- April 25, 2022
- Newsletter
- 617-430-5616
Menu
Menu
Menu
Menu
Menu
Menu
ADVERTISEMENT
ADVERTISEMENT
Background
Colorectal cancer is currently the third most fatal cancer, and its prevalence is gradually increasing in developing countries. CRC, also known as colorectal adenocarcinoma, is a type of cancer that develops from the glandular epithelial cells of the large intestine.
Colorectal Cancer develops when specific epithelial cells acquire a succession of genetic or epigenetic changes that give them a selective advantage. These hyper-proliferative cells cause the incidence of a benign adenoma, which can then progress into cancer and spread around the body for decades.
The colon’s major job is to reabsorb water as well as leftover minerals and nutrients in the chyme. The large intestine is home to a diverse microflora that can break down any leftover starches or proteins. The gastrointestinal epithelium is organized as an axis of crypts and villi to aid absorption.
Colon stem and progenitor cells are found in the crypt’s base. These pluripotent cells are responsible for self-renewal. Progenitor cells migrate out of the crypt and up the villus as they mature into specialized epithelial cells. Paneth, goblet, and enteroendocrine cells, as well as enterocytes, are examples of differentiated epithelial cells.
After about 14 days, when these cells reach the top of the villus, they undergo apoptosis, or programmed cell death, and are shed and removed with the feces.
This process is heavily regulated by a gradient of signaling proteins, the most prevalent of which are Wnt, BMP, and TGF-B.CRCs are a fairly diverse set of illnesses caused by a wide range of mutations and mutagens. As all CRCs have the same driving mutations, developing a “catch-all” molecular therapy has been problematic.
Surgery is still the primary line of treatment in situations with early diagnosis, but it is no longer effective in advanced cases when cancer has metastasized, which is the case in approximately 25% of diagnoses.
The rapid growth of medication resistance and cancer recurrence has hindered the efficacy of neoadjuvant, cytotoxic therapy in such individuals. A better understanding of the pattern of CRC development, environmental and genetic risk factors, and the disease’s molecular evolution can help researchers and doctors prevent and cure this lethal neoplasm.
Epidemiology
Every year, CRC affects an estimated 135,439 new patients in the United States, with CRC accounting for 95,520 cases. When colon and rectum cancers are combined, it is the second-largest cause of mortality in the United States, with an estimated 50,260 fatalities.
Since 2004, the CRC incidence rate has been decreasing by 3% per year while increasing by 2% per year among screened adults below the age of 50.The previous data reflects an increase in screening practices and precancerous lesion excisions.
The incidence of CRC varies over the world, with developed countries having greater rates of incidence than developing countries. Low socioeconomic status is linked to an increased risk of CRC, as well as to inadequate risk behavior and lack of access to medical care.
The lifetime average incidence of CRC in white Americans is 5%, but it is higher in 20% more in males than women, and greater than 25% in African Americans in comparison to non-Hispanic whites.
Epidemiologic findings show a steady shift in the anatomic distribution of CRC from the left-distal colon to the right-sided or proximal end, which is once again linked to more successful left-sided screening methods.
Early identification and improved treatment modalities have contributed to a 51 percent decline in CRC mortality in the United States from 1975 to 2014. According to the National Cancer Institute’s estimation, colorectal cancer has a 65% 5-year survival rate.
Anatomy
Pathophysiology
Most colorectal cancers begin as a tumor on the colon’s or rectum’s inner lining. These growths are referred to as polyps. Some polyps can develop into cancer over many years, however not all polyps turn cancerous.
The likelihood of a polyp developing into cancer is determined by the type of the polyp. Polyps are classified into various types. Adenomatous polyps are polyps that can turn cancerous.
Therefore, adenomas are referred to as a pre-cancerous condition. Tubular, villous, and tubulovillous adenomas are the three forms of adenomas.
Hyperplastic polyps and inflammatory polyps are more common; however, they are not precancerous in most cases. Regular colonoscopies are indicated for individuals who have hyper plastic polyps larger than 1cm.
