ETIOLOGY PATHOGENESIS CLINICAL FEATURES BY ALBIN JOSE 2002

ETIOLOGY PATHOGENESIS CLINICAL FEATURES BY ALBIN JOSE, 2002 MBBS

ANATOMY OF RECTUM l l l FROM RECTOSIGMOID JUNCTION END AT ANORECTAL JUNCTION 18 -20 cm IN LENGTH

ANATOMY CONTD. l RECTUM HAS THREE LATERAL CURVATURES. UPPER AND LOWER CONVEX TO THE RIGHT. MIDDLE CONVEX TO THE LEFT * ON THE MUCOSAL ASPECT – SEMICIRCULAR FOLDS - HOUSTON'S VALVES

ANATOMY CONTD. l THE PART BELOW MIDDLE VALVE AMPULLA OF RECTUM

ANATOMY CONTD. l PERITONEAL RELATIONS UPPER THIRD – IN FRONT AND ON THE LATERAL ASPECTS l MIDDLE THIRD – ANTERIOR SURFACE l LOWER THIRD – NO PERITONEAL COVERING l

ANATOMY CONTD. l ARTERIAL SUPPLY SUPERIOR RECTAL ARTERY MIDDLE RECTAL ARTERY INFERIOR RECTAL ARTERY

ANATOMY CONTD. l VENOUS DRAINAGE SUPERIOR HAEMORRHOIDAL VEINS → RECTAL VEINS → SUPERIOR RECTAL VEIN → INFERIOR MESENTERIC VEIN → PORTAL VEIN l MIDDLE RECTAL VEIN l

ANATOMY CONTD. l LYMPHATIC DRAINAGE UPPER HALF – PARARECTAL AND SIGMOID NODES → INFERIOR MESENTERIC NODES l LOWER HALF – ALONG MIDDLE RECTAL VESSELS TO INTERNAL ILLIAC NODES l

ANATOMY CONTD. l NERVE SUPPLY l SYMPATHETIC ( L 1, L 2) VASOCONSTRICTORS INHIBITORY TO MUSCLES MOTOR TO INTERNAL SPHINCTER PAIN SENSATION

ANTOMY CONTD. l NERVE SUPPLY l PARASYMPATHETIC (S 2, S 3, S 4) MOTOR TO MUSCELES INHIBITORY TO INTERNAL SPHINCTER SENSATION OF DISTENTION

ANATOMY CONTD. RELATIONS (males). BLADDER. SEMINALVESICLES. PROSTATE. URETERS. PELVIC MUSCLES. SACRUM COCCYX

ANATOMY CONTD. RELATIONS (females) l POUCH OF DOUGLAS l UTERUS l CERVIX l POST. VAGINAL WALL l SACRUM COCCYX

CARCINOMA OF RECTUM

CARCINOMA OF RECTUM SECOND COMMENEST VICSERAL TUMOUR OF THE BODY l COMMON ABOVE 50 yrs l YOUNGER AGE – BAD PROGNOSIS l MALE : FEMALE – 1. 2 : 1 l

AETIOLOGY GE 0 GRAPHIC VARIATION l DIETERY FACTORS l PRE EXISTING DISEASES l ADENOMA – CARCINOMA SEQUENCE l HNPCC l ALCOHOLISM, CIGARETTE SMOCKING l PELVIC RADIOTHERAPY l ACROMEGALY l

GEOGRAPHIC VARIATION

DIETERY FACTORS l l l EXCESS CALORIE INTAKE LOW CONTENT OF UNABSORBABLE VEGETABLE FIBRE HIGH CONTENT OF REFINED CARBOHYDRATES INTAKE OF RED MEAT DECREASED INTAKE OF PROTECTIVE MICRONUTRIENTS

PREEXCISTING DISEASES l INFLAMMATORY BOWELDISEASE ULCERATIVE COLITIS 1% PER YEAR AFTER 10 yrs 10% RISK AFTER 20 yrs CROHNS DISEASE 7% RISK AFTER 20 yrs COLONIC STRICTURESADENO CARCINOMA AT THE SITE OF FIBROTIC NARROWING EXCLUDED SEGMENTS AFTER SEGMENTAL BYPASS

PREEXCISTING DISEASES CONTD. l DIVERTICULAR DISEASE FOR LONG DURATION

HNPCC l HEREDITERY NON POLYPOSIS COLON CANCERS 4 – 6 % RECTAL MALIGNANCIES l LYNCH SYNDROME 1. AUTOSOMAL DOMINANT. SITE SPECIFIC WITHIN FAMILY. 4% MAY DEVELOP CARCINOMA l

HNPCC LYNCH SYNDROME 2 l AUTOSOMAL DOMINANT l DELETION OF MISMATCH REPAIR GENE l l COLORECTAL, ENDOMETRIAL, GASTRIC AND OTHER TYPES OF CANCERS

