Michael K. Sanders

Comparison of BISAP, Ranson's, APACHE-II, and CTSI Scores in Predicting Organ Failure, Complications, and Mortality in Acute Pancreatitis

OBJECTIVES:Identification of patients at risk for severe disease early in the course of acute pancreatitis (AP) is an important step to guiding management and improving outcomes. A new prognostic scoring system, the bedside index for severity in AP (BISAP), has been proposed as an accurate method for early identification of patients at risk for in-hospital mortality. The aim of this study was to compare BISAP (blood urea nitrogen >25u2009mg/dl, impaired mental status, systemic inflammatory response syndrome (SIRS), age>60 years, and pleural effusions) with the “traditional” multifactorial scoring systems: Ransons, Acute Physiology and Chronic Health Examination (APACHE)-II, and computed tomography severity index (CTSI) in predicting severity, pancreatic necrosis (PNec), and mortality in a prospective cohort of patients with AP.METHODS:Extensive demographic, radiographic, and laboratory data from consecutive patients with AP admitted or transferred to our institution was collected between June 2003 and September 2007. The BISAP and APACHE-II scores were calculated using data from the first 24u2009h from admission. Predictive accuracy of the scoring systems was measured by the area under the receiver-operating curve (AUC).RESULTS:There were 185 patients with AP (mean age 51.7, 51% males), of which 73% underwent contrast-enhanced CT scan. Forty patients developed organ failure and were classified as severe AP (SAP; 22%). Thirty-six developed PNec (19%), and 7 died (mortality 3.8%). The number of patients with a BISAP score of ≥3 was 26; Ransons ≥3 was 47, APACHE-II ≥8 was 66, and CTSI ≥3 was 59. Of the seven patients that died, one had a BISAP score of 1, two had a score of 2, and four had a score of 3. AUCs for BISAP, Ransons, APACHE-II, and CTSI in predicting SAP are 0.81 (confidence interval (CI) 0.74–0.87), 0.94 (CI 0.89–0.97), 0.78 (CI 0.71–0.84), and 0.84 (CI 0.76–0.89), respectively.CONCLUSIONS:We confirmed that the BISAP score is an accurate means for risk stratification in patients with AP. Its components are clinically relevant and easy to obtain. The prognostic accuracy of BISAP is similar to those of the other scoring systems. We conclude that simple scoring systems may have reached their maximal utility and novel models are needed to further improve predictive accuracy.

Evaluation and Management of Autoimmune Pancreatitis: Experience at a Large US Center

OBJECTIVES:Autoimmune pancreatitis (AIP) is increasingly recognized as a form of chronic pancreatitis. Systematic evaluation and management of AIP in the United States is reported only from one center. Our aim was to review the evaluation and management of AIP at a large tertiary center.METHODS:We retrospectively reviewed information on demographics, clinical presentation, laboratory and imaging findings, extrapancreatic involvement, treatment response, and recurrence in 26 patients with AIP treated at the University of Pittsburgh Medical Center from 1998 to 2007.RESULTS:The median age at presentation was 62.5 years (range: 23–86), 65% were men, and 88% were Caucasians. The most common presentation included new-onset mild abdominal pain (65%), jaundice (62%), and weight loss (42%). Pancreatic mass, enlargement, or prominence on imaging was present in 85% of the patients. Serum IgG4 (immunoglobulin-4) was elevated (>140u2009mg/dl) in 44% (8/18) at presentation. The most common extrapancreatic finding was extrapancreatic/intrahepatic biliary strictures (35%). Peri-pancreatic vascular complications were noted in 23% of the patients. Six patients underwent partial or complete pancreatectomy. Partial or complete response was observed for initial steroid treatment in 19 patients and for methotrexate in 1 patient. Recurrences were common, especially in patients with extrapancreatic manifestations, and usually responded to a combination of steroids and azathioprine. Any one of the commonly used diagnostic criteria (Mayo Clinics HISORt criteria, the Japanese Pancreas Society criteria, Korean diagnostic criteria) was fulfilled in 85% of cases.CONCLUSIONS:In this second major US series, we confirm several findings previously reported in AIP. Our study highlights the presence of vascular complications in a subset of patients with AIP. The current diagnostic criteria may not identify all AIP patients.

