Term: FIMS Week: CBL SESSION Surgery

Transcription

1 Term: FIMS Week: CBL SESSION Surgery CBL Title: Colo-Rectal Cancer CBL Session Coordinators: Coordinators /phone: Key issues that may be addressed in CBL sessions: SUGGESTED LIKELY CASES FOR DISCUSSION Patient selected from pre-admission clinic having elective surgery for colo-rectal cancer KEY POINTS FOR DISCUSSION History: PR bleeding, change of bowel habbit, bloating, abdo pain, weight loss, anaemia, family history, IBD, polyps, previous CC, fitness for surgery (meds-anticoags, CVD, allergies, renal function) Examination: Abdo: mass, hepatomegaly, distension, previous surgery, PR mass/pain/blood, general metastatic check (bone pain, SOB, neuro), and fitness for surgery (CV and respiratory) Investigations FBC: HB microcytic anaemia of blood loss and Fe def, platelets for surgery Fe: iron def LFT: mets CEA for post op follow up EUC: pre op Coag: liver disease and pre op CXR, ECG for surg Colonoscopic: diag and therapeutic for polyps Barium enema: good if colonoscope unable to be done CT cologroaphy: colonoscope better Staging: CT chest, abdo and pelvis for distant spread. MRI for local spread of rectal cancer Management Colonic CA Resection Left hemicolectomy: sigmoid +/- sigmoid Right hemicolectomy: ICV to transverse colon Rectal CA High anterior resection: upper rectum to descending colon Low and ultra low: mid and/or low rectum to descending colon (requires defunctioning ileostomy) Abdo perianal: resection of anus, rectum and sigmoid and formation of permanent colostomy or illiel pouch. Chemo/radiotherapy Australian National University 1 Page 1 of 8

2 For tumours through the bowel wall or with LN involment to reduce recurrence rate of cancer in low rectal. CC Dukes C chemo improves survival and reduces recurrance. Unsure of benefit in Dukes B Review of pathophysiology and anatomy: There is believed to be two pathways leading to carcinoma: The APC/B-caterin (adenoma-cancer sequence) and the microsatelite instability pathway, characterised by genetic lesion in DNA mismatch repair genes. Both lead to accumulations of mutations over time and highlight Knudson s Hypothesis where there is inherited mutation, followed by second and ongoing hits, eventuating in CA. The second hit leads to a loss of heterozygosity (LOH). Colonic adenoma cancer sequence APC: fist hit K-RAS: oncogene that when mutated leads to continuous second messenger activation of cell proliferation. SMADS: reducing TGF-B ability to inhibit cell proliferation Loss of p53: occurs late in carcinogenesis but causes loss of repair Telomerase activation: leading to immortality of the carcinoma (not often seen in adenomas) Molecular genetics of colo-rectal cancer including FAP and HNPCC FAP A condition with a minimum of 100 polyps is necessary for a diagnosis, but as many 2500 can Australian National University 2 Page 2 of 8

3 be present. Prevention includes early detection and prophylactic colectomy in siblings of first degress relatives. Attenuated FAP has less numerous polyps. Gardner is associated with osteoma. WNT is a soluable factor stimulating cell growth via B-Catenin. B-catenin then stumulates cell proliferation via increasing transcription with the assistance of TcF (T-cell factor). B-catenin is neutralised by APC assisted destruction complex when WNT is not present. When APC is not present, transcription of cyclin D1 and MYC go unchecked leading to tumour groiwth. HNPCC AD condition causing mutations to DNA repair genes leading to microsatelite instability. Microsatelites are repeat sequences in the human genome that if mismatched in gene replication causing alteration of their function (most are noncoding, but others code for promoter genes involved in cell growth, i.e. TGF-B, BAX and p53). P53 is part of the repair, cycle arrest and apoptosis. When DNA damage in encountered, p53 is phosphorylated by other genes that sense the damage. It leads to G1 arrest and induces repair genes and apoptosis is repair cannot be achieved. Australian National University 3 Page 3 of 8

