08.10.2014

Colorectal cancer treatment australia

Stage 0 colon cancer may be treated with a local exicision of the lesion, often via a colonoscopy. Almost all patients with stage III colon cancer, after surgery, should receive chemotherapy (adjuvant chemotherapy) with a drug known as 5-fluorouracil given for approximately 8 months.
Chemotherapy is also used for patients with stage IV disease in order to shrink the tumor, lengthen life, and improve quality of life. Radiation therapy is occasionally used in patients with colon cancer, but this is relatively uncommon. Stages of colorectal cancer - The staging of a carcinoma has to do with the size of the tumor, and the degree to which it has penetrated. Science, Technology and Medicine open access publisher.Publish, read and share novel research. This site exercises the 1st amendment right and is used for information and educational purposes only.
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Irinotecan and 5-fluorouracil are the two most commonly used drugs, given either individually or in combination. When the tumor is small and has not penetrated the mucosal layer, it is said to be stage I cancer. Endoscopic Mucosal Resection in a 0-IIa + Is polyp in colon (A-E), with control of the base after one month (F). IntroductionAdenomatous polyps are non-invasive tumours of epithelial cells arising from the mucosa with the potential to become malignant.
Invasive carcinoma in colorectal adenomas: multivariate analysis of patient and adenoma characteristics. Annual report to the nation on the status of cancer 1975 – 2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening and treatment) to reduce future rates. Screening colonoscopy for colorectal cancer prevention: results from a German online registry on 269000 cases. Performance of immunochemical faecal occult blood test in colorectal cancer screening in average-risk population according to possitivity threshold and number of samples. High-grade dysplasia and villous features should not be part of the routine diagnosis of colorectal adenomas. Polyp size and advanced histology in patient undergoing colonoscopy screening: implication for CT colonography. A comparison of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal polyps: a prospective study. High frequency probe EUS-assisted endoscopic mucosal resection: a therapeutic strategy for submucosal tumors of the GI tract. Endoscopic treatment of colorectal benign-appearing lesions 3 cm or larger: techniques and outcome. Successful complete cure en-bloc resection of large nonpedunculated colonic polyps by endoscopic submucosal dissecion: a meta-analysis and systemic review. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Long-term prognosis of well-differentiated adenocarcinoma in endoscopically removed colorectal adenomas. When is endoscopic polypectomy adequate therapy for colonic polyps containing invasive carcinoma? Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Detection of lymphatic invasion in early stage primary colorectal cancer with the monoclonal antibody D2-40.
Correlation between preoperative endoscopic and intraoperative findings in localizing colorectal lesions. High-grade dysplasia and invasive carcinoma in colorectal adenomas: a multivariate analysis of the impact of adenoma and patient characteristics. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. Safety of preoperation endoscopic tattoo with india ink for identification of colonic lesions.
The use of preoperative endoscopic tattooing in laparoscopic colorectal cancer surgery for endoscopically advanced tumors: a prospective comparative clinical study. The usefulness of preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for localization in laparoscopic colorectal surgery. Endoscopic mucosal resection for early colorectal neoplasia: pathologic basis procedures and outcomes. Circulating form of human vascular adhesion protein-1 (VAP-1): decreased serum levels in progression of colorectal cancer and predictive marker of lymphatic and hepatic metastasis. Preoperative serum vascular endothelial growth factor-a is a marker for subsequent recurrence in colorectal cancer patients. Multiple molecular markers as predictors of colorectal cancer in patients with normal perioperative serum carcinoembryonic antigen levels. My articles are in offering to begin to dive deeper into awareness for understanding cancer on physical, emotional and spiritual levels. For stages I, II, and III cancer, removal of a segment of colon containing the tumor and reattachment of the colon is necessary. There is some debate as to whether patients with stage II colon cancer should receive chemotherapy after surgery and patients should discuss this with their oncologist. A new drug, oxaliplatin, is also useful in these patients, but has not yet been approved by the FDA.
Submucosal injection was performed using indigo carmine (A,B), polypectomy was made with electrosurgical knives (C), After polypectomy, a large non bleeding vessel was visualized (D) and cauterized using coagulation forceps (E) and obliterated with an endoclip (F) to reduce the risk of delayed bleeding6.
The adenoma-carcinoma sequence is well known and it is accepted that more than 95% of colon adenocarcinomas arise from adenoma [1]. Class 5 of this pit-pattern classification or an unstructured surface has been shown to correlate well with a diagnosis of malignancy, and can provide important additional information prior to endoscopic treatment. The World Health Organisation (WHO) classifies adenomas into tubular (<20% villous architecture), tubulovillous and villous (80% villous architecture), with approximately 87% of adenomas being tubular, 8% tubulovillous and 5% villous [2]. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Type of resectionThe success of treatment of a malignant polyp depends on the complete resection by polypectomy or surgical intervention.
