Case Report: Chronic pancreatitis in children as the cumulative effect of bilio-pancreatic abnormalities and genetic mutations.

Pancreatitis, in general, is a high-morbidity condition. Genetic conditions and anatomic variants are sometimes seen, especially in children, where biliary etiologies and alcohol are less common than in adults. The decision to intervene, the combined operative-endoscopic strategy, and the timing pose unique challenges. We report the case of a 10-year-old boy with PRSS1 mutation and pancreatic duct duplication, discussing the management and reviewing the recent reports in the Literature.

Secretagogue-induced pancreatitis in mice devoid of chymotrypsin.

The serine protease chymotrypsin protects the pancreas against pancreatitis by degrading trypsinogen, the precursor to the digestive protease trypsin. Taking advantage of previously generated mouse models with either the Ctrb1 gene (encoding chymotrypsin B1) or the Ctrl gene (encoding chymotrypsin-like protease) disrupted, here we generated the novel Ctrb1-del ×Ctrl-KO strain in the C57BL/6N genetic background, which harbors a naturally inactivated Ctrc gene (encoding chymotrypsin C). The newly created mice are devoid of chymotrypsin yet the animals develop normally, breed well, and show no spontaneous phenotype, indicating that chymotrypsin is dispensable under laboratory conditions. When given cerulein, the Ctrb1-del ×Ctrl-KO strain exhibited markedly increased intrapancreatic trypsin activation and more severe acute pancreatitis, relative to wild-type C57BL/6N mice. After the acute episode, Ctrb1-del ×Ctrl-KO mice spontaneously progressed to chronic pancreatitis while C57BL/6N mice recovered rapidly. The cerulein-induced pancreas pathology in Ctrb1-del ×Ctrl-KO mice was highly similar to that previously observed in Ctrb1-del mice, however, trypsin activation was more robust and pancreatitis severity was increased. Taken together, the results confirm and extend prior observations demonstrating that chymotrypsin safeguards the pancreas against pancreatitis by limiting pathologic trypsin activity. In mice, the CTRB1 isoform, which constitutes about 90% of the total chymotrypsin content, is responsible primarily for the anti-trypsin defenses and protection against pancreatitis, however, the minor isoform CTRL also contributes to an appreciable extent.

Chronic pancreatitis of jejunal ectopic pancreas: a rare cause of chronic abdominal pain.

Ectopic pancreas (EP) is an uncommon, congenital focus of pancreatic tissue that is discontinuous with the principal pancreas. A 62-year-old female underwent multiple investigations for chronic epigastric pain. EP was identified intra-operatively. On retrospection, earlier imaging showed a thickened segment of jejunum with inflammation of the surrounding small bowel mesentery, suggestive of jejunal EP pancreatitis. Histology confirmed ectopic pancreatic tissue, with sections of the EP showing evidence of previous acute and chronic pancreatitis. When no cause for chronic abdominal pain is found, diagnostic laparoscopy should be considered, and the small bowel inspected, to further investigate for rare causes of abdominal pain, such as EP.

Vitamin D in blood serum and chronic pancreatitis.

Patients with chronic pancreatitis are at risk of developing malabsorption and malnutrition. Exocrine pancreatic insufficiency is accompanied by decreased serum micronutrient levels and low vitamin D levels are a frequent finding in up to 60-80% of patients. The aim of our prospective study was to investigate vitamin D in the blood serum of subjects with chronic pancreatitis with the possibility of influencing the reduced vitamin D levels with supplementation therapy. MATERIAL AND METHODOLOGY: Fifty patients with chronic pancreatitis and 20 subjects in the control group without gastrointestinal tract diseases, including pancreatic disease, were examined. The vitamin D level in blood serum was determined. The results were evaluated according to the age distribution of subjects with pancreatic disease and according to gender. Patients with low vitamin D levels were treated for 24 weeks with a dose of 1.500.000 IU of vitamin D3 per day, and then blood serum vitamin D levels were determined. RESULTS: In people with chronic pancreatitis, vitamin D levels were statistically significantly reduced compared to the control group. There was no statistically significant relationship of vitamin D with gender and age. Supplementation with vitamin D3 achieved an adjustment of vitamin D level to the level of the control group. CONCLUSION: Blood serum vitamin D levels are significantly reduced in people with chronic pancreatitis. Its correction by oral vitamin D supplementation was effective. Whether this adjustment of levels will be effective also in terms of e.g. beneficial effect on fibrogenesis will require further representative studies, because the limitation of the interpretation of the results of our study is the smaller number of subjects with chronic pancreatitis (Tab. 4, Ref. 29).

Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling.

The peripheral nervous system is a key regulator of cancer progression. In pancreatic ductal adenocarcinoma (PDAC), the sympathetic branch of the autonomic nervous system inhibits cancer development. This inhibition is associated with extensive sympathetic nerve sprouting in early pancreatic cancer precursor lesions. However, the underlying mechanisms behind this process remain unclear. This study aimed to investigate the roles of pancreatic Schwann cells in the structural plasticity of sympathetic neurons. We examined the changes in the number and distribution of Schwann cells in a transgenic mouse model of PDAC and in a model of metaplastic pancreatic lesions induced by chronic inflammation. Schwann cells proliferated and expanded simultaneously with new sympathetic nerve sprouts in metaplastic/neoplastic pancreatic lesions. Sparse genetic labeling showed that individual Schwann cells in these lesions had a more elongated and branched structure than those under physiological conditions. Schwann cells overexpressed neurotrophic factors, including glial cell-derived neurotrophic factor (GDNF). Sympathetic neurons upregulated the GDNF receptors and exhibited enhanced neurite growth in response to GDNF in vitro. Selective genetic deletion of Gdnf in Schwann cells completely blocked sympathetic nerve sprouting in metaplastic pancreatic lesions in vivo. This study demonstrated that pancreatic Schwann cells underwent adaptive reprogramming during early cancer development, supporting a protective antitumor neuronal response. These finding could help to develop new strategies to modulate cancer associated neural plasticity.

Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam mice.

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases.

BACKGROUND: Chymotrypsin C (CTRC) protects the pancreas against unwanted intrapancreatic trypsin activity through degradation of trypsinogen. Loss-of-function CTRC variants increase the risk for chronic pancreatitis (CP). The aim of the present study was to characterize novel CTRC variants found during genetic testing of CP cases at a pediatric pancreatitis center. METHODS: We used next-generation sequencing to screen patients. We analyzed the functional effects of CTRC variants in HEK 293T cells and using purified enzymes. RESULTS: In 5 separate cases, we detected 5 novel heterozygous CTRC variants: c.407C>T (p.Thr136Ile), c.550G>A (p.Ala184Thr), c.627Cdup (p.Ser210Leufs∗?, where the naming indicates a frame shift with no stop codon), c.628T>C (p.Ser210Pro), and c.779A>G (p.Asp260Gly). Functional studies revealed that with the exception of p.Ser210Leufs∗?, the CTRC variants were secreted normally from transfected cells. Enzyme activity of purified variants p.Thr136Ile, p.Ala184Thr, and p.Asp260Gly was similar to that of wild-type CTRC, whereas variant p.Ser210Pro was inactive. The frame-shift variant p.Ser210Leufs∗? was not secreted but accumulated intracellularly, and induced endoplasmic reticulum stress, as judged by elevated mRNA levels of HSPA5 and DDIT3, and increased mRNA splicing of XBP1. CONCLUSIONS: CTRC variants p.Ser210Pro and p.Ser210Leufs∗? abolish CTRC function and should be classified as pathogenic. Mechanistically, variant p.Ser210Pro directly affects the amino acid at the bottom of the substrate-binding pocket while the frame-shift variant promotes misfolding and thereby blocks enzyme secretion. Importantly, 3 of the 5 novel CTRC variants proved to be benign, indicating that functional analysis is indispensable for reliable determination of pathogenicity and the correct interpretation of genetic test results.

A Case of Isolated Splenic Tuberculosis Presenting as a Splenic Abscess Complicated by Rupture Leading to Splenectomy in an Immunocompetent Male.

We report a rare case of splenic tuberculosis (TB) in a male patient with a competent immune system who had no previous record of pulmonary TB. A 56-year-old male patient came to our outpatient department complaining of upper abdominal pain with a few episodes of vomiting for three days. He had alcoholism, smoked for 15 years, and had no past history of diabetes mellitus, hypertension, TB, or HIV. An abdominal ultrasound and CT scan at admission showed pancreatitis with a splenic abscess. After five days of admission, the patient's vitals deteriorated, and he had severe abdominal pain. CT scan suggested a splenic abscess rupture with hemoperitoneum. An emergency exploratory laparotomy was performed, and a splenectomy was done due to the splenic abscess rupture. A cartridge-based nucleic acid amplification test from splenic intracapsular fluid detected a trace Mycobacterium tuberculosis complex. The patient was discharged after starting first-line antitubercular treatment for six months. After three months of follow-up, the patient was doing well with no complaints.

