I. Overview
The incidence and mortality of colorectal cancer (CRC) in China have been on the rise. 2011 incidence and mortality rates of colorectal cancer were 23.03/100,000 and 11.11/100,000, respectively.) The incidence of colorectal cancer is much higher in urban areas than in rural areas, and the incidence of colon cancer is increasing significantly.
Most patients are already in the middle and late stages when they are found.
In order to further standardize colorectal cancer diagnosis and treatment in China, improve the level of colorectal cancer diagnosis and treatment in medical institutions, improve the prognosis of colorectal cancer patients, and guarantee the quality of medical treatment and medical safety, we have established the following guidelines
In order to further regulate colorectal cancer diagnosis and treatment in China, improve the level of colorectal cancer diagnosis and treatment in medical institutions, improve the prognosis of colorectal cancer patients and guarantee medical quality and medical safety, this specification is formulated.
Diagnostic techniques and applications
(A) Clinical manifestations.
Early colorectal cancer may have no obvious symptoms, but the following symptoms may appear when the disease has developed to a certain extent.
1. Change in bowel habit.
2. Change in stool characteristics (thinning, bloody stool, mucus stool, etc.).
3, abdominal pain or abdominal discomfort.
4. Abdominal masses.
5.Symptoms related to intestinal obstruction.
6, anemia and systemic symptoms: such as wasting, weakness, low fever, etc.
(B) Disease history and family history.
1. The development of colorectal cancer may be related to the following diseases: ulcerative colitis, colorectal polyposis, colorectal adenoma, Crohn’s disease, schistosomiasis, etc.
Patients should be asked about the relevant medical history in detail.
2. The incidence of hereditary colorectal cancer accounts for about 6% of the overall incidence of colorectal cancer.
(3) Physical examination
(C) Physical examination.
1.General condition evaluation, general superficial lymph node condition.
2.Abdominal visual examination and palpation, check the presence of intestinal pattern, intestinal peristaltic waves, abdominal masses.
3.rectal finger examination: all suspected colorectal cancer patients must routinely undergo anorectal finger examination. To understand the size, texture, circumference of the intestinal wall, basal mobility, distance from the anal verge, infiltration of the tumor to the outside of the intestine, relationship with the surrounding organs and the presence of pelvic floor implantation of rectal tumor. During finger examination, we must
(ii) Touch carefully to avoid missing the diagnosis; touch gently, do not squeeze, and observe whether the finger stains with blood.
(iv) Laboratory tests.
1.Blood routine: to know whether there is anemia.
2.Urinary routine: observe whether there is hematuria, combine with urological imaging to understand whether the tumor invades the urinary system.
3.Fecal routine: pay attention to the presence of red blood cells and pus cells.
4.Fecal occult blood test: it is important for the diagnosis of small amount of bleeding in gastrointestinal tract.
5.Biochemistry and liver function.
6.Patients with colorectal cancer must be tested for CEA and CA19-9 before diagnosis, treatment, evaluation of efficacy and follow-up; patients with liver metastasis are recommended to be tested for
AFP; CA125 is recommended for patients with suspected ovarian metastasis.
(E) Endoscopy.
Proctoscopy and sigmoidoscopy are suitable for colorectal lesions with low lesion location.
Colonoscopy is recommended for all patients with suspected colorectal cancer, with the following exceptions.
1, poor general condition, difficult to tolerate;
2.Acute peritonitis, intestinal perforation, extensive adhesions in the abdominal cavity;
3.perianal or serious intestinal infection;
4, women during pregnancy and menstruation.
The endoscopy report must include: depth of entry, size of the mass, location from the anal verge, morphology, extent of local infiltration, and for suspicious lesions, pathological biopsy must be performed.
Pathological biopsy must be performed.
Since the colon canal may be crinkled during the examination, there may be errors in the distance of the distal side of the mass from the anal verge as seen by endoscopy.
CT, MRI or barium enema are recommended to clarify the location of the lesion.
