The rate of submandibular gland involvement in patients who underwent neck dissections for oral cavity squamous cell carcinoma at Chris Hani Baragwanath Academic Hospital. DR MOHAMMED NATHIE A research report (NUES7009) submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirement for the degree of Masters of Medicine in Otorhinolaryngology (MFOSENTS60) Johannesburg 2022 II Dedication To my beautiful wife Maryam, For her unconditional love, patience, support, understanding and continuous encouragement To my parents Goolam Hossein and Sayeda, For their support, prayers and encouragement. To my daughter Saarah and our new born son Mohammed Isa For their inspiration. III Declaration I, Mohammed Nathie, declare that this research report is my own, unaided work. It is being submitted for the degree of Master of Medicine in the branch of Otorhinolaryngology at the University of the Witwatersrand, Johannesburg. It has not been submitted before for any degree or examination at this or any other university. (signed by candidate) 08/11/2022 – JOHANNESBURG (date, place) IV Co-Author Declaration Declaration: students contribution to the article(s) and agreement of co-author(s): I, Mohammed Nathie, student number 0703120A, declare that this Research Report is my own work and that I contributed adequately towards research findings published in the article(s) stated below which are included in my Research Report. Signature of student…………………………………….Date……01/08/2022………………………. Name of Primary Supervisor: Dr Yahya Atiya…………………………. Signature of Primary Supervisor………………………Date…01/08/2022………………….…….. Agreement by co-authors: By signing this declaration, the co-author(s) listed below agree to the use of the article by the student as part of his/her Thesis/Dissertation/Research Repot. In cases where the student is not the 1st author of the published article, the primary supervisor must explain (under comments) why the student is entitled to use the paper for his/her degree purposes. Article 1 Title: The rate of submandibular gland involvement in patients who underwent neck dissections for oral cavity squamous cell carcinoma at Chris Hani Baragwanath Academic Hospital. Journal name, year, volume and page numbers: Wits Journal of Clinical Medicine – to be submitted Authors Name Signature Date 1st author Mohammed Nathie 01/08/2022 2nd author Yahya Atiya 01/08/2022 3rd author 4th author 5th author 6th author V Comments by primary Supervisor ……………………………………………………………………………………………………… ……………………………………………………………………………………………. Article 2 Title:…………………………………………………………………………………. Journal name, year, volume and page numbers:…………………………………………… Authors Name Signature Date 1st author 2nd author 3rd author 4th author 5th author 6th author Comments by primary Supervisor ……………………………………………………………………………………………………… ……………………………………………………………………………………………. Article 3 Title:…………………………………………………………………………………. Journal name, year, volume and page numbers:…………………………………………… Authors Name Signature Date 1st author 2nd author 3rd author 4th author 5th author 6th author Comments by primary Supervisor ……………………………………………………………………………………………………… ……………………………………………………………………………………………. VI Letter of Contribution To whom it may concern The MMED titled ‘The rate of submandibular gland involvement in patients who underwent neck dissections for oral cavity squamous cell carcinoma at Chris Hani Baragwanath Academic Hospital’, in submissible format (for the Wits Journal of Clinical Medicine) is primarily my work. I, Dr M Nathie, student number 0703120A, conceived the idea for this study, wrote the protocol, collected all the data personally without any assistance, calculated the statistics with some assistance from a statistician in the protocol phase and assistance from my supervisor, and I wrote the final paper. Dr Y Atiya assisted in a supervisory role with my work. He reviewed the protocol and the manuscript at each stage and provided guidance and the fine tuning and perfecting of the work being submitted. He also helped correct my statistics where needed. Yours Sincerely, Mohammed Nathie Student number 0703120A Supervisor Dr Y Atiya VII Acknowledgements I would like to extend my thanks and appreciation to the following: • My supervisor, Dr Y Atiya, Consultant and Head & Neck Fellow in Otorhinolaryngology at Chris Hani Baragwanath Hospital, for his constructive criticism, invaluable advice and unlimited guidance. • Professor S Maharaj the Academic Head of Department of Otorhinolaryngology – Head and Neck Surgery, for his support, guidance, and motivation • Dr MRI Ahmed, Head of Department of Otorhinolaryngology at Chris Hani Baragwanath, for his encouragement in pursuing this career and with this dissertation. • Dr Y Perner, Academic Head of the Department of Anatomical Pathology, for allowing me access to the NHLS database. • The numerous colleagues and peers who proof-read the manuscript and for providing constructive criticism. • Last, but not least, to my wife and family, for their love, support and encouragement. VIII List of abbreviations CHBAH – Chris Hani Baragwanath Academic Hospital ENT – Ear, nose and throat SCC – Squamous cell carcinoma HNC – Head and neck cancer OSCC – Oral Squamous cell carcinoma HIV – Human immunodeficiency virus HPV – Human papilloma virus 1 TABLE OF CONTENTS Dedication…………………………………………………………………………………..II Declaration………………………………………………………………………………...III Co-Author Declaration…………………………………………………………………….IV Letter of Contribution……………………………………………………………………..VI Acknowledgements……………………………………………………………………….VII List of Abbreviations…………………………………………………………………….VIII Abstract……………………………………………………………………………………..2 Article for Submission………………………………………………………………………3 Introduction…………………………………………………………………………3 Epidemiology……………………………………………………………………….3 Submandibular Gland Involvement in OSCC………………………………………4 Clinical Evaluation………………………………………………………………….5 Classification………………………………………………………………………..6 Management………………………………………………………………………...6 Neck Dissection……………………………………………………………………..7 Materials and Methods……………………………………………………………...8 Results………………………………………………………………………………9 Demographics………………………………………………………………9 Pathological Results……………………………………………………….10 Primary Tumour Location…………………………………………10 Pathological T Stage………………………………………………10 Pathological N Stage………………………………………………10 Level 1B Involvement………………………….………………….10 Rate of Submandibular Gland Involvement…….…………………10 Discussion…………………………………………………………………………12 Conclusion…………………………………………………………………………14 References…………………………………………………………………………15 Tables and Figures Table 1: Changes in American Joint Cancer Committee staging in lip and oral cavity and nasopharynx……………………………………………….17 Table 2: Age and Gender…………………………………………………..17 Figure 1: Primary Tumour Location………………………………………18 Figure 2: Pathological T – Stage…………………………………………..18 Figure 3: Pathological N classification for the patients in this study……...19 Table 3: Level 1B involvement……………………………………………19 Table 4: Cross tabulation by Level 1 B node involvement………………..20 Table 5: Submandibular Gland Involvement and Level 1 B Lymph node..21 Table 6: Gender differentials among patients……………………………..22 Appendix A – Approved Protocol…………………………………………………………23 Appendix B – Ethics Clearance……………………………………………………………24 Appendix C – Change of Title Approval………………………………………………….25 Appendix D – Chris Hani Baragwanath Hospital Otorhinolaryngology HOD Approval Letter……………………………………………………………………………………....26 Appendix E – NHLS Letter……………………………………………………………….27 Appendix F – Medical Advisory Committee CHBAH Letter………………………….…28 Appendix G – Authorship Guidelines for the WITS Journal of Clinical Medicine….…...29 Appendix H – Turnitin Report…………………………………………………………...30 2 Abstract Background Head and neck cancer (HNC) in Africa is increasing in incidence. The most frequent site of HNC is the oral cavity, with the most common histological type being squamous cell carcinoma (SCC). The submandibular gland may be involved by either direct spread (of a primary ipsilateral oral cavity tumour or locally involved lymph node) or from distant primaries outside the head and neck. Objectives To determine the rate of involvement of the submandibular gland in neck dissections for oral cavity squamous cell carcinoma at Chris Hani Baragwanath Academic Hospital. Methods A retrospective audit of the Chris Hani Baragwanath Academic Hospital Department of Otorhinolaryngology theatre register for patients who underwent primary tumour resection and neck dissection for OSCC, between November 2012 and December 2018. Tumour location, clinical and pathological T and N stages were investigated for their relevance to submandibular gland involvement. Results 24 patients were identified, 58.3% male (n=14) and 41.7% female (n=10). The mean age was 57.9 years old. The submandibular gland was involved in one patient (rate=4.2%) and the method of involvement was by means of intraglandular metastasis. Nodal staging, tumour location and the presence of level 1b nodes did not increase risk for submandibular gland involvement. However an advanced T stage was a proven risk factor. Conclusion There is a low rate of submandibular gland (4.2%) involvement in neck dissections for OSCC at Chris Hani Baragwanath Academic Hospital. Oncologically, the sparing of the submandibular gland is safe and sound provided the gland is not suspicious for involvement either radiologically, clinically or at the time of surgery. 