A De Novo CaSR Missense Variant in Combination with Two Inherited Missense Variants in CFTR and SPINK1 Detected in a Patient with Chronic Pancreatitis.

Chronic pancreatitis is often secondary to alcohol abuse, but pancreatitis with no other aetiology is frequently associated with variants in genes encoding proteins related to zymogen granule activation. Our goal was to identify genomic variants in a patient by analyzing an extended panel of genes associated with the intra-pancreatic activation of the trypsin pathway. A 23-year-old woman was addressed at our institution because of chronic pancreatitis of unknown aetiology presenting recurrent episodes since she was the age of four. Next Generation Sequencing was performed to analyze a panel of nine genes associated with pancreatitis (CaSR, CFTR, CPA1, CTRC, CTSB, KRT8, PRSS1, PRSS2, and SPINK1). Three missense variants were found: p.Leu997Phe, maternally inherited, in the CFTR gene; p.Ile73Phe, paternally inherited, in the SPINK1 gene; and p.Phe790Ser, a de novo variant, in the CaSR gene. They were classified, respectively as probably benign, a Variant of Uncertain Significance, and the last one, which has never been described in the literature, as likely being pathogenic following American College of Medical Genetics and Genomics standard guidelines. Extensive intra-pancreatic activation of trypsin pathway gene sequencing detected rare variants that were not found with other gene screening and showed that variants in different genes may interact in contributing to the onset of the pancreatitis phenotype.

CREB activation drives acinar to ductal reprogramming and promote pancreatic cancer progression in animal models of alcoholic chronic pancreatitis.

BACKGROUND AND AIMS: In vivo induction of alcoholic chronic pancreatitis (ACP) causes significant acinar damage, increased fibroinflammatory response, and heightened activation of cyclic response element binding protein 1 (CREB) when compared with alcohol (A) or chronic pancreatitis (CP) mediated pancreatic damage. However, the study elucidating the cooperative interaction between CREB and the oncogenic Kras G12D/+ (Kras*) in promoting pancreatic cancer progression with ACP remains unexplored. METHODS: Experimental ACP induction was established in multiple mouse models, followed by euthanization of the animals at various time intervals during the recovery periods. Tumor latency was determined in these mice cohorts. Here, we established CREB deletion (Creb fl/fl ) in Ptf1a CreERTM/+ ;LSL-Kras G12D+/-(KC) genetic mouse models (KCC-/-). Western blot, phosphokinase array, and qPCR were used to analyze the pancreata of Ptf1a CreERTM+/-, KC and KCC -/- mice. The pancreata of ACP-induced KC mice were subjected to single-cell RNA sequencing (scRNAseq). Further studies involved conducting lineage tracing and acinar cell explant cultures. RESULTS: ACP induction in KC mice had detrimental effects on the pancreatic damage repair mechanism. The persistent existence of acinar cell-derived ductal lesions demonstrated a prolonged state of hyperactivated CREB. Persistent CREB activation leads to acinar cell reprogramming and increased pro-fibrotic inflammation in KC mice. Acinar-specific Creb ablation reduced advanced PanINs lesions, hindered tumor progression, and restored acinar cell function in ACP-induced mouse models. CONCLUSIONS: Our findings demonstrate that CREB cooperates with Kras* to perpetuate an irreversible ADM and PanIN formation. Moreover, CREB sustains oncogenic activity to promote the progression of premalignant lesions toward cancer in the presence of ACP.

Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients.

PURPOSE: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center. METHODS: A retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control. RESULTS: Patients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT. CONCLUSION: Our data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.

A rare case of acute obstructive suppurative pancreatic ductitis (AOSPD) which developed pyogenic spondylitis.

Acute obstructive suppurative pancreatic ductitis (AOSPD) is an acute suppuration of the pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) drainage and intravenous antibiotics treatment is the mainstay of therapy. Herein we describe an extremely rare case of AOSPD leading to pyogenic spondylitis. A 61-year-old male with a past medical history of chronic pancreatitis and diabetes mellitus presented to our hospital with abdominal and dorsal pain, fever, and shock status. Laboratory data showed severe inflammation, disseminated intravascular coagulation, and normal pancreatic enzymes. Computed tomography showed dilated main pancreatic duct and surrounding pancreatic abscesses. Spinal abnormalities were not detected at this point. He was initially diagnosed as infected pancreatic pseudocyst, but did not respond well to conservative intravenous antibiotic treatment. ERCP performed one week later revealed purulent pancreatic juice and the diagnosis was changed to AOSPD. Upon ERCP, we experienced technical difficulty in passing obstructing calculi. However, successful pancreatic drainage was achieved using new dilation and penetration devices. The patient responded quickly to drainage, but later developed pyogenic spondylitis. Our case highlights the difficulty of diagnosing AOSPD, the usefulness of new devices in urgent endoscopic drainage, and underscores the possibility of progression of pyogenic spondylitis even after adequate treatment.

The Role of Endoscopic Ultrasound and Ancillary Techniques in the Diagnosis of Autoimmune Pancreatitis: A Comprehensive Review.

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis with a multifactorial pathogenesis. Historically, it has been classified as type 1 and type 2, according to its clinical and histological features. The diagnosis of AIP is challenging and relies on a combination of clinical, histopathologic, serologic, and imaging characteristics. In the available guidelines, the imaging hallmarks of AIP are based on cross-sectional imaging and cholangiopancreatography retrograde endoscopic findings. Endoscopic ultrasound (EUS) is generally used for pancreatic tissue acquisition to rule out pancreatic cancer and diagnose AIP with limited accuracy. Several papers reported the reliability of EUS for providing informative morphologic features of AIP. Nowadays, the improvement in the resolution of EUS conventional images and the development of new ancillary technologies have further increased the diagnostic yield of EUS: contrast-enhanced EUS and EUS elastography are non-invasive and real-time techniques that strongly support the diagnosis and management of pancreatic diseases. In this review article, we will present the role of conventional EUS and ancillary diagnostic techniques in the diagnosis of AIP to support clinicians and endosonographers in managing this condition.

D-dimer as a Marker of Severity and Prognosis in Acute Pancreatitis.

Background and Objectives: Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU). Methodology: 30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily. Results: D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases (P = 0.04). D-dimer in ICU patients was significantly elevated (P = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate (P = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure. Conclusion: Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.

"Quality of life is impaired in children with chronic pancreatitis: A multicenter study".

BACKGROUND AND OBJECTIVES: The impact of chronic pancreatitis (CP) on quality of life (QOL) of children is not well established. Our objective was to evaluate the QOL, identify contributing factors, and determine the prevalence of anxiety and depression in children with CP in India. METHODS: Children (8-18y old) with CP were prospectively enrolled across three pediatric gastroenterology centres in India. QOL was assessed using the pediatric QOL inventory (PedsQL 4.0) scale, administered to both children and their parents. Anxiety and depression was studied using the Revised Children's Anxiety and Depression Scale (RCADS 25). Contributing factors were identified using binary logistic regression analysis. The data was compared against published QOL data in healthy Indian children. RESULTS: 121 children with CP (boys-57.9 %, age at QOL-14 ± 3.2years) were enrolled. A majority (82.7 %) had pain and advanced disease (Cambridge grade IV- 63.6 %). Children with CP had poorer QOL compared to controls (total score 74.6 ± 16 vs. 87.5 ± 11.1, p < 0.0001). QOL scores were similar across centres. Older children were similar to younger ones, except for a poorer emotional QOL. Taking QOL < -2 standard deviation (SD) of controls, ∼35 % had poor physical (50.9 ± 11.9) and 20 % had poor psychosocial (PS) QOL score (52.1 ± 7.2). On analysis, presence of pain and lower socio-economic status (SES) adversely affected both physical and PS-QOL. Additionally, girls had poorer PS-QOL than boys (Odds ratio 3.1, 95%CI:1.23-7.31). Anxiety and depression were uncommon (2,1.6 %). CONCLUSIONS: Patients with CP had impaired physical and psycho-social QOL. Presence of pain and lower SES adversely affected QOL. Psychiatric comorbidities were uncommon.

Preoperative and Postoperative Predictors of Insulin Independence From Total Pancreatectomy and Islet Autotransplantation.

