Risk of Pancreatic Cancer After Acute Pancreatitis: A Retrospective Analysis of the Korean National Sample Cohort.

BACKGROUND: Acute pancreatitis may increase the risk of pancreatic cancer, although this association remains unclear. Therefore, we aimed to investigate this association. METHODS: We retrospectively analyzed the 2002-2019 Korean National Health Insurance Service-National Sample Cohort using 1:3 propensity score matching for sex and age (acute pancreatitis, n = 4,494; matched controls, n = 13,482). We calculated the hazard ratio (HR) for pancreatic cancer risk in patients with acute pancreatitis using Cox proportional hazards regression. RESULTS: Acute pancreatitis was significantly associated with an increased risk of pancreatic cancer throughout the study period (adjusted HR, 7.56 [95% confidence interval, 5.00-11.41]), which persisted for 2, 2-5, and > 5 years post-diagnosis (19.11 [9.60-38.05], 3.46 [1.35-8.33], and 2.73 [1.21-6.15], respectively). This pancreatitis-related pancreatic cancer risk became insignificant beyond 10 years of follow-up (1.24 [0.24-6.49]). Furthermore, this risk notably increased as the number of recurrent acute pancreatitis episodes increased (1 episode: 5.25 [3.31-8.33], 2 episodes: 11.35 [6.38-20.19], ≥ 3 episodes: 24.58 [13.66-44.26]). CONCLUSION: Following an acute pancreatitis diagnosis, the risk of pancreatic cancer increases significantly in the initial years, with a rapid increase further accentuated with recurrent acute pancreatitis episodes. Additional study is needed to evaluate whether this increased risk of carcinogenesis is attributed to accumulated inflammation.

Etiology and outcome of acute recurrent pancreatitis and chronic pancreatitis.

BACKGROUND: Owing to the lack of data, we aimed to determine the etiology and outcome of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children in Southeast Asia. METHODS: This retrospective study was conducted at a university hospital in Bangkok, Thailand. We included patients aged <18 years who were diagnosed with pancreatitis from 2000 to 2021. RESULTS: Among 155 patients with pancreatitis, 21 (13.5%) were diagnosed with either ARP (n = 7) or CP (n = 14). Clinical manifestations of CP included chronic abdominal pain (n = 10, 71.4%), steatorrhea (n = 8, 57.1%), and diabetes mellitus (n = 1, 7.1%). Positive radiological findings compatible with CP were detected from an abdominal ultrasound, computed tomography, magnetic resonance cholangiopancreatography in 70%, 90.9%, and 92.9% of patients, respectively. Genetic, metabolic, and pancreaticobiliary causes were the major causes of ARP/CP (23.8% each) and the etiologies were unidentified in one-fifth of the patients. Patients with metabolic diseases who had AP were at-risk of developing ARP (hazards ratio [HR], 4.7, 95% confidence interval [CI]: 1.5-13.9). Children with ARP or CP were younger than those with AP (P = 0.04). Approximately two-thirds of patients with CP had growth faltering and they had more episodes of hospitalization due to acute attacks when compared to patients with ARP ( 4 [interquartile range [IQR], 3-6] vs. 3 [IQR, 2-3]; P = 0.02). CONCLUSION: Genetic, metabolic, and pancreaticobiliary diseases were the common etiologies of ARP and CP among children living in a developing country in Southeast Asia. The burden of CP included malnutrition and frequent hospitalization. The findings emphasize the importance of an early etiological diagnosis and monitoring for pancreatic insufficiency in ARP/CP.

Clinical characteristics of acute pancreatitis in children: a single-center experience in Western China.

BACKGROUND: The diagnosis of pediatric pancreatitis has been increasing over the last 20 years. We aimed to compare the clinical characteristics for pediatric acute pancreatitis (AP) with adult AP, and investigate the risk factor for acute recurrent pancreatitis (ARP) in children. METHOD: From June 2013 to June 2019, a total of 130 pediatric patients with AP at the inpatient database were enrolled. Univariate analysis and multivariate Cox regression analysis were performed to identify the risk factors for ARP in children. RESULT: Major etiologic factors in 130 patients were biliary (31.5%), idiopathic (28.5%). The etiology of pancreatitis in children was markedly different from that in adults (p < 0.001). Compared with the adult patients, the pediatric patients had significantly lower severity (p = 0.018) and occurrence rate of pancreatic necrosis (p = 0.041), SIRS (p = 0.021), acute peripancreatic fluid collection (p = 0.014). Univariate and Multivariate Cox regression analysis showed that female (p = 0.020; OR 3.821; 95% CI 1.231-11.861), hypertriglyceridemia (p = 0.045; OR 3.111; 95% CI 1.024-9.447), pancreatic necrosis (p = 0.023; OR 5.768; 95% CI 1.278-26.034) were the independent risk factors of ARP. Hypertriglyceridemia AP had the highest risk of recurrence compared to other etiology (p = 0.035). CONCLUSION: Biliary and idiopathic disease were the major etiologies of AP in children. Children have simpler conditions than adults. Female, hypertriglyceridemia, and pancreatic necrosis were associated with the onset of ARP.

