Prediction of Admission to Intensive Care Unit and 1-Year Mortality After Acute Pancreatitis With Walled-Off Pancreatic Necrosis: A Retrospective, Single-Center Cohort Study.

BACKGROUND AND AIMS: Pancreatic walled-off necrosis (WON) carries significant mortality and morbidity risks, often necessitating intensive care unit (ICU) admission. This retrospective study aimed to evaluate whether routine biochemical parameters at the time of the index endoscopic procedure could predict ICU admission and 1-year mortality following endoscopic treatment of WON. MATERIALS AND METHODS: We retrospectively identified 201 consecutive patients who underwent endoscopic drainage for WON between January 1, 2010, and December 31, 2020. Associations between routine biochemical blood tests and outcomes were assessed using logistic regression models. RESULTS: Within 1 year of the index endoscopy, 31 patients (15.4%) died, and 40 (19.9%) were admitted to the ICU due to sepsis. Preoperative electrolyte disturbances were more prevalent among ICU-admitted patients and nonsurvivors. Hyperkalemia, hypoalbuminemia, and elevated urea were significant predictors of 1-year mortality, while hypernatremia, elevated serum creatinine, and hypoalbuminemia predicted ICU admission. Predictive models exhibited good discriminative ability, with an AUC of 0.84 (95% CI,0,75-0.93) for 1-year mortality and 0.86 (95%CI, 0.79-0.92) for ICU admission. CONCLUSIONS: Preoperative imbalances in routine blood tests effectively predict adverse outcomes in endoscopically treated WON patients.

Effect of aggressive versus conservative hydration for early phase of acute pancreatitis in adult patients: A meta-analysis of 3,127 cases.

BACKGROUND: The advantages of aggressive hydration compared to conservative hydration within 24 h for acute pancreatitis (AP) remain controversial in adult patients. A meta-analysis was undertaken to investigate whether aggressive strategies are more beneficial. METHODS: We searched (on February 1, 2021) PubMed, Embase, and the Cochrane Library for eligible trials that assessed the two therapies and performed a meta-analysis. The primary endpoint was in-hospital mortality. Secondary outcomes were adverse events (e.g., renal failure and pancreatic necrosis) within 24 h of treatment. RESULTS: Five randomized controlled trials and 8 observational trials involving 3127 patients were identified. Patients with severe pancreatitis showed significant difference of in-hospital mortality (OR 1.75; 95% CI 1.32-2.33) in aggressive hydration group, which were less susceptible to study type and age. Patients with severe pancreatitis were likely to develop respiratory failure (OR 5.08; 95% CI 2.31-11.15), persistent SIRS (OR 2.83; 95% CI 1.58-5.04), renal failure (OR 2.58; 95% CI 1.90-3.50) with significant difference. A longer hospital stay was observed in patients with severe pancreatitis (WMD 7.61; 95% CI 5.51-9.71; P < 0.05) in the aggressive hydration group. Higher incidence of pancreatic necrosis (OR 2.34; 95% CI 1.60-3.42; P < 0.05) was major susceptible to observational studies, old patients and mild pancreatitis. CONCLUSIONS: Compared to conservative hydration, aggressive hydration increases in-hospital mortality and the incidence of renal failure, pancreatic necrosis with relatively strong evidence. Further investigation should be designed with a definitive follow-up period and therapeutic goals to address reverse causation bias.

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

BACKGROUND: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. OBJECTIVES: To determine the association between mortality and the development of early IPN. METHODS: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. RESULTS: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Impact of Different Patterns of Organ Failure on Mortality in Acute Necrotizing Pancreatitis.

