Nutritional support in pancreatic cancer patients and its effect on nutritional status: an observational regional HPB network study investigating current practice.

PURPOSE: Preoperative malnutrition is associated with poor postoperative outcomes in patients with pancreatic cancer. This study evaluated the effectiveness of current practice in nutritional support for patients with pancreatic cancer. METHODS: Observational multicenter HPB network study conducted at the Isala Clinics Zwolle, Medical Spectrum Twente, Medical Center Leeuwarden, and University Medical Center Groningen between October 2021 and May 2023. Patients with a suspected pancreatic malignancy scheduled for surgery were screened for malnutrition using the Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire and referred to a dedicated dietician for nutritional support comprising pancreatic enzyme replacement therapy, dietary advice, and nutritional supplements to achieve adequate caloric and protein intake. At baseline, 1 day preoperatively, and 3 months postoperatively, the nutritional status and muscle thickness were evaluated. RESULTS: The study included 30 patients, of whom 12 (40%) classified as malnourished (PG-SGA ≥ 4) at baseline. Compared to well-nourished patients, malnourished patients were younger, were predominantly female, and had a higher body mass index, despite having lost more body weight in the past 6 months. All malnourished patients and 78% of the well-nourished patients received nutritional support. Consequently, a preoperative increase in caloric and protein intake and body weight were observed. Postoperatively, despite a further increase in caloric intake, a considerable decrease in protein intake, body weight, and muscle thickness was observed. CONCLUSION: Malnutrition is prevalent in patients undergoing pancreatic surgery. Nutritional support by a dedicated dietician is effective in enhancing patients' preoperative nutritional status. However, postoperative monitoring of adequate nutritional intake in patients could be improved.

Pancreatic STAT5 activation promotes KrasG12D-induced and inflammation-induced acinar-to-ductal metaplasia and pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.

What defines the "value" of robotic surgery for patients with gastrointestinal cancers? Perspectives from a U.S. Cancer Center.

The use of robotic surgery has experienced rapid growth across diverse medical conditions, with a notable emphasis on gastrointestinal cancers. The advanced technologies incorporated into robotic surgery platforms have played a pivotal role in enabling the safe performance of complex procedures, including gastrectomy and pancreatectomy, through a minimally invasive approach. However, there exists a noteworthy gap in high-level evidence demonstrating that robotic surgery for gastric and pancreatic cancers has substantial benefits compared to traditional open or laparoscopic methods. The primary impediment hindering the broader implementation of robotic surgery is its cost. The escalating healthcare expenses in the United States have prompted healthcare providers and payors to explore patient-centered, value-based healthcare models and reimbursement systems that embrace cost-effectiveness. Thus, it is important to determine what defines the value of robotic surgery. It must either maintain or enhance oncological quality and improve complication rates compared to open procedures. Moreover, its true value should be apparent in patients' expedited recovery and improved quality of life. Another essential aspect of robotic surgery's value lies in minimizing or even eliminating opioid use, even after major operations, offering considerable benefits to the broader public health landscape. A quicker return to oncological therapy has the potential to improve overall oncological outcomes, while a speedier return to work not only alleviates individual financial distress but also positively impacts societal productivity. In this article, we comprehensively review and summarize the current landscape of health economics and value-based care, with a focus on robotic surgery for gastrointestinal cancers.

Prediagnostic whole blood cadmium and molybdenum associated with pancreatic cancer in an American cohort.

Environmental exposures such as cadmium might be contributing to the increasing incidence of pancreatic cancer. Few prospective studies have examined the association between trace elements and pancreatic ductal adenocarcinoma (PDAC). We conducted a nested case-control study in participants aged 55-74 years at baseline from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort to examine the association between 12 trace elements measured in predignostic whole blood and PDAC. From May 1998 through December 2014, 318 incident PDAC cases were identified during follow-up to 16.7 years. Two controls (n = 636) alive when each case was diagnosed were selected and matched by age (+ 5 years), sex, calendar date of blood draw (2-month blocks), and race and ethnic group. We used multivariable adjusted conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Cadmium and molybdenum were associated with PDAC [highest compared to lowest quintile: cadmium OR=1.81; 95% CI: 01.12, 2.95; P-trend = 0.03; molybdenum OR=0.50; 95% CI: 0.32, 0.80; P-trend = 0.02]. The inverse molybdenum association was only observed among ever smokers (OR=0.31, 95% CI: 0.17, 0.58, P-trend= 0.003, P-interaction=0.03) with no association in never smokers. Lead, arsenic, and other trace elements were not associated with PDAC. Our results support that increasing prediagnostic whole blood cadmium increases while molybdenum reduces PDAC risk.

