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The role of laparoscopy and laparoscopic ultrasound in the diagnosis of cystic lesions of the pancreas
Gastrointest Endoscopy Clin N Am 12 (2002) 759 – 767
The role of laparoscopy and laparoscopic ultrasound in the diagnosis of cystic lesions of the pancreas Pinhas P. Schachter, MDa,b,*, Mordechai Shimonov, MDa,b, Abraham Czerniak, MDa,b a
b
Department of Surgery ‘‘A,’’ E Wolfson Medical Center, Holon 58100, Israel Department of Surgery, Sackler School of Medicine, Tel Aviv University, 69978 Tel-Aviv, Israel
With the widespread use of advanced imaging techniques, cystic lesions of the pancreas are now diagnosed relatively frequently. The nature of these lesions varies from benign cysts (serous cystadenoma) or an inflammatory process (pseudocyst) to premalignant (mucinous cystadenoma) or frankly malignant lesions (cystadenocarcinoma) [1,2]. Inflammatory pseudocysts, which represent about 70% of lesions, are actually pancreatic secretions walled-off by a thick fibrotic capsule devoid the epithelial lining characteristic of a cyst. They often resolve spontaneously, but when symptoms persist, drainage is indicated. Serous cystadenomas are benign, small, microcystic lesions usually grouped together in a ‘‘honeycomb’’ fashion. These cysts may grow in size causing pressure symptoms or pain [3]. Mucinous cystadenomas carry a malignant potential. Ten percent to 20% of the resected cysts reveal malignancy at histopathologic examination [4]. Therefore, mucinous cystadenomas and malignant cystadenocarcinomas should be resected. Indeed, about 15% of the pancreatic cysts are actually cystic neoplasms, which are potentially curable with timely resection [5– 8]. Differentiation of various types of pancreatic cysts presents a diagnostic and therapeutic challenge. Clinical presentation may be vague; most patients present with few symptoms, if any. The absence of a history of pancreatitis and normal serum levels of amylase raise the suspicion of a cystic neoplasm. The multitude of invasive and noninvasive diagnostic modalities is confusing, and it may be difficult to choose a particular diagnostic schedule for an individual
* Corresponding author. Department of Surgery ‘‘A,’’ E. Wolfson Medical Center, Holon 58100, Israel. E-mail address: [email protected] (P.P. Schachter). 1052-5157/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved. PII: S 1 0 5 2 - 5 1 5 7 ( 0 2 ) 0 0 0 2 9 - 6
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patient. Modern noninvasive imaging techniques, such as CT, ultrasound, and MRI may disclose features of pancreatic cysts that should raise suspicion that a cystic neoplasm is present; however, these criteria are not uniformly reliable in the final diagnosis of neoplasms [9,10]. ERCP contributes additional information with regard to the relationship of the cyst to the pancreatic ductal system. Demonstration of ductal changes of chronic pancreatitis, or a direct communication of the pancreatic ductal system to the cyst combined with high levels of amylase within the cyst, supports the diagnosis of pseudocyst. Still, in rare instances cystadenomas or cystadenocarcinomas may contain high amylase levels and communicate to the pancreatic ductal system [11 –13]. Aspiration of cystic fluid for analysis and biopsy of the cyst’s wall have been of considerable interest; however, it may be difficult to localize small lesions with sufficient precision to guide the aspiration needle. Moreover, percutaneous CT- or ultrasound-guided needle aspiration carries the risk of needle tract and peritoneal dissemination of tumor cells as well as spillage of malignant cyst’s contents [14]. Even examination of biopsy material obtained during surgery may fail to differentiate cystic lesions correctly in as much as 20% of cases [4]. Endoscopic ultrasound is an important evolving tool enabling detailed visualization and ultrasound-guided fine needle aspiration of most pancreatic cysts because of its close proximity to the lesion [11]. Endoscopic ultrasound has high sensitivity rates for pancreatic lesions, yet specificity rates for malignancy are in the range of 75% to 80% [15]. Endoscopic ultrasound provides morphologic details that contribute to the differentiation of pancreatic cysts [16]. Nevertheless, experienced endosonographists point to some of the technical limitations [11]: a. Endoscopic ultrasound visualization of cystic lesions not in close proximity to the pancreas is difficult. This occurs mainly when pseudocysts develop away from the inferior border of the pancreas. b. Penetration of the endoscopic ultrasound view to adjacent organs (liver, peritoneal cavity) is significantly limited. c. Aspiration and fine needle aspiration can be performed only with a linear endosonoscope. Only one needle pass is usually performed to minimize the danger of leak. d. It is sometimes difficult to place the lesion in close proximity to the gastric or duodenal wall and thus the needle may traverse a length of a normal pancreas. The introduction of laparoscopy and laparoscopic ultrasonography greatly facilitates diagnosis of pancreatic cystic lesions. The sonographic probe is placed under vision directly on the lesion, regardless of its anatomic location. Thus, imaging of the various cystic components and surrounding organs is ideal. Puncture of the cyst is controlled under vision, and aspiration of the cyst’s content with a large bore needle prevents spillage and occlusion of the needle by mucus or debris. A core biopsy is easily obtained for histopathologic examination after the cyst’s content has been removed [17].