3 Article for Submission Th e ra t e o f subm and ibu l ar g land in vo lv em en t in p a t i en t s w ho und erw en t n eck d i s s ec t ion s f or o ra l ca v i ty s quam o us ce l l ca rc i nom a a t C hr i s H an i Ba rag wa nat h A cad em i c H osp i t a l . M N at h i e , MBB Ch ( Wi ts ) F CO RL ( SA ) ; Y A t iy a , MBBC h ( Wi ts ) MME D (O RL ) (W its ) F CO RL (SA ) I FH NOS Fe l lo w I n t rodu c t io n H ead and n eck cance r ( HN C) i n A f r i ca i s i n c r eas in g i n i n c id ence . T h i s i s a t t r i bu t ed to t h e r i s e i n sm okin g h ab i t s ( an d us e o f o th e r t ob acco p r od u c t s ) , a l coh o l us ag e , l i f e s t y l e and d i e t w es t e r n i za t io n , h um an p ap i l l o m a v i r us ( HP V ) , h um an i mmu no d e f i c i en cy v i ru s ( H IV ) , an d un f avo ur ab l e hea l t h po l i c i es . 1 T he mo s t f r eq u en t s i t e o f H NC i s t h e o r a l c av i t y , w i th t h e m os t comm on h i s t o lo g i ca l t y p e be i ng s qu amo us ce l l c a r c i no ma (SCC ) . 2 I t i s e s t i m at ed t ha t a t l e a s t 9 0 % o f o r a l c av i ty c an ce rs a r e s qu am ou s ce l l c a r c in om a. 2 , 3 Ep id em io lo gy G l ob a l l y , o r a l s qu am ou s ce l l c a r c in oma ( OSCC ) i s t h e s ix t h mo s t co mmo n can cer , w h i l e i n d ev e l op in g co u n t r i es i t r ank s th i r d . 1 In t e r n a t i on a l ly , t h e con t in en t o f A s i a i s m os t co mmo nl y a f f ec t ed b y O SCC w i t h a r epo r t ed i n c id en c e o f 3 .8 p e r 10 0 00 0 , w h i l e i n t he A f r i can con t in en t an d So u th Af r i c a , t he i n c i d en ce r a t e p e r 10 0 00 0 i s e s t im at ed a t 2 .6 and 4 r es p ec t iv e ly . 4 O SCC af f ec t s t h e m id d l e -ag e to e l d e r ly p op u l a t i on an d o ccu rs m o re com mo nly i n m en th an wo men . 3 R i sk f ac to r s i d en t i f i ed a r e t o bacco smo ki ng an d a l coh o l , w h ich h av e a sy n e rg i s t i c e f f ec t i n t he ae t i o l og y o f OS CC. 2 , 3 Co n t r i bu to r y ho s t f a c to r s a r e d es c r ibed s u ch as com p rom is ed im mu n e sy s t em s i n H IV - i n fec t ed and t r an sp l an t p a t i en t s . 3 V i r a l c aus e s su ch as HPV h av e b een d e s c r ib ed , h ow ev e r t h e r e i s d i sp a r i t y i n t h e l i t e r a tu r e r ega r d i ng i t s r o l e i n t h e p a t ho g en es i s o f OSCC . 1 , 3 A d d i t i o na l l y , g en e t i c p r ed i s po s i t i o n i n co n d i t i on s su ch as Fan con i ’ s an aemi a , x e r od e rm a 4 p ig men t os um and a t ax i a t e l an g i ec t as i a a r e l i nk ed t o t h e dev e lo pm en t o f h ead an d n eck can ce rs . 3 Subm andibu la r g la nd inv o lv em en t in OS CC O SCC ra r e l y m et as t a s i z es t o t h e s ub man d i bu l a r g l and . 5 Th ey a r e m o re co mmo nl y inv o l v ed b y e i th e r d i r ec t sp r ead (o f a p r i ma r y i ps i l a t e r a l o r a l c av i ty t u mo ur o r l oca l l y i n vo l v ed l ymp h n o de ) o r f r om d i s t an t p r im a r i e s ou t s i de t h e h ead an d n eck , v i a h aem at og eno us s p r ead ; s u ch as t h e lu ng , b r ea s t an d t he u ro g en i t a l sy s t em. 5 - 7 I t i s w e l l d e sc r i b ed t h a t p r im a r y OSCC d o n o t m et a s t as i z e t o t h e s ub m an d ib u l a r g l and v i a h aem ato g en ou s sp r ead . 6 T h e su bm and i bu l a r g l and d o es n o t con t a i n in t r ag l an du l a r l ym ph n o des o r l ym ph o -vas cu l a r s t ru c t u r es . 6 , 8 T h e l ym ph n od e g r ou ps s u r ro un d in g th e sub m an d ib u l a r g l and a r e su b lo ca t io ns o f su b l ev e l 1 B an d a r e i d en t i f i ed as p r eg l an du la r , po s t g l an du l a r , p r ev as cu l a r an d p os tv a scu l a r . 7 T h i s i s i n co n t r as t t o t he p a ro t id g l and which co n t a i ns i n t r ap a r en chy ma l l y mp h no d es . Th e s ig n i f i c an ce o f t h i s i s t h a t t h e p a r o t i d g l an d i s a s i t e fo r i n t r ag l and u la r l ym ph n od e m et as t as es fo r o th e r H NC , wh i ch i s n o t t he cas e f o r t h e s ub m an d ib u l a r g l and . 8 Th i s h a s im p l i ca t i on s f o r t h e su r g i ca l s t r a t eg y ado p t ed t o war ds t h e s ub m an d ib u l a r g l and i n OSC C. E x c i s io n o f t h e su bm and i bu l a r g l an d as p a r t o f a l ev e l 1B d i s s ec t i on o f t he neck i s comm on p r ac t i c e i n s om e cen t r es , du e t o t h e comm on b e l i e f t h a t t h i s w i l l f a c i l i t a t e com pl e t e r em ov a l o f l ym ph n o des in t h e r eg i on o f t he g l an d . 8 Dh i w ak a r e t a l 9 sh o w ed th a t t h e su bm and i bu l a r g l an d can b e s a f e l y p r es e rv ed wh i l s t s t i l l ach i ev in g com pl e t e r emo v a l o f a l l l ymp h no d es i n su b l ev e l 1B i n n eck d i s s ec t i on s . S ubm and ib u l a r g l an d r e s ec t io n i s a s so c i a t ed w i t h s ev e ra l co mpl i ca t i on s t h a t i mp ac t an a t omi ca l ly , p hys io lo g i ca l l y an d f u n c t i on a l ly . Th e an a tom i c a l s t ru c tu r e a f f ec t ed m os t co mm on ly i s t he m a rg in a l m and i bu la r n e r v e ( a b r an ch o f t he f a c i a l n e rv e ) , wh ich r un s 5 u n de r t he s u r f ace o f t h e p l a t ys m a m usc l e i n t h e r eg io n o f t h e s ub m an d ib u l a r g l and . 1 0 In 20 17 , Hi s h am ud d i n e t a l 1 1 r ep or t ed n e r v e co mpl i ca t i on s i n 23 . 3% o f t h e n eck d i s s ec t i on s cas e s do ne in t h e i r c en t r e , wi th t h e m ar g in a l m an d i bu la r n e r v e as t h e m os t co mm onl y i n j u r ed n er v e in 1 3 . 1 % o f a l l neck d i s s ec t io n cas e s . 1 1 In v i ew o f t h e p hy s i o l og i ca l ro l e o f t he su bm and i bu la r g l an d in s a l iv a p r od u c t i on , r em ov a l o f t h e g l and d ec r ea s e s un s t im ul a t ed sa l i v a p r od u c t i on an d r esu l t s i n d ry n ess o f t h e m ou t h ( x e r os tom ia ) . 6 X e r os tom i a i mp a i r s ch ewin g w hi ch a f fec t s n u t r i t i o n a l i n t ak e o f p a t i en t s p os t s ub man d i bu l a r g l and r esec t i on . I t a l so cause s a ch r on i c b u rn in g sens a t io n w i t h i n t h e o ra l c av i ty w h i ch i mp ac t s o n p a t i en t s ’ q u a l i t y o f l i f e . T h e ch ro n i c mu cos a l d r y n es s m ay r es u l t i n f i s su r in g o f t he t on gu e an d l i p s , l o s s o f app e t i t e and we ig h t , d en t a l c a r i es , o r op h a ry ng ea l c and i d i as i s and an gu l a r ch e i l i t i s . 9 Fu n c t io na l l y , m a rg i n a l m an d ib u l a r n e rv e i n ju r y may cause d ys f un c t io n a l d ep re s s i on o f t h e ang u l i o r i s mu sc l e , r e su l t i n g i n d r oo p i ng o f t h e ang l e o f t h e m ou th wh i ch im p a i r s f e ed i ng an d a l t e r s co sm es i s . 1 1 In v i ew o f t h e s e com pl i ca t io ns , r es ec t i on o f t h e s ub mand i bu la r g l and i s no t wi t ho u t r i s ks , an d p r es e rv a t io n s ho u l d b e cons id e red t o r ed u ce co mpl i ca t i on r a t e s an d imp r ov e p a t i en t o u t co m es . 5 , 7 , 9 , 1 2 C l in i ca l ev a lu a t ion D u e to t h e no n - sp ec i f i c p r es en t i ng com pl a i n t s , p a t i en t s w i t h OSC C o f t en p r es en t a t an ad v an ced s t ag e o f t h e d i s eas e p r oce ss . 3 Th e s p ec t ru m of p r e sen t a t io n in c l ud es : p a in , o r a l mu cos a l ch an g es , o r a l c av i ty an d / o r n eck s w el l i n g , u n ex p l a i ned l oo s en i ng o f t e e t h in t h e ab s en ce o f p e r io don t a l d i s ea s e , o dy nop h ag i a , d ys ph ag i a , p e r s i s t en t f o r e i gn b od y s en sa t i on , r edu ced t on gue mo bi l i t y an d a l t e r ed s ens a t io n o f t h e o ra l cav i ty . 2 6 A d e t a i l ed h i s to r y an d com pr eh en s iv e c l in i ca l ex ami n a t io n o f t h e ea r , n os e an d th ro a t , i nc l ud i ng en do s co py m us t be p e r fo r med t o ens u r e t h a t t h e p r i ma r y tum ou r i s i den t i f i ed w h i l e no t m i s s in g a s eco nd p r im a ry o r sy n ch r on o us m et as t a s es . 2 T h e in i t i a l d i ag nos t i c wo r ku p r eq u i r es a b io ps y . In t h e o u t p a t i en t c l i n i c , l e s i ons wh i ch a r e e as i ly a cce ss ib l e m ay b e b i ops i ed us i ng a p u nch f o rceps , co r e n eed le o r f i n e n eed l e as p i r a t io n t e chn iq u es . 3 L e s i on s wh i ch a r e n o t e as i ly a cce ss ed r equ i r e a v i s i t t o t h e o p e ra t i ng t h ea t r e t o ob t a in an ad eq u a t e s amp l e fo r h i s t o l og i ca l an a ly s i s . A v ar i e ty o f im ag ing s tu d i es h av e v a lue in co nf i r mi ng th e d i agn os i s o f OSCC su c h a s : den t a l r ad io g r ap hs , m agn e t i c - r es on an ce im ag in g , u l t r as on og r ap hy , co mp ut ed t om og r ap hy an d ph o t on - emi ss i on t om og r ap hy . 1 3 Each o f t h es e mo d a l i t i e s h a s adv an t ag es an d l imi t a t io ns wh i ch i s b eyo nd t h e s cop e o f t h i s t ex t . L ym ph n od e i den t i f i c a t io n i s d i f f i cu l t t o a ch i ev e b o th c l in i ca l l y and r ad i o l og ica l ly . 1 4 C l ass i f i ca t i on M an ag em ent i s g u id ed by t um ou r h i s to p a t ho l og i ca l c l a s s i f i c a t io n . T h e tu mo ur , no d a l , m e t as t a s es ( T NM ) c l as s i f i c a t io n sys t em i s u n i v er s a l l y ado p t ed a s t h e c l as s i f i c a t i on o f ch o i ce f o r m al i gn an t t um ou rs . 1 5 Th e T ca t ego ry i s de f in ed b y tu mo ur s i ze an d d ep th o f i nv as io n , wh i l e t h e N ca t eg or y i s d e f in ed by r eg i on a l nod a l i nv o l vem en t , and th e M ca t eg o ry i s de f in ed by d i s t an t me t as t as es . T ab l e 1 i l l u s t ra t es t h e TN M c la s s i f i ca t io n o f OSCC acco rd in g to t h e m os t r e cen t r e l e as e o f t h e A mer i can Jo in t C omm i t t e e o n C ance r . 1 5 Ma na gem en t V ar io us t r e a tm en t m od a l i t i e s fo r O SCC ar e av a i l ab l e s u ch as r ad i a t io n , ch emot he r ap y an d su r g i ca l r e s ec t i on . 