(vi) Imaging examination.
1.Colon barium enema examination, especially air-barium double contrast examination is an important means to diagnose colorectal cancer. However, patients suspected to have intestinal obstruction should
be selected with caution.
2.B-type ultrasound: abdominal ultrasound examination can understand whether the patient has recurrence and metastasis and has the advantage of convenience and speed.
3.CT examination: The function of CT examination is to clarify the depth of lesion invasion into the intestinal wall, the extent of extra-mural spread and the site of distant metastasis. At present, the
CT examination of colorectal cancer is recommended for the following aspects.
(1) To provide the staging of colorectal malignancies;
(2) To detect recurrent tumors;
(3) To evaluate the response of the tumor to various treatments;
(4) To elucidate the internal structure and clarify the nature of intrinsic and extrinsic compressive lesions in the intestinal wall found by barium enema or endoscopy;
(5) To evaluate the intra-abdominal masses found by barium enema and clarify the origin of the masses and their relationship with the surrounding organs.
(6) It can determine the location of the tumor.
4.MRI examination: The indications of MRI examination are the same as CT examination. MRI is recommended as a routine examination item for rectal cancer: (1) preoperative staging of rectal cancer;
(2) evaluation of liver metastases of colorectal cancer; (3) suspicion of peritoneal and subperitoneal lesions.
5.Transrectal endoluminal ultrasound: endoluminal ultrasound or endoscopic ultrasound is recommended as a routine examination for the diagnosis and staging of low and middle rectal cancer.
6.PET-CT: It is not recommended for routine use, but can be used as an effective adjuvant examination for patients with complicated conditions and cannot be diagnosed clearly by routine examination.
Preoperative examination suggests stage III or above tumor, and it is recommended for understanding whether there is distant metastasis.
7. Excretory urography: It is not recommended for routine preoperative examination, and is only applicable to patients with large tumors that may invade the urinary tract.
(G) Pathological histological examination.
Pathological biopsy to clarify the nature of occupancy is the basis of colorectal cancer treatment. Cases diagnosed by biopsy as invasive carcinoma undergo standardized colorectal cancer treatment. If
Due to the limitation of biopsy sampling, biopsy pathology cannot determine the depth of infiltration, and cases diagnosed as high-grade intraepithelial neoplasia, clinicians are recommended to integrate other clinical conditions including the presence of cholangiocarcinoma.
If the biopsy pathology cannot determine the depth of infiltration and the diagnosis of high-grade intraepithelial neoplasia, clinicians are advised to determine the treatment plan by combining other clinical conditions, including the presence of vascular cancer emboli and lymphocytic reaction around the cancer. When recurrent or metastatic colorectal cancer is identified, it is recommended to test the tumor tissue for the Ras gene and its gene.
The Ras gene and other related genetic status of the tumor tissue are recommended to guide further treatment.
(viii) Open or laparoscopic exploratory surgery.
Open or laparoscopic exploration is recommended in the following cases.
1. Colorectal tumor is not clearly diagnosed by various diagnostic means and is highly suspected.
2.Intestinal obstruction occurs and conservative treatment is ineffective.
3.Suspected intestinal perforation.
4.Lower gastrointestinal hemorrhage for which conservative treatment is ineffective.
(ix) Diagnostic steps of colorectal cancer.
The steps of colorectal cancer diagnosis are shown in Figure 1. cTNM staging is recommended after diagnosis.
(J) Differential diagnosis of colorectal cancer.
1. Colon cancer is mainly differentiated from the following diseases.
(1) inflammatory bowel disease. This disease can appear diarrhea, mucus stool, pus and blood stool, increased number of stools, abdominal distension, abdominal pain, emaciation, anemia and other symptoms.
The symptoms are similar to those of colon cancer, and colonoscopy and biopsy are effective methods of differentiation.
(2) Appendicitis. Ileocecal cancer may be misdiagnosed as appendicitis due to local pain and pressure. Especially in advanced stage, local necrotic ulceration and infection often occur.