Long-term outcomes of therapeutic ERCP in pediatric patients with pancreas divisum presenting with acute recurrent or chronic pancreatitis.

OBJECTIVES: The aim of this study was to evaluate the long-term outcomes of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for pediatric patients with pancreas divisum (PD) presenting with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). METHODS: Between May 2008 and August 2017, pediatric patients with PD who received endotherapy at Ruijin Hospital were identified and grouped according to clinical presentation, namely ARP and CP. Primary success was defined as patients' improvement in symptoms after index ERCPs, without further intervention or any analgesic. RESULTS: A total of 74 ERCPs were performed in 38 pediatric patients. The frequency of at least 1 genetic mutation identified in patients with ARP and CP was 44.4% and 68.4%, respectively. Patients with CP required more ERCPs than those with ARP (2.4 ±â€¯1.7 vs. 1.1 ±â€¯0.4, P = 0.005). The incidence of post-ERCP complications was 14.9%, including pancreatitis of 13.5% and hemorrhage of 1.4%. During a median follow-up duration of 41 months (range, 12-123 months), the frequency of pancreatitis episodes decreased significantly from 2.31 to 0.45 (P < 0.0001). The 25% recurrence and reintervention rates were estimated at 25 and 48 months, respectively, without significant difference between patients with ARP or CP. There was a nonsignificant trend towards a higher rate of primary success in patients with ARP than those with CP (92.9% vs. 69.6%, P = 0.123). After further endotherapy, 91.3% patients with CP improved clinically. CONCLUSIONS: Therapeutic ERCP is an effective and safe intervention for pediatric patients with symptomatic PD. Patients presenting with CP seem to achieve improvement after additional ERCPs.

Case report on Ansa Pancreatica: An Uncommon Cause Accounting for Recurrent Pancreatitis in Children.

Acute recurrent pancreatitis is a rare entity in children. It can be caused by a number of reasons, anatomical variations being one of them. Panctreatica divisum is the most common form of ductal anomaly while ansa pancreatica has been the least studied and explored. In recurrent pancreatitis, Ansa Pancreatica was recently found to be a key risk factor. It is usually found among adult alcoholics. We submit the report of a rare but important cause of acute recurrent pancreatitis; an 11-year-old child with 2 previous episodes of pancreatitis was diagnosed with ansa pancreati ca on magnetic resonance cholangiopancreatography (MRCP). He was advised to get stenting of Pancreatic duct. To the best of our belief, only another case has been reported in the paediatric population.

Targeted Gene Next-Generation Sequencing in Chinese Children with Chronic Pancreatitis and Acute Recurrent Pancreatitis.

OBJECTIVE: To identify causal mutations in certain genes in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). STUDY DESIGN: After patients were enrolled (CP, 55; ARP, 14) and their clinical characteristics were investigated, we performed next-generation sequencing to detect nucleotide variations among the following 10 genes: cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor, Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), calcium-sensing receptor (CASR), cathepsin B (CTSB), keratin 8 (KRT8), CLAUDIN 2 (CLDN2), carboxypeptidase A1 (CPA1), and ATPase type 8B member 1 (ATP8B1). Mutations were searched against online databases to obtain information on the cause of the diseases. Certain novel mutations were analyzed using the SIFT2 and Polyphen-2 to predict the effect on protein function. RESULTS: There were 45 patients with CP and 10 patients with ARP who harbored 1 or more mutations in these genes; 45 patients had at least 1 mutation related to pancreatitis. Mutations were observed in the PRSS1, SPINK1, and CFTR genes in 17 patients, the CASR gene in 5 patients, and the CTSB, CTRC, and KRT8 genes in 1 patient. Mutations were not found in the CLDN, CPA1, or ATP8B1 genes. We found that mutations in SPINK1 may increase the risk of pancreatic duct stones (OR, 11.07; P = .003). The patients with CFTR mutations had a higher level of serum amylase (316.0 U/L vs 92.5 U/L; P = .026). CONCLUSION: Mutations, especially those in PRSS1, SPINK1, and CFTR, accounted for the major etiologies in Chinese children with CP or ARP. Children presenting mutations in the SPINK1 gene may have a higher risk of developing pancreatic duct stones.

Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment.

This paper reviews the current status of our understanding of the epidemiology, diagnosis, and management of the continuum of pancreatic diseases from acute and recurrent acute pancreatitis to chronic pancreatitis and the diseases that are often linked with pancreatitis including diabetes mellitus and pancreatic cancer. In addition to reviewing the current state of the field, we identify gaps in knowledge that are necessary to address to improve patient outcomes in these conditions.

[Genetic mutations as a cause of acute recurrent pancreatitis in children - case report and literature review].

Acute recurrent pancreatitis is not common in children. The epidemiology, etiology and clinical presentation of pediatric acute recurrent pancreatitis are not well understood. The etiology is diverse and multifactorial, with many cases being idiopathic. The most common etiology of acute recurrent pancreatitis in children are genetic factors, biliary duct disorders, anatomic anomalies of the pancreatobiliary system and metabolic diseases. Mutations are most commonly found in the cationic trypsynogen gene (PRSS1), the pancreatic secretory trypsin inhibitor gene (SPINK1) and the cystic fibrosis transmembrane conductance regulator gene (CFTR). The case described here is that of a 6-year-old boy, without a family history of pancreatitis, who was hospitalized several times over 5 years, with epigastric pain and high serum levels of amylase and lipase. Genetic testing showed a heterozygous variation, c.194+2T>C (IVS3+2T>C) in the SPINK1 gene and variation c.1210-34TG(11) T(5) (IVS8-5T+(TG)11) in the CFTR gene. Other etiological factors also occurred leading to the initiation and relapses of the disease.

Delayed diagnosis of duodenal duplication cyst in a child with recurrent pancreatitis operated by Whipple procedure: a case report.

Children with acute pancreatitis may experience abdominal pain; the causes of which include anatomical abnormalities and medications. The rare anatomical etiology of duodenal duplication cyst is typically asymptomatic and discovered incidentally. The authors present a unique case of a Whipple-operated duodenal duplication cyst. Case presentation: The authors present the case of a 12-year-old Arab male who was admitted to our hospital with worsening, severe epigastric pain, stabbing in nature, and radiating to the back, suggestive of acute pancreatitis. Serum lipase levels were significantly elevated. The patient received appropriate care. His medical history is notable for multiple bouts of pancreatitis in the last 18 months. Previous investigations at other hospitals were mostly unrevealing. A more extensive workup was performed, revealing a duodenal cystic structure. This led to the diagnosis of a duodenal duplication cyst. The Whipple procedure was decided upon due to his recurrent pancreatitis, which caused fibrotic adhesions and anatomic region distortion. The patient underwent surgery and recovered uneventfully. Discussion: Acute pancreatitis in children is frequent and can be caused by unrecognized duodenal duplication cysts. When symptomatic, the majority present with vague abdominal pain. Despite using ultrasound as an adjunctive for diagnosis, the cyst might not become apparent until the condition has progressed to an advanced stage. A delayed diagnosis may result in complications necessitating risky surgeries. Conclusion: Children with recurrent pancreatitis should be evaluated for a duodenal duplication cyst. Early use of computed tomography scans may be necessary to identify the cause and spare the patient from risky procedures like Whipple surgery.

Clinical and paraclinical characteristics in pediatric patients with acute recurrent and chronic pancreatitis: a cohort in Mexico.

BACKGROUND: Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are infrequent clinical entities in pediatric patients, as less than 8% of the literature mentions this population. This study aimed to describe the clinical and paraclinical profile, and the etiology related to patients with ARP and CP attended at a tertiary-level healthcare institute in Mexico. METHODS: We conducted a retrospective study from medical records of patients with ARP and CP attended between 2010 and 2020, analyzing the clinical characteristics, imaging studies, and the etiology associated with each patient. RESULTS: We analyzed 25 patients: 17 were diagnosed with ARP, and eight with CP. The main etiology identified was an anatomical alteration of the pancreatic duct (32%); pancreas divisum was the most prevalent condition. In 48% of the population, the etiology was not identified. The group with CP was higher in frequency for calcifications and dilation of the pancreatic duct (p < 0.005) compared to the ARP group. CONCLUSIONS: The main etiology for ARP and CP was an anatomical alteration of the pancreatic duct; however, in almost half of the cases, no established cause was identified. Although comparing our results with those offered by large cohorts such as the INSPPIRE group can be complex, we found relevant similarities. Currently, the data obtained from this first descriptive study are the foundation for future research in the field of Mexican pediatric pancreatology.

