7. Pre-operative Diagnostics and Surgery – Colorectal Cancer
7.1 Introduction
In the following the general principles of diagnosis and therapy will be shown in a summary fashion for both entities, as long as they apply to both colon and rectal cancer. Unique diagnostic and therapeutic aspects will be listed separately.
The therapy of colorectal cancers should always be planned on the basis of a histopathological examination. A colorectal cancer is defined by atypical epithelial formations infiltrating the submucosa (pT1 or more). Not included are the so-called mucosal cancer or intraepithelial cancer (pTis) that have no metastatic potential and can be treated by local excision alone.
7.2 Definition of Colon and Rectal Cancer
The border between the colon and rectum has been defined differently. The intra- operative assessment using the end of the taeniae or the peritoneal fold is different for each individual and depends upon age, sex, and other factors. The pre-operative determination of the distal tumor margin with a flexible endoscope is unreliable. This is done more reliably by rigid rectoscopy. The anocutaneous line serves as the distal reference point. According to the international documentation system [596][597] rectal cancer have aboral borders of 16cm or less from the anocutaneous line as measured by rigid rectoscopy.
According to UICC 2003, rectal cancer are subdivided according to the distance from the anocutaneous line into cancer of the upper rectal third (12-16cm), the middle rectal third (6-<12 cm), and the lower rectal third (<6cm) [598].
In contrast, in the US [599][600], colon cancer have by definition a distal margin of more than 12 cm and rectal cancer a distal margin of less than 12 cm from the anocutaneous line. This is based on the significantly higher local recurrence rate of tumors with less than 12cm distance from the anocutanoeus line [601].
7.3 Definition Interdisciplinary Tumor Conference
All CRC patients should be presented in an interdisciplinary tumor conference after they have completed their primary therapy (e.g. operation, chemotherapy).
Patients with the following constellations should already be presented before therapy:
- every rectal cancer
- every stage IV colon cancer
- metachronic distant metastases
- local recurrence
- before every local ablative procedure, e.g. RFA/LITT/SIRT
- Consensus
- Consent
Background
Because of the complexity of the colorectal cancer therapy, patients should be discussed in an interdisciplinary tumor conference. Members of the conference should include the following experts: a gastroenterologist, a hematologist/oncologist, a visceral surgeon, a radiotherapist, a radiologist, and a pathologist. To evaluate the primary or secondary resectability of liver metastases, an experienced liver surgeon should be consulted. If one is not available on site, an external second opinion by an expert should be sought.
In certain cases, a presentation at the tumor conference is necessary before therapy has been initiated. For example, for patients with rectal cancer it must be decided upon whether a neoadjuvant therapy should be performed. A study showed that the presentation at a tumor conference and the interdisciplinary determination of a therapy concept significantly reduced the rate of involved circumferential resection margins in the surgical specimen [602]. If distant metastases are present, it must be determined whether a purely palliative concept should be followed or whether the patient can be cured by primary or secondary resection of metastases (especially liver metastases). The frequent presentation of patients with stage UICC IV at the tumor conference has led to an increase in metastasis surgery [603].
Also patients with distant metastases or local recurrences during the disease course should be presented first to the conference to decide on further concepts. Patients with a planned local ablative procedure should also be presented to discuss alternative treatment options.
For colon cancer without distant metastases, an oncologic resection of the cancer is usually done as primary treatment. In this case a pre-operative presentation is not necessary.
A presentation is necessary for all patients after therapy has been completed e.g. following a colorectal cancer operation to discuss the indication for adjuvant therapy. In a British study this procedure led to a higher rate of adjuvant chemotherapy and a significant increase in patient survival [604].
Also patients with distant metastases who have begun primary chemotherapy should be presented again to a tumor conference (with consultation of an experienced liver or lung surgeon) during the course of therapy. A possible secondary resectability should be discussed.
7.4 Pre-Operative Evaluation
7.4.1 Endoscopic Diagnostics
The following examinations should be obligatory components of a pre-operative evaluation of patients with colorectal cancer:
- Digital-rectal examination (Grade of Recommendation: B. Level of Evidence: 5)
- Complete colonoscopy with biopsy (Grade of Recommendation: A. Level of Evidence: 4)
- In the case of an endoscopically non- transversible stenosis, complete colonoscopy 3-6 months postoperatively (Grade of Recommendation: A. Level of Evidence: 3b)
- Consensus
- Strong consensus
Background
The digital-rectal examination allows an initial judgment of the sphincter function as well as the depth of infiltration with deep-localed rectal cancer and allows an assessment of the possibility of sphincter retention.
Before therapy of a patient with a colorectal cancer, a colonoscopy with a biopsy has to be performed. In up to 5% of colorectal cancer synchronous tumors are present. Since these can be missed during intra-operative evaluation, a colonoscopy of the entire colon should be performed [604][605][606]. If for technical reasons a complete colonoscopy is not possible, an alternative radiological procedure should be used (see Chapter 6.1).
Relevance of Virtual Colonoscopy (for stenosing tumors and incomplete colonoscopies)
If a colonoscopy is not complete due to stenosing tumors additionally, a CT- or MRcolonography can be performed pre-operatively. A complete colonoscopy should be performed postoperatively.
- Recommendation grade
- 0: offene Empfehlung (Option) bzgl. einer Maßnahme - verwendete Ausdrucksweise = kann
- Level of evidence
- 4
- Consensus
- Strong consensus
- References
- [458]
If the colonoscopy is incomplete for other reasons (e.g. adhesions), a CT- or MR- colonography should be performed.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 4
- Consensus
- Strong consensus
- References
- [458]
Background
In this case a virtual colonography is a promising alternative [458]. If a complete colonoscopy is not possible due to a stenotic process, a colonoscopy should be done 3 to 6 months after resection. A pre-operative colon contrast enema is of little value and in the case of stenoses has the danger of causing an ileus. Therefore, it is not recommended.
7.4.2 Imaging Procedures
7.4.2.1 The Relevance of Individual Imaging Procedures (except PET) for the Evaluation of Distant Metastases in the Primary Treatment of CRC
An abdominal ultrasound and a conventional chest x-ray in 2 levels should be the basic examination for pre-operative staging of CRC.
If the result is not clear or if distant metastases or infiltration of adjacent organs or structures is suspected, a multi-slice CT of the abdomen and pelvis should be performed. If lung metastases are suspected, a CT of the chest should be performed.
- Consensus
- Consent
Background
The goal of pretherapeutic imaging is to clarify whether distant metastases are present. At the time of initial diagnosis of colon cancer, 25% of patients have distant metastases: in 13% limited to one organ (M1a), in 12% more than one organ or in the peritoneum are involved (M1b). Liver metastases are found in 19%, lung metastases in 3%, and peritoneal metastases in 9%. Other distant metastases located in non-regional lymph nodes (2%), the skin (2%), the ovaries (1%), the bones (<1%), or other locations (2%) are rare.
The incidence of distant metastases for rectal cancer at first diagnosis is 18%: in 12% limited to one organ (M1a), in 6% more than one organ or in the peritoneum are involved (M1b). Distant metastases in the liver are found in 15% and lung metastases in 4%. Other distant metastases are in the peritoneum 3 %, in non-regional lymph nodes 2 %. Distant metastases in skin, bone, brain, ovaries, or other locations are found in less than 1% of patients [Data from the Clinical Cancer Registry of the Surgical University Clinic Erlangen- Nürnberg].
A primary abdominal ultrasound should be used to evaluate the presence of liver metastases (sensitivity 63-86%, specificity 98%) [607][608][609]. If the results are suspicious, if the liver can only be poorly evaluated, or if there is clinical suspicion of liver metastases, a multi-slice CT of the abdomen should be performed (sensitivity 75-83%, specificity 95-98%) [607][610]. A multi-slice CT is also best to attribute metastases to the liver veins, the hilus structures, as well as the vena cava. This is necessary to evaluate the resectability of liver metastases (see Chapter 7.7.5). The extent of liver metastases can be best assessed using MRI (sensitivity and specificity: MRI 80-88% and 93-97%, CT 74-84%, and 95-96%) [607][610].
