With the continuous maturity of surgical treatment technology and the continuous improvement of adjuvant treatment such as chemotherapy, radiotherapy and biotherapy, the treatment of colorectal cancer in China has made great progress in the past two decades and is close to the level of developed countries, but the overall 5-year survival rate of colorectal cancer patients still has a large gap. The fundamental reason is that the early diagnosis and treatment rate of colorectal cancer in China is low, and most of the cases of colorectal cancer are near the middle and late stages when they are found. Therefore, improving the early diagnosis and treatment level of colorectal cancer is the key to further improve the 5-year survival rate of colorectal cancer patients in China. The following are some views on the progress of early diagnosis and treatment of colorectal cancer at home and abroad in recent years combined with the author’s experience.
1.Early diagnosis of colorectal cancer
Colorectal cancer with typical symptoms can be easily diagnosed, but in the early stage, colorectal cancer often appears only some hidden symptoms such as occult blood in stool or some precancerous symptoms such as increased number of bowel movements and intermittent stool bleeding caused by colon adenoma, or even no symptoms at all. To detect these early colorectal cancers without typical clinical symptoms, the most effective way is natural population screening and high-risk group screening and follow-up; popular education on colorectal cancer risk among the population and the reduction of medical leakage and misdiagnosis are important elements that cannot be ignored; improving colonoscopy rate and identification of lesions under colonoscopy is the most direct means to improve the detection rate of early colorectal cancer.
(1) Natural population screening and high-risk group screening and follow-up are the most effective ways to improve the diagnosis rate of early colorectal cancer
a. Natural population screening
Hewitson et al. summarized the 8 to 18 years of screening reports of 320,000 people published in the West in recent years, which showed that the cumulative risk of death from colorectal cancer decreased by 16% on average. A group of 16-year census reports by S.R. Lee et al. showed that the proportion of Dukes A/B stage colorectal cancer detected in the census population was 94%, and the 5-year survival rate after surgery reached more than 75%, while the proportion of Dukes A/B stage colorectal cancer detected in the non-census population was only 29%, and the 5-year survival rate was 33%. Obviously, it is impossible for a developing country with a population of 1.3 billion to achieve universal screening at this stage. However, it is at least possible to conduct screening in natural populations of high-incidence age groups in areas with high colorectal cancer prevalence. Zheng Shu et al. conducted a screening of 62,667 natural population aged >30 years in Jiashan County, Zhejiang Province, a region with high incidence of colorectal cancer, and found 34 cases of colorectal cancer, with an imputed detection rate of 54.3/105, and the proportion of colorectal cancer stage Dukes A/B was 71.4%, which shows the importance of natural population screening.
At present, fecal occult blood test (FOBT) is still the most used for natural population screening, and then colonoscopy is performed for positive patients. Due to the high false positive rate and low specificity of FOBT, which greatly increases the cost of follow-up examinations, some promising stool testing methods have emerged, such as fecal colonic exfoliation cytology and fecal colonic exfoliation cell DNA marker test.
Fecal colonic exfoliative cytology test: Normal intestinal mucosa has 1-5×1010 epithelial cells shed every 24 hours, while the renewal rate of tumor epithelial cells is faster, about 1% of cells are shed into the intestine every day and excreted with feces. The difference is that normal colonic mucosa sheds mainly apoptotic cells, while colorectal cancer tissue sheds mainly a large number of cytokeratin immunostaining positive colonic cells and inflammatory cells, and the shed colonic cells still retain the property of expressing tumor-associated antigens. The collection of fecal colonic exfoliated epithelial cells for routine pathological examination has a high specificity for the diagnosis of malignancy [4].
The DNA markers of fecal colonic exfoliated cells were found to be stable in feces and can be continuously shed from the colonic mucosa, and trace amounts of DNA can be detected in feces using PCR and other amplification techniques. screening test.
b. Screening and follow-up of high-risk groups
It is generally accepted that the following are high-risk groups for colorectal cancer: members over 20 years of age with family history of familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), those with a history of colorectal cancer or intestinal polyps in themselves or first-degree relatives, and those with inflammatory bowel disease, etc. Colonoscopy is required for high-risk subjects.
Family members: FAP is an autosomal dominant disease with a prevalence of 50% in the next generation, an epizootic rate of 95% and a cancer rate of 100%. Therefore, each family member should undergo genetic testing to identify carriers (mutations in the APC gene on the long arm of chromosome 5). If carriers, annual colonoscopy should be performed from the age of 20 years and prophylactic resection of the entire colon should be performed in case of multiple polyps.
