Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.

Stress-induced islet graft loss during the peri-transplantation period reduces the efficacy of islet transplantation. In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo infusion weekly for four doses beginning before surgery in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT). Subjects were followed for 12 months post-TP-IAT. The dose of AAT was safe, as there was no difference in the types and severity of adverse events in participants from both groups. There were some biochemical signals of treatment effect with a higher oxygen consumption rate in AAT islets before transplantation and a lower serum C-peptide (an indicator of islet death) in the AAT group at 15 min after islet infusion. Findings per the statistical analysis plan using a modified intention to treat analysis showed no difference in the C-peptide area under the curve (AUC) following a mixed meal tolerance test at 12 months post-TP-IAT. There was no difference in the secondary and exploratory outcomes. Although AAT therapy did not show improvement in C-peptide AUC in this study, AAT therapy is safe in CP patients and there are experiences gained on optimal clinical trial design in this challenging disease.

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial.

INTRODUCTION: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP. METHODS AND ANALYSIS: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction. PRIMARY OUTCOME: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment. ETHICS AND DISSEMINATION: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies. TRIAL REGISTRATION NUMBER: NCT04996628.

An update on improving long-term outcomes for patients with chronic pancreatitis post-surgery.

INTRODUCTION: Chronic pancreatitis is a common inflammatory disease that severely impairs patients' quality of life, mainly due to abdominal pain which is the most frequent symptom. Current guidelines suggest medical therapy as the first line intervention based on a stepwise use of analgesics (i.e. NSAIDs followed by weak opioids and later by strong oppioids), which is rarely effective in improving pain and often leads to opioid addiction. Interventional procedures are therefore frequently needed. Endoscopic therapy is suggested as the second line of intervention, aiming at decompressing the main pancreatic duct via structure dilatation and ductal stone removal. Endoscopic therapy is usually effective in reducing pain in the short term, but its effects frequently decrease with time and multiple procedures are often required. Surgery is usually reserved as a last resource when medical and endoscopic therapy have failed. Pancreatic surgery is burdened with non negligible morbidity and mortality but is effective in reducing pain and improving quality of life in chronic pancratitis with long lasting effects. AREAS COVERED: Surgical treatment of chronic pancreatitis is based on resection of inflammatory head mass or decompression of the ductal system, alone or in combination, which can be performed using different techniques. In this paper we reviewed the current evidence on the long-term outcomes of this type of surgery in terms of pain relief, quality of life, exocrine end endocrine function, and long-term mortality. EXPERT OPINION: Quality of current evidence on this field is on average poor; a consensus to define clinically significant outcomes is needed in order to correctly design prospective studies that will enable gastroenterologists to understand which patients, and when, will benefit most from surgery and should therefore be referred to surgeons.

Video-Based Indocyanine Green Fluorescence Applied to Robotic Duodenum-Preserving Pancreatic Head Resection.

