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LARYNGEAL CARCINOMA, EPIDEMIOLOGICAL

    AND CLINICAL FEATURES AS SEEN AT KENYATTA

                               NATION...
DECLARATION




I certify that this dissertation is my original work and it has not been presented for a

degree Programme...
ACKNOWLEDGEMENTS

I would like to thank the following persons who assisted me accomplish my project.


   1. Prof. Issac.M...
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  1. 1. LARYNGEAL CARCINOMA, EPIDEMIOLOGICAL AND CLINICAL FEATURES AS SEEN AT KENYATTA NATIONAL HOSPITAL A dissertation submitted in part fulfillment of the award of degree of Masters of Medicine in ENT, Head and Neck Surgery at the University of Nairobi INVESTIGATOR DR. FATHIYA A. ABDALLA MD (Istanbul) SUPERVISOR PROF. ISAAC M. MACHARIA MBCHB, MMed (ENT Surgery) Associate Professor Department of Surgery University of Nairobi
  2. 2. DECLARATION I certify that this dissertation is my original work and it has not been presented for a degree Programme in any other university. Signed………………………………….. Date…………………………………… Dr.Fat-hiya. A.Abdalla This dissertation has been submitted for examination with my approval as a university supervisor. Signed ………………………………….. Date…………………………………………. Prof. Isaac M. Macharia 2
  3. 3. ACKNOWLEDGEMENTS I would like to thank the following persons who assisted me accomplish my project. 1. Prof. Issac.M.Macharia; for his supervision, guidance, criticism, and support during the entire study. 2. Dr.Nailah Kassim; for her encouragement and assistance in the preparation of this manual. 3. My colleagues for their support and input in this project. 4. Mr.Oyugi for the statistical advice. 5. Staff in the departments of ENT, Radiotherapy, Central Registry, Dental Registry, and Histology; for their co-operation and willingness to assist. 6. Lords Healthcare for their internet searches and printing facility. 7. Harleys and GlaxoSmithKline for assisting in my presentations. 8. Last, but not least, my family who are a great pillar of support and encouragement. 3
  4. 4. DEDICATION I dedicate this work to my husband, Mr.Hisham Mwidau, for inspiring me to aim for higher goals in life. 4
  5. 5. Table of Contents Declaration ………………………………………………………….2 Acknowledgements…………………………………………………3 Dedication……………………………………………………………4 Table of Contents……………………………………………………5 List of Figures and Tables ………………………………………...6 Abbreviations ……………………………………………………….7 Abstract ……………………………………………………………..8 Literature Review …………………………………………………..9 Justification of Study ................................................................29 Objectives ………………………………………………………….30 Materials and Methods …………………………………………...31 Ethical Consideration …………………………………………..…36 Results ……………………………………………………………..37 Discussions …………………………………………………….….53 - 54 Recommendations ………………………………………………..55 References ………………………………………………………...56 Appendices ………………………………………………………..64 5
  6. 6. List of Figures and Tables Figure 1: Gender ………………………………………………….37 Figure 2: Age distribution ……………………………………..….38 Figure 3: Geographical distribution ……………………………..39 Figure 4: Smoking habits ………………………………………...40 Figure 5: Alcohol Consumption ………………………………….41 Figure 6: Types of alcohol consumed ………………………….41 Figure 7: Smoking and alcohol ……………………………….…42 Figure 8: Symptoms ……………………………………………...43 Figure 9: Duration of dysphonia (months) ……………………..44 Figure 10: Comparison of DIB versus overall staging …….….45 Figure 11: Neck findings …………………………………….…...46 Figure 12: Tumour sites ………………………………………….47 Figure 13: Histopathological types ……………………………...48 Figure 14: TNM classification ……………………………………49 Figure 15: Treatment modality versus overall staging ………..50 Figure 16: Tracheostomy ………………………………………...51 Figure 17: Head and neck malignancies in the study ………...52 Table 1: Statistics of pack years of smoking …………………..40 6
  7. 7. ABBREVIATION TL Total Laryngectomy RT Radiotherapy HNSCC Head and Neck Squamous Cell Carcinoma AJCC American Joint Committee IUCC International Union Against Cancer RND Radical Neck Dissection MRND Modified Radical Neck Dissection SND Selective Neck Dissection DL Direct Laryngoscopy IL Indirect Laryngoscopy TM Tumour GERD Gastro-oesophageal Reflux Disease FHG Full Hemogram U & E’S Urea and Electrolyte LFT’S Liver Function Tests CXR Chest X-rays (PA view) KNH Kenyatta National Hospital 7
  8. 8. ABSTRACT Carcinoma of the larynx is a common head and neck malignancy. It has a widely varying prevalence in the different regions of the world. This study, a prospective cross- sectional survey, was designed to determine the prevalence of laryngeal carcinoma at Kenyatta National Hospital, and the prevalence of certain risk factors such as smoking and alcohol intake in the same patients. 62 patients with laryngeal cancer and 176 patients with other head and neck malignancies were seen between September 2003 and December 2003. Elderly patients between the ages of 51-70 years who smoked and/or took alcohol were more frequently seen. The male to female ratio of affected patients was 11:1. Most patients were from Central Province, followed by Eastern and Nairobi Provinces. All 62 patients with laryngeal cancer had squamous cell carcinoma. The type most encountered was the well differentiated squamous cell carcinoma. The main presenting symptoms were dysphonia and difficulty in breathing. Most of the patients presented with advanced disease necessitating more radical methods of treatment. The treatment modalities given depended on the stage of disease at presentation. All but a few patients received apt treatment. 8
  9. 9. LITERATURE REVIEW INTRODUCTION Carcinoma of the larynx is a malignancy with a good prognosis when diagnosed and treated early, control rates reaching 95% in certain subsites of the organ (1). Moreover it is larglely a prevantable disease. The incidence of carcinoma of the larynx in the UK is approximately 7.2%(2) and about 20% in the US (3) of all head and neck tumors (2). This places upon the clinician a greater responsibility to carefully evaluate, diagnose and treat the patients, offering a possibility of cure. Until the late 1800s, laryngeal cancer generally was considered a fatal disease that was palliated by tracheostomy and only rarely cured by larygo- fissure. In 1873, Billroth performed the first total laryngectomy (TL); however this procedure was not widely accepted for 20 years. Early experiences with laryngectomy were associated with mortality rates as high as 94-95%. By 1900, improved patient selection and modification of technique resulted in mortality (4) rate of 8.5% and long time survival rose from 4% to 44% . During the 20th century, TL was accepted as the preferred modality for treatment of laryngeal cancer. Later, a trend developed toward voice preservation with the development of conservation laryngeal surgeries, radiation protocols and combined chemotherapy and radiotherapy. 9
