Synopsis  

Endoscopic ultrasonography (EUS) has gained a pivotal role in cancer staging for both gastrointestinal and bronchogenic or mediastinal malignancies, because of its high resolution imaging and ability to sample lesions that are often difficult to access by other methods. As advances in radiologic imaging by multidetector CT, MRI, and positron emission tomography (PET) scanning develop the role of EUS constantly needs to be evaluated, but at present it provides important complementary staging information in many patients with these malignancies. The rationale for, and roles of EUS for cancer staging are discussed in this chapter.

 EUS for cancer staging   

Accurate cancer staging is needed because it:

• provides prognostic information;
  
• guides treatment;
  
• allows researchers to compare similar patient populations.
  

The most commonly accepted reference sources for cancer staging are the American Joint Commission on Cancer (AJCC) Cancer Staging Manual [1] or the very similar International Union Against Cancer (UICC) TNM Classification of Malignant Tumours [2]. These use the tumor–node–metastasis (TNM) staging system and are revised regularly to reflect advances in clinically relevant staging.

Endoscopic ultrasound (EUS is ideally suited for local staging of luminal gastrointestinal tract cancers and pancreatic cancer, because of its ability to image both the layers of the intestinal wall and peri-intestinal lymph nodes and organs. EUS should be used after CT or MRI scan has shown no distant metastatic disease. Additionally, EUS should only be used if the information it provides will have an impact on patient care. Usually this requires close communication with the surgeon and medical oncologist caring for the patient, to determine what information will impact management. EUS staging accuracy is similar among all luminal GI tract and pancreatic cancers, with an approximate T-stage accuracy of 85% and N-stage accuracy of 75%.

 Esophageal cancer staging with EUS   

Approximately 14 250 cases of esophageal cancer are diagnosed annually in the US, of which 13 300 die of their disease [3]. Survival for esophageal cancer depends on cancer stage (Fig. 1), but overall 5-year survival is only 10–20%.

Staging is generally first performed using CT scan to look for distant metastatic disease. EUS is performed after there is no obvious evidence of distant metastases. Positron emission tomography (PET scan is also being increasingly used to evaluate for distant metastatic disease. Laparoscopy can also be used to evaluate intra-abdominal metastatic disease, but is an invasive staging tool.

Esophageal cancer TNM staging   

The TNM staging classification and stage groupings for esophageal cancer are shown in Fig. 2. There is no serosal lining of the oesophagus, and therefore invasion occurs into peri-esophageal fat. Figure 3 shows how the regional lymph nodes for esophageal cancer are defined by the anatomic location of the tumor. Metastatic disease is separated into M1a or M1b based on anatomic location of the esophageal cancer, with M1a disease associated with cervical lymph nodes for upper thoracic tumors, and celiac lymph nodes for distal esophageal cancer (Fig. 4), and M1b being any other distant metastases. For cancers of the gastroesophageal junction, lymph nodes in the celiac and left gastric nodal sites are considered regional N1 disease, and not metastatic disease.

More advanced T-stage disease is associated with greater risk of malignant lymph nodes, with 77% of patients with T3 disease having N1 disease (Fig. 5). Most patients with dysphagia have T3 disease Figs 6 and 7).

It has been suggested that the current esophageal cancer staging system be modified to more precisely reflect prognosis for survival, by dividing stage T1 into T1a (limited to mucosa) and T1b (involves into the submucosa), and also to define lymph node stage based on the number of malignant nodes, with N0, N1 (1–2 LNs), N2 (>= 3 LNs) rather than anatomic location of the nodes [4,5]. To date this has not been validated or agreed internationally.

Technique for performing EUS staging of esophageal cancer   

Upper endoscopy with a forward-viewing endoscope is usually performed first to localize the tumor precisely and to determine whether dilation is needed prior to passing the echoendoscope. Once the echoendoscope is passed into the stomach, ultrasound imaging is performed on withdrawal of the scope. Specific attention is given to determining the extent of tumor wall invasion, aortic involvement, peri-tumor lymph nodes, celiac lymph nodes, and liver metastases.