Contrast-enhanced sonography of the liver and MRI have nearly equal performance characteristics (sensitivity 83-86%, specificity 94-98%). However, it requires adequate quality standards (technical equipment and experience of the examiner) [608][609][611].
Since the multi-slice CT also gives information on the local tumor extension (see below), there is a tendency to implement a primary abdominal CT instead of or in addition to an abdominal ultrasound. However, studies show that only few patients with colon carcinoma who routinely had pre-operative abdominal CTs had a change in further procedures [612][613].
7.4.2.2 Relevance of Pre-Operative Local Staging Using CT (MRI) for Colon Cancer with Regard to Local Spread
A pre-operative staging CT can differentiate between tumors that are limited to the bowel wall and those that have penetrated the wall. However, the evaluation of the nodal status is significantly less reliable. The best results are achieved with multi- slice CTs (MSCT).
- Consensus
- Consent
Background
Neoadjuvant therapy for colon cancer without extensive distant metastases is currently only considered in exceptional cases (e.g. distal sigmoid cancer with very extensive regional lymphogenic metastazation or deep tumorinfiltration reaching the probable conceivable resection margins). However to optimize the therapy algorithm for patients, the use of corresponding pre-operative imaging procedures is increasingly being discussed, e.g. selection for laparoscopic resections or transferal of patients with predictable multi-visceral resections to experienced centers.
The validity of pre-operative abdominal ultrasound examinations is insufficient in this respect. Data on the sensitivity of CTs for local colon cancer staging do not exist. The modern multi-slice CT (MSCT) reaches a high sensitivity (86%) and specificity (78%) with regard to local tumor expansion. However, the detection of local lymph node metastases is much less sensitive (70%) with the same specificity (78%) [614].
7.4.2.3 Relevance of PET-CT
7.4.2.3.1 For Primary Diagnosis of Colorectal Cancer
Background
15 prospective and 5 retrospective cohort studies and case series were identified in the literature search. 13 Studies included patients with colon and rectal carcinomas and 7 trials only rectal carcinoma patients. 14 studies included all patients, 2 retrospective studies only patients with locally advanced rectal cancer, and 1 study included only patients with increased CEA or inconclusive CT imaging. In the studies that were included 10 cases used PET, 6 PET-CT, and 4 PET-CT with CT-colonography. PET was compared to CT +/- other modalities in 14 studies, and with MRI in 3 studies. In 4 studies there was no comparison. 18 cases used histology and clinical course as references and in 2 cases clinical staging was done using the examinations that had been performed.
The sensitivity of PET for distant metastases was high (75-100%) and in a number of cases superior to the method that it was compared [615][620]. In some cases it was not better [616][617][618]. The quality of the method used for comparison is not known. In recent studies with multidector spiral CT there was no significant detectable difference [616][617].
The sensitivity for lymph node metastases was mainly low (29-85%), in 2 retrospective rectal cancer studies 44 and 85% and not better than comparison studies (CT or MRI) [615][616][617][618][619][620][621][622][623].
In the studies the use of PET or PET-CT led to changes in therapeutic procedures in 2- 27% of the cases [616][617][620][623][624][625][626][630][630][627][628][629].
Overall, the data show no conclusive additional benefit of PET for the primary diagnosis of CRC.
7.4.2.3.2 Before Resection of Colorectal Liver Metastases
A PET-CT shall not be performed within 4 weeks after systemic chemotherapy or antibody therapy, because it this significantly reduces its sensitivity.
Background
A preliminary report on the benefit of PET/PET-CT for relapse diagnostics and relapse staging in CRC patients was presented by the IQWIG (Institute for Quality and Economics in Health Care) in August 2011 [636]. Aside from the evaluation of the patient relevant benefit, a systematic evaluation of the prognostic and diagnostic quality of the PET/PET- CT was done. The literature search included a period up to August 2009. More recent publications were mentioned in the text. The guideline recommendations given here are based on the evidence evaluation of the IQWIG report. The Grade of Recommendation was developed under additional inclusion of the clinical evaluation of the procedure. Furthermore, in a more recent literature search from August 2009 – December 2011, a RCT in abstract form [632], 2 systematic reviews [637];[610], a prospective case control study [633], and a retrospective case series [635] were identified. They were also included in the evaluation (for details see evidence report). The previous recommendation of Grade B from the last guideline update in 2008 (9.1.2.1) for PET/PET- CT examinations before resection of colorectal liver metastases with a FONG score > 2 was changed, because the study that led to this recommendation has still not been published as a full article [638].
So far, a RCT as a full publication and 1 RCT in abstract form have been published on the issue of patient-relevant benefit of PET/PET-CT. For patients before resection of CRC liver metastases, a supporting PET/PET-CT has no effect on disease-free or total survival of the patient. Whether supplemental PET-CT examinations help to avoid futile laparotomies as clinical endpoints is not completely resolved. The consensus recommendation here is especially supported by the full published study by Ruers [631] which has, however, methodological weaknesses. In this study 150 patients with colorectal liver metastases who were planned to undergo resections were randomized to 2 study arms (CT or CT plus 18F-FDG PET). The primary study objective was reported in the publication as rate of futile laparotomies that were avoided as a result of the PET examination. This endpoint is relevant for the patient. The study reported no significant difference in survival in the PET-arm. However, a significantly reduced number of "futile laparotomies“ was seen in this study arm. The rate of futile laparotomies was 45% in the control arm and 28% in the PET-arm. This corresponded to a risk reduction of 38% with a very large confidence interval (95% CI, 4-60%, p=0.042). The authors concluded that in one in six patients a laparotomy can be avoided with an additional PET before liver metastasis resection. The secondary endpoint DFS and OS were as follows: DFS: 35.5% versus 29.8 % (p-value = 0.194); OS: 61.3% versus 65.8 % (p-value = 0.378). The study's evidence level was downgraded by the consensus conference (see also IQWIG-report, degrading from Ib to II), because the primary study endpoints mentioned in the study plan were different from the ones in the publication (original endpoint: rate of patients who were disease-free after 9 months).
Another multicenter randomized study that has so far been published as an abstract at the ASCO annual meeting 2011 also investigated this issue [632]. Endpoint of this study was the change in patient management after PET-diagnostics (no operation because of additional results or expansion of surgery compared to the intention without/before PET- diagnostics) in a 2:1 randomization design in CRC patients who seemed suitable for liver resection for liver metastases. 404 patients were randomized (270 patients in the PET/CT-arm, 134 patients without PET). There was no difference in management change between both study arms. Thus, the endpoint was not reached. However, as far as could be deduced from the presentation, about 70% of patients had chemotherapy before PET diagnostics. This significantly reduces the sensitivity of the examination method (see below). It should also be critically noted that the endpoint "change in patient management" in contrast to "reduction of futile operations" was not considered patient relevant.
Several studies point out that the sensitivity of PETs is significantly reduced if they are done within 4 weeks after chemotherapy (evidence level IIa-III). Therefore, a PET is not recommended during this time, because too many false negative cases occur. The issue was not evaluated by the IQWIG report. A larger case control study without randomization was published in 2010 which investigated the sensitivity of PET after chemotherapy [633]. The study found a negative predictive value of only 13.3% and a positive predictive value of 94% with a specificity of 22.2% at an accuracy of 85% if the PET was done within 4 weeks after the end of chemotherapy. The authors concluded that diagnostic PET examinations shortly after chemotherapy administration are not useful. A retrospective study from Australia evaluated PET-results of patients with liver metastases before liver resection [639]. This study was small and heterogeneous. 21 patients were systematically treated before surgery, 53 were not. Correct results were determined using PET for 29% of patients after chemotherapy and 53% without chemotherapy. Underestimated results were observed in 52% in the chemotherapy group and only 34% in the group without chemotherapy. This study underscores that PET examinations shortly after chemotherapy are not useful. Another prospective trial [634] and a retrospective study [635] reached similar results.
7.4.3 Tumor Markers
The CEA-value should be assessed pre-operatively.