  10. 10. EPIDEMIOLOGY Laryngeal cancer affects men more frequently than females with ratios varying in different regions, for example a 4:1 male to female ration in the USA and 10:1 in Spain. There has been a decrease in the ratios in recent years which is thought to be due to increased smoking in females. Laryngeal carcinoma is rarely seen below the age of 40 years, affecting mainly men (2,5,6) with a peak incidence in the seventh decade .Data from the Third National Cancer Survey in the USA have demonstrated a slightly greater prevalence in urban centers(7). The incidence varies worldwide. According to recent data released by the American Cancer society, approximately 10,000 new cases of laryngeal carcinoma are diagnosed each year in the USA and 3,900 deaths occur yearly as a result of this disease(5). Spain has one of the highest rates in the world with an incidence approaching 20 cases per 100,000 persons in some regions. France, Poland and Italy also have high rates of the disease (2,5,6). The prevalence of laryngeal cancer in our country is not documented and no recent data on the incidence exists. A retrospective study on carcinoma of the larynx undertaken 17 years ago at Kenyatta National Hospital showed a total number of 109 (8) patients only, diagnosed and treated for the same over a 10 year period (1973-83) . Since then, there has been an increase in the number of patients managed for cancer of the larynx (9). 10
  11. 11. ANATOMY OF THE LARYNX Embroyology The larynx, an organ of the lower respiratory system begins to develop in the 4th week of life. Laryngotracheal groove, the respiratory primodial develops as a medial outgrowth from the caudal end of the ventral walls of the primodial pharynx. With further evagination forming a pouch like laryngotracheal diverticulum which finally develops into the larynx, trachea, bronchi and the lungs. The epithelial lining of the larynx develops from the endoderm, the cartilages from the 4th and 6th pharyngeal arch and brachial eminence. Laryngeal muscles develop from the myoblasts in the 4th and 6th pairs of the pharyngeal arches, they are innervated by the (10,11) laryngeal branches of the vagus nervous (CNX) that supply these arches . Descriptive Anatomy The larynx is a respiratory organ, set in the respiratory tract between the pharynx and the trachea. Although phonation is important in man, the main function of the larynx is to provide a protective sphincter at the inlet of the air passages. It also provides a blockage to build up pressure for coughing or aiding extreme muscular efforts. 11
  12. 12. The skeletal framework of the larynx is formed of cartilages which are connected by ligaments and membranes and are moved in relation to one another by both intrinsic and extrinsic muscles. The thyroid, cricoid and arytenoids cartilages are composed of hyaline cartilage and with age parts of them ossify. The epiglottic, corniculate and cuneiform cartilages are elastic fibrocartilage. The larynx is divided into 3 regions and sites within each region: - (i) Supraglottic: Comprising of laryngeal surface of the epiglottis, the arylepiglottic folds, the laryngeal surface of arytenoids, the false cords and the ventricles. (ii) Glottis: The 2 vocal cords, the anterior and posterior commissure. (iii) Subglottis: Small area extending from the undersurface of the vocal cords to the lower border of the cricoid cartilage. The division has its basis in embryologic derivation with each side having different lymphatic drainage. The clinical importance of this compartmentalization is that; it provides anatomical basis for partial laryngeal surgeries; determines mode of spread and prognosis of cancer in the three regions and in planning radiotherapy, especially for occult metastasis(12). 12
  13. 13. Laryngeal Skeleton: The major cartilages of the larynx are the thyroid, cricoid, arytenoids and epiglottis. The upper border of the thyroid cartilage is united with the hyoid bone above by the thyrohyoid membrane. The inferior horns of the thyroid cartilages articulates below with the cricoid cartilage by synovial joints. The thyroid cartilage encloses the larynx anteriorly and laterally.Both true vocal cords and the false cords attach to the inside of the thyroid cartilage anteriorly and the vocal process of each arytenoid cartilage posteriorly. The cricoid cartilage anteriorly is united above, through its arch, with the thyroid cartilage by the cricothyroid ligament.Below, the cricoid connects with the trachea by the cricotracheal ligament. Articulating with upper lateral borders of the cricoid laminae are the arytenoid cartilages.Each arytenoid resembles a 3 dimension pyramid. The base of the pyramid is another synovial joint in which the arytenoids cartilage can slide laterally and medially or rotate upon the cricoid cartilage. Laterally, there is a short, blunt muscular process and anteriorly, there is a thinner vocal process, to which the vocal cords are attached. The unpaired epiglottic cartilage, slightly curled, leaf shaped arches diagonally upward and backward from the posterior surface of the anterior portion of the thyroid cartilage to which it is attached by a ligament, the thyroepiglottic ligament. The epiglottis has numerous dehiscences which facilitate tumour spread into the pre-epiglottis space leading to the vallecula and base of tongue (12, 13) . 13
  14. 14. The Laryngeal Musculature: The intrinsic muscles of the larynx are all innervated by the recurrent laryngeal nerve, except cricothyroid muscle that is supplied by superior laryngeal nerve. 1. Posterior cricoarytenoid – The only abductor of the vocal folds functions to open the glottis. Also tenses cords during phonation. 2. Lateral cricoarytenoid – Functions to close the glottis. 3. Transverse arytenoids – The only unpaired muscle of the larynx, functions to approximate bodies of the arytenoids closing the posterior aspect of the glottis. 4. Oblique arytenoids – Functions to close laryngeal introitus. 5. Thyroarytenoid – A very broad muscle, functions to adduct and tense the vocal fold. 6. Cricothyroid – The only one innervated by the superior laryngeal nerve. Functions to (12) increase tension in the vocal folds especially at higher pitch/ frequencies . Blood Supply: Above the vocal folds, blood supply is by the superior laryngeal artery, a branch of the superior thyroid artery. The superior laryngeal veins accompany the artery and empty into the superior thyroid veins. The lower half of the larynx is supplied by the inferior thyroid artery; Venous return is by the inferior laryngeal veins to the inferior thyroid veins (12) . 14
  15. 15. Lymphatic Drainage: The lymphatics of the larynx are separated by the vocal folds into an upper and lower group owing to their different embryologic origin. The upper lymphatics, which are in abundance empty into the upper deep cervical lymph nodes whereas the zone below the vocal folds drain into the lower part of the deep cervical chain often through prelaryngeal and pretracheal nodes.The vocal folds are firmly bound down to the underlying vocal ligaments and this results in an absence of lymph vessels, a fact which accounts for its low rate of metastasis to regional lymph nodes(12). Histology: The epithelium of the larynx is mainly that of respiratory epithelium, i.e. pseudostratified ciliated columnar epithelium. The lingual surface of the epiglottis is covered by stratified squamous epithelium, which also covers the upper parts of laryngeal epiglottic surface and the arylepyglottic folds. The vocal fold, has pseudostratified squamous epithelium on the superior and inferior surfaces with non-keratinized stratified squamous on the contact surface of the cords. The middle layer, known as Lamina propria is composed of 3 parts. Deep to the lamina propria is the thyroarytenoid muscle. The epithelium and the elastic portion of the middle layer are responsible for the “mucosa wave” of vocal fold vibrations in phonation. Mucus glands are freely distributed throughout the mucous membrane, but the vocal folds do not posses any and gets its lubrication from the glands within the saccules (12). 15
