Chronic pancreatitis is defined as a disease of the pancreas in which recurrent inflammatory episodes result in replacement of the pancreatic parenchyma by fibrous connective tissue in individuals with genetic, environmental, and other risk factors. Pain is one of the most important symptoms of chronic pancreatitis and, in many cases, has chronic visceral nociceptive, nociplastic, and even neuropathic components, with evidence of both central and peripheral sensitization, neuroplasticity, and neurogenic inflammation.

The literature on the diagnosis and treatment of pain in chronic pancreatitis was reviewed and summarized.

Treatment of abdominal pain in chronic pancreatitis is guided by pancreatic morphology on imaging, although the correlation between pain symptoms and pathoanatomical changes is not always straightforward. Patients with pancreatic duct obstruction are initially offered endoscopic or surgical therapies, while non-obstructive disease is mostly managed medically. Lifestyle changes and psychological support are of particular importance for all chronic pancreatitis patients. Analgesic options range from non-opioid medications to opioids and adjuvant agents. Interventional pain management may consist of radiofrequency treatment of the splanchnic nerves and spinal cord stimulation. To date, there are no randomized trials supporting their efficacy in the treatment of chronic pancreatitis pain, and the recommendation to consider these treatment options is justified by evidence from observational studies. Possible opioid-sparing effects of interventional pain treatments are important to consider because opioid use and dependency are common in chronic pancreatitis patients and associated with worse outcomes. Celiac plexus block is not generally recommended for chronic pancreatitis due to the limited quality of evidence, overall short duration of effect, and invasiveness of the procedure. Central sensitization can impact the effectiveness of invasive treatments.

Managing pain in chronic pancreatitis is a complex task that requires a multidimensional and individualized approach. Due to the lack of randomized trials, treatment decisions are often guided by expert opinion. Integrating pharmacological and non-pharmacological interventions and collaborating with a multidisciplinary team are key components of effective chronic pancreatitis pain management.

The aim of this study is to illustrate the complexity of pain management in chronic pancreatitis (CP). In this context, pain represents the most common and debilitating symptom, and it deeply affects patient's quality of life. Multiple rating scales (unidimensional, bidimensional and multidimensional) have been proposed to quantify CP pain. However, it represents the result of complex mechanisms, involving genetic, neuropathic and neurogenic factors. Considering all these aspects, the treatment should be discussed in a multidisciplinary setting and it should be approached in a stepwise manner. First, a lifestyle change is recommended and nonsteroidal anti-inflammatory drugs represent the gold standard among medical treatments for CP patients. The second step, after medical approach, is endoscopic therapy, especially for complicated CP. In case of failure, tailored surgery represents the third step and decompressive or resection procedures can be chosen. In conclusion, CP pain's management is challenging considering all these complex aspects and the lack of international protocols.

Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped.

The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data.

Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample.

Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively.

Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

All cells in the body are exposed to physical force in the form of tension, compression, gravity, shear stress, or pressure. Cells convert these mechanical cues into intracellular biochemical signals; this process is an inherent property of all cells and is essential for numerous cellular functions. A cell's ability to respond to force largely depends on the array of mechanical ion channels expressed on the cell surface. Altered mechanosensing impairs conscious senses, such as touch and hearing, and unconscious senses, like blood pressure regulation and gastrointestinal (GI) activity. The GI tract's ability to sense pressure changes and mechanical force is essential for regulating motility, but it also underlies pain originating in the GI tract. Recent identification of the mechanically activated ion channels Piezo1 and Piezo2 in the gut and the effects of abnormal ion channel regulation on cellular function indicate that these channels may play a pathogenic role in disease. Here, we discuss our current understanding of mechanically activated Piezo channels in the pathogenesis of pancreatic and GI diseases, including pancreatitis, diabetes mellitus, irritable bowel syndrome, GI tumors, and inflammatory bowel disease. We also describe how Piezo channels could be important targets for treating GI diseases.

The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro.

C57BL/6 male mice were intraperitoneally injected with caerulein for 6 weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-β1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs).

The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-β1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs.

Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.