OBJECTIVES: Organ failure (OF) and infected necrosis (IN) are the most important predictors of mortality in necrotizing acute pancreatitis (AP). We studied the relationship between timing (onset and duration) and patterns of OF with mortality and the impact of IN on mortality. METHODS: Consecutive patients with necrotizing AP between January 2017 and February 2020 were analyzed retrospectively for OF and its impact on outcome. Organ failure was divided as single OF, simultaneous multiple OF (SiMOF) and sequential multiple OF (SeMOF). Mortality was compared for timing of onset, total duration and patterns of OF. RESULTS: Among 300 patients with necrotizing AP, 174 (58%) had OF. Mortality was not associated with onset of OF (P = 0.683) but with duration of OF (P = 0.006). Mortalities for single OF, SiMOF, and SeMOF were 11.8%, 30.4%, and 69.2% respectively (P < 0.001). On Cox proportional hazard analysis, adjusted hazard ratio of risk of mortality for OF with IN versus IN, SiMOF versus single OF and SeMOF versus single OF was 3.183, 2.878, and 8.956, respectively (P = 0.023, <0.030, and <0.001, respectively). CONCLUSIONS: Duration of OF was associated with increased mortality and SeMOF had worse outcome than single OF and SiMOF.

Synchronous organ failure and infected pancreatic necrosis define genuine critical acute pancreatitis.

BACKGROUND: Critical acute pancreatitis (CAP) was supposed to be strongly associated with the highest risk of adverse outcomes. However, the definition of CAP needs to be further clarified. METHODS: A prospective database with consecutive patients of infected pancreatic necrosis (IPN) at a tertiary hospital was post-hoc analyzed. Patients were assigned to IPN alone, Metachronous-CAP (MCAP) and Synchronous-CAP group (SCAP) according to presence or absence of organ failure (OF) and the crosstalk between OF and IPN. Clinical interventions and outcomes were compared among groups. RESULTS: A total of 248 IPN patients were enrolled and the overall mortality was 25.8%. Compared with MCAP, SCAP was associated with higher mortality (66.2 versus 10.0%) and morbidity (41.2 versus 18.0%), longer duration of OF (median 35.5 versus 12.0 days), ICU length of stay (LOS) (median 28.0 versus 16.0 days) and hospital LOS (median 67.0 versus 60.0 days) (all P < 0.05). The IPN alone and MCAP had comparable mortality (10.8 versus 10.0%), morbidity and hospital LOS, except that MCAP patients were characterized with longer duration of OF and ICU LOS (P < 0.05). CONCLUSIONS: SCAP, characterized with synchronous persistent OF and IPN, was associated with higher mortality and morbidity and should be defined as genuine CAP.

Outcomes in Endoscopic and Operative Transgastric Pancreatic Debridement.

OBJECTIVES: Select patients with anatomically favorable walled off pancreatic necrosis may be treated by endoscopic (Endo-TGD) or operative (OR-TGD) transgastric debridement (TGD). We compared our experience with these 2 approaches. SUMMARY BACKGROUND DATA: Select necrotizing pancreatitis (NP) patients are suitable for TGD which may be accomplished endoscopically or surgically. Limited experience exists contrasting these techniques exists. METHODS: Patients undergoing Endo-TGD and OR-TGD at a single, high-volume pancreatic center between 2008 and 2019 were identified from a prospective database. Patient characteristics, procedural details, and outcomes of these 2 groups were compared. RESULTS: Among 498 NP patients undergoing necrosis intervention, 160 (32%) had TGD: 59 Endo-TGD and 101 OR-TGD. The groups were statistically similar in age, comorbidity, pancreatitis etiology, necrosis anatomy, pancreatitis severity, and timing of TGD from pancreatitis insult. OR-TGD required 1.1 ±â€Š0.5 and Endo-TGD 3.0 ±â€Š2.0 debridements/patient. Fewer hospital readmissions and repeat necrosis interventions, and shorter total inpatient length of stay were observed in OR-TGD patients. New-onset organ failure [Endo-TGD (13%); OR-TGD (13%); P = 1.0] was similar between groups. Hospital length of stay after TGD was significantly longer in patients undergoing Endo-TGD (13.8 ±â€Š20.8 days) compared to OR-TGD (9.4 ±â€Š6.1 days; P = 0.047). Mortality was 7% in Endo-TGD and 1% in OR-TGD (P = 0.04). CONCLUSIONS: Operative and endoscopic transgastric debridement achieve necrosis resolution with different temporal and procedural profiles. Clear multidisciplinary communication is essential to determine appropriate approach to individual necrotizing pancreatitis patients.