Family members: HNPCC family members can be tested according to the pattern of gene mutation in the prevalent carriers, and once the prediction is positive, 80% of the patients may have cancer in the future, and these members should be treated with early intervention. Observations show that gene carriers (hMLH1, hMSH2, hMSH6, hPMS1, hPMS2 and other mismatch repair gene mutations) have an increased risk of colorectal cancer starting at age 20, and small adenomas can develop into cancer quickly.
According to statistics, the cancer rate of ulcerative colitis is related to the duration of the disease, with a cancer rate of 2% after 10 years of disease, 8% after 20 years of disease, and 18% after 30 years of disease. For ulcerative colitis that does not heal for many years and has a wide range of lesions, a full colonoscopy should be performed every one to two years after 8 years of disease; if the lesions only involve the left hemicolectomy, a colonoscopic surveillance can be performed after 15 years of disease.
(2) Population education on colorectal cancer risk and reduction of medical leakage and misdiagnosis are important elements that cannot be ignored at this stage to improve the early diagnosis rate of colorectal cancer in China
a. Population health education
In China, people have been seeking medical treatment only when they have symptoms for decades, lacking the awareness of active attention to health, and there are still many people who insist that intermittent stool bleeding is an attack of hemorrhoids and do not seek medical treatment. In the clinic, we often find that some rectal cancer patients have a history of more than one year, but the reason for their delay in seeking medical attention is that they are mistaken for hemorrhoids and do not pay attention to them. Therefore, to consciously carry out education on colorectal cancer prevention and treatment among the natural population, to encourage people to take the initiative to receive checkups, and to increase their sensitivity to intestinal danger signals is a practical and feasible means that must be given sufficient attention at this stage when universal screening is not possible. In the past five years, Zhejiang Provincial People’s Hospital has carried out outpatient education on colorectal cancer prevention and treatment, and persuaded patients with high-risk factors to undergo colonoscopy as much as possible.
b. Reducing the medical source of missed diagnosis and misdiagnosis
In the clinical investigation of 2573 cases of colorectal cancer treated in Zhejiang Provincial People’s Hospital, we found that 61.6% of the cases were diagnosed only after six months of medical history, 65.3% of which were due to patients’ own negligence, while the other 34.7% of cases were medically missed and misdiagnosed. Among these cases, some clinical doctors treat patients with intermittent irregular bowel movements and mucus stools with “chronic colitis” as a matter of course; some are satisfied with the diagnosis of “hemorrhoids” for patients with intermittent blood in the stool; some even do not even perform anal finger diagnosis and delay the diagnosis of lower rectal cancer. There are also a few cases that have undergone colon gas-barium imaging or colonoscopy, but the diagnosis is still missed because of the low quality of the examination. Therefore, to improve the diagnosis level of clinical doctors and reduce medical leakage and misdiagnosis is also the key to early diagnosis of colorectal cancer.
(3) Improving the rate of colonoscopy and identification of lesions under colonoscopy is the most direct means to improve the detection rate of early colorectal cancer
Colonoscopy is the most direct means to detect colorectal tumors, and any indirect signs found by all other examinations must eventually be confirmed and diagnosed by colonoscopy. In recent years, the emergence of magnification stained endoscopy and narrow band endoscopy has greatly improved the detection rate of microscopic lesions. However, the acceptance rate of the first colonoscopy is obviously limited by the risk and pain of colonoscopy. Therefore, advocating painless colonoscopy, improving the acceptance rate of colonoscopy, mastering advanced colonoscopy techniques and improving the detection rate of lesions are the keys to improve the diagnosis rate of early colorectal cancer.
a. Advocate comfortable endoscopy and improve the acceptance rate of colonoscopy.
Patients’ fear of colonoscopy is the biggest obstacle to accept colonoscopy, and advocating painless colonoscopy can effectively eliminate this obstacle and improve the acceptance rate of colonoscopy. However, it should be emphasized that the risk of complications increases because the patient is unresponsive to the operation during painless colonoscopy, so the operator must have skilled colonoscopy techniques.
b. Mastering advanced colonoscopy techniques to improve the recognition of early colorectal cancer and precancerous lesions.
Endoscopic colorectal lesions are mostly elevated lesions, and flat lesions, although few, are closely related to the occurrence of colorectal cancer. The conventional endoscopy can easily detect bulging lesions, but often misses small flat lesions. Magnified staining endoscopy can outline the lesions by spraying pigment on them, and clearly show the subtle changes in the morphology and arrangement of intestinal mucosal duct openings, thus improving the level of lesion identification. The commonly used pigments are 0.3% Indigo carmine and 0.2% to 0.5% Methylene Blue.
