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The Clinical and Pathological Staging of Gastrointestinal Cancer
PATHOLOGY
blood vessels and by seeding across peritoneal cavities. Thus, it is important that staging procedures take account of these common modes of spread. It is also notable that pathological staging, of major resection specimens taken throughout the gastrointestinal tract, can assess all of these modalities of spread. In general, pathological staging is the most powerful predictor of local recurrence, locoregional recurrence and of long-term survival. As such, it is the most important arbiter of the decision to institute adjuvant therapy, whether chemotherapy or radiotherapy. For example, in colorectal cancer, the Dukes’ stage is the single most important determinant of the decision to give postoperative chemotherapy in the UK. In the gastrointestinal tract, pathological staging is based on the comprehensive assessment of a resection specimen. Therefore, it is inevitably more accurate than clinical staging and is regarded as the ‘gold standard’ for the assessment of the extent of cancer spread. However, even pathological staging is subject to inaccuracies, since it is solely dependent upon the individual pathologist to dissect the specimen accurately and comprehensively. In fact, only in the last few years has it been shown that pathologists, in general, can accurately provide the most useful staging data for the determination of further treatment and prognosis. Much of this improvement has been driven by the introduction of the Calman-Hine report, the policy framework for commissioning cancer services. Many different staging systems have been applied to the various cancers in the gastrointestinal tract, and beyond. However, it is now accepted that standardization is important so that useful information can be exchanged between treatment centres, regionally, nationally and internationally. In the UK, certainly in pathological circles, there has been some resistance to the uptake of standardized international staging systems such as the TNM (see below). There is now increasing realisation that these systems provide the most useful staging data and there is a gradual move toward such standardized, internationally accepted staging systems and away from such time-honoured systems as the Dukes’ classification.
The Clinical and Pathological Staging of Gastrointestinal Cancer Jyoti Gupta Mark N Vipond Neil A Shepherd Staging is defined as the determination of the extent of spread of a malignant tumour. Such a determination can be made both clinically and pathologically. In this article, both of these assessments will be addressed for each of the major forms of gastrointestinal cancer. Clinical staging is undertaken once the diagnosis of gastrointestinal cancer has been made and confirmed, usually by histological examination of biopsy material. For the luminal gastrointestinal tract, such histological confirmation is mandatory, whereas for tumours arising in some organs, perhaps most notably the pancreas, such histological confirmation is sometimes not possible. Using clinical examination and a combination of special investigations, the extent of local invasion and the presence or absence of metastatic disease can be determined. Accurate clinical staging allows the selection of the most appropriate management for the patient, which may be curative or palliative and involve surgical resection, chemotherapy and/or radiotherapy or symptom control alone. Precise clinical staging may also allow the extent of potential surgery to be assessed prior to surgery. Pathological staging refers to the determination of the extent of spread by pathological means, indubitably, and is based on the size and/or extent of the primary lesion, the extent of spread to regional lymph nodes and the presence or absence of blood-borne metastases. Staging should not be confused with pathological grading, which is the degree of cytological differentiation that tumour cells show. In the gastrointestinal tract, tumours can spread by local extension, via lymphatics and
The TNM system The TNM staging system is based on the anatomical extent of spread, which may be determined, both clinically and pathologically. This is assessed in three components: • T refers to the extent of spread of the primary Tumour • N refers to the presence or absence of regional lymph Node spread • M refers to the presence or absence of distant Metastatic disease. Additional information may be provided by using prefixes or suffixes. The TNM system is applied to all gastrointestinal cancers and is universally recognized. Although it has a standardized structure, it does have drawbacks in that it does not always take account of non-anatomic factors important in prognosis and management. It is also imparts confusion because the same T denotation implies spread to different layers in the gut, for oesophagus, stomach and the colorectum (Figure 1). Furthermore, the combining of different parameters in the same stage may not provide optimal information. For instance, colorectal cancer stage pT4 combines serosal involvement with
Jyoti Gupta is a Specialist Registrar in Histopathology at Gloucestershire Royal Hospital, Gloucester, UK. She qualified from St Bartholomew’s Hospital Medical School, London, UK, and has trained in pathology in Bristol and Gloucester, UK. Mark N Vipond is a Consultant Upper Gastrointestinal Surgeon at Gloucestershire Royal Hospital, Gloucester, UK. He trained in surgery primarily in Bristol, UK, and has a special interest in laparoscopic surgery. Neil A Shepherd is a Consultant Histopathologist at Gloucestershire Royal and Cheltenham General Hospitals, Gloucestershire, UK, and Visiting Professor at the University of Cranfield, UK. He has a special interest in the causes, pathology and staging of oesophageal and colorectal cancer.
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spread to contiguous organs, although these two stages have considerably different prognosis and management strategies. Also, the system is constantly being changed and updated, necessitating the use of a reference handbook.