  16. 16. RISK FACTORS There are several factors, environmental and host factors that are clearly associated with increased incidence of laryngeal carcinoma. Tobacco (cigarette) use has been repeatedly implicated in the genesis of laryngeal cancer. Epidemiological data have without fail demonstrated the strong correlation between tobacco usage and laryngeal cancer. Laryngeal cancer is extremely rare in non-smokers. Alcohol has both an independent effect and a significant synergistic affected with tobacco in the genesis of carcinoma of the larynx. (14, 15, 16, 17, 18) The combination of these two increases their relative risk by 50% above that predicted (18). by simple additive effects Asbestos has frequently been suspected as a possible (14, 19). causative agent Other occupational risk factors are exposure to mustard gas, nickel and wood dust in wood workers. (14) Gastrosephageal reflux disease (GERD) is seen to be an aetiologic factor in laryngeal (20) carcinoma .Irradiation, especially in low doses has been identified as carcinogenic to the larynx (21). Studies done suggest that lack of specific micro-nutrients and trace elements to be (22). significantly associated with laryngeal carcinoma Voice abuse and chronic laryngitis is frequently seen in patients with laryngeal carcinoma. 16
  17. 17. Presence of recurrent respiratory papillomatosis should arouse concern regarding (23). possible malignant transformation Genetic susceptibility is another host risk factor (24, 25, 26, 27). linked with laryngeal cancer in certain individuals and ethnic groups PATHOLOGY Over 95% of all primary laryngeal malignancies are squamous cell carcinoma, the others being sarcoma, adenosarcoma, neuroendocrine tumors, adenoid cystic carcinoma and others. (13, 28). Laryngeal squamous cell result from prolonged exposure to recognized carcinogens that cause mucosal changes. These changes from a spectrum from mucosal hyperplesia to metaplasia, dysplasia and tissue atypia associated with or without keratosis. These changes produce surface lesions, leucoplakia or erythroplakia known as premalignant lesions. These lesions are frequently seen to progress to carcinoma in situ and invasive carcinoma. The likelihood of malignant transformation is well correlated with the degree of cellular atypia. A distinct variant of well-differentiated squamous cell carcinoma is the verrucous carcinoma (Ackermans tumour) which makes up a small proportion of all laryngeal carcinomas. 17
  18. 18. Natural histories of the cancers in the various sites are related largely to the anatomy, lymphatic drainage and histologic type.Actual tumour thickness and depth of inversion certainly have an influence on metastasis and survival. (13, 28). DIAGNOSIS Early diagnosis is the key to good survival and cure rates. SYMPTOMS 1) Dysphonia; Hoarseness is a cardinal symptom of laryngeal cancer. This is due to interference of vocal fold mucosa vibration, from tumour invasion of the mucosa or vocalis muscle. 2) Throat discomfort or pain. 3) Neck mass;may be a direct extension to anterior neck, widening of the thyroid cartilage or by nodal metastasis. 4) Airway obstruction; may be the presenting symptom, most commonly in subglottic tumours. This symptom is caused by the mass effect of the tumour and suggests that the tumour is large or in advanced stage. 5) Otalgia ; frequently a presenting symptom of supraglottic lesion 6) Haemoptysis; generally occurs only in large ulcerating tumour 7) Odynophagia; this too is frequently seen in supraglottic lesions 8) Dysphagia; it is associated with large tumours and suggests invasion beyond the confines of the larynx 9) Weight loss; indicative of advanced local disease. 18
  19. 19. EXAMINATION OF THE PATIENT Indirect Laryngoscopy/ Flexible Nasolaryngoscopy Direct Laryngoscopy Stroboscopy General examination of the patient Attention should be paid to: Neck masses Laryngeal crepitation Any signs of involvement of anterior neck IMAGING Chest X-ray(PA view): looking out for distant metastasis CT scan: Supplements clinical determination of the extent of tumour involvement. It is most helpful in documenting deep invasion. Tumour staging is altered in 20.2% of (29). those patients, with most being “up staged” MRI: Is More expensive, but more superior in demonstrating cartilage invasion. Ultrasound: For assessment of neck nodes HISTOLOGICAL EXAMINATION The accepted standard for definitive diagnosis is histopathologic examination of tissue obtained at laryngoscopy and biopsy. 19
  20. 20. LABORATORY INVESTIGATIONS Full Haemogram Urea and Electrolytes Liver function Tests. STAGING Provides a commonality of language that is essential for effective outcome analysis. TNM system was developed by Pierre Denoix (1943-52). The two widely used systems had been those of the American Joint Committee (AJCC) and the International Union against Cancer (UICC). In 1987, the UICC and AJCC revised their systems, thereby facilitating international data exchange. The unified system uses the TNM staging system, which is used principally for squamous cell carcinoma. (30). OBJECTIVES OF STAGING 1. Aid the clinician in planning of treatment 2. Provide a guide to prognosis 3. Assist in evaluation of results of treatment 4. Facilitate the exchange of information between treatment centers 20
  21. 21. TREATMENT Surgery, irradiation, or a combination of the two serves as the mainstay of treatment of laryngeal cancer. Vast experience has been accumulated for both methods and current treatment protocols are largely based on empirical results. Some authors have described neo-adjuvant chemotherapy plus irradiation for tumours that would otherwise require total laryngectomy with good results, or concurrent chemotherapy and radiotherapy. Cytotoxics alone were used for palliative treatment of advanced incurable disease. The Taxoids (eg Paclitaxel ) are the newest group of agents . Most recent reports of ongoing research indicate that exclusive use of chemotherapy is a viable approach to treatment of advanced laryngeal cancer. A pilot trial of TIP ( paclitaxel, ifosfamide, cisplatin ) has showed a small percentage of patients can be rendered disease free with chemotherapy alone (31). The study is ongoing. Specific prognostic factors must be considered in the determination of optimal treatment for a particular patient. These prognostic factors have a significant clinical value, providing information that will influence the management of a given tumour e.g. giving information as to the chance of locoregional recurrence or chance of nodal metastasis in No necks or chance of radio-sensitivity/chemoradio sensitivity, etc. 21