1 6 Th e m an ag em en t r eq u i r e s a m ul t id i sc i p l i n a r y t e am app ro ach in c l ud in g r ep re s en t a t i v es f r om o n co lo gy , o to r h in o l a ry ng o lo gy (E N T ) , o r o - m ax i l l o - f ac i a l , 7 r ad i o t h er apy , sp eech t h e r apy an d r ad io l og y , i nd i v i du a l i s ed t o e ach p a t i en t ’ s b i op sy ch os o c i a l co n t ex t , w h i l e m ax imi z i ng o n co l og ica l c o n t ro l and mi n im iz i ng a l t e r a t i on o f t h e p a t i en t ’ s f o r m an d f un c t io n . 2 3 M ul t ip l e f a c to r s gu i d e t r e a t m en t o p t i on s su ch a s t h e n a tu r e o f t h e t um ou r and s u r g i ca l r e s ec t ab i l i t y , t h e b a l an ce b e t w een r i s k and b en e f i t o f t r e a tm en t r e l a t ed co mpl i ca t io ns o n th e p a t i en t s ’ ag e , co mo rb id d i s eas e s , so c io eco no mi c s t a t us an d qu a l i t y o f l i f e t h e r ea f t e r . 2 , 3 M any cen t r e s ad v i se su r g i ca l r e sec t io n a s , i t p r ov i d es h i s t o pa th o lo g i ca l i n f o rm at i on o n tumo u r s t ag e , g r ad e and s p r ead , w h ich i s e s s en t i a l i n f o rm at i on t o gu i de f u r th e r m an agemen t . 3 N eck d i s s ec t i on T h e su r g i ca l app r oach ad op t ed i s i n d iv id u a l i s ed to t h e pa t i en t ’ s c l i n i ca l an d h i s to pa t ho l og i ca l d i agn os i s . 1 7 E l ec t i v e n eck d i s s ec t io n ( E N D ) i s r e co mm end ed f o r an y tu mo ur w h er e t he r i sk o f o ccu l t n od a l m et a s t as i s i s g r ea t e r t h an 20 %. 2 I t i s e s t im at ed th a t 6 0 % o f p a t i en t s w i t h e a r l y s t ag e OSC C wi l l p r e s en t wi th a c l i n i ca l ly n ega t i v e n eck ( cN 0 ) . 3 In t h e o r a l c av i ty , t h e m aj o r i t y o f t umo u rs w i l l r eq u i r e E ND , r eg a rd l es s o f T s t a tu s , wi t h t h e ex cep t i on o f can cer o f t he h a rd p a l a t e an d up p e r a l v eo l a r r i dg e . 2 T h i s i s i n co n t r as t t o OS CC f lo o r o f t h e m ou th and o r a l t ong u e w hi ch a re m or e l i ke ly t o m e ta s t as i s e t o t h e n eck ; t h e s e pa t i en t s s ho u l d b e o f f e r ed E N D ev en i f t h ey a r e e a r ly s t ag e tu mo ur s ( i f t h e d ep t h o f i nv as ion ex ceeds 4m m) . 3 T h e go a l o f t h i s s u r g i ca l app ro ach i s t o a ch iev e lo co - r eg io n a l co n t ro l an d th us , enh an ce th e cu r e r a t e o f O SCC . 3 A s i gn i f i c an t c l i n i ca l p r og no s t i c a t o r o f su r v i va l i s t h e f i n d in g o f m et as t a s es t o t h e n eck . 1 8 N eck D i s s ec t io n ( ND ) i n c l ud es t he fo l l o win g ty pes : ex t end ed r ad i ca l N D , r ad i ca l N D, mo d i f i ed r ad i ca l N D, mo d i f i ed N D an d se l ec t iv e N D . 1 1 In a l l fo rm s o f ND u s ed to t r e a t OS CC th e su bm and ib u l a r g l an d i s r ou t in e l y r em ov ed . 6 8 N eck d i s s ec t i o n i s a v i t a l p a r t o f t h e su r g i ca l t r e a tm en t fo r OSCC . 6 Wh en in d i ca t ed , n eck d i s sec t io n wi th ad ju v an t r ad i o t h er ap y and ch emo r ad io t h e rapy a r e t h e s t an d a rd o f c a r e i n OSC C. 6 S ubm a nd i bu l a r g l an d r es ec t io n i s a r ou t in e s t ep in n eck d i s s ec t io n , ev en th o ug h t h e r a t e o f su bm an d i bu l a r g l and in vo lv emen t i s v e ry lo w . 1 9 P r e s e rv a t io n o f t he s ub m an d ib u la r g l an d h as b een sh o wn t o i mp ro v e pa t i en t s ’ q u a l i t y o f l i f e . 5 T h e su r g i ca l t r ea tmen t o f ch o i ce i s r e sec t i on o f t h e p r i m ar y t umo u r , w i t h app r op r i a t e n eck d i s sec t io n to ens u r e app ro p r i a t e c l e a r an ce o f m et a s t as e s . 1 6 In v i ew o f t h i s , t h e au t ho r ev a l u a t ed t h e r a t e o f s ub m an d ib u l a r g l and i nv o l vem en t i n pa t i en t s wh o un d e rwen t N D fo r O SCC a t Ch r i s H an i B a r ag w an e t h A cad emi c H os p i t a l (CH B AH ) , i n o r d e r t o d e t e rmi n e t h e f eas i b i l i t y o f sp a r i ng t h e g l an d . Ma t er i a l s a nd Meth ods A f t e r ob t a i n i ng e th i c s ap p ro v a l f r om th e Uni v e rs i t y o f t he Wi t w at e r s r and H um an R es ea r ch E t h i c s C ommi t t e e ( p r o to co l n umb er M 19 09 59 ) , t h e au t ho r r ev i ew ed t he C HB A H D ep a r t men t o f O t o r h i no l a r yn go l ogy t h ea t r e r eg i s t e r fo r p a t i en t s w ho u nd e r w en t p r im a ry tu mo ur r esec t i on an d n eck d i s s ec t io n ( i n c l ud i ng l ev e l 1 d i s s ec t io n ) f o r OSCC , b e t w een N ov em b er 2 0 12 and D ecem b er 2 01 8 . R ou t in e ex c i s io n o f t h e s ubm and ib u l a r g l and w i th accom pan i ed l ev e l 1 B n od es w as d one on a l l p a r t i c ip an t s , r eg ar d l es s o f whe t h er o r n o t u n i l a t e r a l o r b i l a t e r a l n eck d i s s ec t io n w as ca r r i ed ou t . O n ce th e p a t i en t s ’ d e t a i l s w er e o b t a i ned , t h e h i s t op a t ho lo g i ca l r e s u l t s w e re r ev i ewed u s i ng th e rep or t s av a i l ab l e o n th e N a t i on a l H ea l t h L ab or a to ry S e rv i ce s ( N HLS ) da t abas e , w i t h do cum ent ed p e rm is s io n o f t h e head o f an a t omi ca l pa t ho l og y a t t h e N HL S. T h e ex c lus io n c r i t e r i a w e r e p a t i en t s wi th an y o f t h e f o l l o wing : a t u mo u r h i s t o l og y o t he r t han SC C, a p r ev io us h i s t o ry o f h ead an d n eck r ad i o t h er apy , c an cer o ccu r r in g in s i t e s o t h e r t h an th e o r a l c av i t y and f ac to r s t h a t m ak e th e p a t i en t a no n -s u r g i ca l c an d i d a t e i n t h e s tu dy 9 s e t t i ng ( i . e . s t ag e T 4 b t um ou rs , p a t i en t s w i t h d i s t an t m et a s t as i s ) . In t o t a l 2 4 p a t i en t s me t t h e c r i t e r i a , an d t h e i r r es u l t s w e r e rev i ew ed and an a lys ed . C l in i ca l an d Pa th o lo g i ca l Tu mo u r - N od e ( T and N ) s t ag in g o f t he pa t i en t s w as p e r f o r med b as ed on th e A m er i can Jo in t Co mmi t t ee o n C an ce r ( AJC C) s t ag i ng e i gh t h ed i t i o n ; a l l h i s t op a t ho log i ca l r e co rd s co l l e c t ed we r e co nv e r t ed to t h i s m os t up d a t ed v e r s io n o f t h e A JCC Ca ncer s t ag in g m an ua l . 2 0 T um ou r lo ca t io n , c l i n i ca l an d p a t ho l og i ca l T and N s t ag es w er e i nv es t i g a t ed fo r t h e i r r e l ev an ce to l ev e l 1 m et a s t as es an d s ub m an d ib u l a r g l and i nv o l vem en t . D a ta w as an a l ys ed in ST A T A v e r s io n 14 s o f t w are , a t 9 5% C on f i d ence in t e r va l and s i gn i f i c an ce i n t e rp r e t ed a t 5 % l ev e l . F i sh e r ’ s ex ac t t e s t and P ea r so n ch i - s qu a r e t e s t w e r e ca r r i ed ou t t o i d en t i f y po t en t i a l r i sk fa c to r s as so c i a t ed w i t h l ev e l I m e t as t as i s an d su bm and i bu l a r g l and in vo lv em en t . A p -v a l u e o f l e s s t h an 0 . 05 w as accep t ed a s s t a t i s t i c a l l y s i gn i f i c an t . R esu l t s D em og r aph i c s T h e r e su l t s w e r e ca t ego r i s ed acco rd i ng to d em og r aph i c s , p a th o lo g i ca l an d c l in i ca l r es u l t s ( p r im a ry t umo u r lo ca t io n , p r eva l en ce and t yp e o f s ub m an d ib u l a r g l and i nv o l vem en t , p a th o l og ica l T and N ca t eg o r i es , p r ev a l en ce & nu mber o f l ym ph n od es in v o lv ed ) . T h i s s t ud y co ns i s t ed o f 2 4 p a r t i c i p an t s wh e r e 58 .3 % w ere m al e ( n =14 ) and 4 1 . 7 % w er e f em al e ( n =1 0) . Th e m ean ag e o f t h e p a r t i c ip an t s w as 5 7 . 9 y ea rs o l d ( wi t h a r ang e o f 34 – 7 4 yea r s ) . T h e re w e r e 5 4 . 2 % (n =13 ) p a r t i c i p an t s b e t w een 4 1 and 6 0 y ear s , w h i l e 3 7 .5 % ( n =9 ) w e r e m o re t h an 6 0 y ea r s and 8 .3 3 % ( n=2 ) we r e ag ed 21 t o 40 y ea rs . Th e r e w e r e n o p a t i en t s aged l es s t h an 20 . T ab l e 2 i n d i ca t e s t h a t p a r t i c i p an t s w er e m o r e l i k e l y to be m al es ag ed 4 1 -6 0 y ear s ( 64 .3 % vs 4 0 % ) , w i th n o d i f f e ren ces i n p r op or t i on s o f t ho s e aged 60 + y ear s i n t e rm s o f gende r . H o w ev e r , 2 0 % o f f em al e 10 p a t i en t s p r es en t ed in t h e age g r ou p o f 2 1 -4 0 y ear s o l d ; t he r e w e re n o m al e s i n t h i s ag e g r o up . Th us , ov e r a l l , f em al e p a t i en t s p re s en t ed ea r l i e r t h an m a le s . P a th o lo g i ca l R esu l t s P r im a ry tum ou r lo ca t io n Wit h r eg ar ds t o l o ca t i on o f t he p r im a ry t um ou r , t h e m os t f r eq uen t s ub s i t e was th e f l oo r o f t h e m ou t h 33 .3 % ( n =8 ) , t h e l i p 2 9 . 2 % ( n =7 ) an d th e to ng u e 25 % ( n =6 ) . Ot he r t umou r l oca t io n s i t e s we r e : t h e l o wer g in g iv a 4 .2 %( n =1 ) , h a rd p a l a t e 4 . 2% (n =1) , and b ucca l mu cos a 4 . 2% (n =1) . Th e r e w e r e n o tum ou r s o f t h e u pp e r g i ng i v a an d r e t ro mol a r t r i g on e p r e s en t i n t h e s tu dy . (S ee f ig u r e 1 ) P a th o lo g i ca l T - S ta g e Fi gu r e 2 s ho ws p a th o l og ica l T - S t ag e f o r t h e p a t i en t s i n t h i s s t ud y . M os t p a t i en t s w er e p a t ho lo g i ca l l y s t ag ed T 2 tu mou r s (3 7 . 5% ) , f o l lo w ed b y T 1 t um ou r s (2 9 . 2% ) , T 3 t um ou r s ( 20 . 8% ) an d l a s t l y T4 A t um ou rs (1 2 . 5% ) , i n d i ca t in g t h a t p a t i en t s p r es en t wi th a sm al l e r r a th e r t h an l a rg e r p r im a ry . P a th o lo g i ca l N S t ag e T h e m os t com mo n N o d a l s t ag i ng ( N ) w as N0 ( 54 .2 % ) , f o l lo w ed by N 2B ( 2 0 . 