Philippe Ponsot

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.

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.

Long-term Outcome of Biliary and Duodenal Stents in Palliative Treatment of Patients with Unresectable Adenocarcinoma of the Head of Pancreas

BACKGROUND:Life expectancy in patients with unresectable pancreatic cancer has improved by using new chemotherapeutic regimens. Biliary and digestive stenoses can be endoscopically treated in most cases. However, long-term efficacy of these stenting procedures remains unknown.AIM:To evaluate the incidence of biliary and duodenal stenoses as well as technical success and short- and long-term patency of endoscopically deployed stents in patients with unresectable pancreatic cancer.PATIENTS AND METHODS:All consecutive patients with unresectable cancer of the pancreatic head seen between January 1999 and September 2003 in our center were retrospectively studied. Patients with biliary and/or duodenal stenoses underwent endoscopic stent insertion as first intention therapy. Outcomes included technical and clinical success, stent patency, and survival.RESULTS:One hundred patients, median age 65 yr (32–85), with locally advanced (62%) or metastatic (38%) pancreatic cancer were studied. Eighty-three percent received at least one line of chemotherapy. The actuarial median survival was 11 months (0.7–29.3). Biliary and duodenal stenoses occurred in 81 and 25 patients, respectively. A biliary stent was successfully placed in 74 patients (91%). When a self-expandable metallic stent was first introduced (N = 59), a single stent was sufficient in 41 patients (69%) (median duration of stent patency 7 months (0.4–21.1)). Duodenal stenting was successful in 24 patients (96%); among them, 96% required a single stent (median duration of stent patency 6 months [0.5–15.7]). In the 23 patients who developed both biliary and duodenal stenoses, combined stenting was successful in 91% of cases. No major complication or death occurred related to endoscopic treatment.CONCLUSION:Endoscopic palliative treatment of both biliary and duodenal stenoses is safe and effective in the long term, including in patients with combined obstructions. Use of such palliative management is justified as repeat procedures are rarely required even in patients who have a long survival.

Are endoscopic procedures able to predict the benignity of ampullary tumors

BACKGROUND Malignant ampullary tumors (AT) require pancreatico-duodenectomy (PD) for curative treatment whereas benign AT can be appropriately treated by local resection. This study evaluated the accuracy of endoscopic exploration combining side-viewing duodenoscopy (SVD) with forceps biopsies, endoscopic sphincterotomy (ES), and endoscopic ultrasonography (EUS) to distinguish benign AT from malignant one. PATIENTS AND METHODS Twenty-six patients with AT had preoperative SVD with forceps biopsies, including 9 with ES, and EUS. Nodal status was evaluated by EUS in all patients, but could not evaluate parietal spread in 6 in whom ES was previously done. Results of endoscopic examination were compared with pathologic examination after resection (2 local excisions for 2 benign AT, and 24 PD for 20 malignant and 4 benign AT). RESULTS Accuracy of histologic examination of the 26 biopsies of the papilla was 69%. After ES, accuracy of intra-ampullary biopsies was 77%. The EUS had a 75% accuracy for the parietal spread (tumor limited to ampulla or not) and a 69% accuracy for the nodal status. In 11 patients, all explorations were consistent with a benign lesion, but 6 of these patients had a histologically proven malignancy, including one with nodal metastases and two with duodenal involvement. CONCLUSIONS Side-viewing duodenoscopy with biopsies, even after ES, combined with EUS is not accurate enough to preoperatively ensure that an AT is benign. Indication for a local resection based on these explorations alone is not safe.

Clinical and Morphological Features of Duodenal Cystic Dystrophy in Heterotopic Pancreas

BACKGROUND AND AIMS:Cystic dystrophy in heterotopic pancreas (CDHP) is an uncommon complication of pancreatic heterotopia, only described in surgical series, whose natural history is not known. The aim of this study was to determine clinical and morphological features of CDHP in a medical-surgical series of patients and to ascertain the relationship of CDHP with chronic pancreatitis (CP) in the pancreas proper.METHODS:All patients who had duodenal CDHP diagnosed radiologically both with CT scan and endoscopic ultrasonography between 1995 and 2004 were included. The diagnosis was confirmed by surgical specimens when available.RESULTS:One hundred five patients were included (91% men, 86% chronic alcoholic) with a median follow-up of 15 months. The median age at first symptoms was 46 yr. CDHP was associated with CP in the pancreas proper in 71% of patients. Presenting symptoms were pancreatic pain (91%), severe weight loss (73%), acute pancreatitis (45%), vomiting (30%), steatorrhea (23%), diabetes mellitus (20%), jaundice (13%), and upper gastrointestinal hemorrhage (5%). Cysts were multiple in 75% (median 3). The median diameter of the largest cyst was 10 mm. Endoscopy was normal in 36% of patients and showed duodenal stenosis in 52% (complete 6%, incomplete 46%). Surgical treatment was necessary in only 27% of patients (Whipple procedure 16%).CONCLUSIONS:CDHP may arise in patients with or without CP and with or without chronic alcoholism. Symptoms may be severe but warrant surgery in less than one-third of patients.