Japanese scholars Kudo et al. classified the morphology of colorectal mucosal crypts under magnification staining into five types (Pit Patten classification criteria): type I is a round crypts, relatively neatly arranged, no heterogeneity, generally normal glandular duct opening rather than lesions; type II is stellate or papillary, still neatly arranged, no heterogeneity, uniform size of glandular duct opening, mostly inflammatory or hyperplastic lesions rather than adenomatous; type III Type III is divided into two subtypes: ⅢL is called large adenoid type, with larger than normal crypt form, regular arrangement, no structural heterogeneity, and is the basic form of elevated adenoma, of which about 86.7% are adenomas, and the rest are mucosal carcinomas; Ⅲs is called small adenoid type, which is a collection of smaller than normal crypt form, with no branching of the crypt, and is the basic form of depressed tumor. Mucosal carcinoma (28.3%), type IV is branching and gyrus-like, this type of crypt is elevated lesions Ⅰp, Ⅰsp, Ⅰs, similar to coral-like changes are seen in choriocarcinoma features, intra-mucosal carcinoma can account for 37.2%. Tamura et al. found that the consistency between endoscopic and histopathological diagnosis of intestinal mucosal lesions according to Pit Patten’s classification was up to 90% with magnification staining. Hurlstone et al. also found that the sensitivity of magnified staining endoscopy for differentiating neoplastic from non-neoplastic lesions was 98% and the specificity was 92%.
The advent of narrow band endoscopy (NBI) has simplified the staining procedure. NBI can obtain images of mucosal depths of 240 μm, 200 μm and 170 μm with the help of narrow-spectrum light sources at 500 nm, 445 nm and 415 nm, respectively, and the mucosal vascular network appears clear brown due to the maximum absorption of hemoglobin at 415 nm. Hirata M et al. performed a comparative study using NBI magnification endoscopy and stained magnification endoscopy and showed that the diagnostic agreement between them for Pit Pattern was 88% for Type II, 100% for Type IIIs, 98% for Type IIIL, 88% for Type IV, 78% for Type VA and 100% for Type VN. The results showed that NBI endoscopy and stained endoscopy (0% Indigo Carmine) were used to examine 78 patients and Pit Pattern typing of polyps. The results showed that the sensitivity, specificity and accuracy of NBI endoscopy and stained endoscopy were the same in differentiating tumorigenic and non-tumorigenic colorectal polyps. Compared with stained endoscopy, NBI endoscopy can show the mucosal vascular network well, and the contrast between lesions and surrounding tissues is better, which facilitates the detection and diagnosis of flat lesions, and NBI endoscopy only requires switching between two light sources without spraying pigment, which is convenient and time-saving, and avoids the potential harm of pigmented endoscopy to human body.
2.Minimally invasive treatment of early colorectal cancer
The modern concept of surgical oncology treatment believes that the survival quality of tumor patients should be improved as much as possible under the premise of ensuring the requirement of radical treatment. Under the guidance of this concept, minimally invasive treatment of tumor is increasingly valued by doctors and patients. Minimally invasive treatment for early-stage colorectal cancer includes endoscopic snare resection (SR), endoscopic mucosal resection (EMR), endoscopic piecemeal mucosal resection (EPMR), and endoscopic mucosal resection (EMR), (EPMR), endoscopic submucosal dissection (ESD), and combined colonoscopic laparoscopic resection of early colorectal cancer.
According to the endoscopic presentation, early colorectal cancer is generally classified into three types: augmentation type, surface type and lateral spreading tumor (LST). The elevated type, also known as type I, can be divided into the tipped type (Ⅰp), subtip (Ⅰsp) and non-tip type (Ⅰs). The tipped type is usually confined to the mucosa and rarely invades the submucosa (m carcinoma), while the submucosal carcinoma (Sm carcinoma) predominates in the subtip and non-tip types. Surface type, also known as type II, can be divided into surface elevated type (IIa), surface flat type (IIb) and surface depressed type (IIc).LST is a kind of low elevated lesion with stronger lateral growth than superior growth, and the appearance is granular or nodular clusters.