  22. 22. These factors include: (i) Host Factors Age and General Health status. Certainly significant comorbid illness or extreme age would argue against major surgery. Clinical pulmonary dysfunction is of specific importance in consideration of conservation surgery. (32,33). (ii) Tumour Factors Tumour stage: Shown to be an independent prognostic factor for locoregion recurrence and, or tumour specific survival. A higher stage is associated with greater chance of nodal metastasis in laryngeal cancer. (34). Tumour volume: can vary within a single T-stage for many sites and that tumour volume can predict both local and the chance of metastisis(35). Nodal Metastasis: Pathologically proven disease and detection of extra-capsular spread are the most important prognostic factors for survival and locoregional 36, 37, 38 recurrence as shown in most series . The level of nodal metastasis carries some prognostic importance with lower level involvement (i.e. level IV and V) indicating poor survival 38. Tumour Histological Grade: Histological grade of differentiation carries independent prognostic information in terms of survival with the poorly 39,40,41,42 differentiated and anaplastic carrying the worst prognosis . 22
  23. 23. Tumour Site: Tumours from different sites differ in metastasizing potential which in turn is related on distinct anatomic factors e.g. lymphatic drainage patterns, proximity to cartilage. Glottic tumours do better than supraglottic or subglottic tumours. Neoangiogenesis: There are established correlation between neoangiogenesis and disease aggressiveness in many solid tumours. However, in head and neck squamous cell carcinoma, the evidence is controversial 43, 44. Immuno-histochemical and Genetic Markers: A diverse range of antigens studied by immunohistochemistry and at genetic level can be used as prognostic factors. The best studied are P53, Cyclin D1, epidermal growth factor receptor and proliferation markers. Some of these e.g. P53 are molecules which are expressed before/prior to tumour development, hence can also be used for screening 44, 45. (iii) Personal preferences and social circumstances of the patient and family. (iv) Treatment facilities available, including the experience of surgeon and radiotherapist. Thus choice of therapy is contingent on many factors. Treatment may either be curative or palliative for the advanced disease using the aforementioned modalities 23
  24. 24. SUPRAGLOTTIC CANCERS Main considerations of cancers in this site are: - The increased frequency of nodal metastasis (palpable/occult), a fact that argues for treatment of the neck (Fig 3)46. Marginal lesions carry a worse prognosis, behaving more like hypopharyngeal tumours. High incidence of understaging with pre-epiglottic space involvement. 48 Small tumours of the supraglottis T 1 and T2 do well with either surgery or irradiation . Of those irradiated, recurrences occur at the primary site or the neck while patients treated with surgery, recurrences occur in the neck. Surgical salvage for irradiated patients frequently requires TL. The treatment of choice for T 3 and T4 tumours is surgery or combined treatment because of the increased incidence of nodal involvement in these tumours. Radiation therapy yields poor cure rates. Cervical metastatic disease may be treated by radical or functional neck dissection plus radiotherapy. Elective neck dissection for N 0 necks has been advocated by most authors. Current trends are towards conservation surgery, hence achieving laryngeal 48 preservation with improved quality of life when compared to total laryngectomy . Postoperative radiation is employed routinely in those patients with: 1. Bulky primary disease. 2. Histologically involved lymph nodes. 3. Resection margins not free of tumour. 24
  25. 25. GLOTTIC CANCERS Important considerations of glottic cancers are: 1. Vocal cord motion impairment, which denotes penetration of cancer into underlying tissues from submucus membrane stiffness to frank fixation. This has a telling effect of local control and survival rates a fact that is reflected in AJCC staging designation. 2. Presence of tumour at the anterior commissure or on the arytenoids, understaging is frequent and usually occurs because of subglottic or paraglottic extension, often with associated cartilage invasion. Hence making radiotherapy less effective and surgery the treament of choice. 3. Metastasis of early lesions is extremely unlikely, a fact attributed to its poor lymphatic supply. Carcinoma in situ is a highly curable disease, but one should cautious because it is frequently associated with areas of invasive carcinoma. Carcinoma in situ can be treated by radiation therapy, microsurgery of the mucosa (mucosal stripping) or laser vaporization49. T1 and T2 tumours have equal cure rates with either surgery (partial laryngectomy) or 1, 49, 50 radiotherapy, with cure rates over 90% . Treatment of recurrence or treatment failure after radiotherapy is salvage surgery, the procedure of choice being total 51 laryngectomy . Some authors have suggested subdividing T 2 lesions into T2A – with normal vocal cord motility and T 2B – with impaired vocal cord motility T 2B lesions behaving more like T 3 than T2 lesions with lower cure rates than T 2A 1. 25
  26. 26. Some T3 lesions may be treated by partial laryngectomy with larger ones (T 3) requiring near total or total laryngectomy. For some patients with advanced lesions (T 3-T4), studies done have shown chemoradiation to be a good treatment option. Only those patients with complete or partial response to three cycles of chemotherapy can then be given radiotherapy plus or minus RND. Larynx preservation rate of 68% is 52, 53, 54, 55, 56, 57 possible. This is applied for patients with advanced resectable tumours . Cervical metastasis is infrequent even in T 3 glottic carcinoma. Thus elective neck dissection would not appear to be indicated unless transglottic invasion is suspected. Treatment of palpable adenopathy obviously requires neck dissection plus or minus radiotherapy. Extralaryngeal spread of tumour defines T 4 lesions. Irradiation therapy is generally reserved for palliative treatment. Surgical treatment and appropriate management of the neck are critical for the best results. Combined therapy is recommended. SUBGLOTTIC TUMOURS Subglottic cancers are rare. They tend to present late as advanced lesions with cervical metastasis and combined treatment is recommended. Surgical treatment requires total laryngectomy plus all the soft tissues that may possibly be involved, that is the thyroid gland and strap muscles. Post surgery irradiation include the superior mediastinum, and should concentrate on the tracheal-stoma, since stomal recurrence is frequent in 58 subglottic and transglottic tumours . 26