BACKGROUND: Duodenum-preserving pancreatic head resection (DPPHR) serves as a surgical intervention for managing benign and low-grade malignant neoplasms located in the head of the pancreas. This surgical approach enables the thorough excision of pancreatic head lesions, reducing the necessity for digestive tract reconstruction and enhancing the patient's quality of life.1 Performing a minimally invasive DPPHR is a complex surgical procedure, particularly when safeguarding the bile duct and the pancreaticoduodenal arterial arch. Robotic surgery is among the latest innovations in minimally invasive surgery and is widely used in many surgical specialties. It offers advantages such as rotatable surgical instruments, muscle tremor filters and up to 10-15 times three dimensional (3D) visual field,2 and achieves high flexibility and accuracy in surgical operations. Indocyanine green (ICG) fluorescence imaging technology is also applied to provide real-time intraoperative assessment of the biliary system and blood supply, which helps maintain the biliary system's integrity.3,4 We first report the complete procedure of ICG applied to the da Vinci robotic Xi system for preserving the DPPHR. METHODS: A 48-year-old female patient was diagnosed with pancreatic duct stones, chronic pancreatitis, and pancreatogenic diabetes. Enhanced computed tomography (CT) scans revealed pancreatic head stones, pancreatic atrophy, scattered calcifications, and a dilated pancreatic duct. An attempt at endoscopic retrograde cholangiopancreatography (ERCP) treatment was abandoned during hospitalization due to unsuccessful catheterization. Following informed consent from the patient and her family, a robotic DPPHR was conducted utilizing ICG fluorescence imaging technology. Approximately 60 min before the surgery, 2 mg of ICG was injected via the peripheral vein. The individual was positioned in a reclined posture with the upper part of the bed raised to an angle of 30° and a leftward tilt of 15°. Upon entering the abdominal cavity, existing adhesions were meticulously separated and the gastrocolic ligament was opened to expose the pancreas. The lower part of the pancreas was separated and the superior mesenteric vein (SMV) was identified at the inferior boundary of the pancreatic neck. The pancreas was cut upward and the pancreatic duct was severed using scissors. Dissection of the lateral wall of the portal vein-SMV in the pancreatic head segment was performed. Meticulous dissection was carried out along the pancreatic tissue, retracting the uncinate process of the pancreas in an upward and rightward direction. During the dissection, caution was exercised to protect the anterior and posterior pancreaticoduodenal arterial arch. By using ICG fluorescence imaging, the path of the common bile duct was identified and verified. Caution was exercised to avoid injuring the bile duct. After isolating the CBD, the head and uncinate process of the pancreas was entirely excised. Under the fluorescence imaging mode, the wholeness of the CBD was scrutinized for any potential seepage of the contrast agent. Ultimately, a Roux-en-Y end-to-side pancreaticojejunostomy (duct to mucosa) was executed. RESULTS: The surgery took 265 min and the estimated blood loss was about 150 mL. Without any postoperative complications, the patient was released from the hospital 13 days following the surgery. Postoperative pathology confirmed pancreatic duct stones and chronic pancreatitis. We have successfully performed four cases of robotic DPPHR using this technique, with only one patient experiencing a postoperative complication of pulmonary embolism. All patients were discharged successfully without any further complications. CONCLUSIONS: Employing ICG fluorescence imaging in a robotic DPPHR has been demonstrated to be both secure and achievable. This technique potentially provides novel therapeutic perspectives, particularly for patients with ambiguous delineation between pancreatic and biliary ductal structures.

Surgery versus Endoscopy for the Management of Painful Chronic Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Debate exists regarding the optimal treatment for painful chronic pancreatitis (CP). This meta-analysis aims to determine the outcomes of surgical intervention as compared to endoscopy in patients with painful CP. METHODS: A systematic review and meta-analysis including studies from PubMed, Embase, Web of Science, and Cochrane Databases (1995 onwards) was done by two independent reviewers using PRISMA guidelines. Primary outcome was pain relief. RESULTS: Among 8,479 studies, three were randomized trials, comprising a total of 199 patients. Compared with endoscopy, surgery was associated with a lower Izbicki score, both at medium term (mean difference (MD) 21.46, 95% confidence interval (CI) 13.48-29.43, p < 0.00001) and long term (MD: 17.80, 95% CI: 8.36-27.23, p = 0.0002). A higher proportion of surgical patients had some sort of pain relief compared with those who had endoscopy, both at medium term (72% vs. 46%, RR: 1.51, 95% CI: 1.19-1.90, p = 0.0006) and long term (73% vs. 47%, RR: 1.50, 95% CI: 1.19-1.89, p = 0.0007). Complete pain relief was more common in the surgical group compared to the endoscopy group, both at medium term (33% vs. 17%, RR: 1.97, 95% CI: 1.16-3.36, p = 0.01) and long term (35% vs. 18%, RR: 1.92, 95% CI: 1.15-3.20, p = 0.01). The pooled crossover rate from endoscopy to surgery was 22% (22/99). CONCLUSIONS: Surgical treatment in patients with painful CP leads to better pain control, requiring fewer interventions as compared to endoscopic treatment.

Nutrition challenges following total pancreatectomy with islet autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical treatment option for patients with chronic pancreatitis who have not responded to other therapies. TP offers pain relief whereas IAT preserves beta cell mass to reduce endocrine insufficiency. During the surgical procedure, the entire pancreas is removed. Islet cells from the pancreas are then isolated, purified, and infused into the liver via the portal vein. Successful TPIAT relieves pain for a majority of patients but is not without obstacles, specifically gastrointestinal, exocrine, and endocrine challenges. The postoperative phase can be complicated by gastrointestinal symptoms causing patients to have difficulty regaining adequate oral intake. Enteral nutrition is frequently provided as a bridge to oral diet. Patients undergoing TPIAT must be monitored for macronutrient and micronutrient deficiencies following the procedure. Exocrine insufficiency must be treated lifelong with pancreatic enzyme replacement therapy. Endocrine function must be monitored and exogenous insulin provided in the postoperative phase; however, a majority of patients undergoing TPIAT require little or no long-term insulin. Although TPIAT can be a successful option for patients with chronic pancreatitis, nutrition-related concerns must be addressed for optimal recovery.