Endoscopic papillectomy for early ampullary tumors: long-term results from a large multicenter prospective study.

BACKGROUND AND STUDY AIMS Endoscopic papillectomy of early tumors of the ampulla of Vater is an alternative to surgery. This large prospective multicenter study was aimed at evaluating the long-term results of endoscopic papillectomy. PATIENTS AND METHODS Between September 2003 and January 2006, 10 centers included all patients referred for endoscopic papillectomy and meeting the inclusion criteria: biopsies showing at least adenoma, a uT1N0 lesion without intraductal involvement at endoscopic ultrasound (EUS), and no previous treatment. A standardized endoscopic papillectomy was done, with endoscopic monitoring with biopsies 4 - 8 weeks later where complications were recorded and complementary resection performed when necessary. Follow-up with duodenoscopy, biopsies, and EUS was done at 6, 12, 18, 24 and 36 months. Therapeutic success was defined as complete resection (no residual tumor found at early monitoring) without duodenal submucosal invasion in the resection specimen in the case of adenocarcinoma and without relapse during follow-up. RESULTS 93 patients were enrolled. Mortality was 0.9 % and morbidity 35 %, including pancreatitis in 20 %, bleeding 10 %, biliary complications 7 %, perforation 3.6 %, and papillary stenosis in 1.8 %. Adenoma was not confirmed in the resection specimen in 14 patients who were therefore excluded. Initial treatment was insufficient in 9 cases (8 carcinoma with submucosal invasion; 1 persistence of adenoma). During follow-up, 5 patients had tumor recurrence and 7 died from unrelated diseases without recurrence. Finally, 81.0 % of patients were cured (95 % confidence interval 72.3 % - 89.7 %). CONCLUSION Endoscopic papillectomy of selected ampullary tumors is curative in 81.0 % of cases. It must be considered to be the first-line treatment for early tumors of the ampulla of Vater without intraductal invasion.

Chronic esophagitis dissecans: an unrecognized clinicopathologic entity?

BACKGROUND We report the clinical and histologic features of a distinctive form of chronic esophagitis for which we propose the term chronic esophagitis dissecans. METHODS The study group included five patients diagnosed at Hôpital Beaujon, Clichy, from 1988 to 1994. Clinical and endoscopic examinations were performed. Samples of esophageal biopsy specimens were analyzed by histologic and ultrastructural examinations and by immunohistochemistry with antibodies directed against cell adhesion molecules. RESULTS All patients were elderly (mean age, 66 years). They presented the following combination of clinical and endoscopic features: (1) long-standing history of chronic dysphagia, without symptoms of reflux, (2) shedding of mucosal fragments, occurring spontaneously or after mechanical trauma, (3) existence of localized esophageal strictures, (4) lack of concurrent chronic cutaneomucous lesions. Two patients presented with thymoma. Histologic examination showed evidence of mucosal blistering, in the absence of significant inflammatory lesions. Altered cell-cell adhesion was suggested by the reduced number of desmosomes on ultrastructural examination and the decreased expression of immunoreactive intercellular adhesion molecule E-cadherin. CONCLUSION Chronic esophagitis dissecans likely represents a hitherto unrecognized clinicopathologic entity and must be added to the causes of chronic dysphagia.

Diagnosis and management of pancreatic fistulae resulting in pancreatic ascites or pleural effusions in the era of helical CT and magnetic resonance imaging.