  27. 27. ADVANCED CANCER AND PALLIATION End stage or inoperable laryngeal disease may be amenable only to palliation. The goals of palliative treatment are to alleviate pain, allow for adequate airway and nutrition, and provide emotional and social support. The choice of modality (radiotherapy, pharmacologic, surgical, chemotherapy or combination) depends 13 primarily on the multiple patient factors . TREATMENT OF THE NECK No: Controversy exists about the value of elective neck dissection in the face of clinically No disease. Arguments that favour elective neck dissection are based on the finding than > 20% of No necks (supraglottis tumours) harbour histopathologic evidence of metastasis. Hence selective neck dissection to harvest lymph nodes in regions at high risk of metastasis is employed. N1: A high proportion of these do not contain tumour cells, mostly being reactive nodes. Hence treatment will be considered prophylactic. Alternatively, one can just follow-up patient. In supraglottic tumours, rate of metastasis to lymph node is high even for the smallest lesions with upto 32% of negative neck done elective neck dissection turned positive for malignancy. For positive lymph nodes, functional neck dissection is justified. Reduced radiotherapy is an acceptable alternative to surgery for lymph nodes <2 cm. 27
  28. 28. N2: These require radical neck dissection because of high extranodal or extracapsular spread of tumour. In addition to RND, radiotherapy is recommended to reduce the incidence of recurrence. When both sides of the neck are involved, i.e N2c, bilateral RND has a high mobidity and mortality than unilateral. In bilateral neck disease, it is recommended doing a modified neck dissection, preserving the jugular vein and spinal accessory nerve on the least involved side of the neck. N3: These fixed nodes with extra-capsular spread are in-operable and radiotherapy is palliative. 59 ALARYNGEAL REHABILITATION Involvement of a speech therapist is essential in maximizing recovery. Only 20-40% of laryngectomees master oesophageal speech. Electrovibrating devices are helpful during the immediate postoperative period and as a back up. Tracheo-oesophageal puncture (TEP) and placement of silicone valve-like device that is structured to allow air into the neo-gullet but not allow food or liquids out. This resembles the normal voice more than other methods. It can be a primary TEP, inserted at the time of performing the TL or as a secondary procedure. 28
  29. 29. JUSTIFICATION OF THE STUDY Laryngeal carcinoma is a common head and neck tumour. Most available data emanates from the developed world, which might not directly reflect our local situation due to major socio-cultural, economic and environmental differences. This study is aimed at providing data of its epidemiology The data generated from this study could assist in: a) Assessing the burden of the disease. b) Setting of public health intervention programs for primary prevention of this disease. This being a far more cost-effective measure than treatment of established disease whether in early or advanced stage. c) Setting up of local patient management protocols. d) Planning and conducting further detailed epidemiological studies of this disease in the general population. 29
  30. 30. OBJECTIVES BROAD OBJECTIVE To determine the prevalence of Carcinoma of the Larynx in head and neck malignancies and prevalence of certain risk factors associated with laryngeal carcinomas in patients seen at Kenyatta National Hospital. SPECIFIC OBJECTIVES A. To determine the prevalence of Carcinoma of the Larynx in head and neck malignancies B. To determine in the patients with laryngeal carcinoma, the: 1. prevalence of smoking 2. prevalence of alcohol intake 3. socio – demographic distribution 4. histopathologic types seen 5. stage at presentation 6. mode of treatment received 30
  31. 31. MATERIALS AND METHODS STUDY DESIGN This is a hospital based prospective cross-sectional study STUDY AREA Kenyatta National Hospital STUDY POPULATION Patients with carcinoma of the larynx, confirmed by histology who were seen and treated both in the ENT/ Radiotherapy wards and clinics at KNH, during the study period, and satisfied the study inclusion criteria. Patients’ files were retrieved from the Central Records Registry, Dental Department Registry, Radiotherapy Department, and Histology Department Registry. This group of patients were treated in all wards and clinics at KNH with head and neck malignancy confirmed by histology, over the same period of time. This population was used towards calculation of the prevalence of carcinoma of the larynx. SAMPLING TECHNIQUE All patients with head and neck malignancies who satisfied the inclusion criteria were recruited into the study. 31
  32. 32. SAMPLE SIZE The sample size for this study was estimated using the following sample size formula for a one-sample situation 60,61 (Z1- /2)2 P (1-P) n = _________________ d2 where, n = minimum sample size Z1- /2 = 1.96 at 95 % confidence interval P = estimated prevalence from other studies d = margin of precision error (10%) The prevalence of laryngeal carcinoma in other studies was found to vary between 7% and 20%. n = 1.96 x 1.96 x 0.2 x 0.8 0.1 x 0.1 Thus the minimum sample size necessary was 62 patients. PATIENT SELECTION INCLUSION CRITERIA 1. All patients with head and neck malignancies with a histological diagnosis. 2. A duly signed written informed consent from the patient or guardian of patients with carcinoma of the larynx. 32
  33. 33. EXCLUSION CRITERIA Unwillingness to participate in the study (this did not jeopardize patient management). METHODS All the files of patients with carcinoma of the larynx booked for the clinic on a particular day was scrutinized, the files having been obtained from the medical records officer a day before or early in the morning before starting of the clinic. Only those who actually attended the clinic were included in the study. Daily ward rounds to check for patients admitted with carcinoma of the larynx, confirmed by histology, were done. Files of patients with head and neck cancers either seen or admitted in other clinics and wards over the same period were perused. Those meeting the inclusion criterion were included. The medical records were examined for pertinent historical, clinical and demographic data. Those patients with laryngeal carcinoma who met the inclusion criteria were explained to and invited to the study. Informed consent to participate in the study was obtained. For each of the recruited patients with laryngeal cancer, the following was done. 33
  34. 34. CLINICAL METHODS (i) A complete medical history was obtained as per the proforma outlined in appendix I. (ii) Careful examination of the neck, looking out for any cervical lympadenopathy, neck masses or tumour extension to the anterior neck. Those who had been operated on, findings as per the DL operation notes were entered into the questionnaire. (iii) A complete general physical examination was done. (iv) Clinical stage of the disease as per the direct laryngoscopic findings was noted and entered into the questionnaire. (v) Histology of the tumour was recorded. INVESTIGATIONS LABORATORY 1. Full hemogram. 2. Urea and electrolytes. 3. Liver function tests. RADIOLOGY A plain chest x-ray, posterior-anterior view was, to check for distant metastasis. DATA MANAGEMENT All data emanating from this study was entered into questionnaires, and therefrom into a computer data base, cleaned and verified, and analysed using statistical package for social sciences, version 10.0 and Epi6. 34