Streptokinase irrigation through a percutaneous catheter helps decrease the need for necrosectomy and reduces mortality in necrotizing pancreatitis as part of a step-up approach.

BACKGROUND: Percutaneous catheter drainage in pancreatic necrosis with a predominant solid component has a reduced success rate. To improve the efficacy of percutaneous catheter drainage, we used streptokinase in the irrigation fluid in the present study. METHODS: In this retrospective analysis of 4 prospective randomized studies performed at our center from 2014 to 2019, 108 patients were evaluated. We assessed the safety, feasibility, and efficacy of streptokinase irrigation compared to saline irrigation. Data were also analyzed between 50,000 IU and 150,000 IU streptokinase. RESULTS: There were 53 patients in the streptokinase irrigation group and 55 in the saline irrigation group, and both groups were comparable in terms of age, sex, etiology, APACHE II score, and percutaneous catheter drainage characteristics. The modified computerised tomography severity index and modified Marshall score at the onset of pain were significantly higher in the streptokinase group. Sepsis reversal was significantly higher in the streptokinase group (75% vs 36%), and the need for necrosectomy (34% vs 54%) was also lower in the streptokinase group. Mortality was lower in the streptokinase group than in the saline group (32% vs 40%). The incidence of bleeding in the streptokinase group was lower than that in the saline group (7% vs 18%). A higher dose of streptokinase (150,000 IU) resulted in lower rates of necrosectomy, bleeding, and mortality compared to those with 50,000 IU streptokinase. CONCLUSION: Significant reductions in the need for surgery and sepsis reversal were noted in the streptokinase group. The results using 150,000 IU streptokinase were superior to those using 50,000 IU streptokinase.

The impact of fluid resuscitation via colon on patients with severe acute pancreatitis.

Severe acute pancreatitis (SAP) is a life-threatening disease. Fluid Resuscitation Via Colon (FRVC) may be a complementary therapy for early controlled fluid resuscitation. But its clinical application has not been reported. This study aims to explore the impact of FRVC on SAP. All SAP patients with the first onset within 72 h admitted to the hospital were included from January 2014 to December 2018 through electronic databases of Ruijin hospital and were divided into FRVC group (n = 103) and non-FRVC group (n = 78). The clinical differences before and after the therapy between the two groups were analyzed. Of the 181 patients included in the analysis, the FRVC group received more fluid volume and reached the endpoint of blood volume expansion ahead of the non-FRVC group. After the early fluid resuscitation, the inflammation indicators in the FRVC group were lower. The rate of mechanical ventilation and the incidence of hypernatremia also decreased significantly. Using pure water for FRVC was more helpful to reduce hypernatremia. However, Kaplan-Meier 90-day survival between the two groups showed no difference. These results suggest that the combination of FRVC might benefit SAP patients in the early stage of fluid resuscitation, but there is no difference between the prognosis of SAP patients and that of conventional fluid resuscitation. Further prospective study is needed to evaluate the effect of FRVC on SAP patients.

Candidemia indicates poor outcome in patients with infected pancreatic necrosis.

BACKGROUND: Intra-abdominal fungal infection (AFI) and candidemia are common in patients with acute pancreatitis (AP), but with limited and conflicting reports on their clinical impacts. This study aims to evaluate the clinical impacts of AFI and candidemia in infected pancreatic necrosis (IPN). METHODS: A single-centre, prospective cohort including 235 consecutive patients with IPN between January 2010 and September 2020 was analysed to study the clinical impacts of AFI and candidemia. RESULTS: Of the 235 patients with IPN, 69 patients (29.4%) developed AFI and 13 patients (5.5%) developed candidemia. AFI was associated with higher intestinal leakage rate (27.5% vs 12.7%, P = .006), higher pancreatic fistula rate (53.6% vs 34.3%, P = .006) and longer hospital stays (72 vs 58 days, P = .003), but with similar mortality rate compared with patients without AFI (23.2% vs 24.7%, P = .806). However, candidemia was associated with significantly higher mortality rate compared with patients without candidemia (69.2% vs 21.6%, P < .001). Patients with candidemia had higher rate of multiple organ failure and AFI (69.2% vs 36.5%, P = .018; 69.2% vs 27.0%, P = .001, respectively). Multivariable analysis showed that age ≥ 50 years (OR = 2.8; 95% CI, 1.3-5.8; P = .007), severe category (OR = 11.2; 95% CI, 3.5-35.7; P < .001), multidrug-resistant organisms infection (OR = 2.5; 95% CI, 1.0-6.2; P = .039), candidemia (OR = 11.8; 95% CI, 2.5-56.5; P = .002), step-down surgical approach (OR = 3.2; 95% CI, 1.5-7.0; P = .004) were the independent predictors associated with higher mortality in IPN patients. CONCLUSION: Although AFI did not increase the mortality of IPN, patients with candidemia carried significantly higher mortality.