- Consensus
- Strong consensus
CA 19-9 does not increase the conclusiveness of a relapse compared to determining only the CEA-value.
- Consensus
- Strong consensus
The relevance of CA 125 to diagnose ovarian metastases and as a course parameter for further treatments of confirmed peritoneal carcinosis is unknown.
- Consensus
- Strong consensus
Background
In about 30% of all CRCs the tumor marker CEA is increased at the time of first diagnosis [data from the Clinical Cancer Registry of the Surgical University Clinic Erlangen- Nürnberg]
This tumor marker is especially reliable as an indicator for tumor relapse. It is also an independent prognostic factor for liver metastases.
Other tumor markers under discussion are CA 19-9 and CA 125, the latter being a marker for peritoneal cancer [640][641][642].
The detection of circulating DNA and so-called circulating tumor cells in peripheral blood as well as bone marrow has no consequences.
7.4.4 Specific Diagnostics for Rectal Cancer
The prediagnostic work up of a patient with rectal cancer should include a rigid rectoscopy with a statement on the distal tumor or margin.
- Consensus
- Strong consensus
Background
Rigid rectoscopy allows an exact determination of the distance of the distal tumor margin from the dentate line and is of major importance for determining further therapy.
Local staging of rectal cancer should preferably be performed using MRI. If a T1-cancer is suspected, an endoscopie ultrasound should be performed.
The report should include information on the distance of the tumor to the mesorectal fascia.
- Consensus
- Strong consensus
Background
In rectal cancer local staging is essential for further therapy planning. While local removal is sufficient for low-risk T1-carcinomas, for high-risk T1 and T2-cancers a resection according to oncologic criteria is necessary. In Germany, neoadjuvant therapy is recommended if tumor infiltration in the mesorectum (T3) has been identified. If neighboring organs have been infiltrated (T4), neoadjuvant radiochemotherapy is recommended. For T3-cancers there are data which indicate that the extent of the mesorectual infiltration especially the distance from the mesorectal fascia are of important prognostic relevance [643]. This level is the circumferential resection margin (CRM) in the TME. If the mesorectal fascia is infiltrated by the tumor or the distance between the tumor and the fascia is less than 1 mm (CRM+), the local recurrence risk is significantly increased [644]. Another prognostic factor is affected lymph nodes [643].
A number of studies on the value of different methods for local staging of rectal cancer had to be excluded in the literature search, because study collectives also included patients who had had radio-or radiochemotherapy. For further details see the evidence report.
The accuracy of individual diagnostic methods depends on the technical characteristics of the equipment (e.g. multidetector spiral-CT vs. single-slice CT) and the local expertise. An endosonography is often technically not possible if high-grade stenoses are present or the tumors are localized in the proximal rectum.
A meta-analysis which analyzed data on endosonography, MRI, and CT up to 2002 showed that endosonography demonstrated the highest accuracy for T1-cancers [645]. Its high sensitivity and specificity was confirmed in a more recent meta-analysis [646]. MRIs with endorectal spools are a possible alternative for EUS. However, they are more costly, are considered unpleasant by patients, and are established at very few sites. CTs are not suited for diagnosing T1-cancers.
However, to differentiate T2 and T3-cancers, the endosonography was more sensitive than MRI and CT with comparable specificity [645]. For T4-cancers the meta-analysis showed no significant differences between the procedures. Recent individual cohorts demonstrated a higher sensitivity for MRI and occasionally spiral-CT for tumors with mesorectal infiltration (> T2) [647][648][649][650]. However, the accuracy of the CT was significantly lower in the lower third than in the upper two thirds [652]. If it is necessary to show the mesorectal fascia and its association with the tumor, the MRI is currently the most sensitive method [653]. The fascia cannot be demonstrated by endosonography [647].
When evaluating lymph nodes the sensitivity (55-73%) and specificity (74-78%) of all methods are currently insufficient [645][646]. The reasons include, on the one hand, reactive lymph node enlargement and, on the other hand, lymph nodes 5mm and smaller that may contain metastases. Therefore, the indication for neoadjuvant therapy should be made very carefully if it is solely based on suspected lymph nodes seen in pretherapeutic imaging.
Furthermore, it must be considered that the accuracy of the individual methods depends greatly on the local expertise. This is especially true for CTs.
Considering especially the possibility of depicting the mesorectal fascia, many experts currently prefer MRIs for local staging of rectal cancers (with the exception of early cancers).
Excluding short term radiation, neoadjuvant therapy impairs the accuracy of individual diagnostic procedures (see evidence report).
In individual cases the following examinations may be useful:
- Sphincter manometry (Grade of Recommendation: 0 - Level of Evidence: 4)
- Gynecologic examination (Grade of Recommendation: EC)
- Cystoscopy (Grade of Recommendation: EC)
- Consensus
- Strong consensus
Background
In general, sphincter manometry has no relevance for therapy decisions beyond the result of the rectal-digital examination and the differential medical history. In unclear cases , it can make the decision on sphincter retention easier.
If bladder infiltration is suspected, a cytoscopy can be helpful. If the infiltration of the vagina, uterus, or adnexa is suspected, a gynecologic exam should be done. In contrast to the previous guideline, a urine sediment is no longer recommended for rectum or sigma cancers, because the test is too unspecific.
Table 7: Staging of Colorectal Cancer
| Examination | ColonCa | Rectal Ca |
| Complete colonoscopy | X | X |
| CEA | X | X |
| Abdominal ultrasound | X | X |
| Chest x-ray | X | X |
| Rigid rectoscopy | X | |
| Pelvis MRT (CT) with statement on distance between tumor and mesorectal fascia | X | |
| Rectal endosonography for localized tumors | X |
7.5 Surgical Therapy with Curative Intention
7.5.1 Intraoperative Staging
7.5.1.1 Intra-Operative Pathological Examination
In general, rapid sections should be used only if this has direct consequences. The most frequent indication is the evaluation of metastatic spread, e.g. in the peritoneum, in the liver, or in non-regional (e.g. peri-aortal) lymph nodes.
With local surgical excision (full wall excision), the important question is whether a cancer proven by previous biopsy was excised with tumor-free margins.
However, this cannot be adequately determined intra-operatively using rapid sections.
In the case of a deep-seated rectal cancer, rapid section examination of the aboral resection margin can help to decide whether total rectal extirpation should be performed.
With segmental resections of large colon polyps, especially of villous histology, in which pre-operative evaluation failed to confirm an invasive neoplasm, an assessment of malignancy using rapid section is frequently not possible due to technical reasons (examination of multiple tissue blocks!). Therefore in these cases, the use of standard oncological resection is recommended.
In case of adherence of a tumor to neighboring organs it is not possible to determine macroscopically whether an infiltration of the neighboring organs or only a peritumorous inflammatory reaction is present. In such cases, biopsies with rapid sections should be strictly avoided, because of possible local tumor cell dissemination, which can be associated with reduced survival [654]. This is the reason for the en-bloc resection in all cases of tumor adherence to neighboring organs or other structures (see section 7.7.2 on therapy and multivisceral resection).
If the etiology of a focal liver lesion remains unclear, histological examination should be performed.
- Consensus
- Consent
Background
In case of unclear liver lesions (see below) with therapeutic consequences , a histologic work up preferably with a needle biopsy passing through the healthy liver parenchyma should be performed. Incision biopsies should be strictly avoided. Smaller lesions can be completely excised in form of an excision biopsy.
The sentinel-node-biopsy has no relevance for CRC.
- Consensus
- Consent
Background
In malignant melanomas and breast cancers sentinel-node-biopsies are performed. This is done to avoid more extensive dissection that would result in increased morbidity rates in patients with histologically negative sentinel lymph nodes.
With the introduction of laparoscopic surgery methods, it was discussed whether limited resection methods can also be used for CRC if the sentinel-node-biopsy was negative.
In addition, it was questioned whether ultra-staging (immunohistochemical preparation) of the sentinel lymph node would change the tumor stage with the corresponding need for adjuvant therapy [655][656].
An intraoperative inspection and, in case of open surgery, palpation of the liver should be performed in every case, i.e. also in case of an inconspicious preoperative evaluation.
