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• W2150961108 abstract "Pancreatic adenocarcinoma is the fifth leading cause for cancer-related death in the United States.1American Cancer Society.http://www.cancer.orgDate: 2000Google Scholar Unfortunately, limited progress has been made toward developing suitable methods of screening individuals in hopes of identifying the disease at an earlier and potentially curable stage. Despite improvements in medical and surgical therapy, the overall 5-year survival remains at less than 5%.1American Cancer Society.http://www.cancer.orgDate: 2000Google Scholar Substantial resources are expended to achieve these results. Optimizing preoperative staging could better detect resectable lesions while sparing other patients the morbidity, mortality, and expense of unnecessary surgery. In those patients in whom there is a suspicion of a pancreatic mass lesion, evaluation centers on determining operability. Comorbid conditions including cardiovascular, pulmonary, renal, and cerebrovascular disease may preclude operative intervention irrespective of the potential resectability of the tumor. In the best of circumstances, 5-year survival ranges from 7% to 25% post-pancreaticoduodenectomy with perioperative mortality of 2% or less and morbidity of 30% to 50% at institutions with extended experience. 2Trede M Schwall G Saeger HD Survival after pancreatoduodenectomy.Ann Surg. 1990; 211: 447-458Google Scholar, 3Cameron JL Pitt HA Yeo CJ Lillemoe KD Kaufman HS Coleman J One hundred and forty-five consecutive pancreatoduodenectomies without mortality.Ann Surg. 1993; 217: 430-438Google Scholar, 4Livingston EH Welton ML Reber HA The United States' experience with surgery for pancreatic cancer.Int J Pancreatol. 1991; 9: 153-157Google Scholar, 5Nitecki SS Sarr MG Colby TV van Heerden JA Long-term survival after resection for ductal adenocarcinoma of the pancreas: is it really improving?.Ann Surg. 1994; 221: 59-66Google Scholar Although surgical resection alleviates problems associated with biliary and/or duodenal obstruction, performance of a pancreaticoduodenectomy (Whipple procedure) solely for palliative measures has not been demonstrated to improve survival or symptoms. In fact, endoscopic biliary decompression appears superior to surgical decompression with respect to treatment-related complications.6Smith AC Dowsett JF Russell RCG Hatfield ARW Cotton PB Randomized trial of endoscopic stenting versus surgical bypass in malignant low bile duct obstruction.Lancet. 1994; 344: 1655-1660Google Scholar The overall poor prognosis of patients with pancreatic adenocarcinoma must be balanced against the possibility of a potentially curative resection in selected patients. A fatalistic approach of deeming everyone incurable irrespective of the resectability status would be correct greater than 95% of the time.1American Cancer Society.http://www.cancer.orgDate: 2000Google Scholar Thus, our goal should be to properly triage patients with unresectable disease to palliative therapy and accurately identify patients who may undergo a potentially curative surgical treatment. From the start, we recognize this approach will sacrifice our sensitivity for detection of unresectability to optimize our specificity. What defines unresectable pancreatic adenocarcinoma? Certainly broad agreement with respect to metastases and major arterial involvement can be reached. However, mesenteric venous invasion may or may not preclude resection depending on the willingness of the surgeon to perform vascular reconstruction. Additionally, the resectability of tumors invading the retroperitoneum irrespective of the status of vascular involvement may be another area of variation among surgeons. That is, if the tumor invades the retroperitoneal fat but does not extend beyond the anterior plane of the aorta or inferior vena cava, one could anticipate that a resection could be undertaken with negative margins. The influence of these factors will vary among surgeons and must be carefully considered when declaring resectability on the basis of an imaging examination. For the most part, CT of the abdomen has been used for detection and staging of pancreatic adenocarcinoma. In a multicenter study, dynamic thin-section CT was demonstrated to have similar accuracy as MR in predicting resectability (70% versus 70%) of pancreas adenocarcinoma.7Megibow AJ Zhou XH Rotterdam H Francis IR Zerhouni EA Balfe DM et al.Pancreatic adenocarcinoma: CT versus MR imaging in the evaluation of resectability—report of the Radiology Diagnostic Oncology Group.Radiology. 