Immunomodulation Through Beta-D-glucan in Chemically-induced Necrotizing Pancreatitis.

BACKGROUND: Although the ability of ß-D-glucan and monophosphoryl lipid A (MPLA) to modulate immune responses has been studied in human primary cells, their effect on sterile inflammation models such as necrotizing pancreatitis has never been investigated. MATERIALS AND METHODS: 85 male New Zealand rabbits were assigned into following groups: A: control, B: pretreatment with ß-D-glucan 3 d before pancreatitis, C: pretreatment with MPLA 3 d before pancreatitis, D: pretreatment with ß-D-glucan and laminarin 3 d before pancreatitis, E: treatment with ß-D-glucan 1 d after pancreatitis, and F: MPLA 1 d after pancreatitis. Pancreatitis was induced by sodium taurocholate injection into the pancreatic duct and parenchyma. Survival was recorded for 21 d. On days 1, 3, and 7, blood was collected for amylase measurement. Peripheral blood mononuclear cells were isolated and stimulated for tumor necrosis factor alpha and interleukin 10 production. Pancreatic necrosis and tissue bacterial load were assessed. RESULTS: 21-d survival was prolonged after pretreatment or treatment with ß-D-glucan; this benefit was lost with laminarin administration. At sacrifice, pancreatic inflammatory alterations were more prominent in the control group. Bacterial load was lower after pretreatment or treatment with ß-D-glucan and MPLA. Tumor necrosis factor alpha production from stimulated peripheral blood mononuclear cells was significantly decreased, whereas interleukin 10 production remained unaltered after pretreatment or treatment with ß-D- glucan. CONCLUSIONS: ß-D-glucan reduces mortality of experimental pancreatitis in vivo. This is mediated through attenuation of cytokine production and prevention of bacterial translocation.

Necrotizing Pancreatitis from Hypertriglyceridemia: More Severe Disease?

BACKGROUND: Necrotizing pancreatitis (NP) is caused by hypertriglyceridemia (HTG) in up to 10% of patients. Clinical experience suggests that HTG-NP is associated with increased clinical severity; objective evidence is limited and has not been specifically studied in NP. AIM: The aim of this study was to critically evaluate outcomes in HTG-NP. We hypothesized that patients with HTG-NP had significantly increased severity, morbidity, and mortality compared to patients with NP from other etiologies. METHODS: A case-control study of all NP patients treated at a single institution between 2005 and 2018 was performed. Diagnostic criteria of HTG-NP included a serum triglyceride level > 1000 mg/dL and the absence of another specific pancreatitis etiology. To control for differences in age, sex, and comorbidities, non-HTG and HTG patients were matched at a 4:1 ratio using propensity scores. Outcomes were compared between non-HTG and HTG patients. RESULTS: A total of 676 NP patients were treated during the study period. The incidence of HTG-NP was 5.8% (n = 39). The mean peak triglyceride level at diagnosis was 2923 mg/dL (SEM, 417 mg/dL). After propensity matching, no differences were found between non-HTG and HTG patients in CT severity index, degree of glandular necrosis, organ failure, infected necrosis, necrosis intervention, index admission LOS, readmission, total hospital LOS, or disease duration (P = NS). Mortality was similar in non-HTG-NP (7.1%) and HTG-NP (7.7%), P = 1.0. CONCLUSION: In this large, single-institution series, necrotizing pancreatitis caused by hypertriglyceridemia had similar disease severity, morbidity, and mortality as necrotizing pancreatitis caused by other etiologies.