8 %) , t h en N2C ( 1 2 . 5 %) lym ph nod e ca t ego r y / s t ag e . O t he r no d a l s t ag i ng s w e r e N1 (8 . 3% ) an d N2 A ( 4 .2 % ) . (S ee F ig u re 3 ) L eve l 1 B in vo lv em en t T h r ee q u ar t e r s o f t h e p a r t i c i p an t s w ere r ep or t ed t o h av e n o l ev e l 1 B l ym ph no d es (7 5% ) , wh i l e a qu a r t e r (n =6 ) d id h av e n odes p r es en t i n l ev e l 1B . (S ee T ab le 3 ) R a t e o f sub m andibu la r g l and inv o l vem en t S ubm and ib u l a r g l an d in vo l v em en t w as ob s e rv ed i n o n l y on e cas e ( 4 . 2% r a t e ) ou t o f t h e 2 4 , an d th e m et ho d o f su b m and ib u l a r g l and 11 i nv o l vem en t w as an i n t r a - g l and u l a r m et a s t as i s . T h e r em ai nd e r o f t h e 2 3 p a t i en t s d i d n o t h av e th e s ubm and i bu la r g l an d in vo lved by e i t h e r i n t r a -g l and u l a r met a s t as i s , d i re c t t um ou r in v as io n o r i n v as i on by a d j acen t l ev e l 1B o r o t he r n od es . T ab l e 4 i n d i ca t e s t h a t t h e r e w as n o s t a t i s t i c a l ly s ig n i f i c an t a s so c i a t io n b e tw een l ev e l 1B i nv o l vem en t an d gen d e r o f p a r t i c ip an t s ( F i s h er ’ s ex ac t t e s t , p =1 . 000 ) . Ag e o f p a r t i c ip an t s w as a l so n o t s t a t i s t i c a l ly s ig n i f i c an t i n as soc i a t io n wi th l ev e l 1 B in vo l v em en t (F i sh e r ’ s ex ac t t e s t , p =0 .6 78 ) . H ow ev e r , a d i f f e r en ce can b e n o t ed b e t w een th os e ag ed 2 1 -4 0 yea r s , w ho we r e m or e l i k e ly to h av e L ev e l 1B ly mp h no d es i . e . 5 0 % o r 1 ou t o f 2 pa t i en t s i n t h i s ag e g r ou p . T um ou r lo ca t i on w as no t s ig n i f i c an t ly as so c i a t ed wi th l ev e l IB ly mp h no des ( F i she r ' s exac t p= 0 . 63 2) . N o t ew o r t hy r es u l t s su gg es t t h a t t ho s e wi th l i p t u mo ur w er e t h ree t im es mo r e l i k e ly to h av e l ev e l 1B lym ph no d es ( 57 .1 % vs 17 .6 % ) an d th os e wi th to ng u e tum ou r w e r e tw o t i mes l e s s l i k e ly t o l ev e l IB l ym ph no d es . H ow ev e r , a n o t ewo r t hy f i nd in g i s t h a t t h e on ly p a t i en t t o ex h i b i t s ubm and ibu l a r g l an d i nv o l v em en t h ad a p r im a ry l i p t u mo ur w i t h no l ymp h no de in vo l v em en t . T h e p a t ho l og i ca l Tu mo u r ( T) s t ag i ng w as n o t a s s oc i a t ed w i th l ymp h n o des in t h i s s t ud y ( F i s h e r ' s ex ac t =0 . 9 24 ) . Al t ho ug h t he r e su l t s a r e n o t s ig n i f i c an t t h ey p ro v i de an i ns i gh t t ha t t hos e wi th T 2 t um ou rs ( 4 1 . 2 % v s 28 .6 % ) w e r e l e s s l i k e l y t o h av e l ev e l 1B ly mp h no d es and t ho s e wi th T 3 tu mou r s w e r e mo r e l i k e ly t o h av e l ev e l 1B l ym ph n od es ( 1 7 . 6 % vs 2 8 . 6% ) . T ab l e 5 i nd i ca t es t h e r e was n o a s s oc i a t i on b e t w een SM G i nv o lv emen t an d l ev e l 1b l ym ph no d es . O u t o f t he 2 4 p a t i en t s s tu d ied on l y o n e p a t i en t h ad i nv o lv em en t o f t h e su bm an d i bu la r g l and , and th i s w as b y m et a s t as i s t o t h e g l an d i . e . n o d i r ec t i n f i l t r a t i on f ro m p r im ary tum ou r n o r f rom l ev e l 1b n o des . H ow ev er , t h e t ab l e do es i nd i ca t e t h a t f ro m t h e 24 p a t i en t s s tud i ed , 6 h ad l ev e l 1 b n od es p r es en t , w h ich co u ld p o t en t i a l l y b e a s ou r ce o f su bm and i bu l a r g l and in vo l v em en t by d i r ec t 12 s p r ead f r om t h e no d es , h ow ev er t h i s w as no t sh ow n i n t h e d a t a r ev i ew ed . T h e r e w as n o s t a t i s t i c a l l y s ig n i f i c an t a s s o c i a t i on b e t w een n um ber o f l ym ph n od es ( l eve l 1B ) and S MG i nv o lv em en t . T he r e w e r e n o s ig n i f i c an t a s s o c i a t io ns b e tw een c l in i ca l and pa th o l og ica l t um ou r – n o de (N ) an d SMG and l ev e l 1B l ym ph n od es ( F i sh e r ’ s ex ac t t e s t , p =0 . 71 9 ) . T ab l e 6 i nd i ca t e s t h a t m al e p a t i en t s w e r e tw i ce as l i k e ly t o hav e t um ou rs o n t he f lo o r o f t h e mo u t h com pa r ed to f em al e s (4 2 .9 % vs 2 0 %) . T h e r e w e r e no s ign i f i c an t d i f f e r en ces b e t w een ma l e and f ema l e i n t e rm s o f l i p and t on g ue t um ou rs . T h er e s eem to be s l i gh t d i f f e r en ces i n e a r ly - s t ag e can ce r (T 2 ) b e t w een ma l es ( 28 .6 % ) and fem al e s (5 0% ) w h i l s t no d i f f e r en ces a re o bs e r ved in l a t e - s t ag e can ce r ( T 3 and T 4 ) . M a le s ( 28 .6 % ) and f em al es (3 0 %) h ad equ a l ch an ces o f l ev e l 1 b i nv o l vem en t wi th no s i gn i f i c an t d i f f e ren ces ( F i s he r s ex ac t =0 . 54 8 ) . T h e o n l y p a t i en t t o h av e su bm and i bu l a r g l an d i nv o lv em en t w as a m al e p a t i en t . D i f f e r en ces a re n o t ed b e tw een m al e s (1 4 . 3 %) an d f em al e s ( 3 0 %) i n t e rm s o f l ev e l 1B lym ph n odes . T h e r e su l t s s ug g es t t h a t f em al e s w e r e t wi ce as l i k e ly t o dev e lo p l ev e l 1 B l ymp h ad eno p a th y comp ar ed to m al e s . S ig n i f i c an t r esu l t s i n d i ca t e t h a t t h e r e w e r e d i f f e r en ces i n p a t ho log i ca l N ca t ego r y can ce r amo ng t h e p a t i en t s ( F i sh er ' s ex ac t =0 . 05 ) . Ma l e p a t i en t s w e r e m o re l i k e ly to b e a t r i sk o f h i gh e r s t ag ed N ca t ego ry can ce r ( N2 B an d N 2C ) , co mp a r ed t o f em al es wh o w e re m or e a t r i sk o f e a r l y c an cer ( N0 and N 1 ) . L as t ly , m al e s w e r e mo r e a t r i s k o f h av in g 1 o r m or e l ym p h n od es , com p a r ed t o f em al es (5 3 . 8 % vs 2 5 % ) . D is cu ss ion S eve r a l au th or s h av e d e s c r ib ed t h e r a t e o f su bm and i bu l a r g l an d i nv o l vem en t i n OSCC . A cco r d i ng to M a lg on d e e t a l 2 1 t he s ub m an d ib u l a r g l and w as in vo lv ed i n 3 . 0 6% o f OS CC ca ses , w h er e 13 m et a s t as i s w as du e to d i r ec t i nv as io n o f a t um ou r in c l ose p ro x im i ty t o t h e g l and . Y an g e t a l 1 9 i d en t i f i ed i nv o l v em en t o f t h e s ub m an d ib u l a r g l and s in 5 2 ou t o f 2 12 6 p a t i en t s wh o und e r w en t neck d i s s ec t io ns fo r OSCC . S imi l a r ly , C e t in e t a l 6 f ou nd in vo lv em en t o f t h e su bm an d i bu l a r g l an d v i a d i r ec t i nv as i on w as ev id en t i n 2 o u t o f 1 5 5 pa t i en t s , an d th e f lo o r o f m ou th lo ca t io n w as t h e on ly r i sk f ac t o r f o r s ubm and ib u l a r g l an d i nv o l v em en t . In v i ew o f t h i s , sub m an d ib u l a r g l an d p re s e rv a t i on s ho u l d b e cons id e red o n a c as e -b y -ca se b as i s . T h e l im i t ed d a t a f ro m S ou th A f r i c a d es c r i b es t he d i s t r i bu t io n o f h ead an d n eck p r i ma r y can ce r and m et a s t ase s . A s t ud y con du c t ed a t t h e U n iv e rs i t y O f T h e Wi t w at e r s r and o r a l h ea l t h c en t r e r ep or t ed t h e i n c id en ce o f OSCC a t 19 .8 % and i d en t i f i ed th e o r a l c av i ty as t h e m os t co mmo n s i t e o f HNC (1 6 . 4 %) . 2 2 T h e au t ho r i d en t i f i ed o n e S ou th A f r i can b as ed r e t ros p ec t i v e s tu dy b y Lo o ck e t a l 2 3 wh i ch i d en t i f i ed t h e o r a l c av i t y (1 4% ) as t h e comm on es t s i t e f o r p r im a ry H N C, w i th m er e l y on e p a t i en t ( o f t h e 1 07 cas es ) w i t h su bm an d i bu la r g l and i nv o l vem en t . T h e p r im a r y ob j ec t i v e o f t h i s r e t ro sp ec t i v e aud i t w as t o as ce r t a i n t h e r a t e o f su bm an d i bu l a r g l and in vo lv emen t i n n eck d i s s ec t io ns fo r O SCC a t CB HA H . A sum m ar y o f t h e ab o ve r es u l t s s ho w s t h a t 1 p a t i en t (o u t o f t h e 2 4 th a t m et t h e i n c lu s i on c r i t e r i a ) h ad s ub m an d ib u l a r g l and i nv o l vem en t – a r a t e 4 .2 %. T h e p a t i en t w as a m al e , ag ed >6 0 year s o ld , wi t h a p r i ma r y tu mo u r o f t h e l i p , p a th o lo g i ca l T N M s t ag e o f T4 a N0 M0 , i n d i ca t i ng n o n eck n od es w e r e i nv o lv ed . T h e m eth od o f i nv o lv em en t w as by m ean s o f an i n t r ag l and u l a r m et as t as i s , w h i ch i s r a re . T h e no t ab l e r i s k f ac to r s fo r m al ig n an cy i n t h i s p a t i en t w e re ag e (>6 0 ) and g end e r (m al e ) . Th e n o t ab l e r i sk fo r sub m an d ib u l a r g l and i nv o l vem en t w as a l a rg e p r im a ry tu mo ur ; how ev e r t h e p r im a r y s i t e b e i ng l i p , N 0 neck o r ab s en t no des in l eve l 1 b a r e a l l f a c t o r s t h a t u s u a l l y a r e no t a s s oc i a t ed w i t h su bm an d i bu la r g l and in vo lv em en t . In t he m aj o r i t y o f s e r i es , t h e s ub m an d ib u l a r g l and w as in vo lv ed by d i rec t i nv as i on f r om f lo o r o f m ou th tu mo ur s o r t h e i nv o lv ed m an d ib l e . 6 14 A cco rd in g t o t h e l i t e r a t u r e , t h e p r es ence o f l ev e l 1B n od es i n c r ea se s t h e r i sk o f su bm and ib u l a r g l an d in vo lv em en t (b y d i r ec t sp r ead o f a l o ca l l y i nv o l v ed n od e ) . Th i s w as no t sh o wn i n ou r s t ud y . A n o t he r co mp el l i n g f ac t i s t h a t adv an ced no d a l s t a t us i n ou r s t ud y d i d no t i n c r ea s e t h e r i sk o f su bm and i bu l a r g l an d in vo lv em en t . I t i s p a r t i cu l a r l y i n t e r e s t in g t h a t t h e m et hod o f s ub mand ib u l a r g l and i nv o l vem en t w as by m eans o f i n t r ag l an d u l a r m et a s t as i s , a s t h i s i s a r a r e o ccur r en ce i n t h e l i t e r a tu r e . 