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

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

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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.

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DEDICATION

I dedicate this work to my husband, Mr.Hisham Mwidau, for inspiring me to aim for higher goals in life.

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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

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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

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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

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.

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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

rate of 8.5% and long time survival rose from 4% to 44% (4). 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.

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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

with a peak incidence in the seventh decade (2,5,6).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

patients only, diagnosed and treated for the same over a 10 year period (1973-83) (8).

Since then, there has been an increase in the number of patients managed for cancer of

the larynx (9).

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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

laryngeal branches of the vagus nervous (CNX) that supply these arches (10,11).

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.

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).

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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).

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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

increase tension in the vocal folds especially at higher pitch/ frequencies (12).

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).

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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).

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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

by simple additive effects (18). Asbestos has frequently been suspected as a possible

causative agent (14, 19). 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

carcinoma (20).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

significantly associated with laryngeal carcinoma (22). Voice abuse and chronic laryngitis

is frequently seen in patients with laryngeal carcinoma.

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Presence of recurrent respiratory papillomatosis should arouse concern regarding

possible malignant transformation (23). Genetic susceptibility is another host risk factor

linked with laryngeal cancer in certain individuals and ethnic groups (24, 25, 26, 27).

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.

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.

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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

those patients, with most being “up staged” (29).

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.

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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

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.

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

recurrence as shown in most series 36, 37, 38. 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

differentiated and anaplastic carrying the worst prognosis 39,40,41,42.

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

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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.

Small tumours of the supraglottis T1 and T2 do well with either surgery or irradiation 48.

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 T3 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 N0 necks has

been advocated by most authors.

Current trends are towards conservation surgery, hence achieving laryngeal

preservation with improved quality of life when compared to total laryngectomy 48.

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.

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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

radiotherapy, with cure rates over 90% 1, 49, 50. Treatment of recurrence or treatment

failure after radiotherapy is salvage surgery, the procedure of choice being total

laryngectomy 51. Some authors have suggested subdividing T2 lesions into T2A – with

normal vocal cord motility and T2B – with impaired vocal cord motility T2B lesions

behaving more like T3 than T2 lesions with lower cure rates than T2A 1.

26

Some T3 lesions may be treated by partial laryngectomy with larger ones (T3) requiring

near total or total laryngectomy. For some patients with advanced lesions (T3-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

possible. This is applied for patients with advanced resectable tumours 52, 53, 54, 55, 56, 57.

Cervical metastasis is infrequent even in T3 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 T4 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

subglottic and transglottic tumours 58.

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

primarily on the multiple patient factors 13.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

37

RESULTS

Gender

Figure1:Gender

91.9%

8.1%

Male

Female

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.

38

Age distribution

Figure 2: Age distribution

6.5

17.7

37.1

27.4

11.3

0

10

20

30

40

50

60

70

80

90

100

30-40 41-50 51-60 61-70 >70

Age(yrs)

Perc

ent(

%)

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.

39

Geographical distribution

Figure3:Geographical distribution

4.8

11.3

3.3

12.9 14.5

4.8

48.4

0

10

20

30

40

50

60

Western Rift Valley Nyanza Nairobi Eastern Coast Central

Province

Perc

ent(

%)

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%.

40

Smoking habits

Figure 4: Smoking habit

75.8%

24.2%

Yes

No

Table 1: statistics of pack years of smoking

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.

mean median mode std. dev

21.4 19.0 40.0 17.7

41

Alcohol consumption

Figure 5: Alcohol consumption

75.8%

24.2%

Yes

No

Figure 6:Types of alcohol consumed

0

5

10

15

20

25

30

Bottled Traditional Both types Neither

no.

of

patients

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.

42

Smoking and Alcohol

Figure 7:Smoking and Alcohol

0

5

10

15

20

25

30

35

40

45

50

Alcohol alone Smoking alone Both alcohol and

smoking

Neither

no.

of

patients

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.

43

Symptoms

Figure 8: Symptoms

100

72.6

22.6

19.4

17.7

17.7

14.5

0 20 40 60 80 100

Dysphonia

DIB

Dysphagia

Otalgia

Throat pain

Cough

Weight Loss

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).

44

Duration of Dysphonia

Figure 9: Duration of Dysphonia

(months)

24

17

1

10

0

7

0

5

10

15

20

25

30

0-6 7-12 13-18 19-24 25-30 31-36

no. of months

no.

of

patients

The duration ranged between 2 – 84 months, with a mean duration of 17.1 months (median 11 months). The mode was 12 months.

45

DIB versus overall staging at presentation

Figure 10: DIB versus Overall Staging at presentation

51.1

35.6

11.12.2

11.8 11.8

35.341.2

0

10

20

30

40

50

60

70

80

90

100

IV III II I

Overall Staging

Perc

ent(

%)

Yes

No

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.

46

Neck findings

Figure 11: Neck findings

35.5

24.2

17.7

1.6

0 20 40 60 80 100

neck nodes

laryngeal widening

loss of laryngeal

creps

anterior neck

abscess

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.

47

Tumour sites

Figure 12: Tumour Sites

38.7

35.5

17.7

8.1

0 20 40 60 80 100

Glottic

Transglottic

Supraglottic

Undeterminable

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.

48

Histopathologic types

Figure 13: Histopathologic types

53.2

22.6

17.7

4.8

1.6

0 20 40 60 80 100

Well diff.

Moderately Well diff.

Poorly diff.

Anaplastic

Carcinoma in situ

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.

49

TNM Classification

Figure 14: TNM Classification

96.8

64.5

12.916.1

3.2

12.917.7 17.7 17.7

32.3

1.6

29

37.140.3

0

20

40

60

80

100

Primary

Tumour(T)

Node(N) Metastasis(M) Overall

Staging

perc

ent(

%)

x

0

1

2

3

4

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%.

50

Treatment modality versus overall staging at presentation

Figure 15: Treatment versus Overall staging

4

1

2

1

4

5

1

2

11 1

11 11

10

6

1

0

2

4

6

8

10

12

IV III II I

Overall staging

No.

of

Patients

RT/TL/RND

RT/TL/MRND

RT/TL

RT/TL/SND

RT/Salvage TL

RT/CT

RT

Absconded

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.

51

Tracheostomy

Figure 16: Tracheostomy

64.5%

35.5%

Yes

No

The high frequency of tracheostomy is attributed to the late presentation of our patients.

52

Head and neck malignancies in the study

Figure 17: head and neck malignancies

in the study

26.1

20.6

18.5

7.6

5

3.8

3.8

3.4

3.4

3.4

2.9

1.7

0 5 10 15 20 25 30

larynx

oral cavity

nasopharynx

hypopharynx

nasal cavity and sinuses

mandible

sarcoma

oropharynx

thyroid

salivary glands

lymphoma

ear

percent(%)

Carcinoma of the larynx was the most common with a prevalence of 26.1%.

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 Hagembe6 (1985), transglottic tumours were the most frequent. This study has glottic tumours as

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’s

6 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’s6 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.

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.

56

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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.

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._____________________________________________

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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_________________________________________________________________

________________________________________________________________________________

____________________________________________________________________________________

________________________________________________________________________________

_______________________________________________________________________________________

_____

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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

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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 I V

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?

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_____________________________________________________________________________

___________________________________________________________________________________

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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

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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.

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.

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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

T2

T3

N1

N1

N0, N1

M0

M0

M0

Stage IV A*

IV B *

IV C*

T4

Any T1,2,3

Any T

N0, N1

N2

Any N

M0

M0

M1

* New inclusion

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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

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: ________________________________________

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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 ______________________