OBJECTIVE: This study examined the preoperative and postoperative variables associated with 1 year and long-term insulin independence following total pancreatectomy and islet autotransplantation (TPIAT). METHODS: 46 TPIAT patients from 2010 to 2022 in a single hospital system were retrospectively analyzed. Pre- and postoperative variables were compared between short-term (1 year) and long-term (last follow-up after year 1) insulin-independent versus -dependent patients. RESULTS: Nine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed up for a median of 2.8 years (interquartile range [IQR] 1.0, 4.7). Short-term insulin independence was associated with higher median transplanted islet equivalents (IEQ) per kg (6981 vs 4493, P = .02), lower units of basal insulin on discharge (7 vs 12, P = .009), and lower rates of discharge with an insulin regimen (67% vs 100%, P = .006). Odds of short-term insulin independence increased by 80% for every 1000 increase in IEQ per kg (OR 1.80, CI 1.18-3.12, P = .005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42-0.91, P = .003) on average. Long-term insulin independence was also associated with transplanted IEQ per kg. No patient on antihyperglycemic medication before surgery achieved insulin independence. CONCLUSION: Short- and long-term insulin independence after TPIAT is associated with higher transplanted IEQ per kg and immediate postoperative variables that can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT.

Groove pancreatitis presenting with upper gastrointestinal obstruction and abnormal renal function: A case report and literature review.

Groove pancreatitis (GP) is a rare type of chronic pancreatitis characterized by fibrotic lesions localized to the groove between the pancreatic head, duodenum, and common bile duct. We present a case of a 59-year-old male alcoholic with vomiting and renal dysfunction found to have duodenal obstruction and low-density pancreatic head lesions on computed tomography concerning for GP. The patient underwent pancreaticoduodenectomy and pathology confirmed the diagnosis postoperatively. The patient recovered well without complications or relapse at follow-up. Although rare, GP should be included in the differential for pancreatic head masses in middle-aged alcoholics and surgical resection may be necessary for symptom relief and exclusion of malignancy.

Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis.

BACKGROUND AND AIMS: Smoking is recognised as an independent risk factor in the development of chronic pancreatitis (CP). Cystic fibrosis transmembrane conductance regulator (CFTR) function and ductal fluid and bicarbonate secretion are also known to be impaired in CP, so it is crucial to understand the relationships between smoking, pancreatic ductal function and the development of CP. METHODS: We measured sweat chloride (Cl-) concentrations in patients with and without CP, both smokers and non-smokers, to assess CFTR activity. Serum heavy metal levels and tissue cadmium concentrations were determined by mass spectrometry in smoking and non-smoking patients. Guinea pigs were exposed to cigarette smoke, and cigarette smoke extract (CSE) was prepared to characterise its effects on pancreatic HCO3 - and fluid secretion and CFTR function. We administered cerulein to both the smoking and non-smoking groups of mice to induce pancreatitis. RESULTS: Sweat samples from smokers, both with and without CP, exhibited elevated Cl- concentrations compared to those from non-smokers, indicating a decrease in CFTR activity due to smoking. Pancreatic tissues from smokers, regardless of CP status, displayed lower CFTR expression than those from non-smokers. Serum levels of cadmium and mercury, as well as pancreatic tissue cadmium, were increased in smokers. Smoking, CSE, cadmium, mercury and nicotine all hindered fluid and HCO3 - secretion and CFTR activity in pancreatic ductal cells. These effects were mediated by sustained increases in intracellular calcium ([Ca2+]i), depletion of intracellular ATP (ATPi) and mitochondrial membrane depolarisation. CONCLUSION: Smoking impairs pancreatic ductal function and contributes to the development of CP. Heavy metals, notably cadmium, play a significant role in the harmful effects of smoking. KEY POINTS: Smoking and cigarette smoke extract diminish pancreatic ductal fluid and HCO3 - secretion as well as the expression and function of CFTR Cd and Hg concentrations are significantly higher in the serum samples of smokers Cd accumulates in the pancreatic tissue of smokers.

Navigating the Groove: A Unique Case of Groove Pancreatitis.

Groove pancreatitis (GP) is an uncommon form of chronic pancreatitis (CP) that affects the area between the duodenum, the head of the pancreas, and the common bile duct (CBD), which is known as the pancreaticoduodenal groove. Our case is based on a 68-year-old male with a past medical history of alcohol use disorder and a 50-pack-year smoking history who presented with nausea, vomiting, and poor oral intake. Computed tomography (CT) of the abdomen and pelvis showed gastric outlet obstruction due to a 6.0 cm mass in the pancreatic groove and the second portion of the duodenum, with dilation of the pancreatic, intrahepatic, and extrahepatic biliary ducts. In order to rule out malignancy and evaluate the acute symptoms, the patient underwent an open pancreaticoduodenectomy (PD). Pathologic findings and negative tumor markers confirmed GP. This case highlights a rare form of CP that symptomatically and radiographically mimics malignancy, but is benign.