If the pre-operative diagnostics are sufficient, the diagnostic benefit of intra-operative ultrasound to look for further metastases does not justify its effort.
- Consensus
- Consent
Background
Due, nowadays, to the quality of magnetic resonance imaging and computer tomography, during a laparotomy usually only subserosal liver metastases (< 2mm) are additionally detected by intra-operative inspection and palpation.
However, the sensitivity and the positive predictive value of the intra-operative ultrasound examination with contrast medium is very high (in a single series with 24 patients at 100 % each) [657].
7.5.2 Radical Surgical Therapy of Colon Cancer
7.5.2.1 Extent of Lymph Node Dissection
If there is lymphogenic metastazation of the colon cancer, it occurs according to a regular metastazation pattern. At first, it metastasizes longitudinally to both sides of the tumor into the paracolic lymph nodes, then to the intermediary lymph nodes along the radial arteries to the central lymph nodes at the origin of the supplying arteries. The paracolic metastazation never exceeds a distances of more than 10 cm [658][659][660].
The extent of the colon resection is defined by the transsection of the central arteries. Cancer lymph node metastases at the terminal ileum on the right side, however, seldom occur and if so, only in very advanced cancer [661]. Therefore, a resection of the terminal ileum of maximally 10 cm is sufficient for right hemicolectomies.
Oncologic Principles
In colon cancer surgery, the lymph node yield also correlates with the prognosis in nodal negative cancer (UICC II) [662][663].
Resection of cancers of the Coecum and the Ascending Colon
Cancers in this area metastasize centrally via the ileocolic artery and the right colic artery. Accordingly, both vessels must be centrally ligated. However, a real colic artery originating from the superior mesenteric artery is present in less than 15 % of all cases [664]. Accordingly if the vessel is not present, branches leading to the right from the origin of the middle colic artery are centrally ligated. Parts of the major omentum only have to be resected if there is direct tumor contact.
Resection of cancers of the Right Colonic Flexure and Proximal Transverse Colon
For the extended hemicolectomy, the ileocolic artery, the right colic artery (if present), and the middle colic artery are centrally ligated. Accordingly, the distal resection margin is in the area of the left transverse colon. In this tumor localization a lymphogenic metastazation also takes place via the major omentum in the direction of the gastric antrum and on to the pancreatic head [659]. Thus, aside from skeletonizing the greater gastric curvature and resecting the gastroepiploica-dextra-arcade and, thus, parts of the right-sided omentum, the lymph nodes cranial of the pancreatic head should also be dissected.
Resection of cancers of the Middle Transverse Colon
These tumors metastasize via the middle colic artery centrally toward the superior mesenteric artery, and via the left colic artery toward the inferior mesenteric artery. A transverse colon resection includes both colon flexures. If metastazation towards the greater gastric curvature via the major omentum has occurred, a omentum resection corresponding to the tumor site as well as skeletonizing of the greater gastric curvature with removal of these lymph nodes must also be performed. The arcade principle must be observed for the omentum resection (inclusion of the omentum artery within an arcade of 10 cm to both sides of the cancer).
Resection of cancers of the Distal Transverse Colon and Left Colonic Flexure
Here the tumor metastasizes to the right via the middle colic artery and to the left via the left colic artery. Thus, the middle colic artery is centrally ligated and the left colic artery is cut descending from the inferior mesenteric artery . An advantage of the greater radicality of removing the inferior mesenteric artery has not been confirmed. An ascendo-sigmoideo-stomy can be done to restore the continuity. Due to metastazation via the major omentum towards the greater gastric curvature, the left sided parts of the omentum with dissection of the arcade at the greater gastric curvature must also be removed. If the tumor is advanced in this region, the lymph nodes at the left pancreas lower margin may also be affected. These must also be dissected from the isthmus to the pancreas tail.
Resection of cancers of the Colon Descendens
In this case a left hemicolectomy with central ligature of the inferior mesenteric artery is necessary. The distal resection margin lies in the upper third of the rectum, the proximal one in the left flexure region. Accordingly, it may be necessary to resect possible adherent parts of the omentum.
Resection of cancers of the Sigmoid Colon
These tumors metastasize via the sigmoid branches to the origin of the inferior mesenteric artery . The proximal transsection of the bowel is performed in the descending colon with central ligation of the inferior mesenteric artery. For the distal bowel dissection the guidelines for rectal cancers in the upper third of the rectum also apply. However, a distal safety distance of at least 5 cm distal safety distance from the tumor margin must be observed.
Background: For 2 - 4 % of patients lymph node metastases are found close to the origin of the inferior mesenteric artery [665][666].
7.5.2.2 Complete Mesocolic Excision (CME)
Surgical therapy for colon cancers should include the complete mesocolic excision.
- Consensus
- Consent
Background
Analogous to the mesorectum, a mesocolon exists which covers the lymph nodes of the supplying arteries like envelopes.
Analogous to TME for rectal cancer, CME is used for colon cancer surgery. This is done to achieve maximal local radicality with the greatest possible lymph node yield by preparation in predefined anatomical layers with central ligation of the supplying vessels without breaching of the visceral fascia layer.
For colon cancer a complete mesocolic excision is suitable to achieve maximal local radicality with high lymph node yield.
It leads to high quality preparations [667][668]. The higher radiality does not seem to be associated with an increased complication rate [669]. Previous data indicate an improvement of survival rate if CME is consistently performed [667].
The morphometric examination of the colon specimen can be used in the future to objectively evaluate colon cancer specimen.
7.5.2.3 Local Ablative Therapies for Liver Metastases
7.5.2.3.1 Radio-Frequency Ablation (RFA)
An RFA can be performed if non-resectable liver metastases are present or if the general health of the patient does not allow resection, especially following previous liver resection.
Background
The present evidence on the safety and efficacy of radio frequency ablation for colorectal liver metastases is sufficient to recommend this method for patients who either have non-resectable liver metastases, whose health status does not allow resection, or who have previously had a liver resection [670].
The RFA can also primarily be performed in combination with surgical resection.
Recent studies suggest that solitary liver metastases <3cm can be treated using RFA with similarly good results as with resections [671][672]. However, present data on this subject are contradictory and comparative controlled randomized studies still do not exist.
7.5.2.3.2 Selective Internal Radiation Therapy (SIRT)
SIRT to treat disseminated liver metastases of CRC should only be performed in patients who have no other therapy option and only as part of a clinical study.
Background
Patients with absent or limited extrahepatic metastazation, and without options of further systemic chemotherapies show a prolonged median survival and longer interval to progression of liver metastases in individual studies using SIRT (also called radioembolization). There are too few data for a conclusive evaluation especially on survival and quality of life. Therefore, patients who are eligible for SIRT should only be treated as part of clinical studies [673][674].
7.5.2.3.3 Laser Induced Interstitial Thermotherapy (LITT)
Background
The interstitial laser thermo-ablation was a safe and effective method in individual case- series for patients with inoperable CRC liver metastases [675][676]. Data comparing it to percutaneous radiofrequency ablation do not exist. The data are not sufficient for conclusive evaluation especially of survival and quality of life. Therefore, patients who are eligible for LITT should only be treated as part of clinical studies.
7.5.3 Radical Surgical Therapy of Rectal Cancer
As a general rule the curative therapy of rectal cancers requires, in addition to the complete resection of the primary tumor, the partial or total removal of the mesorectum including the regional lymph drainage area (so-called radical resection according to the international documentation system for colorectal cancer) [596][597]. Only in strictly selected cases a curative resection is possible using local measures. The following operative procedures are considered equivalent the criteria of oncological surgery are taken into account. The individual indication is dependent on tumor localization, especially the relation to the dentate line and the levator muscle, the depth of infiltration and the anal sphincter function:
- (deep) anterior rectal resection
- abdominoperineal rectal extirpation
- intersphincteric rectal resection (also described as an abdominal-perianal rectal resection). This operation requires special experience.
It must be noted that for the deep anterior rectal resection an intersphincteral preparation is also frequently necessary to achieve a sufficient safety distance to aboral. This operation method should, however, not be confused with an abdominal peranal preparation.