6 T h e su rg i ca l t e c h n iq u e o f sp a r i ng th e su bm and i bu l a r g l and h as a l re ady b een es t ab l i sh ed by a n umb er o f p r ev io us s t ud i e s . 2 1 Th e b en e f i t i n s p a r in g t h e g l and in p a t i en t s w ho do n’ t r e ce i ve r ad i a t i on i s t h a t a l a r g e r e s e rv o i r fo r s a l iv a i s m ai n t a i n ed . T h i s p ro v i d es p r ed omi n an t ly m u c in ou s b a s a l s a l iv a ry f l o w, r es pon s i b l e fo r m u co s a l l ub r i c a t i o n , m in i mi z i ng th e r i sk o f x e r os tom i a and t he com pl i ca t io ns th e r eo f . I t m ay a l so i mp r ov e t h e r es po ns e o f s i a l ago gu es bo t h d ur in g an d a f t e r r ad i o t h er apy . 9 T h e p os s i b l e p i t f a l l s o f s p a r in g t h e g l and , i s t h a t s om e o to r h in o l a ry ng o l ogy s u rg eons a re o f t h e o p i n io n th a t t h e sp a r ed g l an d can l e ad to t h e p e rcep t io n o f a p e r s i s t en t p a l p ab l e m ass a t t h e s i t e o f t h e p r ev i ou s l ym phad en ec to my , wh i ch co u l d po t en t i a l l y s ca r and caus e co n cer n f o r fo l lo w -u p . 2 1 C on c lus i on O v er a l l , t h e re i s a l o w r a t e o f s ub mand i bu la r g l and ( 4 . 2% ) i nv o l v em en t i n n eck d i s sec t io ns f o r OSCC a t Ch r i s Han i B ar agw an a t h A cad emi c H o sp i t a l . On co lo g ica l l y , t he s p a r in g o f t h e su bm and i bu la r g l and i s s a f e an d so un d p ro v i ded th e g l an d i s no t sus p i c i ou s f o r i nv o l vem en t e i t h e r r ad i o l og ica l ly , c l i n i ca l ly o r a t t h e t ime o f su rg e r y . C on f l i c t o f In t eres t s : N on e 15 R ef eren ces 1 . A d e o l a H , A f r og h eh A, H i l l e J . Th e bu r d en o f h ead an d n eck can ce r i n A f r i c a : t h e s t a tu s qu o and re s ea r ch p r os pec t s . S ou t h A f r i can D en t a l Jo ur n a l . 2 01 9 ;7 3 : 47 7 -8 8 . DO I : 1 0 . 17 15 9 /2 5 19 - 0 1 05 / 20 18 /v 73 no 8 a1 . 2 . Wo l f f K- D , Fo l l man n M, N as t A . T he d i ag no s i s an d t r e a tm e n t o f o r a l c av i ty can ce r . D eu t sch es A r z t eb l a t t i n t e rn a t i o na l . 2 0 12 ; 10 9 (4 8) :8 29 -3 5 . DO I : 1 0 . 32 38 / a rz t eb l . 20 12 .0 82 9 . 3 . M on t e r o PH , P a t e l S G. C an ce r o f t h e o r a l c av i ty . S u rg ica l o n co lo gy c l i n i cs o f N o r th Am er i ca . 2 01 5 ; 24 ( 3 ) :4 91 - 50 8 . D O I : 1 0 . 10 16 / j . so c .2 0 15 .0 3 . 00 6 . 4 . G u p t a N , Gu p t a R , A ch a ry a A K , P a t th i B , G ou d V , R edd y S , e t a l . C h an g i ng T r en ds i n o ra l c an ce r - a g lo b a l s cen a r i o . N ep a l j ou r n a l o f ep i d emi o l og y . 20 1 6 ;6 ( 4 ) :6 13 - 9 . DO I : 1 0 . 31 26 /n j e .v 6 i4 . 17 25 5 . 5 . O k o t u r o EM , T r i ved i N , K ek a t pu r e V , G ang o l i A , Sh e t k a r G , M oh an M, e t a l . A r e t ro sp ec t iv e ev a l ua t i on o f s ub mand ibu l a r g l an d i nv o l vem en t i n o ra l c av i t y c an ce r s : A ca s e f o r g l an d p r e s e r v a t i on 20 12 . 1 3 83 -6 p . 6 . C ak i r C e t in A , D ogan E , O zay H, K umu s O , E rd ag TK , Ka r ab ay N , e t a l . Su bm an d ib u l a r g l and in v as ion an d f eas ib i l i t y o f g l and - s p a r in g n eck d i s s ec t io n i n o r a l c av i t y c a r c in om a. Th e Jo ur n a l o f L a r yn go lo gy & Ot o l og y . 2 01 8 ; 13 2( 5 ) :4 4 6 - 51 . D O I : 1 0 . 10 17 /S 00 22 2 15 11 80 00 59 2 . 7 . A g a r w al G , N ag pu re PS , Ch av an SS . Qu es t i on ab l e N eces s i ty f o r R em ov in g S ub m an d i bu la r Gl an d i n N eck Di s s ec t i on in S qu amo us C e l l C a r c i nom a o f O r a l C av i t y . Ind i an jo u rn a l o f o to l a r yn go log y and h ead an d n eck s u r g e ry : o f f i c i a l pu b l i c a t io n o f t h e A ss oc i a t i on o f O t o l a r y ng o lo g i s t s o f In d i a . 2 01 6 ; 68 (3 ) : 31 4 - 6 . DO I : 10 .1 00 7 / s1 20 70 - 0 1 6- 09 66 - 4 . 8 . T ak es RP , R o b b i ns K T , Woo lg a r JA , R i n a ld o A , S i lv e r CE , O l o f s s on J , e t a l . Qu es t i on ab l e n ecess i t y t o r emo ve t h e s ub m an d ib u l a r g l and i n n eck d i s s ec t ion . H ead & Neck . 2 0 11 ; 33 ( 5 ) :7 43 - 5 . D O I : 1 0 . 10 02 / h ed .21 4 51 . 9 . D h iw ak ar M , R on en O, M al on e J , R ao K , B e l l S , Ph i l l i p s R , e t a l . Fea s ib i l i t y o f su bm and i bu l a r g l and p r e s e r v a t i on i n neck d i s s ec t io n : A p r os pec t i v e an a to mi c ‐p a th o l og ic s tu dy . H ead & Neck . 2 0 11 ; 33 ( 5 ) :6 03 - 9 . D O I : 1 0 . 10 02 / h ed .21 4 99 . 1 0 . K o lo ky t h as A . Lo ng - t e r m su rg i ca l com pl i ca t io ns in t h e o r a l c an ce r p a t i en t : a co mp r eh ens iv e r ev i ew . P a r t I . Jo u r n a l o f o r a l & m ax i l lo f ac i a l r e s ea r ch . 20 10 ;1 (3 ) : e1 - e . DO I : 1 0 . 50 37 / jom r . 2 01 0 . 13 01 . 1 1 . H i s h am ud d in NH AN , A zm an M, Ko ng M H, B ak i M M, Ath a r PPS H , Yu nu s MRM. N eck d i s s ec t i o n fo r h ead an d n eck ma l i gn an c i es : A M al ay s i an 1 3 y ea r s r ev i ew. B an g l ad esh J ou r na l o f M ed i ca l S c i en ce . 20 17 ;1 6 (3 ) : 38 4 - 96 . D O I :1 0 . 33 2 9 /b jms .v 16 i3 .3 28 5 4 . 1 2 . H o w ard BE , Hi nn i M L , N ag e l T H , C h an g Y - H, Ch eng M -R , H ay d en RE . S ub m an d i bu la r Gl an d P r es e r v a t i on d ur in g Co n cu r r en t N eck D i s s ec t io n and Tr ans o ra l S u rg e ry fo r O r op h ar yn g ea l Sq u am ou s C e l l C a r c i no ma . Oto l a r yn g o lo gy – Head and N eck Su rg e r y . 2 0 14 ; 15 0 (4 ) : 58 7 -93 . D O I : 10 .1 17 7 /0 19 4 59 98 13 51 90 41 . 16 1 3 . P ał a sz P , Ad amsk i Ł , G ó rs ka -C h r ząs t ek M , S t a rzyń sk a A , St ud n i a r ek M . C on tem po r a ry D i ag no s t i c Im ag i ng o f O r a l S qu am ou s C e l l C a r c i no ma - A R ev i ew o f L i t e r a t u r e . Po l i s h jo u r n a l o f r ad io lo gy . 2 0 17 ; 82 :1 93 -2 02 . D O I : 1 0 . 12 65 9 /PJ R .9 0 08 92 . 1 4 . G ad ZS , E l -M a l t OA , E l - Sakk a r y MAT , A bd a l A z i z MM . E l ec t i v e N eck D i s sec t i on fo r M an ag em ent o f E a r ly - S t age O r a l T o ng ue C ance r . As i an P ac i f i c j ou rn a l o f c an ce r p r ev en t ion : APJCP . 2 0 18 ; 19 ( 7 ) :1 79 7 -80 3 . DO I : 1 0 . 22 03 4 /A PJC P . 20 18 .1 9 . 7 . 17 9 7 . 1 5 . E t t i ng e r KS , G anr y L , Fe rn and es RP . O r a l C av i t y Can ce r . O ra l M ax i l lo f ac S u rg No r th A m. 2 01 9( 15 58 - 13 65 (E lec t r on i c ) ) . D O I : 1 0 . 10 16 / j . coms .2 01 8 . 08 .0 02 . 1 6 . S p i eg e l J H , B r ys AK , Bh ak t i A , S i ng er M I . M et as t as i s t o t h e s ub m an d ib u l a r g l and i n h ead and n eck ca r c in om as . H ead & Neck . 2 0 04 ; 26 ( 12 ) : 10 64 -8 . D O I : 10 .1 00 2 /h ed . 20 10 9 . 1 7 . S h ah JP , Gi l Z . Cu r r en t co n cep t s i n m an ag em en t o f o r a l can ce r - - s u rg e ry . O r a l on co l og y . 2 00 9 ; 45 (4 - 5 ) :3 9 4 - 40 1 . D O I : 1 0 . 10 16 / j . o r a lo n co lo gy .2 00 8 . 05 .01 7 . 1 8 . R az f a r A , Wa lv ek ar Rr Fau - Me lk an e A , M elk an e A Fau - J oh ns on J T , J oh ns on J t Fau - My e r s EN , M y er s E N. In c i den ce an d p a t t e rn s o f r eg i on a l m et a s t as i s i n ea r ly o r a l s qu amo us ce l l c an ce rs : f e a s i b i l i t y o f s ubman d i bu l a r g l and p r es e r v a t i on . H ead & N eck . 2 0 09 (1 09 7 -0 34 7 ( E l ec t r on i c ) ) . DO I : 1 0 . 1 00 2 /h ed . 21 12 9 . 1 9 . Y an g S , Wang X , Su J Z , Yu G Y . R a te o f Su bm and i bu l a r G l an d In v o lv em en t i n O r a l Sq u am ou s C e l l C ar c in om a . . J O r a l Max i l l o fac S ur g . 2 01 9 (1 53 1 -50 5 3 (E l ec t ro n i c ) ) . D O I : 1 0 . 10 16 / j . j oms .2 01 8 . 12 .0 11 . 2 0 . H u ang SH , O 'Su l l i v an B . O v e rv i ew o f t h e 8 t h E d i t i on TNM Cl a ss i f i c a t io n f o r H ead and N eck C ance r . Cu r r en t t r e a t men t op t io ns i n on co lo gy . 2 01 7 ;1 8 (7 ) : 40 . D O I :1 0 . 10 0 7 / s 11 86 4 -0 17 -0 48 4 -y . 2 1 . M a lg on d e M S, K um ar M. P r ac t i c ab i l i t y o f su bm an d i bu l a r g l an d i n sq u amo us ce l l ca r c in om as o f o r a l c av i t y . Ind i an jo u rn a l o f o to l a r yn go lo gy and h ead an d n eck su rg e r y : o f f i c i a l pu b l i c a t io n o f t h e As so c i a t io n o f O t o l a r y ng o lo g i s t s o f In d i a . 2 01 5 ; 67 (Su p p l 1 ) :1 38 - 4 0 . DO I : 1 0 . 10 07 / s12 0 70 -0 14 - 08 03 -6 . 2 2 . Z w an e N, M oh ang i G , Sh ang ase S . H ead an d n eck can ce rs am on g H IV - po s i t i ve p a t i en t s : A f iv e yea r r e t ro sp ec t iv e s tu d y f rom a J oh ann esb ur g ho sp i t a l , So u th Af r i c a . T h e Jo u rn a l o f t he D en t a l A s so c i a t io n o f S ou t h A f r i c a = D ie Tyd sk r i f v an d i e T an dh ee lk un d ig e V e r en i g in g v an Su id - A f r ik a . 20 18 ;7 3 :1 2 1 - 6 . 2 3 . E b r ah im A K, L oo ck J w Fau - A f r og h eh A, A f r og heh A Fau - H i l l e J , H i l l e J . I s i t on co lo g i ca l l y s a fe t o l e av e th e i p s i l a t e r a l s ub m an d ib u l a r g l and du r i ng n eck d i s sec t i on fo r h ead an d n eck s qu amo us ce l l c a r c i no ma? J ou r na l o f L a r yn go lo gy an d Ot o l og y . 2 0 11 (1 74 8 -5 46 0 ( E l ec t r on i c ) ) . DO I : 1 0 . 1 01 7 /S0 02 22 15 11 10 0 10 95 . 17 T abl e 2 : A ge an d gen d e r A g e g ro up M a le Fem al e T o t a l F r eq P e r c F r eq P e r c F r eq 2 1 -4 0 y ear s 0 0 2 2 0 .0 0 2 4 1 -6 0 y ear s 9 6 4 .2 9 4 4 0 .0 0 1 3 6 0 + y ea rs 5 3 5 .7 1 4 4 0 .0 0 9 T o ta l 1 4 1 0 0 1 0 1 0 0 . 