It is suitable for early colorectal cancer of type Ⅰp and type Ⅰps; EMR is suitable for early colorectal cancer of type Ⅰs, type Ⅱa and type Ⅱb ≤3cm; EPMR is used for early colorectal cancer of type Ⅰs, type Ⅱa and type Ⅱb >3cm; ESD is suitable for early colorectal cancer of type IIc and LST. Except for SR, subfocal saline or epinephrine saline submucosal injection test should be performed before performing other endoscopic resection of early colorectal cancer; if there is no bulge sign after injection, it indicates deep infiltration and is no longer suitable for endoscopic treatment; this test can reduce the incidence of bleeding and intestinal perforation after treatment at the same time; it is also required that the incision margin should exceed the tumor margin by 1 cm as much as possible. ultrasonic endoscopy helps to accurately Ultrasound endoscopy can help to determine the depth of infiltration and the presence or absence of lymph node metastasis. For large tumors with high risk of intestinal perforation during endoscopic treatment, the operation can be performed under laparoscopic surveillance, and laparoscopic intestinal repair can be performed immediately in case of perforation. If there is obvious nonunions and the possibility of deep infiltration or lymph node metastasis is clear by ultrasonic endoscopy, laparoscopic radical resection of colorectal cancer under endoscopic localization can be performed.
Endoscopically resected specimens of early colorectal cancer should undergo postoperative pathological evaluation. Japanese scholars suggest that the following criteria should be met to determine the absence of cancer cells at the margin of the endoscopically resected specimen: the margin of each section should be free of cancer cells; the length of each section should be greater than the length of the cancer in the adjacent sections; the margin of the cancer should be 1.4 mm for highly differentiated tubular adenocarcinoma and 2 mm for moderately differentiated tubular adenocarcinoma. Yasuda et al. showed that EMR resected specimens with vascular infiltration, tumor budding, and significant submucosal infiltration had a significantly increased risk of lymph node metastasis, and these patients should undergo further surgical treatment. Bergmann et al. treated 59 cases of flat colorectal adenomas and 6 cases of early colorectal cancer with EMR or EPMR, with lesion diameters ranging from 10 to 50 mm. postoperative examination of the cases confirmed complete resection except for 2 cases with positive adenoma margins. Complications included one case of bleeding and one case of perforation. Fujishiro et al. reported 35 cases of rectal tumors undergoing ESD, including 17 adenomas, 13 non-invasive carcinomas, 2 Sm1 carcinomas, and 3 Sm2 carcinomas. The complete R0 resection rate was 89%, and 3 Sm2 carcinomas were treated with further surgery. 2 cases (5.7%) had perforation, and all were treated conservatively without recurrence. 31 cases were followed up for 3 years without recurrence. 200 cases of large superficial early colorectal tumors were treated with ESD by Saito et al. Sm2 or Sm3 carcinoma. The mean diameter of the specimens was 38 mm. 10 cases (5%) had perforation, 4 cases (2%) had bleeding, and only 1 case had emergency surgery. The complete resection rate and curative resection rate were 84% and 83%, respectively. It can be seen that as long as the indications are mastered, endoscopic treatment of early colorectal cancer is safe.
From EMR to ESD is a great progress in the endoscopic treatment of early colorectal cancer. ESD treatment for early colorectal cancer can not only obtain similar results as surgical treatment, but also save most patients from the risks of traditional surgical treatment and the serious impact on postoperative quality of life. In Japan and Hong Kong, ESD has become a safe, reliable and effective treatment method for one-time complete resection of intestinal mucosal cancer, and has replaced surgical treatment for some early-stage colorectal cancers.
The combined laparoscopic and colonoscopic operation was performed on 46 cases of colorectal tumors, of which 21 cases were polyps with malignant changes, and all cases had no recurrence after 1-21 months of follow-up. Combined laparoscopic-endoscopic colorectal tumor surgery is a combined laparoscopic and endoscopic technique to perform laparoscopic-assisted endoscopic transintestinal tumor resection and endoscopic localized laparoscopic radical resection of colorectal cancer or tumor localization. This technique allows endoscopic removal of large polyps or transintestinal tumor resection to be performed more safely under laparoscopic surveillance and assistance, avoiding unnecessary extensive resection or radical surgery; while in laparoscopic radical colorectal cancer resection, precise positioning of the enteroscope allows laparoscopic operation to obtain more reliable radical tumor margins. However, some experience in lumpectomy and endoscopic surgery is required for the operator.
Early diagnosis and treatment of colorectal cancer is the weak link in the prevention and treatment project of colorectal cancer in China, which should be given great attention. Strengthening the research on biological behavior of early colorectal cancer, standardizing the diagnostic criteria of early colorectal cancer, improving the level of early diagnosis of colorectal cancer, carrying out multi-center, large sample, randomized controlled clinical studies on minimally invasive treatment such as endoscopic treatment of early colorectal cancer, obtaining extensive evidence-based medical basis and guiding clinical practice with this is the key to improve the overall diagnosis and treatment of colorectal cancer in China.