8: Colon Cancer Flashcards

Question

Clinical features of intestinal ischaemia

Answer 1

- >70 years, slightly more females than males - Acute colonic ischaemia: ○ Sudden onset cramping ○ Left lower abdominal pain ○ Desire to defaecate ○ Passage of blood/bloody diarrhoea ○ Shock and vascular collapse within hours if sever - Surgical intervention required in 10% and should be considered if infarction suspected: ○ Diminished peristaltic sounds ○ Guarding ○ Rebound tenderness

Answer 2

- 30 day mortality is 10%, with appropriate management - Mortality doubled in right-sided colonic disease ○ These patients have a more severe disease course in general ○ May be because right side is supplied by SMA, which also supplies much of the SI ○ Thus, right-sided colonic ischaemia may be the initial presentation of more widespread compromise of intestinal perfusion - Other poor prognostic factors: ○ Coexisting COPD ○ Persistence of symptoms for >2 weeks

Answer 3

CMV colitis: ○ CMV causes ischaemic GI disease due to viral tropism for endothelial cells and resulting localised vascular obstruction. Radiation enterocolitis: ○ Occurs due to irradiation of GI tract ○ due to a combination of epithelial and endothelial injury ○ The presence of highly atypical ‘radiation fibroblasts’ within the stroma provides clue. ○ Acute radiation enteritis manifests as anorexia, abdominal cramps, and malabsorptive diarrhoea ○ Chronic radiation enteritis or colitis is often more indolent and may present as an inflammatory enterocolitis Limited zones of mucosal and mural infarctions may progress to extensive and transmural infarction: ○ If vascular supply is not restored by correction of the insult or, in chronic disease, by development of collateral supplies. ○ The diagnosis of nonocclusive ischaemic enteritis and colitis can be difficult, as symptoms including intermittent bloody diarrhoea and intestinal obstruction are often nonspecific Chronic ischaemia ○ May masquerade as IBD- episodes of intermittent bloody diarrhoea interspersed with periods of healing Necrotising enterocolitis is an acute disorder of the SI and LI that can result in transmural necrosis. ○ Most common acquired GI emergency of neonates ○ frequently presents when oral feeding is initiated. ○ Ischaemic injury is thought to contribute to the pathogenesis ○ Acute on chronic

Answer 4

``` - Classification ○ Non-neoplastic § Hyperplastic § Inflammatory □ Inflammatory □ Benign lymphoid § Hamartomas □ Juvenile □ Peutz-Jeghers ○ Neoplastic § Adenoma □ Tubular □ Tubulovillous □ Villous § Adenocarcinoma § Carcinoid § Non-epithelial □ Lipoma □ Leiomyoma - Morphology ○ Sensile = without stalk ○ Pedunculated = with stalk ```

Answer 5

- Smooth, nodular small protrusions - Pathogenesis ○ Decreased epithelial cell turnover in proliferative zone of intestinal crypt ○ Decreased shedding of surface epithelial cells ○ Piling up of goblet + absorptive cells

Answer 6

``` - Gross ○ Smooth nodular protrusions ○ < 5mm ○ Crests of mucosal folds ○ Groups in left colon - Micro ○ Irregular tufting of epithelial cells on polyp surface ○ Mature goblet + absorptive cells with serrated architecture ```

Answer 7

``` - Pathogenies ( solitary rectal ulcer syndrome) ○ Impaired relaxation of anorectal sphincter ○ Sharp angle at anterior rectal shelf ○ Recurrent abrasion + ulceration of overlying mucosa ○ Chronic injury followed by healing - Morphology ○ Gross § Sessile § Red muscularis propria around ○ Micro § Inflammatory infiltrate § Dilated glands § Proliferative epithelium § Superficial erosions ```

Answer 8

< 5 years ○ SMAD4 / BMPR1A mutations ○ Altered TGF-β signalling pathway ○ Juvenile polyp (sporadic) or juvenile polyposis (syndromic)

Answer 9

``` ○ Gross § Pedunculated, red-brown lesions § Usually < 3cm § Cystic spaces ○ Micro § Thickened lamina propria § Dilated glands filled with mucin + inflammatory debris - Other manifestations ○ Pulmonary AV malformation ○ Hereditary haemorrhagic telangiectasia ○ Digital clubbing ```

Answer 10

- 10-15 years - Pathogenesis ○ STK11 mutation ○ Altered MAP kinase signally pathway

Answer 11

``` ○ Gross § Large and pedunculated § Lobular contour § Small intestine ○ Micro § Arborising network of connective tissue, smooth muscle, lamina propria and glands - Other manifestations ○ Pigmented macules on lips + buccal mucosa ○ Pigmented macules on hands + feet ○ Increased risk of malignancy § Testes § Stomach § Small intestine § Colon § Breast § Pancreas § Lung § Thyroid § Ovary § Uterus ```

Answer 12

- Teenagers - Pathogenesis ○ APC mutation ○ Altered Wnt signalling pathway

Answer 13

``` ○ Gross § Sensile § Adenomatous polyps § Usually < 0.5 cm § Greater than 100 polyps to diagnose ○ Micro § Tubular adenomas - Other manifestations ○ Colorectal adenocarcinomas ○ Congenital hypotrophy of retinal pigment epithelium ○ Tumours and cysts ○ Gardner and Turcot syndrome ```

