Cancer
cervix
	 Predisposing	Factors	:
	 Age	(45+10	years	)
	 Marriage	and	parity	(It	is	related	to	the	practice	of	coitus	than	childbearing.	)
	 	Race
	 	Social	and	economic	factor
  	Coitus		(It	is	accepted	that	spermatozoa	are	themselves	carcinogenic	to		cervical	cells	Cervical	irritation	and	
	 infections	(Herpes	virus	type	II,	operates	like	spermatozoa)
	 	Human	papilloma	virus:
                                               	 Pre-invasive	lesions	:
  1	-	Squamous	Metaplasia	:	It	is	a	benign	condition,	which	is	extremely	common	especially	in	parous	woman.	
	 There	are	no	clinical	symptoms	or	signs.	
	 Etiology:
	 Hormonal	imbalance:	increased	progesterone.
	 Local	irritation:	e.g.	infections.
  Alternation	of	the	pH	of	vagina.	
	 Dysplasia	:	Disordered	growth	or	development	i.e.	restless	epithelium	
    CIN
	 C.I.N	(I):	Mild	dysplasia
  Undifferentiated	cell	occupies	the	lower	1/3	of	epithelium.
	 C.I.N	(11):	Moderate	dysplasia
  Undifferentiated	cells	occupies	the	lower	2/3	of	epithelium	
	 C.I.N	(III):	Sever	dysplasia	+	CIS
  Undifferentiated	cells	occupy	the	entire	epithelium	short	to	the	area	near	the	surface	
	 C.I.S	(Carcinoma	in	Situ):	
  Undifferentiated	cells	replace	the	entire	epithelium,	no	invasion	to	the	basement	membrane	,	indistinguishable	
	 from	invasive	cancer			
	 It	involves	the	surface	epithelium,	crypts	and	glands
	 Site	of	origin:	
	 1)	Transformation	zone
	 2)	Native	squamous	epithelium:
	 Significance	of	CIS:	
	 C.I.S	and	invasive	cancer	can	be	found	in	the	same	cervix.
	 Follow-up	cases	of	C.I.S	without	treatment	à	invasive	cancer	later	in	life.	
	 Micro-invasive	Cancer	:
	 As	carcinoma	in	situ	pulse	finger	like	projections	penetrate	the	stroma	
  The	major	controversy	between	micro-invasion	and	invasive	cancer	is	the	depth	of	invasion.	
    Stromal	reaction:	There	is	edema	and	cellular	infiltration	(lymphocytes,	plasma	cells	and	histocytes)	denoting	
    that	the	immune	response	still	intact
                                                                                 	
	 Diagnosis	of	Pre-invasive	cancer	:
  1.	Vaginal	smear		(drop	of	discharge	is	take	from	the	posterior	fornix	---- it	is	stained	by	Papanicola`s	or	Shorr`s	
	 stain	to	detect	malignant	cell.)
	
  2.	Cervical	smear	(Arye's	wooden	spatula	is	rotated	360	degrees	to	scrap	the	lower	part	of	cervical	canal	and	the	
	 portio-vaginal	part	at	the	external	Os	)
	
	 3	-	Schiller's	iodine	test		(The	cervix	is	stained	with	either	Gram's	stain	or	Logal's	iodine	solution)
	 Normal	cell	----	brown
	 Unhealthy	areas	as	erosion	or	cancer	remain	unstained	due	to	absence	of	glycogen.
	 The	test	is	used	to	select	the	biopsy	sites.	
  4	–	Colposcopy	:	allow	visualization	of	lesions	not	seen	by	naked	eye.	It	helps	to	choose	the	sites	for	biopsy.
	 Schiller's	iodine	test	is	better	done	under	colposcope.
                                                                                                                     	