WTAP/IGF2BP3-mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c-Myc.

BACKGROUND: Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated. METHODS: The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC. RESULTS: GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition. CONCLUSIONS: Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC.

Characterization of Equilibrative Nucleoside Transport of the Pancreatic Cancer Cell Line: Panc-1.

Objectives: Gemcitabine, a first-line chemotherapeutic nucleoside analog drug (NAD) for pancreatic cancer, faces limitations due to drug resistance. Characterizing pancreatic cancer cells' transport characteristics may help identify the mechanisms behind drug resistance, and develop more effective therapeutic strategies. Therefore, in this study, we aimed to determine the nucleoside transport properties of Panc-1 cells, one of the commonly used pancreatic adenocarcinoma cell lines. Materials and Methods: To assess the presence of equilibrative nucleoside transporter-1 (ENT-1) in Panc-1 cells, we performed immunofluorescence staining, western blot analysis, and S-(4-nitrobenzyl)-6-thioinosine (NBTI) binding assays. We also conducted standard uptake assays to measure the sodium-independent uptake of [3H]-labeled chloroadenosine, hypoxanthine, and uridine. In addition, we determined the half-maximal inhibitory concentration (IC50) of gemcitabine. Statistical analyses were performed using GraphPad Prism version 8.0 for Windows. Results: The sodium-independent uptake of [3H]-labeled chloroadenosine, hypoxanthine, and uridine was measured using standard uptake assays, and the transport rates were determined as 111.1 ± 3.4 pmol/mg protein/10 s, 62.5 ± 4.8 pmol/mg protein/10 s, and 101.3 ± 2.5 pmol/mg protein/10 s, respectively. Furthermore, the presence of ENT-1 protein was confirmed using NBTI binding assays (Bmax 1.52 ± 0.1 pmol/mg protein; equilibrium dissociation constant 0.42 ± 0.1 nM). Immunofluorescence assays and western blot analysis also revealed ENT-1 in Panc-1 cells. The determined IC50 of gemcitabine in Panc-1 cells was 2 µM, indicating moderate sensitivity. Conclusion: These results suggest that Panc-1 is a suitable preclinical cellular model for studying NAD transport properties and potential therapies in pancreatic cancer and pharmaceutical research.

Surveillance after surgery for pancreatic cancer: a global scoping review of guidelines and a nordic Survey of contemporary practice.

OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

Fine-needle aspiration technique under endoscopic ultrasound guidance: A technical approach for RNA profiling of pancreatic neoplasms.

BACKGROUND: Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) has been a longstanding challenge. The prognosis of patients with PDAC depends on the stage at diagnosis. It is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA analysis. Most molecular studies are done using paraffin-embedded blocks; however, the integrity of DNA and RNA is often compromised in this format. Moreover, RNA isolated from human pancreatic tissue samples is generally of low quality, in part, because of the high concentration of endogenous pancreatic RNAse activity present. AIM: To assess the potential of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling, including next-generation sequencing (NGS). METHODS: Thirty-four EUS-FNA samples were included in this study: PDAC (n = 15), chronic pancreatitis (n = 5), pancreatic cysts (n = 14), mucinous cysts (mucinous cystic neoplasia/intraductal papillary mucinous neoplasia) n = 7, serous cystic neoplasms n = 5, and pseudocysts n = 2. Cyst material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy (TTNB). Samples were stored at -80 °C until analysis. RNA purity (A260/230, A260/280 ratios), concentration, and integrity (RIN) were assessed. Real-time polymerase chain reaction was conducted on all samples, and small RNA libraries were prepared from solid mass samples. RESULTS: RNA was successfully extracted from 29/34 (85%) EUS-FNA samples: 100% pancreatic adenocarcinoma samples, 100% chronic pancreatitis samples, 70% pancreatic fluid cyst samples, and 50% TTNB samples. The relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples (n = 29) including low-quality RNA specimens. Low concentration and nonoptimal RIN values (no less than 3) of RNA extracted from EUS-FNA samples did not prevent NGS library preparation. The suitability of cyst fluid samples for RNA profiling varied. The quality of RNA extracted from mucinous cyst fluid had a median RIN of 7.7 (5.0-8.2), which was compatible with that from solid neoplasms [6.2 (0-7.8)], whereas the quality of the RNA extracted from all fluids of serous cystic neoplasms and TTNB samples had a RIN of 0. CONCLUSION: The results demonstrate the high potential of EUS-FNA material for RNA profiling of various pancreatic lesions, including low-quality RNA specimens.

