Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Cystic pancreatic neuroendocrine tumors: endoscopic ultrasound and fine-needle aspiration characteristics.

BACKGROUND AND STUDY AIMS: Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients. PATIENTS AND METHODS: From an EUS - FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database. RESULTS: Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS - FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2 %). The median cyst fluid CEA level (n = 15) was 1.1 ng/mL (range 0.3 - 500 ng/mL). Compared with matched patients with mucinous cysts, the median cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common (66.7 % vs. 13.3 %), and diagnostic cytology was more likely (73.3 % vs. 20.0 %). CONCLUSIONS: Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets.

Endoscopic ultrasound-guided fine-needle aspiration for diagnosis of solid pseudopapillary tumors of the pancreas: a multicenter experience.

BACKGROUND AND STUDY AIMS: Solid pseudopapillary tumors of the pancreas are rare, low-grade, epithelial neoplasms that are usually discovered incidentally in young women. Distinguishing solid pseudopapillary tumors from other pancreatic tumors, especially pancreatic endocrine tumors, can be challenging. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in this context remains unclear. The purpose of this study was to describe the endoscopic ultrasound features of solid pseudopapillary tumors and the role of EUS-FNA in the preoperative diagnosis of these tumors. PATIENTS AND METHODS: Patients from five tertiary referral centers with surgically confirmed solid pseudopapillary tumors who had undergone preoperative EUS-FNA were included. The endoscopic ultrasound findings, cytologic descriptions, immunostaining results, operative records, surgical pathology, and results of the most recent clinical follow-up were reviewed. RESULTS: A total of 28 patients were identified (four men [14 %], 24 women [86 %], mean age +/- standard deviation [SD] 35 +/- 10 years). Solid pseudopapillary tumors had been found as incidental findings on cross-sectional imaging in 50 % of cases. The mean tumor size +/- SD was 42 +/- 19.5 mm and the majority were located in the pancreatic body and tail. The endoscopic ultrasound report described a well-defined, echo-poor mass in 86 %; the tumors were solid in 14 patients (50 %), mixed solid and cystic in 11 patients (39 %), and cystic in three patients (11 %). A preoperative diagnosis of solid pseudopapillary tumor was made in 21 patients (75 %) on the basis of EUS-FNA cytology. Surgical resection was performed in all cases. Laparoscopic resection was performed in eight of these patients (29 %). CONCLUSIONS: A solid pseudopapillary tumor should be included in the differential diagnosis of any well-demarcated, echo-poor, solid or mixed solid/cystic pancreatic lesion seen during endoscopic ultrasound, particularly in young women. The diagnostic accuracy of EUS-FNA for solid pseudopapillary tumors was 75 % in this study. A definitive preoperative diagnosis can guide the surgical approach in selected cases.

Natural orifice transesophageal mediastinoscopy and thoracoscopy.

BACKGROUND: Thoracoscopy and mediastinoscopy are common procedures with painful incisions and prominent scars. A natural orifice transesophageal endoscopic surgical (NOTES) approach could reduce pain, eliminate intercostal neuralgia, provide access to the posterior mediastinal compartment, and improve cosmesis. In addition NOTES esophageal access routes also have the potential to replace conventional thoracoscopic approaches for medial or hilar lesions. METHODS: Five healthy Yorkshire swine underwent nonsurvival natural orifice transesophageal mediastinoscopy and thoracoscopy under general anesthesia. An 8- to 9.8-mm video endoscope was introduced into the esophagus, and a 10-cm submucosal tunnel was created with blunt dissection. The endoscope then was passed through the muscular layers of the esophagus into the mediastinal space. The mediastinal compartment, pleura, lung, mediastinal lymph nodes, thoracic duct, vagus nerves, and exterior surface of the esophagus were identified. Mediastinal lymph node resection was easily accomplished. For thoracoscopy, a small incision was created through the pleura, and the endoscope was introduced into the thoracic cavity. The lung, chest wall, pleura, pericardium, and diaphragmatic surface were identified. Pleural biopsies were obtained with endoscopic forceps. The endoscope was withdrawn and the procedure terminated. RESULTS: Mediastinal and thoracic structures could be identified without difficulty via a transesophageal approach. Lymph node resection was easily accomplished. Pleural biopsy under direct visualization was feasible. Selective mainstem bronchus intubation and collapse of the ipsilateral lung facilitated thoracoscopy. In one animal, an inadvertent 4-mm lung incision resulted in a pneumothorax. This was decompressed with a small venting intercostal incision, and the remainder of the procedure was completed without difficulty. CONCLUSIONS: Transesophageal endoscopic mediastinoscopy, lymph node resection, thoracoscopy, and pleural biopsy are feasible and provide excellent visualization of mediastinal and intrathoracic structures. Survival studies will be needed to confirm the safety of this approach.

