or speaking;itisknown that the virus’s mainpoint of entry isrespiratory, followed by theoral andconjunctival mucosae [12,13]. prevention andbiosafety strategies [10,22,23]. The illnessspreads through therespiratory secretions of aninfected person by coughing, established. However, modesof theprinciple infectionhave beenidentified, andthisknowledge hasbeenfundamental indesigningadequate deaths a mortalitywith rate of 4.96%[20,21]. The pathophysiology, andclinicaltherapeutic behaviour of COVID-19are stillnot well SARS-CoV-2is responsible for current the pandemic, in Peru,which onthedate of this writing, reports more than525,000casesand26,000 SARS-CoV-2 clinic shouldbeconstant andfluidto improve thediagnosticaccuracy of theinterventional cytopathology [14,18,19]. ing israre, localisedandeasily controlled,particularlybe borneinmind, should it inpatients with clotting disorders. Communication with the The disadvantages oftechnique the are however, minimal; they mustbeconsidered. From thepointof view of theprocedure, althoughbleed- unsatisfactory results, saving timeinthetherapeutic process decision-making [14,15,18,19]. adequately trained cytopathologist canalsocarryimmediate out assessments onthequality of samplesobtained usingrapid stainingto avoid those performing theprocedure, processingand interpreting thesample theresults beingthemostimportant condition for itssuccess. An racy (sensitivity 80%–100% and specificity around 99%)[7, 8]. It is reproducible with minimal complications, adequatewith staff training for This techniquebenefitsand its are captured indifferentItarticles. is simple,outpatient, rapid,safe, economical andhashighdiagnosticaccu- [15, 17,19,26].During thispandemic,theimportance of interventional cytopathology [12]. Table 1. The previously known advantages of this minimally invasive procedure 3 -

Short Communication and removing PPEisalsoimportantin anarea [11–13,15–25]andshouldbecarriedout designedfor [23]. thispurpose boots,face shieldandsafety glasses.Before andafterprocedure, the itisimportant to wash hands and with soap water. Correctly wearing Staff should usefullPPE which includes:N95(or higher) mask, disposablegown with long sleeves, gloves (preferably nitrile), surgical cap, processes, alladequately trained [15,24]. the cytopathologistshould include responsible for staff takingthesample,andsupport charged with logistics, moving, stainingandtechnical currentsituation requirespresence the ofnecessaryminimum the number of staff ina work area, interventional cytopathology procedures ecancer 2020, 14:1152; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1152 consent. adequatewith illumination [12,23,24]. We recommend ofa checklist thematerials usedduringtheprocedure, includingsignedinformed adequately protected, will accompany them. The procedure should be carried in out an environment specific to this purpose, ventilated and oralthe cavity. Theybe admittedif should alone; is not this possible, amember of healthcare staff from thesameestablishment, who will be The patients should wear amask,preferably surgical, throughoutthe entire procedure [23],except incases wherein thelesionisfound in cases, multidisciplinary evaluation isrecommended to avoid unnecessary exposure [13]. COVID-19status ofpatient the indicatingbe specified, must whether they are positive, suspected or negative. In emergency or controversial the cytopathologist. To thisend, it isimportant that thestudy request includestherelevant clinicaldata andjustification for thestudy. The Interventional cytopathology procedures are carriedoutinaccordance with a planand previous evaluation of the patient’s clinicalhistory by Procedure andprocessing Table 1.Interventional cytopathology: analysis of technical advantages inthecontext of theCOVID-19 pandemic. Risk of infection for operators duringtheprocess Costs Repetition of procedure Evaluation of samplequality Waiting timefor result Sample processing time Risk of complications Need for analgesics Pain Soft tissuetrauma Speed of procedure PPE Number of staff needed Recovery room Special materials andinstruments Need for surgeon Need for surgical risk Coagulation tests Patient acceptance of theprocedure During theexpulsion andextension of thesample Low Immediate May beimmediate Less than24hours Minutes Minimal Usually not needed Minimal Minimal Minutes Complete 1 to 2 No No No No Not essential Yes 4