Early detection of pancreatic cancer in patients with recurrent pancreatitis: A case report.

BACKGROUND: Pancreatic cancer presents a challenge with its low early diagnosis and treatment rates, leading to high metastasis and mortality rates. The median survival time for advanced pancreatic cancer is a mere 3 months. However, there's hope: small pancreatic cancers diagnosed at an early stage (T1) or those less than or equal to 1 cm in diameter boast an impressive 5-year survival rate of nearly 100%. This underscores the critical importance of early pancreatic cancer detection for significantly improving prognosis. CASE SUMMARY: Pancreatic cancer, a malignant tumor of the digestive tract, poses challenges in both diagnosis and treatment due to its occult and atypical clinical symptoms. Clinically, patients with recurrent pancreatitis should be vigilant, as it may be indicative of pancreatic cancer, particularly in middle-aged and elderly patients. Here, we presented the case of a patient who experienced recurrent acute pancreatitis within a span of 2 months. During the initial episode of pancreatitis, routine imaging failed to identify the cause of pancreatic cancer. However, upon recurrence of acute pancreatitis, endoscopic ultrasonography (EUS) revealed a space-occupying lesion approximately 1 cm in size in the pancreatic body. Subsequent EUS coupled with fine-needle aspiration examination demonstrated atypical pancreatic gland epithelium. Ultimately, the patient underwent surgery and was diagnosed with an intraductal papillary mucinous tumor of the pancreas (severe epithelial dysplasia, focal cancer). CONCLUSION: We recommend EUS for patients with recurrent pancreatitis of unknown etiology to exclude early pancreatic cancer.

Neogambogic acid enhances anti-PD-1 immunotherapy efficacy by attenuating suppressive function of MDSCs in pancreatic cancer.

BACKGROUND: Anti-PD-1-based immunotherapy has limited benefits in patients with pancreatic cancer. Accumulating data indicate that natural products exert antitumor activity by remodeling the tumor immune microenvironment. It has been reported that neogambogic acid (NGA), an active natural monomer extracted from Garcinia, has anti-inflammatory and antitumor effects. Nevertheless, there are few systematic studies on the antitumor efficacy and immunomodulatory effects of NGA in pancreatic cancer. METHODS: An orthotopic mouse model of pancreatic cancer was established and were treated with different doses of NGA. Tumor growth and ascites were observed. Flow cytometry and immunohistochemistry (IHC) were used to investigate the tumor immune microenvironment. CD11b+ MDSCs were infused back into mice with pancreatic cancer to observe tumor progression after NGA treatment. Bone marrow cells were induced to differentiate into MDSCs, and the effects of NGA on MDSCs were analyzed and the underlying mechanism was explored. The effects of NGA combined with an anti-PD-1 antibody on pancreatic cancer were further tested. RESULTS: NGA significantly inhibited the tumor growth and improve ascites character in pancreatic cancer model mice. Flow cytometry and IHC analysis revealed that NGA decreased the MDSCs proportion and infiltration in the tumor microenvironment. Moreover, adoptive MDSCs largely attenuated the inhibitory effect of NGA on the progression of pancreatic cancer. In addition, we showed that NGA significantly promoted apoptosis and inhibited the differentiation, migration and immunosuppressive function of MDSCs and decreased level of STAT3 and p-STAT3. Furthermore, we demonstrated that NGA synergistically enhanced the efficacy of anti-PD-1 antibodies against pancreatic cancer. CONCLUSION: NGA inhibited the progression of pancreatic cancer by inhibiting MDSCs in the tumor microenvironment, and enhanced the efficacy of anti-PD-1 therapy in the treatment of pancreatic cancer.

Histone Lactylation Dynamics: Unlocking the Triad of Metabolism, Epigenetics, and Immune Regulation in Metastatic Cascade of Pancreatic Cancer.

Cancer cells rewire metabolism to sculpt the immune tumor microenvironment (TME) and propel tumor advancement, which intricately tied to post-translational modifications. Histone lactylation has emerged as a novel player in modulating protein functions, whereas little is known about its pathological role in pancreatic ductal adenocarcinoma (PDAC) progression. Employing a multi-omics approach encompassing bulk and single-cell RNA sequencing, metabolomics, ATAC-seq, and CUT&Tag methodologies, we unveiled the potential of histone lactylation in prognostic prediction, patient stratification and TME characterization. Notably, "LDHA-H4K12la-immuno-genes" axis has introduced a novel node into the regulatory framework of "metabolism-epigenetics-immunity," shedding new light on the landscape of PDAC progression. Furthermore, the heightened interplay between cancer cells and immune counterparts via Nectin-2 in liver metastasis with elevated HLS unraveled a positive feedback loop in driving immune evasion. Simultaneously, immune cells exhibited altered HLS and autonomous functionality across the metastatic cascade. Consequently, the exploration of innovative combination strategies targeting the metabolism-epigenetics-immunity axis holds promise in curbing distant metastasis and improving survival prospects for individuals grappling with challenges of PDAC.

Pancreatic ductal adenocarcinoma microenvironment: soluble factors and cancer associated fibroblasts as modulators of NK cell functions.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent pancreatic cancer and represents one of the most aggressive human neoplasms. Typically identified at advance stage disease, most PDAC tumors are unresectable and resistant to standard therapies. The immunosuppressive microenvironment in PDAC impedes tumor control but a greater understanding of the complex stromal interactions within the tumor microenvironment (TME) and the development of strategies capable of restoring antitumor effector immune responses could be crucial to fight this aggressive tumor and its spread. Natural killer (NK) cells play a crucial role in cancer immunosurveillance and represent an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target. This review describes some crucial components of the PDAC TME (collagens, soluble factors and fibroblasts) that can influence the presence, phenotype and function of NK cells in PDAC patients tumor tissue. This focused overview highlights the therapeutic relevance of dissecting the complex stromal composition to define new strategies for NK cell-based immunotherapies to improve the treatment of PDAC.

The Long Noncoding RNA PANDAR as a Prognostic and Diagnostic Biomarker in Panceratic Cancer .

Pancreatic cancer (PC) is a lethal complication in the world, affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Most PC patients are confronted with locally metastatic or advanced diseases in the asymptomatic phase, and about 80% have late diagnosis with metastasis. Recently, long noncoding RNAs (lncRNAs) have drawn attention as a novel biological regulation layer. They take part in the regulation of mRNA and can be used as a prognostic factor or drug target. Based on their functions as regulators of PC initiation and progress, the lncRNAs can be categorized as tumor suppressors or oncogenic. They can be considered as a target for finding new biomarkers for prognosis, diagnosis, monitoring, and treating drug response in PC. Therefore, the present study summarizes the lncRNAs role in PC and the probable strategies to deal with their expression and controlling tumorigenesis and detection of the prognosis of PC.

A comparison of target volumes drawn on arterial and venous phase scans during radiation therapy planning for patients with pancreatic cancer: the PANCRINJ study.

BACKGROUND: The planification of radiation therapy (RT) for pancreatic cancer (PC) requires a dosimetric computed tomography (CT) scan to define the gross tumor volume (GTV). The main objective of this study was to compare the inter-observer variability in RT planning between the arterial and the venous phases following intravenous contrast. METHODS: PANCRINJ was a prospective monocentric study that included twenty patients with non-metastatic PC. Patients underwent a pre-therapeutic CT scan at the arterial and venous phases. The delineation of the GTV was performed by one radiologist (gold standard) and two senior radiation oncologists (operators). The primary objective was to compare the Jaccard conformity index (JCI) for the GTVs computed between the GS (gold standard) and the operators between the arterial and the venous phases with a Wilcoxon signed rank test for paired samples. The secondary endpoints were the geographical miss index (GMI), the kappa index, the intra-operator variability, and the dose-volume histograms between the arterial and venous phases. RESULTS: The median JCI for the arterial and venous phases were 0.50 (range, 0.17-0.64) and 0.41 (range, 0.23-0.61) (p = 0.10) respectively. The median GS-GTV was statistically significantly smaller compared to the operators at the arterial (p < 0.0001) and venous phases (p < 0.001), respectively. The GMI were low with few tumors missed for all patients with a median GMI of 0.07 (range, 0-0.79) and 0.05 (range, 0-0.39) at the arterial and venous phases, respectively (p = 0.15). There was a moderate agreement between the radiation oncologists with a median kappa index of 0.52 (range 0.38-0.57) on the arterial phase, and 0.52 (range 0.36-0.57) on the venous phase (p = 0.08). The intra-observer variability for GTV delineation was lower at the venous phase than at the arterial phase for the two operators. There was no significant difference between the arterial and the venous phases regarding the dose-volume histogram for the operators. CONCLUSIONS: Our results showed inter- and intra-observer variability in delineating GTV for PC without significant differences between the arterial and the venous phases. The use of both phases should be encouraged. Our findings suggest the need to provide training for radiation oncologists in pancreatic imaging and to collaborate within a multidisciplinary team.

Preoperative metabolic syndrome and prognosis after pancreatectomy for pancreatic cancer: A retrospective study.

BACKGROUND: We conducted a retrospective study to investigate the impact of metabolic syndrome (MetS), its individual components, and the number of metabolic risk factors on the prognosis of pancreatic cancer (PC) following pancreatectomy. METHODS: MetS was defined as meeting any three of the following criteria: (1) waist circumference ≥85 cm in men or ≥80 cm in women; (2) triglycerides ≥150 mg/dL or receiving drug treatment for elevated triglycerides; (3) high-density lipoprotein cholesterol <40 mg/dL in men or <50 mg/dL in women or receiving drug treatment for reduced HDL-C; (4) systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg or receiving drug treatment for hypertension; and (5) fasting glucose, (FG) ≥100 mg/dL or receiving drug treatment for elevated glucose. The hazard ratio (HR) and 95% confidence interval (CI) were calculated by the Cox regression model. RESULTS: Six hundred and seven patients who underwent radical resection for PC were enrolled in this study. Among them, 352 patients presented with preoperative MetS. MetS was associated with shorter overall survival (OS) but not with shorter disease-free survival (DFS). The adjusted HR (95% CI) for the poor OS in patients with 3, 4, and 5 metabolic risk components (vs. ≤ 2) were 1.32 (1.03-1.84), 1.64 (1.18-2.29), and 1.96 (1.27-3.04), respectively (p < 0.05). Elevated FG emerged as a significant predictor for poor OS and DFS. CONCLUSIONS: This study highlights that preoperative MetS serves as a significant predictor for OS in patients with PC, with its predictive value escalating as the number of metabolic risk components increases.

A powerful machine learning approach to identify interactions of differentially abundant gut microbial subsets in patients with metastatic and non-metastatic pancreatic cancer.

Pancreatic cancer has a dismal prognosis, as it is often diagnosed at stage IV of the disease and is characterized by metastatic spread. Gut microbiota and its metabolites have been suggested to influence the metastatic spread by modulating the host immune system or by promoting angiogenesis. To date, the gut microbial profiles of metastatic and non-metastatic patients need to be explored. Taking advantage of the 16S metagenomic sequencing and the PEnalized LOgistic Regression Analysis (PELORA) we identified clusters of bacteria with differential abundances between metastatic and non-metastatic patients. An overall increase in Gram-negative bacteria in metastatic patients compared to non-metastatic ones was identified using this method. Furthermore, to gain more insight into how gut microbes can predict metastases, a machine learning approach (iterative Random Forest) was performed. Iterative Random Forest analysis revealed which microorganisms were characterized by a different level of relative abundance between metastatic and non-metastatic patients and established a functional relationship between the relative abundance and the probability of having metastases. At the species level, the following bacteria were found to have the highest discriminatory power: Anaerostipes hadrus, Coprobacter secundus, Clostridium sp. 619, Roseburia inulinivorans, Porphyromonas and Odoribacter at the genus level, and Rhodospirillaceae, Clostridiaceae and Peptococcaceae at the family level. Finally, these data were intertwined with those from a metabolomics analysis on fecal samples of patients with or without metastasis to better understand the role of gut microbiota in the metastatic process. Artificial intelligence has been applied in different areas of the medical field. Translating its application in the field of gut microbiota analysis may help fully exploit the potential information contained in such a large amount of data aiming to open up new supportive areas of intervention in the management of cancer.