4 Australian National University Pathology of colo-rectal cancer including interpretation of structural pathology report See report structure in CPC book. Not really sure of what they wanted here Anatomy of colon and rectum including Blood supply Lymphatic and venous drainage Immediate anatomical relationships Pelvic anatomy I thought that just cutting and pasting anatomy text it might be easier to just use the Australian National University 4 Page 4 of 8

5 books. Physiology of colonic function Secretions: Mucus is produced in large quantities in the large intestine to protect the intestinal wall from excoriation, provides an adherent medium for holding fecal matter together, protects the intestinal wall from bacterial activity and with the alkalinity of the secretion (ph of 8.0 caused by large amounts of sodium bicarbonate) provides a barrier to keep acids formed in the feces from attacking the intestinal wall. Absorption: bicarbonate is exchanged for Ci and Na is absorbed at a higher rate than in the small intestine due to the stronger tight junctions. Water follow at a max rate of 5-8lts/day. Most of this occurs in the proximal section. In addition to Na, Cl absorption, bacterial activity produces vitamin K, vitamin B 12, thiamine and riboflavin, which are also utilized. Investigations: Diagnostic pathology: See the Well Adult ICCH CBL for when FOBT and colonoscopy is done for particular at risk popullations Faecal occult blood testing Colonoscopy and biopsy Clinico-pathologic staging of colon and rectal cancer TNM Australian National University 5 Page 5 of 8

6 Dukes Dukes A: Invasion into but not through the bowel wall Dukes B: Invasion through the bowel wall but not involving lymph nodes Dukes C: Involvement of lymph nodes Dukes D: Widespread metastases Imaging: Barium studies o Enema o Virtual colonoscopy CT MRI Ultasound and endo-rectal ultrasound Diagnosis: Patient s perspective: Helping patient through treatment and back into usual activities Understanding impact of treatment including side effects of treatment Understanding physical and psychological impact of stoma and stoma care Management: see above Multidisciplinary approach to treatment roles of surgery, and radiotherapy and chemotherapy Types of surgery Management of emergency presentation Community/Primary Care Issues: Research needs/issues to debate: Rectal bleeding: any male that presents with Fe def anemia means GIT CA until proven otherwise Altered bowel habit Characteristics of abdominal and anal pain Clinical manifestation of advanced disease Australian National University 6 Page 6 of 8

7 Acute presentations Right sided CA are called to clinical attention by fatigue, weakness and Fe deficiency anaemia. Left sided produce occult bleeding constipation, diarrhoea, crampy LIF discomfort. Indication for surgery, chemotherapy and radiotherapy (see above) Follow up protocol after treatment CEA for post surgery screen, CT and coloscopy after one year for polyp though no improvement to survival. Pt visit at 3mth, 6mth and every year for 3-5 years even though no benefit seen in mortality. Aspect of local treatment at variance with published guidelines Aspects of individuals treatment that lack evidence base can these be clarified with research CLINICAL SCIENCES PAL Discuss legal obligations on General Practitioner to follow-up after referral of patient for colonoscopy for suspected bowel cancer. Consider in this context Kalikarinos case. POPULATION HEALTH Incidence of colo-rectal cancer in our community and globally Rationale for community based screening program to detect colo-rectal cancer Specific conditions and behaviours which predispose to colo-rectal cancer Is this disease a risk factor for other conditions? Explain. What preventive strategies are available for this illness? INDIGENOUS HEALTH SOCIAL FOUNDATION OF MEDICINE RURAL ISSUES RESOURCES Sabiston - Textbook of surgery; 17 th edition 2004; Chapter 48; pages , Australian National University 7 Page 7 of 8

8 1466 NH & MRC Guidelines for treatment of colo-rectal cancer National Hospital Morbidity datacube. AIHW. Mathers C, Vos T and Stevenson C. The Burden of Disease and Injury in Australia. AIHW Canberra (Including Annex Tables D). AIHW Australia s Health Cat no AUS 73. Canberra AIHW. Theme percentages: Medical Sci: % PPD: % Population Health: % Clinical skills: % Frameworks involved: SFM Keywords: Australian National University 8 Page 8 of 8