Traditional serrated adenomas (TSA) and sessile serrated polyps (SSP) are polyps frequently treated as adenomas because their incidence presents an increased risk of colorectal cancer.
Other factors that can increase an individual’s risk of developing colorectal cancer are:
Another precancerous condition is dysplasia. It indicates that the cells in a polyp or the lining of the colon or rectum appear abnormal, but they haven’t turned cancerous yet.
Etiology
The non-cancerous expansion of mucosal epithelial cells is frequently the first sign of CRC. Polyps are benign growths that can grow slowly for 10–20 years before turning malignant. An adenoma or polyp formed from granular cells, which create the mucus that coats the large intestine is the most prevalent type.
Although the risk of cancer increases as the polyp grows larger, only approximately 10% of all adenomas develop into invasive cancers. Adenocarcinoma is an invasive cancer that arises from such polyps and accounts for 96 percent of all CRCs.
CRCs that grow through the colon or rectum’s wall can pass through blood or lymphatic vessels, allowing them to spread to distant organs or lymph nodes. The stage of a CRC diagnosis, and consequently the prognosis, is determined by the extent of the invasion.
Polyps that have not yet entered the colon or rectum wall are classified as in situ cancers and are not reported as CRCs. Cancers that have developed into the wall but not yet spread beyond it are known as local cancers.
Regional cancers have spread to local lymph nodes or tissues, whereas distant cancers have spread to distant organs with capillary beds where they have taken root, such as the lungs or liver, via the bloodstream.
Certain dietary and lifestyle decisions can cause intestinal inflammation and alter intestinal microbiota to stimulate an immune response, both of which can help polyps grow and become cancerous.
Similarly, genetic, or spontaneous mutations in oncogenes and tumor-suppressor genes might give particular mucosal cells a selective advantage, promoting hyper-proliferation and, eventually, carcinogenesis. CRC can be prevented with lifestyle changes, early colorectal screening, and genetic testing.
Genetics
Inherited gene mutations are responsible for a very small percentage of colorectal cancers. Four of these DNA changes and their effects on the growth of cells have been studied.
Prognostic Factors
According to the National Cancer Institute’s SEER database, the prognosis of the patient relies heavily on how far the cancer has spread. The 5-year survival rates for colon and rectal cancer are determined by the three stages of its spread, namely the localized, regional, and distant stages.
The figures presented in the SEER database have not taken factors such as age, overall health, and response to treatment into account, considering them might present a different prognosis. They are also exclusively applicable to the stage of the cancer during diagnosis.
The 5-year survival rates for patients diagnosed with colon cancer between 2011-2017 are:
The 5-year survival rates for patients diagnosed with rectal cancer between 2011-2017 are:
Clinical History
Physical Examination
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
Weekly Dose:
Initial Dose:
400
mg/m^2
Intravenous (IV)
over 2hrs, and Maintenance Dose:250 mg per m2 given IV over 1hr once a week
BIWEEKLY: 500 mg per m2 IV over 2hrs every two weeks
In Combination with Encorafenib:
400 mg per m2 IV is taken as the initial dose over 2hrs, and the Maintenance Dose is 250 mg per m2 IV over 1hr once a week until disease progression or unacceptable toxicity seen
comments:
Cetuximab with or without Irinotecan or FOLFIRI (irinotecan, fluorouracil, leucovorin), and this should be taken weekly or biweekly
Hence continue the treatment until disease progression or unacceptable toxicity observed
8
mg/kg
Solution
Intravenous (IV)
every 2 weeks
1
hr
Continue the therapy until disease progression or unacceptable toxicity occurs If the 1st infusion is tolerable, then go with subsequent infusions given over 30 minutes
6
mg/kg
Solution
Intravenous (IV)
every 2 weeks