If at all possible, a continence-preserving procedure should be chosen with regard to the future quality of life. With poor sphincter function, instead of a deep resection a permanent colostomy should be preferred which depending on the safety margin to the pelvic floor should be performed in form of a rectal exstirpation or preserving the pelvic floor.
7.5.3.1 General Oncologic Principles
Surgical therapy should adhere to the following principles:
Removal of the regional lymph drainage areas with resection of the inferior mesenteric artery at least distal to the origin of the left colic artery. The central dissection of the inferior mesenteric artery close to its origin has no prognostic significance; however, it is often necessary due to technical reasons for the mobilization of the left hemicolon used for reconstruction [677]. However, anatomical studies show that in many cases a deep anastomosis is also possible without central ligation [678]. A benefit of lymph node dissection at the origin of the inferior mesenteric artery proximal to the exit of the left colic artery has not been shown (level of evidence: 2b) [679][680][681][682].
- The complete removal of the mesorectum for cancers in the middle and lower part of the rectum and the partial mesorectal excision for cancers in the upper third of the rectum through sharp dissection along the anatomical structures between the fascia pelvis visceralis and parietalis (total mesorectal excision TME) [683][684].
- The observance of an appropriate safety distance (see below).
- As a rule, the en-bloc resection of tumor-adhering organs (multivisceral resection) to prevent local tumor cell dissemination [685].
- Protection of the autonomic pelvic nerves (hypogastric nerves, inferior and superior plexus [686][687].
The systematic dissection of lateral lymph nodes along the internal iliac artery and its branches should not be done without justified suspicion of metastases. It increases the perioperative morbidity without confirmed oncologic benefit.
7.5.3.2 Approach to Tumors of the Upper Third of the Rectum
With tumors of the upper third of the rectum, resection of the rectum with partial mesorectal excision 5 cm distal to the macroscopic tumor border, measured in- vivo should be performed. The mesorectum should be dissected horizontally without proximal thinning (no coning).
7.5.3.3 Approach to Tumors of the Middle and Lower Third of the Rectum
With tumors of the middle and lower third of the rectum, a total mesorectal excision (TME) should be performed up to the pelvic floor, preserving the superior and inferior hypogastric plexus and the hypogastric nerves.
For low-grade tumors with high or moderate differentiation in the lower third of the rectum, a safety margin of 1-2cm in-situ is sufficient. With high-grade tumors (G3/4), a larger safety margin must be attempted.
After neoadjuvant radiochemotherapy, an aboral distance of 0.5cm may also be acceptable to avert an otherwise necessary extirpation. Intraoperative frozen sections should confirm that the aboral resection margin is tumor-free.
Background
For cancers of the lower third (as an alternative to the otherwise recommended rectal extirpation) an intersphincteric rectal resection can be performed (also called the abdominal-perianal rectal resection), if - under observance of the above-mentioned safety margins - the puborectal loop is not infiltrated. This operation requires special experience.
7.5.3.4 Reconstruction After Total Mesorectal Excision
After total mesorectal resection with an anastamosis near the anal sphincter, significant functional disorders can occur. These are dependent on the choice of the reconstruction method. Some possibilities available include:
- a straight colo-anal anastomosis
- a colon-J-pouch
- a transverse coloplasty
- a side-to-end anastomosis
For reconstruction after deep anterior resection, a straight colo-anal anastomosis should usually not be used (if anatomically possible) because of the better functional results.
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 1a
- Consensus
- Strong consensus
- References
- [705]
The side-to-end anastomosis may be as good as the colon-J-pouch.
- Level of evidence
- 2a
- Consensus
- Strong consensus
Background
The disadvantages of a straight colo-anal anastomosis have been clearly shown. Especially in the first two postoperative years, they result in an increased stool frequency as well as poor continence and quality of life [705]. When constructing a J-pouch the loop length should not exceed 6 cm to prevent emptying problems [708]. The only larger prospective randomized study on the differential use of different reconstructions shows that a J-pouch construction was technically possible in 74% of patients [705]. Compared to a transverse coloplastic, the J-pouch in this study was better with respect to stool frequency and incontinence score. Although a meta-analysis including the Fazio-study put the conclusion on stool frequency into perspective, it considered neither the long- term results of the Fazio-study nor the data on incontinence [707]. Since studies with sufficient case numbers are still missing, definite conclusions on the role of side-to-end anastomosis cannot be made [709].
7.5.3.5 Decision to Preserve the Sphincter
Even in cases in which sphincter preservation was initially regarded as impossible, a sphincter preserving rectal resection may become possible using neoadjuvant radiochemotherapy. Therefore, a re-evaluation should be performed no earlier than 6 weeks after completion of radiochemotherapy.
- Consensus
- Strong consensus
Background
A reduction of tumor mass especially for low tumors is one important aspect for sphincter preservation. There seems to be an advantage for neoadjuvant radiochemotherapy. However, its effects do not become identifiable until several weeks after completion. This means that the surgery method cannot be chosen until the time of surgery after neoadjuvant radiochemotherapy has been completed [710]. Imaging procedures are not helpful in evaluating the response [711].
7.5.3.6 Approach in Case of Complete Response after Neoadjuvant Therapy
In rare cases in which after neoadjuvant radiochemotherapy a tumor is no longer detectable clinically, endoscopically, or with imaging procedures (endosonography and MRI, alternatively also CT), it can be considered not to perform a resection. Detailed information on the poor validation of this approach and the willingness of the patient undergo regular follow up at short intervals to have very close knit follow- ups for at least 5 years is required.
- Consensus
- Consent
Background
A Brazilian study in 265 patients with rectal cancer showed that after neoadjuvant therapy a tumor was no longer detectable in 26.8% of the patients. These patients had no surgery and underwent follow-ups [712]. After a median follow-up of 57.3 months, two patients (2.8%) had an endoluminal relapse and in three patients (4.8%) systemic metastases were found. The authors postulated that for patients with complete response after neoadjuvant radiochemotherapy a follow-up without surgery may be sufficient. However, it must be considered that this was not a randomized study. Furthermore, it is not known if these results can also be achieved outside of Brazil.
7.5.3.7 Rectal-Exstirpation
For low tumors with infiltration of the anal canal/sphincter which cannot be operated with sphincter preservation, an abdomino-perineal extirpation in the form of "cylindrical" resection including the levator ani should be performed.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 3b
- Consensus
- Consent
Background
In rectal-exstirpation the preparation rate with insufficient lateral safety margins is classically increased [713]. The oncologic results are poorer compared to sphincter preserving interventions with comparable tumor stages [714]. The extralevatoric "cylindrical“ resection leads to better safety margins and should be viewed as the superior method even without randomized studies [668].
Grade of Recommendation O:
After neoadjuvant radio-(chemo-)-therapy and/or with larger perineal defects, perineal wound healing disorders can be reduced using primary plastic reconstruction with a myocutaneous flap.
- Level of evidence
- 3b
- Consensus
- Consent
- References
- [715]
Background
The rate of perineal wound healing disorders is high especially after neoadjuvant radiation and with larger defects. However, the use of different plastic reconstruction methods remains an individual decision, which must take the special anatomical availability, the chance of secondary morbidity of the donor site defect, the surgical complexity, and the available surgical expertise into consideration [715].
7.5.4 Stoma-Construction
A temporary deviation stoma should be performed for radical surgery of rectal cancer with TME and deep anastomosis.
- Consensus
- Strong consensus
Colostomies and ileostomies are equally good as deviation stomas.
- Consensus
- Strong consensus
Background
A protective stoma can reduce the morbidity especially of clinically relevant anastamosis insufficiencies and urgent relaparotomies [716]. If primary deviation stomas are avoided, the long-term rate of permanent stomata is by no means lower [717]. There are arguments for both types of protective stomas, even if recent meta-analyses favor ileostomies [718][719].
Stoma construction should be discussed and planned with the patient as early as possible before the operation.
- Consensus
- Strong consensus
The stoma position should be marked pre-operatively.