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Method Laparoscopy and laparoscopic ultrasonography (LAPUS) are performed under general anesthesia by a standard technique. A disposable 10-mm cannula is introduced at the umbilicus and inspection of the abdominal cavity is performed with a 30° telescope (Sharplan i-Sight, Digital computer-based video camera, Sharplan Usight, Tel-Aviv, Israel). An additional 10-mm cannula for direct-contact LAPUS is inserted usually in the right upper abdominal quadrant. This position may change according to the location of the cyst. LAPUS is performed with a 10-mm 8-Mhz sectoral contact ultrasound probe (Sharplan u-sight intraoperative laparoscopic ultrasound system). The laparoscopic probe is equipped with a fingertip adjustable viewing angle from 0 to 45°, both right and left. The system enables simultaneous view of the laparoscopic and ultrasonographic images using ‘‘picture in picture’’ visual mixing (Sharplan, bisight, digital video mixer). The Doppler system is useful in differentiating cystic lesions from venous and arterial vessels and is applied routinely before puncture of the cyst. LAPUS guided biopsy is performed with an 18-gauge biopsy needle (Quick core biopsy needle, Cook, Bloomington, IN, USA) (Fig. 1). LAPUS guided puncture of the cyst is performed with a large-bore needle, followed by immediate aspiration of the cyst to prevent spillage of cystic contents and peritoneal dissemination [6]. The cystic fluid is submitted to cytologic analysis to check for glycogen staining cells or the presence of mucus and chemical determination of tumor markers and amylase levels. A core biopsy of the cystic wall (in instances of a cystic wall of 2 mm or thicker) and intracystic structures is obtained for histopathologic examination without the damage of traversing the pancreas, duodenum, or stomach in the process. Communication of the cyst to the pancreatic ductal system can be evaluated by injection of contrast media into the cyst and intraoperative cystopancreatogram. A combination of the various ultrasonographic cystic and pancreatic parameters, with the results of histopathologic, cytologic, and cystic fluid aspirate analysis enables accurate diagnosis and appropriate management of these patients.
Chronic pancreatitis and pancreatic cystic lesions The association between chronic pancreatitis and pancreatic tumors is well established [18]. Parenchymal changes such as fibrosis and calcification that enhance the hyperechoic ultrasonographic appearance of the pancreas, as well as demonstration of ductal changes, are characteristic of chronic pancreatitis. A direct communication between the ductal system and the cyst together with high levels of amylase within the cyst suggests the diagnosis of a pseudocyst as demonstrated. In the rare instance of the so-called ductectatic cystic neoplasm or intraductal papillary mucinous tumors (IPTM), a neoplastic transformation in one of the
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Fig. 1. LAPUS guided biopsy. (A) Laparoscopic view of the probe and needle. (B) Ultrasound guided biopsy. The line indicates the imaginary needle passage.
Fig. 2. LAPUS view of serous cystadenoma of pancreas. (A) A thin-walled cyst containing turbid fluid. (B) Septae within the cyst are noted (arrow).
Fig. 3. LAPUS view of mucinous cystadenoma of pancreas. (A) Ultrasound view of an irregular cystic wall. (B) A solid, papillary component of the cystic wall (arrow). (From Schachter P, Avni Y, Gvirtz G, et al. The impact of laparoscopy and laparoscopic ultrasound on the management of pancreatic cystic lesions. Arch Surg 2000;135:262; with permission.)