Tumour (T) staging by EUS is compatible with the TNM system and accurately assigns the T stage in 85% of patients. EUS is significantly more accurate than CT for lymph node staging, although the criteria for identifying malignant lymph nodes relies on morphological criteria: size (>10 mm), circularity,
The staging of oesophageal and gastric cancer Clinical staging in oesophago-gastric cancer is of vital importance in determining clinical management. Optimal treatment for these tumours is surgical resection, but the mortality and morbidity associated with oesophagectomy or gastrectomy demands that accurate preoperative clinical staging is performed to select patients with potentially curable disease. Clinical staging is achieved by: Clinical examination – cervical lymphadenopathy, hepatic enlargement or ascites would all suggest metastatic disease. Histological confirmation should be sought by FNA, biopsy or ascitic tap for cytology. Chest X-ray – which may indicate pulmonary metastases. Computed tomography (CT) scan – this is the modality of choice for detecting distant solid-organ metastases in the liver or lung for both oesophageal and gastric cancer. Local invasion of the middle oesophagus, but not cervical oesophagus or oesophago-gastric junction, is well demonstrated by CT. It is much less accurate in detecting lymph node metastases and is better for subdiaphragmatic nodes than mediastinal ones. MRI – this has similar accuracy to CT for mediastinal invasion and liver metastases, but CT is generally preferred. Endoluminal ultrasound (EUS) (Figure 2) – this uses a 7.5–12 MHz probe on a side-viewing endoscope to visualise the oesophageal and gastric wall. The depth of penetration is up to 12 cm, allowing the detection of lymph nodes and local invasion, but EUS is poor for detecting distant metastases.
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2 Endoluminal ultrasound (EUS) demonstration of a T2 oesophageal tumour that does not breach the oesophageal muscularis propria. Lymph nodes (LN) appear benign (AO = aorta).
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sharp demarcation and hypo-echoicity are the main features associated with malignancy. Accuracy of lymph node staging for oesophago-gastric cancer is approximately 85% In one-third of patients with oesophageal cancer, it may not be possible to pass the EUS endoscope because of stenosis. Of these patients, 90% will have advanced node-positive disease. An ultrasound mini-probe may be used if it is thought the findings will influence clinical management. Laparoscopy – this should be performed for all gastric and lower third oesophageal tumours. This allows visualization of the primary tumour to determine serosal involvement and local invasion. The diaphragm, peritoneum, omentum and liver are inspected for secondary deposits and biopsies may be taken. Combined with laparoscopic ultrasound, the liver and local lymph nodes may be examined; again relying on the morphological architecture to determine secondary malignancy. Mediastinoscopy – this is rarely used and is of limited value. Bronchoscopy – this is useful in upper and middle third oesophageal tumours to detect tracheo-bronchial involvement. In summary, for all patients with oesophago-gastric cancer, a combination of CT scanning and EUS can provide a clinical staging accuracy of about 90% (Figure 3). Additionally, bronchoscopy can provide useful information for upper oesophageal tumours and laparoscopy for lower third oesophageal and all gastric tumours. The resection specimen provides definitive pathological staging. Examination of the resection specimen enables assessment of resection margins, in particular the circumferential margin in oesophageal cancer. The presence of tumour within 1 mm of the circumferential margin has been reported to be an important independent prognostic variable and there is now a requirement for it to be reported routinely. This is particularly important as it predicts the likelihood of local recurrence. In more locally advanced carcinoma as well as metastatic disease, death usually occurs before local complications become apparent. T1 and T2 tumours of the oesophagus are usually completely resectable. However, lymph node metastases are present in 20–30% of tumours that invade the submucosa. The TNM classification is the most commonly used pathological staging system in oesophageal and gastric cancer. In addition to the TNM categories, a residual tumour denotation, R, is used to indicate postoperative status of the tumour. In the Japanese classification of gastric cancer, the presence of hepatic (H) and peritoneal (P) metastasis is also taken into account. The
WNM system originally described by Skinner et al has been shown to be superior to the TNM. The W represents degree of wall penetration, N indicates nodal status (N0 = no lymph nodes, N1 = 1–4 lymph nodes, N2 = >5 lymph nodes) and M refers to absence or presence of metastases. In Japan, studies have been performed to assess the usefulness of the Dukes’ classification to resectable oesophageal squamous cell carcinoma. It has been shown that the Dukes’ staging system could incorporate the number of positive lymph nodes, which correlated well with tumour progression. They proposed Dukes’ A could be used as criteria for early oesophageal carcinoma. The use of the Dukes’ classification has also been proposed as a useful staging system in gastric carcinoma. However, the TNM staging system currently remains the mainstay of pathological staging systems in oesophageal and gastric carcinoma (Figures 4 and 5). The staging of small intestinal cancer Carcinomas of the small bowel are rare. The TNM classification is most commonly applied to small bowel carcinomas whether they arise in the duodenum, jejunum or ileum. The TNM system is slightly different for carcinomas of the ampulla of Vater
TNM staging classification of oesophageal cancer T1 T2 T3 T4 N1 M1
For tumour of lower thoracic oesophagus M1a Coeliac nodes involved M1b Other distant metastasis For tumour of upper thoracic oesophagus M1a Cervical nodes involved M1b Other distant metastasis For tumour of mid-thoracic oesophagus M1b Distant metastasis including non-regional lymph nodes 4