OBJECTIVES Diagnosis of internal pancreatic fistulae (IPF) resulting in ascites or pleural effusions may be facilitated by multislice helical CT-scan and MR-pancreatography [MRP]). Conservative treatment with parenteral nutrition and somatostatin analogues (+/- pancreatic stenting) yields varying results. We aimed to evaluate the usefulness of helical CT and MRP in the diagnosis of IPF. The outcome of patients when the following stepwise treatment algorithm is applied is also descried: i) conservative (enteral nutrition and somatostatin analogues); ii) endoscopic stenting; iii) surgery. METHODS Sixteen consecutive patients (13 M; median age 42 (14-54) yrs) with chronic pancreatitis (alcoholic 15, hereditary 1) and an IPF were prospectively included between March-01 to December-03. All serous effusions (ascites, N=10; pleural effusion, N=6) contained high lipase [median: 7800 (506-59000) U/mL]. Patients with fistulae communicating with pancreatic pseudocysts were not included. RESULTS The diagnosis of IPF and its site were determined in 12/16 patients by CT and 14/15 patients by MRP (site of rupture: head: N=5; isthmus: N=5; body-tail: N=6) and confirmed by ERCP or surgery in 9. Localized atrophy of pancreatic parenchyma adjacent to pancreatic duct rupture was observed in 12 patients (75%). The median follow-up was 30 months (18-51). Early surgery was required in 3 patients (2 with infection of serous fluid at initial aspiration analysis). Thirteen entered the treatment algorithm: - seven patients responded favorably (54%) to conservative treatment (enteral nutrition and somatostatin analogues); - pancreatic stenting, possible in 4 of 6 patients, was successful in closing the IPF in 2; - surgery was required in the 4 remaining patients. Preoperative localization of the rupture site was possible in all patients using non-invasive imaging thus guiding elective intervention in all patients requiring surgery. CONCLUSION Helical CT scan and MRP are useful in localizing MPD rupture sites and fistulae and may obviate the need for pancreatic opacification. A systematic treatment algorithm can be safely used starting with medical strategies (enteral nutrition safely replacing the parenteral route) progressing to endoscopy and finally surgery. Overall about 44% of patients require surgery initially or at follow-up.

Severe Cholangitis Following Pancreaticoduodenectomy for Pseudotumoral Form of Lymphoplasmacytic Sclerosing Pancreatitis

Cholangitis associated with lymphoplasmacytic sclerosing pancreatitis may occur simultaneously or following diagnosis of pancreatitis. The natural history following inappropriate pancreatic surgery and treatment of cholangitis in this setting are ill-defined. Three patients underwent pancreaticoduodenectomy for pseudotumoral lymphoplasmacytic sclerosing pancreatitis. Jaundice or ascending cholangitis revealed severe biliary strictures at 1, 6, and 11 months, respectively, following surgery. Treatment combining corticosteroids with or without biliary stenting was efficacious in all patients. One patient with subsequent clinical and morphological relapse responded well to reintroduction of steroids. Biliary changes appeared to be immune-related based on pathological examination and response to corticosteroids.

3485 Cystogastrostomy with 10 french stent entirely performed under endosonography guidance for pancreatic pseudocyst.

Background: the main complication under endoscopic drainage of large retrogastric pancreatic pseudo-cyst (PPC) is bleeding due to the presence of segmentary portal hypertension. EUS has been recommanded for optimal localization of the puncture site. We describe our experience with cystogastrostomy entirely guided by EUS using a new generation interventionnal echo-endoscope with large channel allowing the placement of a 10 French stent. Methods : Cystogastrostomy was performed in 2 patients for symptomatic PPC. The etiology of both PPC was alcoolic calcified chronic pancreatitis. The indication of drainage was chronic pain and weight loss with persistence of the PPC in case n°1 and chronic pain with augmentation of the size of the PPC in case n°2. Through the papilla endoscopic treatment was not possible in both cases. Spiral CT demonstrated a 8 cm retro-gastric PPC in case n°1 and several retrogastric PPC (diameter ranged from 4 to 7 cm) in case n°2. Some debris were present in case n°1 without evidence of recent bleeding. Considerable segmentary portal hypertension with gastric varices were demonstrated at CT in both cases. We used the new electronic therapeutic echo-endoscope Olympus UC T 30 with a 3.7 mm working channel and a bridge. Results : Endoscopy reveals a bulging lesion in case n°1 and no bulging lesion in case n°2. EUS showed echo-free PPC in both cases with dependent debris in case n°1. Gastric varices located into the gastric wall in front of the PPC were demonstrated in both cases. The distance between the gastric lumen and the cyst was 4 mm and 6 mm respectively. The procedure began by the puncture with the needle-knife under direct ultrasound visualization in a site without varices. Then a 400 cm guide wire was passed through the catheter and coiled under fluoroscopy guidance within the cystic cavity. The catheter was removed and a dilatation with a 6 mm balloon catheter was performed. A 10 French double-pigtail endoprosthesis was then inserted over a guide catheter into the PPC cavity in each case. No bleeding or no other complications post procedure. Both patients were able to leave the hospital after 24 hours. At 12 weeks follow-up, they had no recurrent symptoms, and US revealed resolution of PPC in both cases. Conclusion : PPC drainage using a large channel therapeutic echo-endoscope allowing the placement of 10 French stent is an easy, efficient and safe procedure which is particularly useful in case of segmentary portal hypertension.