Risk of residual disease or recurrent carcinoma in favourable and unfavourable histology 4.8. The probability of high grade dysplasia and carcinomatous transformation increases with polyp size, a villous component, when there are many polyps or the age at diagnosis is more than 60 years [2]. When en-bloc removal of a polyp is performed, it is possible to assess the depth of infiltration of the tumour cells and whether the margin is affected. The neoplasia is considered to be advanced when polyp size is 1 cm or more, there is a villous component or a high degree of dysplasia.


Mixed polyps also have the ability to become malignant, as does hyperplastic polyposis syndrome. However, this technique frequently results in piecemeal removal when applied to sessile and flat malignant polyps. More than 25% of advanced polyps are located in the area proximal to the splenic flexure [3]. En-bloc removal is advantageous because it allows full histological evaluation of the complete resection and is associated with lower recurrence rates than piecemeal removal [25]. Endoscopic submucosal dissection (ESD) has been found to be particularly useful for the removal of sessile or flat adenomatous lesions. Mad cow disease (also known as bovine spongiform encephalopathy, or BSE), is a well-known brain disease. In an asymptomatic population of people over 50 years old who underwent direct colonoscopy, there was a 0.8% prevalence of adenocarcinoma of which 50% were carcinoma “in situ” or in stage I [8,9].
It has an advantage over other endoscopic techniques in that it allows en-bloc removal of large (>2 cm) colonic lesions. During screening programmes, adenocarcinomas have been detected in between 3% - 4.6% of those who undergo colonoscopy following a positive immunological faecal occult blood test result [10,11]. In ESD an electrosurgical cutting device is used to carefully dissect the deeper layers of the submucosa to remove neoplastic lesions in the mucosa.
One form of CJD, variant Creutzfeldt-Jakob disease (vCJD), first appeared in humans in 1996 about a decade after mad cow first appeared. HistologyCarcinoma "in situ", intramucosal carcinoma, high displasia or intraepithelial carcinoma is the stage at which there is no involvement of the muscularis mucosa. The Centers for Disease Control and Prevention states that scientists believe that this decade was the exact amount of time needed for mad cow to mutate into a form that could affect humans (CDC, 2012).
Level of invasion of adenocarcinoma into the polyp and polypectomy resection marginHaggitt et al.
Intramucosal carcinoma is a carcinoma characterized by the invasion into the lamina propria.When the carcinoma spreads to the submucosa, the polyp is considered to have become malignant, being able to spread to lymph nodes or distant sites.
In this study, level 1 described invasive adenocarcinoma limited to the polyp head, level 2 included involvement of the neck, level 3 corresponded to adenocarcinoma cells in the stalk, and level 4 to invasion, adenocarcinoma cells infiltrating the submucosa at the level of the adjacent bowel wall. The tumours that affect the submucosa are classified as T1 and correspond to Stage I of the TNM staging system. In this system, invasive adenocarcinoma in a sessile polyp by definition had level 4 invasion. In prion disease, these proteins are abnormally folded, form clumps, and destroy nerve cells. The term pseudoinvasion refers to the presence of glandular epithelium of the mucosa beneath the muscularis mucosa in colonic polyps. When they infect a mammal, the normal proteins start to take on the incorrect structure as well.
These lesions have no malignant potential and should be management in a similar way to adenomas [13]. More recently, some authors have proposed an additional histological classification system based on the grade of cell differentiation at the lesion margins and on the size and depth of invasion of the submucosa. Pseudoinvasion usually occurs in large polyps (>1 cm), especially those with long stalks, and is most commonly found in polyps of the sigmoid colon. When less than one-third of the submucosa is invaded the stage is sm1, and if more than two-thirds is invaded the stage is sm3, while stage sm2 is intermediate with invasion of cancer into the middle third. Islands of adenomatous epithelium are displaced through the muscularis mucosa and are found within the submucosa of the stalk.
It has been shown that penetration of cancerous cells is associated with a risk of lymphatic spread [29-32].
The displaced glandular tissue usually has rounded not infiltrative, contours, carries with it a small amount of lamina propria, and is cytologically identical to the overlying adenomatous component.
The risk of relapse ranges from 0% to 2% in malignant polyps with a margin of resection greater than 1 mm. In addition, inflammation and granulation tissue, can be found.Cystic dilatation of the displaced glands with mucin distention is also not uncommon in pseudoinvasion because mucin produced by the entrapped glands has no means of reaching the lumen.
If the resection margin is involved, or is less than 1 mm, the percentage of relapse ranges between 21% and 33% [30]. Occasionally, rupture of dilated glands occurs with acellularmucin extravasation and there is a subsequent inflammatory response. Specifically, in mucinous carcinoma, the mucin pools contain malignant cells, a feature lacking in pseudoinvasion.
For these reasons, it is highly recommended that level sections and second opinions, are obtained in cases of polyps with potential pseudoinvasion [14].
Signet ring cell or mucinous adenocarcinoma, composed of hyperchromatic cells arranged into solid sheets and forming absorptive glands, with 5% to 50% glandular differentiation. Sporadic CJD occurs when there is a spontaneous mutation of normal proteins to the abnormal prion type. According to the National Institute of Neurological Disorders and Stroke, 85 percent of CJD cases are sporadic (NINDS, 2003). Indeed, the WHO book on tumors of the digestive system, does not contain a list of criteria for high-grade dysplasia in adenomas [15,16].
Lymphatic invasionLymphatic invasion is defined as tumour cells within a true endothelial-lined channel in the absence of red blood cells [33]. However in general, high-grade dysplasia entails more substantial changes and includes carcinoma "in situ". The risk of lymphatic spread has been estimated by histological study of resected specimens. Among these changes we consider architectural alteration, often resembling the glandular arrangement of adenomas and cytologic abnormalities, principally cellular and nuclear pleomorphism, nuclear hyperchromatism, loss of nuclear polarity, and marked stratification of nuclei.
Since lymphatics do not penetrate much beyond the muscularis mucosae, focal cancer that has not invaded through this layer appears to present little or no risk of lymph node spread [34].
The near absence of lymphatics within the mucosa has been proposed as the reason for the observed lack of malignant potential (lymph node metastasis) observed in polyps showing only intramucosal carcinoma. Not all these features are necessarily present to the same degree in all dysplastic epithelia, while low-grade dysplasia manifests these same changes but to a lesser degree [15,16]. However, this theory has been challenged by studies using more sensitive techniques to detect lymphatic vessels.
Studies using the relatively new antibody D2-40, which stains lymphatic but not blood vessel endothelium, have shown that lymphatic present in the stalk and mucosa of adenomas and undergo proliferation, are early invasive cancers. Prognostic factorsMany factors have been associated with a higher probability of residual disease or recurrent carcinoma.
Lymphatic channels are often present near nests of infiltrating tumours in malignant polyps [35,36].
MorphologyMorphology is described as polypoid (pedunculated or sessil) and nonpolypoid (flat or ulcerated) subtypes according to the Paris classification [17]. There are no recognized guidelines for establishing the presence of lymphatic invasion (for example, the number of sections or immunostains needed to identify lymphatic vessels).


When it appears in cattle, it is referred to as mad cow disease, or BSE (bovine spongiform encephalopathy).
The type of polyp and its morphology can guide the endoscopist towards its potential malignancy [2,18,19]. For example, in a study in which five pathologists assessed the lymphatic invasion of 140 malignant polyps, they agreed (4 out of 5 observers) on only 17 cases [37].The intra and inter-observer variability in the interpretation of samples received among even the most expert histopathologists can be high and often leads to diagnostic uncertainties [37]. According to the Mayo Clinic, vCJD affects mostly young people in their 20s (Mayo Clinic, 2010). These features include the size, the presence of depressed ulceration, irregular contours, deformity, a short and immobile stalk and the inability to elevate a sessile polyp when a submucosal bleb is formed. In such suspicious lesions, as well as in flat or depressed lesions, diagnosis can be carried out using chromoendoscopy and magnification techniques that can highlight abnormalities of glandular cytoarchitecture and reveal information concerning the extent of submucosal invasion [20,21].
However, its use is not yet routine, and technical issues such as loss of a suspicious focus in level sections limits the usefulness of special stains in this setting.
The presence of lymphatic invasion has been proposed by some researchers as an indication for colectomy.
However, few malignant polyps with lymphatic invasion have been reported, and most of them have had positive margins, grade 3 invasive adenocarcinoma (as defined above), or both [5]. Vascular invasionThe presence of vascular invasion is defined as cancer in an endothelial-lined channel surrounded by a smooth muscle wall [35]. On the other hand, in the absence of unfavourable features, polypectomy is considered curative.
Sometimes, specimens do not lend themselves to proper analysis for any reason (piecemeal removal or poor orientation) result in a default decision to resect.
However, there were relapses or tumours in the area of the resection in only 8 (1%) patients with favourable histological criteria.
Only one study described incidence higher than 5% in malignant polyps with favourable histology [40] and the study itself has been widely criticized from subsequent reviews [5]. By contrast, in malignant polyps with unfavourable histology, the risk of relapse or residual lesions ranges between 10% and 39% [5,14,29,39]. Marking with India InkIn 1975, Ponsky and King [41] published the first case in which marking with India ink was used with the purpose of locating the polyp during the surgical procedure. Sometimes to locate the base of the polyp after polypectomy or during surgery is extremely difficult. All the endoscopicallyunresectable polyps in patients in whom surgery would be considered, should be tattooed. Among the criteria that should hint the endoscopist about the presence of malignancy in the polyps is size, an irregular surface or a flat or excavated morphology [2,18,42,43].The size of the polyp is an important factor that indicates malignancy [42,44-46].