Staging accuracy of imaging in oesophago-gastric carcinoma Imaging
CT EUS CT + EUS
Depth of invasion (T) 40% 85% 90%
TNM staging classification of gastric cancer
Lymph node Distant Staging involvement metastases accuracy (N) (M) 50% 80% 90%
85% 40% 90%
T1 T2 T3 T4 N1 N2 N3
45% 70% 80%
Tumour involves lamina propria and/or submucosa Tumour involves muscularis propria and/or subserosa Tumour penetrates serosa Tumour involves adjacent structures 1 to 6 nodes involved 7 to 15 nodes involved >15 nodes involved
5
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Tumour involves lamina propria and/or submucosa Tumour involves muscularis propria Tumour involves adventitial tissues Tumour involves adjacent structures Regional nodes involved Distant metastases
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CT scan – this may provide some information about the extent of spread of a primary tumour in the colon or rectum. However, its main use is in the detection and accurate localization of hepatic metastases within the liver (Figure 6). MRI – this is proposed as a useful means of staging primary rectal tumours, although many still consider CT scan as effective. MRI may give useful additional information about rectal tumours, especially if local resection is being considered. In recent studies, MRI with endorectal coil has been shown to be the most accurate predictor of pathological stage in rectal cancer. Despite previous comments concerning the reducing popularity of the Dukes’ classification, it remains the mainstay staging system in the management of colorectal cancer in the UK. Elsewhere, TNM staging systems are much more popular and these are of increasing importance in the UK. Dukes introduced his ABC classification in 1932 and it was originally applied only to rectal cancer, but has subsequently been successfully applied to all large intestinal cancers. Subsequent modifications of the Dukes’ system, such as the Kirklin-Dockerty, Astler-Coller, Australian Clinico-Pathological System (ACPS) and GundersonSosin systems, have added only a little useful information and have really served only to confuse an already complicated area of cancer management. Dukes himself added to the confusion by modifying his own system in 1957, although the modified Dukes–Bussey system is currently the one used most often in the UK and is that recommended by national (and some international) cancer staging guidelines (Figure 7). Although the Dukes’ classification is simple and reproducible, audits have shown that it is not well understood by nonspecialists, and this is not aided by the number of modifications to the system. For accurate pathological staging, the resection specimen must be examined meticulously, so that the most accurate data can be obtained to accurately predict prognosis. During the macroscopic and microscopic examination, the pathologist needs to identify accurately the extent of local spread, including an assessment of the relationship between the tumour and the deep (radial, circumferential, mesorectal) margin, especially in rectal cancer. Various studies have shown that involvement of this margin is the most important determinant of local recurrence, which is associated with an extremely adverse prognosis. The use of preoperative radiotherapy can significantly reduce involvement of this margin. In addition, the pathologist must achieve a harvest of all lymph nodes within the lymphatic field of the tumour: the presence or absence of lymph node involvement, itself the most important parameter influencing the decision to institute adjuvant therapy (as it determines whether or not the tumour is Dukes’ stage C), is directly proportional to the number of lymph nodes examined. The most important pathological prognostic factors in colorectal carcinoma are: • the extent of local spread • involvement of margins, especially the radial/circumferential/ mesorectal margin in rectal carcinoma • extramural venous spread • number of involved lymph nodes • peritoneal involvement • involvement of contiguous organs • tumour perforation.
compared with other sites and some have applied a modified Dukes’-type system to cancers at this site. Preoperative staging of these cancers is unusual, as the diagnosis is frequently not made until after resection. For cancers diagnosed prior to surgery (e.g. duodenal cancer) chest X-ray and ultrasound (or CT) of the liver are useful to exclude distant metastases and should be performed after resection in other cases. The staging of large intestinal cancer Clinical staging for colorectal carcinoma has been relatively neglected until recently. This is because the most effective therapy, even in the presence of metastases, has been the surgical removal of the primary tumour. However, new interventions have led to an altered perspective. For example, for patients with rectal cancer and metastatic disease, an intraluminal metal stent will give effective palliation and avoid a major laparotomy. For effective clinical staging of colorectal cancer, the following should be considered: Clinical examination – this may identify hepatic enlargement, ascites or Sister Joseph’s nodule (signifying umbilical involvement by metastatic cancer). Rectal examination can assess fixity of a rectal tumour. Colonoscopy – colonoscopy or barium enema should be performed to exclude synchronous lesions. Chest X-ray – this is essential to detect pulmonary metastases. Ultrasound – this is now routinely used to determine the presence of liver metastases preoperatively. Transrectal ultrasound will determine the local extent of rectal carcinoma through the wall of the rectum and involvement of adjacent structures. It is less reliable in detecting lymph node metastases. This improved diagnostic information is important when considering local treatment for a rectal cancer. Intra-operative ultrasound is helpful during colorectal resection for a patient with known hepatic metastases to accurately localize the site and number of metastases if hepatic resection is to be considered.