EUS of stenotic esophageal tumors   

Approximately one-third of tumors will have esophageal narrowing which prevents passage of the echoendoscope. The reason for passing the scope distal to the stricture is to evaluate for celiac lymphadenopathy, as well as staging the remainder of the tumor. Early studies using EUS to stage esophageal cancer found up to a 24% risk of esophageal perforation if esophageal dilation was performed prior to EUS [6]. However, this may have been related to the larger diameter and less tapered tips of the original EUS scopes. More recent studies suggest careful dilation may be safe. When dilation is performed, it is usually performed using either through-the-scope balloons or Savary dilators, the goal being to dilate gently the esophageal stricture up to approximately 45 Fr to allow passage of the echoendoscope. Great care must still be taken when dilating esophageal cancers to prevent perforation. If the echoendoscope cannot pass after dilation, then EUS can still partially assess the esophageal tumor, by either wedging the echoendoscope into the tumor, by using a thin wire-guided esophageal echoendoscope that does not have fiberoptic or videoendoscopy capability, or by using a catheter ultrasound probe passed through the scope.

EUS evaluation of superficial tumors   

Standard echoendoscopes (7.5 MHz, 12 MHz) can be used to evaluate superficial esophageal tumors (Fig. 8), but the low frequency may limit resolution. Higher frequency catheter probes (12, 20, and 30 MHz) provide better resolution to define mucosal vs. submucosal involvement (Fig. 7). However, the greater the frequency the less the depth of penetration, which limits visualization of adjacent lymph nodes and sometimes the true depth of penetration of the tumor.

EUS evaluation of lymph nodes   

The general EUS criteria for malignant lymph nodes include a short axis size > 10 mm, round shape, sharply demarcated borders, and echo-poor (hypoechoic) sonographic features (Fig. 9)[7]. If all four of these criteria are met, the sensitivity is 80–100%, however, only 25% of malignant lymph nodes have all these criteria [7,8]. Additionally, many endosonographers consider any round hypoechoic lymph node immediately adjacent to a tumor to be malignant. The number of nodes identified at EUS also correlates with prognosis and should be documented.

EUS-FNA of peri-esophageal lymph nodes   

Trans-esophageal or transgastric EUS fine-needle aspiration (FNA) (Fig. 10) can be used to biopsy any malignant-appearing lymph nodes. Transintestinal FNA is not performed if the needle would need to pass through luminal tumor first, in order to avoid false positive EUS-FNA cytology because of sampling of the primary tumor, and also to avoid inadvertent seeding of a benign lymph node with tumor. Another problem with EUS-FNA of lymph nodes is that a negative FNA cytology could be sampling error. The greatest utility of EUS-FNA is for diagnosing celiac lymph nodes, which might change management—celiac nodal involvement is staged as M1a disease and signals unresectability and a poor prognosis in esophageal cancer.

Accuracy and limitations of EUS staging of esophageal cancer   

The overall staging accuracy of esophageal cancer for T-stage is 85% and for N-stage 75% using diagnostic EUS [9]. The addition of EUS-FNA slightly increases the N-stage accuracy to 85% [10].

Limitations of T-stage accuracy result from overstaging or understaging. EUS tends to overstage tumors more often than understage. This is because EUS images cannot distinguish tumor from peri-tumoral inflammation. Distortion of the imaging plane due to tumor compression can also result in tangential imaging which causes the lesion to appear to have greater depth of invasion than it does. This problem is mostly seen in staging pathologic T1 and T2 tumors. Understaging may occur if there is microscopic tumor invasion, or if there is an esophageal stricture that prevents visualization of more advanced disease.

Limitations of N-stage accuracy for EUS include limitations of the morphologic appearance of the lymph nodes. Additionally, if there is a stricture, peri-esophageal or celiac lymph nodes distal to the stricture may not be visualized. Limitations of N-stage accuracy for EUS-FNA staging are that a negative FNA cytology does not completely exclude malignancy. Additionally, there is the possibility of false positive EUS-FNA cytology, as one well-designed study reported a false positive rate of 7% for EUS-FNA cytology of peri-esophageal cancer lymph nodes [10].