INTRODUCCIÓN: La pancreatitis aguda recurrente (PAR) y crónica (PC) son entidades poco frecuentes en la edad pediátrica; sin embargo, menos del 8% de la literatura hace referencia a esta población. El objetivo de este estudio fue describir el perfil clínico, paraclínico y etiologías vinculadas en los pacientes con PAR y PC atendidos en una institución de tercer nivel de atención en México. MÉTODOS: Se realizó un estudio retrospectivo de los expedientes de los pacientes con PAR y PC atendidos entre 2010 a 2020, analizando las características clínicas, estudios de imagen y etiologías asociadas en cada uno de los pacientes. RESULTADOS: Se analizaron 25 pacientes, 17 con diagnóstico de PAR y ocho con PC. La principal etiología identificada correspondió a las alteraciones anatómicas del conducto pancreático (32%); el páncreas divisum fue la entidad más prevalente. En el 48% de la población no se pudo identificar una etiología. El grupo con PC presentó mayor frecuencia de calcificaciones y dilatación ductal pancreática (p < 0.005) en comparación al grupo de PAR. CONCLUSIONES: La principal etiología de PAR y PC identificada en nuestro estudio corresponde a las alteraciones anatómicas del conducto pancreático; sin embargo, en casi la mitad de los casos, no se tiene una causa establecida. Aunque es complicado comparar nuestros resultados con los ofrecidos por las grandes cohortes del grupo INSPPIRE, sí encontramos similitudes relevantes. Los datos obtenidos en este primer estudio descriptivo son la base para futuras investigaciones en el ámbito de la pancreatología pediátrica mexicana.

Acute recurrent pancreatitis in a child with pancreatic divisum- A case report.

Introduction and importance: In children, acute recurrent pancreatitis is attributed to pancreato-biliary anomalies, hereditary pancreatitis and cystic fibrosis. Pancreatic divisum is a common congenital ductal anomaly that leads to recurrence of pancreatitis. Case presentation: A 13 years old female presented with clinical features of acute recurrent pancreatitis. After ruling out common causes, magnetic resonance cholangiopancreatography was done which showed pancreatic divisum. Her symptoms resolved following duodenum preserving pancreatic head resection. Discussion: Acute recurrent pancreatitis is attributed to raised intrapancreatic dorsal ductal pressure due to ductal anomalies especially pancreatic divisum (PD). It is the embryological failure in the fusion of the dorsal and ventral ductal system. PD is further classified into a classical subtype where there is complete failure of ductal fusion and an incomplete subtype where there is partial fusion of the ductal system. The diagnosis is commonly done through abdominal imaging with secretin enhanced magnetic resonance cholangiopancreatography being the choice of imaging modality. The initial approach is endoscopic intervention unless patients present with signs of pancreatic fibrosis where a duodenum preserving pancreatic head resection can be carried out. Conclusion: A keen suspicion should be given towards anatomical or structural variants in absence of common etiologies. Early identification and management of pancreatic divisum prevents the recurrence of pancreatitis.

CFTR:F508d/A613T Mutation Is Associated With Recurrent Episodes of Pancreatitis.

Pancreatic insufficiency (PI) is found in 85% of individuals with cystic fibrosis (CF). Of the remaining who are pancreatic sufficient (PS), there is potential for developing pancreatitis, and is described in ~20% of PS individuals. We report a case of a 17.5-year-old female presenting with acute recurrent pancreatitis (ARP) and PS, later diagnosed with CF. This is the first reported case of ARP in an individual with a F508d/A613T genotype. To date, there are only 6 other individuals with this genotype, and the mechanisms of it causing ARP and no overt respiratory symptoms of CF are unclear. Her diagnosis occurred 10 years after her initial presentation of pancreatitis, highlighting the importance of screening for CFTR mutations in the workup for ARP with no clear etiology.

Enlargement of the Pancreas in Children Diagnosed with Acute Pancreatitis: An Approach Based on P/V Ratio.

Background Acute pancreatitis is a reversible inflammation of the pancreatic parenchyma. Enlargement of the pancreas is often envisaged in such conditions. This study evaluates P/V ratio, as a marker to decide pancreatic enlargement in disease condition. Purpose The aim of this study was to develop imaging-based diagnostic criterion for acute pancreatitis in children based on P/V ratio. Material and Methods This study included 37 children with acute pancreatitis and 283 children asymptomatic for pancreatic disorders, from a single hospital center. The age of children ranged between 2 and 18 years. P/V ratio, which is the ratio of greatest anteroposterior dimension of the head, body, and tail of the pancreas relative to the transverse lumbar vertebral body, was obtained for each child through ultrasonographic examination. Age-adjusted receiver operating characteristics (AROC) analysis was performed on P/V ratio at presentation for each pancreatic region, and the sensitivity at 90% specificity, the threshold errors, and the corresponding cutoffs were obtained. The enlargement assessment was also done after clinical recovery by referring to the cutoffs of respective regions. Results AROC analysis for males and females resulted into a maximum sensitivity of 83.33 and 81.67%, respectively, at 90% specificity for head. The error thresholds for both the groups were same, i.e., 0.098, indicating that 90% of the observations had errors less than the threshold. The corresponding P/V ratio cutoff for males and females was 0.43 and 0.42, respectively. Conclusion Radiologists and clinicians can refer a cutoff value of 0.4 for each region, along with hypoechogenicity, to decide about enlargement of the pancreas in acute pancreatitis condition.

Risk factors for the progression from acute recurrent to chronic pancreatitis among children in China.

Background: Risk factors for progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children are poorly understood. Aim: To summarize the clinical characteristics of children with ARP and CP, identify the risk factors of CP, and investigate the factors associated with rapid progression from initial onset of ARP to CP. Methods: The following variables were included in the risk factor analysis: sex, age at onset, family history, pancreas or biliary tract structural abnormalities, and genetic variations. Univariate and multivariate logistic regression analyses were used to assess the risk factors of CP. The Kaplan-Meier curves of the ARP progression to CP for various risk factor groupings were constructed and compared using the log-rank test. The Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR) of progression to CP for each risk variable. Results: In total, 276 children were studied, of whom 136 progressed to CP. Among them, 41 had pancreatic duct obstructive disease; 105 underwent genetic testing, of whom 68 were found to have genetic variations. Among the remaining 140 patients who did not progress to CP, 61 had biliary obstructions. Forty-three of these children underwent genetic testing, and 15 were found to have genetic variations. Risk factor analysis showed that children with gene mutations were at a higher risk of progressing to CP [odds ratio (OR) = 3.482; 95% confidence interval (CI): 1.444-8.398; P = 0.005]; children with pancreas divisum (PD) had a higher risk of CP than those without (OR = 8.665; 95% CI: 1.884, 9.851; P = 0.006). Further, children whose first ARP occurred at an older age might develop CP faster (HR = 1.070; 95% CI: 1.003, 1.141; P = 0.039). Children with gene mutations had a faster rate of progression to CP after onset than children without gene mutations (HR = 1.607; 95% CI: 1.024, 2.522; P = 0.039), PRSS1 gene mutations were more associated (P = 0.025). There was no difference in the rate of progression from ARP to CP in children with PD (P = 0.887); however, endoscopic retrograde cholangiopancreatography (ERCP) intervention delayed the progression to CP in ARP patients with PD (P = 0.033). Conclusion: PRSS1 gene mutations and PD are key risk factors for ARP progression to CP in children. PD itself does not affect the disease progression rate, but therapeutic ERCP can be beneficial to patients with ARP with symptomatic PD and delay the progression to CP.

Hereditary pancreatitis: An updated review in pediatrics.

Hereditary Pancreatitis (HP) has emerged as a significant cause of acute, acute recurrent and chronic pancreatitis in the pediatric population. Given that it presents similarly to other causes of pancreatitis, a positive family history and/or isolation of a gene mutation are vital in its designation. Inheritance patterns remain complex, but mutations involving the PRSS1, SPINK1, CFTR and CTRC genes are commonly implicated. Since being first described in 1952, dozens of genetic alterations that modify the action of pancreatic enzymes have been identified. Among children, these variants have been isolated in more than 50% of patients with chronic pancreatitis. Recent research has noted that such mutations in PRSS1, SPINK1 and CFTR genes are also associated with a faster progression from acute pancreatitis to chronic pancreatitis. Patients with HP are at increased risk of developing diabetes mellitus, exocrine pancreatic insufficiency, and pancreatic adenocarcinoma. Management follows a multi-disciplinary approach with avoidance of triggers, surveillance of associated conditions, treatment of pancreatic insufficiency and use of endoscopic and surgical interventions for complications. With significant sequela, morbidity and a progressive nature, a thorough understanding of the etiology, pathophysiologic mechanisms, diagnostic evaluation, current management strategies and future research considerations for this evolving disease entity in pediatrics is warranted.