00 2 4 Close Table 1: Changes in American Joint Cancer Committee staging in lip and oral cavity and nasopharynx 18 F ig ure 1 : P r im a ry t um ou r lo ca t io n F ig ure 2 P a t ho l og ica l T - S t ag e Distribution of tumour location sites (n = 24 patients). Buccal mucosa Floor of mouth Hard palate Lip Lower gingiva Tongue 19 F ig ure 3 : pa th o l og i ca l N c l a s s i f i c a t ion fo r t h e p a t i en t s i n t h i s s tu dy . T abl e 3 : Lev e l 1 B inv o l v em en t Variable Category Freq. Percent Level 1B lymph nodes No 18 75 Yes 6 25 Total 24 100 20 T abl e 4 : C r os s t abu l a t i on b y L ev e l 1 B n od e in vo lv em en t Level 1 B node involvement Variable Category No Yes Total Fisher's exact Freq Perc Freq Perc Freq Gender Male 10 58.824 4 57.143 14 1.000 Female 7 41.176 3 42.857 10 Age group 21-40 years 1 5.8824 1 14.286 2 0.678 41-60 years 10 58.824 3 42.857 13 60+ years 6 35.294 3 42.857 9 Site of primary tumour Buccal mucosa 1 5.8824 0 0 1 0.632 Floor of mouth 6 35.294 2 28.571 8 Hard palate 1 5.8824 0 0 1 Lip 3 17.647 4 57.143 7 Lower gingiva 1 5.8824 0 0 1 Tongue 5 29.412 1 14.286 6 T-category T1 5 29.412 2 28.571 7 0.924 T2 7 41.176 2 28.571 9 T3 3 17.647 2 28.571 5 T4A 2 11.765 1 14.286 3 Total 17 100 7 100 24 21 T abl e 5 : S ub m and i bu la r g l and i nv o l vem en t and l ev e l IB L ym ph n od e Sub mandibular gland involvement and level IB Lymph node Variable Category No Yes Total Fisher's exact Freq Perc Freq Perc Freq Number of lymph nodes: Level 1B 0 17 100 1 14.286 18 0 1 0 0 5 71.429 5 2 0 0 1 14.286 1 N Category N0 12 70.59 1 14.286 13 0.7197 N1 0 0 2 28.571 2 N2A 0 0 1 14.286 1 N2B 4 23.53 1 14.286 5 N2C 1 5.88 2 28.571 3 Missing 1 6.25 2 28.571 3 0.05 Number of lymph nodes involved None 11 64.706 1 14.286 12 More than 1 3 17.647 4 57.143 7 One 2 11.765 0 0 2 22 T abl e 6 : G en d e r d i f f e r en t i a l s amo ng th e p a t i en t s Variable Category Male Female Yes Fisher's exact Freq Perc Freq Perc Freq Site of primary tumour Buccal mucosa 0 - 1 10.00 1 0.562 Floor of mouth 6 42.86 2 20.00 8 Hard palate 1 7.14 0 - 1 Lip 4 28.57 3 30.00 7 Lower gingiva 0 - 1 10.00 1 Tongue 3 21.43 3 30.00 6 T Category T1 4 28.57 3 30.00 7 0.548 T2 4 28.57 5 50.00 9 T3 3 21.43 2 20.00 5 T4A 3 21.43 0 - 3 Level 1B 0 11 78.57 7 70.00 18 0.777 1 2 14.29 3 30.00 5 2 1 7.14 0 - 1 N Category N0 6 42.86 7 70.00 13 0.05 N1 0 - 2 20.00 2 N2A 1 7.14 0 - 1 N2B 5 35.71 0 - 5 N2C 2 14.29 1 10.00 3 Number of lymph nodes involved None 6 46.15 6 75.00 12 0.53 More than 1 5 38.46 2 25.00 7 One 2 15.38 0 - 2 23 Appendix A – Approved Protocol A protocol in planning for a Research Report (NEUS7009) in part fulfilment towards the degree of Master of Medicine in Otorhinolaryngology, university code MFOSENTS60. Candidate: Dr Mohammed Nathie Student number: 0703120A Supervisor: Dr Yahya Atiya Division: OTORHINOLARYNGOLOGY-HEAD NECK SURGERY Department: Neurosciences School of Clinical Medicine Faculty of Health Sciences University of the Witwatersrand. Johannesburg Proposed title: The rate of submandibular gland involvement in patients undergoing elective Neck Dissection for Oral Cavity Squamous cell carcinoma at Chris Hani Baragwanath Academic Hospital. i Declaration I, Mohammed Nathie, declare that this research report is my own, unaided work. It is being submitted for the degree of Master of Medicine in the branch of Otorhinolaryngology at the University of the Witwatersrand, Johannesburg. It has not been submitted before for any degree or examination at this or any other university. (signed by candidate) 13/02/2019 – JOHANNESBURG (date, place) ii List of abbreviations CHBAH – Chris Hani Baragwanath Academic Hospital ENT – Ear, nose and throat SCC – Squamous cell carcinoma HNC – Head and neck cancer OSCC – Oral Squamous cell carcinoma HIV – Human immunodeficiency virus HPV – Human papilloma virus iii Table of contents: Declaration .............................................................................................................................................. i 1. Introduction .................................................................................................................................... 1 1.1. Background 1 1.2. Statement of the problem 1 1.3. Justification for the research 2 2. Literature review 2 3. Research question 9 4. Aim 9 5. Methodology .................................................................................................................................. 9 5.1. Research design 9 5.2. Study population 9 5.2.1. Inclusion and exclusion criteria 9 5.3. Study period 10 5.4. Study location 10 5.5. Data collection 10 5.6. Data analysis ........................................................................................................................... 11 5.7. Significance of this study ...................................................................................................... 12 6. Limitations .................................................................................................................................... 12 7. Ethical considerations ................................................................................................................ 12 8. Timing ........................................................................................................................................... 13 1. Introduction 1.1. Background Head and neck cancer (HNC) in Africa is increasing in incidence. This is attributed to the rise of smoking habits (and use of other tobacco products), lifestyle and diet westernization, increase use of alcohol, human papilloma virus (HPV), human immunodeficiency virus (HIV), and health policies which are unfavourable. 1 The most frequent site of HNC is the oral cavity and squamous cell carcinoma (SCC) is the commonest histological type. It is estimated that at least 90% of oral cavity cancers are squamous cell carcinoma.2, 3 Neck dissection is a vital part of the surgical treatment; which together with adjuvant radiotherapy and chemoradiotherapy, when indicated, are the treatment for oral SCC(OSCC). 4 Submandibular gland resection is a routine step in neck dissection, even though the rate of submandibular gland involvement is very low.5 Preservation of the submandibular gland has been shown to have better outcomes in patients’ quality of life.6 1.2. Statement of the problem Globally, oral cavity SCC is the sixth most common cancer, while in developing countries it ranks third1 The surgical treatment of choice is resection of the primary tumour with appropriate neck dissection to ensure no metastases are missed.7 Although tumour metastasis to the submandibular gland is uncommon, it has been routinely resected resulting in significant alterations in the oral health, hygiene, nutrition and quality of life of patients post-surgical resection.4 There is literature to support the lack of involvement of submandibular glands as a site of metastases in primary OSCC5. This has not been investigated in our setting at Chris Hani Baragwanath Academic Hospital (CHBAH). 1.3. Justification for the research The routine resection of the submandibular gland has a negative impact on the patients’ long term oral health and quality of life. Therefore, this retrospective audit aims to describe whether or not involvement of the submandibular glands exists in neck dissections of patients who underwent excision of OSCC at CHBAH. 2. Literature review 2.1. Epidemiology Internationally the continent of Asia is most commonly affected by OSCC with a reported incidence of 3.8 per 100 000, while in the African continent and South Africa, the incidence rate per 100 000 is estimated at 2.6 and 4 respectively.8 OSCC affects the middle-age to elderly population and occurs more commonly in men than women.3 Risk factors identified are tobacco smoking and alcohol which have a synergistic effect in the aetiology of OSCC.2, 3 Contributory host factors are described such as compromised immune systems in HIV-infected as well as transplant patients.3 Viral causes such as HPV have been described, however there is disparity in the literature regarding its role in the pathogenesis of OSCC.1, 3 Additionally, genetic predisposition in conditions such as Fanconi’s anaemia, xeroderma pigmentosum and ataxia telangiectasia are linked to the development of head and neck cancers.3 Presenting features are non-specific leading to missed diagnosis and more commonly presentation with advanced disease and thus, higher mortality.3 2.2. Oral cavity anatomy The anatomy of the oral cavity is defined superiorly by the junction of the soft and hard palate and inferiorly from vermillion border of the lips to the circumvallate papillae of the tongue.3 There are eight anatomical subsites of the oral cavity namely: hard palate, retromolar trigone, upper and lower gum, buccal mucosa, oral tongue, floor of mouth and lip.3 The most common subsite of origin of OSCC is the anterior two- thirds of the tongue.9 2.3. Submandibular gland and physiology The submandibular glands are paired major salivary glands located beneath the floor of the mouth and contributes to both basal unstimulated and stimulated saliva production.10 Saliva, which moistens the oral cavity, contains mucous, amylase, bicarbonate, lactoferrin and immunoglobulins.11 Amylase enables the digestion of starch, while mucous assists the lubrication of food and eases swallowing.11 Bicarbonate alkalinises the saliva enabling the buffering of acidic bacterial enzymes and preserving the mineral integrity of teeth. Lactoferrin and immunoglobulins assists in immune function and maintenance of oral hygiene.11 In view of these crucial functions, the absence of the submandibular gland has implications for lack of oral hygiene, teeth integrity, nutrition and quality of life of the affected