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Non-functioning pancreatic neuroendocrine tumours (NF-pNETs) are potentially malignant neoplasms that are detected with increasing frequency. The management of small (≤ 2 cm) asymptomatic NF-pNETs remains an area of controversy and clinical dilemma. Follow-up seems to be a reasonable strategy because of the relatively limited metastatic potential of these tumours, the good clinical prognosis, and considering the high complication rate associated with surgery. However, some studies show metastatic potential of these tumours, fuelling an ongoing debate in the literature regarding their management. Making the decision to observe or perform surgery is thus not an easy task. New, promising therapeutic methods involving ablation under endoscopic ultrasound (EUS) guidance with ethanol or radiofrequency ablation have been applied for these lesions with good clinical outcomes but only with short-term follow-up data. In this review, we address the emerging question of when to follow-up and when to perform surgery for small asymptomatic pancreatic tumours, with consideration of the potential of ablative therapies.

Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET. Methods: Using the AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography–mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients. Results: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients (p.adj < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = −1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86. Conclusions: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients’ condition, helping with pharmacological treatment or dietary strategies.

Yersiniosis is a zoonosis caused by the Yersinia bacterium. The route of infection is most commonly oral and is caused by consumption of Yersinia-contaminated food. The clinical presentations of chronic yersiniosis are abdominal pain, diarrhea, relapsing arthritis, and skin lesions, that is, nodular erythema. The diagnosis is based on culture-dependent identification of Yersinia in stool, positive serologic test results, or molecular techniques. The treatment of choice is combination antibiotic therapy. Mild forms of the disease do not usually require treatment. Yersiniosis frequently mimics or confounds other chronic intestinal and extraintestinal inflammatory conditions, particularly Crohn’s disease. Therefore, diagnosis of yersiniosis may be a challenge for medical practitioners. Not including Yersinia infection in the differential diagnosis of abdominal symptoms can lead to an incorrect diagnosis and inappropriate treatment. This review summarises the current knowledge of Yersinia enterocolitica and pseudotuberculosis infection, with special focus on differential diagnosis between this infection and Crohn’s disease.

Crohn’s disease (CD) may affect the entire gastrointestinal tract including its upper part. However, this aspect is poorly addressed in scientific literature and considered a rare finding. Here we aimed to prospectively investigate the prevalence, characteristics and clinical significance of upper gastrointestinal tract involvement in patients with CD, with particular focus on stomach bamboo joint-like appearance (BJA), Helicobacterpylori status and presence of microscopic changes. 375 prospectively recruited patients were included. In CD patients the prevalence of gastric and duodenal, but not esophageal, mucosal lesions, such as gastric mucosal inflammation, duodenal edema, ulcerations, and duodenal bulb deformation was significantly higher (at least p H.pylori negative individuals were analyzed. Moreover, BJA of the stomach and in case of H.pylori negative patients also duodenal bulb deformation were detected exclusively in CD patients. Presence of BJA lesion was not significantly associated with neither duration of the disease nor use/history of biologic treatment. Despite absence of H.pylori infection microscopic features of chronic gastritis were found in almost all (93.5%) patients, and in 31% of controls (p H.pylori negative gastritis are present.

The gastric microbiota in Crohn’s disease (CD) has not been studied. The purpose of the study was to evaluate differences of stomach microbiota between CD patients and controls. DNA was extracted from gastric mucosal and fluid samples, from 24 CD patients and 19 controls. 16S rRNA gene sequencing identified 1511 operational taxonomic units (OTUs), of which 239 passed the low abundance and low variance filters. All but one CD patients were HP negative. Fifteen bacterial phyla were identified in at least one mucosal or fluid site. Of these, Bacteroidota and Firmicutes accounted for 70% of all phyla. Proteobacteria, Actinobacteriota, and Fusobacteriota combined accounted for 27%. There was significant difference in the relative abundance of Bacteroidota, Proteobacteria, Fusobacteriota, and Campilobacterota between CD patients and controls only in gastric corpus samples. In gastric liquid, there was a significant difference only in Actinobacteriota. Pairwise comparison identified 67 differentially abundant OTUs in at least one site. Of these, 13 were present in more than one comparison, and four differentiating OTUs (Neisseriaceae, Neisseria, Absconditabacteriales, and Microbacteriaceae) were identified at all tested sites. The results reveal significant changes in gastric microbial profiles (beta diversity, phylum, and individual taxa levels) between H. pylori-negative CD patients and controls.