6 A CT scan demonstrating multiple hepatic metastases from a primary rectosigmoid carcinoma. In this case the tumour was stented rather than resected because of the metastatic disease.
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The modified Dukes–Bussey staging system for colorectal cancer Stage A B C1 C2
Description Tumour within bowel wall, but not penetrating completely the muscularis propria, without lymph node involvement Tumour penetrating through the full thickness of the muscularis propria into extramural tissue, without lymph node involvement Metastasis(es) to regional lymph nodes, with the ‘highest’ node uninvolved Metastasis(es) to regional lymph nodes, with the ‘highest’ node involved
Five year survival rate* 95% 75% 40% <10%
* These rates vary in different series depending on series, treatment and other factors.
7
cell carcinoma is the predominant cancer type in the anal region. Perianal tumours may be treated by excisional surgery, but anal canal tumours are now not usually subjected to surgery but are treated by chemoradiotherapy. Once again, therefore, it is evident that accurate clinical staging is important in determining choice of treatment. This is undertaken by: Trans-rectal ultrasound – this demonstrates depth of invasion and/or sphincter involvement and may detect lymph nodes. MRI – this is considered superior to CT. It complements ultrasound in detecting depth of invasion, but may also demonstrate inguinal or internal iliac node involvement. Complete pathological staging is only possible if the lesion has been completely excised. As already indicated, this rarely occurs now as most anal canal tumours are treated by chemoradiotherapy. Treatment failures may undergo abdominoperineal resection and the subsequent requirement for accurate pathological staging. These tumours (Figure 9) are staged according to the TNM classification using a similar system to that applied to skin cancers. u
TNM staging classification of colorectal cancer T1 T2 T3 T4 N0 N1 N2
Tumour involves only submucosa Tumour involves submucosa and muscularis propria Tumour involves mesorectum or subserosa, i.e. nonperitonealized pericolic/perirectal tissues Tumour involves peritoneum or other organs or structures No lymph nodes involved ≤3 regional lymph nodes involved >3 regional lymph nodes involved
8
TNM staging classification of anal cancer T1 T2 T3 T4 N1 N2 N3
Tumour size ≤2 cm Tumour size >2 to 5 cm Tumour size >5 cm Adjacent organ(s) involvement Perirectal nodal involvement Unilateral internal iliac/inguinal nodal involvement Perirectal and inguinal/bilateral internal iliac/inguinal nodal involvement
FURTHER READING Griffin S M, Raines S A, Eds. Upper Gastrointestinal Surgery. London: WB Saunders, 1997. Jerby B L, Milsom J W. Role of laparoscopy in the staging of gastrointestinal cancer. Oncology 1998; 12(9): 1353–60. Kwok H, Bissett I P, Hill G L. Preoperative staging of rectal cancer. Int J Colorectal Dis 2000; 15(1): 9–20. Montgomery R C, Ridge J A. Radiologic staging of gastrointestinal cancer. Semin Surg Oncol 1998; 15(3): 143–50. Nicholls R J, Dozois R R, Eds. Surgery of the Colon and Rectum. Edinburgh: Churchill Livingstone, 1997. Skinner D B, Little A G, Ferguson M K, Soriano A, Staszak V M. Selection of operation for esophageal cancer based on staging. Ann Surg 1986; 204(4): 391–401. TNM Classification of Malignant Tumours, 5th edition. UICC. New York: Wiley-Liss, 1997.
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Staging systems provide a combination of some, or many, of these factors. The Dukes’ classification is concerned with only the pathological findings within the resection specimen. The TNM system provides possibly the most comprehensive staging assessment of colorectal cancer but, it has to be admitted, the Dukes’ classification remains the most popular staging system for colorectal cancer in the UK (Figure 8). Current UK recommendations are that both the Dukes’ and TNM systems are recorded for all colorectal cancers, together with those factors listed above which also influence prognosis and the decision to administer adjuvant therapy. The staging of carcinomas of the anal region Carcinoma of the anus constitutes about 2% of cancers of the large bowel. Unlike other parts of the gastrointestinal tract where adenocarcinoma is the most common tumour type, squamous
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CROSS REFERENCE Petersen V C, Biddlestone L R, Shepherd N A. The spread of tumours and tumour markers. Surgery 2001; 19(3): iv–vii.