Endoscopic drainage with local infusion of antibiotics to avoid necrosectomy of infected walled-off necrosis.

BACKGROUND: Current treatment of infected pancreatic necrosis (IPN) follows a step-up approach. Our group designed a step-up protocol that associates endoscopic drainage with local infusion of antibiotics through transmural nasocystic catheter. Aim of our study was to evaluate our step-up protocol for IPN in terms of proportion of patients avoiding necrosectomy. METHODS: Retrospective analysis of patients admitted with acute pancreatitis (AP) between January 2015 and December 2018. The number of patients who responded to each therapeutic step were analysed: step 1, systemic antibiotics; step 2, endoscopic transmural drainage and local infusion of antibiotics; step 3, endoscopic necrosectomy. RESULTS: 1158 patients with AP were included. 110 patients (8.4%) suffered from necrotising pancreatitis; 48 of them had IPN (42.6% of necrotising pancreatitis) and were treated with systemic antibiotics. Nineteen patients (39.6% of IPN) responded and did not required any invasive therapy. Six patients with IPN on systemic antibiotics died within the first 4 weeks of disease before step 2 could be applied. Urgent surgical necrosectomy in the first 4 weeks was performed in three additional patients. Endoscopic drainage and local antibiotic therapy was performed in the remaining 20 patients; 9 (45% of them) did well and 9 patients underwent necrosectomy (18.7% of IPN). Two patients died on drainage. Overall mortality of the total cohort of AP was 2.53% CONCLUSIONS: Addition of local infusion of antibiotics to endoscopic drainage avoids the need of necrosectomy in half of patients with IPN not responding to systemic antibiotics.

Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate.

OBJECTIVE: The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation. DESIGN: C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed. RESULTS: Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Escherichia coli and an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects. CONCLUSION: Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.

Risk of Venous Thromboembolism in Acute Necrotizing Pancreatitis: A Large Database Study.

OBJECTIVES: Studies on the incidence of venous thromboembolism (VTE) in acute pancreatitis (AP) are scarce. We conducted a large database study to evaluate this relationship. METHODS: Data were extracted from a large electronic health record (Explorys; IBM Watson Health, Armonk, NY). We identified patients with AP in 2018 and 2019, analyzing VTE incidence at 30 days after diagnosis of AP. Univariate and multivariate analyses were performed to identify risk factors associated with VTE. RESULTS: A total of 25,620 cases of acute necrotizing pancreatitis (ANP) and 155,800 cases of acute nonnecrotizing pancreatitis (ANNP) were identified. The incidence of VTE was 7.1% for ANP, compared with 2.8% in ANNP (P < 0.001). On multivariate analysis, ANP conferred significantly greater odds of VTE (adjusted odds ratio, 2.78; 95% confidence interval, 2.73-2.84; P < 0.001), independent of other variables. In those with ANP, the presence of VTE was associated with a significantly higher mortality (23.5% vs 15.9%, P < 0.001). CONCLUSIONS: Acute necrotizing pancreatitis carries near 2.5-fold risk of VTE, and a 3-fold risk of PE, compared with those with ANNP. Venous thromboembolism development in ANP is associated with higher mortality.

Duodenal complications in necrotizing pancreatitis: Challenges of an overlooked complication.

BACKGROUND: Duodenal complications of necrotizing pancreatitis (NP) are challenging and understudied. We sought to characterize the demographics and clinical course of NP patients with duodenal complications. METHODS: Single institution retrospective review of 687 NP patients treated from 2005 to 2018. RESULTS: Duodenal complications developed in 40 (6%) patients including fistula in 11 (2%) and stricture in 29 (4%) patients. Patients with duodenal complications had increased computed tomography severity index (CTSI), degree of glandular necrosis, organ failure, infected necrosis, and disease duration. Mortality from NP was increased in patients with duodenal fistula (36%) compared to patients with duodenal stricture (7%) and patients without duodenal complications (9%). Surgical management of duodenal complications was required in 9/11 (82%) patients with fistula and 17/29 (59%) patients with stricture. CONCLUSIONS: Duodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.