Defining the criteria for local resection of ampullary neoplasms.

OBJECTIVES: To delineate factors determined preoperatively, which predict successful local resection of ampullary neoplasms. DESIGN: Retrospective review of case series of the author's experience from 1988 through 1995. The median follow-up of patients with malignancies was 29 months. SETTING: Tertiary care university teaching hospital. PATIENTS: Twenty-seven patients underwent surgery. The decision to perform either an ampullectomy or pancreaticoduodenectomy (PD) was based on the size of the lesion, the presence of a "field defect" (ie, familial polyposis), depth of invasion determined by preoperative endoscopic ultrasound, and extent of pancreatic and bile duct involvement seen on endoscopic retrograde cholangiopancreatography. INTERVENTIONS: Fourteen patients underwent ampullectomy, 12 patients underwent PD, and one patient had a retroperitoneal node biopsy performed without resection of the primary tumor. MAIN OUTCOME MEASURES: Resectability, morbidity, and mortality. RESULTS: Depth of invasion was accurately determined in nine of 12 patients studied by preoperative endoscopic ultrasound. Preoperative endoscopic biopsy specimens were obtained in 21 patients and were inaccurate in seven of 21 cases. The length of stay following local resection was 10.5 +/- 3.7 days vs 15.4 +/- 5.8 days following PD (P=.02). One patient died following PD, and there were no deaths following ampullectomy. Six of 12 patients undergoing PD had postoperative complications vs two of 14 patients undergoing local resection. CONCLUSIONS: Ampullectomy is the procedure of choice for resecting benign lesions smaller than 3 cm, small neuroendocrine tumors, and T1 carcinomas of the ampulla. While endoscopic ultrasonography is helpful in identifying stage T1 lesions suitable for local resection, no preoperative test proved accurate enough to substitute for clinical judgment and intraoperative pathological confirmation.

Immunoreactive cholecystokinin in human and rat plasma: correlation of pancreatic secretion in response to CCK.

Immunoreactive cholecystokinin (CCK) levels in human and rat plasma are described using a radioimmunoassay specific for the biologically active sulfated end of CCK. This assay detected significant changes in plasma cholecystokinin levels during intrajejunal administration of amino acids and intravenous infusions of CCK-8 which were followed by increased pancreatic secretion. In humans, the concentration (pg/ml) of plasma cholecystokinin increased from 10.8 to 18.9 following intrajejunal amino acid instillation and from 15.4 to 31.1 during CCK infusion, while pancreatic trypsin secretion increased more than 15 fold. Ingestion of a test meal also caused a rapid and significant elevation (P less than 0.05) in both plasma CCK (14.5-21.7 pg/ml) and gastrin (50-160 pg/ml) levels. In the rat, an injection of 46 ng of CCK-8 produced a 300% increase in immunoreactive plasma CCK levels (2 min) and caused peak pancreatic protein secretion within 5 min; 4 fold lower doses (11.5 ng) elevated plasma CCK by 38% and pancreatic protein secretion to a small but significant extent. The ability of this assay to detect various forms of sulfated CCK in human plasma was also determined. Following gel chromatography on Sephadex G-50, at least three different immunoreactive peaks were found in plasma from fasted subjects and after intrajejunal amino acid stimulation. While the lower molecular weight CCK peptides (CCK-8 and CCK-12) were detected in plasma from both fasted and stimulated subjects, the larger form (CCK-33) was only present in measurable concentrations after amino acid infusion. The simultaneous measurement of increased plasma CCK levels and pancreatic secretion and the changes in the distribution of CCK peptides following amino acid infusion provides strong support that this assay detects physiologically relevant changes in biologically active CCK peptides.