ADENOMA – CARCINOMA SEQUENCE PROPOSED BY VOGELSTIEN l ADENOCARCINOMA DEVELOP FROM PREEXCISTING ADENOMA l

ADENOMA – CARCINOMA SEQUENCE CONTD. l l l HIGH PREVELENCE ADENOMA HAS HIGH PREVELENCE OF CARCINOMA DISTRIBUTI 0 N OF ADENOMA WITHIN THE RECTUM IS COMPARABLE TO THAT OF CARCINOMA IN CASE OF EARLY INVASIVE Ca , SORROUNDING TISSUE SHOWS PRECEDING CHANGES OF EVOLUTION

ADENOMA –CARCINOMA SEQUENCE CONTD. l l PEAK INCIDENCE OF ADENOMA ANTEDATES BY SOME YEARS THE PEAK OF Ca RECTUM RISK OF Ca DECLINES WITH REMOVAL OF ALL IDENTIFIED ADENOMAS

ADENOMA –CARCINOMA SEQUENCE CONTD. l RISK OF DELOPING CARCIN 0 OMA NUMBER l SIZE – LARGE l TYPE – VILLOUS COMPONENT l

AETIOLOGY CONTD. l ALCOHOLISM l CIGARETTE SMOCKING

MOLECULAR CARCINOGENESIS l APC/β-CATENIN l PATHWAY MICROSATELLITE INSTABILITY MECHANISM

APC/β-CATENIN PATHWAY l l l LOSS OF APC TUMOUR SUPPRESSOR GENE LONG ARM OF CHROMOSOME 5 80% OF SPORADIC CASES ACCUMULATED β-CATENIN TRANSLOCATES TO THE NUCLEUS TRANSCRIPTION OF MYC & CYCLIN D PROMOTE CELLULAR PROLIFERATIONADENOMAS DEVELOP

APC/β-CATENIN PATHWAY CONTD. l POINT MUTATION IN K-RAS GENE EXCESSIVE ACTIVATION OF THIS GENE l PROMOTES MITOSIS AND PREVENTS APOPTOSIS l 50 % OF ALL RECTAL CARCINOMAS l

APC/β-CATENIN PATHWAY CONTD. l 18 q 21 DELETION l CANCER SUPPRESSOR GENE LOST IN 6070 % OF CANCERS DCC GENE DPC 4 , SMAD 4 SMD 2 ENCODE FOR TGF-β REGULATOR OF CELL CYCLE l l

APC/β-CATENIN PATHWAY CONTD. l l LOSS OF TP 53 GENE IN 70 -80% OF CANCERS

APC/β-CATENIN PATHWAY CONTD.

MICROSATELLITE INSTABILITY l l l l 10 -15% OF RECTAL CANCERS NO MORPHOLOGICALLY IDENTIFIABLE CHANGES LOSS OF DNA REPAIR GENES REPETITIVE DNA SEQUENCES BECOME UNSTABLE DURING REPLICATION TGF-β GENE BAX GENE LOSS OF MLH 1 GENE LOSS OF THESE RESULTS IN LOSS OF APOPTOSIS AND A DYSREGULATED GROWTH

MICROSATELLITE INSTABILITY

PATHOLOGY l MACROSCOPICAL l ANNULAR ENCIRCLING LESIONS NAPKIN RING CONSTRICTIONS CENTRAL ULCERATIONS WITH ELEVATED MARGINS PAPILLEFEROUS INFILTRATING TYPE EARLY LESIONS ARE SMALL BUTTON LIKE AREAS OF ELEVATION l l

MICROSCOPICAL l 95% ARE ADENOCARCINOMAS

MICROSCOPICAL l 10% OF THESE ARE COLLOID CARCINOMAS

MICROSCOPICAL l 5 % ARE UNDIFFERENTIATED CARCINOMA SIGNET CELL CARCINOMA ADENO-SQUAMOS

HISTOLOGICAL WELLDIFFERENTIATED l MODERATELY DIFFERENTIATED l POORLY DIFFERENTIATEDANAPLASTIC l

SPREAD OF THE CARCINOMA l l LOCAL SPREAD LYMPHATIC HAEMATOGENOUS SPREAD PERITONEAL DISSEMINATION

LOCAL SPREAD l l CIRCUMFERENTIAL SORROUNDING MESORECTUM

LOCAL SPREAD ANTERIORl IN MALES PROSTATE, BLADDER& SEMINAL VESICLES. l l. IN FEMALES UTERUS , CERVIX, POSTERIOR WALL OF VAGINA, POUCH OF DOUGLAS

LOCAL SPREAD POSTERIOR SACRUM&SACRAL PLEXUS l LATERAL- URETER l DOWNWARD- ANAPLASTIC CARCINOMA l

LYMPHATIC l l ABOVE THE PERITONEAL REFLECTION- TO THE INFERIOR MESENTERIC NODES BELOW THIS LEVEL TO ABOUT 1 -2 cm OF THE ANAL ORIFICE IS ALSO TO THE INFERIOR MESENTERIC NODES IN THE FIELD OF MIDDLE RECTAL ARTERIES SPREAD ALONG THESE VESSELS PRE AORTIC, INTERNAL ILLIAC AND SACRAL LYMPH NODES