Evolving Technique for Puestow-Type Procedure for Chronic Pancreatitis: The Combined Roux-en-Y Proximal End-to-Side and Distal Longitudinal Pancreatojejunostomy.

BACKGROUND The goal of surgical procedures in chronic pancreatitis is to establish drainage of the duct throughout the gland as well as resect any inflammatory masses if present. Conventionally, for patients with a dilated pancreatic duct without inflammatory masses, a drainage procedure in the form of a longitudinal pancreatojejunostomy (or Partington-Rochelle modification of the Puestow procedure) is the procedure of choice. CASE REPORT In present case, a patient with chronic pancreatitis was evaluated for surgical management, but extensive intraductal and parenchymal pancreaticolithiasis throughout the entire gland considerably restricted access to the duct. A novel combined Roux-en-Y partial longitudinal pancreatojejunostomy of the body and tail with an end-to-side pancreatojejunostomy of the head was fashioned to facilitate drainage of the entire pancreas, without resection of any parenchyma. The patient's immediate postoperative course was uncomplicated, and at her 30-day follow-up, she had been without pain and had been tolerating a diet, with additional pancreatic enzyme supplementation. CONCLUSIONS Roux-en-Y partial longitudinal pancreatojejunostomy (or modified Puestow procedure) should be considered a viable option for the surgical management of chronic pancreatitis with extensive pancreaticolithiasis, with good short-term outcomes. It underscores the importance of leveraging anatomic limitations to expand the choice of drainage procedure for chronic pancreatitis. This procedure should be considered in those patients with significant pancreaticolithiasis, where clear visualization of the main pancreatic duct is limited, precluding a lengthy pancreatojejunostomy.

Risk Factors for Post-Endoscopic Retrograde Cholangio-Pancreatography Pancreatitis in Children With Chronic Pancreatitis and Its Prediction Using 4-Hour Postprocedure Serum Amylase and Lipase Levels.

BACKGROUND: Post-endoscopic retrograde cholangio-pancreatography pancreatitis (PEP) is seen in 3% to 16% of children undergoing therapeutic endoscopic retrograde cholangio-pancreatography (ERCP). We evaluated the risk factors of PEP and utility of 4-hour post-ERCP amylase and lipase for early prediction of PEP in children with chronic pancreatitis (CP). MATERIALS AND METHODS: Thirty children with CP (boys 20, 14.3 [interquartile range, 9.3-16] years) who underwent 62 ERCP procedures were studied. Clinical and procedural details with outcome were noted. Serum amylase and lipase were measured before, 4 hours, and 24 hours after ERCP. Multivariate analysis was done to identify risk factors for PEP. Cutoff scores of 4-hour amylase and lipase were identified. RESULTS: PEP occurred in 14.5% (9/62) of ERCP procedures (mild, 8; moderate, 1) with no mortality. On univariate analysis, endoscopic sphincterotomy ( P = 0.04), difficult cannulation ( P = 0.004), and prior PEP ( P = 0.036) were risk factors, while prior ERCP ( P = 0.04) was protective. Difficult cannulation (odds ratio, 5.83; 95% confidence interval, 1.329-25.592) was the independent risk factor on multivariate analysis overall and for first ERCP session alone. Amylase >3.3 times upper limit of normal (ULN) and lipase of >5 times ULN at 4 hours had best sensitivity and specificity for diagnosis of PEP. All cases with PEP were symptomatic by 6 hours and none had amylase/lipase <3 ULN at 4 hours. Amylase/lipase of <3 ULN at 4 hours could exclude PEP with good sensitivity (100%) and specificity (76% and 81%, respectively). CONCLUSIONS: PEP occurred in 14.5% of procedures in children with CP, with difficult cannulation being the independent risk factor. Asymptomatic patients with 4-hour amylase/lipase <3 times ULN can be safely discharged.