1995; 195: 327-332Google Scholar The introduction of faster helical CT scanners and higher Telsa strength MR units with various imaging sequences and contrast agents are now providing even better performance characteristics. Recent studies have demonstrated resectability accuracy of 81% and 96%, respectively for CT and MR.8Sheridan MB Ward J Guthrie JA Spencer JA Craven CM Wilson D et al.Dynamic contrast-enhanced MR imaging and dual-phase helical CT in the preoperative assessment of suspected pancreatic cancer: a comparative study with receiver operating characteristic analysis.AJR Am J Roentgenol. 1999; 173: 585-590Google Scholar In the setting of this recent progress, where does EUS fit in? In 1992, Rösch et al.9Rösch T Braig C Gain T Feuerbach S Siewert JR Schusdziarra V et al.Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Comparison with conventional sonography, computed tomography, and angiography.Gastroenterology. 1992; 102: 188-199Google Scholar described the superiority of EUS over CT, transabdominal US and angiography in staging pancreatic adenocarcinoma. In a consecutive series of 46 patients with pancreatic carcinoma and 14 patients with ampullary carcinoma, EUS accuracy for portal venous involvement (95%) was superior to angiography (85%), CT (75%), and transabdominal US (55%). More recently, Gress et al.10Gress FG Hawes RH Savides TJ Ikenberry SO Cummings O Kopecky K et al.Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience.Gastrointest Endosc. 1999; 50: 786-791Google Scholar reaffirmed these findings (Table 1).Table 1EUS in pancreatic adenocarcinomaStaging accuracyVascular invasionnTNResectabilitySensitivitySpecificityRösch (videotape review)12Rösch T Dittler HJ Strobel K Meining A Schusdziarra V Lorenz R et al.Endoscopic ultrasound criteria of vascular invasion in the staging of pancreatic head cancer: a blind re-evaluation of videotapes.Gastrointest Endosc. 2000; 52: 469-477Abstract Full Text Full Text PDF Scopus (126) Google Scholar75———43%91%Ahmad11Ahmad NA Lewis JD Ginsberg GG Rosato EF Morris JB Kochman ML Endoscopic ultrasound in preoperative staging of pancreatic cancer.Gastrointest Endosc. 2000; 52: 463-468Abstract Full Text Full Text PDF Scopus (95) Google Scholar8969%54%46%——Gress10Gress FG Hawes RH Savides TJ Ikenberry SO Cummings O Kopecky K et al.Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience.Gastrointest Endosc. 1999; 50: 786-791Google Scholar8185%72%93%91%96%Legmann16Legmann P Vignaux O Dousset B Baraza AJ Palazzo L Dumontier I et al.Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.AJR Am J Roentgenol. 1998; 170: 1315-1322Google Scholar22*90%86%90%86%93%*Included five ampullary tumors. Open table in a new tab Both studies compared EUS with nonhelical CT which invariably influenced results in favor of EUS. In this issue of Gastrointestinal Endoscopy we discover that EUS staging of pancreatic adenocarcinoma is substantially different from that described in earlier studies. 11Ahmad NA Lewis JD Ginsberg GG Rosato EF Morris JB Kochman ML Endoscopic ultrasound in preoperative staging of pancreatic cancer.Gastrointest Endosc. 2000; 52: 463-468Abstract Full Text Full Text PDF Scopus (95) Google Scholar, 12Rösch T Dittler HJ Strobel K Meining A Schusdziarra V Lorenz R et al.Endoscopic ultrasound criteria of vascular invasion in the staging of pancreatic head cancer: a blind re-evaluation of videotapes.Gastrointest Endosc. 2000; 52: 469-477Abstract Full Text Full Text PDF Scopus (126) Google Scholar Ahmad et al.11Ahmad NA Lewis JD Ginsberg GG Rosato EF Morris JB Kochman ML Endoscopic ultrasound in preoperative staging of pancreatic cancer.Gastrointest Endosc. 2000; 52: 463-468Abstract Full Text Full Text PDF Scopus (95) Google Scholar describe a retrospective review of 89 patients with pancreatic adenocarcinoma who underwent preoperative EUS. In this study, patients underwent EUS unless “unequivocal distant metastases or vascular involvement were identified on prior cross-sectional imaging.” Whipple resection was possible in 44 (49%) patients with 14 of these having negative resection margins and no lymph node metastases. The overall T and N staging accuracy of EUS was 69% and 54%, respectively. The positive predictive value for EUS in determining resectability was 46%. Factors suggested by the authors that resulted in overstaging by EUS included overassessment of vascular involvement and the presence of chronic pancreatitis/inflammation on EUS and histopathology. Understaging by EUS was often in the context of tumors greater than 3 cm in size or major arterial or superior mesenteric vein involvement not detected by EUS. Rösch et al.12Rösch T Dittler HJ Strobel K Meining A Schusdziarra V Lorenz R et al.Endoscopic ultrasound criteria of vascular invasion in the staging of pancreatic head cancer: a blind re-evaluation of videotapes.Gastrointest Endosc. 