Dynamic frailty: Objective physiological assessment to guide management in necrotizing pancreatitis.

BACKGROUND: Physical frailty as a measure of physiological reserve is an important yet understudied topic in necrotizing pancreatitis. We measured frailty metrics in patients with necrotizing pancreatitis at baseline and at 1 month to assess dynamic change. We hypothesized that greater baseline frailty and steeper decline in frailty biomarkers are associated with worse outcomes in necrotizing pancreatitis. METHODS: A retrospective analysis of an institutional, necrotizing pancreatitis-specific database was performed. First order outcomes were organ failure, infected necrosis, step-up approach failure, and mortality. Baseline frailty assessment included measurement of comorbid diseases (modified frailty index), nutritional status (prognostic nutritional index), and radiologic sarcopenia (psoas muscle index, Hounsfield unit average calculation). Dynamic frailty was evaluated using psoas muscle index and Hounsfield unit average calculation. Significant associations between baseline and dynamic frailty with outcomes were analyzed. RESULTS: Three hundred and forty-one patients were included in this study. Most patients were male (65%) with biliary etiology of necrotizing pancreatitis (46%). Baseline comorbid diseases and baseline sarcopenia were not associated with first order outcomes. Lower baseline prognostic nutritional index was associated with organ failure (P < .001) and infected necrosis (P < .001). After 30 days, 25% of patients became sarcopenic. Larger declines in all sarcopenia metrics were associated with organ failure, infected necrosis, and/or death (P < .05). Lower psoas area and density were independent risk factors for organ failure and infected necrosis. CONCLUSION: Dynamic changes in sarcopenia-focused frailty metrics were significantly and consistently associated with organ failure, infected necrosis, and death. Further development of a dynamic frailty index to objectively guide decision-making in necrotizing pancreatitis is warranted.

Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer.

To evaluate the clinical efficacy and feasibility of proton beam radiotherapy (PBT) using the simultaneous integrated boost (SIB) technique in locally advanced pancreatic cancer (LAPC), 81 LAPC patients receiving PBT using SIB technique were analyzed. The prescribed doses to planning target volume (PTV)1 and PTV2 were 45 or 50 GyE and 30 GyE in 10 fractions, respectively. Of 81 patients, 18 patients received PBT without upfront and maintenance chemotherapy (group I), 44 received PBT followed by maintenance chemotherapy (group II), and 19 received PBT after upfront chemotherapy followed by maintenance chemotherapy (n = 16) (group III). The median follow-up time was 19.6 months (range 2.3-57.6 months), and the median overall survival (OS) times of all patients and of those in groups I, II, and III were 19.3 months (95% confidence interval [CI] 16.8-21.7 months), 15.3 months (95% CI 12.9-17.7 months), 18.3 months (95% CI 15.9-20.7 months), and 26.1 months (95% CI 17.8-34.3 months), respectively (p = 0.043). Acute and late grade ≥ 3 toxicities related to PBT were not observed. PBT with the SIB technique showed promising OS for LAPC patients with a safe toxicity profile, and intensive combinations of PBT and chemotherapy could improve OS in these patients.

Efficacy of Early Percutaneous Catheter Drainage in Acute Pancreatitis of Varying Severity Associated With Sterile Acute Inflammatory Pancreatic Fluid Collection.