EUS re-staging of esophageal cancer after chemoradiation   

The accuracy of EUS staging after chemoradiation of esophageal cancer is markedly decreased because of inflammation and fibrosis, with an accuracy rate of only 40% [11,12]. The utility of re-staging cancer after chemoradiation depends on whether it can give prognostic information, and more importantly, whether the oncologist and surgeon managing the patient will use this information to decide further treatment. Upper endoscopy alone, however, may be the most useful means of re-staging patients, because this will define which 25% of patients who have undergone preoperative chemoradiation have had a complete pathologic response [12]. There are some preliminary EUS studies which suggest that a reduction in maximal cross-sectional area of the tumor is more reliable than standard TNM determination by radial EUS, but it is presently unknown if this will translate into altered clinical care [11,13]. Future studies evaluating 3-D tumor volumes by EUS are awaited.

A very promising possible use of EUS for re-staging esophageal cancer involves patients with esophageal adenocarcinoma who have a malignant celiac lymph node. Some expert esophageal cancer surgeons have proposed that if repeat EUS-FNA of the celiac node does not reveal any residual cancer, then the patient may proceed on to surgical resection, but if there is any residual tumor, then surgery should not be undertaken because it would not improve survival.

Impact of EUS staging on esophageal cancer management   

The impact of EUS staging of esophageal cancer depends somewhat on local institutional biases. The exact role of preoperative chemoradiation is still debated, although it is commonly given for suspected stage T3 or N1 tumors. Tumors with adjacent organ invasion (T4) (Fig. 7) or distant metastases are generally considered unresectable. Figure 12 shows the usual impact of EUS staging of esophageal cancer on patient management.

 Gastric cancer staging with EUS   

Approximately 90% of all gastric neoplasms are adenocarcinomas [1,2]. The overall 5-year survival is approximately 15–20%, and increases to approximately 55% if the tumor is limited to the stomach [1,2]. In the USA in 2004 there were approximately 22 710 new cases diagnosed and 11 780 deaths from gastric cancer [3].

Gastric cancer TNM staging   

TNM staging for gastric cancer differs slightly from esophageal and rectal luminal tumors, in that stage T2 is subdivided, and the number of regional lymph nodes is assessed (rather than their anatomic location). The TNM staging system and the tumor stage groupings for gastric cancer are shown in Fig. 13. Note that early stage gastric cancers can have malignant regional lymph nodes.

EUS staging of advanced gastric adenocarcinoma   

Most patients with gastric cancer in Western countries present with symptoms of abdominal pain, gastric obstruction, or bleeding. These tumors are generally bulky and locally advanced at the time of diagnosis. Because most patients with advanced gastric adenocarcinoma will undergo surgical resection without preoperative chemoradiation for palliation, the main role of EUS is to identify patients with tumors that invade into adjacent organs (Fig. 14) and who would not be operative candidates. Similarly, EUS can identify small volume ascites not detectable by other methods and which can be sampled by EUS-FNA (Fig. 15).

EUS staging of early gastric adenocarcinoma   

Early gastric cancer is most commonly detected during endoscopic screening programs in high risk parts of the world such as Asia. Lesions which are limited to the mucosal layer are amenable to attempted endoscopic mucosal resection (EMR). It is quite useful to perform EUS before attempting EMR in order to make sure there is no submucosal invasion, and to make sure there are no malignant-appearing peri-gastric lymph nodes, which would preclude attempted endoscopic resection. Imaging with higher frequency 20 MHz or 30 MHz catheter probes may be more useful for determining submucosal invasion than a dedicated 7.5/12 MHz echoendoscope. EUS has a T-stage accuracy of 80–90% for determination of early gastric cancer [14].

EUS staging of gastric MALT lymphoma   

Mucosal-associated lymphoid tissue (MALT) lymphoma of the stomach is unique in that it is almost always associated with Helicobacter pylori infection. Antibiotic treatment to eradicate H. pylori infection can lead to regression of the MALT lymphoma. EUS is useful in that patients with MALT limited to the mucosal/submucosal layers are likely to have complete response to antibiotic therapy, while those with invasion deeper than the submucosa are much less likely to respond to antibiotics [15,16].