- Consensus
- Consent
An ileostomy should be constructed prominently (> 1 cm). A colostomy should be constructed with slight elevation.
- Consensus
- Strong consensus
Background
The pre-operative information on the stoma construction should be given by the treating physician and a correspondingly trained nurse (stoma therapist). A meeting with an affected person from a self-help group - if available - should be offered. The stoma marking can be done by a trained nurse/stoma therapist. However, the doctor is responsible for the correct marking of the stoma and, thus, the correct construction. To determine the best position, it is necessary to mark the stoma position while lying down, sitting, and standing.
A postoperative stoma therapy should ensure that patients or if they are not able, their family or caregivers can independently perform the stoma care (base plate change, stoma bag emptying and change), that the supply with stoma material is ensured, and that if necessary, a stoma therapist is available. An irrigation should be offered to the colostomy carrier. In individual studies pre-operative stoma marking and the implementation of stoma therapists reduced the postoperative stoma complication rate [720][721]. Furthermore, a prospective study reported that pre-operative stoma counseling makes postoperative care easier [722].
7.5.5 Local Excision of Rectal Cancers
Local surgical excision of rectal cancers (full wall excision) as the only treatment is only recommended for pT1 cancers with a diameter up to 3cm, good or moderate differentiation, without lymph vessel invasion (low-risk histology). However, complete resection (R0) is required.
Background
Also in low-risk cases, the risk of local recurrence is higher compared to radical surgery, but local therapy is associated with reduced morbidity, mortality, and better functional results is higher compared to radical surgery. Therefore, the risk-benefit must be considered individually for each patient [727][728]. There is much to suggest that for local excision the transanal endoscopic microsurgical methods are superior to open transanal excision using a spreader [729][730].
There was no agreement on the relevance of sm-classifications to assess "low-risk“ or "high-risk“. T1-cancers with deep submucosal infiltration (sm3, according to some series even sm2) are considered by other authors and guidelines as high-risk constellations that should be treated with radical surgery [731][732][733][734].
With T1 high-risk cancers (G3/4 and/or lymph vessel invasion) and with T2 cancers, the probability of lymphatic spread is around 10-20%, so that in general local excision alone cannot be recommended. (see also section 6.4)
Background
If a "high-risk“ constellation is known before treatment, the primary operation should be radical. If a high-risk constellation does not become apparent until transanal full wall resection, the secondary radical revision surgery within one month is not associated with a poorer prognosis than with a primary radical procedure [731][735]. If the patient refuses radical revision surgery in this situation, an adjuvant radiotherapy may be considered.
7.6 Laparoscopic Surgery
Laparoscopic colon and rectal cancer resections can be performed with comparable results to open surgical techniques if the surgeon has appropriate expertise and the selection is appropriate. [6]
[6]: The word “may” is not contradictory to the recommendation grade A, as the recommendation grade refers to the equivalency of both methods.
The quality of the surgical specimen should be documented by the pathologist.
- Consensus
- Strong consensus
Background
Even if laparoscopic colorectal resections take more time to perform, numerous randomized studies indicate that in the short-term peri-operative surgical morbidity is lower than after conventional operations with unchanged overall morbidity and mortality [736]. In the incisional hernias, adhesion-related revision operations, or regional and systemic tumor relapses [737][738]. Systematic reviews and meta-analyses show equivalent oncologic long-term results especially for colon cancer. The data on rectal cancer were still insufficient. However, in the meantime, robust long-term results of the British CLASICC-study have been published despite initial problems with surrogate- parameters in the rectal cancer subgroup [740]. This study demonstrates oncologic safety of laparoscopic surgery for both colon and rectal cancer [741]. No strict criteria have been validated for defining special laparoscopic expertise that is without doubt necessary.
Recent operation procedures (e.g. robotics, NOTES) cannot be recommended, because of insufficient data outside of studies.
- Consensus
- Strong consensus
Background
The DaVinci-telemanipulation-system - the only "robot" established in clinical routine - has been used in several series for laparoscopic total mesorectal excisions [741][742]. Since neither short-term benefits nor long-term oncologic equivalency have been proven, this method must still be viewed as experimental. The same is true to an even greater extent for transgastral, transvaginal, or transanal access and specimen extraction.
7.7 Special Situations
7.7.1 Surgical Therapy of Peritoneal Carcinomatosis
For patients with isolated and limited peritoneal carcinosis a cytoreductive operation with subsequent hyperthermal intraperitoneal chemotherapy (HIPEC) can be performed done if the following criteria are fulfilled:
- PCI (peritoneal cancer index) < 20
- No extraabdominal metastases
- Possibility of macroscopic complete removal or destruction of all tumor manifestations
- Therapy at a specialized center
These procedures should preferably be performed as part of a trial
Background
So far, there is only one completed randomized study comparing systematic chemotherapy and cytoreductive surgery with HIPEC [744]. This study demonstrated also long-term that surgical therapy of peritoneal carcinosis leads to significantly better disease-specific survival [745]. If macroscopic tumor eradication was achieved, the 5- year-survival was 45%. It must be noted that the control arm only received a 5-FU-based systemic therapy. Thus, despite numerous non-randomized studies [746] with promising results, it has not been conclusively defined which patients benefit from surgical therapy with HIPEC compared to modern systemic polychemotherapy.
7.7.2 Multivisceral Resection
In the case of adherence of a tumor to neighboring organs it is not possible to determine macroscopically whether an infiltration of the neighboring organs or only a peritumorous inflammatory reaction is present. In such cases, biopsies and frozen sections should be strictly avoided, because of the possibility of local tumor cell dissemination, which can be associated with reduced survival [654]. This is the basis for performing an en-bloc resection in all cases of tumor adherence to neighboring organs or other structures (multivisceral resection). In the case of rectal cancer total pelvic exenteration can be necessary.
7.7.3 Multiple Cancers of the Colon and Rectum
In these cases a colectomy should not always be performed, instead the procedure should take into account the requirements of each individual tumor. This might require the construction of several anastomoses.
7.7.4 Emergency Surgery
In the setting of ileus, tumor perforation, or colorectal perforation with a stenotic tumor the procedure performed depends on the individual situation. If possible, the preferred surgical option is a radical resection according to the standard oncological procedures. In appropriately selected cases of ileus due to colorectal cancer, the placement of an endoluminal stent can be discussed [Khot, U. P. et al. 2002]. An ileus usually accompanies a rectal cancer only in very advanced cases, so that nearly always a neoadjuvant radio/chemotherapy should be undertaken. Therefore, in this situation a colostoma of the right transverse colon is often constructed. Tumor-associated bleeding is only rarely relevant for further decisions regarding therapy.
7.7.5 Resection of Liver Metastases
Compared to a two-stage procedure, the simultaneous resection of liver metastases most likely does not have an influence on the long-term survival if suitable patients are selected.
- Consensus
- Strong consensus
In case of certain comorbidities and older age (>70 years), the simultaneous resection of the primary tumor and liver metastases may lead to higher postoperative mortality.
- Consensus
- Consent
A multimodal two-stage procedure should be chosen in case of multiple synchronic liver metastases.
- Consensus
- Consent
Background
The decision to perform simultaneous resection of liver metastases on top of resection of the primary tumor must be considered under several aspects:
- If it is a right-sided colon resection, the liver is usually easily accessible due to the positioning of the patient and the incision path (except for very obese patients, a very large fatty liver). In case of a left-sided colon and rectal operation with the according patient positioning the liver access is much more difficult.
- Resection of individual peripheral metastases may also be performed without substantial difficulty if the patient is positioned as done for left-sided resections. Especially formal right-sided resections (e.g. right hemihepatectomy) are only acceptable with right-sided resections, because of the corresponding access.
- Especially small individual metastases are often followed by an advanced metachronic metastazation. Therefore, it is also justified, despite technical resectability, to wait and see if liver metastazation progresses and if necessary to perform systemic chemotherapy in the meantime.
Furthermore for rectal cancer, individual surgeons advocate the concept of primary liver resection without resection of the primary tumor or other preceding procedures such as neoadjuvant chemotherapy or neoadjuvant radiochemotherapy.
7.7.6 Extensive Distant Metastazation and Asymptomatic Primary Tumor
Stage IV patients with extensive liver metastazation ("metastasis liver") and asymptomatic primary tumor (no stenosis symptoms, no bleeding that needs transfusions) may undergo primary chemotherapy without resection of the primary tumor.
Background
Extensive non-resectable distant metastases usually determine the prognosis of patients with this type of metastazation. If ileus symptoms are present due to the primary tumor or if transfusions are necessary due to bleeding, prompt resection of the primary tumor (with few exceptions) is essential. If the primary tumor is asymptomatic it is, however, still not clear whether resection has a benefit for the patient. The start of chemotherapy has to be postponed because of the operation. A meta-analysis of 8 retrospective descriptive studies (from 1985-2005) showed prolonged survival for patients with resection of their primary tumor in 7 studies [747]. However, these studies were not randomized i.e. the reason for the allocation of patients to primary surgery or primary chemotherapy groups remains unknown. Furthermore, the median survival of 6 months found in some chemotherapy groups seems lower than would be expected with the chemotherapy protocols available today. The risk that during the course of primary chemotherapy surgery due to ileus or perforation becomes necessary is small according to current data (about 7%) [748]. The initiation of chemotherapy with retention of the asymptomatic primary tumor with extensive distant metastazation, thus, seems justified. The role of resection of primary tumors with extensive distant metastazation is currently being studied in a randomized study (Synchronous-study, study number ISRCTN30964555).
7.7.7 Patients with HNPCC (Hereditary Non-Polyposis Colorectal Cancer)
Prophylactic colectomy or proctocolectomy in HNPCC mutation carriers shall not be performed.
A subtotal colectomy in patients with a cancer should not generally be done, but should be discussed individually with the patient.
- Consensus
- Strong consensus
After cancer resection in addition to the usual follow-up-colonoscopic must be performed in the same interval as preoperatively. (see also Chapter 5.2.2.1)
Background
Since regular screening nearly always detects cancers in stage UICC I/II or even as premalignant adenomas [268][269] and there is incomplete penetrance of the disease, a prophylactic colectomy or proctocolectomy is not recommended.
If a cancer is detected, patients will have oncologic resections. The risk of CRC in the remaining colon and the risk of extracolic neoplasia is, however, increased. Thus, these patients must undergo an intensive postoperative follow-up. The usual follow-up for sporadic CRC should be combined with a HNPCC-specific prevention program for CRC and extracolic tumors. It is currently not known whether an extended prophylactic resection for the prevention of metachronic CRC is better than continuous surveillance. Previous data from retrospective case series are insufficient and due to national differences in screening intervals not applicable to Germany (for further information see Chapter 5.2.2.1).
7.7.8 Cancers in Familial Adenomatous Polyposis (FAP)
The procedure of choice for FAP patients is a proctocolectomy with ileo-anal pouch including a lymph node dissection depending on the localization of the carcinoma and the resulting consequences (e.g. radial vessel cutting, total mesorectal excision). Depending on anal sphincter function or an incurable tumor stage, a proctocolectomy or a limited resection can be carried out.
In attenuated FAP with only minimal involvement of the rectum, an ileorectostomy is recommended (see also 5.2.2.2)
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 3b
- Consensus
- Strong consensus
- References
- [301]
7.7.9 Cancers in Ulcerative Colitis
The preferred procedure is a proctocolectomy with an ileo-anal pouch (IAAP), if sensible according to oncological or functional considerations.
- Level of evidence
- 3b
- Consensus
- Strong consensus
For further recommendations and information e.g. on the procedures for surveillance colonoscopies, see the S3 Guideline Diagnostics and Therapy of Ulcerative colitis [395].
7.8 Postoperative Histopathological Examination
7.8.1 Cancer-Grading Based on MSI-H
Poorly differentiated adenocarcinomas including mucinous adenocarcinomas and undifferentiated cancers should be tested immunohistochemically for the expression of hMLH1 and hMSH2. If there is no hMLH1 or hMSH2 expression, they should be classified as low-grade.
- Consensus
- Consent
Background
CRCs with high-grade microsatellite instability (MSI-H) have a significantly better prognosis and lower distant metastazation rate than CRC with microsatellite stability (MSS) or low-grade microsatellite instability (MSI-L) [749][750][751][752]. Furthermore, it was shown that poorly differentiated (G3) adenocarcinomas and also mucinous adenocarcinomas which have been graded as G3 have a significantly better prognosis if MSI-H is present than if MSS or MSI-L are found [753][754]. Therefore, if there are indications for MSI-H, poorly differentiated adenocarcinomas including mucinous adenocarcinoma and undifferentiated colon cancer should not be graded as high-grade but as low-grade.
The immunohistochemical evidence of lack of hMLH1 or hMSH2 expression is as important for the prognosis as MSI-H [755]. Due to its sensitivity and specificity, it can be used as a simple and inexpensive substitute for molecular MSI testing for MSI- associated prognosis evaluations [756][757][758][759]. The immunohistochemistry for hMLH1 and hMSH2 detects sporadic MSI-H-carcinomas and some of the MSI-H-carcinomas in Lynch- syndrome. The connection of CRC with Lynch-syndrome cannot be reliably assessed with this test and requires additional testing.
7.8.2 Number of LN to be Removed
12 or more lymph nodes shall be removed and examined.
- Consensus
- Strong consensus
The ratio of tested and affected lymph nodes should be documented.
- Consensus
- Strong consensus
The greater the number of affected and examined lymph nodes, the better the prognosis of patients with CRC UICC-stage II and III.
The number of affected and examined lymph nodes can be used as a surrogate marker for the quality of treatment.
The size of a lymph node does not correlate with the probability of metastazation.
- Consensus
- Strong consensus
Background
The number of affected and examined lymph nodes depends not only on the tumor biology, but also on the surgeon and pathologist. The 7th edition of the UICC-TNM- classification 2010 specifies that for category „pN0“ a regional lymphadenectomy and histological examination of usually twelve or more lymph nodes should be done.
Although the quality of studies on the number of lymph nodes is poor, it is still true that patients with a larger number of removed and examined lymph nodes have a better prognosis in UICC-stage II and III. The correlation has been repeatedly demonstrated in cohort studies such as in 3411 stage II and III patients of the so-called intergroup-trials [663]. The so-called INTACC-study with 3491 patients also showed that the prognosis correlates with removed/examined lymph nodes [760]. However, not only the number of lymph node metastases is important, but also the number of lymph nodes in general. Both studies showed a prognostic effect even for nodal negative tumors which correlated with the number of removed/examined lymph nodes [761].
This effect was demonstrated in numerous cohorts [762][763][764][765].
The number of lymph nodes can be used as a surrogate marker for the treatment and diagnosis quality of the surgeon as well as the pathologist.
The "optimal number" of lymph nodes to be removed/examined for correct staging is controversial in the literature. However, it is definite that twelve lymph nodes are not sufficient. The sole histopathological examination of the largest lymph nodes in the preparation is not sufficient, because the lymph node size does not correlate with the probability of metastazation.
In the literature it is suggested to report the ratio of examined to affected lymph nodes [766][767][768].
For patients who have had pre-operative radiochemotherapy for locally advanced rectal cancer the number of lymph nodes is smaller. An analysis of 615 patients who were operated for primary rectal adenocarcinoma showed that 33% fewer lymph nodes were found if a neoadjuvant therapy had been performed pre-operatively [769].
7.8.3 Relevance of Distance Between the Tumor Margin and Resection Area of the Mesocolon in Colon Cancer
Analogous to the quality evaluation of the resection in rectal cancer, the quality of the colon cancer resection should also be categorized as follows:
Grade 1 (good): intact mesorectum
Grade 2 (moderate): mesorectal surface irregularities
Grade 3 (poor): defects down to the muscularis propria or the tumor
These assessments should be made by a pathologist.