	 5.	Biopsy:	It	must	done	in	every	case	to	confirm	diagnosis
    Wedge	biopsy:	It	is	taken	from	suspected	lesions;	it	must	include	healthy	area	for	comparison
    Fractional	biopsy:	Several	curettes	are	taken	from	around	the	external	Os,	then	from	the	cervical	canal	than	the	
    endometrium.
    Cone	biopsy:	This	includes	half	of	the	portio-vaginalis,	its	apex	reaches	below	the	internal	Os,	it	is	divided	serially	
    for	microscopic	examination
    Ring	biopsy:	The	whole	epithelium	around	the	external	Os	is	removed	and	examined,	as	carcinoma	usually	starts	
    at	the	squamo-columnar	junction	(Transformation	zone).	
	 Papanicolous	Classification
	 Class	(I):	-----	Negative,	only	normal	cells.
    Class	(II):-----	Negative,	some	atypical	cells	but	no	signs	of	malignancy.
    Class	(III):----	Doubtful,	some	typical	cells,	only	suggestive	but	not	diagnostic	of	malignancy	
    Class	(IV):-----	Positive	isolated	atypical	cells
	 Class	(V):-----	Positive,	numerous	atypical	cells.
	
                                                   	 Invasive	Cancer
	 Types	of	cancer
    -Squamous	call	carcinoma	92-95%
    -	Columnar	cell	carcinoma	5%.
    - Mixed	growth	(Adeno-epithelioma)	1:2%
    Sites
	 1	-	Carcinoma	of	portio-vaginalis	(Ectocervical)	95%:	Arise	from	the	squamous	epithelium.
	 2	-	Endocervical	carcinoma	5:10%:	Arise	from	the	columnar	epithelium	lining	the	cervical	canal
	 Broder's	classifications	:	
	   It	is	a	histological	classification	to	detect	prognosis:
	   Grade	(II):	----0-25%	undifferentiated	cells
	   Grade	(III):-----	25-50%	undifferentiated	cells.
	   Grade	(VI):-----	50-75%	undifferentiated	cells
    Grade	(V):------	75-100%	undifferentiated	cells.
    Spread
	 A.	Direct	spread:	
	   Downward:	to	vagina
	   Upward:	to	body	of	uterus
	   Forwards:	to	bladder
	   Backwards:	along	the	utero	sacral	ligament	to	rectum
    Laterally:	late	to	the	parametrium	where	it	may	cause	obstruction	of	ureters	by	compression	leading	to	
    hydroureters	and	hydronephrosis	and	finally	uremia,	which	is	the	commonest	cause	of	death.	
	 B.	Lymphatic	spread
	   It	occurs	early	in	the	disease,	the	glands	involved	are:
	   Paracervical	glands:	at	the	crossing	of	ureters.
	   The	external	iliac	glands.
	   The	internal	iliac	glands.
	   The	obturator	glands:	1:3	in	number	near	the	obturator	foramen.	
	   Lateral	sacral	gland:	in	the	sacral	cavity	and	promontary.
    Internal	and	external	iliac	glands	à	the	common	iliac	glands	àlower	aortic	glands.
	 C.	Blood	stream:	late	in	the	disease
    D.	Surface	implantation:	
  Malignant	calls	may	be	implanted	in	the	vagina,	vulva,	pelvic	cavity,	or	abdominal		wound	after	Wertheim's	
	 operation.
	