2000; 52: 469-477Abstract Full Text Full Text PDF Scopus (126) Google Scholar critically reappraised the ability of EUS to ascertain mesenteric venous invasion in the setting of pancreatic adenocarcinoma. Seventy-five patients who underwent EUS for staging had videotape recordings of selected segments of their EUS examination reviewed by the lead investigator. During this review no clinical information (beyond the suspicion for a neoplasm) or the results of other imaging tests were available. A composite gold standard for comparison was used including surgical resection (n = 41), exploration with biopsy (n = 10), or unequivocal positive angiographic evidence for vascular involvement (n = 24). The overall sensitivity and specificity of EUS in the diagnosis of mesenteric venous invasion was 43% and 91%, respectively, when using the criteria of (1) visualization of tumor in the lumen, (2) complete vessel obstruction, and/or (3) collateral vessels detected by EUS. Less stringent criteria (tumor/vessel interface irregularity) improved sensitivity (62%) at the expense of specificity (79%). The interpretation generated at the time of the EUS (when all clinical information and imaging data were available to the operator) provided a sensitivity of 80% (p = 0.007 versus retrospective videotape review) and specificity of 91% in predicting mesenteric venous invasion. Collectively, these studies suggest that the initial enthusiasm for EUS staging of pancreatic adenocarcinoma may now require some moderation. However, before we acquiesce in this regard, let us evaluate the strengths and weaknesses of these articles. Perhaps the most problematic area in studying the staging accuracy of any imaging method in pancreatic adenocarcinoma centers on the relative carat weight of the gold standard. The high rate of recurrence even in the setting of margin negative surgical resection suggests that pancreatic adenocarcinoma is often a systemic disease at the time of diagnosis. This is supported by studies documenting a high prevalence of occult lymph node metastases as assessed by immunocytochemistry in patients with lymph node negative status on standard histopathologic examination.13Hosch SB Knoefel WT Metz S Stoecklein N Niendorf A Broelsch CE et al.Early lymphatic tumor cell dissemination in pancreatic cancer: frequency and prognostic significance.Pancreas. 1997; 15: 154-159Google Scholar Furthermore, the surgeon may overestimate or underestimate mesenteric venous invasion at the time of exploration. Furukawa et al.14Furukawa H Kosuge T Mukai K Iwata R Kanai Y Shimada K et al.Helical computed tomography in the diagnosis of portal vein invasion by pancreatic head carcinoma: usefulness for selecting surgical procedures and predicting the outcome.Arch Surg. 1998; 133: 61-65Google Scholar reported on 27 patients with pancreatic adenocarcinoma of whom 18 (67%) underwent combined resection of the portal and superior mesenteric vein when the surgeon suspected invasion based on intraoperative assessment. In 13 patients invasion was documented, however, 5 (28%) were found to be without invasion on microscopic examination of the resected vein. Conversely, Ishikawa et al.15Ishikawa O Ohigashi H Sasaki Y Nakano H Furukawa H Imaoka S et al.Intraoperative cytodiagnosis for detecting a minute invasion of the portal vein during pancreatoduodenectomy for adenocarcinoma of the pancreatic head.Am J Surg. 1998; 175: 477-481Google Scholar performed 23 intraoperative cytology touch preps of the portal/superior mesenteric venous confluence region after complete resection of pancreatic head tumors was performed. In 7 patients the cytology was positive and therefore resection of the confluence was undertaken. In 6 of these 7 patients microscopic mesenteric venous invasion was identified on histopathology. Collectively, these studies indicate inherent limitations of surgical staging and histopathology staging of pancreatic adenocarcinoma. In the series of Ahmad et al.,11Ahmad NA Lewis JD Ginsberg GG Rosato EF Morris JB Kochman ML Endoscopic ultrasound in preoperative staging of pancreatic cancer.Gastrointest Endosc. 