  35. 35. Prevalences were determined as percentages of the study population. Data was analysed and presented in the form of tables, pie charts and graphs. Any associations determined is considered statistically significant at a P value less than or equal to 0.05. UTILITY The outcome of this study determined the prevalence and characteristics of carcinoma of the larynx and the prevalence of its major risk factors in our local population for which there is no recent data available. The study will help in planning for primary and secondary intervention programs, for laryngeal cancer in our population, this being a more cost-effective approach than treatment of established and advanced disease for a developing nation like ours with scarce resources. It will also help in planning of training of some of the much needed team players in management of laryngeal cancer patients like speech therapists who are currently scarce while the population of laryngectomees is growing bigger. The data obtained could assist in further designing and conducting studies in this area. 35
  36. 36. ETHICAL CONSIDERATIONS The study was undertaken after approval by the Department of ENT, University of Nairobi, and the Ethical Research Committees, KNH. All patients recruited into the study were given a full explanation of the study and written informed consent was sought from them. The study did not in any way interfere with the standard management of the patients. All information will be treated in the strictest confidence. STUDY DURATION September 2003 to December 2003 36
  37. 37. RESULTS Gender Figure1:Gender 8.1% Male Female 91.9% Of the 62 patients with laryngeal cancer, 57 (91.9%) were male and 5 (8.1%) were female, giving an 11:1 male to female ratio. 37
  38. 38. Age distribution Figure 2: Age distribution 100 90 80 70 Percent(%) 60 50 37.1 40 27.4 30 17.7 20 11.3 6.5 10 0 30-40 41-50 51-60 61-70 >70 Age(yrs) Laryngeal cancer occurred most frequently between the ages of 50 – 70 yrs for both sexes. The mean age was 57.8 yrs (median 58 yrs). The youngest affected patient was 30 yrs, while the oldest was 80 yrs of age. 38
  39. 39. Geographical distribution Figure3:Geographical distribution 60 48.4 50 Percent(%) 40 30 20 14.5 11.3 12.9 10 4.8 4.8 3.3 0 Western Rift Valley Nyanza Nairobi Eastern Coast Central Province The highest population was from Central Province with 48.4%, followed by Eastern with 14.5%, then Nairobi with 13%. This could be attributed to their close proximity to KNH. Nyanza had the lowest with 3.2%. 39
  40. 40. Smoking habits Figure 4: Smoking habit 24.2% Yes No 75.8% Table 1: statistics of pack years of smoking mean median mode std. dev 21.4 19.0 40.0 17.7 Majority of patients are smokers, 47 (75.8%) patients.15 (24.2%) patients had never smoked. This is a significant rate. 46 of the 47 smokers had >2 pack years. 40
  41. 41. Alcohol consumption Figure 5: Alcohol consumption 24.2% Yes No 75.8% Figure 6:Types of alcohol consumed 30 25 no. of patients 20 15 10 5 0 Bottled Traditional Both types Neither 47 (75.8%) had consumed alcohol, while 15 (24.2%) had not. The study showed most patients consumed both bottled and traditional brews. Majority of patients were either unwilling or could not recall the exact volume of alcohol consumed over any period of time. 41
  42. 42. Smoking and Alcohol Figure 7:Smoking and Alcohol 50 45 40 no. of patients 35 30 25 20 15 10 5 0 Alcohol alone Smoking alone Both alcohol and Neither smoking Both smoking and alcohol was seen to be more prevalent in the patients with laryngeal carcinoma. 51 patients (82.4%) had either been smoking and or consumed alcohol. Only 11 patients (17.7%) had taken neither. 42
  43. 43. Symptoms Figure 8: Symptoms Weight Loss 14.5 Cough 17.7 Throat pain 17.7 Otalgia 19.4 Dysphagia 22.6 DIB 72.6 Dysphonia 100 0 20 40 60 80 100 percent(%) The most common symptom is dysphonia, seen in all of the 62 patients (100%). Difficulty in breathing (DIB) was the second most common symptom, seen in 45 (72.6%), with a mean duration of 7.9 weeks (median 4 weeks). 43
  44. 44. Duration of Dysphonia Figure 9: Duration of Dysphonia (months) 30 24 25 no. of patients 20 17 15 10 10 7 5 1 0 0 0-6 7-12 13-18 19-24 25-30 31-36 no. of months The duration ranged between 2 – 84 months, with a mean duration of 17.1 months (median 11 months). The mode was 12 months. 44
  45. 45. DIB versus overall staging at presentation Figure 10: DIB versus Overall Staging at presentation 100 90 80 70 Percent(%) 60 51.1 Yes 50 41.2 35.6 35.3 No 40 30 20 11.8 11.8 11.1 10 2.2 0 IV III II I Overall Staging DIB was found to be statistically related to Stage IV with a relative risk of 4.34, at a 95% confidence interval of 1.15-16.47, and p value of 0.005. 45
  46. 46. Neck findings Figure 11: Neck findings anterior neck 1.6 abscess loss of laryngeal 17.7 creps laryngeal widening 24.2 neck nodes 35.5 0 20 40 60 80 100 Percent(%) 22 (35.5%) patients presented with lymphadenopathy, 15 (24.2%) with laryngeal widening, 11 (17.7%) patients with loss of laryngeal creps, and only 1 (1.6%) patient with anterior neck abscess. 46
  47. 47. Tumour sites Figure 12: Tumour Sites Undeterminable 8.1 Supraglottic 17.7 Transglottic 35.5 Glottic 38.7 0 20 40 60 80 100 Percent (%) The most common tumour site of laryngeal cancer was glottic, with 24 (38.7%) patients, followed by transglottic with 22 (35.5%), then supraglottic with 11 (17.7%). 5 (8.1%) had tumours filling the supraglottic area, preventing determination of inferior extent of disease on DL. No subglottic tumours were encountered. 47
  48. 48. Histopathologic types Figure 13: Histopathologic types Carcinoma in situ 1.6 Anaplastic 4.8 Poorly diff. 17.7 Moderately Well diff. 22.6 Well diff. 53.2 0 20 40 60 80 100 Percent(%) All 62 had squamous cell carcinoma. The most frequent type seen was the well differentiated with 33 (53.2%) patients, followed by mod. well differentiated with 14 (27.6%), then by the poorly diff. type with 11 (17.7%), and anaplastic with 3 (4.8%) patients. Carcinoma in situ was the least with only 1(1.6%) patient. 48
  49. 49. TNM Classification Figure 14: TNM Classification x 100 96.8 0 80 1 64.5 2 percent(%) 60 3 4 40.3 37.1 40 32.3 29 17.7 17.7 17.7 20 12.9 16.1 12.9 1.6 3.2 0 Primary Node(N) Metastasis(M) Overall Tumour(T) Staging Most of the patients with laryngeal cancer came in Stage III and IV, with a number of 18(29.0%) and 25(40.3%) patients respectively, and a cumulative frequency of 69.3%. 49
  50. 50. Treatment modality versus overall staging at presentation Figure 15: Treatment versus Overall staging 12 11 11 10 RT/TL/RND 10 RT/TL/MRND No. of Patients 8 RT/TL 6 RT/TL/SND 6 5 4 4 RT/Salvage TL 4 RT/CT 2 2 RT 2 1 1 11 1 1 1 Absconded 0 IV III II I Overall staging Most patients had optimal treatment for stage. RT was given at a dose of 60 Grays for 6 weeks, except for 1 patient who was given 66 Gy due to the very aggressive nature of his tumour. Cytotoxics used were Cisplatin and 5FU.1 patient who was in stage IV absconded treatment. 50
  51. 51. Tracheostomy Figure 16: Tracheostomy 35.5% Yes No 64.5% The high frequency of tracheostomy is attributed to the late presentation of our patients. 51
  52. 52. Head and neck malignancies in the study Figure 17: head and neck malignancies in the study ear 1.7 lymphoma 2.9 salivary glands 3.4 thyroid 3.4 oropharynx 3.4 sarcoma 3.8 mandible 3.8 nasal cavity and sinuses 5 hypopharynx 7.6 nasopharynx 18.5 oral cavity 20.6 larynx 26.1 0 5 10 15 20 25 30 percent(%) Carcinoma of the larynx was the most common with a prevalence of 26.1%. 52
