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.
Background & Aims Although surgery is the standard technique for drainage of pancreatic pseudocysts, use of endoscopic methods is increasing. We performed a single-center, open-label, randomized ...trial to compare endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage. Methods Patients with pancreatic pseudocysts underwent endoscopic (n = 20) or surgical cystogastrostomy (n = 20). The primary end point was pseudocyst recurrence after a 24-month follow-up period. Secondary end points were treatment success or failure, complications, re-interventions, length of hospital stay, physical and mental health scores, and total costs. Results At the end of the follow-up period, none of the patients who received endoscopic therapy had a pseudocyst recurrence, compared with 1 patient treated surgically. There were no differences in treatment successes, complications, or re-interventions between the groups. However, the length of hospital stay was shorter for patients who underwent endoscopic cystogastrostomy (median, 2 days, vs 6 days in the surgery group; P < .001). Although there were no differences in physical component scores and mental health component scores (MCS) between groups at baseline on the Medical Outcomes Study 36-Item Short-Form General Survey questionnaire, longitudinal analysis showed significantly better physical component scores ( P = .019) and mental health component scores ( P = .025) for the endoscopy treatment group. The total mean cost was lower for patients managed by endoscopy than surgery ($7011 vs $15,052; P = .003). Conclusions In a randomized trial comparing endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage, none of the patients in the endoscopy group had pseudocyst recurrence during the follow-up period, therefore there is no evidence that surgical cystogastrostomy is superior. However, endoscopic treatment was associated with shorter hospital stays, better physical and mental health of patients, and lower cost. Trial Registration: ClinicalTrials.gov : NCT00826501.
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 ≤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.
Objectives
Endoscopy is a minimally invasive technique for the drainage of peripancreatic fluid collections. This study evaluated the clinical outcomes and predictors of treatment success in ...consecutive patients undergoing endoscopic transmural drainage of peripancreatic fluid collections.
Methods
This is a retrospective study of patients who underwent endoscopic drainage of peripancreatic fluid collections over 7 years. Prior to drainage, an ERCP was attempted for stent placement in all patients with a pancreatic duct leak. Drainages were performed using conventional endoscopy or endoscopic ultrasound. Transmural stents and/or drainage catheters were deployed and endoscopic necrosectomy was undertaken when required. Data on clinical outcomes and complications were collected prospectively.
Results
A total of 211 patients underwent drainage of peripancreatic fluid collections that was classified as pseudocyst in 45%, abscess in 28%, and necrosis in 27%. Mean diameter of the fluid collection was 100.6 mm, and 34.5% of patients had pancreatic duct stent placement. Median duration of follow-up was 356 days. Treatment success was 85.3% and was higher for pseudocyst and abscess compared to necrosis (93.5% vs. 63.2%,
p
< 0.0001). Complications were encountered in 17 patients (8.5%) and was higher for drainage of necrosis than pseudocyst or abscess (15.8% vs. 5.2%,
p
= 0.02). Treatment success was more likely for patients with pseudocyst or abscess than necrosis (adjusted OR = 7.6, 95% CI 2.9, 20.1,
p
< 0.0001) when adjusted for serum albumin and white cell count, type of endoscopic modality or accessory used, pancreatic duct stenting, luminal compression, size and location of fluid collection.
Conclusions
Endoscopic therapy is a highly effective technique for the management of patients with non-necrotic peripancreatic fluid collections.
Introduction
Although mortality rates from pancreatectomy have decreased worldwide, death remains an infrequent but profound event at an individual practice level. Root-cause analysis is a ...retrospective method commonly employed to understand adverse events. We evaluate whether emerging mortality risk assessment tools sufficiently predict and account for actual clinical events that are often identified by root-cause analysis.
Methods
We assembled a Pancreatic Surgery Mortality Study Group comprised of 36 pancreatic surgeons from 15 institutions in 4 countries. Mortalities after pancreatectomy (30 and 90 days) were accrued from 2000 to 2010. For root-cause analysis, each surgeon “deconstructed” the clinical events preceding a death to determine cause. We next tested whether mortality risk assessment tools (ASA, POSSUM, Charlson, SOAR, and NSQIP) could predict those patients who would die (
n
= 218) and compared their prognostic accuracy against a cohort of resections in which no patient died (
n
= 1,177).
Results
Two hundred eighteen deaths (184 Whipple’s resection, 18 distal pancreatectomies, and 16 total pancreatectomies) were identified from 11,559 pancreatectomies performed by surgeons whose experience averaged 14.5 years. Overall 30- and 90-day mortalities were 0.96% and 1.89%, respectively. Individual surgeon rates ranged from 0% to 4.7%. Only 5 patients died intraoperatively, while the other 213 succumbed at a median of 29 days. Mean patient age was 70 years old (38% were >75 years old). Malignancy was the indication in 90% of cases, mostly pancreatic cancer (57%). Median operative time was 365 min and estimated blood loss was 700 cc (range, 100–16,000 cc). Vascular repair or multivisceral resections were required for 19.7% and 15.1%, respectively. Seventy-seven percent had a variety of major complications before death. Eighty-seven percent required intensive care unit care, 55% were transfused, and 35% were reoperated upon. Fifty percent died during the index admission, while another 11% died after a readmission. Almost half (
n
= 107) expired between 31 and 90 days. Only 11% had autopsies. Operation-related complications contributed to 40% of deaths, with pancreatic fistula being the most evident (14%). Technical errors (21%) and poor patient selection (15%) were cited by surgeons. Of deaths, 5.5% had associated cancer progression—all occurring between 31 and 90 days. Even after root-cause scrutiny, the ultimate cause of death could not be determined for a quarter of the patients—most often between 31 and 90 days. While assorted risk models predicted mortality with variable discrimination from nonmortalities, they consistently underestimated the actual mortality events we report.