2000; 52: 463-468Abstract Full Text Full Text PDF Scopus (95) Google Scholar 30 of the 44 patients with resection (68%) had positive margins suggesting the extent of microscopic invasion could not be fully determined. Clearly, more sophisticated techniques are needed to strengthen the gold standard. This might include the above described methods in addition to careful histopathologic assessment of the margins along the portal vein groove and remaining areas of the retroperitoneum. In the study by Rösch et al.,12Rösch T Dittler HJ Strobel K Meining A Schusdziarra V Lorenz R et al.Endoscopic ultrasound criteria of vascular invasion in the staging of pancreatic head cancer: a blind re-evaluation of videotapes.Gastrointest Endosc. 2000; 52: 469-477Abstract Full Text Full Text PDF Scopus (126) Google Scholar we must be concerned about the employment of another imaging test as a component of the gold standard. An earlier publication by these investigators reported a sensitivity and specificity of 45% and 100%, respectively, for angiography in determining mesenteric venous invasion.9Rösch T Braig C Gain T Feuerbach S Siewert JR Schusdziarra V et al.Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Comparison with conventional sonography, computed tomography, and angiography.Gastroenterology. 1992; 102: 188-199Google Scholar In the current study they use angiography examinations in which “unequivocal evidence of invasion was present.” This may have excluded patients in whom EUS was more sensitive and provided correct information despite an equivocal angiogram. Furthermore, the investigators excluded 141 patients from analysis due to incomplete staging information. Because we are not told otherwise we must presume that, in these 141 patients, the EUS was performed to assist in patient management, particularly as it related to surgical intervention. The effect of the selection bias is difficult to discount. Finally, the 37% decrement in vascular invasion assessment on the retrospective review must be tempered by the absence of complete videotape recordings representing the entirety of the EUS examination. Although the pertinent aspects were believed to be included on recorded segments viewed by the observer, it is impossible to separate what influence an incomplete videotape may have when considered together with the blinding to other clinical data and other imaging studies. Perhaps the unrecorded segments of the examination held the information necessary for an improvement in performance. The positive predictive value of EUS in determining resectability (46%) described by Ahmad et al.11Ahmad NA Lewis JD Ginsberg GG Rosato EF Morris JB Kochman ML Endoscopic ultrasound in preoperative staging of pancreatic cancer.Gastrointest Endosc. 2000; 52: 463-468Abstract Full Text Full Text PDF Scopus (95) Google Scholar is concerning. EUS determination of resectability was made post hoc through staging analysis and was not necessarily a determination offered by the EUS examiner. Specifically, EUS tumor stages T1 through T3 that did not have lymph node metastases outside of the peritumoral region were classified as resectable in the data analysis. Patients with mesenteric venous invasion on EUS were not considered resectable. This creates a problem in that some T3 tumors may be unresectable due to extensive invasion of the retroperitoneum even in the absence of vascular invasion. Additionally, at the time of surgery, when mesenteric venous invasion was suspected, a resection with venous reconstruction was not undertaken. Nonetheless, the authors clearly demonstrate problems with EUS specificity for vascular involvement in that 7 of 41 patients staged as T4 by EUS had negative resection margins. However, when two thirds of patients had positive margins after resection, it is difficult to ascertain whether or not the patients staged as T3 by histopathology and believed to have T4 tumors on EUS were correctly classified as EUS staging errors. Furthermore, this performance of EUS was in a group of patients in whom prior cross-sectional imaging failed to identify “unequivocal distant metastases or vascular involvement.” This selection bias would be expected to result in diminished accuracy for EUS. Exclusion of patients with distant metastases or severe portal hypertension from assessment of local regional