The clinical manifestations include elevated body temperature, increased white blood cell count, local pressure pain or palpable mass, which is often diagnosed as appendiceal abscess and needs to be differentiated.
(3) Intestinal tuberculosis. It is more common in China, and the common sites are in the terminal ileum, cecum and ascending colon. Common symptoms include abdominal pain, diarrhea and constipation alternately.
Some patients may have low fever, anemia, wasting, weakness and abdominal masses, which are similar to those of colon cancer. However, systemic symptoms are more obvious in patients with intestinal tuberculosis.
However, the systemic symptoms of intestinal tuberculosis patients are more obvious, such as afternoon low fever or irregular fever, night sweats, wasting and weakness, which need to be distinguished.
(4) Colon polyps. The main symptom can be blood in the stool, and some patients can also have pus-like stool, similar to colon cancer, barium enema examination can be shown as
The filling defect, colonoscopy and biopsy is an effective way to differentiate.
(5) Schistosomal granuloma. In a few cases, it can become cancerous. Combining history of schistosome infection, examination of eggs in stool, barium enema and fiberoptic colonoscopy and biopsy can help identify schistosomal granulomas.
Colonoscopy and biopsy can help to identify.
(6) Amoebic granuloma. There may be symptoms of intestinal obstruction or abdominal masses similar to colon cancer. Amoebic granuloma can be found in patients with this disease during fecal examination.
Amoebic trophozoites and cysts can be found during stool examination, and barium enema examination often reveals a large unilateral defect or circular cut.
(7) Lymphoma. Lymphoma occurs in the terminal ileum, cecum and ascending colon, but also in the descending colon and rectum. Lymphoma is similar to colon cancer in terms of history and clinical
Lymphoma is similar to colon cancer in terms of history and clinical manifestations, but bleeding is less common because the mucosa is relatively intact. The differential diagnosis mainly relies on biopsy under colonoscopy to clarify the diagnosis.
In addition to the above diseases, rectal cancer should also be differentiated from the following diseases.
(1) Hemorrhoids. Hemorrhoids are usually painless blood in stool, and the blood is bright red and does not mix with stool, while rectal cancer blood in stool is often accompanied by mucus and appears as mucus blood stool and rectal irritation.
The symptoms of rectal irritation are often accompanied by mucus. Patients with blood in the stool must be routinely examined by rectal finger.
(2) Anal fistula. Anal fistulas are often caused by perianal abscesses due to sinusitis. Patients with a history of perianal abscess, local redness and pain, and rectal cancer symptoms differ significantly, so it is easy to differentiate.
The difference between the symptoms and those of rectal cancer is relatively obvious and easy to distinguish.
(3) Amoebic enteritis. The symptoms are abdominal pain and diarrhea, and the lesion involving the rectum may be accompanied by shortness of breath. The stool is dark red or purplish blood and mucus.
Enteritis can cause proliferation of granulation and fibrous tissue, thickening of the intestinal wall and narrowing of the intestinal lumen, which can be easily misdiagnosed as rectal cancer, and fiberoptic colonoscopy and biopsy are effective means of differentiation.
Fibroscopy and biopsy are effective means of differentiation.
(4) Rectal polyps. The main symptom is blood in the stool, colonoscopy and biopsy are effective means of differentiation.
Pathological evaluation
(a) Specimen fixation standards.
1.Fixing solution: 10% is recommended. Neutral buffered formalin fixative, avoid the use of fixative containing heavy metals.
2, the amount of fixative: must. ≥. 5-10 times the volume of the fixed specimen.
3, fixation temperature: normal room temperature.
4, fixation time: specimens should be dissected and fixed as soon as possible, and the time between dissection and start of fixation should not exceed 30 minutes. It is recommended that the specimen be dissected by the pathologist.
Specimen dissection is recommended.
Endoscopic resection of adenoma or biopsy specimens: ≥ 6 hours, ≤ 48 hours.