    Complications
    -	Pyometra:	The	malignant	tissues	obstruct	the	cervical	gland	and	the	endometrial	secretions	act	nidus	for	
	   infection.
	   -	Vesico-vaginal	fistula.
	   -	Rect-vaginal	fistula.
	   -	Hydroureter	and	hydronephrosis.
    -	Uremia.
    Cause	of	Death
	   	-	Uremia:	the	commonest	cause	of	death	(50%),	due	to	ureteric	obstruction	and	ascending	infection.
	   -	Malignant	cachexia
	   -	Infections:	Parametritis	and	peritonitis.
	   -	Sever	bleeding	from	eroding	big	blood	vessels.
	   -	Pulmonary	embolism.
	   -	Metastasis	to	vital	organs.
    -	Complications	of	treatment.
    Clinical	picture
    1.	Sx:	1)	Bleeding:	The	bleeding	is	usually	the	first	symptoms,	it	starts	as	contact	bleeding	after	coitus,	douching,	
    or	vaginal	examination;	later	on	the	bleeding	becomes	irregular	and	variable	in	amount
    2)	Vaginal	discharge:	At	first	it	is	watery	or	serous	discharge	due	to	epithelial	hyperactivity,	then	with	ulceration	
    and	infection,	it	becomes	blood	stained	discharge	and	offensive	with	may	necrotic	debris
    3)	Pains:	It	is	late	symptom	Indicating	involving	of	tissues	outside	the	cervix	by	cancer	tissues	or	infection:
	 4	-Cachexia
    2.	Signs:	In	late	cases,	the	lesion	appears	in	the	form	of	nodule,	polyp,	cauliflower	mass,	ulcer	or	barrel	shaped	
	 cervix.
  Lesions	are	characterized	by:	Bleeding	on	touch	–	Induration	–	Friability	-	Necrosis	and	infection.	Rectal	
  examination	should	be	done	in	very	case	to	detect	rectal	involvement.
	 Investigations
	 Cervical	biopsy
	 Cystoscopy:	to	diagnose	bladder	involvement.
	 Proctoscopy:	to	diagnose	rectal	involvement.
	 Plain	X-ray	Chest,	spines	and	pelvic	bones
  Examination	under	anesthesia
	 Prognosis
	 Depends	upon:
	 -Extent	of	growth	at	the	time	of	treatment.
	 -Site:	Endocervical	growth	is	more	dangerous	(late	diagnosis)
	 -Naked	eye	appearance:	Hypertrophic	type	has	a	bad	prognosis.
  -Histological	type:	Adenocarcinoma	is	the	worst	not	only	due	to	its	radio-resistance	but	also	due	to	its	higher	
	 malignancy	power	to	infiltrate.
	 -Age:	The	younger	the	more	fulminating	growth.
	 -Ureteric	obstruction	has	a	bad	prognosis
                                                                                                                     	
    Clinical	Staging	(FIGO)
    Stage	(0):	Carcinoma	in	situ	or	intra-epithelial	carcinoma.	Cases	of	stage	(0)	should	not	be	included	in	any	
    therapeutic	statistics.	
    Stage	(I):	Carcinoma	confined	to	the	cervix,	extension	to	the	corpus	should	be	disregarded:
                 •   Stage	Ia:	Microinvasive	carcinoma.
                 •   Stage	Ib:	All	other	cases	of	stage	I.	
    Stage	(II):	Carcinoma	extends	beyond	the	cervix,	but	not	reached	the	lateral	pelvic	wall:
                 •   Stage	IIa:	Infiltration	of	the	upper	2/3	of	the	vagina
                 •   Stage	IIb:	Infiltration	of	one	or	both	parametrium,	but	not	reaches	the	lateral	pelvic	wall.	
	 Stage	(III):	
	 -	Carcinoma	extends	to	the	lateral	pelvic	wall
  -	Carcinoma	infiltrates	the	lower	1/3	of	the	vagina.
                 •   Stage	IIIa:	No	infiltration	to	the	lateral	pelvic	wall
                 •   Stage	IIIa:	Infiltration	and	fixation	to	the	lateral	pelvic	wall	
	 Stage	(IV):	
                 •   Stage	IVa:	Extension	to	bladder	or	rectal	mucosa
                 •   Stage	IVb:	distant	metastasis
    Treatment	Scheme
    Stage	(I):		Surgery.	|	Radiotherapy.	
	 Stage	(II):	Surgery	followed	by	radiotherapy.
	 Radiotherapy	followed	by	surgery.
  Taussing	operation
	   Stage	(III)	and	(IV):	
	   Palliative	surgery.
	   Palliative	radiotherapy.
	   Relive	of	pain	in	advanced	cancer.