 Rectal cancer staging with EUS   

There are 41 000 new cases of rectal cancer diagnosed in the United States each year [3]. Management of rectal cancer differs from colon cancer in that accurate preoperative staging determines the type of surgical approach to the rectal tumors and possible preoperative chemoradiation.

Rectal cancer TNM staging   

The TNM classification for rectal cancer is shown in Fig. 16. Note that N-status depends on the number of malignant regional lymph nodes. Also note that iliac nodes are considered regional lymph nodes in rectal cancer.

Pathologic staging of rectal cancer   

Most rectal cancers are at an advanced stage at diagnosis, with 75% of patients with rectal cancer presenting with stage T3 or greater, and/or N1 disease [17]. Lymph node metastases increase with T-stage, with approximate prevalence rates for T1 = 10%, T2 = 25%, and T3/4 = 50% [18,19].

Surgical management of rectal cancer   

Rectal cancer is managed differently to colonic cancer because of the limited ability of surgery to achieve clear distal margins due to the end of the rectum, and the limited ability to obtain clear radial margins because of space restraints in the pelvis.

Tumors more than 5 cm from the dentate line can be removed with a transabdominal low anterior resection, which removes the tumor, provides good radial and longitudinal margins, and allows for lymph node sampling. Tumors located within 5 cm of the dentate line usually require a complete abdominoperineal resection (APR) with permanent colostomy in order to obtain radial and longitudinal margins, as well as lymph node sampling. Transanal excision can be attempted for tumors located within 5 cm of the dentate line, and which are suspected to be pathologic stage T1, N0 or superficial T2, N0, in an effort to avoid APR and colostomy.

The main problem with traditional rectal cancer surgery is local recurrence, with rates of up to 30% reported. Recurrence rates have been reported to decrease to 20% after chemoradiation, 10% after either total mesorectal excision or preoperative radiation and traditional surgery, and 2% after preoperative radiation and total mesorectal excision [20].

Management algorithm for rectal cancer (Fig. 17)   

A general algorithm for management of rectal cancer is that if the patient is suspected to have pathologic T3 and/or N1 stage tumor, then preoperative chemoradiation is given, followed by surgery. If the lesion is staged as a T1 tumor, then either transanal or low anterior resection is performed. If the tumor is stage T2, therapy is individualized in terms of either preoperative chemoradiation or proceeding directly to surgery.

Technique for performing EUS rectal cancer staging   

Local staging with rectal EUS is usually performed after CT scan has excluded distant metastatic disease. Ultrasound staging can be performed either using a rigid ultrasound probe or a flexible echoendoscope. The advantage of the flexible echoendoscopes is direct endoscopic visualization of the tumor, in addition to ultrasound visualization.

Patient preparation is usually either with two enemas administered a few hours before the procedure as is done for flexible sigmoidoscopy, or possibly with full bowel preparation as for colonoscopy. Conscious sedation is generally not used, except in the occasional situation where the patient has significant pain from the tumor. A standard video flexible sigmoidoscope is generally used first in order to localize the lesion, assess the adequacy of the bowel prep, and to position the patient such that the lesion is in a dependent position so that it can be covered with water for good transmission of the ultrasound waves. The sigmoidoscope is withdrawn and replaced with the radial echoendoscope.

In order to assess T-stage, the scope is advanced to the tumor, water is instilled in the rectum, air in the lumen is removed with suction, and the echoendoscope balloon is partially filled with water. The transducer is placed perpendicular to the long axis of the tumor, and a few centimeters away from the tumor for the optimal focal length for the ultrasound. The scope is moved across the length of the tumor, and attention focused on depth of wall invasion, invasion into peri-rectal fat, and involvement of adjacent organs such as the bladder, prostate, seminal vesicles, vagina, or anal sphincters.