Surgical specimens: ≥ 12 hours, ≤ 48 hours.
(B) sampling requirements.
1. Biopsy specimens.
(1) Check the number of clinical specimens sent for examination, and all biopsy specimens sent for examination must be taken.
(2) Wrap the specimen in gauze or soft permeable paper to avoid loss.
(3) Include no more than 5 biopsy specimens in each wax block and adjust appropriately according to tissue size.
2. Endoscopically resected adenoma specimens.
(1) It is recommended that specimens sent for examination be fixed by the surgeon with ink marking the cut edge of the tip and then spreading the nail plate and placing it in fixative solution.
(2) It is recommended to record the size of the tumor and the distance of each orientation from the incision margin.
(3) The sampling of polypectomy specimens: First, the cut edge of the polyp, the presence or absence of the tip and the diameter of the tip should be clarified. The polyps are divided into non-tip (Is) and subtip (Isp)
The polyps are divided into non-tip (Is) and subtip (Isp) types, and the sampling should be done in a way that the tip margin can be evaluated objectively and correctly.
It is recommended to take the specimen in the following way: when the diameter of the tibial margin is > 2 mm, the specimen is cut perpendicular to the horizontal plane of the tibial margin at a distance of about 1 mm from the center of the tibial margin.
When the diameter of the tibial margin is >2 mm, the specimen should be cut vertically in the horizontal plane of the tibial margin at a distance of about 1 mm from the center of the tibial margin, and then all the specimens should be taken at 2-3 mm intervals parallel to this cut.
If the diameter of the tip cut edge is ≤ 2 mm, the complete cross section should be cut horizontally along the tip cut edge, and then all specimens should be taken at 2-3 mm intervals perpendicular to the horizontal plane of the tip cut edge. It is recommended that all specimens be taken in the same embedding direction.
It is recommended that all specimens be taken in the same embedding direction. The orientation of the tissue block is recorded.
3. Surgical specimens.
(1) Intestinal wall and tumor.
①. Describe and record the general type of tumor. Cut the tumor specimen along the long axis of the intestinal wall and perpendicular to the intestinal wall.
The deepest tumor infiltration should be at least 1 full thickness of tumor and intestinal wall tissue to determine the deepest level of tumor invasion.
The deepest tumor infiltration should be at least 1 full thickness of tumor and intestinal wall tissue to determine the deepest level of tumor invasion. The tissue that can show the relationship between the tumor and the adjacent mucosa should be excised.
②. Excision of the distal and proximal surgical margins. It is recommended to excise the tethered/peri-annular margins, and in cases of suspected positive tethered/peri-annular margins, it is recommended to excise the tumor in accordance with the portion marked in ink by the surgeon.
In cases of suspected positive tethered/peri-annular margins, it is recommended to cut the portion marked by the surgeon in ink. It is recommended that the different margins be marked separately as much as possible.
③. The distance of the tumor from the distal and proximal margins should be recorded.
④. If the intestinal specimen contains the ileocecal region or the anal canal or anus, it should be taken from the ileocecal flap, the dentate line, the anal verge, and the appendix.
If the tumor involves the above-mentioned areas, a tissue block should be cut to adequately show the extent of the lesion.
⑤. The pathologist is recommended to systematically examine the surgical specimens, including the integrity of the mesentery and the circumferential margin.
This is an important index to evaluate the quality of total rectal mesenteric resection.
(2) Lymph nodes.
It is recommended that surgeons send lymph nodes for examination in groups according to local anatomical signs and intraoperative observations, which is beneficial to the localization of the lymph node drainage area.
The pathologist detects lymph nodes in the specimen in accordance with the following principles in the absence of medical advice or markings from the surgeon grouping the lymph nodes for examination.
All lymph nodes should be sampled (a minimum of 12 lymph nodes is recommended. Patients who have received preoperative treatment may have fewer than 12 lymph nodes). All
Lymph nodes that are negative to the naked eye should be sent intact, and lymph nodes that are positive to the naked eye may be partially excised and sent for examination.
