© Springer Science+Business Media Dordrecht and People’s Medical Publishing House 2017Xinyu Qin, Jianmin Xu and Yunshi Zhong (eds.)Multidisciplinary Management of Liver Metastases in Colorectal Cancer10.1007/978-94-017-7755-1_1
1. Present Situation and Prospect of Diagnosis and Treatment of Colorectal Cancer
Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
1.1 Epidemiological Trend of Colorectal Cancer
1.1.1 Distribution Rule of Colorectal Cancer in the World
Colorectal cancer (CRC) is one of the most common malignant tumors. The probability of suffering from colorectal cancer in a person’s life is 6 %. There are about 1.20 million new colorectal cancer cases in the world each year. Nearly 600,000 people die of colorectal cancer each year. Among all malignant tumors, both incidence and mortality of colorectal cancer are in the third position. In recent years, incidence and mortality of colorectal cancer in western-developed countries have decreased a little, whereas incidence of colorectal cancer in developing countries has still showed a rising trend .
1.1.2 Distribution Rule of Colorectal Cancer in China
Among all malignant tumors, incidence and mortality of colorectal cancer are in the third and fifth position, respectively, with a slight difference in different regions. In 2000, there were about 150,000 new colorectal cancer cases in our country, and nearly 80,000 patients died of colorectal cancer, and it showed a rising trend . Over the past 20 years, epidemiological trend of colorectal cancer in our country has changed and showed some new characteristics: (1) Colorectal cancer showed a trend from low to high incidence. As the population base of our country is great, the absolute number of cases suffering from colorectal cancer and cases that die of colorectal cancer have surpassed that in the United States in recent years. (2) Rising trend of incidence of colon cancer is more significant than that of rectal cancer. (3) Low rectal cancer accounts for a high proportion, and early-stage colorectal cancer accounts for a low proportion. (4) Young people (<30 years old) account for a high proportion; average age of rectal cancer cases shows a trend of approaching to the level in developed countries .
1.2 Diagnosis of Colorectal Cancer
1.2.1 Significance of Diagnosis of Early-Stage Colorectal Cancer
Radical surgical resection is the only opportunity to cure colorectal cancer confined in the intestinal wall. Therefore, it has 80 % of the opportunity to cure colorectal cancer still confined in the intestinal wall in definite diagnosis and nearly 90 % of 5-year survival rate after performing radical surgical resection. However, if there is lymph node metastasis, 5-year survival rate will decrease to 60 % or so . In general, earlier stage of colorectal cancer leads to a higher survival rate, and natural prognosis study on colorectal cancer indicates that early discovery is the most important measure to reduce disease-related mortality.
As onset of colorectal cancer is not obvious, clinical manifestation lacks specificity. About 60 % of colorectal cancer cases have had lymph node metastasis or distant metastasis when diagnosed . Therefore, overall prognosis of colorectal cancer is still not optimistic at present. Although pathogeny of colorectal cancer is not clear, there have already been many reports on pathogeny-related risk factors during the course of development in the order of “normal mucosa-adenoma-adenocarcinoma,” which provides the possibility of colorectal cancer screening and early diagnosis.
Zheng Shu et al. carried out colorectal cancer screening by adoption of fecal occult blood test (FOBT) combined with sequential screening scheme. Eight-year follow-up results show that case fatality rate of colorectal cancer of screening group is lower than that of control group by 14.7 %, of which that of rectal cancer is reduced by 31.2 %, which indicates that primary prevention may intervene in and prevent the occurrence of colorectal cancer and secondary prevention can still reduce case fatality rate after occurrence of tumor . Data of US National Polyp Study demonstrate that adenoma canceration rate is directly proportional to age and size of adenoma. Resection of adenoma may significantly reduce incidence rate of colorectal cancer .