EUS-guided fiducial placement for stereotactic body radiotherapy in locally advanced and recurrent pancreatic cancer

BACKGROUNDnStereotactic body radiotherapy (SBRT) has been approved for the treatment of locally advanced pancreatic cancer. Placement of gold fiducials is required for real-time tracking and delivery of a high-dose therapeutic beam of radiation to the tumor. Traditionally, fiducials have been placed either intraoperatively or percutaneously. Recently, EUS-guided fiducial placement has been reported, but the safety and feasibility of this approach is not well defined.nnnOBJECTIVEnThe aim of this study was to determine the safety, feasibility, and limitations of EUS-guided placement of 0.8 x 5.0 mm fiducials via a 19-gauge needle for locally advanced and recurrent pancreatic cancer.nnnDESIGNnProspective study of patients with either locally advanced or recurrent pancreatic cancer referred for EUS-guided fiducial placement for SBRT at our institution over a 3-year period.nnnSETTINGnTertiary referral center conducting >1800 EUS procedures annually.nnnMAIN OUTCOME MEASUREMENTSnPrimary outcome measurements included success, complications, and technical limitations of EUS-guided fiducial placement in pancreatic cancer. In addition, the percentage of patients successfully completing SBRT after EUS-guided fiducial placement was determined.nnnRESULTSnA total of 51 patients (mean age 73 years; 57% male) with locally advanced (n = 36) and recurrent (n = 15) pancreatic cancer were referred for EUS-guided fiducial placement. Fiducials were successfully placed in 46 patients (90%), with technical failures occurring in 4 patients (8%) with recurrent cancer after pancreaticoduodenectomy. In 3 patients (7%), the fiducials spontaneously migrated from the original site of injection, thereby requiring a second EUS procedure for placement of additional fiducials. Of the 46 patients with fiducials placed under EUS guidance, 42 patients (91%) successfully completed SBRT. Two patients experienced disease progression before SBRT, 1 patient was lost to follow-up, and 1 patient experienced a complication at ERCP that precluded further therapy. Only 1 complication (2%), of mild pancreatitis, occurred in a patient undergoing simultaneous placement of fiducials and celiac plexus neurolysis for intractable abdominal pain.nnnLIMITATIONSnSingle-center experience and lack of a formal follow-up protocol to assess for complications.nnnCONCLUSIONnEUS-guided fiducial placement for SBRT in locally advanced and recurrent pancreatic cancer is safe and feasible. Successful placement was achieved in 90% of patients, with a low complication rate (2%). Furthermore, 91% of patients successfully completed SBRT after EUS-guided fiducial delivery. Although fiducials can spontaneously migrate from the initial injection site, the rate of migration is relatively low (7%), and no migration-related complications occurred over the course of this study. Limitations to EUS-guided fiducial placement may include surgically altered anatomy (pancreaticoduodenectomy) in patients with recurrent pancreatic cancer.

Lymphoepithelial Cysts of the Pancreas: An EUS Case Series

BACKGROUNDnLymphoepithelial cysts (LEC) of the pancreas are rare benign lesions that can be misdiagnosed as pancreatic masses or cystic neoplasms. With widespread use of abdominal cross-sectional imaging, more pancreatic lesions are being discovered, with EUS being used to further evaluate the abnormality.nnnOBJECTIVEnOur purpose was to describe EUS and cyst aspirate features of LEC of the pancreas.nnnDESIGNnCase series.nnnSETTINGnSingle tertiary referral center.nnnPATIENTSnNine patients with lymphoepithelial cysts who underwent EUS-FNA.nnnRESULTSnFive male and 4 female patients were identified (mean age 51 years). All lesions were discovered by CT and described as peripancreatic in 67% of cases (6/9). EUS examination described a solid-appearing hypoechoic and heterogeneous mass with subtle postacoustic enhancement in 5 of 9 cases. Four lesions were described as purely cystic: 2 were septated, 1 was unilocular, and 1 had internal papillary fronds. Mean cyst size was 5.2 cm (range 1.7-12 cm). Cyst aspirates revealed a thick milky, creamy, or frothy aspirate in 56% of cases (5/9). Cyst cytologic examination revealed squamous material (nucleated/anucleated cells or keratin debris) in all cases. Lymphocytes were seen in 56% of aspirates (5/9). Carcinoembryonic antigen (CEA) levels were obtained in 5 cases (median 6.5 ng/mL [range 2.9-493.4 ng/mL]). Six patients have avoided surgery on the basis of EUS-FNA cytologic results confirming the diagnosis of LEC. Three patients underwent surgical resection: 2 for symptomatic lesions and 1 for concern for a mucinous cystic neoplasm given an elevated aspirate CEA level. Surgical pathologic examination confirmed LEC in each.nnnLIMITATIONSnRetrospective single-center study.nnnCONCLUSIONSnLEC should be considered whenever a large, well-defined solid or cystic peripheral pancreatic lesion is found. A thick milky, creamy, or frothy aspirate is common. The presence of squamous material and lymphocytes on cytologic examination is diagnostic of LEC. Aspirate CEA level may be elevated and should be considered in conjunction with cytologic results to avoid misdiagnosis as a mucinous cystic neoplasm. Asymptomatic LEC should be managed conservatively.

