John D. Christein

Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos)

BACKGROUND Although prior studies evaluated the role of EUS and EGD for drainage of pancreatic pseudocysts, there are no randomized trials that compared the technical outcomes between both modalities. OBJECTIVE To compare the rate of technical success between EUS and EGD for transmural drainage of pancreatic pseudocysts. STUDY DESIGN A prospective randomized trial. SETTING A tertiary-referral center. PATIENTS Those with a history of pancreatitis and symptomatic pancreatic pseudocysts that measured greater than 4 cm in size who were referred for endoscopic transmural drainage. Patients with pancreatic abscess or necrosis were excluded. MAIN OUTCOME MEASUREMENTS Technical success was defined as the ability to access and drain a pseudocyst by placement of transmural stents. Complications were assessed at 24 hours and at day 30. Treatment success was defined as the complete resolution or decrease in size of the pseudocyst to <or=2 cm on CT in association with clinical resolution of symptoms at 6 weeks of follow-up. RESULTS Thirty patients were randomized to undergo pseudocyst drainage by EUS (n = 15) or EGD (n = 15) over a 6-month period. Of the 15 patients randomized to EUS, drainage was not undertaken in one, because an alternative diagnosis of biliary cystadenoma was established at EUS and was excluded (after randomization) from analysis. The mean age of the patients was 47 years; 62% were men (18/29). Except for their sex, there was no difference in patient or clinical characteristics between the 2 cohorts. Although all the patients (n = 14) randomized to an EUS underwent successful drainage (100%), the procedure was technically successful in only 5 of 15 patients (33%) randomized to an EGD (P < .001). All 10 patients who failed drainage by EGD underwent successful drainage of the pseudocyst on a crossover to EUS. There was no significant difference in the rates of treatment success between EUS and EGD after stenting, either by intention-to-treat (ITT) analysis (100% vs 87%; P = .48) or as-treated analysis (95.8% vs 80%; P = .32). Major procedure-related bleeding was encountered in 2 patients in whom drainage by EGD was attempted; one resulted in death and the other necessitated a blood transfusion. No significant difference was observed between EUS and EGD with regard to complications either by ITT (0% vs 13%; P = .48) or as-treated analyses (4% vs 20%; P = .32). Technical success was significantly greater for EUS than EGD, even after adjusting for luminal compression and sex (adjusted exact odds ratio 39.4; P = .001). LIMITATION Short duration of follow-up. CONCLUSIONS When available, EUS should be considered as the first-line treatment modality for endoscopic drainage of pancreatic pseudocysts given its high technical success rate.

Serum Biomarker Panels for the Detection of Pancreatic Cancer

Purpose: Serum–biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations. Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers. Results: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19–9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19–9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19–9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19–9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19–9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer. Conclusions: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations. Clin Cancer Res; 17(4); 805–16. ©2010 AACR.

EUS Versus Surgical Cyst-Gastrostomy for Management of Pancreatic Pseudocysts

BACKGROUND Although EUS-guided cyst-gastrostomy is increasingly being performed, there are no studies that compare the clinical outcomes and cost-effectiveness with surgical cyst-gastrostomy. OBJECTIVES To compare the clinical outcomes of EUS-guided cyst-gastrostomy with surgical cyst-gastrostomy for the management of patients with uncomplicated pancreatic pseudocysts and to perform a cost analysis of each treatment modality. DESIGN A retrospective case-controlled study. SETTING A tertiary-referral center. PATIENTS Consecutive patients with uncomplicated pancreatic pseudocysts managed by surgical and EUS-guided cyst-gastrostomy. METHODS An independent observer blinded to all clinic outcomes matched each patient who underwent a surgical cyst-gastrostomy with 2 patients who underwent an EUS-guided cyst-gastrostomy for age, etiology of pancreatitis, and the size of the pseudocyst. MAIN OUTCOME MEASUREMENTS Rates of treatment success, complications, and reinterventions; length of postprocedure hospital stay; and cost associated with each treatment modality. RESULTS Ten patients (6 men; mean age 42.3 years, range 22-65 years) who underwent surgical cyst-gastrostomy were matched with 20 patients who underwent an EUS-guided cyst-gastrostomy. There were no significant differences in demographics, major comorbidities, and clinical characteristics between both cohorts. Although there were no significant differences in rates of treatment success (100% vs 95%, P = .36), procedural complications (none in either cohort), or reinterventions (10% vs 0%, P = .13) between surgery versus an EUS-guided cyst-gastrostomy, the mean length of a postprocedure hospital stay for an EUS-guided cyst-gastrostomy was significantly shorter than for surgical cyst-gastrostomy (2.65 vs 6.5 days, P = .008). The average direct cost per case for EUS-guided cyst-gastrostomy was significantly less when compared with surgical cyst-gastrostomy (

Multiple transluminal gateway technique for EUS-guided drainage of symptomatic walled-off pancreatic necrosis

9077 vs

Durability of portal venous reconstruction following resection during pancreaticoduodenectomy.

14,815, P = .01), which corresponded to a cost savings of

Frequency of complications during EUS-guided drainage of pancreatic fluid collections in 148 consecutive patients.

5738 per patient. LIMITATIONS Retrospective, nonrandomized design; patients with pancreatic abscess or necrosis were not evaluated; a limited sample size and a short duration of follow-up. CONCLUSIONS EUS-guided cyst-gastrostomy should be considered as a first-line treatment approach for patients with uncomplicated pancreatic pseudocysts, because the procedure is cost saving and is associated with a shorter length of a postprocedure hospital stay when compared with surgical cyst-gastrostomy. There was no significant difference in clinical outcomes between both treatment modalities.