individual.4 2.4. Submandibular gland involvement in OSCC OSCC rarely metastasizes to the submandibular gland.6 They are more commonly involved by either direct spread (of a primary ipsilateral oral cavity tumour or locally involved lymph node) or from distant primaries outside the head and neck, via haematogenous spread; such as the lung, breast and the urogenital system.4, 6, 12 It is well described that primary OSCC do not metastasize to the submandibular gland via haematogenous spread.4 The submandibular gland does not contain intraglandular lymph nodes or lympho-vascular structures.4, 10 The lymph node groups surrounding the submandibular gland are sublocations of sub level 1B and are identified as preglandular, postglandular, prevascular and postvascular.12 This is in contrast to the parotid gland which contains intraparenchymal lymph nodes. The significance of this is that the parotid gland is a site for intraglandular lymph node metastases for other HNC, which is not the case for the submandibular gland.10 This has implications for the surgical strategy adopted towards the submandibular gland in OSCC. Excision of the submandibular gland as part of a level 1B dissection of the neck is routine practice, due to the common belief that this will facilitate complete removal of lymph nodes in the region of the gland.10 Dhiwakar et al13 showed that the submandibular gland can be safely preserved whilst still achieving complete removal of all lymph nodes in sub level 1B in neck dissections. Submandibular gland resection is associated with several complications that impact anatomically, physiologically and functionally. The anatomical structure affected most commonly is the marginal mandibular nerve which is a branch of the facial nerve (VII) which runs under the surface of the platysma muscle in the region of the submandibular gland.14 In 2017, Hishamuddin et al15 reported nerve complications in 23.3% of the neck dissections cases done in their centre. This study further identified, the marginal mandibular nerve as the most commonly injured nerve in neck dissections with a 13.1% rate of occurrence in all neck dissection cases.15 In view of the physiological role of the submandibular gland in saliva production, removal of the gland decreases unstimulated saliva production and results in dryness of the mouth (xerostomia).4 Xerostomia impairs chewing which affects nutritional intake of patients post submandibular gland resection. It also causes a chronic burning sensation within the oral cavity which impacts on patients’ quality of life. The chronic mucosal dryness may result in fissuring of the tongue and lips, loss of appetite and weight, dental caries, oropharyngeal candidiasis and angular cheilitis.13 Functionally, marginal mandibular nerve injury may cause dysfunctional depression of the anguli oris muscle, resulting in drooping of the angle of the mouth which impairs feeding and alters cosmesis.15 In view of these complications, resection of the submandibular gland is not a benign procedure and preservation should be considered to reduce complication rates and improve patient outcomes.6, 12, 13, 16 Several authors have described the rate of submandibular gland involvement in OSCC. According to Malgonde et al11 the submandibular gland was involved in 3.06% of OSCC cases, where metastasis was due to direct invasion of a tumour in close proximity to the gland. Yang et al5 identified involvement of the submandibular glands in 52 out of 2 126 patients who underwent neck dissections for OSCC. Similarly, Cetin et al4 found involvement of the submandibular gland via direct invasion was evident in 2 out of 155 patients, and the floor of mouth location was the only risk factor for submandibular gland involvement. In view of this, submandibular gland preservation should be considered on a case by case basis. The author did not identify literature on the rate of submandibular gland involvement in OSCC in South Africa and Africa as a whole. According to the literature, this is attributed to the lack of quality data management in resource constraint settings.8 The limited data from South Africa does not describe the rate of submandibular gland involvement, but rather describes the distribution of head and neck primary cancer and metastases. A study conducted at the University Of The Witwatersrand oral health centre reported the incidence of OSCC at 19.8% and identified the oral cavity as the most common site of HNC (16.4%).17 A SA based retrospective study by Loock et al 18 similarly identified the oral cavity (14%) as the commonest site for primary HNC, with merely one patient (of the 107 cases) with submandibular gland involvement. 2.5. Classification The tumour, nodal, metastases (TNM) classification system is universally adopted as the classification of choice for malignant tumours.9 The T category is defined by tumour size and depth of invasion, while the N category is defined by regional nodal involvement, and the M category is defined by distant metastases. Table 19 illustrates the TNM classification of OSCC according to the most recent release of the American Joint Committee on Cancer.9 Close Table 1: Changes in American Joint Cancer Committee staging in lip and oral cavity and nasopharynx 2.6. Clinical evaluation Due to the non-specific presenting complaints, patients with OSCC often present late at an advanced stage of the disease process.3 The spectrum of presentation includes: pain, oral mucosal changes, oral cavity and/or neck swelling, unexplained loosening of teeth in the absence of periodontal disease, odynophagia, dysphagia, persistent foreign body sensation, reduced tongue mobility, altered sensation of the oral cavity.2 A detailed history and comprehensive clinical examination of the ear, nose and throat, including endoscopy must be performed to ensure that the primary tumour is identified while not missing a second primary or synchronous metastases.2 The initial diagnostic workup requires a biopsy. In the outpatient clinic, lesions which are accessible, may be the biopsy sample site for adequate tissue diagnosis, using a punch forceps, core needle or fine needle aspiration.3 A variety of imaging studies have value in confirming the diagnosis of OSCC such as: dental radiographs, magnetic-resonance imaging, ultrasonography, computed tomography and photon-emission tomography.19 Each of these modalities has advantages and limitations which is beyond the scope of this text. Lymph node identification is difficult to achieve both clinically and radiologically.20 2.7. Management Various treatment modalities for OSCC are available such as radiation, chemotherapy and surgical resection.7 The management requires a multidisciplinary team approach including representatives from oncology, ENT, oromaxillofacial, radiotherapy and radiology, who individualise to each patients’ biopsychosocial context, while maximizing oncological control and minimizing alteration of the patient’s form and function.2 3 Multiple factors guide treatment options such as the nature of the tumour and surgical resectability, the balance between risk and benefit of treatment related complications on the patients’ age, comorbid diseases, socioeconomic status and quality of life thereafter. 2, 3 Many centres advise surgical resection as, it provides histopathological information on tumour stage, grade and spread, which is essential information to guide further management.3 2.8. Neck dissection The surgical approach adopted is individualised to the patients clinical and histopathological diagnosis.21 Elective neck dissection (END) is recommended for any tumour where the risk of occult nodal metastasis is greater than 20%.2 It is estimated that 60% of patients with early stage OSCC will present with a clinically negative neck (cN0).3 In the oral cavity, the majority of tumours will require END, regardless of T status, with the exception of cancer of the hard palate and upper alveolar ridge.2 This is in contrast to OSCC floor of the mouth and oral tongue which are more likely to metastasise to the neck; these patients should be offered END even if they are early stage tumours (if the thickness exceeds 4mm).3 The goal of this surgical approach is to achieve loco-regional control and thus, enhance the cure rate of OSCC.3 A significant clinical prognosticator of survival is the finding of metastases to the neck.22 ND include the following types: extended radical ND, radical ND, modified radical ND, modified ND and selective ND.15 In all forms of ND used to treat OSCC the submandibular gland is routinely removed.4 2.9. Outcomes It is estimated that one fifth of patients treated for oral cavity cancer experience local tumour recurrence of 76% within 2 years, therefore it is advised these patients receive long term follow up.2 3. Research question What is the rate of submandibular gland involvement in patients who underwent neck dissection for oral cavity squamous cell carcinoma? 4. Aim • To determine the rate of SMG involvement in neck dissection specimens of patients undergoing surgery for OSCC • To determine the feasibility of SMG preservation at neck dissection. 5. Methodology 5.1. Research design This will be a retrospective clinical audit. 5.2. Study population The study will include all patients who had undergone elective neck dissection at CHBAH, as part of surgical treatment for OSCC. The expected number of records examined will be approximately 50 patients. 5.2.1. Inclusion and exclusion criteria Inclusion criteria for this study will be: • Histopathologically confirmed SCC of the oral cavity • Surgery as the primary treatment modality Exclusion criteria for this study will be: • Tumour histology other than SCC • Patients with a previous history of head and neck radiotherapy • Patients with cancer occurring in sites other than the oral cavity. 