Endoscopic Therapy is Effective for Patients with Chronic Pancreatitis

BACKGROUND & AIMSnEndoscopic therapy (ET) frequently is used to treat patients with painful chronic pancreatitis (CP), but little is known about outcomes of patients for whom ET was not successful who then underwent surgery, or outcomes after ET compared with only medical treatment. We evaluated use and long-term effectiveness of ET in a well-defined cohort of patients with CP.nnnMETHODSnWe analyzed data from 146 patients with CP who participated in the North American Pancreatitis Study 2 at the University of Pittsburgh Medical Center from 2000 to 2006; 71 (49%) patients received ET at the University of Pittsburgh Medical Center. Success of ET and surgery were defined by cessation of narcotic therapy and resolution of episodes of acute pancreatitis. Disease progression was followed up from its onset until January 1, 2011 (mean, 8.2 ± 4.7 y).nnnRESULTSnPatients who underwent ET had more symptoms (pain, recurrent pancreatitis) and had more complex pancreatic morphology (based on imaging) than patients who received medical therapy. ET had a high rate of technical success (60 of 71 cases; 85%); its rates of clinical success were 51% for 28 of 55 patients for whom follow-up data were available (mean time, 4.8 ± 3.0 y) and 50% for 12 of 24 patients who underwent surgery after receiving ET. Patients who responded to ET were significantly older, had a shorter duration of disease before ET, had less constant pain, and required fewer daily narcotics than patients who did not respond to ET. Among the 36 symptomatic patients who received medical therapy and were followed up for a mean period of 5.7 ± 4.1 years, 31% improved and 53% had no change in symptoms; of these, 21% underwent surgery.nnnCONCLUSIONSnET is clinically successful for 50% of patients with symptomatic CP. When ET is not successful, surgery has successful outcomes in 50% of patients. Symptoms resolve in 31% of symptomatic patients who receive only medical therapy.

Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis

Pancreatic lymphoepithelial cysts are rare benign cysts that cannot be reliably differentiated from neoplastic mucinous cysts preoperatively. Although elevated cyst fluid carcinoembryonic antigen (CEA) levels support a diagnosis of a mucinous cyst, the finding of increased CEA levels in lymphoepithelial cysts prompted this study. Nine resected lymphoepithelial cysts were examined for expression of CEA, carbohydrate antigen (CA) 19-9, CK7, p63, PAS-D and a panel of mucins. The pathology data were correlated with clinical information, including serum, cyst fluid and imaging studies. By computed tomography scan, although most lymphoepithelial cysts appeared cystic, 23% were described as masses. The endoscopic ultrasound findings were variable, but the lymphoepithelial cysts tended to be hypoechoic cystic lesions or masses. On cytology, 44% of the cysts had squamous cells, 67% had glandular cells and 56% had atypical cells. The cysts were resected because of size ≥3u2009cm (89%), symptoms (44%) and/or elevated cyst fluid CEA levels (33%). The cyst fluid CEA levels in the three cysts tested were >450u2009ng/ml. Histopathologically, all cysts were lined by mature, stratified squamous-type cells and produced keratin. Mucous cells were present in 78% of the cysts. The immunohistochemical profile of the squamous lining was CK7+, p63+, MUC1+, MUC4+, MUC2−, MUC5AC− and MUC6−. Even though lymphoepithelial cysts are lined by squamous-type epithelium, all our resected lymphoepithelial cysts expressed CEA and/or CA19-9, many contained mucous cells, and three exhibited markedly elevated cyst fluid CEA levels. Although cyst fluid CEA levels >200u2009ng/ml support the diagnosis of mucinous neoplasms, this study emphasizes the need for clinicians and pathologists to recognize that lymphoepithelial cysts can mimic neoplastic mucinous cysts clinically, radiographically and on cyst fluid CEA analysis.

Validation of a prediction rule to maximize curative (R0) resection of early-stage pancreatic adenocarcinoma

BACKGROUNDnThe surgeons contribution to patients with localized pancreatic adenocarcinoma (PAC) is a margin negative (R0) resection. We hypothesized that a prediction rule based on pre-operative imaging would maximize the R0 resection rate while reducing non-therapeutic intervention.nnnMETHODSnThe prediction rule was developed using computed tomography (CT) and endoscopic ultrasound (EUS) data from 65 patients with biopsy-proven PAC who underwent attempted resection. The rule classified patients as low or high risk for non-R0 outcome and was validated in 78 subsequent patients.nnnRESULTSnMODEL VARIABLES WERE: any evidence of vascular involvement on CT; EUS stage and EUS size dichotomized at 2.6 cm. In the validation cohort, 77% underwent resection and 58% achieved R0 status. If only patients in the low-risk group underwent surgery, the prediction rule would have increased the resection rate to 92% and the R0 rate to 73%. The R0 rate was 40% higher in low-risk compared with high-risk patients (P < 0.001). High risk was associated with a 67% rate of non-curative surgery (unresectable disease and metastases).nnnCONCLUSIONnThe prediction rule identified patients most likely to benefit from resection for PAC using pre-operative CT and EUS findings. Model predictions would have increased the R0 rate and reduced non-therapeutic interventions.