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Fig. 4. LAPUS view of mucinous cystadenoma of pancreas. (A) LAPUS view demonstrating a thinwalled, benign appearing cystic lesion. (B) Puncture and aspiration of the cystic content results in collapse of the cyst revealing a previously hidden solid mass (arrow).
Fig. 5. LAPUS appearance of a benign cystic lesion. (A) The cystic lesion in close proximity to blood vessels. SMV, superior mesenteric vein; SMA, superior mesenteric artery. (B) Maneuvering the US probe creates a US ‘‘window’’ enabling puncture of a thick-walled benign cyst.
Fig. 6. LAPUS evaluation of a cystic lesion of the pancreas. (A) The cystic lesion is in close proximity to another small ‘‘cyst’’ The arrow indicates the SMA. (B) Doppler study of the suspect ‘‘cyst’’ demonstrates it to be the SMA.
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pancreatic ducts creates a cyst that does communicate with the ductal system [12,13]. These lesions consist of a dilated pancreatic duct with a cystic and mass component that are difficult to differentiate from chronic pancreatitis, yet a small nodule may be visualized in the wall of the dilated pancreatic duct [11].
The presence of additional cystic lesions Additional small cysts suggest the diagnosis of serous cystadenoma. These lesions are characteristically composed of multiple small cysts separated by thin walls without any internal structure. LAPUS enables demonstration of additional small lesions, 3 mm and larger in diameter. Indeed, small cysts not visualized by previous imaging modalities were detected by LAPUS in three of our patients. Larger serous cystadenomas may contain turbid fluid, septae, and calcifications (Fig. 2) or even communicate with the ductal system, raising the possibility of a mucinous cystadenoma [19,20].
The nature of the cyst’s wall (thickness/uniformity/regularity) We have learned to consider the ultrasonographic characteristics of the wall of the cyst as an important parameter for differentiation. Thus, a uniformly thin (1 –2mm) and regular wall is suggestive of a benign nature. Pseudocysts are an exception, characteristically having a thickened wall [21]. An irregular or focally thickened cystic wall or a solid component within the wall as demonstrated in eight of our patients suggests a rather malignant potential (Fig. 3). Only one patient with a focally thickened cystic wall component was found to have a serous cystadenoma. Irregularity of the cystic wall or a mass adjacent to the cyst may sometimes become apparent after aspiration and collapse of the cyst (Fig. 4). Such a mass is highly suggestive of a malignant cystadenoma [22].
Biopsy and aspiration of cystic components The LAPUS study offers greater ultrasound maneuverability, creating an ‘‘ultrasound window’’ for biopsy, even in patients where proximity to the mesenteric vessels precluded CT- or endoscopic-guided puncture (Fig. 5). We recommend routine use of the Doppler system before puncture of the cyst to identify blood vessels in the nearby surroundings of the cyst and certify a safe ultrasonographic window for the needle passage (Fig. 6). Direct contact of the ultrasound probe prevents passage of the needle through other tissues. In our experience, a thin ( < 1 mm) cystic wall is the only instance when obtaining an adequate biopsy is not possible; however, in most such cases biopsy is actually not needed for diagnosis. After aspiration of the cystic fluid one should carefully screen the surrounding pancreatic tissue for previously hidden masses.
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Histologic analysis of the cystic wall and cytologic examinations of the cystic aspirate contribute important information to the diagnosis. Glycogen staining cells and the absence of mucin in the aspirate are diagnostic of a serous cystadenoma, yet only 50% of aspirate cytology is positive in serous cystadenoma [23]. In our experience most serous cystadenoma aspirates are acellular, although in one case pancreatic ductal cells without atypia were obtained. The fluid of pseudocysts usually contains necrotic tissue, blood, and debris. Cytology can show pancreatic cells, inflammatory cells, or leukocytes. There should be no epithelial cells or mucin in the aspirate. LAPUS offers an advantage over endoscopic ultrasound because there is no contamination of the aspirate with gastric or duodenal epithelial cells, which can result in a false-positive cytologic analysis for mucinous cystadenoma. Aspiration of mucoid fluid and the presence of epithelial cells confirm the diagnosis of a mucous cystadenoma, but epithelial cells
Fig. 7. Algorithm for evaluation of patients with pancreatic cystic lesions.