Chronic pancreatitis (CP) is a chronic progressive inflammatory disease of the pancreas, caused by multiple factors and accompanied by irreversible impairment of pancreatic internal and external secretory functions. Pathologically, atrophy of the pancreatic acini, tissue fibrosis or calcification, focal edema, inflammation, and necrosis are observed. Clinical manifestations include recurrent or persistent abdominal pain, diarrhea, emaciation, and diabetes. In addition, CP is prone to develop into pancreatic cancer(PC) due to persistent inflammation and fibrosis. The disease course is prolonged and the clinical prognosis is poor. Currently, clinical treatment of CP is still based on symptomatic treatment and there is a lack of effective etiological treatment. Encouragingly, experiments have shown that a variety of active substances have great potential in the etiological treatment of chronic pancreatitis. In this paper, we will review the pathogenesis of CP, as well as the research progress on anti-inflammatory and anti-fibrotic therapies, which will provide new ideas for the development of subsequent clinical studies and formulation of effective treatment programs, and help prevent CP from developing into pancreatic cancer and reduce the prevalence of PC as much as possible.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

There is conflicting evidence regarding autoimmune pancreatitis (AIP) association with pancreatic and non-pancreatic cancers. Literature lacks data on overall prevalence of malignancies in autoimmune pancreatitis.

Given the lack of definite evidence, we aimed to pool and summarize data from available literature regarding prevalence of different malignancies in AIP.

We conducted a systematic search of MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science through February 16, 2021, to include observational studies assessing the incidence of cancer in AIP. We used the DerSimonian-Laird method with random effects for meta-analysis. Pooled prevalence, 95% confidence interval (CI), and I² statistic are reported.

A total of 17 studies with 2746 patients were included assessing the prevalence of cancer in AIP. The overall prevalence of cancer in AIP was 9.6% [95% confidence interval (CI), 5.7-13.5%]. The cancers with the highest prevalence in AIP population were gastric and colorectal cancer, with prevalence of 1.3% (95% CI, 0.5-2.1%) and 1.2% (95% CI, 0.6-1.8%), respectively.

We demonstrate the prevalence of different cancers in AIP. Inflammatory surge in AIP and subsequent carcinogenesis is one explanation for this association. Moreover, AIP can be a paraneoplastic syndrome manifestation of malignancies.

Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous.

PubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD.

Four thousand one hundred and twenty-one records were identified and 547 screened; finally, 124 studies were included in the review. AP is the most frequent pancreatic manifestation in IBD; the majority of AP cases in IBD are due to gallstones and drugs but cases of idiopathic AP are increasingly reported. AIP is a rare disease, but a strong association with IBD has been demonstrated, especially for type 2 and ulcerative colitis. The pathogenetic link between IBD and AIP remains unclear, but an immune-mediated pathway seems plausible. An association between CP and PEI with IBD has also been suggested, but data are to date scarce and conflicting.

This is the first systematic review of the association between IBD and pancreatic diseases. Gallstones and drugs should be considered the most probable causes of AP in IBD, with type 2 AIP also being possible.

The use of surgical drains is a very common practice after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. This is the third update of a previously published Cochrane Review to address the uncertain benifits of prophylactic abdominal drainage in pancreatic surgery.

To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal.

In this updated review, we re-searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and the Chinese Biomedical Literature Database (CBM) on 08 February 2021.

We included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery.

Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We conducted the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. We used GRADE to assess the certainty of the evidence for important outcomes.