The probability of dysplasia could be up to 38,5% in those larger than 1 cm [47].The flat or ulcerated lesions have a higher risk of high-grade dysplasia or carcinoma [22,48-50]. Our endoscopists usually marked large polyps, polyps resected in a fragmented manner and polyps with proximal location. However, in a multivariate analysis only proximal location was significant associated with marking.
It is known that flat polyps, with a greater potential for malignancy, are most frequently located in the right colon [37,39]. TreatmentPrior to removal of the polyp, it is difficult to know whether the polyp is malignant or not. Some features, as we have mentioned earlier, can give some indication of the degree of malignancy. Regardless of the morphological characteristics, a polyp is normally removed when detected. Polypectomy should be performed en bloc, since this is essential to establish and define favourable or unfavourable histological criteria.
In just a few cases, only polyp biopsies are performed, such a lack of coagulation data, polyp could be difficult to remove at that point in time, or the patient being on antiplatelet drugs or anticoagulants.
The indication for a malignant polyp with sessile morphology, regardless of favourable histological criteria, is surgery [10], especially in patients younger than 50 years old, who tend to present fewer surgical complications [59]. Surgical treatment is recommended for malignant polyps with pedunculated morphology which have unfavourable histological criteria (partial polyp resection, poorly differentiated carcinoma, vascular or lymphatic invasion, or lesions ?1 mm from the polypectomy) [10]. On the other hand, for malignant polyps with pedunculated morphology but with favourable histological criteria, polypectomy is considered to be curative (Figure 7). Non-invasive high grade neoplasia regardless of their morphology, are considered to be cured with polypectomy.
Submucosal injection was performed using indigo carmine (A,B), polypectomy was made with electrosurgical knives (C), After polypectomy, a large non bleeding vessel was visualized (D) and cauterized using coagulation forceps (E) and obliterated with an endoclip (F) to reduce the risk of delayed bleedingHowever, until now in many pathology reports were not reported histological criteria.
For example at the University of Minnesota between 1987 and 2000, 83% of the reports are not angiolymphatic vessel invasion, 69% not reported the depth of invasion by cancer cells and 22% no stated the degree of tumour differentiation [60]. Beside the agreement among experienced pathologists was poor with respect to histological grade of differentiated carcinoma and angiolymphatic vessel invasion [60].Endoscopic submucosal dissection (ESD) has emerged as a possible technique to successfully resect malignant colonic polyps en bloc [26,61].
The occurence of distant metastases is correlated to T-stage and, after radical resection of T1 tumours, the 5-year rate of metastases is about 10% [62], similar to other locations of malignant polyps. About 50% of the local recurrences following local resection are curable if the patients are included in an intensive follow-up programme. Local resection should be offered to patients whenever the individually calculated risk of short-term mortality after major surgery exceeds twice the additional risk of local recurrence added by local procedures.
However, medications can be used to treat some of the mental changes and personality abnormalities that occur.
An adequate preoperative evaluation of the patient's general health is essential before deciding the modality of treatment for the individual T1 rectum cancer patient.In recent years, various serum markers been identified in an effort to establish which patients could benefit from surgical treatment and from a more strict follow up. Treatment is usually focused on making patients comfortable and to help them function safely in their environment. These markers include metalloproteinase 7, vascular adhesion proteins, vascular endothelial growth factors and cytokeratins [63-66]. The majority of markers have been studied in patients operated on for colon cancer with infiltration of the lamina propria (equivalent to or higher than T2), so these results cannot readily be extrapolated to malignant colorectal polyps.6.
Follow-upIn cases of non-invasive high grade neoplasia and malignant polyps with pedunculated morphology and favourable histological criteria, it is recommended that a colonoscopy be carried out three months after taking the biopsy [1,43].If this is normal, a further check-up is advised after one year, three years and five year [43].
Some authors suggest that if the results within three months are negative, subsequent monitoring should be the same as that offered to patients with non-malignant adenomas [35,44].
Associated risk factors include age, number of polyps (5 or more), size (greater than 1 cm), villous architecture, proximal location, and being male. Smoking, body mass index, family history of CRC, and degree of dysplasia were not found to be associated with higher risks of advanced adenoma or cancer [45].There have been reports of cases of malignant pedunculated polyps with unfavourable histological criteria which, despite no findings of residual carcinoma in the intestine wall or lymph node involvement, are found on follow up to have distant metastasis, even five years after surgery [4,5]. ConclusionEn brief, the adenoma-carcinoma sequence is well known and polypectomy has proven to reduce the incidence of CRC. However, the success of treatment depends on the complete resection and the future follow up of the base of polypectomy.




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