Role of cholecystokinin in the regulation of the interdigestive phase of pancreatic secretion.

The rate of pancreatic secretion during the interdigestive state varies with the phase of interdigestive motility. During phases II and III of interdigestive motility, pancreatic secretion is greatest, and minimal during phases I and IV. Pancreatic polypeptide and motilin have been reported to be increased during phases II and III but do not appear to be responsible for the stimulation of pancreatic secretion. We have investigated the role of cholecystokinin (CCK) in regulating pancreatic secretion during the interdigestive state. Eight volunteers underwent a study of interdigestive duodenal motility with a catheter that collected pancreatic secretions at the ligament of Treitz. The phase of motility was correlated with the output of trypsin and the plasma CCK levels. The output of trypsin during phases II and III was 0.9 +/- 0.2 and 1.0 +/- 0.2 mg/kg/h, respectively, and decreased to 0.3 +/- 0.1 mg/kg/h during phase IV-I (p less than 0.05). To determine if the output of trypsin during phases II and III was responsible for the increases in plasma CCK, the effect of intraduodenal trypsin, 3 mg/kg/h, in five volunteers was determined. The infusion significantly increased the output of trypsin to a mean of 3.1 +/- 1.9 mg/kg/h (p less than 0.05). The plasma CCK concentration increased with intraduodenal trypsin from 20.4 +/- 5 to 26.4 +/- 3.7 pg/ml (p less than 0.05). The infusion study was repeated in two volunteers with heat-inactivated trypsin. The mean CCK level rose from 19.6 +/- 4 to 23.8 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic cancer staging. Endoscopic ultrasonography criteria for vascular invasion.

Endoscopic ultrasound (EUS) is the most sensitive imaging test available for examining the pancreas and associated structures. Small (< 2 cm) pancreatic malignancies can be detected with accuracy rates of more than 90%. Several EUS criteria have been proposed for their ability to diagnose malignant venous invasion. Although obstruction of a mesenteric vein and the resulting venous collaterals is a specific sign of unresectability, it is a rather insensitive parameter. As an alternative, signs of venous wall invasion, such as "irregular wall" have been proposed as being sensitive (67%-100%) and specific (100%) for malignant invasion of mesenteric veins. EUS appears to be particularly sensitive for detecting invasion of the portal and splenic veins. In contrast, the superior mesentera veins are more difficult to image with EUS and the results of staging of pancreatic masses demonstrate poor sensitivity (12%-17%) for detecting vascular invasion of the superior mesenteric vein.

EUS diagnosis of cystic lesions of the pancreas.

BACKGROUND: Cystic tumors of the pancreas are composed of benign, premalignant, malignant, and inflammatory lesions that are traditionally difficult to diagnose. Most of the tumors are initially detected on CT/US scanning, but often the morphological characteristics are insufficient for making a definitive diagnosis. Endoscopic ultrasound (EUS) may be an ideal tool for imaging of these lesions because it can provide highly detailed imaging without interference by bowel or air. Furthermore, EUS can direct fine needle aspiration of the lesions, providing cyst fluid for cytologic examination. The findings of cyst fluid cytology can be complemented by the use of cyst fluid tumor makers such as CEA. Using the morphologic appearance by endosonography, the results of cytology, and tumor marker analysis, EUS can often differentiate between benign, malignant, and inflammatory cystic lesions of the pancreas.

Cholescintigraphy in the diagnosis of the complications of laparoscopic cholecystectomy.

Cholescintigraphy has been used to diagnose postoperative bile leaks and obstructions after open cholecystectomy. This imaging technique has been found to be sensitive for detecting bile leaks that arise from cholecystectomy and defects in the filling and emptying of bile ducts. These observations can be applied to patients who are suspected of having bile duct injury after laparoscopic cholecystectomy. Cholescintigraphy can detect a variety of bile leaks including those arising from the gallbladder fossa, cystic duct, and the common bile duct. In addition, cholescintigraphy can be used for management of patients after stenting or bypass surgery, to assess bile flow and operative sites for any residual bile leaks. Postoperative bile duct obstructions can also be seen with cholescintigraphy. In this article we discuss a comprehensive postoperative strategy for the management and diagnosis of biliary defects after laparoscopic cholecystectomy with cholescintigraphy.

