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Introduction

Colorectal cancer is a common disease. 1 in 20 people will develop the disease, 1/2 of those will die from it. A big burden on the Australian community, with a high mortality.

Scenarios

  • 80 year old woman, short of breath, severely anaemic (iron deficiency).
  • 35 year old woman, bright red rectal bleeding, small pellet-like stools.
  • 67 year old man, abdominal pain and a colon mass identified on examination. Epigastric fullness and changed bowel habit. There was a fine-needle aspiration of a CT-detected mass in his abdomen that was an enlarged left-lobe of the liver (histology: adenocarcinoma -- possibilities = pancreatic primary or colorectal primary). Colonoscopy: Turns out that he has an obstructing lesion in the descending colon. Debate as to whether to offer him chemotherapy with palliative intent, or, because he's incredibly fit, perhaps we should offer him a resection in the hope that it prevents the tumour from obstructing further, bleeding and whether we can, with the new generation of chemotherapeutic agents, prolong his survival with the known liver disease he has.

Epidemiology

  • Disease of the developed world, longevity and affluence (animal proteins and saturated fats and low in complex carbohydrates, to develop the substrates needed for the disease).
  • Commonest invasive cancer via haematogenous spread.

Progression

  • Colorectal cancer is a curable disease because it develops from adenomas (can cure the precursor lesion first).
  • The vast majority of colorectal cancers develop from adenomas, which can be excised to prevent the development of the carcinoma.
  • The Vogelstein-Fearon progression describes how adenomatous polyps develop into colorectal cancer. This shows the DNA changes that change normal mucosa into cancer.
  • Genes include APC, k-RAS, dcc and p53. Chromosomal changes allow the development of more and more instability, and then the development of cancer.
  • Most people progress through this slowly, so we only need to scope people every 4-5 years. Some progress more quickly, so we shorten their colonoscopic surveillance times (to try to detect the late adenomas and carcinomas before they arise).
  • Polyp is an elevation of the mucosa of the colon. At the head of the polyp, the genetic accumulation of abnormalities occurs. Finally a carcinoma may arise. If the carcinoma is contained by the lamina propria, it is carcinoma in situ (severe displasia). As soon as it breaches the mucosa and heads into the submucosa it is a malignancy (a colorectal cancer) and needs to be treated as such.
  • We describe the pathology of the adenocarcinoma as being well-, moderately well- or poorly-differentiated. This has some prognostic implications.

Staging

  • Describe cancers having spread through the bowel wall in terms of lymph node involvement, whether they're pericolic or at the apex of the resection, to distant organs (liver or lung, bone or brain, and also to the peritoneal cavity).
  • Clearly the prognosis of colorectal cancer depends on the stage at which we detect the tumour.
  • The previous classical way of staging colorectal cancer was to use Dukes' classification:
    • A - cancer confined to the muscularis, but not through it
    • B - cancer through the muscularis and into the serosa, possibly through adjacent organs
    • C - the tumour had demonstrated metastatic potential and gone to pericolic or other lymph nodes
    • D - the tumour had spread far and wide, particularly to liver and lungs.
  • The prognosis is different for each of these stages of cancer. 5 year prognosis:
    • A = 95%, B=80%, C=50%, D<10%.
  • These numbers are about 7 years old. With the advent of urinoteecam and oxaliplatin, and all the entuximabs (EGF receptor antibody blockers), the prognoses for each stage are increasing. The 5 year survival of Dukes D is now 10-15%.

Prevention of colorectal cancer

  • reduce overall fat intake <25% of overall calories
  • slight state of starvation (reduced energy intake)
  • fibre - more complex carbohydrate improves transit time, reduces exposure of colon mucosa to carcinogen. Fruit/vegetables: Perhaps vegetable matter in the stool helps bind some of the carcinogens.
  • selenium supplementation may decrease carcinogenic effect of the stool
  • low dose aspirin prevents formation of polyps, therefore prevents cancer