Short Communication ecancer 2020, 14:1152; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1152 anatomical region. cabinet of the shiftto minimise therisk of infection. Ideally, only a cell block shouldbe performed, and the sample manipulated in a Class II biosafety each institution [29]. The reusable equipment, suchasthesafety glassesand visor, shouldbedisinfected or thrown away according to thebiosafety rulesof disinfected On finishing the procedure, the equipment andthesurfaces that have been in contact with the sample and the patient must becleanedand laboratory to colour theslide,assessquality andgive apreliminary assessment. immediate evaluations, especially inthesamepuncture location [23,24,27] . The recommendation isto move thealready fixed sampleto the the useof asystem of physical barriers duringtheexpulsionand extension process (Figure 1).In thiscontext, itisprudent to not carry out [23],followedsample the by immediate fixationalcoholin 96% andstaining with Papanicolaouor hematoxylin eosin[22]. Another option is be gentleneedle should and that cytopathologist,the wearing PPE,shouldmaintain full the greatestdistance possible whilst manipulating If thisisnotpossible, analternative isproposedby Indian the Academy of Cytologists, who suggestthat expulsion of thematerial from the authors recommendthat, after piercing,be transferredsample the to thelaboratory to beprocessed inaClassIIbiosafety cabinet sion ofpointing thesample, bevelthe ofneedle downwards the andincontact with theslideto minimiseaeration of thesample [15].Some the numberminimising of passes(three or four), anddesignating onefor useasasamplefor thecell block. The criticalpoint isintheexpul- favouring FNA versusnor FNC, thenumber ofto samples take (passes) or thenumber of slidesto prepare. In our experience, we suggest Theoperator.the techniqueupon chosen depends Inbibliographic the review, we didnot findany evidence thelevel about of protection, Figure 1. Acrylic isolation booth to reduce thepossibility of contamination by aerosols atthetime of expulsionand extension. in alcohol asafundamental step to inactivate the virus andprotectthe laboratory staff. we shouldreplace thepremise of ‘correctand early diagnosis’, ‘correctwith diagnosis’, and opportune prioritisingthefixation of thesample are potentially infected,infection the routes andhigh virulence of SARS-CoV-2, as well asits survival onsurfaces isproven [12,13,27,28], ogy isfundamental for decisionmaking [13, . 22, 23,24] To that effect, andconsidering that currently themajority of fresh biological samples continuingmends interventionswith innecessaryas thosepatientssuch cases, oncologicalwith diseasesandin which interventional cytol- mentadequate biosafety measures forcytology the laboratory andtheinterventional area to continue functioning. The literature recom- Thestrategies health designedto combatand theneedtopandemic continuethis patients supporting cancerwith hasforced usto imple- The challenge: to continue to function [29].The cytologicalreport wouldbe prepared inaconventional form andaccording to theinternational recommendations for each [28]. Afterwards, all disposable material, including thePPE, should be thrown in out a container with a bio-hazard disposal bag [28, 29]. In casesinvolving patients who have tested positive for COVID-19, the procedure should be scheduledfor the end [15, 25]. 5

Short Communication ecancer 2020, 14:1152; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1152 the biosafety protocols to protect thehealthof thehealthcare workers, afundamental mainstay for continued aid. roleprocess, inthediagnostic adapting itself to‘new theso-called normal’ for thebenefitof thepatients. It isalso very important to maximise larly for patients oncologicalwith diseases. The area of interventional cytopathology for alltheaforementioned advantagesreinforce must its tices, inadequate biosecurity protocols andthescarcity of materials andteams. These deficiencies shouldnot limitcontinued care, particu- The COVID-19has demonstratedpandemic to theentire world, mainly to low-and middle-income countries, theshortages inmedicalprac lowed. ofnorms establishment.health the In of cases infectioncommunity,in the theprotocols, which have already beenestablished, will befol- this immediately to management andOccupational Health and/or Epidemiology to establishtheprocedure to follow inaccordance with the SARS-CoV-2infection, or hasbeenpotentially exposedto the virus duringtheprocedure or preparation ofcommunicate thesample,must Any member of theinterventional cytopathology team who hashadextended contact with apatient having asuspected or confirmed trained staff andpermanent communication with thetreating doctor. one adequateincludes environment for theprocedure andanother for processing; useof complete equipment PPE; for thetechnique; Interventionalcytopathology continue should area,as afunctioning but allthemeansnecessarywith for thebiosafety of thestaff. This Conclusions recommendations. aretions trained, andthatthey followbiosafetyapplicable the measures ineachlaboratory [12,13,27]. pathology offices, trying wherever possibleto have only oneperson per office. It isalsoimportant that allstaff who participate ininterven- and they shouldkeep socialdistance aminimum of 1.5metres [24,25,27].It isrecommended that thisdistance to alsobeapplied the avoiding overcrowding. To reduce contactbetween tolimiting people,strictly necessary staff for both samplecollection andprocessing, washing, correct hygiene practices, properlyshift scheduled work andrefreshment breaks andstaggeredbe minimal should inorder to Measuresbiosafetystrict shouldinclude procedures personalinclude which protection usingadequate equipment (PPE),frequent hand Table 2.Summary of recommendations for interventional cytopathology duringCOVID-19. • • • • • • • • • • ing of thesamplebeperformed inaClassIIbiosafety cabinet. been any technical complications or problems with thePPEduringprocedure.Ideally, itisrecommended that thetechnical process- Tell theappropriate person aboutany staff contact with apatient with suspectedor confirmed SARS-CoV-2 infection, or if there have must becleanedanddisinfected.The cytological report will beproduced inaconventional form. fix theslidein96%alcohol.On finishing,theequipment, physical environment andsurfaces incontact with thesampleandpatient greatest distance possibleduringpreparation for extension.Carry outevaluations immediately onfresh samplesonly if itisnecessary and Expulsion of thematerial from theneedleshouldbegentle, with thebevel pointing down andincontact with theslide,and with the Whenever possible,limitthenumber of samplesobtained (one of themfor thecell block). The patient should wear asurgical maskthroughout theentire procedure. glasses.The procedure shouldbecarriedoutina ventilated environment, and whenever possiblethepatient shouldbeadmittedalone. Staff shouldusefullPPE:N95or higher mask,longsleeved gown, gloves (preferably nitrile), surgical cap,boots, face shieldandsafety with soapand water before andafter theprocedure. Positive or suspected COVID-19 patients shouldbescheduledat theendof theshiftto avoid contaminating the work area.Wash hands negative. The study request shouldincludecomplete clinicalinformation andindicate whether thepatient isCOVID-19 positive, suspected or Conserve minimalsocialdistancingof 1.5m. Scheduled shift work and/or staggered shifts. Healthcare professional older than60or with co-morbidities shouldavoid working. Table 2gives asummary of the 6 -

Short Communication ecancer 2020, 14:1152; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1152 2. 1. References The authors state that this work isself-financed. Funding The authors have not declared any conflicts of interest. Conflicts of interest

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