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blood vessels and by seeding across peritoneal cavities. Thus, it is important that staging procedures take account of these common modes of spread. It is also notable that pathological staging, of major resection specimens taken throughout the gastrointestinal tract, can assess all of these modalities of spread. In general, pathological staging is the most powerful predictor of local recurrence, locoregional recurrence and of long-term survival. As such, it is the most important arbiter of the decision to institute adjuvant therapy, whether chemotherapy or radiotherapy. For example, in colorectal cancer, the Dukes’ stage is the single most important determinant of the decision to give postoperative chemotherapy in the UK. In the gastrointestinal tract, pathological staging is based on the comprehensive assessment of a resection specimen. Therefore, it is inevitably more accurate than clinical staging and is regarded as the ‘gold standard’ for the assessment of the extent of cancer spread. However, even pathological staging is subject to inaccuracies, since it is solely dependent upon the individual pathologist to dissect the specimen accurately and comprehensively. In fact, only in the last few years has it been shown that pathologists, in general, can accurately provide the most useful staging data for the determination of further treatment and prognosis. Much of this improvement has been driven by the introduction of the Calman-Hine report, the policy framework for commissioning cancer services. Many different staging systems have been applied to the various cancers in the gastrointestinal tract, and beyond. However, it is now accepted that standardization is important so that useful information can be exchanged between treatment centres, regionally, nationally and internationally. In the UK, certainly in pathological circles, there has been some resistance to the uptake of standardized international staging systems such as the TNM (see below). There is now increasing realisation that these systems provide the most useful staging data and there is a gradual move toward such standardized, internationally accepted staging systems and away from such time-honoured systems as the Dukes’ classification.
The Clinical and Pathological Staging of Gastrointestinal Cancer Jyoti Gupta Mark N Vipond Neil A Shepherd Staging is defined as the determination of the extent of spread of a malignant tumour. Such a determination can be made both clinically and pathologically. In this article, both of these assessments will be addressed for each of the major forms of gastrointestinal cancer. Clinical staging is undertaken once the diagnosis of gastrointestinal cancer has been made and confirmed, usually by histological examination of biopsy material. For the luminal gastrointestinal tract, such histological confirmation is mandatory, whereas for tumours arising in some organs, perhaps most notably the pancreas, such histological confirmation is sometimes not possible. Using clinical examination and a combination of special investigations, the extent of local invasion and the presence or absence of metastatic disease can be determined. Accurate clinical staging allows the selection of the most appropriate management for the patient, which may be curative or palliative and involve surgical resection, chemotherapy and/or radiotherapy or symptom control alone. Precise clinical staging may also allow the extent of potential surgery to be assessed prior to surgery. Pathological staging refers to the determination of the extent of spread by pathological means, indubitably, and is based on the size and/or extent of the primary lesion, the extent of spread to regional lymph nodes and the presence or absence of blood-borne metastases. Staging should not be confused with pathological grading, which is the degree of cytological differentiation that tumour cells show. In the gastrointestinal tract, tumours can spread by local extension, via lymphatics and
The TNM system The TNM staging system is based on the anatomical extent of spread, which may be determined, both clinically and pathologically. This is assessed in three components: • T refers to the extent of spread of the primary Tumour • N refers to the presence or absence of regional lymph Node spread • M refers to the presence or absence of distant Metastatic disease. Additional information may be provided by using prefixes or suffixes. The TNM system is applied to all gastrointestinal cancers and is universally recognized. Although it has a standardized structure, it does have drawbacks in that it does not always take account of non-anatomic factors important in prognosis and management. It is also imparts confusion because the same T denotation implies spread to different layers in the gut, for oesophagus, stomach and the colorectum (Figure 1). Furthermore, the combining of different parameters in the same stage may not provide optimal information. For instance, colorectal cancer stage pT4 combines serosal involvement with
Jyoti Gupta is a Specialist Registrar in Histopathology at Gloucestershire Royal Hospital, Gloucester, UK. She qualified from St Bartholomew’s Hospital Medical School, London, UK, and has trained in pathology in Bristol and Gloucester, UK. Mark N Vipond is a Consultant Upper Gastrointestinal Surgeon at Gloucestershire Royal Hospital, Gloucester, UK. He trained in surgery primarily in Bristol, UK, and has a special interest in laparoscopic surgery. Neil A Shepherd is a Consultant Histopathologist at Gloucestershire Royal and Cheltenham General Hospitals, Gloucestershire, UK, and Visiting Professor at the University of Cranfield, UK. He has a special interest in the causes, pathology and staging of oesophageal and colorectal cancer.
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spread to contiguous organs, although these two stages have considerably different prognosis and management strategies. Also, the system is constantly being changed and updated, necessitating the use of a reference handbook.
Tumour (T) staging by EUS is compatible with the TNM system and accurately assigns the T stage in 85% of patients. EUS is significantly more accurate than CT for lymph node staging, although the criteria for identifying malignant lymph nodes relies on morphological criteria: size (>10 mm), circularity,
The staging of oesophageal and gastric cancer Clinical staging in oesophago-gastric cancer is of vital importance in determining clinical management. Optimal treatment for these tumours is surgical resection, but the mortality and morbidity associated with oesophagectomy or gastrectomy demands that accurate preoperative clinical staging is performed to select patients with potentially curable disease. Clinical staging is achieved by: Clinical examination – cervical lymphadenopathy, hepatic enlargement or ascites would all suggest metastatic disease. Histological confirmation should be sought by FNA, biopsy or ascitic tap for cytology. Chest X-ray – which may indicate pulmonary metastases. Computed tomography (CT) scan – this is the modality of choice for detecting distant solid-organ metastases in the liver or lung for both oesophageal and gastric cancer. Local invasion of the middle oesophagus, but not cervical oesophagus or oesophago-gastric junction, is well demonstrated by CT. It is much less accurate in detecting lymph node metastases and is better for subdiaphragmatic nodes than mediastinal ones. MRI – this has similar accuracy to CT for mediastinal invasion and liver metastases, but CT is generally preferred. Endoluminal ultrasound (EUS) (Figure 2) – this uses a 7.5–12 MHz probe on a side-viewing endoscope to visualise the oesophageal and gastric wall. The depth of penetration is up to 12 cm, allowing the detection of lymph nodes and local invasion, but EUS is poor for detecting distant metastases.
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2 Endoluminal ultrasound (EUS) demonstration of a T2 oesophageal tumour that does not breach the oesophageal muscularis propria. Lymph nodes (LN) appear benign (AO = aorta).
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sharp demarcation and hypo-echoicity are the main features associated with malignancy. Accuracy of lymph node staging for oesophago-gastric cancer is approximately 85% In one-third of patients with oesophageal cancer, it may not be possible to pass the EUS endoscope because of stenosis. Of these patients, 90% will have advanced node-positive disease. An ultrasound mini-probe may be used if it is thought the findings will influence clinical management. Laparoscopy – this should be performed for all gastric and lower third oesophageal tumours. This allows visualization of the primary tumour to determine serosal involvement and local invasion. The diaphragm, peritoneum, omentum and liver are inspected for secondary deposits and biopsies may be taken. Combined with laparoscopic ultrasound, the liver and local lymph nodes may be examined; again relying on the morphological architecture to determine secondary malignancy. Mediastinoscopy – this is rarely used and is of limited value. Bronchoscopy – this is useful in upper and middle third oesophageal tumours to detect tracheo-bronchial involvement. In summary, for all patients with oesophago-gastric cancer, a combination of CT scanning and EUS can provide a clinical staging accuracy of about 90% (Figure 3). Additionally, bronchoscopy can provide useful information for upper oesophageal tumours and laparoscopy for lower third oesophageal and all gastric tumours. The resection specimen provides definitive pathological staging. Examination of the resection specimen enables assessment of resection margins, in particular the circumferential margin in oesophageal cancer. The presence of tumour within 1 mm of the circumferential margin has been reported to be an important independent prognostic variable and there is now a requirement for it to be reported routinely. This is particularly important as it predicts the likelihood of local recurrence. In more locally advanced carcinoma as well as metastatic disease, death usually occurs before local complications become apparent. T1 and T2 tumours of the oesophagus are usually completely resectable. However, lymph node metastases are present in 20–30% of tumours that invade the submucosa. The TNM classification is the most commonly used pathological staging system in oesophageal and gastric cancer. In addition to the TNM categories, a residual tumour denotation, R, is used to indicate postoperative status of the tumour. In the Japanese classification of gastric cancer, the presence of hepatic (H) and peritoneal (P) metastasis is also taken into account. The
WNM system originally described by Skinner et al has been shown to be superior to the TNM. The W represents degree of wall penetration, N indicates nodal status (N0 = no lymph nodes, N1 = 1–4 lymph nodes, N2 = >5 lymph nodes) and M refers to absence or presence of metastases. In Japan, studies have been performed to assess the usefulness of the Dukes’ classification to resectable oesophageal squamous cell carcinoma. It has been shown that the Dukes’ staging system could incorporate the number of positive lymph nodes, which correlated well with tumour progression. They proposed Dukes’ A could be used as criteria for early oesophageal carcinoma. The use of the Dukes’ classification has also been proposed as a useful staging system in gastric carcinoma. However, the TNM staging system currently remains the mainstay of pathological staging systems in oesophageal and gastric carcinoma (Figures 4 and 5). The staging of small intestinal cancer Carcinomas of the small bowel are rare. The TNM classification is most commonly applied to small bowel carcinomas whether they arise in the duodenum, jejunum or ileum. The TNM system is slightly different for carcinomas of the ampulla of Vater
TNM staging classification of oesophageal cancer T1 T2 T3 T4 N1 M1
For tumour of lower thoracic oesophagus M1a Coeliac nodes involved M1b Other distant metastasis For tumour of upper thoracic oesophagus M1a Cervical nodes involved M1b Other distant metastasis For tumour of mid-thoracic oesophagus M1b Distant metastasis including non-regional lymph nodes 4
