Tossapol Kerdsirichairat

Total Pancreatectomy With Islet Autotransplantation Improves Quality of Life in Patients With Refractory Recurrent Acute Pancreatitis

BACKGROUND & AIMSnTherapeutic options are limited for patients with recurrent acute pancreatitis who have intractable symptoms despite maximal endoscopic and medical treatment, but equivocal or no morphologic or functional evidence of chronic pancreatitis. We performed a prospective observational cohort study to determine the efficacy of total pancreatectomy with islet autotransplantation (TPIAT) for these patients.nnnMETHODSnWe collected data from all patients undergoing TPIAT at the University of Minnesota from 2007 through 2013; 49 patients (42 female; mean age, 32.8 ± 7.8 years) had a diagnosis of recurrent acute pancreatitis not provoked by intervention, with negative or equivocal findings from nondiagnostic imaging or pancreatic function tests for chronic pancreatitis, and intractable pain between episodes. Data on insulin use, narcotic requirements, pain scores, and health-related quality of life were collected before TPIAT; 3 months, 6 months, and 1 year afterward; and then yearly.nnnRESULTSnAll 49 patients studied required narcotics before TPIAT (45 daily users and 4 intermittent users); 2 had insulin-treated diabetes. At 1 year after TPIAT, 22 out of 48 patients (46%) reported no use of narcotic pain medications (P < .001 vs baseline). Health-related quality of life score, measured by the physical and mental component summary score, increased by approximately 1 standard deviation from the population mean (P < .001 for the physical component summary; Pxa0= .019 for the mental component summary). At 1 year after TPIAT, 21xa0out of 48xa0patients (45%) were insulin independent; their mean percent glycosylated hemoglobin A1c at 1 year after TPIAT was 6.0% ± 0.9% (5.2% ± 0.6% pre-TPIAT).nnnCONCLUSIONSnPatients with recurrent acute pancreatitis but lacking clear chronic pancreatitis benefit from TPIAT, with outcomes similar to those previously described for patients with chronic pancreatitis (improved quality of life and reduced narcotic use). For these patients who have otherwise limited surgical treatment options, TPIAT can be considered when medical and endoscopic therapies have failed.

Urgent ERCP with pancreatic stent placement or replacement for salvage of post-ERCP pancreatitis

BACKGROUND AND STUDY AIMSnUrgent placement or replacement of pancreatic stents shortly after endoscopic retrograde cholangiopancreatography (ERCP) might attenuate the course of evolving post-ERCP pancreatitis (PEP).nnnPATIENTS AND METHODSnSalvage ERCP with de novo pancreatic stent placement or replacement of outwardly migrated stents was performed within 2u200a-u200a48 hours in patients with evolving PEP accompanied by severe pain, systemic inflammatory response syndrome (SIRS), and major elevations in serum amylase and lipase. Serial pain scores, amylase and lipase levels, and hospital course were studied.nnnRESULTSnPEP according to Cotton consensus criteria developed after 64 (2u200a%) of 3216 ERCPs over 3 years. Of the 64 patients with PEP, 14 underwent salvage ERCP (5 without and 9 with prior pancreatic stents, 7 of which had migrated outwards prematurely). All patients had SIRS and a high score (≥u200a3) for the bedside index for severity in acute pancreatitis. Median clinical onset of PEP was at 5 hours (range 0u200a-u200a68 hours) in patients with prophylactic pancreatic stents vs. 2 hours (range 0.5u200a-u200a2.5 hours) in patients without prophylactic pancreatic stents (Pu200a<u200a0.05). Salvage ERCP was performed at a median of 10 hours (interquartile range [IQR] 2.4u200a-u200a22.7 hours). Improvement in pain, amylase, lipase, and resolution of SIRS were statistically significant at 24 hours after salvage ERCP (Pu200a=u200a0.003). Median length of hospital stay was 2 days (IQR 1u200a-u200a4.75). No necrotizing pancreatitis or late complications occurred.nnnCONCLUSIONnUrgent salvage ERCP with de novo pancreatic stent placement or replacement of a migrated stent is a novel approach in the setting of early PEP, and was associated with rapid resolution of clinical pancreatitis and reduction in levels of amylase and lipase.

Endoscopic Drainage of >50% of Liver in Malignant Hilar Biliary Obstruction Using Metallic or Fenestrated Plastic Stents

Objectives:Endoscopic drainage of complex hilar tumors has generally resulted in poor outcomes. Drainage of >50% of liver volume has been proposed as optimal, but not evaluated using long multifenestrated plastic stents (MFPS) or self-expanding metal stents (SEMS). We evaluated outcomes of endoscopic drainage of malignant hilar strictures using optimal strategy and stents, and determined factors associated with stent patency, survival, and complications.Methods:Cross-sectional study was conducted at an academic center over 5 years. MFPS (10 French or 8.5 French) or open-cell SEMS were used for palliation of unresectable malignant hilar strictures, with imaging-targeted drainage of as many sectors as needed to drain >50% of viable liver volume. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan–Meier analysis.Results:77 patients with malignant hilar biliary strictures (median Bismuth IV) underwent targeted stenting (41 MFPS and 36 SEMS). Comparing MFPS vs. SEMS, technical success (95.1 vs. 97.2%, P=0.64), clinical success (75.6 vs. 83.3%, P=0.40), frequency of multiple stents (23/41 vs. 25/36, P=0.19), survival and adverse events were similar, but stent patency was significantly shorter (P<0.0001). Factors associated with survival were Karnofsky score and serum bilirubin level at presentation. Outcomes were independent of Bismuth class with acceptable results in Bismuth III and IV.Conclusions:Endoscopic biliary drainage with MFPS or open-cell SEMS targeting >50% of viable liver resulted in effective palliation in patients with complex malignant hilar biliary strictures. Patency was shorter in the MFPS group, but similar survival and complications were found when comparing MFPS and SEMS group.