We identified a total of nine RCTs with 1892 participants. Drain use versus no drain use We included four RCTs with 1110 participants, randomised to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. Low-certainty evidence suggests that drain use may reduce 90-day mortality (RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants). Compared with no drain use, low-certainty evidence suggests that drain use may result in little to no difference in 30-day mortality (RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants), wound infection rate (RR 0.98, 95% CI 0.68 to 1.41; four studies, 1055 participants), length of hospital stay (MD -0.14 days, 95% CI -0.79 to 0.51; three studies, 876 participants), the need for additional open procedures for postoperative complications (RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants), and quality of life (105 points versus 104 points; measured with the pancreas-specific quality of life questionnaire (scale 0 to 144, higher values indicating a better quality of life); one study, 399 participants). There was one drain-related complication in the drainage group (0.2%). Moderate-certainty evidence suggests that drain use probably resulted in little to no difference in morbidity (RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants). The evidence was very uncertain about the effect of drain use on intra-abdominal infection rate (RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-certainty evidence), and the need for additional radiological interventions for postoperative complications (RR 0.87, 95% CI 0.40 to 1.87; three studies, 660 participants; very low-certainty evidence). Active versus passive drain We included two RCTs involving 383 participants, randomised to the active drain group (N = 194) and the passive drain group (N = 189) after pancreatic surgery. Compared with a passive drain, the evidence was very uncertain about the effect of an active drain on 30-day mortality (RR 1.23, 95% CI 0.30 to 5.06; two studies, 382 participants; very low-certainty evidence), intra-abdominal infection rate (RR 0.87, 95% CI 0.21 to 3.66; two studies, 321 participants; very low-certainty evidence), wound infection rate (RR 0.92, 95% CI 0.44 to 1.90; two studies, 321 participants; very low-certainty evidence), morbidity (RR 0.97, 95% CI 0.53 to 1.77; two studies, 382 participants; very low-certainty evidence), length of hospital stay (MD -0.79 days, 95% CI -2.63 to 1.04; two studies, 321 participants; very low-certainty evidence), and the need for additional open procedures for postoperative complications (RR 0.44, 95% CI 0.11 to 1.83; two studies, 321 participants; very low-certainty evidence). There was no drain-related complication in either group. Early versus late drain removal We included three RCTs involving 399 participants with a low risk of postoperative pancreatic fistula, randomised to the early drain removal group (N = 200) and the late drain removal group (N = 199) after pancreatic surgery. Compared to late drain removal, the evidence was very uncertain about the effect of early drain removal on 30-day mortality (RR 0.99, 95% CI 0.06 to 15.45; three studies, 399 participants; very low-certainty evidence), wound infection rate (RR 1.32, 95% CI 0.45 to 3.85; two studies, 285 participants; very low-certainty evidence), hospital costs (SMD -0.22, 95% CI -0.59 to 0.14; two studies, 258 participants; very low-certainty evidence), the need for additional open procedures for postoperative complications (RR 0.77, 95% CI 0.28 to 2.10; three studies, 399 participants; very low-certainty evidence), and the need for additional radiological procedures for postoperative complications (RR 1.00, 95% CI 0.21 to 4.79; one study, 144 participants; very low-certainty evidence). We found that early drain removal may reduce intra-abdominal infection rate (RR 0.44, 95% CI 0.22 to 0.89; two studies, 285 participants; very low-certainty evidence), morbidity (RR 0.49, 95% CI 0.30 to 0.81; two studies, 258 participants; very low-certainty evidence), and length of hospital stay (MD -2.20 days, 95% CI -3.52 to -0.87; three studies, 399 participants; very low-certainty evidence), but the evidence was very uncertain. None of the studies reported on drain-related complications.

Compared with no drain use, it is unclear whether routine drain use has any effect on mortality at 30 days or postoperative complications after pancreatic surgery. Compared with no drain use, low-certainty evidence suggests that routine drain use may reduce mortality at 90 days. Compared with a passive drain, the evidence is very uncertain about the effect of an active drain on mortality at 30 days or postoperative complications. Compared with late drain removal, early drain removal may reduce intra-abdominal infection rate, morbidity, and length of hospital stay for people with low risk of postoperative pancreatic fistula, but the evidence is very uncertain.

The high incidence of osteopathy among patients with chronic pancreatitis (CP) has garnered increased attention over recent years. The aims of this study were to assess the prevalence and risk factors for osteopathy in Chinese patients with CP.

This was a cross-sectional study of CP patients from a large center in China; patients were recruited between 31 January 2017 and 31 January 2018. Bone density and laboratory tests, including bone-related biochemical, inflammatory, and hormone parameters, were assessed prospectively. Differences between patients with and without osteopathy were analyzed. Logistic regression analysis was used to investigate associations between variables.

In total, 104 CP patients were enrolled in this study (68.3% idiopathic and 31.7% alcoholic). According to the M-ANNHEIM classification, 87.5% of the patients were at an early stage (0-II). Osteopenia was diagnosed in 30.8% of patients and osteoporosis in 5.8%; thus, a total of 36.5% of patients presented with osteopathy. In multivariate analysis, the independent risk factors for osteopathy in CP patients were age (OR = 1.04; 95% CI = 1.00-1.08; P = 0.030), BMI (OR = 0.72; 95% CI = 0.58-0.89; P = 0.003), and PTH (OR = 0.96; 95% CI = 0.93-1.00; P = 0.022).