EUS-FNA Mutational Analysis in Differentiating Autoimmune Pancreatitis and Pancreatic Cancer

Background/Aims: Autoimmune pancreatitis (AIP) may mimic pancreatic cancer (PC). The detection of DNA mutations in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) material may improve discrimination between AIP and PC and is the context for this study. Methods: In a retrospective study, archived EUS-FNA material from patients with AIP and PC at two centers was analyzed for KRAS mutations and loss-of-heterozygosity analysis involving 18 microsatellite markers. KRAS status and the fractional allelic loss (number of affected microsatellites divided by informative ones) were compared for AIP and PC. Results: Thirty-two patients with 33 samples were studied. There were 16 patients with AIP (17 samples) and 16 patients with PC. DNA amplification failed in 7 samples. Of 25 patients (26 samples), 14 had AIP (7 male, age 57 ± 17 years; mean ± SD) and 11 had PC (7 male, age 65 ± 14 years; mean ± SD). Cytology results for AIP were inflammatory = 3, inconclusive = 10, suspicious for malignancy = 2 and for PC were malignant = 5, suspicious for malignancy = 4 and inconclusive = 2, respectively. KRAS mutation was detected in none of the AIP cases and 10/11 PC cases (91%, Pearson χ2 = 22.16, p < 0.001) or 10/16 PC cases (63%) accounting for PC cases with failed DNA amplification. Mean (±SD) fractional allelic loss for the AIP cases (0.16 ± 0.15) was not significantly different from the PC cases (0.26 ± 0.19). Conclusions: A KRAS mutation in EUS/FNA material from a pancreatic mass is associated with malignancy and may help discriminate from benign conditions such as AIP.

Metastatic risk of diminutive rectal carcinoid tumors: a need for surveillance rectal ultrasound?

v f p The term “karzinoide” was first used by Oberndorfer in 1907 to describe tumors that resembled adenocarcinomas yet behaved in a more benign fashion. Synonymous with ow-grade (World Health Organization [WHO] grade 1) ell-differentiated neuroendocrine tumor,2,3 carcinoids are the most common type of neuroendocrine tumor seen in the GI tract.4 They are most frequently found in the ileum, followed by the cecum and then the rectum.5 Rectal carcinoid tumors reportedly constitute approximately 1% to 2% of all rectal tumors, and their incidence is increasing, likely because of the increased use of screening colonoscopy and the resultant incidental detection.5,6 The WHO classification describes rectal carcinoids as low-grade malignant, even in the presence of metastasis.7 Historically, tumor size has been the most studied rectal carcinoid characteristic in regard to metastatic risk. Tumors 10 mm in size were thought to have negligible metastatic risk, thus justifying local or endoscopic excision.5,6,8 Howver, more recent studies contest tumor size alone, showng that depth of invasion, lymphovascular invasion (LVI), nd mitotic rate are also important risk factors for etastasis.9-11 Currently, no surveillance recommendations exist for small rectal carcinoids that have been locally excised or removed endoscopically. Some suggest that if the lesion is small ( 10 mm) without evidence of lymphatic invasion or elevated mitotic rate, no surveillance is necessary.9,11-13 Today, endoscopic rectal ultrasound (RUS) is frequently used to assess rectal carcinoid tumors and to direct therapy based on size, depth of invasion, and presence of metastatic lymph nodes (LNs). We sought to review our expe-

EUS-guided rendezvous for the treatment of pancreaticopleural fistula in a patient with chronic pancreatitis and pancreas pseudodivisum

Pancreatic duct (PD) disruption can result from acute and chronic pancreatitis, abdominal trauma, pancreatic malignancy, and surgery. Conservative management involves pancreatic rest with either hyperalimentation or nasojejunal feeding, initiation of somatostatin analogues, and/or pancreatic enzyme supplements. Unfortunately, medical therapy may be ineffective. Transpapillary stent placement is a safe and effective technique for managing ductal disruption. However, conventional stent placement may be difficult because of altered anatomy, PD strictures, and difficult cannulation. EUS-guided rendezvous has been reported for antegrade access to both the biliary duct and PD. We report a case of chronic pancreatitis with pancreas pseudodivisum complicated by ductal disruption and a pancreaticopleural fistula, subsequently treated with EUS-guided rendezvous and stent placement after failed conventional ERCP and medical therapy.