Conclusion
Root-cause analysis suggests that risk prediction should include, if not emphasize, operative factors related to pancreatectomy. While risk models can distinguish between mortalities and nonmortalities in a collective fashion, they vastly miscalculate the actual chance of death on an individual basis. This study reveals the contributions of both comorbidities and aggressive surgical decisions to mortality.
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 ($9077 vs $14,815, P = .01), which corresponded to a cost savings of $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.
Background Differences in the behavior of postoperative pancreatic fistulas (POPF) have been described after various pancreatic resections. Here, we compare POPFs after pancreatoduodenectomy (PD) and ...distal pancreatectomy (DP) using the average complication burden (ACB), a quantitative measure of complication burden. Methods From 2001 to 2014, 837 DPs and 1,533 PDs were performed by 14 surgeons at 4 institutions. POPFs were categorized by International Study Group on Pancreatic Fistula standards as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). ACB values were derived from fistula severity scores based on the Modified Accordion Severity Grading. The ACB of POPFs was compared between PD and DP. Results POPFs were more common after DP compared with PD (34.5 vs 27.2%; P < .001); however, the incidence of any complication was greater after PD (64.9 vs 53.2%; P < .001). When POPFs occurred, they were more likely to be the highest-graded complication after DP compared with PD (65.1 vs 51.6%; P < .001). ACB significantly varied between PDs and DPs for grade C POPFs (0.804 vs 0.611; P < .001). POPFs accounted for 31.2% of the overall complication burden after DP compared with 17.5% of the burden after PD. ACB differed significantly across both institutions and surgeons in terms of POPFs, nonfistulous complications, and overall complications (all P < .05). Conclusion Although POPFs occur less frequently after PD, they are associated with a greater complication burden compared with DP. ACB varies significantly between health care providers, suggesting the need for risk-adjusted comparisons of complication severity. Using ACB to evaluate a distinct morbidity has the potential to aid in assessing the impact of procedure-specific complications.
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.
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.
Methods: All patients who underwent EUS‐guided PFC drainage over 7 years were enrolled. Indications, demographics, technical details, complications, surgical interventions, and final outcomes were prospectively recorded.
Results: Of 148 patients who underwent EUS, PFC was located in the pancreatic body in 84 (56.8%), in the tail in 45 (30.4%), in the head in 15 (10.1%), and in the uncinate region in four patients (2.7%). Perforation was encountered at the site of transmural stenting in two patients (1.3%, 95% confidence interval CI: 0.41–4.76) with a pseudocyst in the uncinate region that was drained transgastrically. When compared to other locations, perforation was more common with PFC involving the uncinate region (0% vs 50%, P = 0.0005). Other complications included bleeding in one (0.67%, 95% CI: 0.16, 3.68), stent migration in 1 (0.67%, 95% CI: 0.16, 3.68), and infection in four patients (2.7%, 95% CI: 1.09, 6.73). Bleeding occurred in a patient with underlying acquired factor VIII inhibitors, stent migration in a patient who underwent drainage via the gastric cardia, and infection in two patients with pseudocysts and two with necrosis. While two patients who developed post‐procedural infection and one with stent migration were managed endoscopically, both perforations required surgery. Surgical debridement was performed in two patients who developed infection with successful outcomes in one, and death from underlying comorbidity in the other.
Conclusions: Complications are rare during EUS‐guided drainage of PFC and can be managed successfully in most patients.
Introduction
International Study Group of Pancreatic Fistula (ISGPF) grade C postoperative pancreatic fistulas (POPF) are the greatest contributor to major morbidity and mortality following ...pancreatoduodenectomy (PD); however, their infrequent occurrence has hindered deeper analysis. This study sought to develop a predictive algorithm, which could facilitate effective management of this challenging complication.
Methods
Data were accrued from 4301 PDs worldwide. Demographics, postoperative management, and microbiological characteristics of grade C POPFs were evaluated. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) preoperative and intraoperative variables were compared between grade C POPFs and a 639-case sample of non-grade C POPFs. Risk factors for grade C POPF formation were identified using regression analysis.
Results
Grade C POPFs developed in 79 patients (1.8 %). Deaths (90 days) occurred in 2.0 % (
N
= 88) of the overall series, with 35 % (
N
= 25) occurring in the presence of a grade C POPF. Reoperations occurred 72.2 % of the time. The rates of single- and multi-system organ failure were 28.2 and 39.7 %, respectively. Mortality rates escalated with pulmonary, renal, and neurologic organ failure, but they were unaffected by reoperation(s). The median number of complications incurred was four (IQR: 2–5), and the median duration of hospital stay was 32 (IQR: 21–54) days. Warning signs for impending grade C POPFs most often presented on postoperative day (POD) 6. Adjuvant chemotherapy might have benefited 55.7 % of grade C POPF patients, yet it was delayed in 25.6 % and never delivered in 67.4 % of these patients. Predictive models for grade C POPF occurrence based on preoperative factors alone and preoperative and intraoperative factors yielded areas under the receiver operating characteristic curve of 0.73 and 0.84 (both
P
< 0.000001), respectively.
Conclusion
This global study represents the largest analysis of grade C POPFs following PD. It describes the severe burden that grade C POPFs incur on patients, with high rates of reoperation and infection, while also potentially worsening overall survival by causing death and delay/omission of adjuvant therapy. Additionally, aggressive clinical management for these POPFs did not improve or worsen 90-day mortality. Predictive tools developed through these data may provide value in managing this difficult complication.
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