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are present in only 48% of the cases [17]. In our experience mucinous fluid was found in 70% (7 of 10 patients), yet epithelial cells were revealed only in one case. The presence of mucin, malignant cells, and determination of neoplastic markers in the cystic fluid are useful in differentiating mucinous from serous cystic lesions, whereas high pancreatic enzyme content usually suggests a pseudocyst. Markers commonly studied examined are carcinoembryonic antigen (CEA), carbohydrate 19.9 (Ca 19.9), Ca 15.3, Ca 72.4, and tissue polypeptide antigen (TPA) [6,15,24,25]. Data obtained from our patients supports the high specificity of increased CEA and Ca 19.9 levels in mucinous cystadenomas and carcinomas. We, like others [4], have learned to consider raised CEA levels more important than Ca19.9 levels that may be elevated in benign conditions. However, our single false positive patient with serous cystadenoma had significantly increased levels of both CEA and Ca 19.9. Decisions regarding resection of a particular cyst are based upon analysis of all obtained information. Indeed, the demonstration of malignancy or mucinous cyst components are a clear indication for resection, but in the absence of this information, the decision is based on the ultrasonographic nature of the cystic wall, histologic analysis, and the levels of tumor markers obtained from the cystic aspirate. Therefore, an algorithm for evaluation of patients with pancreatic cystic lesions is most important (Fig. 7). In conclusion, LAPUS study, the biopsy of the cystic wall, and analysis of the cystic aspirate, although expensive and rather invasive procedures, significantly contribute to the differential diagnosis of pancreatic cystic lesions.
References [1] Warshaw AL, Compton C, Lewandrowski KB, Cardenosa G, Mueller PR. Cystic tumors of the pancreas: new clinical, radiologic and pathologic observations in 67 patients. Ann Surg 1990; 212:432 – 45. [2] Compagno J, Oertel J. Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol 1978;69:573 – 80. [3] Siech M, Tripp K, Schmidt-Rohlfing B, Mattfeldt T, Widmaier U, Gansuage F, et al. Cystic tumors of the pancreas: diagnostic accuracy, pathologic observations and surgical consequences. Langenbecks Arch Surg 1998;383:56 – 61. [4] Lewandrowski KB, Southern JF, Pins M, Compton CC, Warshaw AL. Cyst fluid analysis in the differential diagnosis of pancreatic cysts: a comparison of pseudocysts, serous cystadenomas, mucinous cystic neoplasms, and mucinous cystadenocarcinoma. Ann Surg 1993;217:41 – 7. [5] Lumsden A, Bradley EL. Pseudocyst or cystic neoplasm?: Differential diagnosis and initial management of cystic pancreatic lesions. Hepatogastroenterology 1989;36:462 – 7. [6] Yang JM, Southern JF, Warshaw AL, Lewandrowski KB. Proliferation tissue polypeptide antigen distinguishes malignant mucinous cystadenocarcinoma from benign cystic tumors and pseudocysts. Am J Surg 1996;171:126 – 9. [7] Warshaw AL, Rutledge PL. Cystic tumors mistaken for pancreatic pseudocysts. Ann Surg 1987; 205:393 – 8. [8] Becker WF, Welsh RA, Pratt HS. Cystadenoma and cystadenocarcinoma of the pancreas. Ann Surg 1965;161:845 – 63.