Symptoms of colorectal cancer

  • rectal bleeding, particularly if dark and mixed with the stool, suggests a bleeding point in the colon high enough for it to mix with the stool
  • bright red bleeding can mean either a benign lesion (haemorrhoids or anal fissure) or a distal rectal cancer or anal cancer. It is worth taking a history and determining from the patient what they mean by rectal bleeding
  • new altered bowel habit is sinister
  • tenesmus - uncomfortable incomplete evacuations. Usually from a distal rectal cancer occupying space in the rectum, mimicking the feeling of fullness in the rectum usually caused by a stool. Usually can be diagnosed with a glove examination, however they also need a colonoscopy to clear the rest of the colon
  • mucous stool - green slime through the anus that arises from adenomatous tissue or even the cancer itself - clearly this represents a change in bowel habit and warrants investigation
  • on the right side of the colon, given that the blood lost from the colon mucosa/carcinoma, is a long way from the anus, there is time for that blood to be altered. We call this occult bleeding. Classic = elderly patient who slowly becomes anaemic unaware of blood loss. Classical presentation is ischaemic heart disease, weakness, fatigue, shortness of breath. "An iron deficient anaemic patient over 50 or 60 warrants colonoscopy until proven otherwise". The commonest cause of anaemia is occult bleeding from the right side of the colon.
  • family history: FAP etc, account for 1% of colorectal cancer -- develop carpet of thousands of adenomas. These patients invariably without colectomy. This is only 1% of colorectal cancers, most people develop colorectal cancer sporadically. Perhaps up to 4-5% of patients have HNPCC
    • MMR mutation; they develop particularly right-sided mucus-secreting colon cancer early in life.
  • We take their genetic information - it has prognostic information for their families and also screening information. It also has implications for urothelial malignancies and other GIT malignancies.
  • Past history of cancer, particularly colon cancer or colonic polyps makes us worry about metastases and subsequent cancers.
  • Inflammatory bowel diseases, particularly ulcerative colitis, cause chronic inflammation of the mucosa and predispose to cancer. This means that those patients are kept under close surveillance so we can detect any cancer early and offer colectomy.

Diagnosis

  • History, examination (rectal exam)
  • Sigmoidoscopy - cash-strapped parts, can't look at entire colon with a flexible fibre-optic cable to look at the left side of the colon (will catch most cancers, but not all)
  • Colonoscopy (gold standard, full bowel preparation, can take biopsy, study all components of the colon right up to the caecum)
  • Barium enema (used if there is an obstruction of the colon or if it's too twisted)
  • Biopsy via colonoscopy is sent to pathology to determine the nature of the carcinoma. We then do a CT scan of the chest and abdomen, looking for lung or liver mets. Usually we proceed to surgery on the colon, but if the metastases are wide-spread and there is clear evidence that the prognosis is particularly poor, then that does affect the surgical management. Don't offer patients extensive surgery with prolonged hospital stays and a slow recovery if their expected survival is only a few months.
  • We use anal ultrasound to discover rectal tumours. We more commonly use MRI for rectal cancers. CT scans are the most widely used form of complex radiology but they don't have great use within the pelvis. The bony walls of the pelvis generate artefacts, the CT bounces off calcium and we don't get good delineation of the pelvic structures. MRIs give us excellent definition of the anatomy of the rectum, prostate, sacrum, pelvic sidewalls. Most people do stage rectal cancers with MRI to determine if these patients require chemoradiotherapy or surgery and in what sequence.
  • Blood tests: check Hb to make sure patient hasn't been bleeding significantly and is now profoundly anaemic. Widespread liver mets may already be disordering the liver function. We check other parameters for pre-operative assessment.
  • PET scans are done at the outset in USA -- patient is injected with radioisotope. The isotope localises in tissues that are metabolically active. These tissues are seen as a hotspot on the PET scan. Fuse the PET scan with a CT scan to get both functional and anatomical information. *This is the most sensitive way of staging the patient at the outset. In Australia we normally just use a CT of the chest and abdomen, and maintain the PET scan for studying the patient after the initial colorectal cancer resection and prior to chemotherapy.
  • Applecore lesions are visible on barium enema. The stenosis of the large bowel is generated by the almost-opposing edges of the growing tumour. *Proximal to the apple core lesion is dilatation of the colon, common as they're developing incipient obstruction. Distal to that, the rectum is dilated due to hydrostatic pressure of the contrast.
  • We normally like to use a colonoscopy. Normal mucosa in the foreground and distance, with a polypoid, slightly-ulcerated and bleeding lesion in the middle ground. Biopsy of the lesion widely, showing severe adenoma over most of the lesion, but the centre of the lesion is cancer.

Once we make the diagnosis and confirm it histologically, we order a CT scan.

  • IV-contrast CT scan may reveal widespread liver mets (lytic or hypo dense lesions involving all segments of the liver). This would render the patient inoperable. Even though liver surgery is rapidly advancing, this is too much. If the liver mets are confined to just the Lt or Rt side of the liver, Lt or Rt hemihepatectomy can be performed. However, if it's widespread, we offer chemoradiotherapy, injection of phenol or alcohol or cryotherapy with chemotherapeutic patients. These are the patients with a 5 year survival formally <10% but, with newer adjuvant treatments, may be approaching 15%.