The present study indicates that hereditary colorectal cancer accounts for about 20 % of the total colorectal cancer. The most common hereditary colorectal cancer includes familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). The former relates to APC gene mutation, whose manifestation is more than 100 diffuse adenomatous polyps in the large intestine, or there is definite familial history or hyperplasia occurs in congenital retinal pigment epithelium although the number of polyps is less than 100, while the latter relates to mismatch repair gene (hMLH1, hMSH2, hPMS1, hPMS2, etc.) mutation, whose manifestation is familial aggregation, where tumors are mostly located at the right colon, and extra-colorectal tumors frequently occur. Therefore, mutation detection of the abovementioned genes may provide reference for early discovery of hereditary colorectal cancer .
Because of the living standard, hygiene and health consciousness, and technical reasons, even in relatively developed provinces and municipalities in our country, the large-scale survey system including endoscopy for colorectal cancer, as established in European- and American-developed countries, has not been established; early diagnosis rate of colorectal cancer is low in our country. Overall 5-year survival rate is not so satisfactory either. How to establish an effective and convenient survey system to provide intervention and prevention during the course of development in the order of “normal mucosa-adenoma-adenocarcinoma” or realize early diagnosis after tumor is formed, which is a topic that each of us – colorectal surgeons – must consider carefully.
1.2.2 Significance of Digital Rectal Examination in Diagnosis of Colorectal Cancer
Digital rectal examination (DRE), as a simple and important examination method, has great significance in early discovery of anal canal cancer and rectal cancer. As mentioned above, incidence of low rectal cancer is high in our country. About 75 % of rectal cancer may be touched when conducting digital rectal examination. Among the cases where diagnosis of rectal cancer is delayed, about 85 % do not receive digital rectal examination. In addition, DRE may help judge the site and size of rectal tumor and its relation with adjacent tissues, such as prostate, vagina, etc., and if there is pelvic-planted metastatic node of colon cancer, etc., and provide reference for making clinical decisions. Therefore, digital rectal examination has important significance in the diagnosis and treatment of rectal cancer. If a patient has symptoms such as there is blood in his stool or his defecation habit changes or his stool deforms, conventional digital rectal examination should be conducted.
1.2.3 Significance of Endoscopy in Diagnosis of Colorectal Cancer
Endoscopy includes proctoscopy, sigmoidoscopy, and colonoscopy. At present digital rectal examination and colon fiberscopy are the basic means to examine colorectal cancer. Electronic colon fiberscopy is widely used in clinical applications. Endoscopy can examine the total colon, can even examine the pathological changes in the terminal ileum, and may obtain pathological biopsy simultaneously to define the nature of pathological changes. What should be stressed is that when a great colorectal tumor is discovered by colonoscopy, making the intestinal cavity become too narrow to allow the colonoscope body to pass, endoscopy has been unable to examine the total large intestine mucosa before operation. So the intestinal canal that has been examined by preoperative colonoscope should be examined more carefully during operation. When necessary, intraoperative colonoscope may be used for further examination to avoid omission of missed diagnosis of simultaneous multiple primary carcinoma or other adenomas.
It is indubitable that endoscopy is sensitive to the diagnosis of colorectal cancer, whereas such examination method still has some limitation. For example, examination results are affected by examinator’s operation level. Study shows that about 13 % of 5–9 mm adenomas and 27 % of less than 5 mm adenomas are missed in diagnosis. Even if the size of tumor mass is greater than 1 cm, the rate of missed diagnosis still reaches nearly 6 % . In addition, such examination may be affected by the blind spot of the endoscope and has such risks as perforation, bleeding, or even death. Despite this, no other examination method can replace the important role of endoscopy in the diagnosis of colorectal cancer at present.
1.2.4 Other Diagnostic Examination
18.104.22.168 Fecal Occult Blood Test
Since Greegor took fecal occult blood test (FOBT) as screening method in 1967, FOBT has still been the main screening method except digital rectal examination and endoscopy up till now. Results of a study that involves 300,000 objects and follows up them more than 18 years show that sequential FOBT may reduce mortality by 13–33 % . However, as colorectal cancer often does not cause bleeding at early stage, sensitivity of FOBT examination of colorectal cancer is only 27–57 %, and that of adenoma is only 8 % . Food containing peroxide may cause false-positive FOBT result. Therefore, positive FOBT result cannot definitely diagnose colorectal cancer or adenoma. It just indicates the possibility. Further examination and confirmation are needed.