Rectal neuroendocrine tumors (rNETs) are potentially malignant lesions. In our study, we aimed to retrospectively check whether the rectal neuroendocrine tumors were found in colonoscopy examinations carried out as a part of Polish colonoscopy screening program (PCSP).We retrospectively analyzed the colonoscopy and histopathological database of examinations conducted as a part of PCSP in our institution in the years 2005-2021. We also checked the method by which the tumor was removed, its characteristics based on photo documentations and followed up the patients.The 10568 colonoscopy examinations were performed in PCSP in the years 2005-2021. Seven patients with a mean age of 53 with rNETs (1 in every 1510 colonoscopy) were detected. The polyp mean size was 5 mm. All the lesions were well differentiated tumors. First half of the colonoscopy examinations was performed in the years 2005-2012 and in that time three rNETs were detected, four rNETs were detected in the years 2012-2021. Even despite their typical appearance the neuroendocrine origin was not suspected in majority of cases and all tumors, except one, were removed with improper method. One of the patients underwent transanal endoscopic microsurgery of the scar. All patients are disease free in median follow-up of 108 months.Rectal NETs are detected in the screening colonoscopy program. In majority of cases, they are not suspected by endoscopists on colonoscopy, but diagnosed after removal in histopathological examinations. There is a need of education of endoscopists in recognition and methods of treatment of rNETs.

A growing number of studies indicate the potential involvement of various populations of bone marrow-derived stem cells (BMSCs) in tissue repair. However, the mobilization of BMSCs to the peripheral blood (PB) in acute and chronic pancreatitis (AP and CP) has not been investigated. A total of 78 patients were assigned into AP, CP, and healthy control groups in this study. Using flow cytometry, we found that VSELs, EPCs, and $CD133^{+}SCs$ were mobilized to the PB of patients with both AP and CP. Interestingly, AP and CP patients exhibited lower absolute number of circulating MSCs in the PB compared to healthy individuals. SC mobilization to the PB was more evident in patients with AP than CP and in patients with moderate/severe AP than mild AP. Using ELISA, we found a significantly increased HGF concentration in the PB of patients with AP and $SDF1\alpha$ in the PB of patients with CP. We noted a significant positive correlation between $SDF1\alpha$ concentration and the mobilized population of $CD133^{+}SCs$ in AP and between C5a and the mobilized population of VSELs moderate/severe AP. Thus, bone marrow-derived SCs may play a role in the regeneration of pancreatic tissue in both AP and CP, and mobilization of VSELs to the PB depends on the severity of AP.

Crohn's disease is an inflammatory disorder that can affect the entire gastrointestinal tract but typically involves the ileocecal region. Before endoscopy was widely used, involvement of the esophagus, stomach, and duodenum was thought to be rare. Recent publications demonstrated that not only are upper gastrointestinal lesions common in Crohn's disease (affecting up to 75% of the patients), but they also present characteristic endoscopic findings with potential clinical significance. It was suggested that lesions in the stomach with a bamboo joint-like appearance might be an endoscopic biomarker for Crohn's disease. It was also found that this occurrence is related to a more severe disease course. Our review summarizes the literature, as well as our own observations and considerations, concerning the issue of upper gastrointestinal involvement in Crohn's disease and its clinical meaning.