Motor function of the gallbladder: measurement and clinical significance.

Abnormalities in gallbladder emptying commonly occur in gallstone patients. Similar changes can be found in patients without gallstones that have disease that may predispose to stones, such as diabetes. Decreased contractility of the gallbladder can be measured clinically with variety of radiological techniques, and ultrasonography seems to have a number of advantages over others. In addition to a role in pathogenesis, decreased gallbladder emptying may determine the clearance of gallstones from the gallbladder during dissolution and after lithotripsy.

64-Slice multidetector row CT angiography of the abdomen: comparison of low versus high concentration iodinated contrast media in a porcine model.

OBJECTIVE: In this study we aimed to assess the image quality and degree of vascular enhancement using low-concentration contrast media (LCCM) (300 mg I ml(-1)) and high-concentration contrast media (HCCM) (370 mg I ml(-1)) on 64-slice multidetector row CT (MDCT) abdominal CT angiography (CTA). In addition, we aimed to study the feasibility of using HCCM with a reduced total iodine dose. METHODS: CTA of the abdomen on a 64-slice MDCT was performed on 15 anaesthetised pigs. Study pigs were divided into three groups of five each based on the iodine concentration and dose received: Group A (LCCM; 300 mg I ml(-1)), Group B (HCCM; 370 mg I ml(-1)) and Group C HCCM with 20% less iodine dose. The total iodine injected was kept constant (600 mg kg(-1)) in Groups A and B. Qualitative and quantitative analyses were performed to study and compare each group for image quality, visibility of the branch order of the superior mesenteric artery (SMA), artefacts, degree of enhancement in the aorta and main stem arteries and uniformity of enhancement in the aorta. Groups were compared using the analysis of variance test. RESULTS: The image quality of 64-slice MDCT angiography was excellent with a mean score of 4.63 and confident visualisation of the third to fifth order branches of the SMA in all groups. Group B demonstrated superior vascular enhancement, as compared with Groups A and C (p≤0.05). Uniform aortic enhancement was achieved with the use of LCCM and HCCM with 20% less iodine dose. CONCLUSION: 64-slice MDCT angiography of the abdomen was of excellent quality. HCCM improves contrast enhancement and overall CTA image quality and allows the iodine dose to be reduced.

Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery.

BACKGROUND: Despite advances in cross-sectional imaging and the use of molecular markers, distinguishing between benign and malignant cysts remains a clinical challenge. AIMS: To identify both preoperative clinical and cyst characteristics at the time of EUS that predict malignancy. METHODS: A retrospective analysis was performed on consecutive patients with pancreatic cysts who underwent endoscopic ultrasound (EUS) and surgical resection from May 1996 to December 2007 at a tertiary centre. Clinical history, EUS characteristics, cytology, tumour markers and surgical histology were collected. Predictors of malignancy were determined by univariate and multivariate analysis using logistic regression. RESULTS: A total of 153 patients underwent a EUS and subsequent surgical intervention.Of the 153 patients, 57 (37%) had a histological diagnosis of malignancy. On univariate analysis, older age (P < 0.001), male gender (P = 0.010), jaundice (P = 0.039), history of other malignancy (P = 0.036), associated mass in cyst (P = 0.004) and malignant cytology (P < 0.001) were found to be associated with malignancy. History of pancreatitis (P = 0.008) and endoscopist impression of pseudocyst (P = 0.001) were found to be associated with benign cysts. Multivariate analysis found that only older age [Odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01-1.08], male gender (OR, 2.26; 95% CI, 1.08-4.73) and malignant cytology (OR, 6.60; 95% CI, 2.02-21.58) were independent predictors of malignancy. CONCLUSIONS: Older age, male gender and malignant cytology from EUS predict malignancy at surgical resection. These characteristics may be used to estimate the probability of malignancy in a cyst and aid in management.

Optical coherence tomography imaging for cancer diagnosis and therapy guidance.

