The conception of MPCC is reported by Warren S research in 1941, and studies have shown that the incidence of it is rare . Now, we are does a miniature literature review of SC’s clinical features, diagnosis, treatment, prognosis, pathology and pathogenic mechanism.
The manifestations of SC were similar to the isolated colorectal cancer. There are not obvious symptoms in the early stage . However, there will be a lot of symptoms when cancer ruptures to form ulcers, infection or tumor obstruction. Firstly, the most important is rectal stimulation symptoms, which includes frequent bowel movements, changes in bowel habits, anus drop feeling, tenesmus and lower abdominal pain in tumor advanced-stage. Secondly, the symptom of intestinal lumen stenosis is very common. The tumor growing, infiltrate intestinal wall muscle layer and tumor ulceration lead to intestinal stenosis, which causes stool deformation, thinner. Next, patient will have symptoms of incomplete intestinal obstruction that includes abdominal pain, abdominal distension, hyperactive bowel sounds and so on when partial intestinal obstruction occurs. Next, there are symptoms of cancer infection, which mainly for stool surface with blood and mucus, even pus and blood stool. What’s more, tumor invades prostate and bladder, which causes symptoms of urinary frequency, odynuria, hematuria. Severe and persistent sacrococcygeal pain occurred when the anterior sacral nerve was invaded . There are corresponding clinical manifestations when liver, lung and bone have metastases. Finally, in addition to the clinical manifestations of the first primary cancer, the clinical symptoms of the second primary colorectal cancer mainly include change of stool habits, abdominal pain, anemia, bleeding (from anus or ostomy), ileus, and abdominal mass [6, 7].
Some studies suggested that compared with isolated colorectal cancer, SC usually has a low stage (I or II) and a low grade, and synchronous colorectal cancer has some different clinical characteristics . At first, it has a lower incidence. Some research has shown that the incidence of synchronous colorectal cancer is between 1.1% and 8.1% of colorectal cancer . Secondly, many studies have indicated that SC are significant gender differences. Men are more likely to have SC than women . Next, compared with isolated colorectal cancer, there was no significant difference in the age group of SC . What’s more, several studies have reported that the most common sites of SC are sigmoid colon and rectum , but other research have reported that it is more likely to occur in the proximal colon, especially in the ascending colon . Many studies have found that it tends to occur in the same or similar areas of the large intestine, but a large proportion of concurrent tumors occur in different areas of the large intestine . From these clinical feature we concluded that colonoscopy is very important for the diagnosis of colorectal cancer.
The standard of diagnosis for synchronous multiple primary carcinoma were proposed by Moertel. There are follow six requirements for diagnose it. (1). each tumor was pathologically confirmed as carcinoma. (2). It must be ruled out as the spread or metastasis of another cancer. (3). All tumors diagnosed at the same time or within 6 months are synchronous cracinoma (SC); if the tumor is diagnosed more than 6 months after the first tumor is found which defined as metachronous carcinoma (MC). (4). At the same time, two tumors must not be located in the same or adjacent intestinal segment. If they are located in the same intestinal segment, must be diagnosed with different pathologic types of tumors or between the normal bowel segments. (5). Metachronous tumor must be at least 5cm away from the anastomosis after resection of the first tumor, and the anastomosis should be normal. (6). Patients with ulcerative colitis or familial adenomatosis should be excluded . The following points should be noted in MPCC diagnosis and treatment. (1). Preoperative examination of colorectal cancer should examine the whole large intestine to avoid the omission of the SC. Some studies reported that the detection rate of barium perfusion in MPCC was 50% and that in colonoscopy was only 76.7% . This is due to a tumor of a certain size can cause intestinal cavity narrow. Therefore, barium meal and colonoscopy are difficult to enter, generally can only find the most distant cancer foci, proximal cancer foci difficult to find. (2). Regular colonoscopy should be performed after post-operation, especially appear diarrhea, abdominal distension, abdominal pain and bloody stool, in order to detect tumor recurrence or MPCC and Early treatment. (3). No matter SC or MC, or how many tumor foci there are, tumor growth is slow and metastases late. The prognosis is good, if early detection, diagnosis and treatment.
