[THE MULTIDISCIPLINARY APPROACH TO ACUTE NECROTIZING PANCREATITIS].

INTRODUCTION: Acute pancreatitis is among the most common gastrointestinal diseases, and a major cause of hospitalization and morbidity. Gallstones and alcohol abuse are the most common causes of acute pancreatitis. Other etiologies include hypertriglyceridemia, medications, post- endoscopic retrograde cholangiopancreatography (ERCP), trauma, hypercalcemia, infections and toxins, anatomic anomalies, etc. In most cases acute pancreatitis is a mild self-limiting disease. However, up to 20% of patients develop severe pancreatitis with pancreatic necrosis, which possess high rates of multi-organ failure and mortality. Conservative management of acute necrotizing pancreatitis includes fluid resuscitation, nutritional support, and broad spectrum antibiotics for infected necrotic peripancreatic fluid collection (PFC). Indications for further invasive interventions include infected necrotic PFC and/or persistent severe symptoms due to mass effect. Current clinical management algorithms favor endoscopic ultrasound (EUS)-guided drainage of PFCs. In case of a large collection or extension to the paracolic gutters, a percutaneous drainage is indicated. Dual modalities (percutaneous together with endoscopic drainage) possess lower rates of pancreatic-cutaneous fistulas, shorter length of hospitalization and less endoscopic interventions. Direct endoscopic necrosectomy should be considered when the patient fails to improve despite endoscopic and percutaneous drainage. A multidisciplinary approach, which involves advanced endoscopists, interventional radiologists, pancreaticobiliary surgeons as well as nutrition and infectious disease specialists, is needed for the optimal management of severe necrotizing pancreatitis.

Endoscopic Ultrasound-Guided Drainage of Pancreatic Fluid Collections: Not All Queries Are Already Solved.

Pancreatic fluid collections (PFCs) are well-known complications of acute pancreatitis. The overinfection of these collections leads to a worsening of the prognosis with an increase in the morbidity and mortality rate. The primary strategy for managing infected pancreatic necrosis (IPN) or symptomatic PFCs is a minimally invasive step-up approach, with endosonography-guided (EUS-guided) transmural drainage and debridement as the preferred and less invasive method. Different stents are available to drain PFCs: self-expandable metal stents (SEMSs), double pigtail stents (DPPSs), or lumen-apposing metal stents (LAMSs). In particular, LAMSs are useful when direct endoscopic necrosectomy is needed, as they allow easy access to the necrotic cavity; however, the rate of adverse events is not negligible, and to date, the superiority over DPPSs is still debated. Moreover, the timing for necrosectomy, the drainage technique, and the concurrent medical management are still debated. In this review, we focus attention on indications, timing, techniques, complications, and particularly on aspects that remain under debate concerning the EUS-guided drainage of PFCs.

The Use of PuraStat® in the Management of Walled-Off Pancreatic Necrosis Drained Using Lumen-Apposing Metal Stents: A Case Series.

Background and Objectives: Bleeding is one of the most feared and frequent adverse events in the case of EUS-guided drainage of WOPN using lumen-apposing metal stents (LAMSs) and of direct endoscopic necrosectomy (DEN). When it occurs, its management is still controversial. In the last few years, PuraStat, a novel hemostatic peptide gel has been introduced, expanding the toolbox of the endoscopic hemostatic agents. The aim of this case series was to evaluate the safety and efficacy of PuraStat in preventing and controlling bleeding of WOPN drainage using LAMSs. Materials and Methods: This is a multicenter, retrospective pilot study from three high-volume centers in Italy, including all consecutive patients treated with the novel hemostatic peptide gel after LAMSs placement for the drainage of symptomatic WOPN between 2019 and 2022. Results: A total of 10 patients were included. All patients underwent at least one session of DEN. Technical success of PuraStat was achieved in 100% of patients. In seven cases PuraStat was placed for post-DEN bleeding prevention, with one patient experiencing bleeding after DEN. In three cases, on the other hand, PuraStat was placed to manage active bleeding: two cases of oozing were successfully controlled with gel application, and a massive spurting from a retroperitoneal vessel required subsequent angiography. No re-bleeding occurred. No PuraStat-related adverse events were reported. Conclusions: This novel peptide gel could represent a promising hemostatic device, both in preventing and managing active bleeding after EUS-guided drainage of WON. Further prospective studies are needed to confirm its efficacy.