5.3. Study period The study will extend from 1st January 2014 to 31st December 2018. 5.4. Study location The study will be conducted in the clinical unit of Otorhinolaryngology at the Chris Hani Baragwanath Hospital in Soweto, Johannesburg, South Africa. CHBAH is a tertiary level teaching hospital affiliated to the University of the Witwatersrand. 5.5. Data collection Patients will be identified from two sources: • ENT Operating Theatre register • ENT Ward Admissions register The operating theatre register will be used as a primary reference to identify eligible patients. The ward admission register will be used as a secondary reference to identify patients whose theatre record is unclear or lacking detail (incorrectly spelt names, missing or partial hospital numbers). All patients who are clearly identified from the theatre register will be recorded as part of the initial sample population. This information will then be used to interrogate the database of the National Health Laboratory Services (NHLS), and all findings will be recorded into one of the following categories: • Histology report, in which a histological analysis was performed on the specimen. • No result, in which no result was found on the database. • Incomplete or incorrect information, in which insufficient information was available to perform the interrogation. Patients identified exclusively from the secondary reference will be cross checked against their recorded laboratory findings and will be included in the study population. If these patients lack sufficient information, they will not be included in the study sample. The following data will be recorded for each patient: • Hospital registration number • Age • Sex • Presenting complaint • Clinical findings • Date of surgery • Site of primary tumour • Histological result All data will be recorded electronically using Microsoft Access and Microsoft Excel. 5.6. Data analysis • Microsoft Access 2010 for data storage, retrieval and selection. • Microsoft Excel 2010 for descriptive analysis, summary statistics and comparison of sample means. • Statistica (Statsoft GmBH) software for statistical analysis • Standard statistical methods will be used. Student’s t test will be used to analyse continuous data and the Chi Square (X2) test for ordinal data. A probability (p) value of less than (or equal to) 0.05 is regarded as significant. In the event that numbers are too low to use the Chi square test, Fischer’s exact test will be used. • Microsoft Word 2010 for final documentation and presentation. 5.7. Significance of this study • To identify the rate of involvement of the submandibular gland in patients with oral cavity SCC. The author’s hypothesis is that in this audit the patients who underwent neck dissection for resection of OCSCC did not have metastatic spread to the submandibular glands and preservation should have been considered. • Decrease surgical time during neck dissections • Improve quality of life for the patient (oral hygiene, nutrition) • Reduce surgical morbidity • Reduce marginal mandibular nerve injury 5.8. Funding No funding is required for this study. The minimal costs (approx. R500) associated with printing and binding will borne by the principle investigator. 6. Limitations • Inadequate patient numbers • Inadequate patient records • Cross-sectional study 7. Ethical considerations In view of this study being a retrospective audit, no patient consent is required. The study will commence after approval by the Human Research Ethics Committee of the University of the Witwatersrand. All data will be confidential and stored on a password-protected database, to which the author alone will have access. Permission will be obtained from the clinical and academic HODs of ENT at CHBAH, as well as the CEO of CHBAH, and the HOD of the NHLS, to conduct the study and access records. 8. Timing Activity Feb 2019 March 2019 April 2019 June-Nov 2019 Dec 2019 Jan 2020 Feb 2020 Proposal preparation Literature review Proposal submission Ethics and postgrad approval Data collection Data analysis Write and submission References 1. Adeola H, Afrogheh A, Hille J. The burden of head and neck cancer in Africa: the status quo and research prospects. S. Afr. dent. j. 2019;73:477-88. DOI:10.17159/2519- 0105/2018/v73no8a1. 2. Wolff K-D, Follmann M, Nast A. The diagnosis and treatment of oral cavity cancer. Deutsches Arzteblatt international. 2012;109(48):829-35. DOI:10.3238/arztebl.2012.0829. 3. Montero PH, Patel SG. Cancer of the oral cavity. Surgical oncology clinics of North America. 2015;24(3):491-508. DOI:10.1016/j.soc.2015.03.006. 4. Cakir Cetin A, Dogan E, Ozay H, Kumus O, Erdag TK, Karabay N, et al. Submandibular gland invasion and feasibility of gland-sparing neck dissection in oral cavity carcinoma. The Journal of Laryngology & Otology. 2018;132(5):446-51. DOI:10.1017/S0022215118000592. 5. Yang S, Wang X, Su JZ, Yu GY. Rate of Submandibular Gland Involvement in Oral Squamous Cell Carcinoma. . J Oral Maxillofac Surg. 2019(1531-5053 (Electronic)). DOI:10.1016/j.joms.2018.12.011. 6. Okoturo EM, Trivedi N, Kekatpure V, Gangoli A, Shetkar G, Mohan M, et al. A retrospective evaluation of submandibular gland involvement in oral cavity cancers: A case for gland preservation2012. 1383-6 p. 7. Spiegel JH, Brys AK, Bhakti A, Singer MI. Metastasis to the submandibular gland in head and neck carcinomas. Head & Neck. 2004;26(12):1064-8. DOI:10.1002/hed.20109. 8. Gupta N, Gupta R, Acharya AK, Patthi B, Goud V, Reddy S, et al. Changing Trends in oral cancer - a global scenario. Nepal journal of epidemiology. 2016;6(4):613-9. DOI:10.3126/nje.v6i4.17255. 9. Ettinger KS, Ganry L, Fernandes RP. Oral Cavity Cancer. Oral Maxillofac Surg North Am. 2019(1558-1365 (Electronic)). DOI:10.1016/j.coms.2018.08.002. 10. Takes RP, Robbins KT, Woolgar JA, Rinaldo A, Silver CE, Olofsson J, et al. Questionable necessity to remove the submandibular gland in neck dissection. Head & Neck. 2011;33(5):743-5. DOI:10.1002/hed.21451. 11. Malgonde MS, Kumar M. Practicability of submandibular gland in squamous cell carcinomas of oral cavity. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2015;67(Suppl 1):138-40. DOI:10.1007/s12070-014-0803-6. 12. Agarwal G, Nagpure PS, Chavan SS. Questionable Necessity for Removing Submandibular Gland in Neck Dissection in Squamous Cell Carcinoma of Oral Cavity. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2016;68(3):314-6. DOI:10.1007/s12070-016-0966-4. 13. Dhiwakar M, Ronen O, Malone J, Rao K, Bell S, Phillips R, et al. Feasibility of submandibular gland preservation in neck dissection: A prospective anatomic‐pathologic study. Head & Neck. 2011;33(5):603-9. DOI:10.1002/hed.21499. 14. Kolokythas A. Long-term surgical complications in the oral cancer patient: a comprehensive review. Part I. Journal of oral & maxillofacial research. 2010;1(3):e1-e. DOI:10.5037/jomr.2010.1301. 15. Hishamuddin NHAN, Azman M, Kong MH, Baki MM, Athar PPSH, Yunus MRM. Neck dissection for head and neck malignancies: A Malaysian 13 years review. Bangladesh Journal of Medical Science. 2017;16(3):384-96. DOI:10.3329/bjms.v16i3.32854. 16. Howard BE, Hinni ML, Nagel TH, Chang Y-H, Cheng M-R, Hayden RE. Submandibular Gland Preservation during Concurrent Neck Dissection and Transoral Surgery for Oropharyngeal Squamous Cell Carcinoma. Otolaryngology–Head and Neck Surgery. 2014;150(4):587-93. DOI:10.1177/0194599813519041. 17. Zwane N, Mohangi G, Shangase S. Head and neck cancers among HIV-positive patients: A five year retrospective study from a Johannesburg hospital, South Africa. The Journal of the Dental Association of South Africa = Die Tydskrif van die Tandheelkundige Vereniging van Suid-Afrika. 2018;73:121-6. 18. Ebrahim AK, Loock Jw Fau - Afrogheh A, Afrogheh A Fau - Hille J, Hille J. Is it oncologically safe to leave the ipsilateral submandibular gland during neck dissection for head and neck squamous cell carcinoma? Journal of Laryngology and Otology. 2011(1748- 5460 (Electronic)). DOI:10.1017/S0022215111001095. 19. Pałasz P, Adamski Ł, Górska-Chrząstek M, Starzyńska A, Studniarek M. Contemporary Diagnostic Imaging of Oral Squamous Cell Carcinoma - A Review of Literature. Polish journal of radiology. 2017;82:193-202. DOI:10.12659/PJR.900892. 20. Gad ZS, El-Malt OA, El-Sakkary MAT, Abdal Aziz MM. Elective Neck Dissection for Management of Early- Stage Oral Tongue Cancer. Asian Pacific journal of cancer prevention : APJCP. 2018;19(7):1797-803. DOI:10.22034/APJCP.2018.19.7.1797. 21. Shah JP, Gil Z. Current concepts in management of oral cancer--surgery. Oral oncology. 2009;45(4-5):394-401. DOI:10.1016/j.oraloncology.2008.05.017. 22. Razfar A, Walvekar Rr Fau - Melkane A, Melkane A Fau - Johnson JT, Johnson Jt Fau - Myers EN, Myers EN. Incidence and patterns of regional metastasis in early oral squamous cell cancers: feasibility of submandibular gland preservation. Head & Neck. 2009(1097-0347 (Electronic)). DOI:10.1002/hed.21129. Appendix A: Data collection sheet Study Number Age <20 21-40 41-60 >60 Gender Male Female Site of primary tumour Floor or mouth Tongue Lip Lower gingiva Upper gingiva Retromolar trigone Hard palate Buccal mucosa T category T1 T2 T3 T4a T4b Submandibular gland involvement Yes No Method of submandibular gland involvement Direct invasion from primary tumour Direct invasion from level 1B Intraglandular metastasis Level 1B lymph nodes Yes No Number of lymph nodes involved Appendix B – Ethics Clearance 24 Appendix C - Change of Title Approval 25 Appendix D – Chris Hani Baragwanath Hospital Otorhinolaryngology HOD Approval letter 26 Appendix E – NHLS letter 27 Appendix F – Medical Advisory Committee CHBAH Letter 28 Appendix G – Authorship Guidelines for the WITS Journal of Clinical Medicine 29 Appendix H – Turnitin Report 30