Optical Coherence Tomography (OCT) is an emerging optical technology that has shown great promise for early cancer detection. Using backreflected light to visualize tissue microstructure, OCT can provide information on nuclear size and shape, nuclear-to-cytoplasmic ratio, and the organization and structure of glands. It can also provide functional information, like blood flow, tissue birefringence, etc. These capabilities could potentially be employed in three ways: as a primary diagnostic test to replace biopsy, as a screening tool to direct biopsy, and as a diagnostic tool to guide therapy and monitor therapy response. In this paper we present an application of OCT for pancreatic cancer diagnosis and therapy guidance.

Management and outcomes of pancreatic cystic lesions.

The management of pancreatic cystic lesions offers a challenge to clinicians. Mucinous cystic lesions pose a low risk of the development of neoplasia that must be taken into account in long-term management. Although the natural history has not been well defined, it is likely that malignant change in the mucinous epithelium takes place over years, very similar to what is observed with Barrett's esophagus. The traditional therapy of mucinous cystic lesions has been surgical resection. Lesions in the head of the pancreas will require a Whipple resection whereas tail lesions are managed with a distal pancreatectomy and splenectomy. In patients at high risk for surgical resection, the risk/benefit ratio may be excessively high, not supporting the use of resection therapy. Ethanol ablation therapy has been thoroughly studied in hepatic, renal, and thyroid cysts. Epithelial ablation with ethanol appears to be highly effective and relatively safe. Recently, ethanol ablation has been evaluated in pancreatic cystic neoplasms. In macrocystic lesions between 1 and 5 cm, ethanol lavage will result in epithelial ablation and cyst resolution in a high percentage of patients. Pancreatitis is rarely observed clinically and is not present in resection specimens. A randomised prospective clinical trial is currently underway.

Feasibility of endoscopic ultrasound-guided portal vein embolization with Enteryx.

BACKGROUND: Portal vein embolization (PVE) has been used as a preoperative strategy to induce hepatic lobar atrophy and contralateral lobe hypertrophy. We determined the feasibility of endoscopic ultrasound (EUS)-guided Enteryx (EVAL/ethylene-vinyl alcohol copolymer) embolization of the portal vein (EUS-PVE) in an animal model as a potential, minimally invasive, endoscopic technique. METHODS: EUS-guided embolization of the portal vein (EUS-PVE) using Enteryx was performed in a Yorkshire breed swine. Portal pressure measurements were obtained before and after vascular embolization. The animal was carefully monitored for seven days for evidence of abdominal pain, shock, or bleeding. An upper abdominal contrast-CT scan was performed to verify the location of the embolus. RESULTS: The PV pressure increased from 3 mmHg at baseline to a mean of 15 mmHg after EUS-PVE. The CT-scan on day 4 demonstrated Enteryx in the main portal vein with extension into the left branch. At sacrifice on day 7, a solid thrombus was visible grossly and histologically inside the main portal vein and the left branch of the portal vein. CONCLUSIONS: Selective embolization of the portal vein by EUS guidance appears to be feasible and a potential, minimally invasive, preoperative treatment option for patients undergoing extensive hepatectomy.

Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy.

BACKGROUND AND STUDY AIMS: The widespread use of cholangioscopy in the management of difficult choledocholithiasis has been limited by the need for two expert operators. This report describes the use of a technique of single-operator duodenoscope-assisted cholangioscopy (SODAC) in the successful management of 75 patients with choledocholithiasis. PATIENTS AND METHODS: The single-operator technique, allowing simultaneous control of both the duodenoscope and cholangioscope, was prospectively studied between June 1999 and June 2001 in the diagnosis and treatment of choledocholithiasis. RESULTS: A total of 109 SODAC procedures were conducted in 75 patients to manage choledocholithiasis. The indications were: firstly, SODAC-guided electrohydraulic lithotripsy (EHL) of stones in which conventional methods, including mechanical lithotripsy, had not been successful (52 SODAC procedures in 26 patients); and secondly, direct visualization of the biliary tree after cholangiography to assess the presence of stones (57 SODAC procedures in 49 patients). The locations and numbers of the stones, but not their size, were predictive of the number of SODAC-guided lithotripsy sessions required. All of the patients were free of stones at the end of the study period, and no complications were recorded. CONCLUSIONS: Single-operator SODAC-guided electrohydraulic lithotripsy was effective in the treatment of difficult cases of choledocholithiasis in which conventional methods had previously failed. The technique may allow increased use of cholangioscopy in the management of choledocholithiasis.