Answer 14

- Benign polyps that have the potential to develop into cancerous polyps - Adenoma-carcinoma sequence ○ Normal mucosa § First hit mutations of cancer suppressor genes ○ Mucosa at risk § Second hit methylation abnormalities + normal allele activation ○ Adenoma § Protooncogene mutations § Homozygous loss of cancer suppressor genes § COX-2 overexpression ○ Carcinoma § Additional mutations § Gross chromosomal mutations

Answer 15

``` - Micro ○ Tubular adenoma § Smooth surface § Tubular glands § Pedunculated ○ Tubulovillous adenoma § Tubular pattern § Vertical villi ○ Villous adenoma § Sessile § Finger-like villi ○ Well-differentiated § Necrotic debris § Glandular structure ○ Poorly differentiated § Very few glands ○ Signet-ring morphology § Signet ring cells § Extracellular mucin pool ```

Answer 16

- Depths of invasion | - Presence of lymph node metastases

Answer 17

- Older age - Low fibre diet ○ Decreased stool bulk ○ Alters intestinal microbiome ○ By-products of bacterial metabolism cause oxidative damage ○ Slower transit means longer contact with mucosa - High alcohol intake - Reduced exercise - High red and processed meat diet - Obesity - Tobacco

Answer 18

- Adenoma-carcinoma pathway - 80% of sporadic cases ○ Early APC mutation § Methylation/inactivation of other active copy § β-catenin mutations ○ Increase in cytoplasmic β-catenin levels ○ β-catenin translocate to nucleus ○ Binds with TCF ○ Gene transcription ○ Proliferation - Mismatch repair pathway ○ Mutation of DNA mismatch repair genes ○ Accumulation of mutations in microsatellite repeats ○ Coding/promotor regions of the genes affects ○ Stops inhibition of colonic epithelial cell proliferation

Answer 19

- Gross ○ Exophytic, polypoid mass ○ May be ulcerated, haemorrhagic ○ Distal – more likely to be annular and cause obstruction ○ Napkin-ring constriction - Histology ○ Irregular, crowded glands and cells ○ Tall columnar cells packed together with hyperchromatic nuclei ○ Accumulation of connective tissue (stromal desmoplastic response) -> firm tumour

Answer 20

- Asymptomatic picked up through screening - Symptomatic disease ○ Bleeding, anaemia, change in bowel habit, tenesmus, palpable mass, hepatomegaly - Obstruction, perforation, peritonitis, death

Answer 21

``` - Most important factors ○ Depth of invasion ○ Lymph node metastases - Age and comorbidity - Carcinoembryonic antigen - Obstruction and perforation ```

Answer 22

- Confirm diagnosis - Inform prognosis - Plan individual treatment - Audit pathology services - Evaluate the quality of other clinical services - Collect data for cancer registration and epidemiology - Facilitate research - Provide education - Plan service delivery

Answer 23

- Confirm surgery was necessary - Place patient in correct disease stage - Inform necessity of adjuvant chemotherapy - Determine involvement of circumferential resection margin (CRM) - Frequency of CRM involvement - Assess effects of preoperative therapy - Audit diagnostic and surgical procedures - Facilitate improvements in quality of surgery - Help predict prognosis ○ Those with risk factors for worse prognosis -> harsher treatments § High grade § Mucinous type § Depth of invasion § Presence of lymph node metastasis

Answer 24

- Nature of resection - Site of tumour - Detected as part of screening programme - Histological type of tumour - PMHx and FHx - Preoperative stage - Preoperative therapy - Type of surgery - Type and dissection plane of operation

Answer 25

- Whole process takes 15-20 mins - saes time on fixing - Freeze and cut sample in cryostat machine at minus 25 - Staining - Observe down microscope - Used in unexpected intraoperative encounter (emergency surgery) but commonly resected regardless or to evaluate surgical margin

Answer 26

- Primary tumour ○ TX = tumour cannot be assessed ○ T0 = no evidence of primary tumour ○ T1 = tumour invades submucosa ○ T2 = tumour invades muscularis propria ○ T3 = invades subserosa or non-peritonealised pericolic/perirectal tissues ○ T4 = further invasion § T4a = tumour perforates peritoneum § T4b = tumour directly invades other organs or structures - Regional lymph nodes ○ NX = regional lymph nodes cannot be assessed ○ N0 = no regional lymph node metastatic disease ○ N1 = metastatic disease in 1-3 regional lymph nodes § N1a = in 1 regional lymph node § N1b = in 2-3 regional lymph nodes § N1c = satellites in subserosa or non-peritonealised pericolic/perirectal tissues ○ N2 = metastatic disease in 4+ regional lymph nodes § N2a = in 4-6 regional lymph nodes § N2b = in 7+ regional lymph nodes - Distant metastatic disease ○ M0 = no metastatic disease ○ M1 = distant metastatic disease § M1a = confined to one organ without peritoneal metastases § M1b = in more than one organ § M1c = to the peritoneum +/- other organ involvement

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8: Colon Cancer Flashcards

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