This study is the first to report the prevalence of osteopathy in Chinese patients with CP. It found that age and low BMI are significant risk factors for osteopathy. Low PTH (but within the normal range) showed a weak association with osteopathy, which warrants further exploration.

Background and Objectives: The clinical manifestations and course of chronic pancreatitis (CP) are often nonspecific and variable, hampering diagnosis of the risk of exocrine pancreatic insufficiency (EPI). Development of new, reproducible, and non-invasive methods to diagnose EPI is therefore a major priority. The objective of this metabolomic study was to identify novel biomarkers associated with EPI. Materials and Methods: We analyzed 53 samples from patients with CP, 32 with and 21 without EPI, using an untargeted metabolomics workflow based on hydrophilic interaction chromatography coupled to high-resolution mass spectrometry. Principal component and partial least squares-discriminant analyses showed significant between-group differentiation, and univariate and multivariate analyses identified potential candidate metabolites that significantly differed between samples from CP patients with EPI and those without EPI. Results: Excellent results were obtained using a six-metabolic panel to diagnose the presence of EPI in CP patients (area under the ROC curve = 0.785). Conclusions: This study confirms the usefulness of metabolomics in this disease setting, allowing the identification of novel biomarkers to differentiate between the presence and absence of EPI in CP patients.

Chronic pancreatitis (CP) is a progressive condition caused by several factors and characterised by pancreatic fibrosis and dysfunction. However, CP is difficult to diagnose at an early stage. Various advanced methods including endoscopic ultrasound based elastography and confocal laser endomicroscopy have been used to diagnose early CP, although no unified diagnostic standards have been established. In the past, the diagnosis was mainly based on imaging, and no comprehensive evaluations were performed. This review describes and compares the advantages and limitations of the traditional and latest diagnostic modalities and suggests guidelines for the standardisation of the methods used to diagnose early CP.

Malnutrition is a commonly encountered issue in patients with alcohol-associated liver disease. The role of nutritional supplementation in the management of alcohol-associated liver disease is integral to patient outcomes-it has been shown to decrease rates of hepatic encephalopathy, improve outcomes post-liver transplant, reduce 90-day hospital readmissions and lower mortality. Despite these benefits, many studies have shown nutritional support to be an underutilised tool in the care of patients with alcohol-associated liver disease.

To review the epidemiology, pathophysiology, recommendations for nutritional assessment and supplementation, as well as future directions for research of the relationship between nutrition and alcohol-associated liver disease.

A literature search was conducted via PubMed using MeSH terms to inform this narrative review.

Decreased dietary intake, socioeconomic status, impaired absorption of nutrients and increased free radical species are implicated in the pathophysiology of malnutrition in alcohol-associated liver disease.

Malnutrition is common in alcohol-associated liver disease, and physicians should be aware of its association with poor clinical outcomes. Routine nutritional assessment, involvement of a dietician and nutritional supplementation are recommended to improve clinical outcomes in patients with alcohol-associated liver disease.

Due to difficulty in early diagnosis of chronic pancreatitis (CP), it is urgent to find novel biomarkers to detect CP. Exosomal microRNAs (Exo-miRNAs) located in the serum may be potential diagnostic and therapeutic targets for CP.

To identify differentially expressed Exo-miRNAs (DE-Exo-miRNAs) in the serum of CP patients, we performed a bioinformatics analysis.

The dataset GSE128508 was downloaded from the Gene Expression Omnibus (GEO) database. The analysis was carried out using BRB-ArrayTools and significance analysis of microarrays (SAM). The target genes of DE-S-Exo-miRNAs were predicted by miRWalk databases. Further gene ontology (GO) term and Kyoto Encyclopedia of Genomes (KEGG) pathway analyses were performed with plug-in ClueGO in Cytoscape software 3.7.0. Subsequently, the interaction regulatory network between encoded proteins of target genes was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and analyzed using plug-in Molecular Complex Detection (MCODE) and cytoHubba in Cytoscape software 3.7.0.

We identified 227 DE-Exo-miRNAs in the serum. Further analysis using the miRWalk database identified 5164 target genes of these miRNAs. The protein-protein interaction (PPI) regulatory network of 1912 potential target genes for hub 10 up-regulated miRNAs with high degrees and one down-regulated miRNAs were constructed using the STRING database and Cytoscape software. The functional analysis using Cytoscape software tool highlighted that target genes involved in pancreatic cancer. Acinar-ductal metaplasia (ADM) in the inflammatory environment of CP is a precursor of pancreatic cancer. Subsequently, we constructed a network of target genes associated with ADM and their miRNAs.

Exo-miRNAs in the serum as well as their target genes may be promising targets for the early diagnosis and treatment of CP. In addition, we identified potential Exo-miRNAs involved in ADM that is a precursor of pancreatic cancer associated with CP.

Chronic pancreatitis (CP) is characterized by a wide range of irreversible fibro-inflammatory diseases with largely ambiguous pathogenesis. Although neddylation pathway has been implicated in regulating immune responses, whether the dysregulation of neddylation is involved in the progression of CP and how neddylation regulates the inflammatory microenvironment of CP have not yet been reported. Here, we demonstrate that global inactivation of neddylation pathway by MLN4924 significantly exacerbates chronic pancreatitis. The increased M2 macrophage infiltration, mediated by the upregulated chemokine (C-C motif) ligand 5 (CCL5), is responsible for the enhanced pancreatitis-promoting activity of MLN4924. Both CCL5 blockade and macrophage depletion contribute to alleviating pancreatic fibrosis and inflammation in MLN4924-treated CP mice. Mechanistic investigation identifies that inactivation of Cullin-RING ligases (CRLs) stabilizes cellular levels of hypoxia-inducible factor 1α (HIF-1α), which increases CCL5 expression by promoting CCL5 transactivation. Clinically, UBE2M expression remarkably decreases in human CP tissues compared with normal specimens and the levels of CCL5 and M2 marker CD163 are negatively correlated with UBE2M intensity, suggesting that neddylation is involved in the pathogenesis of pancreatitis. Hence, our studies reveal a neddylation-associated immunopathogenesis of chronic pancreatitis and provide new ideas for the disease treatment.

Pancreatic duct stones are direct sequelae of chronic pancreatitis (CP) and can occur in ∼50% of patients. Selection of the appropriate treatment method for pancreatic duct stones depends on location, size and number of stones. We present a patient with upper abdominal pain and weight loss for the previous 3 months. Diagnostic workup detected a chronic inflammation of the pancreas with stone in the main pancreatic duct and a nodular lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography was performed without success. Given the rise in incidence and prevalence of CP, the potential complications and high mortality rate, it is imperative that physicians understand the risk factors, disease process and management of this disease. Pancreaticoduodenectomy in patients with CP is a feasible option for the treatment of focal cystic lesions to the head of the pancreas associated to pancreatic stone in selected cases.

Pancreatic disorders cause a broad spectrum of clinical diseases, mainly including acute and chronic pancreatitis and pancreatic cancer, and are associated with high global rates of morbidity and mortality. Unfortunately, the pathogenesis of pancreatic disease remains obscure, and there is a lack of specific treatments. T lymphocytes (T cells) play a vital role in the adaptive immune systems of multicellular organisms. During pancreatic disease development, local imbalances in T-cell subsets in inflammatory and tumor environments and the circulation have been observed. Furthermore, agents targeting T cells have been shown to reverse the natural course of pancreatic diseases. In this review, we have discussed the clinical relevance of T-cell alterations as a potential outcome predictor and the underlying mechanisms, as well as the present status of immunotherapy targeting T cells in pancreatitis and neoplasms. The breakthrough findings summarized in this review have important implications for innovative drug development and the prospective use of immunotherapy for pancreatitis and pancreatic cancer.

Pancreatic cancer is one of the most challenging adenocarcinomas due to its hostile molecular behavior and complex tumor microenvironment. It has been recently postulated that pancreatic stellate cells (PSCs), the resident lipid-storing cells of the pancreas, are important components of the tumor microenvironment as they can transdifferentiate into highly proliferative myofibroblasts in the context of tissue injury. Targeting tumor-stromal crosstalk in the tumor microenvironment has emerged as a promising therapeutic strategy against pancreatic cancer progression and metastasis. This chapter brings a broad view on the biological and pathological role of PSCs in the pancreas, activated stellate cells in the onset of tissue fibrosis, and tumor progression with particular emphasis on the bidirectional interactions between tumor cells and PSCs. Further, potential therapeutic regimens targeting activated PSCs in the pre-clinical and clinical trials are discussed.