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#Pathology
Adenocarcinoma of the colon is the most common malig- nancy of the GI tract and is a major cause of morbidity and mortality worldwide.
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#Pathology
The dietary factors most closely associated with increased risk of colorectal cancer are low intake of unabsorbable vegetable fiber and high intake of refined carbohydrates and fat.
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#Pathology
It is theorized that reduced fiber content leads to decreased stool bulk and altered composition of the intestinal micro- biota. This change may increase synthesis of potentially toxic oxidative by-products of bacterial metabolism, which would be expected to remain in contact with the colonic mucosa for longer periods of time as a result of reduced stool bulk. High fat intake also enhances hepatic synthesis of cholesterol and bile acids, which can be converted into carcinogens by intestinal bacteria.
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#Pathology
In addition to dietary modification, pharmacologic chemoprevention is possible. Aspirin and other NSAIDs have a protective effect. This is consistent with studies showing that some NSAIDs cause polyp regression in FAP patients in whom the rectum was left in place after colectomy. It is suspected that this effect is mediated by inhibition of the enzyme COX-2, which is highly expressed in 90% of colorectal carcinomas and 40% to 90% of adenomas. COX-2 is necessary for production of prostaglandin E 2 ,
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pathogenesis of colorectal carcinoma
#Pathology #abdomen #surgery

two genetic pathways have been described: the APC/β-catenin pathway, which is activated in the classic adenoma-carcinoma sequence,