(3) Recommended volume of the tissue block: no larger than 2×1.5×0.3 cm.
(3) The principles of specimen handling and preservation time frame after sampling.
1. Preservation of the remaining specimens. The remaining tissues were preserved in the standard fixative and always maintained adequate amount of fixative and formaldehyde concentration to avoid
Specimens dried out or tissue decay due to insufficient amount or concentration of fixative; to be ready for supplemental sampling according to the diagnostic needs of microscopic observation; or to be ready for the
The pathological diagnosis report is issued after the receipt of clinical feedback to review the bulk of the specimen or additional sampling.
2. Time limit for processing of remaining specimens. It is recommended that after 2 weeks of issuance of the diagnostic pathology report, no clinical feedback is received, and no review is requested due to disagreement of external consultation.
After the request for review due to differences in opinion of outside hospitals, the hospital can deal with it by itself.
(IV) Pathological types.
1. Early colorectal cancer.
Cancer cells penetrating through the mucosal layer of colorectum and infiltrating into the submucosa, but not involving the intrinsic muscle layer, regardless of whether there is lymph node metastasis, is called early colorectal
cancer (pT1). If the epithelium is heavily heterogeneous and the depth of infiltration cannot be judged, it is called high-grade intraepithelial neoplasia, and if the cancer tissue infiltrates the lamina propria, it is called intra-mucosal cancer.
intra-mucosal carcinoma.
It is recommended to measure and grade the depth of submucosal infiltration in early colorectal cancer, i.e. SM1 (submucosal infiltration depth ≤ 1 mm) and
SM2 (depth of submucosal infiltration > 1mm).
2. Broad types of progressive colorectal cancer.
(1) Augmentation type. Any tumor whose main body protrudes into the intestinal lumen belongs to this type.
(2) Ulcerated type. Any tumor that forms ulcers deep into or through the muscle layer belongs to this type.
(3) Infiltrative type. The tumor infiltrates diffusely into all layers of the intestinal wall, thickening the local intestinal wall, but there is often no obvious ulcer or bulge on the surface.
3. Histological types
(1) Adenocarcinoma;
(2) Mucinous adenocarcinoma;
(3) Indolent cell carcinoma;
(4) Squamous carcinoma;
(5) Adenosquamous carcinoma;
(6) Medullary carcinoma;
(7) Undifferentiated carcinoma;
(8) Other;
(9) Carcinoma, the type of which could not be determined.
4. Histological grading.
The histological grading criteria of colorectal cancer are shown in Table 1.
Table 1. Histological grading criteria of colorectal cancer (based on WHO 2010)
Criteria Degree of differentiation Digital grading a Descriptive grading
>95% Glandular duct formation Highly differentiated 1 Low grade
5.%-95% Glandular duct formation Intermediate differentiation 2 Low grade
0.49% glandular duct formation low differentiation 3 high level
High level of microsatellite instability b unequal unequal low level
Note: a,. Undifferentiated carcinoma (grade 4)… This category refers to the absence of glandular duct formation, mucus production, neuroendocrine, squamous or sarcomatoid differentiation; b,.
MSI-H.
* The above grading criteria are for adenocarcinoma.
(E) Content of pathology report.
1 Pathology report contents and requirements for biopsy specimens.
(1) Basic information of the patient and the information of the sending examination.
(2) If there is intraepithelial neoplasia (heterogeneous hyperplasia), report the grading.
(3) In case of invasive carcinoma, distinguish the histological type.
(4) When colorectal cancer is identified, testing for mismatch repair (MMR) proteins (MLH1, MSH2, MSH6,.PMS2) and Ki-67 is recommended.
expression.
Clinicians should be aware that biopsy pathology cannot fully determine the depth of infiltration due to biopsy depth limitations, so tumor tissue may be confined to the mucosa.