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[9] Bastid C, Sahel J, Sastre B, Schurgers P, Sarles H. Mucinous cystadenocarcinoma of the pancreas: ultrasonographic findings in 5 cases. Acta Radiol 1989;30:45 – 7. [10] Johnson CD, Stephens DH, Charboneau JW, Carpenter HA, Welch TJ. Cystic pancreatic tumors: CT and sonographic assessment. Am J Roentgenol 1988;151:1133 – 8. [11] Brugge WR. The role of EUS in the diagnosis of cystic lesions of the pancreas. Gastrointest Endosc 2000;52(Suppl 6):S18 – 22. [12] Itai Y, Ohhashi K, Nagai H. ‘‘Duct ectatic’’ mucinous cystadenoma and cystadenocarcinoma of the pancreas. Radiology 1986;161:697 – 700. [13] Furukawa T, Takahashi T, Kobari M, Matsuno S. The mucous-hypersecreting tumor of the pancreas. Cancer 1992;70:1505 – 13. [14] Wiersema MJ, Vilmann P, Giovannini M, Chang KJ, Wiersma LM. Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology 1997;112:1087 – 95. [15] Yamaguchi K, Enjoji M. Cystic neoplasms of the pancreas. Gastroenterology 1987;92:1934 – 43. [16] Koito K, Namieno T, Nagakawa T, Shyonai T, Hirokawa N, Morita K. Solitary cystic tumor of the pancreas: EUS-pathologic correlation. Gastrointest Endosc 1997;45:268 – 76. [17] Sperti C, Pasquali C, Guolo P, Polverosi R, Liessi G, Pedrazzoli S. Serum tumor markers and cyst fluid analysis are useful for the diagnosis of pancreatic cystic tumors. Cancer 1996;78: 237 – 43. [18] Yeo CJ, Sarr MG. Cystic and pseudocystic diseases of the pancreas. Curr Prob Surg 1994;31(3): 165 – 252. [19] Torresan F, Casadei R, Solmi L, Marrano D, Gandolfi L. The role of ultrasound in the differential diagnosis of serous and mucinous cystic tumours of the pancreas. Eur J Gastroenterol Hepatol 1997;9:169 – 72. [20] Gouhiri M, Soyer P, Barbagelatta M, Rymer R. Macrocystic serous cystadenoma of the pancreas: CT and endosonographic features. Abdom Imaging 1999;24:72 – 4. [21] Schachter P, Avni Y, Gvirtz G, et al. The impact of laparoscopy and laparoscopic ultrasound on the management of pancreatic cystic lesions. Arch Surg 2000;135:260 – 4. [22] Centeno BA, Warshaw AL, Mayo-Smith W, Southern JF, Lewandrowski KB. Cytologic diagnosis of pancreatic cystic lesions: a prospective study of 28 percutaneous aspirates. Acta Cytol 1997;41:972 – 80. [23] Carlson SK, Johnson CD, Brandt KR, Batts KP, Salomao DR. Pancreatic cystic neoplasms: the role and sensitivity of needle aspiration and biopsy. Abdom Imaging 1998;23:387 – 93. [24] Tatsuta M, Iishi H, Ichii M, Noguchi S, Yamamoto R, Yamamura H, et al. Values of carcioembryonic antigen, elastase-1, and carbohydrate antigen determinant in aspirated pancreatic cystic fluid in the diagnosis of cysts of the pancreas. Cancer 1986;57:1836 – 9. [25] Hammel P, Voitot H, Vilgrain V, Levy P, Ruszniewski P, Bernades P. Diagnostic value of CA 72 – 4 and carcinoembryonic antigen determination in the fluid of pancreatic cystic lesions. Eur J Gastroenterol Hepatol 1998; 10:345 – 8.
The role of laparoscopy and laparoscopic ultrasound in the diagnosis of cystic lesions of the pancreas Pinhas P. Schachter, MDa,b,*, Mordechai Shimonov, MDa,b, Abraham Czerniak, MDa,b a
b
Department of Surgery ‘‘A,’’ E Wolfson Medical Center, Holon 58100, Israel Department of Surgery, Sackler School of Medicine, Tel Aviv University, 69978 Tel-Aviv, Israel
With the widespread use of advanced imaging techniques, cystic lesions of the pancreas are now diagnosed relatively frequently. The nature of these lesions varies from benign cysts (serous cystadenoma) or an inflammatory process (pseudocyst) to premalignant (mucinous cystadenoma) or frankly malignant lesions (cystadenocarcinoma) [1,2]. Inflammatory pseudocysts, which represent about 70% of lesions, are actually pancreatic secretions walled-off by a thick fibrotic capsule devoid the epithelial lining characteristic of a cyst. They often resolve spontaneously, but when symptoms persist, drainage is indicated. Serous cystadenomas are benign, small, microcystic lesions usually grouped together in a ‘‘honeycomb’’ fashion. These cysts may grow in size causing pressure symptoms or pain [3]. Mucinous cystadenomas carry a malignant potential. Ten percent to 20% of the resected cysts reveal