HAEMATOGENOUS SPREAD l l l VIA THE VENOUS SYSTEM ANAPLASTIC AND RAPIDLY GROWING TUMOURS SITES. LIVER- 34%. LUNGS- 22%. ADRENALS- 11%. BRAIN, BONE, OVARY - 33%

PERITONEAL DISSEMINATION l FOLLOW PENETRATION OF PERITONEAL CAVITY BY A HIGH LYING RECTAL CARCINOMA

CLINICAL FEATURES l BLEEDING l EARLIEST, COMMON SYMPTOM FRESH BLEEDING BLOOD STAINING STOOLS BLOOD STAINING THE UNDER CLOTHINGS l l l

CLINICALFEATURES CONTD. l SENSE OF INCOMPLETE DEFECATION TENESMUS - CANCERS OF LOWER RECTUM l SPURIOUS DIARRHOEA l BLOODY SLIME l

CLINICAL FEATURES CONTD. l ALTERATION IN BOWEL HABIT EARLY MORNING BLOODY DIARRHOEA l ANNULAR CARCINOMA- INCREASING CONSTIPATIION l GROWTH AT AMPULLA OF RECTUMEARLY MORNING DIARRHOEA l

CLINICAL FEATURES CONTD. l PAIN COLICKY TYPE- ADVANCED GROWTH AT RECTOSIGMOID JUNCTION SEVERE – DEEP CARCINOMATOUS ULCER ERODES THE PROSTATE OR BLADDER PAIN IN BACK OR SCIATICA – SACRAL PLEXUS

CLINICAL FEATURES CONTD. l WEIGHT LOSS l ANAEMIA

EXAMINATION l ABDOMINAL EXAMINATION l NORMAL IN EARLY LESIONS ADVANCED GROWTHSSIGNS OF LARGE INTESTINAL OBSTRUCTION, COLON LOADED WITH FAECES MAY BE FELT LIVER PALPATED FOR METASTASIS ASCITES l l l

EXAMINATION CONTD. l l PER RECTAL EXAMINATION EARLY CASES – PLATEAU OR A NODULE WITH AN INDURATED BASE CENTRE ULCERATION – SHALLOW DEPRESSION WITH EVERTED RAISED EDGES FINGER SMEARED WITH BLOOD OR MUCOPURELENT MATERIAL TINGED WITH BLOOD

PER RECTAL EXAMINATION l CARCINOMA OF LOWER PART AFFECTED LYMPH NODES MAY BE FELT

EXAMINATION CONTD. l IN FEMALES VAGINAL EXAMINATION SHOULD BE DONE

SUMMARY

STAGING OF CANCER l DUKES STAGING l A- GROWTH LIMITED TO THE RECTAL WALL

STAGING l B- THE GROWTH EXTENDED TO THE EXTRA RECTAL TISSUE BUT NO METASTASIS TO REGIONAL LYMPH NODES

STAGING l C- THERE ARE SECONDARY DEPOSITS IN THE REGIONAL LYMPHNODES. C 1 - LOCAL PARARECTAL LYMPHNODES ALONE. C 2 - NODES ACCOMPANYING THE SUPPLYING VESSELS

STAGING l D- PRESENCE OF WIDE SPREAD METASTASIS

STAGING l ASTER COLLER STAGING l A- MUCOSA ONLY

ASTER-COLLER STAGING l B 1 - SUBMUCOSA INVOLVED

ASTER-COLLER STAGING l B 2 - MUSCULARIS INVOLVED

ASTER-COLLER STAGING l C 1 - INVOLVEMENT OF MUSCULARIS AND NODES

ASTER-COLLER STAGING l C 2 - INVOLVEMENT OF SEROSA AND NODES

ASTER-COLLER STAGING l D- DISTANT METASTASIS

TNM STAGING l l l Tx – PRIMARY TUMOUR CANNOT BE ASSESSED Tis – CONFINED TO THE MUCOSA T 1 - EXTEND UPTO SUBMUCOSA T 2 – EXTENDS INTO THE MUSCULARIS PROPRIA T 3 – EXTENDS IN TO THE SUB SEROSA BUT NOT TO ADJACENT STRUCTURES T 4 – INVOLVES ADJACENT STRUCTURES

TNM STAGING Nx – CANNOT BE ASSESSED l N O – NO LYMPH NODE METS. l N 1 – CANCER CELLS FOUND IN 1 TO 3 NEARBY NODES l N 2 – CANCER CELLS IN 4 OR MORE NODES l N 3 – CANCER CELLS IN NODES ALONG NAMED VESSELS l

TNM STAGING Mx – DISTANT METS. CANNOT BE ASSESSED l M 0 – NO DISTANT METS. l M 1 – DISTANT METS. PRESENT l