Long-term quality of life between duodenum-preserving pancreatic head resection and pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: The authors aimed to compare the differences in quality of life (QOL) and overall survival (OS) between duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD) during long-term follow-up. DPPHR and PD have been shown to be effective in alleviating symptoms and controlling malignancies, but there is ongoing debate over whether DPPHR has an advantage over PD in terms of long-term benefits. METHOD: The authors searched the PubMed, Cochrane, Embase, and Web of Science databases for relevant studies comparing DPPHR and PD published before 1 May 2023. This study was registered with PROSPERO. Randomised controlled trials and non-randomised studies were included. The Mantel-Haenszel model and inverse variance method were used as statistical approaches for data synthesis. Subgroup analyses were conducted to evaluate the heterogeneity of the results. The primary outcome was the global QOL score, measured using the QLQ-C30 system. RESULTS: The authors analysed ten studies involving 976 patients (456 DPPHR and 520 PD). The global QOL score did not differ significantly between the DPPHR and PD groups [standard mean difference (SMD) 0.21, 95% CI (-0.05, 0.46), P =0.109, I2 =70%]; however, the OS time of patients with DPPHR was significantly improved [hazard ratio 0.59, 95% CI (0.44, 0.77), P <0.001, I2 =0%]. The follow-up length may be an important source of heterogeneity. Studies with follow-up length between two to seven years showed better global QOL for DPPHR than for PD [SMD 0.43, 95% CI (0.23, 0.64), P <0.001, I2 =0%]. There were no significant differences between the two groups in any of the functional scales of the QLQ-C30 system (all P >0.05). On the symptom scale, patients in the DPPHR group had lower scores for fatigue, nausea and vomiting, loss of appetite, insomnia, and diarrhoea than those in the PD group (all P <0.05). CONCLUSIONS: There were no significant differences in global QOL scores between the two surgeries; however, DPPHR had advantages over PD in terms of safer perioperative outcomes, lower long-term symptom scores, and longer OS times. Therefore, DPPHR should be recommended over PD for the treatment of benign pancreatic diseases and low-grade malignant tumours.

Patient reported outcomes of duodenum-preserving pancreatic head resection in chronic pancreatitis: high effectivity is impaired by prolonged non-surgical management.

BACKGROUND: Chronic pancreatitis (CP) causes suffering and socioeconomic burden. This study evaluated perioperative results and patient-reported outcomes (PRO) in CP patients treated with duodenum-preserving pancreatic head resection (DPPHR). METHODS: Data were analyzed of CP patients undergoing DPPHR between 01/2001-10/2014. PROs were measured using a specifically designed questionnaire and the EORTC QLQ-C30/PAN26. Associations between treatment variables and PROs were examined. RESULTS: Of 332 patients who received DPPHR, most (n = 251, 75.6%) underwent the Berne modification. Surgical morbidity was 21.5% (n = 71) and 90-day mortality 1.5% (n = 5). Median follow-up was 79.9 months, 5-year survival 90.5%, and 1.8% of patients developed pancreatic cancer. Of 283 patients alive, 178 (62.9%) returned questionnaires. Referral for surgery was self-initiated (38.0% of cases), by gastroenterologists (27.5%) and by general practitioners (21.1%). QoL improved in 78.7% of patients, remained stable in 12.1%, and worsened in 9.1%. Median Izbicki scores decreased from 90 to 5 points after surgery (p < 0.0001). Time from diagnosis to DPPHR was an independent, proportional predictor of a higher postoperative Izbicki score (p = 0.04). CONCLUSION: DPPHR is an effective, safe treatment for CP. A delay in surgery decreases surgical effectivity, hence CP patients should be referred to surgery early to ensure satisfactory outcomes.

Two-devices-in-one-channel method for fractured pancreatic duct stent retrieval in a case of severe chronic pancreatitis.

When a pancreatic plastic stent for symptomatic chronic pancreatitis breaks during its removal, severe pancreatic duct stenosis may complicate its retrieval. Takuma and colleagues report on the successful retrieval of a fragmented and displaced pancreatic plastic stent by applying the two-device-in-one-channel method using forceps and a snare.

Nutrition support in the pediatric total pancreatectomy with islet autotransplantation recipient.

For children with diminished quality of life and chronic pain caused by acute recurrent or chronic pancreatitis who are undergoing total pancreatectomy with islet autotransplantation, postoperative nutrition support has several unique characteristics. Surgical complications may lead to delays in nutrition support initiation or require modifications to the regimen. Early postoperative dysmotility requires the use of temporary enteral nutrition until this improves. The resultant complete exocrine pancreatic insufficiency necessitates lifelong pancreatic enzyme replacement therapy and fat-soluble vitamin supplementation. A low-oxalate diet is recommended to prevent kidney stones. Carbohydrate counting is needed for the provision of short-term insulin dosing and possibly long-term as well, depending on the transplanted islet yield. Children should have careful nutrition assessment and monitoring at several follow-up visits during the first year, then annually, and at any time with concerns.