Introduction Rectal neuroendocrine neoplasms (rNENs) are potentially metastatic lesions. False endoscopic diagnosis and subsequent treatment may lead to nonradical resection and metastases. Objectives This study aimed to analyze the clinical characteristics of rNENs, investigate whether the lesion origin was suspected by endoscopists during examination and if those lesions were subsequently removed using the appropriate method, and assess the outcomes of patients after curative and noncurative resections. Patients and methods We analyzed the records of patients hospitalized in our department (2006-2019) with a diagnosis of rNENs. We included 40 patients with rNENs, evaluated their clinical characteristics, and investigated whether the neuroendocrine origin of the lesions was suspected on endoscopy. We compared the outcomes of patients treated with the proper method (endoscopic submucosal dissection / endoscopic mucosal resection [ESD / EMR]) and those treated with polypectomy. Results Abnormalities appeared as typical, yellowish subepithelial lesions (n = 24), lesions resembling hyperplastic polyps (n = 12), or tumors with central depression (n = 4). The median size was 5.5 mm and most of them were G1 lesions (n = 36). Only 14 of them were suspected to be of neuroendocrine origin at the first endoscopic examination, and 12 were removed by ESD / EMR. The remaining tumors (n = 26) were removed using polypectomy. Most of the patients were disease‑free at follow‑up, but 2 patients after polypectomy and a single patient after nonradical ESD developed metastases. Conclusion In most cases, the origin of the lesion was not suspected on colonoscopy and subsequently the tumor was removed using an inappropriate method. Endoscopists do not follow the guidelines when dealing with patients with rNENs and more emphasis should be placed on education on the management of rNENs.

Rectal neuroendocrine tumours are subepithelial lesions that are potentially malignant. Although the biology of these lesions has become increasingly understood and their management has been established, the endoscopic management of these tumours remains controversial. Recent studies demonstrated that compliance with guidelines is poor, and the majority of rectal neuroendocrine tumours are removed by an improper method, making management more complex and putting patients at risk of metastatic spread. Thus, there is a need to educate physicians who care for patients with these disorders. Our review has some tips and pointers for preventing mistakes in primary treatment and salvage therapy after polypectomy.

Cystic pancreatic tumors are detected with increasing frequency and remain a clinical problem. Since they have different potential of malignancy the management and decision making process is a hard task. Guidelines, concerning pancreatic cystic tumors indicate the management with mucinous, serous cystic pancreatic neoplasms and solid pseudopappilary tumor, while the management with pancreatic cystic neuroendocrine tumors is not included into these standards. This review tries to answer the question are the cystic pancreatic neuroendocrine tumors different entity from solid tumors of neuroendocrine origin.The management and differential diagnosis of these neoplasms with special focus on features on imaging studies allowing preoperative diagnosis are discussed.

The case of a 76-year-old patient, with a history of melanoma, admitted to the department of gastroenterology with symptoms of hypovolemic shock, caused by massive gastrointestinal bleeding. Clot-covered melanoma metastases were detected in both gastroduodenoscopy and colonoscopy. Gastrointestinal melanoma metastases are found in the majority of patients with advanced melanoma during autopsy; however, they are rarely detected in intravital studies and can be misdiagnosed as other benign lesions in endoscopy. In cases of patients with history of melanoma, metastases should be considered as the cause of non-specific abdominal symptoms, anemia, or bleeding from the gastrointestinal tract.

Not required for Clinical Vignette.

Mediastinal pseudocysts are a rare complication of acute pancreatitis. Lack of uniform treatment standards makes the management of this condition a clinical challenge. We report the case of a 43-year-old patient who presented with a left pleural effusion. Pleural fluid revealed a high amylase concentration consistent with a pancreaticopleural fistula. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a disruption of the pancreatic duct with free outflow of contrast medium into the thoracic cavity. A pancreatic stent was placed. The second day after the ERCP, the patient developed septic shock and was admitted to the intensive care unit. Computed tomography (CT) revealed mediastinal pseudocysts and bilateral pleural effusions. After bilateral drainage of the pleural cavities, the patient improved clinically, and a follow-up CT scan showed that the fluid collection and pseudocysts had resolved. We discuss the optimal strategies for diagnosing and treating patients with pancreatic thoracic pseudocysts and fistulas, as well as review the management of these conditions.