  53. 53. DISCUSSION Globally, laryngeal carcinoma shows wide variation in disease burden 3, 4, 5. From this study, it is determined that laryngeal cancer is the most common malignancy in head and neck. From the total of 238 inducted into the study, 62 were those with laryngeal carcinoma making a prevalence of 26.1%. Robin and Olofosson showed the prevalence of laryngeal cancer in UK to be 11.1% 4. Males are consistently affected more than females worldwide, though the ratio changes 3, 4, 5 . In Kenya, from the study the male to female ratio is 11:1. In Hagembe’s 6 (1985) study at KNH, there was a lower ratio of 5:1.There is an increase in male predominance, contrary to the decrease seen in the Western world 4. Could this difference be attributed to our population being exposed to other risk factors not considered in this study? Patients below the age of 40 are rarely affected. The peak age range is 51-60 yrs in our study, while that in other studies (Boyle et al, Baclays et al) 5 is 70 yrs. The youngest patient seen was a 30 yr old female, and the oldest was an 80 yr old male. Previous studies have conclusively proven that tobacco and alcohol are carcinogenic in laryngeal cancer 11, 12, 13, 14, 15. It was not the aim of this study to correlate smoking and alcohol with carcinoma of the larynx, but to show the prevalence of smoking and alcohol use in our patients. The outcome of this study clearly shows a significant rate of 75.8% for both smoking and alcohol consumption. Geographically, 48% of our patients hail from the Central Province. 14% come from Eastern and 13% from Nairobi. These are regions closest to KNH in proximity, and probably not a true representation of the actual distribution of the disease in the country. Nyanza had the lowest with 4%. Clinically, all the 62 patients presented with dysphonia. The lowest duration here was 2 months. Most of these patients presented late with an average of 17 months of dysphonia. Due to their late presentation, 72.6% also came in with difficulty in breathing. Other symptoms seen in this study were dysphagia (22.6%), cough (17.7%), neck pains (17.7%), otalgia (19.4%), and weight loss 14.5%. Most common neck findings were enlarged lymph nodes at 35.5%. 24.2% had laryngeal widening and 17.7% had loss of laryngeal crepitations. One patient alone was seen with an anterior neck abscess. The tumour sites in laryngeal carcinoma show variations the world over. In Hagembe 6 (1985), transglottic tumours were the most frequent. This study has glottic tumours as 53
  54. 54. the commonest (38.7%), followed by transglottic (35.5%), supraglottic (17.7%), and undeterminable sites (8.1%). Histopathologically, all 62 (100%) patients had squamous cell carcinoma. Most studies cite >95% 3, 25, 26.The most encountered type was the well differentiated type seen in 53.2%, as in Hagembe’s6 with 40%. Stage of presentation was advanced for many, with T4 tumours making up 37.1% and overall stage of IV for 40.3%. This finding is similar to that of Hagembe’s 6 study. Their correlation to difficulty in breathing was statistically significant with a RR=4.34, 95% CI of 1.15-16.47, and p value of 0.005. 64.5% needed a tracheostomy. Only 2 patients (3.2%) were seen to have distant metastases to the lungs. Majority had MX (96.8%). Treatment modalities given were mostly dependent on the stage of disease. For most, the treatment modalities offered were apt for their stage of presentation. Early presentation (stages I & II) was treated with radiotherapy alone except for one who had TL and post-operative radiotherapy, whose tumour had advanced. Of the 43 patients with advanced disease (stages III and IV), 21 had surgery and post- operative radiotherapy. 8 more were advised to have surgery but declined. Another 6 had inoperable disease or co-morbidity, hence radiotherapy was given with palliative intent. The remaining 8 patients with advanced disease and with no identifiable contraindication for surgical intervention were given radiotherapy alone. The combined modality option was apparently not offered to them. All but one of these last 8 patients were referrals to the KNH Radiotherapy Dept. from other hospitals. The ENT team here had not been consulted. 54
  55. 55. RECOMMENDATIONS 1. Launch public health awareness campaigns on disease prevention and early detection. Laryngeal cancer is largely a preventable disease. 2. Educate primary healthcare providers in the peripheries on early disease detection and prevention. 3. Treatment protocols should be standardized and adhered to by all ENT, head and neck surgeons and radio-oncologists. 4. Patients diagnosed outside KNH should be discussed at the Tumour Board for a joint assessment and optimal treatment planning. 5. Improve reporting of patients’ clinical data by the medical healthcare providers by having a standardized proforma for inputting patients’ data and thus affording uniformity. This would subsequently provide better patient management and relevant information for research purposes. 6. Encourage more research in laryngeal cancer with more emphasis on other etiological factors in our environment. 7. Computerize all registries, hence making data retrieval faster and more accurate. 55
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  64. 64. APPENDICES APPENDIX I: STUDY PROFORMA Study No._______________________________ Name __________________________________ Address: P.O.Box _________________________ Telephone _______________________ IP No ______________Date_________________ Age ____________________________________ Sex: Male __________ : Female __________ Present Residence_______________________________ Previous residence( If less than 5 yrs in present residence)_____________ Occupation ______________________________ RISK FACTORS 1. Alcohol Did or do you take alcohol? Yes No if yes, what kind of alcohol? Beer Spirits Local brews What is the duration of alcohol intake in no. of years? _________________ years. How much alcohol was consumed in units/day? < 7 units 7 – 21 units > 21 units 2. Smoking Did or do you smoke? Smoking Used to smoke Never smoked If smoking or smoked in the past, how many sticks per day? _________ sticks/day. 64
  65. 65. When did you stop smoking? _________________ From the above, what is the number of pack years No of cigarette sticks per day X duration in years = pack years 20 _____________ pack years. DIAGNOSIS Presenting symptoms and signs 1. Progressive unremitting dysphonia (hoarseness of voice) Yes No If yes, for how long? _____________ years/months. 2. Difficulty in breathing (Dyspnoea/stridor) Yes No If yes, for how long? ________________ days/weeks. 3. Was there any pain? Yes No If yes, where was it localised? ______________ 4. Weight loss? Yes No 5. Was there any neck swelling? Yes No If yes, where was the neck swelling ?___________________________ 6. Is there any cough, chest pain or abdominal pain? Yes No If yes,explain._____________________________________________ 65