Staging accuracy of imaging in oesophago-gastric carcinoma Imaging
CT EUS CT + EUS
Depth of invasion (T) 40% 85% 90%
TNM staging classification of gastric cancer
Lymph node Distant Staging involvement metastases accuracy (N) (M) 50% 80% 90%
85% 40% 90%
T1 T2 T3 T4 N1 N2 N3
45% 70% 80%
Tumour involves lamina propria and/or submucosa Tumour involves muscularis propria and/or subserosa Tumour penetrates serosa Tumour involves adjacent structures 1 to 6 nodes involved 7 to 15 nodes involved >15 nodes involved
5
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Tumour involves lamina propria and/or submucosa Tumour involves muscularis propria Tumour involves adventitial tissues Tumour involves adjacent structures Regional nodes involved Distant metastases
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CT scan – this may provide some information about the extent of spread of a primary tumour in the colon or rectum. However, its main use is in the detection and accurate localization of hepatic metastases within the liver (Figure 6). MRI – this is proposed as a useful means of staging primary rectal tumours, although many still consider CT scan as effective. MRI may give useful additional information about rectal tumours, especially if local resection is being considered. In recent studies, MRI with endorectal coil has been shown to be the most accurate predictor of pathological stage in rectal cancer. Despite previous comments concerning the reducing popularity of the Dukes’ classification, it remains the mainstay staging system in the management of colorectal cancer in the UK. Elsewhere, TNM staging systems are much more popular and these are of increasing importance in the UK. Dukes introduced his ABC classification in 1932 and it was originally applied only to rectal cancer, but has subsequently been successfully applied to all large intestinal cancers. Subsequent modifications of the Dukes’ system, such as the Kirklin-Dockerty, Astler-Coller, Australian Clinico-Pathological System (ACPS) and GundersonSosin systems, have added only a little useful information and have really served only to confuse an already complicated area of cancer management. Dukes himself added to the confusion by modifying his own system in 1957, although the modified Dukes–Bussey system is currently the one used most often in the UK and is that recommended by national (and some international) cancer staging guidelines (Figure 7). Although the Dukes’ classification is simple and reproducible, audits have shown that it is not well understood by nonspecialists, and this is not aided by the number of modifications to the system. For accurate pathological staging, the resection specimen must be examined meticulously, so that the most accurate data can be obtained to accurately predict prognosis. During the macroscopic and microscopic examination, the pathologist needs to identify accurately the extent of local spread, including an assessment of the relationship between the tumour and the deep (radial, circumferential, mesorectal) margin, especially in rectal cancer. Various studies have shown that involvement of this margin is the most important determinant of local recurrence, which is associated with an extremely adverse prognosis. The use of preoperative radiotherapy can significantly reduce involvement of this margin. In addition, the pathologist must achieve a harvest of all lymph nodes within the lymphatic field of the tumour: the presence or absence of lymph node involvement, itself the most important parameter influencing the decision to institute adjuvant therapy (as it determines whether or not the tumour is Dukes’ stage C), is directly proportional to the number of lymph nodes examined. The most important pathological prognostic factors in colorectal carcinoma are: • the extent of local spread • involvement of margins, especially the radial/circumferential/ mesorectal margin in rectal carcinoma • extramural venous spread • number of involved lymph nodes • peritoneal involvement • involvement of contiguous organs • tumour perforation.
compared with other sites and some have applied a modified Dukes’-type system to cancers at this site. Preoperative staging of these cancers is unusual, as the diagnosis is frequently not made until after resection. For cancers diagnosed prior to surgery (e.g. duodenal cancer) chest X-ray and ultrasound (or CT) of the liver are useful to exclude distant metastases and should be performed after resection in other cases. The staging of large intestinal cancer Clinical staging for colorectal carcinoma has been relatively neglected until recently. This is because the most effective therapy, even in the presence of metastases, has been the surgical removal of the primary tumour. However, new interventions have led to an altered perspective. For example, for patients with rectal cancer and metastatic disease, an intraluminal metal stent will give effective palliation and avoid a major laparotomy. For effective clinical staging of colorectal cancer, the following should be considered: Clinical examination – this may identify hepatic enlargement, ascites or Sister Joseph’s nodule (signifying umbilical involvement by metastatic cancer). Rectal examination can assess fixity of a rectal tumour. Colonoscopy – colonoscopy or barium enema should be performed to exclude synchronous lesions. Chest X-ray – this is essential to detect pulmonary metastases. Ultrasound – this is now routinely used to determine the presence of liver metastases preoperatively. Transrectal ultrasound will determine the local extent of rectal carcinoma through the wall of the rectum and involvement of adjacent structures. It is less reliable in detecting lymph node metastases. This improved diagnostic information is important when considering local treatment for a rectal cancer. Intra-operative ultrasound is helpful during colorectal resection for a patient with known hepatic metastases to accurately localize the site and number of metastases if hepatic resection is to be considered.