staging accuracy might be expected to reduce the accuracy of EUS. Both studies excluded these patients from analysis of vascular invasion due to incomplete staging information. These patients with more advanced disease cannot be ethically explored to an extent needed to determine the locoregional spread. Intuitively, one might expect patients with distant metastases to also have more advanced local disease, thereby removing from the analysis those patients in whom EUS might perform more favorably. Based on these reports, what recommendations can be made regarding the preoperative staging of patients with known or suspected pancreatic adenocarcinoma? Recent publications support the view that dual-phase helical CT, in which imaging occurs during an arterial/pancreatic and then hepatic contrast phase enhancement, is an accurate means of determining resectability. 16Legmann P Vignaux O Dousset B Baraza AJ Palazzo L Dumontier I et al.Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.AJR Am J Roentgenol. 1998; 170: 1315-1322Google Scholar, 17Nishiharu T Yamashita Y Abe Y Mitsuzaki K Tsuchigame T Nakayama Y et al.Local extension of pancreatic carcinoma: assessment with thin-section helical CT versus with breath-hold fast MR imaging—ROC analysis.Radiology. 1999; 212: 445-452Google Scholar In a study of 22 patients with pancreatic or ampullary carcinoma, Legmann et al.16Legmann P Vignaux O Dousset B Baraza AJ Palazzo L Dumontier I et al.Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.AJR Am J Roentgenol. 1998; 170: 1315-1322Google Scholar described similar sensitivity (92% versus 100%) for mass detection and accuracy of resectability determination (90% versus 90%) for dual-phase helical CT and EUS. Recent reports suggest that state of the art MR may provide similar performance characteristics while also enhancing sensitivity for smaller lesions.8Sheridan MB Ward J Guthrie JA Spencer JA Craven CM Wilson D et al.Dynamic contrast-enhanced MR imaging and dual-phase helical CT in the preoperative assessment of suspected pancreatic cancer: a comparative study with receiver operating characteristic analysis.AJR Am J Roentgenol. 1999; 173: 585-590Google Scholar Which of these two is superior-dual-phase helical CT or state of the art MR-is unclear due to conflicting results among comparison studies. 8Sheridan MB Ward J Guthrie JA Spencer JA Craven CM Wilson D et al.Dynamic contrast-enhanced MR imaging and dual-phase helical CT in the preoperative assessment of suspected pancreatic cancer: a comparative study with receiver operating characteristic analysis.AJR Am J Roentgenol. 1999; 173: 585-590Google Scholar, 17Nishiharu T Yamashita Y Abe Y Mitsuzaki K Tsuchigame T Nakayama Y et al.Local extension of pancreatic carcinoma: assessment with thin-section helical CT versus with breath-hold fast MR imaging—ROC analysis.Radiology. 1999; 212: 445-452Google Scholar The high accuracy of CT/MR in determining locoregional spread and distant metastases suggests the role for EUS will become restricted to those patients with small tumors not detected by CT and/or MR as well as patients in whom CT/MR are inconclusive regarding extent of locoregional spread. In this setting, EUS criteria for vascular involvement that optimize specificity (tumor within the lumen and/or encasement/obstruction) should be used to minimize the possibility that a patient is not denied the opportunity of a potentially curative operation. We recognize that this group may be more problematic because these individuals will have larger neoplasms for which EUS may have greater difficulty in ascertaining disease extent. Specifically, the area of interest relative to vascular invasion typically requires imaging through the entire extent of the tumor. Current equipment with radial or curved linear scanning transducers results in progressive deterioration in resolution as depth of imaging increases. This geometry coupled with the higher US frequencies used results in diminished depth of penetration limiting our ability to visualize the region surrounding the portal vein and superior mesenteric vein. Improvements in equipment design may overcome these problems. Contrast agents, harmonic imaging, and tissue Doppler are techniques which might improve resolution and permit differentiation of peritumoral inflammatory changes from neoplasm. More sophisticated US processors available for transabdominal US that are the technologic basis for these techniques have not yet been adapted to dedicated echoendoscopes. Sharing of technology between companies with expertise in endoscope design and companies with expertise in US transducer and processor design is mandatory to allow clinicians to access these advances in imaging. Traditionally, surgical treatment of pancreas head tumors has been a Whipple resection. Some surgeons have advocated a more radical resection to include removal of more peripancreatic soft tissue and lymph nodes.18Pedrazzoli S DiCarlo V Dionigi R Mosca F Pederzoli P Pasquali C et al.Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas. A multicenter, prospective, randomized study.Ann Surg. 1998; 228: 508-517Google Scholar In a multicenter prospective randomized trial involving 81 patients comparing a standard versus extended lymphadenectomy with pancreaticoduodenectomy in adenocarcinoma of the head of the pancreas, no difference in perioperative morbidity or mortality were identified.18Pedrazzoli S DiCarlo V Dionigi R Mosca F Pederzoli P Pasquali C et al.Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas. A multicenter, prospective, randomized study.Ann Surg. 1998; 228: 508-517Google Scholar Although overall survival was similar in both groups, a trend existed for longer survival in node positive patients treated with an extended rather than standard lymphadenectomy. Although further investigation is needed, these results suggest that EUS may be useful in triaging patients to extent of surgery. Specifically, the accuracy of lymph node staging with EUS appears to be superior to CT.16Legmann P Vignaux O Dousset B Baraza AJ Palazzo L Dumontier I et al.Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.AJR Am J Roentgenol. 1998; 170: 1315-1322Google Scholar If further investigation supports the value of an extended or radical Whipple in node-positive disease, EUS may play an important role because nodal status determination before resection may be otherwise problematic. The role of fine-needle aspiration biopsy during EUS was not covered by either of the articles in this issue of the Journal. In those patients in whom the concern for a pancreatic neoplasm with distant lymphadenopathy exists, a biopsy can be performed to identify metastatic disease. Additionally, one can clarify the diagnosis of malignancy in a patient with a pancreas mass who is reluctant to undergo a surgical resection in the absence of confirmation of neoplasm. We recognize, however, that a negative biopsy of a pancreatic mass lesion where there is a suspicion of neoplasm should still relegate the otherwise operable patient to surgical intervention due to the risk of false-negative biopsies. This approach invariably will lead to a small number of patients (4% to 6%) with clinically suspected pancreatic malignancy undergoing a pancreaticoduodenectomy for what is ultimately discovered to be benign disease. 19Van Gulick TM Reeders JW Bosma A Moojen TM Smits NJ Allema JH et al.Incidence and clinical findings of benign, inflammatory disease in patients resected for presumed pancreatic head cancer.Gastrointest Endosc. 1997; 46: 417-423Google Scholar, 20Smith CD Behrns KE van Heerden JA Sarr MG Radical pancreatoduodenectomy for misdiagnosed pancreatic mass.Br J Surg. 1994; 81: 585-589Google Scholar As with any new technology, the role of EUS in the evaluation of pancreatic adenocarcinoma is undergoing an evolution. The initial enthusiasm for EUS generated by detection of pancreas mass lesions not visualized by other means was further encouraged through studies supporting a high locoregional staging accuracy in pancreatic adenocarcinoma. We have come to recognize that advances in CT/MR have improved locoregional staging performance so that the advantage for EUS has diminished. (Detection of distant metastatic disease remains the domain of CT and MR.) Currently, EUS appears to have a niche in (1) identifying neoplasms not imaged by other means and (2) allowing EUS FNA of pancreatic tumors and/or lymphadenopathy not readily accessible by percutaneous techniques. Whether EUS will be helpful in clarifying locoregional spread when CT or MR are equivocal requires further investigation. The rapid advances in body imaging necessitate improvements in EUS equipment to allow for a continued role in these challenging patients." @default.
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• W2150961108 title "Role of EUS in the evaluation of pancreatic adenocarcinoma" @default.
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