ipilimumab 1 mg per kg given IV over 30 minutes every 3 weeks with nivolumab 3 mg per kg given IV over 30 minutes on the same day for 4 doses
After completing four doses of combination, nivolumab is given as a single agent
Continue the therapy until disease progression or unacceptable toxicity occurs
0.25
mg/kg
once a day
Intra-arterial continuous infusion for 14 days for a cycle of 5 weeks, continue for 6 cycles with dexamethasone and heparin
Start floxuridine therapy 2 weeks after 6 cycles of fluorouracil and leucovorin
Dose Adjustments
Reduce the dose by 20% of the usual dose for the following conditions:
o Serum bilirubin 1.2 x ULN or alkaline phosphatase 1.2 x ULN
o Baseline AST is 3 to <4 times the baseline value
Reduce the dose by 50% of the usual dose for the following conditions:
o Serum bilirubin 1.5 x ULN or alkaline phosphatase 1.5 x ULN
o AST is 4 to <5 times the baseline value
Discontinue the dose if any of the following adverse reactions appear:
o White blood count < 3,500/mm3
o Platelet count <1,00,000/mm3
o Vomiting, diarrhea or gastrointestinal bleeding/ulceration
Age: >50 years
75-100 mg orally daily
400 mg/m² of intravenous pyelogram on 1st day,
then 2400-3000 mg/m² intravenously as a continuous infusion for 46 hours every 2 weeks combined with leucovorin and/or oxaliplatin/irinotecan
regorafenib is indicated to treat metastatic colorectal cancer in patients who have undergone fluoropyrimidine- / oxaliplatin- / irinotecan-based chemotherapy
A dose of 40 mg is administered four times daily for the initial 21 days of every 28-day cycle
The medication is continued until the disease is reduced to acceptable toxicity
Indicated for metastatic colorectal cancer that is resistant to or has advanced after receiving oxaliplatin, it is recommended in conjunction with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI):
4mg/kg intravenous every two weeks
On the day of therapy, give before any FOLFIRI regimen component
Advanced stage of colorectal carcinoma:
Day 1: 85 mg/m² Oxaliplatin Intravenous (IV) + 200 mg/m² leucovorin Intravenous (IV) infused over 2 hours
Following 5-FU 400 mg/m² Intravenous (IV) bolus over 2-4 minutes
Next 5-FU 600 mg/m² Intravenous (IV) infusion over 22 hours
Day 2: WITHOUT oxaliplatin following Same regimen
continue for every 2 weeks
Adjuvant stage III colon cancer:
Course is 12 cycles
continue every 2 weeks,with the above scheduled dose for 6 months
Tumour excision is followed by adjuvant therapy
Indicated for Colorectal Cancer
It is used as 1st line treatment (leucovorin and 5-fluorouracil) for CRC (metastatic colorectal cancer) and also used for progressed or recurred CRC after fluorouracil-based treatment
Monotherapy
Pre-treatment should be given to patients with antiemetic drugs
For patients who experience cholinergic symptoms, atropine is given
Schedule-1 (every week): 125 mg/m² Intravenously infused over 1 hour 30 min on days 1, 8, 15, 22 and after that, two weeks off, and then repeat it
Schedule-2 (one time every three weeks): 350 mg/m² Intravenously infused over 30-90 min every 3 weeks
As per protocol, adjust the dose
Combination therapy
Pre-treatment should be given to patients with antiemetic drugs
For patients who experience cholinergic symptoms, atropine is given
Schedule-1 (Six weeks cycle) infusion with the leucovorin and 5-fluorouracil: 180 mg/m² Intravenously infused over 30-90 min one time on days 1,15,29 after that, infused with 5-fluorouracil and leucovorin; on day-43 next cycle starts
Schedule-2 (Six weeks cycle) bolus with the leucovorin and 5-fluorouracil: 125 mg/m² on days 1,8,15,22 (infused over 90 minutes); after that, bolus dose with 5-fluorouracil and leucovorin
As per protocol, adjust the dose
Indicated for Advanced colorectal cancer
Three daily divided doses of 300 mg/m2 tegafur in combination with 672 mg/m2 uracil orally with calcium folinate
These doses are administered over a 28-day cycle, followed by a seven-day treatment-free interval
Safety and efficacy not studied
Age:>12yrs
ipilimumab 1 mg per kg given IV over 30 minutes every 3 weeks with nivolumab 3 mg per kg given IV over 30 minutes on the same day for 4 doses
After completing four doses of combination, nivolumab is given as a single agent.
Continue the therapy until disease progression or unacceptable toxicity occurs.
Safety and efficacy not established in pediatrics
Future Trends
References
https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html”>https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html
https://www.ncbi.nlm.nih.gov/books/NBK470380/”>https://www.ncbi.nlm.nih.gov/books/NBK470380/
ADVERTISEMENT
Colorectal cancer is currently the third most fatal cancer, and its prevalence is gradually increasing in developing countries. CRC, also known as colorectal adenocarcinoma, is a type of cancer that develops from the glandular epithelial cells of the large intestine.
Colorectal Cancer develops when specific epithelial cells acquire a succession of genetic or epigenetic changes that give them a selective advantage. These hyper-proliferative cells cause the incidence of a benign adenoma, which can then progress into cancer and spread around the body for decades.
The colon’s major job is to reabsorb water as well as leftover minerals and nutrients in the chyme. The large intestine is home to a diverse microflora that can break down any leftover starches or proteins. The gastrointestinal epithelium is organized as an axis of crypts and villi to aid absorption.
Colon stem and progenitor cells are found in the crypt’s base. These pluripotent cells are responsible for self-renewal. Progenitor cells migrate out of the crypt and up the villus as they mature into specialized epithelial cells. Paneth, goblet, and enteroendocrine cells, as well as enterocytes, are examples of differentiated epithelial cells.
After about 14 days, when these cells reach the top of the villus, they undergo apoptosis, or programmed cell death, and are shed and removed with the feces.
This process is heavily regulated by a gradient of signaling proteins, the most prevalent of which are Wnt, BMP, and TGF-B.CRCs are a fairly diverse set of illnesses caused by a wide range of mutations and mutagens. As all CRCs have the same driving mutations, developing a “catch-all” molecular therapy has been problematic.
Surgery is still the primary line of treatment in situations with early diagnosis, but it is no longer effective in advanced cases when cancer has metastasized, which is the case in approximately 25% of diagnoses.
The rapid growth of medication resistance and cancer recurrence has hindered the efficacy of neoadjuvant, cytotoxic therapy in such individuals. A better understanding of the pattern of CRC development, environmental and genetic risk factors, and the disease’s molecular evolution can help researchers and doctors prevent and cure this lethal neoplasm.
Every year, CRC affects an estimated 135,439 new patients in the United States, with CRC accounting for 95,520 cases. When colon and rectum cancers are combined, it is the second-largest cause of mortality in the United States, with an estimated 50,260 fatalities.
Since 2004, the CRC incidence rate has been decreasing by 3% per year while increasing by 2% per year among screened adults below the age of 50.The previous data reflects an increase in screening practices and precancerous lesion excisions.
The incidence of CRC varies over the world, with developed countries having greater rates of incidence than developing countries. Low socioeconomic status is linked to an increased risk of CRC, as well as to inadequate risk behavior and lack of access to medical care.
The lifetime average incidence of CRC in white Americans is 5%, but it is higher in 20% more in males than women, and greater than 25% in African Americans in comparison to non-Hispanic whites.
Epidemiologic findings show a steady shift in the anatomic distribution of CRC from the left-distal colon to the right-sided or proximal end, which is once again linked to more successful left-sided screening methods.
Early identification and improved treatment modalities have contributed to a 51 percent decline in CRC mortality in the United States from 1975 to 2014. According to the National Cancer Institute’s estimation, colorectal cancer has a 65% 5-year survival rate.
Most colorectal cancers begin as a tumor on the colon’s or rectum’s inner lining. These growths are referred to as polyps. Some polyps can develop into cancer over many years, however not all polyps turn cancerous.
The likelihood of a polyp developing into cancer is determined by the type of the polyp. Polyps are classified into various types. Adenomatous polyps are polyps that can turn cancerous.
Therefore, adenomas are referred to as a pre-cancerous condition. Tubular, villous, and tubulovillous adenomas are the three forms of adenomas.
Hyperplastic polyps and inflammatory polyps are more common; however, they are not precancerous in most cases. Regular colonoscopies are indicated for individuals who have hyper plastic polyps larger than 1cm.
Traditional serrated adenomas (TSA) and sessile serrated polyps (SSP) are polyps frequently treated as adenomas because their incidence presents an increased risk of colorectal cancer.
Other factors that can increase an individual’s risk of developing colorectal cancer are:
Another precancerous condition is dysplasia. It indicates that the cells in a polyp or the lining of the colon or rectum appear abnormal, but they haven’t turned cancerous yet.
The non-cancerous expansion of mucosal epithelial cells is frequently the first sign of CRC. Polyps are benign growths that can grow slowly for 10–20 years before turning malignant. An adenoma or polyp formed from granular cells, which create the mucus that coats the large intestine is the most prevalent type.
Although the risk of cancer increases as the polyp grows larger, only approximately 10% of all adenomas develop into invasive cancers. Adenocarcinoma is an invasive cancer that arises from such polyps and accounts for 96 percent of all CRCs.
CRCs that grow through the colon or rectum’s wall can pass through blood or lymphatic vessels, allowing them to spread to distant organs or lymph nodes. The stage of a CRC diagnosis, and consequently the prognosis, is determined by the extent of the invasion.
Polyps that have not yet entered the colon or rectum wall are classified as in situ cancers and are not reported as CRCs. Cancers that have developed into the wall but not yet spread beyond it are known as local cancers.
Regional cancers have spread to local lymph nodes or tissues, whereas distant cancers have spread to distant organs with capillary beds where they have taken root, such as the lungs or liver, via the bloodstream.
Certain dietary and lifestyle decisions can cause intestinal inflammation and alter intestinal microbiota to stimulate an immune response, both of which can help polyps grow and become cancerous.
Similarly, genetic, or spontaneous mutations in oncogenes and tumor-suppressor genes might give particular mucosal cells a selective advantage, promoting hyper-proliferation and, eventually, carcinogenesis. CRC can be prevented with lifestyle changes, early colorectal screening, and genetic testing.
Inherited gene mutations are responsible for a very small percentage of colorectal cancers. Four of these DNA changes and their effects on the growth of cells have been studied.
According to the National Cancer Institute’s SEER database, the prognosis of the patient relies heavily on how far the cancer has spread. The 5-year survival rates for colon and rectal cancer are determined by the three stages of its spread, namely the localized, regional, and distant stages.
The figures presented in the SEER database have not taken factors such as age, overall health, and response to treatment into account, considering them might present a different prognosis. They are also exclusively applicable to the stage of the cancer during diagnosis.
The 5-year survival rates for patients diagnosed with colon cancer between 2011-2017 are:
The 5-year survival rates for patients diagnosed with rectal cancer between 2011-2017 are:
Weekly Dose:
Initial Dose:
400
mg/m^2
Intravenous (IV)
over 2hrs, and Maintenance Dose:250 mg per m2 given IV over 1hr once a week
BIWEEKLY: 500 mg per m2 IV over 2hrs every two weeks
In Combination with Encorafenib:
400 mg per m2 IV is taken as the initial dose over 2hrs, and the Maintenance Dose is 250 mg per m2 IV over 1hr once a week until disease progression or unacceptable toxicity seen
comments:
Cetuximab with or without Irinotecan or FOLFIRI (irinotecan, fluorouracil, leucovorin), and this should be taken weekly or biweekly
Hence continue the treatment until disease progression or unacceptable toxicity observed
8
mg/kg
Solution
Intravenous (IV)
every 2 weeks
1
hr
Continue the therapy until disease progression or unacceptable toxicity occurs If the 1st infusion is tolerable, then go with subsequent infusions given over 30 minutes
6
mg/kg
Solution
Intravenous (IV)
every 2 weeks
ipilimumab 1 mg per kg given IV over 30 minutes every 3 weeks with nivolumab 3 mg per kg given IV over 30 minutes on the same day for 4 doses
After completing four doses of combination, nivolumab is given as a single agent
Continue the therapy until disease progression or unacceptable toxicity occurs
0.25
mg/kg
once a day
Intra-arterial continuous infusion for 14 days for a cycle of 5 weeks, continue for 6 cycles with dexamethasone and heparin
Start floxuridine therapy 2 weeks after 6 cycles of fluorouracil and leucovorin
Dose Adjustments
Reduce the dose by 20% of the usual dose for the following conditions:
o Serum bilirubin 1.2 x ULN or alkaline phosphatase 1.2 x ULN
o Baseline AST is 3 to <4 times the baseline value
Reduce the dose by 50% of the usual dose for the following conditions:
o Serum bilirubin 1.5 x ULN or alkaline phosphatase 1.5 x ULN
o AST is 4 to <5 times the baseline value
Discontinue the dose if any of the following adverse reactions appear:
o White blood count < 3,500/mm3
o Platelet count <1,00,000/mm3
o Vomiting, diarrhea or gastrointestinal bleeding/ulceration
Age: >50 years
75-100 mg orally daily
400 mg/m² of intravenous pyelogram on 1st day,
then 2400-3000 mg/m² intravenously as a continuous infusion for 46 hours every 2 weeks combined with leucovorin and/or oxaliplatin/irinotecan
regorafenib is indicated to treat metastatic colorectal cancer in patients who have undergone fluoropyrimidine- / oxaliplatin- / irinotecan-based chemotherapy
A dose of 40 mg is administered four times daily for the initial 21 days of every 28-day cycle
The medication is continued until the disease is reduced to acceptable toxicity
Indicated for metastatic colorectal cancer that is resistant to or has advanced after receiving oxaliplatin, it is recommended in conjunction with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI):
4mg/kg intravenous every two weeks
On the day of therapy, give before any FOLFIRI regimen component
Advanced stage of colorectal carcinoma:
Day 1: 85 mg/m² Oxaliplatin Intravenous (IV) + 200 mg/m² leucovorin Intravenous (IV) infused over 2 hours
Following 5-FU 400 mg/m² Intravenous (IV) bolus over 2-4 minutes
Next 5-FU 600 mg/m² Intravenous (IV) infusion over 22 hours
Day 2: WITHOUT oxaliplatin following Same regimen
continue for every 2 weeks
Adjuvant stage III colon cancer:
Course is 12 cycles
continue every 2 weeks,with the above scheduled dose for 6 months
Tumour excision is followed by adjuvant therapy
Indicated for Colorectal Cancer
It is used as 1st line treatment (leucovorin and 5-fluorouracil) for CRC (metastatic colorectal cancer) and also used for progressed or recurred CRC after fluorouracil-based treatment
Monotherapy
Pre-treatment should be given to patients with antiemetic drugs
For patients who experience cholinergic symptoms, atropine is given
Schedule-1 (every week): 125 mg/m² Intravenously infused over 1 hour 30 min on days 1, 8, 15, 22 and after that, two weeks off, and then repeat it
Schedule-2 (one time every three weeks): 350 mg/m² Intravenously infused over 30-90 min every 3 weeks
As per protocol, adjust the dose
Combination therapy
Pre-treatment should be given to patients with antiemetic drugs
For patients who experience cholinergic symptoms, atropine is given
Schedule-1 (Six weeks cycle) infusion with the leucovorin and 5-fluorouracil: 180 mg/m² Intravenously infused over 30-90 min one time on days 1,15,29 after that, infused with 5-fluorouracil and leucovorin; on day-43 next cycle starts
Schedule-2 (Six weeks cycle) bolus with the leucovorin and 5-fluorouracil: 125 mg/m² on days 1,8,15,22 (infused over 90 minutes); after that, bolus dose with 5-fluorouracil and leucovorin
As per protocol, adjust the dose
Indicated for Advanced colorectal cancer
Three daily divided doses of 300 mg/m2 tegafur in combination with 672 mg/m2 uracil orally with calcium folinate
These doses are administered over a 28-day cycle, followed by a seven-day treatment-free interval
Safety and efficacy not studied
Age:>12yrs
ipilimumab 1 mg per kg given IV over 30 minutes every 3 weeks with nivolumab 3 mg per kg given IV over 30 minutes on the same day for 4 doses
After completing four doses of combination, nivolumab is given as a single agent.
Continue the therapy until disease progression or unacceptable toxicity occurs.
Safety and efficacy not established in pediatrics
Refer adult dosing
https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html”>https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html
https://www.ncbi.nlm.nih.gov/books/NBK470380/”>https://www.ncbi.nlm.nih.gov/books/NBK470380/
Colorectal cancer is currently the third most fatal cancer, and its prevalence is gradually increasing in developing countries. CRC, also known as colorectal adenocarcinoma, is a type of cancer that develops from the glandular epithelial cells of the large intestine.
Colorectal Cancer develops when specific epithelial cells acquire a succession of genetic or epigenetic changes that give them a selective advantage. These hyper-proliferative cells cause the incidence of a benign adenoma, which can then progress into cancer and spread around the body for decades.
The colon’s major job is to reabsorb water as well as leftover minerals and nutrients in the chyme. The large intestine is home to a diverse microflora that can break down any leftover starches or proteins. The gastrointestinal epithelium is organized as an axis of crypts and villi to aid absorption.
Colon stem and progenitor cells are found in the crypt’s base. These pluripotent cells are responsible for self-renewal. Progenitor cells migrate out of the crypt and up the villus as they mature into specialized epithelial cells. Paneth, goblet, and enteroendocrine cells, as well as enterocytes, are examples of differentiated epithelial cells.
After about 14 days, when these cells reach the top of the villus, they undergo apoptosis, or programmed cell death, and are shed and removed with the feces.
This process is heavily regulated by a gradient of signaling proteins, the most prevalent of which are Wnt, BMP, and TGF-B.CRCs are a fairly diverse set of illnesses caused by a wide range of mutations and mutagens. As all CRCs have the same driving mutations, developing a “catch-all” molecular therapy has been problematic.
Surgery is still the primary line of treatment in situations with early diagnosis, but it is no longer effective in advanced cases when cancer has metastasized, which is the case in approximately 25% of diagnoses.
The rapid growth of medication resistance and cancer recurrence has hindered the efficacy of neoadjuvant, cytotoxic therapy in such individuals. A better understanding of the pattern of CRC development, environmental and genetic risk factors, and the disease’s molecular evolution can help researchers and doctors prevent and cure this lethal neoplasm.
Every year, CRC affects an estimated 135,439 new patients in the United States, with CRC accounting for 95,520 cases. When colon and rectum cancers are combined, it is the second-largest cause of mortality in the United States, with an estimated 50,260 fatalities.
Since 2004, the CRC incidence rate has been decreasing by 3% per year while increasing by 2% per year among screened adults below the age of 50.The previous data reflects an increase in screening practices and precancerous lesion excisions.
The incidence of CRC varies over the world, with developed countries having greater rates of incidence than developing countries. Low socioeconomic status is linked to an increased risk of CRC, as well as to inadequate risk behavior and lack of access to medical care.
The lifetime average incidence of CRC in white Americans is 5%, but it is higher in 20% more in males than women, and greater than 25% in African Americans in comparison to non-Hispanic whites.
Epidemiologic findings show a steady shift in the anatomic distribution of CRC from the left-distal colon to the right-sided or proximal end, which is once again linked to more successful left-sided screening methods.
Early identification and improved treatment modalities have contributed to a 51 percent decline in CRC mortality in the United States from 1975 to 2014. According to the National Cancer Institute’s estimation, colorectal cancer has a 65% 5-year survival rate.
Most colorectal cancers begin as a tumor on the colon’s or rectum’s inner lining. These growths are referred to as polyps. Some polyps can develop into cancer over many years, however not all polyps turn cancerous.
The likelihood of a polyp developing into cancer is determined by the type of the polyp. Polyps are classified into various types. Adenomatous polyps are polyps that can turn cancerous.
Therefore, adenomas are referred to as a pre-cancerous condition. Tubular, villous, and tubulovillous adenomas are the three forms of adenomas.
Hyperplastic polyps and inflammatory polyps are more common; however, they are not precancerous in most cases. Regular colonoscopies are indicated for individuals who have hyper plastic polyps larger than 1cm.
Traditional serrated adenomas (TSA) and sessile serrated polyps (SSP) are polyps frequently treated as adenomas because their incidence presents an increased risk of colorectal cancer.
Other factors that can increase an individual’s risk of developing colorectal cancer are:
Another precancerous condition is dysplasia. It indicates that the cells in a polyp or the lining of the colon or rectum appear abnormal, but they haven’t turned cancerous yet.
The non-cancerous expansion of mucosal epithelial cells is frequently the first sign of CRC. Polyps are benign growths that can grow slowly for 10–20 years before turning malignant. An adenoma or polyp formed from granular cells, which create the mucus that coats the large intestine is the most prevalent type.
Although the risk of cancer increases as the polyp grows larger, only approximately 10% of all adenomas develop into invasive cancers. Adenocarcinoma is an invasive cancer that arises from such polyps and accounts for 96 percent of all CRCs.
CRCs that grow through the colon or rectum’s wall can pass through blood or lymphatic vessels, allowing them to spread to distant organs or lymph nodes. The stage of a CRC diagnosis, and consequently the prognosis, is determined by the extent of the invasion.
Polyps that have not yet entered the colon or rectum wall are classified as in situ cancers and are not reported as CRCs. Cancers that have developed into the wall but not yet spread beyond it are known as local cancers.
Regional cancers have spread to local lymph nodes or tissues, whereas distant cancers have spread to distant organs with capillary beds where they have taken root, such as the lungs or liver, via the bloodstream.
Certain dietary and lifestyle decisions can cause intestinal inflammation and alter intestinal microbiota to stimulate an immune response, both of which can help polyps grow and become cancerous.
Similarly, genetic, or spontaneous mutations in oncogenes and tumor-suppressor genes might give particular mucosal cells a selective advantage, promoting hyper-proliferation and, eventually, carcinogenesis. CRC can be prevented with lifestyle changes, early colorectal screening, and genetic testing.
Inherited gene mutations are responsible for a very small percentage of colorectal cancers. Four of these DNA changes and their effects on the growth of cells have been studied.
According to the National Cancer Institute’s SEER database, the prognosis of the patient relies heavily on how far the cancer has spread. The 5-year survival rates for colon and rectal cancer are determined by the three stages of its spread, namely the localized, regional, and distant stages.
The figures presented in the SEER database have not taken factors such as age, overall health, and response to treatment into account, considering them might present a different prognosis. They are also exclusively applicable to the stage of the cancer during diagnosis.
The 5-year survival rates for patients diagnosed with colon cancer between 2011-2017 are:
The 5-year survival rates for patients diagnosed with rectal cancer between 2011-2017 are:
https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html”>https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html
https://www.ncbi.nlm.nih.gov/books/NBK470380/”>https://www.ncbi.nlm.nih.gov/books/NBK470380/
Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
USA – BOSTON
60 Roberts Drive, Suite 313
North Adams, MA 01247
INDIA – PUNE
7, Shree Krishna, 2nd Floor, Opp Kiosk Koffee, Shirole Lane, Off FC Road, Pune 411004, Maharashtra
Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
MASSACHUSETTS – USA
60 Roberts Drive, Suite 313,
North Adams, MA 01247
MAHARASHTRA – INDIA
7, Shree Krishna, 2nd Floor,
Opp Kiosk Koffee,
Shirole Lane, Off FC Road,
Pune 411004, Maharashtra
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
On course completion, you will receive a full-sized presentation quality digital certificate.
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