6 A CT scan demonstrating multiple hepatic metastases from a primary rectosigmoid carcinoma. In this case the tumour was stented rather than resected because of the metastatic disease.
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The modified Dukes–Bussey staging system for colorectal cancer Stage A B C1 C2
Description Tumour within bowel wall, but not penetrating completely the muscularis propria, without lymph node involvement Tumour penetrating through the full thickness of the muscularis propria into extramural tissue, without lymph node involvement Metastasis(es) to regional lymph nodes, with the ‘highest’ node uninvolved Metastasis(es) to regional lymph nodes, with the ‘highest’ node involved
Five year survival rate* 95% 75% 40% <10%
* These rates vary in different series depending on series, treatment and other factors.
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cell carcinoma is the predominant cancer type in the anal region. Perianal tumours may be treated by excisional surgery, but anal canal tumours are now not usually subjected to surgery but are treated by chemoradiotherapy. Once again, therefore, it is evident that accurate clinical staging is important in determining choice of treatment. This is undertaken by: Trans-rectal ultrasound – this demonstrates depth of invasion and/or sphincter involvement and may detect lymph nodes. MRI – this is considered superior to CT. It complements ultrasound in detecting depth of invasion, but may also demonstrate inguinal or internal iliac node involvement. Complete pathological staging is only possible if the lesion has been completely excised. As already indicated, this rarely occurs now as most anal canal tumours are treated by chemoradiotherapy. Treatment failures may undergo abdominoperineal resection and the subsequent requirement for accurate pathological staging. These tumours (Figure 9) are staged according to the TNM classification using a similar system to that applied to skin cancers. u
TNM staging classification of colorectal cancer T1 T2 T3 T4 N0 N1 N2
Tumour involves only submucosa Tumour involves submucosa and muscularis propria Tumour involves mesorectum or subserosa, i.e. nonperitonealized pericolic/perirectal tissues Tumour involves peritoneum or other organs or structures No lymph nodes involved ≤3 regional lymph nodes involved >3 regional lymph nodes involved
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TNM staging classification of anal cancer T1 T2 T3 T4 N1 N2 N3
Tumour size ≤2 cm Tumour size >2 to 5 cm Tumour size >5 cm Adjacent organ(s) involvement Perirectal nodal involvement Unilateral internal iliac/inguinal nodal involvement Perirectal and inguinal/bilateral internal iliac/inguinal nodal involvement
FURTHER READING Griffin S M, Raines S A, Eds. Upper Gastrointestinal Surgery. London: WB Saunders, 1997. Jerby B L, Milsom J W. Role of laparoscopy in the staging of gastrointestinal cancer. Oncology 1998; 12(9): 1353–60. Kwok H, Bissett I P, Hill G L. Preoperative staging of rectal cancer. Int J Colorectal Dis 2000; 15(1): 9–20. Montgomery R C, Ridge J A. Radiologic staging of gastrointestinal cancer. Semin Surg Oncol 1998; 15(3): 143–50. Nicholls R J, Dozois R R, Eds. Surgery of the Colon and Rectum. Edinburgh: Churchill Livingstone, 1997. Skinner D B, Little A G, Ferguson M K, Soriano A, Staszak V M. Selection of operation for esophageal cancer based on staging. Ann Surg 1986; 204(4): 391–401. TNM Classification of Malignant Tumours, 5th edition. UICC. New York: Wiley-Liss, 1997.
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Staging systems provide a combination of some, or many, of these factors. The Dukes’ classification is concerned with only the pathological findings within the resection specimen. The TNM system provides possibly the most comprehensive staging assessment of colorectal cancer but, it has to be admitted, the Dukes’ classification remains the most popular staging system for colorectal cancer in the UK (Figure 8). Current UK recommendations are that both the Dukes’ and TNM systems are recorded for all colorectal cancers, together with those factors listed above which also influence prognosis and the decision to administer adjuvant therapy. The staging of carcinomas of the anal region Carcinoma of the anus constitutes about 2% of cancers of the large bowel. Unlike other parts of the gastrointestinal tract where adenocarcinoma is the most common tumour type, squamous
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CROSS REFERENCE Petersen V C, Biddlestone L R, Shepherd N A. The spread of tumours and tumour markers. Surgery 2001; 19(3): iv–vii.
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