Natural products as inhibitors against pancreatic cancer cell proliferation and invasion: possible mechanisms.

Pancreatic cancer is one of the gastrointestinal tumors with the lowest survival rate and the worst prognosis. At the time of diagnosis, the majority of patients have missed the opportunity for radical surgical resection and opt for chemotherapy as their primary treatment choice. And drug resistance emerges during the application of the most widely used chemotherapeutic regimens such as modified FOLFIRINOX regimen, gemcitabine monotherapy or 5-Fluorouracil combination therapy, which further reduces the therapeutic efficacy. Therefore, it is urgent to explore better treatment strategies for pancreatic cancer. In recent years, more and more studies have found that natural products have significant anti-pancreatic cancer properties. In this paper, we reviewed the possible mechanisms by which natural products inhibit the proliferation and invasion of pancreatic cancer cells, including the possible mechanisms of targeting the inhibition of the growth and proliferation regulatory pathways of pancreatic cancer cells, inducing apoptosis and autophagy of pancreatic cancer cells, inhibiting the EMT process of pancreatic cancer cells, and inhibiting the angiogenesis of pancreatic cancer. Meanwhile, natural products have also hindered the progress of their basic and clinical research due to the complexity of their composition and the limitation of biological extraction technology. Further exploration of the specific molecular mechanisms of natural products to inhibit the proliferation and invasion of pancreatic cancer cells, optimization of purification and preparation techniques, and enrichment of basic and clinical trials to verify their efficacy and safety may be the future direction of natural products in the field of anti-pancreatic cancer research.

Colloid Carcinoma of the Pancreas: A Rare Initial Presentation of Lynch Syndrome.

Patients with Lynch syndrome, most commonly associated with colorectal cancer, have an increased risk of developing other tumors including pancreatic ductal adenocarcinoma and precursor lesions, such as intraductal papillary mucinous neoplasms. Here, we present a case of a man in his early 20s who presented with a retroperitoneal mass involving the head of the pancreas. Following a pancreaticoduodenectomy combined with para-aortic lymphadenectomy, a pathologic diagnosis of colloid carcinoma, also known as mucinous noncystic carcinoma, of the pancreas was reported. Further testing established the diagnosis of Lynch syndrome. This case is unique because colloid carcinoma of the pancreas is rare and has never been reported as an initial presentation of Lynch syndrome.

Effect of smoking cessation on the likelihood of pancreatitis and pancreatic cancer.

INTRODUCTION: Tobacco smoking is a major risk factor for various diseases worldwide, including pancreatic exocrine diseases such as pancreatitis and pancreatic cancer (PC). Currently, few studies have examined the impact of smoking cessation on the likelihood of common pancreatic exocrine diseases. This study sought to determine whether smoking cessation would reduce pancreatitis and PC morbidity. METHODS: This cohort study used data from the UK Biobank (UKB) to examine the association between smoking status and the likelihood of pancreatitis and PC among 492855 participants. The subjects were divided into never smokers, ex-smokers, and current smokers. Using a multivariate-adjusted binary logistic regression model, we analyzed the relationship between different smoking conditions and the likelihood of pancreatitis and PC. Further, we studied the impact of smoking cessation on pancreatitis and PC compared with current smoking. RESULTS: After adjusting for potential confounders, current smokers had higher odds for acute pancreatitis (AP) (AOR=1.38; 95% CI: 1.18-1.61), chronic pancreatitis (CP) (AOR=3.29; 95% CI: 2.35-4.62) and PC (AOR=1.72; 95% CI: 1.42-2.09). People who quit smoking had comparable odds for the diseases as those who never smoked. Compared with current smokers, ex-smokers had reduced odds for AP (AOR=0.76; 95% CI: 0.64-0.89), CP (AOR=0.31; 95% CI: 0.21-0.46), and PC (AOR=0.62; 95% CI: 0.50-0.76). Subgroup analysis revealed reduced odds for these pancreatic diseases in males and females. CONCLUSIONS: Smokers have an increased odds for pancreatitis and pancreatic cancer. Moreover, smoking cessation can significantly reduce the odds for acute pancreatitis, chronic pancreatitis and pancreatic cancer.

Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)-GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor promotion and immune evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept toward considering GHR antagonists to improve chemotherapeutic outcomes in the highly chemoresistant PDAC.