Surgery is considered to be the best treatment for MPCC. The choice of surgical method should be based on the location, spacing, range of the tumor and the patient's age, basic condition and other comprehensive considerations. At present, there are two kinds of surgical methods for SC: One is total colectomy, the other is radical resection of colon by segmental resection. There are four main types of extensive total colectomy. Firstly, total colectomy and permanent ileostomy, which has advantage of permanently avoiding postoperative colonic recurrence. However, it has many disadvantages, including poor postoperative intestinal function and complications, such as large trauma, slow postoperative recovery, postoperative diarrhea, electrolyte disorders, and low quality of life. Studies have shown that the surgical method apply to this cases that rectal cancer with low rectal carcinoma or ileorectal anastomosis after total colectomy. Secondly, total colon resection and rectal ileostomy. Many studies indicated that it applied for patient that has multiple tumor lesions in the colon but no lesions in the rectum. However, the disadvantage is that the retained rectum still has the possibility of tumor recurrence. Thirdly, subtotal resection of colon and anastomosis of ascending colon and rectum. The advantages of this operation are simple, safe and less complications, and it is beneficial to postoperative colonoscopy examination. What is more, the patient had good defecation function after operation. However, the disadvantage is that the number of times for defecation increased, and the retention of the rectum still has the possibility tumor recurrence. Finally, the method is total colectomy combination with rectal mucosal exfoliation combination with ileum bag anal anastomosis, which removes the entire large intestine mucosa, preventing mucosa canceration while preserving the sphincter muscle function that controls defecation. However, the operation is difficult, low penetration rate, high incidence of complications, especially anastomotic fistula, pelvic infection, and poor postoperative intestinal function. Radical resection of colon is a combination of partial resection of colon [15, 16, 17]. There are four surgical methods of partial colon resection: (1) Right half colon resection; (2) Left semicolon resection; (3) Sigmoidectomy; (4) Complete rectal resection. These surgical methods can not only ensure the complete excision of the lesion, but also retain the function of the colon to the greatest extent, which with less complication and improves the quality of life [18, 19, 20]. Nevertheless, if we find lymph node or adjacent viscera metastasis during the operation, simultaneous lymph node dissection or resection of the metastases is necessary. At present, however, there is a little research on this field and lack of long-term postoperative follow-up data. As for the surgical treatment of MC, some studies suggest that the resection scope should be expand, especially for patients with positive family history of colorectal cancer and those with more than three tumor foci, especially hereditary non-polyposis colorectal cancer (HNPCC) patients should undergo subtotal colectomy . Other research suggested that heterochronous segmental resection of colon, radical resection of colorectal cancer performed for each tumor foci and we should strengthen postoperative follow-up and radical resection should be performed when we found out that recurrence of the disease, should be performed for patient with MC . Postoperative chemotherapy for MPCC includes mFOLFOX6, FOLFIRI, CapeOX, single capecitabine . However, there is no evidence that postoperative chemotherapy can prolong its recurrence time and life.
The follow-up methods included colonoscopy, rectal examination and finger examination of ostomy, fecal occult blood, serum carcinoembryonic, CT, MRI and other imaging examinations1. However, it should be noted that the diagnosis of recurrence and MPCC at the same time, and must attention to the extra-intestinal multiple primary cancer. Many studies have shown that the prognosis of SC is better than that of isolated colorectal cancer . However, Oya et al reported that there was no difference between the prognosis of SC and that of single carcinoma . Wang et al indicated that the second primary cancer was better than the first primary cancer in neoplasm differentiation and staging .
Many studies have shown that the association between SC and adenomas is stronger than that between isolated colorectal carcinoma. There is increasing evidence that serrate adenoma and hyperplastic polyp are closely related to synchronous colorectal cancer . Many studies indicated that patients with serrated polyps are usually BRAF V600E positive and CIMP-H . Other studies have indicated that the incidence of MPCC is higher in patients with ulcerative colitis, and significantly higher than that of crohn's disease . There are two mechanisms of SC: MSI and gene mutation. Compared with isolated colorectal cancer, MSI-H is more significant in MPCC, especially in SSAs-induced MSI-H, and its overall survival (OS) rate is higher . At present, there are two mechanisms lead to MSI-H. The one is mutation of mismatch repair genes. The other is methylation of mismatch repair genes, especially in BRAF-related methylation on MLH1 promoters is closely related to it. Some studies suggest that the SSA-related SC is more likely to occur in older women, and also presents MSI-H and BRAF V600E mutations. But its prognosis is good. Other research suggested that the SSA-related synchronous colorectal cancer always expression loss of MSI-H, MLH1 and PMS2 and co-existence of SSA and BRAF V600E mutations, which usually occur in those patients that over the age of 65 and the tumor involved the right half of the colon [25, 28, 29, 30]. Other studies indicated that in addition to MSI, p-53, K-RAS and GSRM1 mutations are also correlated with it [31, 32, 33]. According to a retrospective case study, mucinous adenocarcinoma is more common in SC than in isolated colorectal cancer . Some studies indicated that tumor stem cell markers CD44 and CD133 mRNA are highly expressed in synchronous colorectal cancer liver metastasis, but the expression of CD44 and CD133 mRNA in SC is rarely reported .