Distal Pancreatic Necrosis After Splenic Angioembolization.

Pancreatic ischemia with necrosis is an extremely rare complication of splenic angioembolization (SAE). A 48-year-old male with a grade IV blunt splenic injury underwent angiography which demonstrated no active bleeding or pseudoaneurysm. Proximal SAE was performed. One week later, he developed severe sepsis. Repeat CT imaging showed nonperfusion of the distal pancreas, and laparotomy found necrosis of approximately 40% of the pancreas. Distal pancreatectomy and splenectomy were performed. He endured a prolonged hospital course with multiple complications. Clinicians should have a high index of suspicion for ischemic complications after SAE when sepsis develops.

[Intraluminal endoscopy in diagnosis and treatment of fluid collections in acute pancreatitis]. / Rol' vnutriprosvetnoi endoskopii v diagnostike i lechenii zhidkostnykh skoplenii pri ostrom pankreatite.

OBJECTIVE: To improve treatment outcomes in patients with acute pancreatitis through a differentiated approach to transluminal drainage. MATERIAL AND METHODS: There were 1074 patients with acute pancreatitis between January 2018 and December 2021 at the Sklifosovsky Research Institute for Emergency Care. EUS was used as a final diagnostic method to determine localization, dimensions, shape and contours of fluid collections. We also assessed content, presence or absence of a capsule and connection with pancreatic ductal system, possibility of intraluminal drainage under EUS control. A plastic stent with rounded ends was installed if homogeneous hypo- and anechoic cavity with clear even contours was detected. The same measure was applied in case of aspiration of serous or serous-hemorrhagic fluid. The indication for installation of covered self-expanding endoprosthesis was inhomogeneous anechoic fluid collection with hyperechoic inclusions (sequesters) and cloudy purulent content. Patients with necrotic forms underwent insertion of a cystonasal drainage tube 7Fr for sanitation of the cavity with 0.05% aqueous chlorhexidine solution. Endoscopic sequestrectomy was performed every 24-48 hours. Stent was removed in 6 (for encapsulated peripancreatic fluid collections) or 1 month (for other types of fluid collections) after discharge. RESULTS: According to the EUS data, endoscopic TLD was performed in 63 (46%) out of 136 patients with fluid collections. Among 63 patients with TLD, connection with pancreatic ductal system was found in 5 (7.9%) patients. These ones underwent pancreaticoduodenal stenting. Twenty-two patients underwent elective sequestrectomy after stenting of necrotic types of fluid collections with fully covered self-expanding stents. Additional percutaneous drainage was required in 11 (45.8%) of 24 patients. Complicated postoperative period was observed in 4 (6.3%) patients with acute necrotic fluid collections (bleeding from the area of pancreatogenic destruction). Four (6.3%) patients died. Autopsy revealed resolution of purulent-inflammatory process in all patients. CONCLUSION: Intraluminal surgery is possible not only for homogeneous delimited fluid collections, but also for advanced lesions including infected destructions. This approach allows us to consider endoscopic intraluminal drainage as the final minimally invasive method of surgical treatment of pancreatic necrosis. Its effectiveness is up to 45.8%.