Cystic pancreatic tumors are detected with increasing frequency and remain a clinical problem. Since they have different potential of malignancy the management and decision making process is a hard task. Guidelines, concerning pancreatic cystic tumors indicate the management with mucinous, serous cystic pancreatic neoplasms and solid pseudopappilary tumor, while the management with pancreatic cystic neuroendocrine tumors is not included into these standards. This review tries to answer the question are the cystic pancreatic neuroendocrine tumors different entity from solid tumors of neuroendocrine origin.The management and differential diagnosis of these neoplasms with special focus on features on imaging studies allowing preoperative diagnosis are discussed.

Von Hippel-Lindau disease is rare autosomal dominant disorder that results from mutation of VHL gene. Typical manifestations of this syndrome include haemangioblastomas of retina, cerebellum and spinal cord, endolymphatic sac tumors, clear cell cancer and kidney cysts, pheochromocytoma, pancreatic cysts and neuroendocrine tumors. The differential diagnosis of pancreatic lesions in patients with von Hippel Lindau syndrome plays an important role. The pancreas in VHL disease is not only site of benign lesions (cysts, serous systic adenomas) but also of potentially malignant (neuroendocrine) and malignant tumors(metastases).The gastroenterological manifestations can be the first symptoms of von Hippel-Lindau disease.

Gastrointestinal organs are involved in the course of von Hippel Lindau disease. Typically pancreas in von Hippel Lindau syndrome is a site of cystic and solid tumors. Differential diagnosis of pancreatic lesions includes benign lesions (cysts, serous cystic adenomas), potentially malignant (neuroendocrine) and malignant tumors(metastases).In this work we present a patient with VHL syndrome with pancreatic cysts and neuroendocrine tumor.

Introduction: EUS-guided ethanol ablation of insulinoma is a new method of treatment of this neuroendocrine tumour. Ablation is recommended in patients who are poor surgical candidates or refuse surgery. We present a case of an 81-year-old female with symptomatic insulinoma, treated successfully with EUS-guided alcoholic ablation, along with a literature review including 28 other previously described cases. The effectiveness, safety of the therapy, and technical procedure-related issues are summarised. To the best of our knowledge, this is the first described case of successful insulinoma EUS-guided ablation in Poland. Material and methods: We searched the PubMed/Medline database to identify cases of EUS-guided alcoholic ablation. Our analysis included 14 articles (case reports or case series), with a total of 27 patients and 31 tumours described, published before February 2017. Results: The described tumours were relatively small (mean 13 mm), and the most common location was pancreatic head. The mean ethanol volume injected to the tumour was 1.8 ml and the concentration of infused alcohol varied from 95% to 98%.Side effects were observed in six cases; apart from one, they were mild and self-limiting. There was only one severe adverse event, treated conservatively with success. The median follow-up was 14.4 months (2–55 months). In all described cases ablation led to improvement of the symptoms and normalisation of glycaemia. Conclusions: The EUS-guided alcoholic ablation of insulinoma is a safe and effective method of treatment in patients who are poor surgical candidates and/or refuse surgery. The adverse effects are rare and mild and were observed when the volume of injected ethanol was equal to or above 3.0 ml. However, the data is limited, the follow-up is relatively short, and prospective studies are needed to confirm the long-term effects of treatment. The study shows also that there are important procedural differences (concentration and volume of alcohol, needle gauge, number of sessions) between the endoscopists, which should be specified.

Various independent studies indicate involvement of different populations of bone marrow-derived stem cells in the process of tissue regeneration. In inflammatory disorders bone marrow stem cells are mobilized into peripherial blood and further to different organs, where they take part in tissue regeneration. Experimental studies have shown that bone marrow stem cells play a pivotal role in regeneration of endo and egzocrine pancreas and have a role in pathogenesis of pancreatitis, diabetes and pancreatic neoplasms. Our review summarize available scientific data about different populations of bone marrow stem cells and their role in pathogenesis of inflammatory disorders with special focus on the role of these cells in pancreatic regeneration and their influence on development of pancreatitis. Presented data show also therapeutic potential of bone marrow stem cells in pancreatitis.