OBJECTIVE: The aim of the study was to evaluate the efficacy of early percutaneous catheter drainage (PCD) for sterile acute inflammatory pancreatic fluid collection (AIPFC) in acute pancreatitis (AP) of varying severity. METHODS: Retrospective analyses were performed based on the presence of sterile AIPFC and different AP severities according to 2012 Revised Atlanta Classification. RESULTS: Early PCD contributed to obvious decreases in operation rate (OR, P = 0.006), infection rate (IR, P = 0.020), and mortality (P = 0.009) in severe AP (SAP). In moderate SAP with sterile AIPFCs, however, early PCD was associated with increased OR (P = 0.009) and IR (P = 0.040). Subgroup analysis revealed that early PCD led to remarkable decreases in OR for patients with persistent organ failure (OF) within 3 days (P = 0.024 for single OF, P = 0.039 for multiple OF) and in mortality for patients with multiple OF (P = 0.041 for OF within 3 days and P = 0.055 for 3-14 days). Moreover, lower mortality was found in SAP patients with early PCD-induced infections than with spontaneous infections (P = 0.027). CONCLUSIONS: Early PCD may improve the prognosis of SAP with drainable sterile AIPFCs by reducing the OR, IR, and mortality.

Early on-demand drainage versus standard management among acute necrotizing pancreatitis patients complicated by persistent organ failure: The protocol for an open-label multi-center randomized controlled trial.

INTRODUCTION/AIM: Pancreatic necrosis occurs in a quarter of patients with acute pancreatitis, many of whom form an acute necrotic collection (ANC). The current standard treatment is to defer percutaneous catheter drainage (PCD) until the latter becomes "walled off," which takes approximately four weeks. The majority of patients that develop persistent organ failure (POF), the primary determinant of mortality, do so within four weeks. To defer PCD until after four weeks may result in a worse outcome because of a missed opportunity to treat early infection and thereby reduce the severity and/or duration of POF. This study is aimed to compare the clinical outcome of the current standard approach with early on-demand PCD in acute necrotizing pancreatitis (ANP) patients with ANC and POF. METHODS/DESIGN: This is an open-label, multi-center, parallel, randomized, controlled trial. All patients with ANP who develop POF during the first week of onset will be screened for eligibility. In total, 120 study subjects will be randomized to either early on-demand PCD or standard care. Patients assigned to the former will receive PCD when they show signs of decompensation like new-onset OF, aggravation of pre-existent OF, and persistent OF for more than a week. The primary composite endpoint is major complication and/or death. Patients will be followed until discharge or death with an additional follow-up 90 days after randomization. DISCUSSION: This study challenges the standard 4-week delay before PCD and will answer the question whether early on-demand PCD is associated with a lower incidence of major complications and/or death.

The continuum of complications in survivors of necrotizing pancreatitis.

BACKGROUND: Necrotizing pancreatitis survivors develop complications beyond infected necrosis that often require invasive intervention. Remarkably few data have cataloged these late complications after acute necrotizing pancreatitis resolution. We sought to identify the types and incidence of complications after necrotizing pancreatitis. DESIGN: An observational study was performed evaluating 647 patients with necrotizing pancreatitis captured in a single-institution database between 2005 and 2017 at a tertiary care hospital. Retrospective review and analysis of newly diagnosed conditions attributable to necrotizing pancreatitis was performed. Exclusion criteria included the following: death before disease resolution (n = 57, 9%) and patients lost to follow-up (n = 12, 2%). RESULTS: A total of 578 patients were followed for a median of 46 months (range, 8 months to 15 y) after necrotizing pancreatitis. In 489 (85%) patients 1 or more complications developed and included symptomatic disconnected pancreatic duct syndrome (285 of 578, 49%), splanchnic vein thrombosis (257 of 572, 45%), new endocrine insufficiency (195 of 549, 35%), new exocrine insufficiency (108 of 571, 19%), symptomatic chronic pancreatitis (93 of 571, 16%), incisional hernia (89 of 420, 21%), biliary stricture (90 of 576, 16%), chronic pain (44 of 575, 8%), gastrointestinal fistula (44 of 578, 8%), pancreatic duct stricture (30 of 578, 5%), and duodenal stricture (28 of 578, 5%). During the follow-up period, a total of 340 (59%) patients required an invasive intervention after necrotizing pancreatitis resolution. Invasive pancreatobiliary intervention was required in 230 (40%) patients. CONCLUSION: Late complications are common in necrotizing pancreatitis survivors. A broad variety of problems manifest themselves after resolution of the acute disease process and often require invasive intervention. Necrotizing pancreatitis patients should be followed lifelong by experienced clinicians.