Investigating misdiagnosis of suspected cancer among patients undergoing pancreatoduodenectomy: three decades of experience.

BACKGROUND: Diagnostic error can result in pancreatoduodenectomy (PD) being mistakenly performed for benign disease. The aims of this study were to observe the error rate in PD over three decades and identify characteristics of benign disease that can mimic malignancy. METHODS: Patients with a benign histological diagnosis after having PD performed for suspected malignancy between 1988 and 2019 were selected for review. Preoperative clinical features, imaging and pathological samples were reviewed alongside resection specimens to identify features that may have led to misdiagnosis. RESULTS: Over the study period, 1812 patients underwent PD for suspected malignancy and 97 (5.2 %) of these had a final benign diagnosis. The rate of benign cases reduced across the study period. Some 62 patients proceeded to surgery without a preoperative tissue diagnosis; the decision to operate was made upon clinical and radiologic features alone. There were six patients who had a preoperative pathological sample suspicious for malignancy, of which two had autoimmune pancreatitis in the postoperative histology specimen. DISCUSSION: Benign conditions, notably autoimmune and chronic pancreatitis, can mimic malignancy even with the use of EUS-FNA. The results of all available diagnostic modalities should be interpreted by a multidisciplinary team and honest discussions with the patient should follow.

Mapping global new-onset, worsening, and resolution of diabetes following partial pancreatectomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Partial pancreatectomy, commonly used for chronic pancreatitis, or pancreatic lesions, has diverse impacts on endocrine and metabolism system. The study aims to determine the global prevalence of new-onset, worsening, and resolution of diabetes following partial pancreatectomy. METHODS: The authors searched PubMed, Embase, Web of Science, and Cochrane Library from inception to October, 2023. DerSimonian-Laird random-effects model with Logit transformation was used. Sensitivity analysis, meta-regression, and subgroup analysis were employed to investigate determinants of the prevalence of new-onset diabetes. RESULTS: A total of 82 studies involving 13 257 patients were included. The overall prevalence of new-onset diabetes after partial pancreatectomy was 17.1%. Univariate meta-regression indicated that study size was the cause of heterogeneity. Multivariable analysis suggested that income of country or area had the highest predictor importance (49.7%). For subgroup analysis, the prevalence of new-onset diabetes varied from 7.6% (France, 95% CI: 4.3-13.0) to 38.0% (UK, 95% CI: 28.2-48.8, P <0.01) across different countries. Patients with surgical indications for chronic pancreatitis exhibited a higher prevalence (30.7%, 95% CI: 21.8-41.3) than those with pancreatic lesions (16.4%, 95% CI: 14.3-18.7, P <0.01). The type of surgical procedure also influenced the prevalence, with distal pancreatectomy having the highest prevalence (23.7%, 95% CI: 22.2-25.3, P <0.01). Moreover, the prevalence of worsening and resolution of preoperative diabetes was 41.1 and 25.8%, respectively. CONCLUSIONS: Postoperative diabetes has a relatively high prevalence in patients undergoing partial pancreatectomy, which calls for attention and dedicated action from primary care physicians, specialists, and health policy makers alike.

Effectiveness of pancreatic stent placement in pediatric patients with acute recurrent and chronic pancreatitis.

BACKGROUND: The use of pancreatic prostheses in children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) has evolved. The main established indication is the treatment of persistent abdominal pain. This study aimed to evaluate the efficacy of pancreatic stenting for refractory abdominal pain in pediatric patients with ARP and CP. METHODS: We conducted a retrospective case series study. We included patients under 16 years of age diagnosed with ARP and CP in the study. Endoscopic retrograde cholangiopancreatography (ERCP) was performed with the insertion of one and later two pancreatic stents. We evaluated abdominal symptoms before and after treatment, number of changes, duration of treatment, and complications with follow-up at 24 months and after withdrawal. RESULTS: Nine patients with ARP and CP were included in the study: six with undetermined etiology and three with pancreas divisum. The mean age was 12.4 years. Prosthesis placement relieved abdominal pain in 100% of cases, with 3.2 replacement sessions every 6.2 months for 27.4 months, and mild complications (15.7%). One patient experienced pain on removal of the prosthesis and required bypass surgery. CONCLUSION: Pancreatic stent placement in patients with refractory abdominal pain with ARP and CP proved to be effective and safe, providing medium-term symptom relief and minimal complications.