malignancy at histopathologic examination [4]. Therefore, mucinous cystadenomas and malignant cystadenocarcinomas should be resected. Indeed, about 15% of the pancreatic cysts are actually cystic neoplasms, which are potentially curable with timely resection [5– 8]. Differentiation of various types of pancreatic cysts presents a diagnostic and therapeutic challenge. Clinical presentation may be vague; most patients present with few symptoms, if any. The absence of a history of pancreatitis and normal serum levels of amylase raise the suspicion of a cystic neoplasm. The multitude of invasive and noninvasive diagnostic modalities is confusing, and it may be difficult to choose a particular diagnostic schedule for an individual
* Corresponding author. Department of Surgery ‘‘A,’’ E. Wolfson Medical Center, Holon 58100, Israel. E-mail address: [email protected] (P.P. Schachter). 1052-5157/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved. PII: S 1 0 5 2 - 5 1 5 7 ( 0 2 ) 0 0 0 2 9 - 6
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patient. Modern noninvasive imaging techniques, such as CT, ultrasound, and MRI may disclose features of pancreatic cysts that should raise suspicion that a cystic neoplasm is present; however, these criteria are not uniformly reliable in the final diagnosis of neoplasms [9,10]. ERCP contributes additional information with regard to the relationship of the cyst to the pancreatic ductal system. Demonstration of ductal changes of chronic pancreatitis, or a direct communication of the pancreatic ductal system to the cyst combined with high levels of amylase within the cyst, supports the diagnosis of pseudocyst. Still, in rare instances cystadenomas or cystadenocarcinomas may contain high amylase levels and communicate to the pancreatic ductal system [11 –13]. Aspiration of cystic fluid for analysis and biopsy of the cyst’s wall have been of considerable interest; however, it may be difficult to localize small lesions with sufficient precision to guide the aspiration needle. Moreover, percutaneous CT- or ultrasound-guided needle aspiration carries the risk of needle tract and peritoneal dissemination of tumor cells as well as spillage of malignant cyst’s contents [14]. Even examination of biopsy material obtained during surgery may fail to differentiate cystic lesions correctly in as much as 20% of cases [4]. Endoscopic ultrasound is an important evolving tool enabling detailed visualization and ultrasound-guided fine needle aspiration of most pancreatic cysts because of its close proximity to the lesion [11]. Endoscopic ultrasound has high sensitivity rates for pancreatic lesions, yet specificity rates for malignancy are in the range of 75% to 80% [15]. Endoscopic ultrasound provides morphologic details that contribute to the differentiation of pancreatic cysts [16]. Nevertheless, experienced endosonographists point to some of the technical limitations [11]: a. Endoscopic ultrasound visualization of cystic lesions not in close proximity to the pancreas is difficult. This occurs mainly when pseudocysts develop away from the inferior border of the pancreas. b. Penetration of the endoscopic ultrasound view to adjacent organs (liver, peritoneal cavity) is significantly limited. c. Aspiration and fine needle aspiration can be performed only with a linear endosonoscope. Only one needle pass is usually performed to minimize the danger of leak. d. It is sometimes difficult to place the lesion in close proximity to the gastric or duodenal wall and thus the needle may traverse a length of a normal pancreas. The introduction of laparoscopy and laparoscopic ultrasonography greatly facilitates diagnosis of pancreatic cystic lesions. The sonographic probe is placed under vision directly on the lesion, regardless of its anatomic location. Thus, imaging of the various cystic components and surrounding organs is ideal. Puncture of the cyst is controlled under vision, and aspiration of the cyst’s content with a large bore needle prevents spillage and occlusion of the needle by mucus or debris. A core biopsy is easily obtained for histopathologic examination after the cyst’s content has been removed [17].
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Method Laparoscopy and laparoscopic ultrasonography (LAPUS) are performed under general anesthesia by a standard technique. A disposable 10-mm cannula is introduced at the umbilicus and inspection of the abdominal cavity is performed with a 30° telescope (Sharplan i-Sight, Digital computer-based video camera, Sharplan Usight, Tel-Aviv, Israel). An additional 10-mm cannula for direct-contact LAPUS is inserted usually in the right upper abdominal quadrant. This position may change according to the location of the cyst. LAPUS is performed with a 10-mm 8-Mhz sectoral contact ultrasound probe (Sharplan u-sight intraoperative laparoscopic ultrasound system). The laparoscopic probe is equipped with a fingertip adjustable viewing angle from 0 to 45°, both right and left. The system enables simultaneous view of the laparoscopic and ultrasonographic images using ‘‘picture in picture’’ visual mixing (Sharplan, bisight, digital video mixer). The Doppler system is useful in differentiating cystic lesions from venous and arterial vessels and is applied routinely before puncture of the cyst. LAPUS guided biopsy is performed with an 18-gauge biopsy needle (Quick core biopsy needle, Cook, Bloomington, IN, USA) (Fig. 1). LAPUS guided puncture of the cyst is performed with a large-bore needle, followed by immediate aspiration of the cyst to prevent spillage of cystic contents and peritoneal dissemination [6]. The cystic fluid is submitted to cytologic analysis to check for glycogen staining cells or the presence of mucus and chemical determination of tumor markers and amylase levels. A core biopsy of the cystic wall (in instances of a cystic wall of 2 mm or thicker) and intracystic structures is obtained for histopathologic examination without the damage of traversing the pancreas, duodenum, or stomach in the process. Communication of the cyst to the pancreatic ductal system can be evaluated by injection of contrast media into the cyst and intraoperative cystopancreatogram. A combination of the various ultrasonographic cystic and pancreatic parameters, with the results of histopathologic, cytologic, and cystic fluid aspirate analysis enables accurate diagnosis and appropriate management of these patients.
Chronic pancreatitis and pancreatic cystic lesions The association between chronic pancreatitis and pancreatic tumors is well established [18]. Parenchymal changes such as fibrosis and calcification that enhance the hyperechoic ultrasonographic appearance of the pancreas, as well as demonstration of ductal changes, are characteristic of chronic pancreatitis. A direct communication between the ductal system and the cyst together with high levels of amylase within the cyst suggests the diagnosis of a pseudocyst as demonstrated. In the rare instance of the so-called ductectatic cystic neoplasm or intraductal papillary mucinous tumors (IPTM), a neoplastic transformation in one of the
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Fig. 1. LAPUS guided biopsy. (A) Laparoscopic view of the probe and needle. (B) Ultrasound guided biopsy. The line indicates the imaginary needle passage.
Fig. 2. LAPUS view of serous cystadenoma of pancreas. (A) A thin-walled cyst containing turbid fluid. (B) Septae within the cyst are noted (arrow).
Fig. 3. LAPUS view of mucinous cystadenoma of pancreas. (A) Ultrasound view of an irregular cystic wall. (B) A solid, papillary component of the cystic wall (arrow). (From Schachter P, Avni Y, Gvirtz G, et al. The impact of laparoscopy and laparoscopic ultrasound on the management of pancreatic cystic lesions. Arch Surg 2000;135:262; with permission.)
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Fig. 4. LAPUS view of mucinous cystadenoma of pancreas. (A) LAPUS view demonstrating a thinwalled, benign appearing cystic lesion. (B) Puncture and aspiration of the cystic content results in collapse of the cyst revealing a previously hidden solid mass (arrow).
Fig. 5. LAPUS appearance of a benign cystic lesion. (A) The cystic lesion in close proximity to blood vessels. SMV, superior mesenteric vein; SMA, superior mesenteric artery. (B) Maneuvering the US probe creates a US ‘‘window’’ enabling puncture of a thick-walled benign cyst.
Fig. 6. LAPUS evaluation of a cystic lesion of the pancreas. (A) The cystic lesion is in close proximity to another small ‘‘cyst’’ The arrow indicates the SMA. (B) Doppler study of the suspect ‘‘cyst’’ demonstrates it to be the SMA.
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pancreatic ducts creates a cyst that does communicate with the ductal system [12,13]. These lesions consist of a dilated pancreatic duct with a cystic and mass component that are difficult to differentiate from chronic pancreatitis, yet a small nodule may be visualized in the wall of the dilated pancreatic duct [11].
The presence of additional cystic lesions Additional small cysts suggest the diagnosis of serous cystadenoma. These lesions are characteristically composed of multiple small cysts separated by thin walls without any internal structure. LAPUS enables demonstration of additional small lesions, 3 mm and larger in diameter. Indeed, small cysts not visualized by previous imaging modalities were detected by LAPUS in three of our patients. Larger serous cystadenomas may contain turbid fluid, septae, and calcifications (Fig. 2) or even communicate with the ductal system, raising the possibility of a mucinous cystadenoma [19,20].
The nature of the cyst’s wall (thickness/uniformity/regularity) We have learned to consider the ultrasonographic characteristics of the wall of the cyst as an important parameter for differentiation. Thus, a uniformly thin (1 –2mm) and regular wall is suggestive of a benign nature. Pseudocysts are an exception, characteristically having a thickened wall [21]. An irregular or focally thickened cystic wall or a solid component within the wall as demonstrated in eight of our patients suggests a rather malignant potential (Fig. 3). Only one patient with a focally thickened cystic wall component was found to have a serous cystadenoma. Irregularity of the cystic wall or a mass adjacent to the cyst may sometimes become apparent after aspiration and collapse of the cyst (Fig. 4). Such a mass is highly suggestive of a malignant cystadenoma [22].
Biopsy and aspiration of cystic components The LAPUS study offers greater ultrasound maneuverability, creating an ‘‘ultrasound window’’ for biopsy, even in patients where proximity to the mesenteric vessels precluded CT- or endoscopic-guided puncture (Fig. 5). We recommend routine use of the Doppler system before puncture of the cyst to identify blood vessels in the nearby surroundings of the cyst and certify a safe ultrasonographic window for the needle passage (Fig. 6). Direct contact of the ultrasound probe prevents passage of the needle through other tissues. In our experience, a thin ( < 1 mm) cystic wall is the only instance when obtaining an adequate biopsy is not possible; however, in most such cases biopsy is actually not needed for diagnosis. After aspiration of the cystic fluid one should carefully screen the surrounding pancreatic tissue for previously hidden masses.
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Histologic analysis of the cystic wall and cytologic examinations of the cystic aspirate contribute important information to the diagnosis. Glycogen staining cells and the absence of mucin in the aspirate are diagnostic of a serous cystadenoma, yet only 50% of aspirate cytology is positive in serous cystadenoma [23]. In our experience most serous cystadenoma aspirates are acellular, although in one case pancreatic ductal cells without atypia were obtained. The fluid of pseudocysts usually contains necrotic tissue, blood, and debris. Cytology can show pancreatic cells, inflammatory cells, or leukocytes. There should be no epithelial cells or mucin in the aspirate. LAPUS offers an advantage over endoscopic ultrasound because there is no contamination of the aspirate with gastric or duodenal epithelial cells, which can result in a false-positive cytologic analysis for mucinous cystadenoma. Aspiration of mucoid fluid and the presence of epithelial cells confirm the diagnosis of a mucous cystadenoma, but epithelial cells
Fig. 7. Algorithm for evaluation of patients with pancreatic cystic lesions.
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are present in only 48% of the cases [17]. In our experience mucinous fluid was found in 70% (7 of 10 patients), yet epithelial cells were revealed only in one case. The presence of mucin, malignant cells, and determination of neoplastic markers in the cystic fluid are useful in differentiating mucinous from serous cystic lesions, whereas high pancreatic enzyme content usually suggests a pseudocyst. Markers commonly studied examined are carcinoembryonic antigen (CEA), carbohydrate 19.9 (Ca 19.9), Ca 15.3, Ca 72.4, and tissue polypeptide antigen (TPA) [6,15,24,25]. Data obtained from our patients supports the high specificity of increased CEA and Ca 19.9 levels in mucinous cystadenomas and carcinomas. We, like others [4], have learned to consider raised CEA levels more important than Ca19.9 levels that may be elevated in benign conditions. However, our single false positive patient with serous cystadenoma had significantly increased levels of both CEA and Ca 19.9. Decisions regarding resection of a particular cyst are based upon analysis of all obtained information. Indeed, the demonstration of malignancy or mucinous cyst components are a clear indication for resection, but in the absence of this information, the decision is based on the ultrasonographic nature of the cystic wall, histologic analysis, and the levels of tumor markers obtained from the cystic aspirate. Therefore, an algorithm for evaluation of patients with pancreatic cystic lesions is most important (Fig. 7). In conclusion, LAPUS study, the biopsy of the cystic wall, and analysis of the cystic aspirate, although expensive and rather invasive procedures, significantly contribute to the differential diagnosis of pancreatic cystic lesions.
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