In order to assess N-stage, the scope is initially advanced under endoscopic guidance to approximately 25 cm from the dentate line. Water is instilled into the balloon, and air is removed with suction from the lumen. Initially attention is focused on visualizing the iliac vessels, which are present at 25 cm, to look for any iliac nodes. The scope is then slowly withdrawn, constantly suctioning air from the lumen, in order to evaluate for any peri-rectal lymph nodes.

EUS staging of rectal cancer   

Tumors generally appear as hypoechoic masses. Often it is not possible to tell with certainty if a tumor invades a certain level, or just abuts the level. Given this difficulty, it is acceptable to give a more descriptive staging, such as stating that the tumor invades the muscularis propria and may barely invade into the peri-rectal fat (either T2 or superficial T3, (Fig. 18). Malignant-appearing lymph nodes are generally round, hypoechoic, well-demarcated, and > 10 mm diameter. However, because peri-rectal lymph nodes are rarely seen in non-malignant transrectal ultrasound, even small (< 10 mm) peri-tumoral lymph nodes are often considered likely to be malignant by EUS.

Accuracy of EUS in staging rectal cancer   

Summaries of published literature on rectal cancer staging suggest that the T-stage accuracy is approximately 85%, and the N-stage accuracy approximately 75% [20].

When EUS staging is incorrect for depth of penetration, it is generally because of overstaging rather than understaging. This overstaging occurs because ultrasound cannot distinguish tumor from peri-tumor inflammation, and because of tangential imaging that can increase the appearance of a tumor. Overstaging is most common for stage T2 tumors, which can appear by EUS to be T3 tumors. Lymph node accuracy is limited by the ability to distinguish malignant from inflammatory lymph nodes.

EUS vs. CT and MRI for rectal cancer staging   

Most comparative studies show a greater T-stage and N-stage accuracy for EUS vs. CT scan [20]. EUS and MRI are more similar in staging accuracy.

A cost–effectiveness analysis of three different staging strategies (abdominal and pelvic CT vs. abdominal CT plus EUS vs. abdominal CT plus pelvic MRI) found that abdominal CT plus EUS is the most cost-effective approach for non-metastatic proximal rectal cancer [21].

EUS/FNA for rectal cancer lymph node staging   

It is possible that transrectal EUS-guided FNA of peri-rectal lymph nodes could improve nodal staging accuracy. However, most peri-rectal lymph nodes are usually adjacent to the primary tumor, which precludes EUS-FNA because the needle would traverse the primary tumor to reach the node, which risks either a false positive cytology or possibly seeding a benign node with tumor. Additionally, most malignant peri-rectal lymph nodes are associated with stage T3 or greater stage, and so if there is T3 disease then it is likely the visualized nodes are malignant. One prospective study did not find any increase in sensitivity or change in management with the addition of EUS-FNA compared to EUS alone for diagnosing malignant peri-rectal lymph nodes [21]. EUS-FNA of peri-rectal lymph nodes may be important in occasional cases where the T-stage is T1 or T2, but there are lymph nodes located in a position which can undergo FNA without traversing the primary tumor (Fig. 19).

Stenotic rectal tumors   

Approximately 15% of rectal cancers cannot be completely evaluated due to tumor stenosis which prevents passage of the ultrasound probe. If this occurs, the echoendoscope can usually be wedged into the distal margin of the tumor, which provides partial staging information about T and N stage. Usually these are at least stage T3 tumors.

Rectal EUS staging after radiation therapy   

The accuracy of EUS for staging rectal cancer after radiation therapy is markedly decreased due to postradiation edema, inflammation, fibrosis, and necrosis. Staging accuracy after radiation is only 50%, with a 40% overstaging rate [23,24].

Colon cancer staging with EUS   

Colon cancers are not staged with EUS because the treatment here involves surgical resection, which will provide definitive anatomic staging. There are no treatment algorithms which incorporate EUS staging for colon cancer.