  66. 66. 7. Was there any otalgia? Yes No 8. Was there any dysphagia? Yes No CLINICAL EXAMINATION. Neck Examination Findings: 1. Nodal Involvement______________________________________________________________ 2. Other Findings:_________________________________________________________________ ________________________________________________________________________________ ________________________________________________________________________________ ________________________________________________________________________________ Indirect Laryngoscopy/Flexible Nasolaryngoscopy________________________________________ ________________________________________________________________________________ ________________________________________________________________________________ DirectLaryngoscopy_________________________________________________________________ ________________________________________________________________________________ ____________________________________________________________________________________ ________________________________________________________________________________ _______________________________________________________________________________________ _____ 66
  67. 67. INVESTIGATIONS 1. FHG Yes No If yes, Normal findings Abnormal findings If abnormal, state abnormal findings _____________________________________ 2. U & E’s Yes No If yes, Normal findings Abnormal findings If abnormal, state the abnormality ________________________________ 3. LFT’s Yes No If yes, Normal findings Abnormal findings If abnormal, state the abnormal findings _________________________________ 4. CXR Yes No If yes, Normal Abnormal If abnormal, state the pathologic findings 67
  68. 68. 5. Tissue histopathology Anaplastic Poorly differenciated Moderately differenciated Well differenciated Carcinoma in situ STAGING (Using UICC, TNM classification system) 1. Tumour (T) T1 T2 T3 T4 2. Node NO N1 N2 N3 3. Distant metastasis MO MX M1 4.Overall Stage I II III IV MODE OF MANAGEMENT 1. Radiotherapy Yes No If yes, Pre- operatively Post -operatively Alone Given alone or with neoadjuvant chemotherapy Alone With chemotherapy Was it for treatment of primary site, or neck or for both? 68
  69. 69. Primary site Neck Both What was the total dose give? _____________ Gy , over _______weeks (duration) 2. Surgery Yes No If yes, what type of surgery was done? Total laryngectomy Radical neck dissection Modified radical neck dissection (Describe)_______________________________________________ Selective neck dissection (Describe)________________________________________________ Tracheostomy 3. Combined modalities Surgery and radiotherapy Chemoradiation +/- Salvage Surgery Radiotherapy+/-SalvageSurgery Patient’s choice of treatment The treatment received, was it the recommended treatment modality? Yes _____ No _____ If the answer is No, please explain reason for declining_____________________________________________________________________________ ___________________________________________________________________________________ 69
  70. 70. APPENDIX II: Malignancies of head and neck included in the study Oral cavity Oropharynx Nasopharynx Hypopharynx Nasal cavity and sinuses Larynx Thyroid Lymphomas Sarcoma Salivary gland Ear Mandible 70
  71. 71. APPENDIX III: TNM STAGING TUMOUR (T) SUPRAGLOTTIS: T1: Tumour Limited to one subsite, normal vocal cord mobility. T2: Tumour Involving mucosa of more than one adjacent site of supraglottis or glottis or adjacent region outside the supraglottis without fixation. T3: Limited to the larynx with vocal cord fixation or invades postcricoid area, pre-epiglottic tissues or base of tongue. T4: Extends beyond the larynx. GLOTTIS: T1: Tumour limited to vocal cord(s). T2: Supraglottis or sub-glottic extension, with normal/impaired cord mobility. T3: Vocal Cord(s) fixation. 71
  72. 72. T4: Extends beyond the larynx. SUBGLOTTIS: T1: Tumour is limited to subglottis. T2: Extends to vocal cord(s) with normal/impaired mobility. T3: Vocal Cord fixation. T4: Extends beyond the larynx. REGIONAL LYMPH NODES (N) Nx: Regional lymph node cannot be assessed No: No regional lymph nodes. N1: Metastasis in single ipsilateral LN 3cm or less ( <-3cm) N2a: Metastasis in single ipsilateral LN, 3-6 cm in widest diameter. N2b: Metastasis in multiple ipsilateral LNs, none greater than 6 cm. N2c: Metastasis in bilateral or contralateral LN none greater than 6cm N3: Metastasis in LN greater than 6 cm. DISTANT METASTASIS (M) Mx: Distant metastasis cannot be assessed. Mo: No distant metastasis. 72
  73. 73. M1: Distant metastasis. APPENDIX IV: Overall staging grouping for laryngeal cancer (UICC 1997) Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T1 N1 M0 T2 N1 M0 T3 N0, N1 M0 Stage IV A* T4 N0, N1 M0 IV B * Any T1,2,3 N2 M0 IV C* Any T Any N M1 * New inclusion 73
  74. 74. APPENDIX V: QUANTIFICATION OF ALCOHOL 1 Unit of alcohol is equal to -------------------------------1/2 a pint of beer “ -------------------------------1 single measure of distilled spirits i.e 2ml “ --------------------------------1 glass of wine or 1 glass Sherry 74
  75. 75. APPENDIX VI: INFORMED CONSENT This is to certify that I_______________________________the patient/ guardian to ________________________,of p.o.box______________have consented to participate in this study of carcinoma of the larynx. I have been informed that this study will be looking at the size of this disease in our population and risk factors associated with it . I/patient will be required to give a detailed and accurate history of the illness. I/patient will be required to give blood for investigations and do a chest X-ray. I/patient is entitled to request for results at any given time. I/patient have also been assured that participation in the study is voluntary. Participation, refusal or withdrawal from the study will not hamper treatment and that confidentiality will be observed. Patient’s Name and signature:______________________________ Guardian’s name and signature:_____________________________ Relationship to patient:____________________________________ Date: ________________________________________ Investigating officer: ___________________________________ Signature: ________________________________________ 75
  76. 76. Kukubali Kwa Mgojwa Mimi, mgojwa / mlezi_______________________wa kutoka____________________ nina kubali kujiunga na utafiti huu wa seretani ya koo. Nime elezwa kwamba, utafiti huu ni juu ya kima cha ugonjwa kwenye uma wetu na uraibu wa sigara na pombe inavoonekana kwa wagojwa wa seretani ya koo. Nina / Tuna fahamu kwamba, mgonjwa atalazimika kutowa historia kwa ukamilifu kuhusu ugonjwa wake. Pia, ninafahamu kwamba,mgonjwa atalazimika kutowa damu na kupigwa picha ya kifua.Mimi kama Mgonjwa / Mlezi, nina haki ya kuitisha majibu ya uchunguzi wakati wowote. Mimi kama Mgonjwa / Mlezi nimehakikishiwa kwamba nina weza kukubali au kukata kujiunga na utafiti huu , haita zuwiya kupata kwa mgojwa tiba ya kikamilifu. Siri za mgonjwa, zitahifadhiwa. Jina na sahihi ya Mgonjwa _______________________________ Jina na sahihi ya Mlezi __________________________________ Uhusiano Baina ya Mlezi Na Mgonjwa______________________ Tarehe________________________________________________ Jina na sahihi ya Afisa wa uchunguzi ______________________ 76

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