- Consensus
- Consent
Background
There are no data comparable to rectal cancer on the circumferential safety margins of primary tumors in colon cancer. In addition, in colon cancer the chance of reaching a sufficient circumferential safety margin to adjacent structures or organs is much more frequent despite extensive deep-infiltration of the primary tumor. In rare cases this is not possible (e.g. for sigma-carcinoma, which is located on the iliacal vessels).
Therefore, when appropiate, analogous to rectal cancer, the circumferential safety margin should be documented.
However in the meantime, publications analogous to those for rectal cancer on the quality of the evaluation of colon cancer resections have become available. Similar to rectal cancer, it has been confirmed that tears down to the muscularis propria or reaching the tumor lead to a poorer survival rate (a 15% lower 5-year-survival rate with tears muscularis propria vs. mesorectum). In the case of lymph node metastases (UICC stage III) the difference is more pronounced (27% higher survival rate after 5 year follow- up) than if lymph node metastases are absent [770][771].
7.8.4 Relevance of Distance From the Circumferential Resection Margin (CRM-Classification) with Colon and Rectal Cancer
The circumferential safety margin is negative if it measures 1mm or more (R0 "wide“). A circumferential safety margin is positive if the circumferential safety margin is less than 1mm (R0 "close“) or if tumor tissue reaches it directly (R1). The distance should be documented quantitively.
- Consensus
- Strong consensus
Background
According to the official definition of the AJCC, the residual tumor is defined as R1 if the cancer actually histologically reaches the resection margin (RR).
However, especially publications from The Netherlands and Great Britain have shown that a circumferential safety margin of less than 1mm also significantly increases the local recurrence risk for rectal cancer (3-year local recurrence rate: 6% for CRM- and 17% for CRM+ ; 3-year tumor-free survival rate 79% for CRM- and 50% for CRM+ [644][772].
Whether a safety margin of less than 2mm leads to a poorer prognosis is controversial [773][774].
7.8.5 Relevance of Documenting the Quality of the TME-Preparation
Since the quality of the surgical resection specimens according to the abovementioned categories allows conclusions on the prognosis of local recurrence, it must be described in the pathohistological report as follows:
The quality of the resection specimens is graded by the integrity of the mesorectal fascia in 3 categories:
- Grade1 (good): mesorectal fascia is intact
- Grade 2 (moderate): intramesorectal surface tearing
- Grade 3 (poor): tearing down to the muscularis propria or the tumor
In case of rectal extirpation, preparation irregularities and tumor positive circumferential safety margins are not as frequent with a complete resection of the levator musculature. [829]
Therefore, the pathohistological report must describe the radicality in the levator musculature region. The following categories should be used:
- Grade 1 (good): levator musculature included in resection, no opening of the intestine or tumor
- Grade 2 (moderate): muscularis propria intact, no opening of the intestine or tumor
- Grade 3 (poor): parts of the muscularis propria are missing or opening of the intestine or tumor
The analysis has to be performed by a pathologist.
- Consensus
- Consent
Background
The quality of the rectal resection specimen significantly influences the local recurrence rate. If the mesorectum remained intact, the 5-year tumor-free survival was 65% compared to 47% with a defective mesorectum (P<0.05) [775]. After a 3 year follow-up, the local recurrence rate with intact mesorectal fascia was 4% (3–6%), 7% (5–11%) with intramesorectal tearing, and 13% (8–21%) if tearing had reached the muscularis proprialayer [772]
For the evaluation of preparations after rectal extirpation a distinction is made between cylindrical and standard excisions. Following a cylindrical excision, the circumferential resection margin is not as frequently affected and perforations are also significantly less frequent [770][776]. To date, data on the effect on the local recurrence and survival rate do not exist.
The quality evaluation of the surgical specimen should be performed according to the abovementioned criteria by a pathologist and not the surgeon.
The following data are obligatory components of the pathology report:
Tumor type according to WHO classification (Level of Evidence: 1c)
- Tumor invasion depth (pT-classification) (Level of Evidence: 1c)
- Regional lymph node status (pN classification) (Level of Evidence: 1c)
- Number of lymph nodes examined (Level of Evidence: 1c)
- Minimum number of lymph nodes to be examined:12 (Level of Evidence: 2a)
- Grading (Level of Evidence: 2a)
- Distance from the resection margins (with rectal cancer, circumferential) (Level of Evidence: 2a)
- R-Classification (Level of Evidence: 1c)
Background
Increasingly and especially after neoadjuvant radiochemotherapy, the degree of remission achieved is histologically classified according to Dworak [790].
Testing for microsatellite instability may be performed in case of suspected HNPCC.
7.9 Psychooncological Aspects
Psychooncological care should be included in the overall therapy concept. [7]
[7]Taken from the interdisciplinary S3-guideline for the diagnostics, therapy and follow-up of breast cancer. 832. Kreienberg, R., et al. Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Informationszentrum für Standards in der Onkologie (ISTO), Deutsche Krebsgesellschaft e.V., 2008. 1. Aktualisierung
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 1b
- References
- [791] [792] [793] [794] [795] [796] [797] [798] [799] [800] [801] [802] [803] [804] [805] [806] [807] [808] [809] [810] [811] [812] [813] [814] [815] [816] [817] [818]
All patients should be informed early by a physician about the possibilities of psychooncological support. [8]
[8] Taken from the interdisciplinary S3-guideline for the diagnostics, therapy and follow-up of breast cancer. 803. Ibid.
Background
Throughout the course of cancer, psychological burden and disorders requiring treatment occur with a frequency of 20 – 35% (cancer patients with any tumor location and stage). Most common are adaptive (F 43.12), next acute stress (F 43.0), followed by depressive disorders (major depression 8-20%, dysthymia 5-15%) [793][794][795][796]. For the CRC patient group the numbers are similar [797][798]. Advanced disease stage, marked functional impairment, and high somatic discomfort are associated with a high risk of psychological disorders [799]. The additional creation of colostomies is usually an invasive change for affected patients. Its acceptance is harder the more impairing the functional limitations are and the more massive the physical disfigurement is perceived. The patient's self-esteem can be greatly reduced as a result of a stoma, so that physical, sports, and social activities as well as going back to work are experienced as difficult and burdening. This can lead to psychological impairments. Especially the external physical change that can be seen as a result of the stoma makes adjustment difficult and leads to self-esteem and adaptive disorders up to depression [798][800]. For many affected patients the feelings of shame and disgust as well as the fear of filth and smell become a great psychological burden so that the need for intimacy is of secondary importance. Thus, stoma carriers often feel that their sex life is negatively affected [801].
A large proportion of psychological disorders in tumor patients is not correctly diagnosed and is insufficiently treated [795][802][803]. This results in negative affects on patients' physical wellbeing, functional status, symptoms (pain, nausea, fatigue), and quality of life. Therefore, the patient's psychological health should be assessed regularly during the course of the illness i.e. in all crisis phases and at times of expected high burden. Recent studies argue for the efficacy of prevention/follow-up-based psychosocial interventions for tumor patients [794][804][805]. Prevention/follow-up measures include the answering of some simple targeted questions by the patient either in personal contact or with the help of questionnaires. Different screening procedures are available for the identification of patients with high psychological burden or comorbidities that require treatment. An overview of different screening methods can be found in [806], which can be obtained online under www.pso-ag.de.
Professional psychological support/co-therapy should be available to all patients and their families. It can be performed by psychosomatic or psychiatric counseling/liaison services, by psycho-oncologic staff in organ and onocologic expert centers, or by including practicing physicians or psychological psychotherapists with psycho-oncologic qualification [807][808][809]. It should be done in close cooperation and with feedback to the treating physicians and nurses.
All CRC patients should be informed by their medical therapist (doctors and nurses) about the professional psychological support that is available.
The efficacy of different psycho-educative and psychotherapeutic interventions in tumor patients for symptom reduction (depression, anxiety, pain, fatigue), disease processing, and improvement of the quality of life has been confirmed [792][803][810][811][812][813][814][815][816][817][818].
In addition, look at the S3-Guideline Psychooncology,
AWMF -Registernummer: 032/051OL: http://www.leitlinienprogramm- onkologie.de/leitlinien/psychoonkologie/
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