Pancreatitis aguda / Acute pancreatitis

La pancreatitis aguda continúa siendo una de las patologías más relevantes en los servicios de aparato digestivo, destacando la litiasis y el alcohol como las causas principales. Presenta unos criterios diagnósticos bien establecidos y unas indicaciones específicas para la realización de pruebas de imagen, considerando de gran utilidad la ecografía abdominal en el estudio etiológico y la tomografía computarizada abdominal para la estratificación del riesgo y estudio de complicaciones locales. Una fluidoterapia basada en metas, el uso precoz de la nutrición por vía oral y una adecuada analgesia constituyen los pilares básicos del manejo inicial. La antibioterapia está indicada en casos de necrosis infectada o infecciones extrapancreáticas pero no ha demostrado beneficio como profilaxis en pancreatitis aguda necrotizante. En la última década se han desarrollado abordajes mínimamente invasivos que han cambiado radicalmente el tratamiento de las necrosis encapsuladas mejorando la tasa de complicaciones, estancia hospitalaria y calidad de vida de los pacientes. (AU)

Acute pancreatitis is nowadays one of the most common diseases among gastroenterology disorders, being gallstones and alcohol the main etiologies. Diagnostic criteria and indications of different imaging techniques are well defined, so that abdominal ultrasound is useful for etiological diagnosis whereas computarized tomography is better for risk stratification and local complications assessment. Goal directed fludtherapy, early starting of oral feeding and pain management are the mainstay of early treatment in acute pancreatitis. Antibiotics are useful when infected necrosis or extra pancreatic infections are documented or suspected but no as prophylaxis in sterile necrotizing pancreatitis. Minimally invasive approaches have emerged in the last decade for walled off necrosis management, improving complication rates, quality of life and length of hospital stay when compared with open surgery. (AU)

[Acute pancreatitis]. / Pancreatitis aguda.

Acute pancreatitis is nowadays one of the most common diseases among gastroenterology disorders, being gallstones and alcohol the main etiologies. Diagnostic criteria and indications of different imaging techniques are well defined, so that abdominal ultrasound is useful for etiological diagnosis whereas computarized tomography is better for risk stratification and local complications assessment. Goal directed fludtherapy, early starting of oral feeding and pain management are the mainstay of early treatment in acute pancreatitis. Antibiotics are useful when infected necrosis or extra pancreatic infections are documented or suspected but no as prophylaxis in sterile necrotizing pancreatitis. Minimally invasive approaches have emerged in the last decade for walled off necrosis management, improving complication rates, quality of life and length of hospital stay when compared with open surgery.

Prediction and management of bleeding during endoscopic necrosectomy for pancreatic walled-off necrosis: results of a large retrospective cohort at a tertiary referral center.

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) provide an endoscopic method for management of walled-off necrosis (WON) and a gateway for the performance of endoscopic necrosectomy (EN). However, bleeding may occur in up to 20% of EN procedures. Predictive factors for bleeding in this patient population are unknown, and there is no agreed-on algorithm for the management of bleeding. The aim of this study was to evaluate preprocedural risk factors for bleeding in patients undergoing endoscopic drainage or EN for WON. METHODS: A retrospective cohort of patients undergoing EN for WON was reviewed. Demographics, comorbidities, concurrent medications, and etiology of pancreatitis were recorded. Pre-, peri-, and postprocedural clinical variables were compared using the χ2 test and independent t test. RESULTS: Between June 2014 and October 2020, 536 ENs were performed in 151 patients. Intraprocedural bleeding occurred during 28 procedures (5.2%) in 18 patients (11.9%). Endoscopic hemostasis was attempted in 8 patients (10 procedures). Eight patients (10 procedures) in total were treated by interventional radiology (IR). Thrombocytopenia (P = .006) and cirrhosis (P = .049) were associated with intraprocedural bleeding, although thrombocytopenia was present in only 1 patient. Identification of a vessel within the cavity endoscopically was also associated with bleeding (P < .001). On multivariate analysis, identification of a vessel within the cavity endoscopically remained a strong predictor of bleeding (P < .001), whereas cirrhosis was no longer significant. Patients who required IR for hemostasis were transfused with significantly more blood before the procedure than patients who did not (3.4 units vs .67 units, P = .002). CONCLUSIONS: EN for WON was associated with a 5.2% per-procedure risk of bleeding and an 11.9% per-patient bleeding risk. Identification of a vessel within the cavity during endoscopy is predictive of bleeding during EN. Patients who require more transfusions before endoscopy may require earlier intervention by IR.