The clinician should be aware that the biopsy pathology cannot fully determine the depth of infiltration due to the depth of biopsy, so the tumor may be a high-grade intraepithelial neoplasia or intramucosal carcinoma limited to the mucosa.
2. Content and requirements of pathology report of endoscopically resected adenoma specimens.
(1) Basic information of the patient and the information of the sending examination.
(2) Size of the tumor.
(3) Grading of intraepithelial neoplasia (heterogeneous hyperplasia).
(4) In case of infiltrative carcinoma, report the histological staging, grading, depth of infiltration, cutting edge condition, vascular invasion, and mismatch repair of cancer tissue
(4) In case of invasive carcinoma, the histological staging, grading, depth of infiltration, cutting edge, vascular invasion, mismatch repair (MMR) protein (MLH1, MSH2, MSH6,.PMS2) expression were reported.
Positive pT1, grade 3 and 4 differentiation, vascular invasion, and incisional margins should be followed by surgical expansion of the resection. In other cases, enteroscopic resection
is sufficient, but regular postoperative follow-up is required.
(1) Histologic features with a good prognosis include: grade 1 or 2 differentiation, no vascular or lymphovascular infiltration, and “negative cut margins”.
(ii) Histological features with poor prognosis include: grade 3 or 4 differentiation, vascular and lymphatic infiltration, and “positive cut margins”.
③ Positive cut margin is defined as: tumor less than 1mm from the cut margin or cancer cells visible at the cut margin of the electric knife.
3. Contents and requirements of pathological report of surgical specimen.
(1) Basic information of the patient and the information of the examination.
(2) General conditions: tumor size, general type, depth of infiltration seen by naked eye, length of resected intestinal canal at both ends from the distal and proximal ends of the tumor.
(3)Tumor differentiation degree ( tumor staging, grading ).
(4) Depth of tumor infiltration (T staging) (T staging or ypT is determined based on viable tumor cells, and specimens treated with neoadjuvant therapy within
The cell-free mucus lake is not considered as tumor residual ).
(5) The number of lymph nodes detected and the number of positive lymph nodes (N staging); and extra-lymph node tumor implantation (ENTD, Extra.Nodal.
Tumor.Deposit), which refers to an irregular tumor solid nodule deposited in the peri-colorectal fatty tissue away from the primary tumor margin without residual
lymph node histological evidence, but distributed on the lymphatic drainage pathway of the tumor.
(6) The status of the proximal and distal cutaneous margins.
(7) It is recommended to report the status of the tethered/peri-annular margins (if the tumor is in close proximity to the margins, the distance between the tumor and the margins should be measured and reported microscopically.
If the tumor is close to the margin, the distance between the tumor and the margin should be measured and reported under the microscope, and a positive margin should be reported within 1 mm from the margin.)
(8) Assessment of the efficacy of neoadjuvant radiotherapy (or, and) chemotherapy
1.Complete response No tumor residue
2.Moderate response Few tumor residues
3.Low response Most tumor residue
4.No response
(9) Vascular invasion ( V for vascular, V1 for microscopic vascular infiltration, V2 for visual vascular infiltration, L for lymphatic vessels). It is recommended that as much as possible
It is recommended to differentiate between vascular and lymphatic infiltrations as much as possible.
(10) Nerve invasion.
(11) Expression of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6,.PMS2). It is recommended to selectively detect the mismatch repair protein’s
gene status and methylation status.
(12) For recurrent or metastatic colorectal cancer, K-ras, N-ras, and BRAF gene status are recommended. If no surgical resection specimen is available
can be determined from biopsy specimens.
The prerequisite for a complete pathology report is that the clinician completes a detailed pathology request form, describing in detail the surgical findings and relevant clinical ancillary findings and clearly labeling the lymph nodes.
The lymph nodes are clearly marked. Mutual communication, trust and cooperation between clinicians and pathologists are the basis for establishing correct staging and guiding clinical treatment.