22.214.171.124 Double-Contrast Barium Enema
Double-contrast barium enema (DCBE) is one of the important examination methods for colon cancer, with little significance in the diagnosis of low rectal cancer. As sensitivity and specificity of DCBE on the discovery of colorectal cancer are not as good as endoscopy, and endoscopy may conduct pathological biopsy or excise adenoma simultaneously, clinical application of DCBE becomes less and less. However, reoperative tumor localization of DCBE is better than that of endoscopy.
126.96.36.199 CTC and MRC
Sensitivity and accuracy of computed tomography colonography (CTC) to discover colorectal cancer are almost equivalent to that of traditional colon fiberscopy . So it is also called virtual colonoscopy. In addition, CTC can still examine colorectal cancer infiltration and adjacent tissue involvement to a certain degree, especially whether rectal cancer invades the bladder, uterus, and pelvic wall or not, and at the same time examine whether there is lymph node beside the intestine or not, and whether there is lymph node metastasis beside the abdominal aorta or not, which has important significance in the preoperative staging of colorectal cancer and selection of treatment scheme.
Magnetic resonance colonography (MRC) is superior to CTC in the aspects of judgment of rectum and anal canal cancer infiltration and diffusion range, preoperative staging, identification and diagnosis of postoperative recurrence, etc. Both examination methods are noninvasive, but results are greatly affected by machine, X-ray image-reading level, etc.
188.8.131.52 Endorectal Ultrasound Examination
Endorectal ultrasound (ERUS) examination may clearly display five hierarchies of the intestinal wall, i.e., the mucosa, muscularis mucosa, submucosa, muscularis propria, and serosa, and can provide visual judgment on thickness of each hierarchy and homogeneity of echo. It can provide a general judgment on rectal tumor size, infiltration depth, relation with adjacent tissues, etc., and thereby relatively reliable preoperative staging can be determined. Especially when rectal tumor is small and infiltration depth is T1/T2, ERUS has important reference value for selection of treatment scheme of low rectal cancer.
184.108.40.206 Positron Emission Tomography
Positron emission tomography (PET) relies on high metabolism of tumor cells that is different from normal tissues and makes a judgment on whether there is tumor or not after examination of local metabolism of the human body. It has important reference value especially in judgment if there is postoperative local recurrence or distant metastasis of colorectal cancer and reaction of the human body to chemotherapy drugs. It is a noninvasive examination mean with highest sensitivity and specificity at present, which can discover about 5 mm-size pathological changes.
1.3 Present Situation of Treatment of Colorectal Cancer
1.3.1 Selection of Operation Method
Basic principles of colorectal cancer operation are to (1) pay attention to “no-touch isolation technique,” (2) appropriate intestinal segment resection, and (3) normative lymphadenectomy. As for simultaneous multiple primary carcinoma, surgical resection should be strictly subject to colorectal cancer operation principles, respectively.
220.127.116.11 Operation Method for Colon Cancer
Determination of operation method for colon cancer depends on the site of tumor and its relation with the peripheral organs, including the right colectomy, transverse colectomy, left colectomy, sigmoid colectomy, and related extended resection. If tumor is big, locally invades peripheral organs, such as colon cancer of hepatic flexure invades gallbladder and right kidney, colon cancer of splenic flexure invades spleen and left kidney, transverse colon cancer invades gastric wall, etc, we can conduct the extended radical resection for colon cancer and internal organs. Complete resection will result in good effect.
Surgical treatment for obstructive colon cancer is aimed at eliminating obstruction, excising tumor, and restoring the smoothness of the intestinal canal. As for the right colon cancer obstruction, there is no dispute on performing first-stage resection and anastomosis. As for the left colon cancer obstruction, whether or not to perform first-stage tumor resection or first-stage anastomosis should depend on systematic status of patient, local infiltration of tumor, and surgeon’s technical level. Because of the popularization and application of intraoperative intestinal tract lavage, the progress of nutritional support treatment, and the development of surgical ICU in recent years, more and more scholars prefer to first-stage resection and anastomosis for obstructive left colon cancer patients in feasible conditions.