Pancreatic Apoplexy: Fulminant Necrotizing Pancreatitis Leading to Completion Pancreatectomy Within 3 Days After Partial Pancreaticoduodenectomy.

OBJECTIVES: Patient characteristics with postoperative acute necrotizing pancreatitis and completion pancreatectomy (CP) after pancreaticoduodenectomy (PD) remain unclear. METHODS: Data from all patients who underwent a PD with need for CP (January 2011-December 2019) at a German University Hospital were analyzed regarding the indications and timing of CP, laboratory and histopathological findings, and overall outcome. RESULTS: Six hundred twelve patients underwent PD, 33 (5.4%) of them needed a CP. Indications were grade C pancreatic fistula with or without biliary leak (46% and 12%), biliary leak (6%), and hemorrhage due to pancreatic fistula (36%). Eight patients (24%) underwent CP within 3 days after PD. These fulminant courses ("pancreatic apoplexy") were accompanied by significantly higher levels of lactate dehydrogenase, C-reactive protein, serum amylase, serum lipase, drain amylase, and drain lipase compared with patients with CP after the third day. Pancreatic apoplexy was histologically associated with higher rates of pancreatic necrosis (P = 0.044) and hemorrhage (P = 0.001). A trend toward higher mortality was observed (75% vs 36%, P = 0.058). CONCLUSIONS: Pancreatic apoplexy, defined as fulminant necrotizing pancreatitis after PD leading to CP within 3 days, is associated with characteristic laboratory and histopathological findings and a trend to higher mortality.

Infected pancreatic necrosis and retroperitoneal abscess associated with Lactobacillus paracasei.

Infected pancreatic necrosis is a postpancreatitis complication that is mainly caused by Enterobacteriaceae and Enterococci. Here, we have reported a very rare case of Lactobacillus paracasei bacteraemia associated with infected pancreatic necrosis and retroperitoneal abscess. In addition to the diagnosis of diabetic ketoacidosis, blood test results revealed a high inflammatory status. CT of the abdomen revealed pancreatic walled-off necrosis. Blood culture and aspiration fluid culture revealed positivity for L. paracasei, leading to the diagnosis of infected pancreatic necrosis. The abscess had spread in the retroperitoneal space later. The patient recovered after receiving antibiotic treatment and endoscopic and percutaneous drainage. L. paracasei can cause invasive infection, including infected pancreatic necrosis and retroperitoneal abscess, which requires aggressive therapy.

Endoscopic transmural drainage tailored to quantity of necrotic debris versus laparoscopic transmural internal drainage for walled-off necrosis in acute pancreatitis: A randomized controlled trial.

BACKGROUND AND AIMS: Both endoscopic and laparoscopic transmural internal drainage are practiced for drainage of walled-off necrosis (WON) following acute pancreatitis (AP) but the superiority of either is not established. Our aim was to compare transperitoneal laparoscopic drainage with endoscopic drainage using either lumen apposing metal stents (LAMS) or plastic stents tailored to the amount of necrotic debris in WON. METHODS: In a randomized controlled trial, adequately powered to exclude the null hypothesis, patients with symptomatic WON were randomized to either endoscopic or laparoscopic drainage. In the endoscopy group, two plastic stents were placed if the WON contained <1/3rd necrotic debris and a LAMS was placed if it was >1/3rd. Primary outcome was resolution of WON within 4 weeks without re-intervention for secondary infection. Secondary outcome was overall success (resolution of WON at 6 months) and adverse events. RESULTS: Forty patients were randomized: 20 to each group. Baseline characteristics were comparable between the groups. Primary outcome was similar between the groups [16 (80%) in laparoscopy and 15 (75%) in endoscopy group; p = 0.89]. The overall success was similar [18 (90%) in laparoscopy vs. 17 (85%) in endoscopy; p = 0.9]. Median duration of hospital stay was shorter in endoscopy group [4 (4-8) vs. 6 days (5-9); p = 0.03]. Adverse events were comparable between the groups. CONCLUSION: Laparoscopic drainage was not superior to endoscopic transmural drainage with placement of multiple plastic stent or LAMS depending on the amount of necrotic debris for symptomatic WON in AP. The hospital stay was shorter with the endoscopic approach.