 Anal cancer staging with EUS   

There were approximately 4010 new cases of anal cancer diagnosed in the USA in 2004, with 580 deaths from this malignancy [3]. Anal canal cancer is usually squamous cell carcinoma. Staging plays a somewhat less important role in management of anal cancer compared to other GI tract cancers, because most patients receive radiation therapy alone as definitive treatment, unless there is an extremely large tumor or obvious metastatic disease. Staging of anal cancer also differs from rectal cancer staging in that the actual dimensions of the tumor define T-stage, rather than depth of invasion. Anal cancer TNM staging is shown in Fig. 20. EUS can be used to help stage anal cancer and may help in determining the extent of radiation, especially if lymph nodes are involved [25].

 Pancreatic cancer   

There were estimated to be 31 860 new cases of pancreatic cancer and 31 270 deaths from pancreatic cancer in the United States in 2004. The 5-year survival rate after surgery is 3%, but if surgery achieves clear margins and negative lymph nodes, the 5-year survival rate is nearly 25% [26].

Staging of pancreatic cancer   

The currently used staging system for pancreatic cancer based on the 2002 American Joint Commission on Cancer (AJCC) Cancer staging manual, 6th edition [1] is shown in Fig. 21.

EUS staging of pancreatic cancer (Figs 12,13)   

It is important to note that most of the published literature on pancreatic cancer staging with EUS is based on the 5th edition of the AJCC Cancer staging manual. In the 5th edition staging system, stage T4 tumors involved any of the major vascular structures (portal vein, superior mesenteric vein (SMV), superior mesenteric artery (SMA), or celiac artery). However, the 2002 6th edition staging system classifies stage T3 tumors as involving either the portal vein or SMV, while T4 tumors are reserved for invasion of the SMA or celiac artery. The impetus for this change relates to the possibility of performing pancreatic resection with portal vein reconstruction in selected cases with minimal portal vein or SMV involvement, and reserving stage T4 designation for technically inoperable tumors. The implication of this is that the published TNM staging accuracy for pancreatic cancer is not based on the current staging system. It is unknown how this will change the reported staging accuracy of EUS.

Most studies show that the EUS T-stage accuracy for pancreatic cancer is approximately 85%, and the N-stage accuracy is 75% [27–30]. However, more recent studies suggest the staging accuracy may be lower. A study from the University of Pennsylvania found the T-stage accuracy to be 69%, and the N-stage accuracy to be 54% [31]. Another study from Germany reviewed videotapes of EUS cases of pancreatic tumors who had surgical or angiographic documentation of vascular invasion, and found that sensitivity and specificity for detecting vascular invasion were 43% and 91%, respectively [32].

Combination of EUS and CT/MRI for pancreatic cancer staging and determining resectability   

Data is emerging that, because neither EUS nor CT nor MRI is highly accurate in determining resectability, a combination of the tests may be the best staging strategy. A study comparing EUS and MRI found that the positive predictive value (PPV) of EUS for predicting resectability was 69% compared to 77% for MRI, but the combined PPV of EUS + MRI was 89%, and the PPV for unresectability if both agreed was 76% [33]. Another study comparing EUS, CT, and MRI found that TNM accuracy for EUS, CT, and MRI was 40, 46, and 36%, respectively [34]. Accuracy for predicting tumor resectability for EUS, CT, and MRI was 67, 83, and 75%, respectively, with the combination of CT + EUS having an accuracy of 87%. A cost minimization analysis favored the sequential strategy of first performing helical CT scan, followed by EUS as a confirmatory test in those patients with potentially resectable tumors.

Nearly all of the comparative data between EUS and CT for pancreatic cancer evaluation have involved older generation CT scanners. Image resolution and speed have improved with the introduction of multidetector CT. Preliminary results from a study from the Mayo Clinic comparing multidetector CT(MDCT) scan to EUS and MRI found that the accuracy for predicting resectability was 83% for MDCT, 81% for MRI, and 78% for EUS, and that the combination of EUS + MDCT had an accuracy of 95% for predicting resectability [35]. In contrast, a well-designed study from Indiana University revealed that both EUS and MDCT have similar rates of determining resectability of pancreatic cancer, and that the combination of the two was no better than either alone. This would suggest that MDCT might be used as the primary modality for determining resectability, especially as it would be anticipated to have improved accuracy with further advances in CT technology.

EUS-FNA for staging pancreatic cancer   

Trans-duodenal or transgastric EUS-FNA has a 90% sensitivity for obtaining a cytologic diagnosis of carcinoma in pancreatic cancer. The utility of EUS-FNA in affecting management depends on the local institutional approach to pancreatic cancer. If involved lymph nodes are not felt to preclude surgical resection, because the nodes will be removed in the surgical specimen, then FNA of the nodes will not change management and is not needed. EUS-FNA of undetected liver or mediastinal metastatic lesions is safe and potentially quite important, as this would preclude patients from undergoing attempted surgical resection due to metastatic disease [36,37]. EUS-FNA to establish a tissue diagnosis is often helpful and/or necessary to allow patients to undergo adjuvant therapy or to enter clinical trials.

Recommendations for EUS staging of pancreatic cancer   

The most prudent approach to using EUS for pancreatic cancer seems to be in conjunction with a good CT (i.e. multidetector CT using pancreatic protocol) or MRI. EUS should only be performed after CT or MRI show no obvious evidence of distant metastatic disease. If both tests suggest the patient is unresectable, then the patient does not go to surgery. If both tests suggest the patient is resectable, then the patient proceeds to surgery. If there is disagreement between the two tests, then the decision to operate should be on a case-by-case basis after informed discussion with the patient.

 Ampullary cancer   

It can sometimes be difficult to distinguish ampullary cancer from pancreatic, duodenal, or bile duct cancer. Accurate local staging is potentially important in centers where ampullary resection is performed [38]. However, in most cases locally staging is usually not critical, as most patients will undergo a pancreatic head resection. The staging criteria are shown in Fig. 24. A recent study found that EUS had a staging accuracy of 82% for T-stage and 71% for N-stage [39]. EUS can often detect small ampullary neoplasms when other imaging modalities reveal biliary or pancreatic ductal dilatation but no evidence of a mass [Fig. 25]. It is also often possible to tell whether small lesions have penetrated the duodenal muscularis and invaded the pancreas, in which case Whipple's resection is necessary.

 Extrahepatic bile duct cancer   

The staging system for extrahepatic bile duct cancer is shown in Fig. 26. Transduodenal EUS has been reported to have staging accuracy of 85% [40]. Transpapillary intraductal catheter probe EUS may also be helpful in staging these tumors [41,42].

 Future trends and outstanding issues   

The TNM staging classification of cancers is regularly updated to take account of new information about tumor behavior and endosonographers need to be constantly aware of this if they are to provide accurate staging information. In esophageal cancer, problems with the classification and accuracy of staging of junctional tumors exist and need to be clarified. Which, if any, patients with superficial lesions need EUS prior to endoscopic mucosal resection is also a subject of debate at present. The number of identified lymph nodes, not just their location, may predict prognosis and this may need to be incorporated into staging systems. Accuracy for lymph node staging remains problematic and further improvements in this area are needed. Whether or not analysis of molecular markers in EUS-FNA aspirates from lymph nodes will help in this regard requires study. Larger studies of the utility of EUS re-staging after neoadjuvant therapy are also awaited with interest.

In pancreatic cancer, other imaging modalities such as multidetector CT and MRI are improving all the time and new comparative studies of EUS with these modalities are necessary. Molecular studies of pancreatic FNA samples are underway and in the near future results of microarray and proteomic analysis on pancreatic samples obtained by EUS will be reported, hopefully pointing the way to a new role for EUS in diagnosis and staging of this malignancy.

In lung cancer, similar studies have already been reported and hopefully further studies will corroborate these promising results. Endobronchial ultrasound (EBUS) with FNA, discussed in the chapter by Dr Eloubeidi, is showing great promise and is likely to become widely used in the next few years. How it fits into the diagnostic and staging algorithm remains to be decided but it may be possible to combine EUS and EBUS to allow almost complete mediastinal staging without resort to more invasive techniques, and this is already under study.

In summary, EUS has a firmly established role in cancer staging but this role may continue to evolve as non-invasive imaging techniques improve, with a greater emphasis on obtaining tissue for cytology, histology, and molecular marker analysis.

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