Surgical treatments for colorectal cancer

  • Surgery is the primary treatment aiming to cure colorectal cancer.
  • Most people request that the patients have a full bowel preparation.
  • There are probably better results if you dedicate yourself to just one branch of surgery.
  • The surgery is described according to the anatomical blood supply of the colon that you're taking out.
  • Right side of the colon is supplied from branches of the superior mesenteric artery. Those branches are the ileocolic, right colic and right branch of the middle colic. Those arteries have to be divided at their origin so that the lymph nodes along those arteries can be harvested with the resection. Those lymph nodes may contain metastases. So, by taking them you're curing the patient but also offering prognostic information (pathologist determines whether those lymph nodes are involved, and from that histological stage, we decide whether they need chemotherapy).
  • The cancer of the caecum or ascending colon is treated with a right hemicolectomy, the small bowel is then joined to the remaining colon (somewhere along the transverse patient), and the patient makes a good and rapid recovery, and there's very little change in overall bowel habit: 3 hours of operating, a week in hospital, and then home.
  • If the colon cancer is further along the transverse colon, we need to take the right colic, ileocolic, all the middle colic vessels and base the anastamosis (or healing point) on the small bowel mesentery and what's left of the Lt colic vessels (from the IMA, a whole new vascular distribution; a more tenuous vascular task). This increases the morbidity of the surgery and the rate of anastamotic leak.
  • Further around on the colon and into the rectum, we form a high anterior resection (anterior = we come entirely through the anterior abdominal wall). We remove the sigmoid colon where the cancer is, and take the lymph nodes along the blood vessels supplying that part of the tumour.
  • More complex is when the tumour is close to the anus. These are the patients who may need permanent colostomy (or temporary loop ileostomies).
  • The further the tumour gets toward the anus, the more difficult it is to get beyond the tumour and get a stapling device onto the rectum close to the anus, and join the patient up.
  • Where before, in the more simple surgeries, the leak rate may be about 1%, the leak rate for a colorectal anastamosis close to the pelvic floor might be up to 10%.
  • A leak is disastrous: it kills the patient (if it doesn't kill them, it decreases their function greatly and they become incredibly sick). We like to mitigate against the effects of leak via a temporary bag.
  • The temporary bag is a loop ileostomy brought out through the right side of the abdomen. The ileum is the final bit of small bowel before you reach the colon. The ileostomy is there for 12 weeks. It diverts the faecal stream into a bag, and prevents the patient becoming fatally sick if they have an anastomotic leak in the pelvis.
  • Patients hate the bag - it reminds them of their sickness and requires lifestyle adjustment, but it's for the best. Having assured that the anastomosis has worked properly (using radiography), we put the bowel back together.
  • Abdominoperineal resection: abdomen = anterior approach. Perineal = perineal approach as well.
    • Abdominal approach involves dissecting out the colon, rectum and anus from the anterior aspect, and harvest all nodes. Then there is an external component, with a separate shield-like incision around the anus itself, dissection and excision of the anal canal. The patient ends up with a hole in the pelvic floor.
    • This is a very deforming surgery, great morbidity to the patient. It's associated with great loss of pelvic floor, bladder and sexual function. We only ever do it for malignancy close to the anus where we're unable to preserve the anus with various tricks to get a stapling device beneath the tumour on the rectum above.
  • For a low rectal cancer, we would prefer to get a stapling device beneath it and generate an anastamosis beneath the stapling device. You need about 2-5 cm of normal tissue beyond the tumour to be assured of oncological clearance. Anything closer than that may generate an anastamotic recurrence.

Complications of surgery

  • anastomotic leakage (1% for abdominal surgery, 10% for surgery deep in the pelvis) -- these patients are sick, stay in hospital for weeks, further surgery and unexpected stomas.
  • wound infection is more common (cutting segments of bowel out, which is full of bacteria. Even with antibiotics, patients can get infected. The patient gets a red-hot wound, possibly becomes pyrexic.) The patients will do well long-term
  • bleeding. Stents for ischaemic heart disease, the long course of antibiotics after that, anticoagulatives and anti-platelet agents, we can reduce this. These patients have a 5-10% chance of bleeding. The problem with haematomas is that they're the perfect culture medium for bacteria (from the bowel).
  • sexual dysfunction (psychological blow of deforming surgery, the dissection necessarily goes close to pelvic autonomics. Some people quote a penile/vaginal dysfunction after surgery transiently. 20% chance of loss of sexual function permanently. Function after surgery is impaired in some way.
  • the colon has to be mobilised from the retroperitoneum. In the retroperitoneum we have both ureters. Ureteric injury is about 0.25-1%. If we cobble the ureter, we need urologists to reconstruct those for us, otherwise the patients become hydronephrotic and get renal failure.
  • when we take splenic flexures down, we do generate splenic bleeding. This sometimes leads to splenectomy, which increases the morbidity and mortality of the surgery.