18.104.22.168 Operation Method for Rectal Cancer
In recent years, discussion on operation method for rectal cancer focuses on how to make patients obtain the highest living quality in the condition of ensuring radical treatment of tumor. Radical treatment of tumor must ensure complete resection of tumor, low local recurrence rate, and long survival time. Improvement of quality is mainly reflected by anal preservation rate, postoperative defecation function, sexual function, etc. Therefore, a great deal of clinical study concentrates on the comparison of advantages and disadvantages between low anterior resection (LAR) and abdominoperineal resection (APR) or discussion on the safety of local resection for rectal cancer.
The study on biological behaviors of low rectal cancer infiltration and metastasis indicates that appropriate distance between the remote resection margin of low rectal cancer and the tumor is 2 cm. This concept causes LAR operation to be widely generalized. Combined with total mesorectal excision (TME), it has preserved most patients’ anuses, while those patients had to receive APR operation in the past. There is no significant difference in operative complications, recurrence rate, and survival rate of both operation methods, but living quality of the patients that receive LAR operation is obviously better.
Sexual dysfunction is a common postoperative complication of rectal cancer. Along with the increase in young rectal cancer patients and extension of survival time, their requirement for living quality is also gradually improved. Sexual dysfunction increasingly attracts attention from rectal cancer patients. Pelvic autonomic nerve preservation (PANP) is an operation method that identifies and preserves the pelvic autonomic nerve on the premise of ensuring radical treatment of tumor. PANP plays a significant role in the prevention from postoperative sexual desire disorder of rectal cancer, erectile dysfunction, ejaculation dysfunction, urinary dysfunction, and vagina ache. The author’s unit compared male patients’ erectile function, ejaculation function, local recurrence rate, and 5-year survival rate between 105 cases that received PANP operation and 110 cases that received no PANP. It discovered that incidence rate of sexual dysfunction among patients that received PANP radical resection of rectal cancer is about 30 %, equivalent to that of patients that received sigmoid colectomy, but obviously lower than that of patients that received conventional Miles – 43–67 %; PANP also plays a significant role in protecting postoperative sexual function of female patients, whereas the effect is not significant in posterior pelvis dissection [12–15].
The key to PANP operation is to get familiar with anatomical characteristics of the pelvic autonomic nerve and lymphatic metastasis rule of each segment of rectal cancer, pay attention to the sense of anatomical hierarchy during operation, and fully expose operative field when conducting operation below the peritoneal reflection. Serious damage to the autonomic nerve is likely to occur at the following sites: (1) the left trunk of the abdominal aortic plexus when cutting the inferior mesenteric vessel, (2) the superior hypogastric plexus and hypogastric nerve in posterior rectal separation, (3) the inferior hypogastric plexus and pelvic autonomic nerve in lateral separation of the rectum, and (4) the erectile nerve in anterior hepatic separation . PANP operation requires the surgeon to have a rich operative experience and anatomical knowledge. In our country, such kind of operations is mainly limited to a few large hospitals, which needs further generalization.
There are more and more study reports related to local resection of rectal cancer. Theoretical basis of such kind of operation is that when pathological change is limited in the mucosa and not beyond the muscularis mucosa, there is almost no lymph node metastasis risk; but when pathological change invades the submucosa, the probability of occurrence of lymph node metastasis is nearly 5 %. So when pathological change is limited in the mucosa or muscularis mucosa, radical treatment can be achieved just by resecting the site of pathological change instead of local lymphadenectomy. After local resection, patients are subject to the risk of postoperative local recurrence and metastasis. So indication of local resection of rectal cancer should be strictly controlled, and overall consideration should be made according to preoperative staging, pathological situation, and systemic status. A scholar had once reported that when pathological change is limited at T1, there is no significant difference in recurrence rate and 5-year survival rate between local resection and traditional APR results [17–19]. Although these study results are encouraging, when pathological change is limited at T2, whether or not local resection is suitable and whether or not auxiliary chemoradiotherapy is needed after local resection operation are the topics not solved yet. Along with in-depth screening work for high-risk population of colorectal cancer, undoubtedly more and more early-stage colorectal cancer will be discovered. As one of the important operation methods, more and more attention will be paid to rectal cancer local resection and it will be more and more widely used. Its safety and effectiveness urgently need demonstration through large-scale multicenter randomized clinical research.