Pancreatic cancer remains one of the deadliest solid tumors in humans and an unsolved problem of today's medicine. Experimental studies reveal that the heterogeneous and complex pancreatic cancer microenvironment is responsible, not only for cancer growth, spread, development of metastases, but also for cancer recurrence and chemotherapy resistance. Chemotherapy affecting the cancer stroma is still under clinical and experimental research and remains hope for cure of pancreatic cancer. We present the cancer microenvironment characteristics and summary of experimental studies with use of agents affecting pancreatic cancer stroma.

Background/Aims Recent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting. Methods In this study, we examined the levels of a broad panel of cytokines, including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα) and granulocyte-colony stimulating factor (G-CSF) in patients with pancreatic adenocarcinoma (n = 43), other pancreatic malignancies (neuroendocrine [n = 10] and solid pseudopapillary tumors [n = 3]), and healthy individuals (n = 41). Results We found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p

Various experimental studies indicate potential involvement of bone marrow (BM)-derived stem cells (SCs) in malignancy development and progression. In this study, we comprehensively analysed systemic trafficking of various populations of BM-derived SCs (BMSCs), i.e., mesenchymal, haematopoietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), and of recently discovered population of very small embryonic/epiblast-like SCs (VSELs) in pancreatic cancer patients. Circulating CD133(+)/Lin(-)/CD45(-)/CD34(+) cells enriched for HSCs, CD105(+)/STRO-1(+)/CD45(-) cells enriched for MSCs, CD34(+)/KDR(+)/CD31(+)/CD45(-) cells enriched for EPCs and small CXCR4(+) CD34(+) CD133(+) subsets of Lin(-) CD45(-) cells that correspond to VSELs were enumerated and sorted from blood samples derived from 29 patients with pancreatic cancer, and 19 healthy controls. In addition, plasma levels of stromal-derived factor-1 (SDF-1), growth/inhibitory factors and sphingosine-1-phosphate (S1P; chemoattractants for SCs), as well as, of complement cascade (CC) molecules (C3a, C5a and C5b-9/membrane attack complex--MAC) were measured. Higher numbers of circulating VSELs and MSCs were detected in pancreatic cancer patients (P < 0.05 and 0.01 respectively). This trafficking of BMSCs was associated with significantly elevated C5a (P < 0.05) and C5b-9/MAC (P < 0.005) levels together with S1P concentrations detected in plasma of cancer patients, and seemed to be executed in a SDF-1 independent manner. In conclusion, we demonstrated that in patients with pancreatic cancer, intensified peripheral trafficking of selected populations of BMSCs occurs. This phenomenon seems to correlate with systemic activation of the CC, hepatocyte growth factor and S1P levels. In contrast to previous studies, we demonstrate herein that systemic SDF-1 levels do not seem to be linked with increased mobilization of stem cells in patients with pancreatic cancer.

Various experimental studies suggest that pancreatic malignancies may originate from stem cells. Recently we reported that in patients with pancreatic tumors intensified trafficking of selected populations of bone marrow (BM)-derived stem cells (SCs) is observed, and this is associated with activity of the complement cascade (Starzynska et al. JCMM 2013). Unfortunately the mechanisms responsible for this “selective” mobilization of BMSCs are not fully known. However, it is hypothesized that various chemokines may participate in this process. In this study we analyzed levels of interleukins (IL-1, IL-6, IL-8, IL-10, IL-12, IL-17 and IL-23) together with granulocyte-colony stimulating factor (G-CSF) and tumor necrosis factor-alpha (TNF α ) in patients with pancreatic neoplasms ( n = 26) and control individuals ( n = 32), and verified whether these molecules are associated with previously observed phenomenon of selective BMSCs egress in patients with pancreatic neoplasms. Our results demonstrated that in patients with pancreatic neoplasms significantly (up to 3 times) higher levels of IL-6, IL-8, IL-10 and TNFα are observed (in all cases at least P P = 0.002). No significant differences in IL-1, IL-12 nor G-CSF levels were stated. In our study, IL-6, IL-8 and TNFα levels negatively correlated with the absolute numbers of circulating hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs) (in all cases at least P r = 0.57; P P α may be involved into orchestration of intensified BMSCs trafficking in patients with pancreatic tumors. Clinical value of these molecules must be assessed in further studies. Supported by MNiSW Grant (402 423038).