Reply to three letters: Dubravcsik et al, Murion et al and Fan et al The horse must come before the cart ….

We very much appreciate the interest generated by our recent publication in Endoscopy entitled “Urgent ERCP with pancreatic stent placement or replacement for salvage of post-ERCP pancreatitis” [1]. In the paper, we presented the second ever published case series involving placement of a pancreatic stent shortly after onset of pancreatitis, with the aim of ameliorating the course of predicted severe post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Patients included were those without a pancreatic stent, and those patients in whom a pancreatic stent had migrated out prematurely. Dramatic resolution of predicted severe pancreatitis occurred in all patients. Three letters were sent to the Editor regarding this paper, and we have been asked to respond to all three collectively. Murino et al. were concerned that the selection of patients for salvage represented only 14 of the 57 patients in the cohort, and wondered whether this introduced selection bias; they would have liked to have seen a comparison of outcomes with those not offered salvage therapy. Our response to this question is as follows. As clearly stated in the abstract and methods section, the 14 patients were selected for early repeat ERCP because they had predictors of severe pancreatitis, as defined by extreme pain and dramatic elevations of pancreatic enzymes combined with systemic inflammatory response syndrome (SIRS) and a bedside index for severity in acute pancreatitis (BISAP) score of≥3.Collectively, SIRS and BISAP scores are now considered to be the best early predictors of severity of acute pancreatitis [2]. The other patients, who were not offered salvage pancreatic stenting, did not have such predictors of severe pancreatitis, and therefore would represent a very different comparison group with limited validity as their progress and condition were not a cause for concern. In terms of the definition of pancreatitis–pain and elevated amylase/lipase at 24 hours–we agree that patients undergoing salvage ERCP before that time did not technically meet the definition of PEP. However, waiting 24 hours would likely have been too late. The concept of this intervention, as with placing prophylactic pancreatic stents in the first place, or giving rectal nonsteroidal anti-inflammatory drugs (NSAIDS), is to interrupt the inciting process that leads to the pancreatitis inflammatory process before it has had time to evolve. Finally, Murino et al. raised concerns that the data should be considered carefully until a well-performed randomized trial can be conducted. We agree. In the final sentences of the paper, we stated that “Confirmation of safety and efficacy of salvage stenting would require a prospective controlled trial in which patients with predicted moderate to severe early PEP were randomized to early intervention with pancreatic stent placement or replacement compared with conservative management. Until then, the current data should be considered as hypothesis generating rather than a recommendation for practice.” Ma et al. raised a similar suggestion for a randomized controlled trial. They suggest that we should have randomized the patients to intervention or standard conservative management. We would like to point out that prior to our paper, the only prior published report consisted of a similar paper by Madácsy et al., which involved only six patients [3]. We presented our paper as a hypothesis-generating study. If both series were combined, the total number of patients reported to undergo salvage ERCP is a mere 20.To conduct a valid randomized trial, we would first require treatment effect estimates compared with control, which is essential to generate meaningful sample size calculations. The treatment effect can only be estimated from previous treatment and data. In other words, the horse has to come before the cart! Finally, Dubravscik et al., the very authors responsible for the pioneer report of “salvage” ERCP, raised yet more valid points, and also emphasized the need for a randomized controlled trial. We agree with their perspective, as stated in our final sentence in the discussion mentioned above. We do, however, disagree with one point. Very early outward stent migration was clearly temporally associated with moderately delayed onset PEP in our trial, as evidenced by normal serum lipase and amylase at 2 hours in many of the patients with protective pancreatic stents whowithin the next day developed severe pain and hyperenzymemia, correlating with documented early passage of the pancreatic stent. Delayed pancreatitis in such patients is not consistent with the natural course of acute recurrent pancreatitis, as only 3 of 14 patients undergoing salvage ERCP had such an indication for the original ERCP. The duration required for effective prophylactic pancreatic stenting has never been investigated, especially in patients suffering thermal injury to the pancreatic sphincter from interventions such as ampullectomy and pancreatic sphincterotomy. We suggest that such patients require a more prolonged duration of prophylactic stenting to allow thermal-induced edema to subside, and that the finding of more delayed onset of PEP in patients with a pancreatic stent, and especially in those with migrated stent, further reflects the importance of maintaining pancreatic drainage for at least several days. We also agree with the authors concern that failed placement of a pancreatic stent will induce more damage than no intervention, as shown by our group 10 years ago [4], and reinforced by a recent paper from the University of Michigan/Indiana University [5]. Thus, salvage ERCP is only likely to be of potential benefit in centers with extensive experience and success with pancreatic stent placement. To summarize, we agree with all three authors writing letters to the Editor that a randomized controlled trial is in order. Challenges will be: 1) accurate estimation of treatment effect; 2) adequate sample size calculations, which will likely be very large; 3) difficulty recruiting adequate numbers of patients at expert centers because of the rarity of predicted severe PEP; and 4) funding for such a trial. We encourage all those working in the global ERCP community to consider undertaking such a trial. In the meantime, it seems reasonable to consider salvage stenting only for patients with predicted severe PEP as determined by SIRS and BISAP score, and only at expert centers with a proven very high rate of success at pancreatic stent placement.