and the MSI pathway, which is associated with defects

in DNA mismatch repair and accumulation of mutations

in microsatellite repeat regions of the genome

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#Pathology
Epigenetic events, the most common of which is methylation-induced gene silencing, may enhance progression along either pathway.
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#Pathology
The classic adenoma-carcinoma sequence accounts for up to 80% of sporadic cancers and typically includes mutation of APC early in the neoplastic process (Fig. 17.49). Both copies of the APC gene must be functionally inactivated, either by mutation or by epigenetic events, for adenomas to develop. The APC protein normally binds to and promotes degradation of β-catenin, a component of the Wnt signal- ing pathway (Chapter 7). With loss of APC function, β-catenin accumulates and translocates to the nucleus, where it forms a complex with the DNA-binding factor TCF and activates the transcription of genes, including MYC and cyclin D1, that promote proliferation. The critical role of β-catenin in this pathway is demonstrated by the fact that many colon cancers without APC mutations harbor β-catenin mutations that prevent APC-dependent degradation, thereby allowing β-catenin to accumulate and activate Wnt signaling. Additional mutations accu- mulate including activating mutations in KRAS that promote growth and prevent apoptosis.
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#Pathology
Carcinogenesis is also associated with mutations in tumor suppressor genes such as those encoding SMAD2 and SMAD4, which are effectors of TGF-β signaling. Because TGF-β signaling normally inhibits the cell cycle, loss of these genes may allow unrestrained cell growth. The tumor suppressor gene TP53 is mutated in 70% to 80% of colon cancers but is uncommonly affected in adenomas, suggesting that TP53 mutations also occur at later stages of tumor progression. Loss of function of TP53 and other tumor suppressor genes is often caused by chromosomal deletions, dem- onstrating the chromosomal instability that is a hallmark of the APC/β-catenin pathway. Alternatively, tumor suppressor genes may be silenced by methylation of CpG-rich zones, or CpG islands, within the 5′ region that frequently includes the promoter and transcriptional start site of some genes. Telomerase expression also increases as lesions become more advanced.
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#Surgery
The most common abnormality found in colorectal cancer is mutation in the Wnt signaling pathway, which increases cell signalling activity. The mutations can be inherited or acquired. The most commonly mutated gene is the APC gene, which results in accumulation of the β-catenin protein. β-catenin activates the transcription of various proto-oncogenes that are responsible for normal cell renewal and differentiation, but when overexpressed can cause cancer. Many other muta- tions, other than in the Wnt signaling pathway, are found in colorectal cancer, and include mutations in the TP53 gene that controls normal cell division and death, and mutations in genes responsible for programmed cell death, such as the gene encoding transforming growth factor (TGF)-β and DCC (deleted in colorectal cancer). Other genetic abnormalities include overexpression of oncogenes, including genes encod- ing the proteins KRAS (Kirsten rat sarcoma homologue), RAF (rapidly accelerated fibrosarcoma) and PI3K (phospho- inositide 3-kinase), which lead to increased cell proliferation, and inactivation of tumour suppressor genes, such as PTEN (phosphatase and tensin homologue), which normally inacti- vates the PI3K signalling pathway. In addition to gene mutations, colorectal cancers fre- quently exhibit epigenetic alterations – cellular or physiolog- ical effects resulting from external or environmental factors that switch genes on or off. Epigenetic alterations can affect hundreds of genes and include changes in the expression of microRNAs (miRNA), hypermethylation or hypomethyl- ation of CpG islands of protein-encoding genes, and alter- ations in histones and chromosomal architecture, all of which can influence gene expression.
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#Surgery
The most common is hereditary nonpolyposis colorectal can- cer (HNPCC or Lynch syndrome), which accounts for 3% of people with colorectal cancer. Other syndromes include Gardner syndrome and familial adenomatous polyposis (FAP).
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#Surgery
Often, the early symptoms are so insignificant that the patient does not seek advice for 6 months or more, and the diagnosis is often delayed in younger patients as the symptoms are attributed to benign causes.
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#Surgery
Bleeding is the earliest and most common symptom. Typi- cally, the bleeding is bright red in colour and painless.
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#Surgery
The patient experiences a sensation of needing to evacuate the rectum but is unable to pass a motion. This is an import- ant early symptom and is almost invariably present in patients with tumours of the lower half of the rectum. The patient may endeavour to empty the rectum several times a day (spurious diarrhoea), often with the passage of flatus and a little blood- stained mucus (‘bloody slime’).
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#Surgery
There is frequently a change in bowel habit, with a tendency to more frequent defaecation and the passage of looser stool. A patient who has to get up early in order to defaecate, or one who passes blood and mucus in addition to faeces (‘early- morning bloody diarrhoea’),
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#Surgery
Although a change to looser stools is more common, patients with a stenosing carcinoma at the rectosigmoid junction may complain of increasing constipation.
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#Surgery
Pain is a late symptom, but pain of a colicky character may accompany advanced tumours of the rectosigmoid, owing to a degree of obstruction. Advanced cancers invading outside the mesorectum may infiltrate the prostate or bladder ante- riorly or the sacral plexus posteriorly, giving rise to severe, intractable pain.
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#Surgery
Abdominal examination is normal in early cases. Occasion- ally, in patients with stenosing tumours at the rectosigmoid junction, signs of subacute large bowel obstruction may be present, with abdominal distension. If large-volume liver metastases are present, an enlarged liver may be palpable along with other signs, such as cachexia. Occasionally, it may be possible to elicit ascites if there is widespread peritoneal dissemination.
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#Surgery
In many cases where the neoplasm is situated within 7–8 cm of the anal verge it can be felt on digital rectal examination as an elevated, irregular and hard endoluminal mass. When the centre ulcerates, a shallow depression will be felt with raised and everted edges
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#Surgery
the neoplasm is mobile, tethered or fixed, and to estimate the distance of the lower margin from the top of the anal sphincter complex: these factors are important in assessing resectablility and methods of reconstruction follow- ing excisional surgery.
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#Surgery
In females, a vaginal examination may be useful if involvement of the posterior vaginal wall is suspected.
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#Surgery
A colonoscopy is required in most patients to exclude a syn- chronous tumour, be it an adenoma or carcinoma.
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#Surgery
If a full colonoscopy is not possible, for example where there is a ste- nosing cancer, a CT colonography or barium enema can be performed.
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clinical features of colorectal cancer based on location
#Pathology #abdomen #surgery
Cecal and other right- sided colon cancers are most often called to clinical attention by the appearance of fatigue and weakness due to iron deficiency anemia. Thus, it is a clinical maxim that the underlying cause of iron deficiency anemia in an older man or postmenopausal woman is GI cancer until proven oth- erwise. Left-sided colorectal adenocarcinomas may produce occult bleeding, changes in bowel habits, or cramping and left lower quadrant discomfort.
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Flashcard 6771645746444

Tags
#Surgery #abdomen #has-images
Question
Diagnosis and assessment of colorectal cancer

#Surgery


statusnot learnedmeasured difficulty37% [default]last interval [days]               
repetition number in this series0memorised on               scheduled repetition               
scheduled repetition interval               last repetition or drill

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local spread of colorectal carcinoma
#Surgery #abdomen
Local spread occurs circumferentially rather than in a longitu- dinal direction. After the muscular coat has been penetrated, the growth spreads into the surrounding mesorectum, but is initially limited by the mesorectal fascia. If penetration occurs anteriorly, the prostate, seminal vesicles or bladder become involved in the male; in the female, the vagina or the uterus is invaded. In either sex, if the penetration is lateral, a ureter may become involved, while posterior penetration may reach the sacrum and the sacral plexus. Downward spread for more than a few centimetres is rare.
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#Surgery
Assessment of spread should include CT of the chest, abdomen and pelvis to exclude distant metastases
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#Surgery
ositron emission tomog- raphy (PET) scanning can be helpful in identifying metasta- ses if imaging is otherwise equivocal.
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#Surgery
Endoluminal ultrasound, performed using a probe placed in the rectal lumen, can be used to assess the local spread of low rectal cancers (Figure 73.16), and is particularly useful in patients being considered for transanal endoluminal exci- sion. CT is not particularly accurate in local staging; this is usually performed using MRI, which allows assessment of the circumferential resection margin and lymph node status
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