1.3.2 Significance of Total Mesorectal Excision in Rectal Cancer Treatment
22.214.171.124 Definition of Total Mesorectal Excision
Total mesorectal excision (TME) is to conduct sharp separation in the clearance between the visceral pelvic fascia and parietal pelvic fascia of the anterior sacral under direct view during the radical resection of middle and lower-segment rectal cancer so as to completely resect the visceral pelvic fascia as well as fat, connective tissue, blood vessel, and lymphoid tissue at the back side of the rectum that it wraps, making resected part of the mesorectum at the far end of the tumor not less than 5 cm and distance from the intestinal canal resected to lower edge of the tumor not less than 2 cm.
126.96.36.199 Significance of Total Mesorectal Excision
The TME principle, proposed by Heald in 1982, is one of the basic principles that should be observed in the operation of middle and low rectal cancer at present. It has great significance in reducing postoperative local recurrence rate of rectal cancer and improving anal preservation rate. TME places emphasis on sharp separation between the visceral pelvic fascia and parietal pelvic fascia, completeness of the visceral pelvic fascia, avoidance of residual tumor in the mesorectum, and reduction of postoperative local recurrence rate. In 1995, McCall et al. analyzed over 10,000 colorectal cancer cases. Data showed that overall local recurrence rate was 18 %, of which 1033 cases received TME operation; recurrence rate was only 7 % . In 1998, Kockerling et al. also reported 1581 colorectal cancer cases, of which local recurrence rate of rectal cancer of the cases that received no TME was 39 %, while local recurrence rate of the cases that received TME operation was only 10 % . In the past, it was thought that the intestinal canal resected should be 5 cm from lower edge of tumor. But on the premise of TME, a distance of 2 cm has been enough from resection margin at remote end to lower edge of tumor, which makes about 77 % patients obtain radical treatment and preserve their anuses . Furthermore, TME places emphasis on separation between two pelvic fascias under the direct view and realizes PANP operation. It plays an important role in prevention from postoperative micturition dysfunction and sexual dysfunction of rectal cancer patients .
But a report showed that compared with the previous operations, TME would increase operation time, intraoperative bleeding amount, incidence rate of anastomotic leakage, and hospitalization time [23, 24]. These are closely associated with surgeon’s operating level. A study showed that TME operation carried out by specialist physicians of colorectal cancer can not only shorten operation time, reduce bleeding amount, and reduce operative complications, but also significantly decrease local recurrence rate and increase 5-year survival rate [21, 25–27]. Many European and American countries have realized this problem and implemented colorectal specialist physicians training system. But in our country, there is no standardized training and access system for colorectal specialist physicians.
1.3.3 Dispute on Lateral Pelvic Lymphadenectomy for Rectal Cancer
Eastern and western scholars always have dispute on whether or not conventional lateral pelvic lymphadenectomy (LPLD) should be performed for rectal cancer. Most Japanese scholars believe that lateral lymph node metastasis rate is between 14 and 29 %. Lateral lymphadenectomy may result in reduction of postoperative local recurrence rate by nearly 50 % and increase in 5-year survival rate by about 10 %. Therefore, conventional lateral pelvic lymphadenectomy is recommended. Japanese scholars proposed extended radical resection for rectal cancer by dissection of Clearance A, B, and C of the peripheral connective tissues of the rectum, of which A is the tissue resected by the aforesaid TME, B is the inside dissection of the internal iliac artery of the lateral lymph node, and C is the outside dissection of the internal iliac artery of the lateral lymph node, including obturator lymphadenectomy. Takahashi analyzed 764 rectal cancer cases that received the abovementioned three-clearance dissection, of which lateral lymph node metastasis occurred in 66 cases; cases with lateral lymph node metastasis account for 8.6 % of all rectal cancer cases and account for 16.4 % of low rectal cancer cases (less than 5 cm above dentate line). Therefore, the author’s opinion is that rectal cancer patients should receive extended dissection . Domestic study carried out by Dong Xinshu et al. showed that among 782 cases of rectal cancer patients, lateral lymph node metastasis occurred in 64 cases; cases with lateral lymph node metastasis account for 8.2 % of all rectal cancer cases, of which lateral lymph node metastasis rate of rectal cancer below the peritoneal reflection is 12.5 %, while lateral lymph node metastasis rate of rectal cancer above the peritoneal reflection is 1.3 %. Based on this, the author thinks that upper metastasis and lateral metastasis are different paths. As for the rectal cancer below the peritoneal reflection, conventional lymphadenectomy should be performed . But Grinnell in the United States reported that positive rate of the lateral lymph node is only 1.9 %. In addition, the author thinks that lateral lymph node metastasis should belong to distant metastasis; dissection has no clinical significance. Therefore, lateral pelvic lymphadenectomy is not recommended . Why the study results between eastern and western scholars are so different? Yano et al. recently studied and compared many years of literature of both parties to the dispute and think that difference in the results of both parties is likely caused by different rectal cancer staging concept between east and west. If staging standard of rectal cancer is unified, lateral lymph node metastasis of low rectal cancer perhaps may result in similar positive rate in Japan and western countries .
As range of lateral lymphadenectomy is big, incidence rate of postoperative micturition and sexual dysfunction caused by intraoperative damage to the pelvic autonomic nerve also increases. For this reason, some scholars proposed extended radical resection of PANP, called as “functional extended radical resection.” After performing this operation, 62.3 % and 57.1 % of the patients can maintain normal erectile and sexual functions, respectively, and postoperative 5-year survival rate is 61.2 % . However, Wan Yuanlian et al. also reported that lateral dissection may reduce pelvic recurrence from 17.7 % by adoption of traditional radical resection to 5.6 %, but there is no significant improvement of 5-year survival rate. Further analysis was conducted on the cases that had lateral lymph node metastasis and received radical resection and lateral dissection. Recurrence still occurred in 80 % of the patients within 2 years after operation; distant metastasis occurred in 75 % of the patients, and 3- and 5-year survival rate after operation was only 16.7 % and 0, which indicates that as lateral metastasis breaks through the barrier of fascia propria, it is not only local pathological change in the pelvic cavity, but also belongs to a part of pathological change of the whole body. Lateral dissection can reduce local recurrence rate, but cannot significantly improve survival rate [33, 34].
From the above analysis, although rectal cancer lateral lymphadenectomy can reduce postoperative local recurrence rate, great dispute still exists on the significance of dissection. Lymphatic diversion path and rule of middle and low rectal cancer need further illustration. Whether or not biological behaviors of lateral lymph node metastasis belong to a part of systemic metastasis requires further study and demonstration, and whether or not conventional lateral lymphadenectomy should be conducted for rectal cancer below the peritoneal reflection needs validation through multicenter randomized clinical trial on a large size of samples.
1.3.4 Laparoscopic Radical Resection of Colorectal Cancer
In 1991, Jacobs M reported laparoscopic radical resection of colorectal cancer for the first time. Through nearly 20 years of development, laparoscopic radical resection of colorectal cancer has achieved great development. Laparoscopic radical resection of colorectal cancer should observe all basic principles for open operation. As range of surgical resection is big, operative gap is small, and field of vision is often disturbed by the small intestine, there is some difficulty to perform such operation. Along with the accumulation of experience and development of advanced devices, laparoscopic-assisted resection of colorectal cancer increasingly becomes mature, and its safety and effectiveness are also recognized by many scholars both at home and abroad.