Favorable response after radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis: A case report.

BACKGROUND: There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm (IPMN), who are surgically intolerant and require less invasive treatment options, which are limited. In the present study, we report a case of IPMN presenting with acute recurrent pancreatitis (ARP), in which radiation therapy effectively prevented further attacks of ARP and reduced tumor volume. CASE SUMMARY: An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst. Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas, with dilated pancreatic ducts and mural nodules. The patient was diagnosed with mixed-type IPMN, and five years later, he developed ARP. Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks. Surgery was considered clinically inappropriate because of his old age and comorbidities. He was referred to our department for radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy. An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation. Fourteen months later, he remains symptom-free from ARP. CONCLUSION: This case highlights the important role of radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

Digestive outcomes in Cystic fibrosis.

Cystic fibrosis (CF) is the most frequent life-limiting autosomal recessive disease in Caucasians, affecting the respiratory tract, but also the pancreas, gut, and hepatobiliary tract. CF is caused by variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Prognosis of CF has markedly improved over the last 20 years because of the management in CF centers and recent introduction of CFTR modulators, aimed at correcting the defective CFTR protein. There are nowadays more CF adults than children, with a predicted median survival age of around 50 years in high-income countries. Around 85% of CF patients have pancreatic insufficiency present at birth. Gastroesophageal reflux disease (GERD) is more frequent in CF patients, but its role on decline in lung health is controversial. Distal small bowel obstruction syndrome (DIOS) caused by meconium-like stool plugs occurs at any age after the neonatal period, affecting up to 15-20% of CF patients. Because of increased life expectancy, most CF patients are expected to live to their fifties or beyond, when cancer is more frequent. In addition, CF is associated with a higher risk for GI malignancy as compared with the general population. Colorectal cancer represents the most significant risk, and colonoscopy-based screening is recommended from 40 years of age onwards. Other digestive outcomes in CF reviewed in this paper include meconium ileus, Clostridium difficile infection, intussusception, acute appendicitis, small intestinal bacterial overgrowth, appendiceal mucocele and rectal prolapse. Every CF Center should comprise a gastroenterologist with expertise in the care of CF patients.

Acute Recurrent Pancreatitis and COVID-19 Infection: A Case Report with Literature Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection typically presents with respiratory symptoms, although presentation with gastrointestinal symptoms is not uncommon. Coronavirus disease 2019 (COVID-19) presenting as acute pancreatitis is rare. There are several etiological factors for acute recurrent pancreatitis, but its association with COVID-19 disease is not yet known. We present an unusual case of recurrent attacks of acute pancreatitis in a young woman with SARS-CoV-2 infection, which was diagnosed early but had a rapid downhill course in the second attack with a fatal outcome.

Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain's pain circuitry.

BACKGROUND: Acute pancreatitis (AP) and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis. The validated caerulein- (CAE) induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study. AIM: To determine efficacy of acetyl-L-carnitine (ALC) to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis. METHODS: Pancreatitis was induced with 6 hly intraperitoneal (i.p.) injections of CAE (50 µg/kg), 3 d a week for 6 wk in male C57BL/6J mice. Starting in week 4, mice received either vehicle or ALC until experiment's end. Mechanical hyper-sensitivity was assessed with von Frey filaments. Heat hypersensitivity was determined with the hotplate test. Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests. Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1 (Iba1). RESULTS: Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies, indicating ongoing pain. Treatment with ALC attenuated inflammation-induced hypersensitivity, but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted. Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls. Treatment with ALC resulted in increased numbers of rearing activity events, but time spent in "safety" was not changed. After all the abdominal injections, pancreata were translucent if excised at experiment's end and opaque if excised on the subsequent day, indicative of spontaneous healing. Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC. Microglial Iba1 immunostaining was significantly increased in hippocampus, thalamus (intralaminar nuclei), hypothalamus, and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves. CONCLUSION: CAE-induced pancreatitis caused increased pain-related behaviors, pancreatic fibrosis, and brain microglial changes. ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections.