Laurent Palazzo

Localization of Pancreatic Endocrine Tumors by Endoscopic Ultrasonography

BACKGROUND After a pancreatic endocrine tumor has been diagnosed on the basis of clinical signs and the results of laboratory tests, localization of the tumor by the usual imaging procedures fails in as many as 40 to 60 percent of patients. Endoscopic ultrasonography, a sensitive test for small carcinomas of the pancreas, might also be useful in patients with endocrine tumors of the pancreas that cannot be localized by conventional methods. METHODS We studied 37 patients later shown to have 39 endocrine tumors of the pancreas who had negative results on transabdominal ultrasonography and CT. All the patients underwent endoscopic ultrasonography, and 22 also underwent selective angiography. All the tumors were confirmed by surgical excision and immunohistologic examination; they consisted of 31 insulinomas, 7 gastrinomas, and 1 glucagonoma, 0.5 to 2.5 cm (mean, 1.4 cm) in diameter. All but one of the patients were cured of their disease, as ascertained by at least six months of clinical and laboratory follow-up. RESULTS Using endoscopic ultrasonography, we were able to localize 32 of the 39 tumors (sensitivity, 82 percent); no tumor was incorrectly localized. The size of the tumors was very similar (within 2 mm) to that predicted by endoscopic ultrasonography. Among the 22 patients who underwent both angiography and endoscopic ultrasonography, ultrasonography was significantly more sensitive than angiography for tumor localization (sensitivity, 82 percent vs. 27 percent). Among 19 control patients without pancreatic endocrine tumors, endoscopic ultrasonography was negative in 18 (specificity, 95 percent). CONCLUSIONS Endoscopic ultrasonography is a highly sensitive and specific procedure for the localization of pancreatic endocrine tumors. It should be considered for the preoperative localization of such tumors once the clinical and laboratory diagnosis has been established.

Performance of endosonography-guided fine needle aspiration and biopsy in the diagnosis of pancreatic cystic lesions

OBJECTIVE:Preoperative diagnosis of cystic lesions of the pancreas remains difficult despite improvement in imaging modalities and cystic fluid analysis. The aim of our study was to assess the performance of endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration (FNA) in the diagnosis of pancreatic cystic lesions.METHODS:Data from a series of 127 consecutive patients with pancreatic cystic lesions were prospectively studied. EUS and EUS-guided FNA were performed in all patients, and cystic material was used for cytological and histological analysis as well as for biochemical and tumor markers analysis. Performance of EUS diagnosis, biochemical and tumor markers, and FNA diagnosis were compared with the final histological diagnosis obtained at surgery or postmortem examination. Sixty-seven patients underwent surgery and therefore constituted our study group.RESULTS:EUS provided a tentative diagnosis in 113 cases (89%). Cytohistological FNA provided a diagnosis in 98 cases (77%). When the results of EUS and EUS-guided FNA were compared with the final diagnosis (67 cases), EUS correctly identified 49 cases (73%), whereas FNA correctly identified 65 cases (97%). Sensitivity, specificity, positive predictive value, and negative predictive value of EUS and EUS-guided FNA to indicate whether a lesion needed further surgery were 71% and 97%, 30% and 100%, 49% and 100%, and 40% and 95%, respectively. Carbohydrate antigen 19–9 > 50,000 U/ml had a 15% sensitivity and a 81% specificity to distinguish mucinous cysts from other cystic lesions, whereas it had a 86% sensitivity and a 85% specificity to distinguish cystadenocarcinoma from other cystic lesions.CONCLUSIONS:EUS-guided FNA is a valuable tool in the preoperative diagnostic assessment of pancreatic cystic lesions.

Intraductal papillary and mucinous tumors of the pancreas: accuracy of preoperative computed tomography, endoscopic retrograde pancreatography and endoscopic ultrasonography, and long-term outcome in a large surgical series

BACKGROUND Few data are available on the accuracy of preoperative imaging or on long-term outcome after surgery for intraductal papillary and mucinous tumors of the pancreas. The aims of this study were to assess the following: (1) the accuracy of preoperative computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography for determination of tumor invasion and pancreatic extension as compared with surgical findings; (2) the long-term outcome after surgery. METHODS Forty-seven patients who underwent surgery between 1980 and 1995 for pathologically diagnosed intraductal papillary and mucinous tumors were included in this study. The findings of available computed tomography (n = 25), endoscopic retrograde pancreatography (n = 29), and endoscopic ultrasonography (n = 21) were reviewed by experienced clinicians blinded to pathologic diagnosis to assess tumor invasion and pancreatic extension. Pathologic specimens were reviewed by experienced pathologists. Postoperative follow-up data were analyzed. RESULTS Histologic features of invasive carcinoma were found in 43% of patients, severe dysplasia in 21%, and mild or moderate dysplasia in 36%. The overall accuracy of computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography in distinguishing between invasive and noninvasive tumors were, respectively, 76%, 79%, and 76%. The overall 3-year disease-free survival rate was 63%, but it was 21% among patients with invasive carcinoma at surgery (p < 0.001). CONCLUSIONS This study emphasizes the need for early surgical resection in patients with suspected intraductal papillary and mucinous tumors of the pancreas because of the high frequency of invasive carcinoma and the inadequacy of preoperative imaging for assessing malignancy.

Diagnosis of choledocholithiasis by endoscopic ultrasonography

BACKGROUND/AIMS Endoscopic ultrasonography is a promising procedure for the diagnosis of extrahepatic cholestasis. Accuracy for the diagnosis of choledocholithiasis by ultrasonography and computed tomography were prospectively compared with endoscopic ultrasonography in 62 consecutive patients. METHODS Final diagnosis was determined by endoscopic retrograde cholangiography with or without sphincterotomy or intraoperative cholangiography with or without choledochoscopy. All of the patients had abdominal ultrasonography, computed tomography, endoscopic ultrasonography, and either an endoscopic retrograde (n = 40) or intraoperative cholangiography (n = 32) performed. RESULTS Choledocholithiasis was confirmed in 22 patients. Thirteen patients had a stone with a diameter < 1 cm, and 14 had a nonenlarged common bile duct. Endoscopic ultrasonography was more sensitive (97%) than ultrasonography (25%; P < 0.0001) and computed tomography (75%; P < 0.02). Specificity and positive predictive value were not significantly different. Negative predictive value of endoscopic ultrasonography (97%) was better than that of ultrasonography (56%; P < 0.0001) and computed tomography (78%; P < 0.02). Results were unchanged after six patients in whom the absence of choledocholithiasis was considered probable after follow-up were excluded. Endoscopic ultrasonography results did not depend on stone diameter or common bile duct dilatation. CONCLUSIONS Endoscopic ultrasonography appears to be the best diagnostic tool for the diagnosis of choledocholithiasis compared with other noninvasive procedures.

Value of endoscopic ultrasonography in the diagnosis of common bile duct stones: comparison with surgical exploration and ERCP.

An accurate and safe preoperative method of imaging the common bile duct is essential for the proper diagnosis of calculous biliary tract disease, especially in the current era of laparoscopic cholecystectomy. The value of endoscopic ultrasonography in detecting common duct stones has been reported, albeit in small series. The aim of this retrospective study was to assess the accuracy of EUS in a large series of patients. We compared EUS to direct cholangiography in the evaluation of 422 patients for common duct stones. Ductal stones were imaged by EUS in 168 patients (43.4%). No complications were encountered. EUS failed in 2.3% of cases, ERCP failed in 8.3%, and surgical exploration failed in 0.5%. Comparison of EUS with surgical exploration in 185 patients showed a sensitivity of 94.9%, a specificity of 97.8%, and an accuracy of 95.9%. EUS was compared to ERCP in 219 patients. All common duct stones found by ERCP were evident by EUS. Concordance was obtained in 91.3% of cases. Review of videotapes disclosed 3 false-positives and 16 unequivocal true-positives. We conclude that EUS is a safe and highly accurate means of detecting common duct stones and should be proposed before laparoscopic cholecystectomy in patients at risk of choledocholithiasis.

Intraductal papillary mucinous tumors of the pancreas: the preoperative value of cytologic and histopathologic diagnosis

BACKGROUND The preoperative diagnosis of intraductal papillary mucinous tumors of the pancreas must be as certain as possible because removal of a large portion of the pancreas or even total pancreatectomy may be necessary. The value of cytologic and histopathologic analysis of specimens obtained by preoperative endoscopic investigations is unknown. The aim of this study was to assess the value of such analyses of specimens obtained by EUS-guided FNA and/or biopsy, or transpapillary biopsy specimens obtained during endoscopic retrograde pancreatography for the diagnosis of intraductal papillary mucinous tumors of the pancreas and for the detection of malignancy. METHODS Between 1992 and 2001, 42 patients (22 men, 20 women; median age 64 years) underwent surgical resection for intraductal papillary mucinous tumors of the pancreas and had preoperative pancreatic tissue sampling. In the case of isolated dilatation of pancreatic ducts, pancreatic juice was obtained by EUS-guided FNA for cytologic analysis. In the presence of a solid lesion or main pancreatic duct stenosis, biopsy specimens were obtained by EUS-guided FNA biopsy or endoscopic retrograde pancreatography, which permitted histopathologic assessment. The accuracy of cytology and histopathology was evaluated for the following: (1) positive diagnosis of intraductal papillary mucinous tumors of the pancreas and (2) assessment of malignancy, by comparison with histopathologic examination of surgical resection specimens. RESULTS Cytologic analysis was performed in 19 patients; it was positive in 4 (21%) and noninformative in 15 (79%). Histopathologic analysis was performed in 23 patients; it was positive in 21 (91%) and negative in 2 (9%). Histopathologic analysis yielded a positive result in 83% of patients who did not have extrusion of mucus from a patulous papilla. The sensitivity, specificity, and positive and negative predictive values of histopathologic analysis for the diagnosis of malignancy were, respectively, 44%, 100%, 100%, and 33%. When histopathologic analysis was positive, the tumor grade was similar to that determined by final histopathologic examination in 38% of patients, whereas the grade was underestimated in 62%. No complication occurred as a result of tissue sampling. CONCLUSIONS The sensitivity of histopathologic analysis of EUS-guided FNA biopsy specimens or transpapillary biopsy specimens is 91% for the positive diagnosis of intraductal papillary mucinous tumors of the pancreas with a solid component, which is of particular interest as extrusion mucus from the papilla was absent in most patients. Histopathologic analysis of biopsy specimens of malignant intraductal papillary mucinous tumors of the pancreas often underestimates tumor grade. The result for cytologic analysis of juice obtained from dilated pancreatic ducts is disappointing.

Macrocystic pancreatic cystadenoma: the role of EUS and cyst fluid analysis in distinguishing mucinous and serous lesions

BACKGROUND Benign pancreatic serous cystadenoma usually is morphologically distinguishable from mucinous cystadenomas, which require resection because of their malignant potential. A macrocystic variant of serous cystadenoma recently has been described, rendering this important distinction more difficult. The aim of this study was to determine the EUS and tumor marker characteristics of mucinous cystadenoma compared with macrocystic serous cystadenomas. METHODS Medical records for consecutive patients seen between 1995 and 2002, with a histopathologic diagnosis of mucinous cystadenoma or macrocystic serous cystadenoma after surgery, who had undergone a detailed EUS examination, including EUS-guided FNA, were retrospectively reviewed. RESULTS A resection specimen was available for 32 mucinous cystadenomas and 9 macrocystic serous cystadenomas. No significant differences were observed with regard to clinical data (age, gender, presence of symptoms), lesion size, and location within the pancreas. All mucinous cystadenomas had a discernible cyst wall (thickened, 66%; focal parietal nodules, 25%) compared with 56% of macrocystic serous cystadenomas (p<0.0001). A thick echo content also was more frequent in mucinous cystadenoma (56% vs. 11%; p=0.04; statistical significance removed by the Bonferroni correction). Microcysts were only observed in macrocystic serous cystadenomas (44%; p=0.0008). The combination of a cyst wall that is thickened and the absence of microcysts had a sensitivity of 100% and specificity of 78% for the diagnosis of mucinous cystadenoma compared with macrocystic serous cystadenoma. Although intracystic carbohydrate-associated antigen 72-4 and mucins M1 were non-discriminatory, low carcinoembryonic antigen (<5 ng/mL) and carbohydrate-associated antigen 19-9 (<50,000 U/mL) values were found in macrocystic serous lesions (respectively, 100% and 100%; p=0.0002 and p=0.0002). CONCLUSIONS Although there is considerable overlap, helpful EUS characteristics that differentiate mucinous cystadenoma from macrocystic serous cystadenoma include a thick cyst wall and microcysts. These features, coupled with analysis of aspirated fluid for tumor markers (especially carcinoembryonic antigen), should help to confirm the diagnosis.

Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas

OBJECTIVE:Treatment of intraductal papillary and mucinous tumors of pancreas (IPMT) usually requires surgery. The objective of this study was to evaluate the risk of recurrence in patients after surgery according to the histological nature of the neoplasm and the type of surgery.METHODS:The outcome of 45 patients who underwent partial pancreatectomy (n = 35) or total pancreatectomy (n = 10) for IPMT was studied according to the nature of the neoplasm (invasive carcinoma or noninvasive neoplasm), type of surgery (partial or total pancreatectomy), and lymph nodes status.RESULTS:The overall 3-yr actuarial survival rate was 83%. Death occurred in seven of 20 (35%) patients with invasive carcinoma and in one of 26 (4%) patients with noninvasive tumors (p < 0.05). There were two recurrences in the seven patients with noninvasive neoplasm who underwent partial pancreatectomy with involved resection margins, and none in the 13 patients with disease-free margins. In patients with invasive carcinoma, there was one recurrence after total pancreatectomy, six after partial pancreatectomy with disease-free margins and six after partial pancreatectomy with involved margins. In patients with invasive carcinoma, total pancreatectomy and the absence of lymph nodes involvement were independently associated with a low risk of recurrence.CONCLUSIONS:IPMT may be managed as follows: 1) in patients with noninvasive neoplasms, partial pancreatic resection should be guided by frozen section examination until disease-free margins are obtained; and 2) in patients with invasive carcinoma, total pancreatectomy seems most likely to cure the patient, but should be discussed according to the general status and the age.

ENDOSONOGRAPHY: PROMISING METHOD FOR DIAGNOSIS OF EXTRAHEPATIC CHOLESTASIS

Endosonography, ultrasonography, and computed tomography (CT) were carried out prospectively in 52 patients with extrahepatic cholestasis. 35 patients had extrahepatic biliary obstructions (21 tumorous, 14 non-tumorous) and 17, with recent gallstone migration within the bile duct, had no extrahepatic obstruction at the time of investigation. The definitive diagnosis was established by surgery (in 39 patients), by transendoscopic sphincterotomy (11 patients), or by retrograde biliary opacification (2 patients). Endosonography was significantly more sensitive than ultrasonography or CT (100% vs 80% and 83%, respectively) in making a positive diagnosis of obstruction. Endosonography was also significantly more accurate than ultrasonography or CT (97% vs 49% and 66%) in diagnosing the cause of the obstruction and more effective in the assessment of the locoregional spread of tumorous obstructions (75% vs 38% and 62%). Thus, endosonography was superior to ultrasonography and CT in the diagnosis and staging of biliary obstructions.

Intraductal Papillary Mucinous Neoplasms of the Pancreas: Performance of Pancreatic Fluid Analysis for Positive Diagnosis and the Prediction of Malignancy

INTRODUCTION:The preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMN) of the pancreas must be as reliable as possible because large or even total pancreatectomy may be necessary. Early diagnosis of malignant forms is important to improve prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been confirmed in cystic lesions of the pancreas. It is not known if these results can be applied to IPMN.AIMS: To determine the levels of biochemical and tumor markers in fluid from EUS-FNA in patients with IPMN and to assess the impact on the diagnosis of IPMN.PATIENTS AND METHODS:In total, 41 patients (14 men, median age 64 yr) underwent EUS-FNA before surgical resection of IPMN in our center. Levels of amylase, lipase, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19.9, and CA 72.4 were measured in the cyst fluid. The performance of the markers was retrospectively evaluated for: (a) a positive diagnosis of IPMN, using cutoffs validated in the literature for mucinous pancreatic lesions and (b) an assessment of malignancy (i.e., high-grade dysplasia or invasive carcinoma) compared with the final pathological examination of the surgical specimen.RESULTS: EUS-FNA was performed in dilated branch ducts (BD) in 39 cases and in the main pancreatic duct in 2 cases. No serious complications occurred. The median fluid levels of amylase, lipase, CEA, CA 19.9, and CA 72.4 were 20,155 U/mL, 59,500 U/mL, 173 ng/mL, 6,400 U/mL, and 11.5 U/mL, respectively. A CEA level >200 ng/mL and a CA 72.4 >40 U/mL had a 44% and a 39% sensitivity, respectively, for the diagnosis of IPMN. The levels of CEA, CA 19.9, and CA 72.4 were significantly different between benign and malignant IPMN. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of a CEA level >200 ng/mL for the diagnosis of malignant IPMN were 90%, 71%, 50%, and 96%, respectively. The sensitivity, specificity, PPV, and NPV of a CA 72.4 level >40 U/mL for this purpose were 87.5%, 73%, 47%, and 96%, respectively.CONCLUSION: CEA and CA 72.4 in pancreatic cyst fluid have excellent NPVs in the preoperative differential diagnosis of benign versus malignant IPMN, and might reinforce the decision of not to operate on patients with BD-type without predictive factors of malignancy.