Endoscopic drainage for management of infected necrosis following EUS-TA in a patient with pancreatic cancer: A case report.

RATIONALE: Endoscopic ultrasonography-guided tissue acquisition (EUS-TA) has become the norm for the diagnosis of pancreatic solid lesions. EUS-TA is relatively safe, but various complications can occur. Infected pancreatic necrosis (IPN) is a rare but serious complication. The latest guidelines suggest that all invasive interventions in patients with IPN should be delayed until walled-off necrosis appears. PATIENT CONCERNS: A 73-year-old man was referred to our hospital with double primary cancers including gallbladder and pancreas. We performed EUS-TA on metastatic pancreatic tail cancer to confirm histologic diagnosis. Six days after the procedure, he developed abdominal pain and fever. DIAGNOSES: The patient's laboratory findings showed leukocytosis and C-reactive protein elevation. Fluid collection around pancreas tail and stomach was detected in computed tomography (CT) scan, and the patient was diagnosed with IPN. INTERVENTIONS AND OUTCOMES: EUS-guided endoscopic transmural drainage (EUS-TD) was performed for the treatment of IPN. Two days after the procedure with antibiotics, his CRP level decreased abruptly, and he received chemotherapy for the treatment of pancreatic ductal adenocarcinoma (PDAC) 5 days after the procedure. He was discharged from our hospital without complications 15 days after chemotherapy. LESSONS: In selected patients with PDAC, early endoscopic drainage may be recommended as treatment for IPN resulting from complications of EUS-TA.

Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis.

BACKGROUND: The MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients' quality of life. CASE: A 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient's clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient's refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death. CONCLUSION: The pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and ß-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.

Hypercalcemia of Malignancy and Acute Pancreatitis.

OBJECTIVES: Hypercalcemia of malignancy confers a poor prognosis. This systematic review evaluated published cases of hypercalcemia of malignancy presenting with acute pancreatitis (AP), in terms of clinical presentation and outcomes. METHODS: A comprehensive review of PubMed and Embase until March 18, 2020, was conducted. Studies were included if they reported on patients with hypercalcemia of malignancy and AP with attempts to exclude other etiologies of hypercalcemia and AP. Two independent reviewers selected and appraised studies using the Murad tool. RESULTS: Thirty-seven cases were identified. Mean (standard deviation) age was 44.8 (2.46) years. Mean (standard deviation) presenting corrected calcium was 14.5 (0.46) mg/dL. Parathyroid carcinoma (21.6%) and multiple myeloma (21.6%) were the most common malignancies. Cases were classified as severe (37.8%), mild (21.6%), and moderately severe (18.9%), whereas 21.6% did not report severity. Necrotizing pancreatitis developed in 21.6% of cases. Most cases were treated with intravenous hydration and bisphosphonates or calcitonin/calcitonin analogues. Mortality was 32.4% during the same presentation of AP. Among mortality cases, 10 of 12 had severe AP, and 5 of 12 had necrotizing pancreatitis. Degree of hypercalcemia did not influence mortality. CONCLUSION: Acute pancreatitis associated with hypercalcemia of malignancy is rare. One in 3 patients with this presentation may not survive AP.

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.

Pseudoaneurysm of the gastroduodenal artery with arterio-duodenal fistulization secondary to acute pancreatitis: an unusual endoscopic diagnosis

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