The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models

BACKGROUND Walled-off pancreatic necrosis often leads to severe clinical deterioration necessitating open debridement or endoscopic necrosectomy. A new EUS-based approach was devised to manage this condition by creating multiple transluminal gateways to facilitate effective drainage of the necrotic contents. OBJECTIVE To compare treatment outcomes between patients with walled-off pancreatic necrosis managed endoscopically by a multiple transluminal gateway technique (MTGT) or a conventional drainage technique (CDT). DESIGN Retrospective study. SETTING Tertiary-care referral center. PATIENTS This study involved patients with severe acute pancreatitis complicated by walled-off pancreatic necrosis managed endoscopically. INTERVENTION In MTGT, 2 or 3 transmural tracts were created by using EUS guidance between the necrotic cavity and the GI lumen. While one tract was used to flush normal saline solution via a nasocystic catheter, multiple stents were deployed in others to facilitate drainage of necrotic contents. In the CDT, two stents with a nasocystic catheter were deployed via 1 transmural tract. MAIN OUTCOME MEASUREMENTS Resolution of symptoms, radiological findings on follow-up CT, and the need for subsequent surgery or endoscopic necrosectomy. RESULTS Of 60 patients with symptomatic walled-off pancreatic necrosis, 12 (3 women, mean age 55.1 years) were managed by MTGT and 48 (12 women, mean age 55.2 years) by CDT. Treatment was successful in 11 of 12 (91.7%) patients managed by MTGT versus 25 of 48 (52.1%) managed by CDT (P = .01). Although 1 patient in the MTGT cohort required endoscopic necrosectomy, in the CDT cohort, 17 required surgery, 3 underwent endoscopic necrosectomy, and 3 died of multiple-organ failure. Treatment success was more likely for patients treated by MTGT than by CDT (adjusted odds ratio = 9.24; 95% confidence interval, 1.08-79.02; P = .04) when we adjusted for the size of the walled-off pancreatic necrosis and pancreatic duct stent placement. LIMITATIONS Selective patient population. CONCLUSION The EUS-guided MTGT is an effective treatment option for the management of symptomatic walled-off pancreatic necrosis because it obviates the need for surgery and endoscopic necrosectomy and its attendant procedure-related morbidity. Prospective studies are required to confirm these preliminary but promising data.

Prophylactic octreotide for pancreatoduodenectomy: more harm than good?

Venous resection and reconstruction is becoming more common during pancreaticoduodenectomy (PD). There are multiple options for reconstruction of the mesenteric venous system ranging from primary repair to grafting with autologous or synthetic material. Few studies report on the patency rates and long-term morbidity of these repairs. We sought to describe our experience with venous reconstruction during PD with specific attention to patency and long-term morbidity and mortality. Thrombosis rates of mesenteric venous reconstruction during PD are low, with low associated morbidity. In this retrospective cohort, clinical, operative, and pathologic data were collected from consecutive patients for 1988 through 2003. Graft patency on follow-up imaging studies was determined, and short- as well as long-term morbidity and mortality were recorded. Sixty-four patients underwent PD with venous resection/reconstruction from 1988 through 2003. Mean patient age was 63 years, with pancreatic ductal adenocarcinoma as the pathology in 88%. Reconstruction consisted of primary lateral venorrhaphy in 29 (45%), PTFE graft in 18 (28%), primary end-to-end repair in 13 (20%), and autologous vein graft in 4 (6%). There was one perioperative death (2%). Follow-up imaging to assess patency was available for a mean of 12.2 months postoperatively. Eleven thromboses were diagnosed at a mean of 11.9 months. Three thromboses (5%) were noted within 30 days and full anticoagulation was chosen. Fifty-three percent of patients received anticoagulation with aspirin, warfarin, or clopidogrel based upon surgeon preference. There was no difference in thrombosis rates between those receiving anticoagulation and those who did not (P=0.65). In those patients with thrombosis outside the acute time period, morbidity was limited to ascites in three patients and splenic vein thrombosis with uncomplicated esophageal varices in another patient. Mesenteric venous resection and reconstruction during PD has a high patency rate, and those reconstructions that do thrombose are associated with a low morbidity. The majority of reconstruction thromboses that occurred late were associated with recurrence.

Applying Proteomic-Based Biomarker Tools for the Accurate Diagnosis of Pancreatic Cancer

Background and Aim:  The aim of the present study was to evaluate the frequency of complications during endoscopic ultrasound (EUS)‐guided drainage of pancreatic fluid collections (PFC), identify contributing factors, and report on management outcomes.

Risk-adjusted Outcomes of Clinically Relevant Pancreatic Fistula Following Pancreatoduodenectomy: A Model for Performance Evaluation.

The primary aim of this study was to evaluate the antitumor efficacy of the bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (tumorgraft) models. A secondary aim of the study was to evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors, as has been reported for other tumor types. We used five PDAC tumorgraft models that retain specific characteristics of tumors of origin to evaluate the antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg daily for 21 or 28 days). Expression analyses were performed with tumors harvested from host mice after treatment with JQ1 or vehicle control. An nCounter PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes was used to identify gene products affected by JQ1. Quantitative RT–PCR, immunohistochemistry and immunoblots were carried out to confirm that changes in RNA expression reflected changes in protein expression. JQ1 inhibited the growth of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation; but induced no consistent change in expression of c-Myc protein. Expression profiling identified CDC25B, a regulator of cell cycle progression, as one of the three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05). Inhibition of tumor progression was more closely related to decreased expression of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that inhibit the function of proteins with bromodomains merit further investigation for treating PDAC tumors. Work is ongoing in our laboratory to identify effective drug combinations that include JQ1.