Adjuvant therapy

  • basis used to be 5-flurourosil. This affects DNA replication in S phase.
  • leucovorin was added for its synergistic effect with 5-FU
  • platinum analogues like salyplatinum and the psiotoxins like irinotecan, while adding slightly to the morbidity of the chemotherapy, does significantly improve the efficacy.
  • for all comers, there is a 5-year 65% survival of colon cancer (irrespective of stage). That is probably improved by about 30% by chemotherapy, BUT the patient has to invest the time, money and morale to maintain a long routine of hospital stays, injections, fatigue, nausea, to complete the chemotherapeutic protocol. If the patients bail out partially through chemotherapy, they get far less benefit (they only get the full benefit if they stick with it)
  • with locally advanced rectal cancer, given that the rectum is far down in the bony walls of the pelvis, we really can't go out more widely than the rectum. We can't take cortex off the pelvic side walls.
  • in an attempt to reduce local recurrence in the pelvis, we offer local radiotherapy. This reduces the chance of local recurrence by sterilising pelvic sidewalls and picking up micro-metastases that may have already been shed
  • radiotherapy is often offered with chemotherapy (a radio sensitiser for their treatments).
  • a point of differentiation between rectal and colon cancer is we study the rectal cancer more closely than the colon cancer.
  • radiotherapy has extensive side effects. In young women, radiotherapy almost certainly sterilises the patient. Even with ovarian shielding, it would probably prevent ovulation, probably precipitate early menopause, and definitely impairs uterine function. There aren't any documented pregnancies after pelvic radiotherapy.
  • pelvic radiotherapy is a big decision and we need evidence to support its use: the evidence is through ultrasound. Sound probe at 5-8 MHz interrogates the lesion and determines the depth of invasion of the rectal tumour, and allows the study of the perirectal nodes, if they're enlarged.
  • may offer pelvic radiotherapy on the basis of ultrasound alone.
  • we prefer MRI studies: provides objective, reproducible images that can be studied by others.

Pre-operative radiotherapy prior to surgery is given to patients with determined lymph node involvement Sometimes, the rectal cancer is so well treated by chemoradiotherapy. But microscopically, we see nests of viable colorectal cells that can only be excised by surgery.

Case studies

80 year old woman with dyspnoea and weight loss

  • iron deficiency anaemic (Hb = 50)
  • transferred packed cells
  • colonoscopy = ascending colon cancer
  • studied with abdominal and chest CTs, with no lung or liver metastases
  • despite age, we put her up for resection, she was studied by anaesthetists, who determined that despite her age, she was fit
  • we carried out right hemicolectomy (laparascopic). The laparoscopic approach decreased the size of the wounds, the stay in hospital, and improved her return to her normal activities.
  • pathology revealed a T3 N0 tumour. Clearly she didn't need chemotherapy

35 year old woman with bright red rectal bleeding

  • rectal exam revealed a low rectal cancer, incredibly uncommon in a woman of that age
  • received chemoradiotherapy
  • required abdominoperineal resection: a huge blow to the lady, unable to work during adjuvant treatment, unable to bear more children
  • has done well oncologically, but the surgery and the radiotherapy changed her life forever

67 year old man

  • very fit, no previous history of colorectal cancer
  • epigastric fullness and slight change in bowel habit (used to be large and full, but now pellet-like)
  • abdominal mass found to be an enlarged Lt lobe of the liver
  • had a fine-needle aspiration of the liver transcutaneously (a bit of a no-no: may seed the malignant cells through the abdominal wall): confirmed an adenocarcinoma
  • proceeded to colonoscopy because the most common primary for an adenocarcinoma met in the liver is the colon
  • had a Lt sided colon cancer biopsy proven
  • will present him at a colon cancer meeting on monday to determine whether his widespread liver disease and his known obstructing colon cancer is best treated either with colonic stent, palliative intent, or whether we should offer him colonic resection and hope that the newer generation of chemotherapeutic agents prolongs his survival.
  • with luck and his overall fitness, he has a 15% chance of making 5 years.