INTRODUCCIÓN: El uso de prótesis pancreáticas en niños con pancreatitis aguda recurrente (PAR) y crónica (PC) ha evolucionado. La principal indicación establecida es el tratamiento del dolor abdominal persistente. El objetivo de este estudio fue evaluar la eficacia del uso prótesis pancreática para el dolor abdominal refractario en pacientes pediátricos con PAR y PC, sin respuesta a manejo conservador. MÉTODOS: Se llevó a cabo un estudio retrospectivo de serie de casos. Se incluyeron pacientes menores de 16 años con diagnóstico de PAR y PC. Se realizó una colangio pancreatografía retrograda endoscópica (CPRE) para introducir inicialmente una y posteriormente dos prótesis pancreáticas. Se evaluaron síntomas abdominales antes y después del tratamiento, número de recambios, duración del tratamiento y complicaciones con seguimiento a 24 meses y posterior a su retiro. RESULTADOS: Se incluyeron 9 pacientes con PAR y PC: seis de etiología no determinada y tres con páncreas divisum. La edad promedio fue de 12.4 años. La colocación de prótesis alivió el dolor abdominal en el 100%, con 3.2 sesiones de recambio cada 6.2 meses en 27.4 meses, y complicaciones leves (15.7%). Un paciente presentó dolor al retirar las prótesis y requirió cirugía derivativa. CONCLUSIONES: El uso de prótesis pancreática en pacientes con dolor abdominal refractario con PAR y PC demostró ser eficaz y seguro al aliviar los síntomas a mediano plazo con mínimas complicaciones.

Quality of life after endoscopic procedures for chronic pancreatitis: A multicentre study.

BACKGROUND: Chronic Pancreatitis (CP) causes morphological changes in the pancreatic tissue, leading to complications and pain, which may require endoscopic interventions. OBJECTIVE: Our aim was to determine the frequency of endoscopic procedures (EP) in CP patients and to analyse pain and quality of life (QoL) in these patients after their EP. METHODS: This study included 1327 CP patients from the Scandinavian Baltic Pancreatic Club (SBPC) database including four countries and eight centres. We analysed patients undergoing EPs and gathered information on the EP, pancreatic function, pain, disease and duration. The EORTC C-30 QoL questionnaire was gathered prospectively and multivariable analysis was conducted on independent parameters between the groups. The reference population had no interventions (n = 870). RESULTS: 260 CP patients (22%) underwent EPs, median one year (range 0-39 years) after CP diagnosis. 68% were males. The median age was 59 (20-90) years. Most common aetiological factors were alcohol in 65% and smoking in 71%. Extracorporeal shock wave lithotripsy (ESWL) was used in 6% of the CP population and in 21% of the EP group. Biliary duct stenting was performed on 37% and pancreatic stenting was performed on 56% of the patients. There was no difference in pain patterns between patients who had pancreatic stenting and the reference population. The EP group had slightly better QoL (p = 0.047), functioning and fewer symptoms than the reference population, in the multivariable analysis there was no interaction effect analysis between the groups. The pancreatic stent group had better QoL and the same amount of pain than the reference group. The patients who needed later surgery (23%) had more pain (p = 0.043) and fatigue (p = 0.021). CONCLUSIONS: One in five of the CP patients underwent EP. These patients scored higher on QoL responses and had better symptom scores. CP patients who had pancreatic stenting performed had the same pain patterns as the reference population. Randomised prospective trials are needed to determine the effect of endoscopy procedures on CP patients.

Update on Total Pancreatectomy With Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation is a therapeutic option to effectively achieve pain relief and improvements in quality of life for selected patients with debilitating pain from chronic pancreatitis. The understanding of the best application and clinical execution of this procedure is in evolution, with outcomes studies and clinical trials in progress.

Clinical and biological significance of circulating miRNAs in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation.

BACKGROUND: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes. METHODS: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool. RESULTS: Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet-specific, acinar cell-specific and liver-specific miRNAs were elevated at 6 h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre-transplant levels 1-year post-transplant. Circulating miRNAs measured before and 6 h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post-transplant. CONCLUSIONS: miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation.