Causal associations of tea consumption on risk of pancreatic adenocarcinoma and the mediating role of vascular endothelial growth factor D levels.

Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.

Rapidly progressive central retinal pigmented epithelium atrophy after Ivospemin (SBP-101) treatment for pancreatic adenocarcinoma.

Purpose: We report a case of retinal toxicity induced by SBP-101, a polyamine inhibitor for the treatment of metastatic pancreatic adenocarcinoma, presenting as rapidly progressive bilateral central retinal pigmented epithelium (RPE) atrophy in a patient with a silent ocular history. Observations: A 69-year-old female patient with a metastatic pancreatic adenocarcinoma visited our retina clinic referring a 6-months history of blurred vision and progressive visual field loss. One year before, she started administration of SBP-101 combined with nab-paclitaxel and gemcitabine to treat her malignancy. Baseline ophthalmological examination showed bilateral healthy retina an 20/20 visual acuity (VA). After the second monthly cycle of SBP-101, the patient experienced significant visual loss in both eyes, with VA decreasing to 20/50 in right eye (RE) and to 20/40 in left eye (LE). In the suspect of a cancer associated retinopathy (CAR), the patient underwent bilateral injection of intravitreal slow-releasing dexamethasone, with poor clinical outcomes. Concomitant testing for anti-enolase and anti-recoverin antibodies gave negative results, while electroretinography showed borderline but within the limit values in both eyes. At 6 months, VA was 20/5000 in RE and 20/4000 in LE and the patient referred significant limitations in everyday life. Ultra-wide field fundus photography showed a bilateral, roundish area of irregular pigment loss involving the entire macula and extending beyond the arcades. Ultra-wide autofluorescence showed a central area of hypo-autofluorescence surrounded by a ring of alternating hyper- and hypo-autofluorescence areas. Optical coherence tomography showed bilateral atrophy of the subfoveal RPE and disruption of the ellipsoid zone. Optic disc examination was within the limits. No treatment was possible. Conclusion and Importance: In conclusion, ophthalmologists should be aware of the existence of a sight-threatening side effect of SPB-101 administration, since we highlighted a massive bilateral RPE atrophy rapidly developing after the second drug injection.

Sister Mary Joseph's Nodule as a Cutaneous Expression of Metastatic Pancreatic Adenocarcinoma.

A Sister Mary Joseph's nodule (SMJN) is characterized by a palpable umbilical nodule and is often a clinical indicator of the metastasis of an advanced abdominal or pelvic malignancy. Observing the cutaneous manifestation of an abdomino-pelvic malignancy is a relatively rare phenomenon due to the appearance of visible changes in the later stages of the disease. With the pancreas being a less common primary tumor site for SMJN, this case report describes a 57-year-old male diagnosed with metastatic pancreatic adenocarcinoma with a SMJN. With a history of alcohol use disorder and alcohol pancreatitis, this patient presented to the Emergency Department with worsening abdominal pain and vomiting. A computed tomography (CT) scan with intravenous (IV) contrast revealed a mass in the patient's rectum and a lobulated mass traversing the anterior abdominal wall, which extended into the umbilicus. A physical exam revealed the presence of an umbilical lesion. A biopsy of the umbilical lesion revealed metastatic adenocarcinoma that favored pancreaticobiliary origin. The results of the umbilical biopsy and CT imaging established the diagnosis of SMJN secondary to pancreatic cancer metastasis to the umbilicus.

Early Onset Pancreatic Adenocarcinoma (EOPAC): presentation, clinical course and treatment outcomes in comparison to Average Onset Pancreatic Adenocarcinoma (AOPAC): a retrospective cohort study.

BACKGROUND: Pancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study. PATIENTS AND METHODS: A retrospective analysis of patients' records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included. RESULTS: The study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013). CONCLUSION: Patients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt.

Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) for Pancreatic Adenocarcinoma: A Review.

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest neoplasms in the world. Although various advancements in the treatment and management of this disease have been made, no significant overall survival benefit has been achieved. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been proposed as a treatment for patients who are unfit for surgery or with inoperable PDAC. We conducted a literature review of the PubMed and Embase databases to identify and analyze studies on the use of EUS-RFA in inoperable PDAC. Eleven studies with a total of 122 patients were analyzed to assess the population characteristics, feasibility and safety of the procedure, and overall survival of the population. Technical success was achieved in 95.1% of cases, and no intraoperative complications were reported. The most common early complication reported was abdominal pain (21 out of 122 patients) with a total early complication rate of 29.6%, and none of these complications affected hospital stays or post-procedure recovery. Late complications were reported in four patients (3.2%). Post-procedure cytoreduction was achieved in all patients, although disease progression was reported in 119 of 122 patients. The overall survival rate did not differ from that reported in the literature. We found that EUS-RFA could be a valid palliative option for inoperable patients, a bridge for surgery reducing the size of the tumor and its vascular relationship, or a first-line therapy in a subset of selected patients. Larger cohort and prospective studies should be conducted to establish guidelines for this procedure.

Splenic rupture secondary to pancreatic malignancy invasion: A rare case.

Malignancy is a rare etiology of splenic rupture, with most documented cases resulting from hematologic cancers. There have been very few reports of splenic rupture resulting from invasion or metastasis of adenocarcinoma and even fewer reports resulting from specifically pancreatic adenocarcinoma. In this case report, we outline the clinical course of a 60-year-old male with splenic rupture and hemoperitoneum following a ground level fall who was transferred to the Shock Trauma Center (STC) from a local emergency department. Outside of the ruptured spleen, no other traumatic injuries were found on examination or imaging. Due to the initial concern for traumatic etiology, exploratory laparotomy was performed with splenectomy and distal pancreatectomy. Postoperative pathology results revealed pancreatic adenocarcinoma with splenic invasion staged pT3N0. This report provides a novel example of splenic rupture in the background of locally advanced pancreatic adenocarcinoma and further solidifies the importance of maintaining a broad differential in cases of seemingly innocuous trauma.

An unusual pAIR: Anti-PKM2 antibody and occult pancreatic adenocarcinoma.

Purpose: To describe the clinical, laboratory and multimodal imaging findings in paraneoplastic autoimmune retinopathy (p-AIR) associated with anti-pyruvate kinase M2 antibody (anti-PKM2) and occult pancreatic adenocarcinoma. Observations: A 70 year old male with blurred vision, nyctalopia and concurrent difficulty with glucose control had retinal vascular attenuation and diffuse punctate pigment clumping in both eyes. Multimodal imaging demonstrated corresponding stippled hypofluorescence on fluorescein angiography, stippled hyperautofluorescence and a hyperautoflourescent macular ring with fundus autofluorescence, and focal hyperreflectivity at the level of the RPE-Bruch's membrane complex with diffuse loss of outer retinal layers on ocular coherence tomography. In addition, diffuse ganglion cell loss and severe visual field constriction were present. Genetic testing for retinitis pigmentosa was normal. Screening for anti-retinal antibodies was positive for only anti-PKM2. Systemic evaluation revealed previously undiagnosed adenocarcinoma of the pancreas. Conclusions and importance: Anti-PKM2 in the setting of autoimmune retinopathy may be associated with occult pancreatic cancer. The diagnosis of pAIR should be considered and systemic investigation for occult malignancy initiated even in the absence of more commonly associated anti-retinal antibodies.

Comprehensive bioinformatics analysis of the prognostic value and immune infiltration of CAPN2 in pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with a poor prognosis, highlighting an urgent requirement for effective biomarkers for its early diagnosis and prognosis prediction. CAPN2, a calcium-dependent protease, has been implicated in various cancers, but its role in PAAD remains unclear. METHODS: In this study, we utilized multiple bioinformatics methods, including differential expression, survival, correlation, and enrichment analyses, to investigate the prognostic value of CAPN2 in PAAD using data from the TCGA and GEO databases. Additionally, the correlation between CAPN2 expression and the tumor microenvironment (TME), immunotherapy potential, and drug sensitivity was also explored. RESULTS: CAPN2 was upregulated in PAAD tissues and was correlated with higher tumor grade. And high expression of CAPN2 was significantly associated with reduced overall survival, establishing it as an independent prognostic biomarker for PAAD. Enrichment analysis implicated that CAPN2 was involved in multiple biological processes and pathways associated with tumor immunity. Furthermore, CAPN2 expression had a negative correlation with immune cell infiltration and a positive association with tumor mutational burden, which may have potential implications for immunotherapy strategies. CONCLUSIONS: CAPN2 is a promising biomarker for PAAD prognosis and a potential therapeutic target. Its association with the TME and immunotherapy response highlights its importance in PAAD progression and patient outcomes, warranting further investigation into its role and potential clinical applications.

A comparative analysis of robotic versus laparoscopic total pancreatectomy: insights from the National Cancer Database.

Total pancreatectomy is a complex procedure used in the management of pancreatic cancer. While minimally invasive techniques have been increasingly adopted, limited data exist comparing robotic total pancreatectomy (RTP) and laparoscopic total pancreatectomy (LTP). This study evaluates the utilization, short- and long-term outcomes of RTP and LTP using the National Cancer Database. Patients with stages I-III pancreatic adenocarcinoma who underwent RTP or LTP between 2010 and 2019 were identified. Patient demographics, treatment characteristics, pathologic outcomes, postoperative outcomes, and overall survival were compared. Multivariable logistic regression and Cox proportional-hazards models were used to assess the association of surgical approach with outcomes. Of the 995 patients included, 188 (19%) underwent RTP and 807 (81%) underwent LTP. The utilization of minimally invasive techniques increased over time, with RTP accounting for 24% of cases in 2019. RTP had lower conversion rates than LTP (16% vs. 24%, p = 0.031), but this difference was not significant after adjusting for confounders. Postoperative outcomes, including length of stay, 30-day readmission, and 30- and 90-day mortality, were similar between RTP and LTP. The median overall survival was 22.3 months for RTP and 23.6 months for LTP (p = 0.647). RTP and LTP demonstrate comparable perioperative, pathological, and oncological outcomes for the management of pancreatic adenocarcinoma. Despite the increasing adoption of minimally invasive total pancreatectomy, it remains a rare operation and should be performed in experienced centers to optimize outcomes.

Modeling Overall Survival in Patients With Pancreatic Cancer From a Pooled Analysis of Phase II Trials.

BACKGROUND: We evaluated the validity of surrogacy of progression-free survival (PFS) or time-to-progression (TTP) and overall response rate (ORR) in phase II trials of pancreatic ductal adenocarcinoma (PDAC). In addition, we explored the impact of predictive variables on overall survival (OS) and developed an optimal OS model. METHODS: We analyzed 1867 clinical endpoint from 619 phase II PDAC trials with a systematic search from PubMed. Endpoint correlations were determined by Spearman's rank correlation. The assessed predictive factors included PFS/TTP, treatment size, therapy type, stage, and previous treatment. The relationship between predictors and OS was explored by a gamma generalized linear model (GLM) with a log-link function and compared with linear models. RESULTS: The Spearman rank correlation coefficient between PFS/TTP and OS was 0.88 (95% confidence interval [CI] 0.85-0.89; p < 0.0001; n = 610) and between ORR and OS was 0.58 (0.52-0.64; p < 0.0001; n = 514). Model comparison favored the GLM model over the linear model, offering more accurate predictions for higher OS values. Consequently, PFS/TTP was the strongest predictor (pseudo-R2 = 0.75), with 1 added median PFS/TTP month associated with 13% (95% CI 13%-14%) increase in median OS. Subgroup analysis revealed that chemotherapy conferred significantly longer OS compared to targeted therapy in 1-Agent and 2-Agent trials, exhibiting a "very large" and "medium" effect size, respectively (rank biserial, rrb = 0.40 [95% CI 0.22-0.56] and rrb = 0.29 [0.16-0.41], both p < 0.0001), although inconsistent efficacy in 3-Agent trials (rrb = 0.12 [-0.07-0.30], p = 0.21). CONCLUSIONS: PFS/TTP is a more reliable surrogate than ORR and a strong predictor of OS in phase II trials of pancreatic cancer. Moreover, gamma GLM (log-link function) is a robust tool for modeling positively skewed survival data with non-constant variance, thus can be applied to other cancers' OS data of such nature.

HKDC1 promotes autophagy and proliferation in pancreatic adenocarcinoma through interaction with PARP1 and poly(ADP-ribosyl)ation.

BACKGROUND: HKDC1 has been shown to play an important role in promoting malignant progression of pancreatic adenocarcinoma (PAAD), but the exact mechanism is unclear. This study aimed to investigate the function of HKDC1 in autophagy activation and cell proliferation. METHODS: By GSEA analysis of TCGA data of PAAD, we found that HKDC1 was closely associated with autophagy. We evaluated the effects of HKDC1 knockdown and overexpression on the expression of LC3B, an autophagy marker, and Cyclin D1 and PCNA, cell proliferation-associated proteins, by Western blotting (WB) and transmission electron microscopy (TEM) analysis. RESULTS: Knockdown of HKDC1 decreased LC3B expression and led to a decrease in the accumulation of autophagic vesicles and autophagic lysosomes, while overexpression of HKDC1 produced the opposite effect. Meanwhile, HKDC1 overexpression significantly promoted the proliferation of PAAD cells and increased the expression levels of Cyclin D1 and PCNA. Further studies showed that HKDC1 enhanced PARP1's own poly ADP-ribosylation (PARylation) activity by interacting with PARP1, which in turn promoted autophagy. In vivo experiments showed that knockdown of HKDC1 significantly inhibited the growth of pancreatic cancer cells in nude mice in vivo, reduced tumor volume and weight, and down-regulated the expression of PARP1, LC3, Cyclin D1 and PCNA. CONCLUSION: HKDC1 plays a critical role in the malignant progression of PAAD by activating autophagy and promoting cell proliferation. Our findings suggest that targeting HKDC1 and its downstream signaling pathways may provide novel strategies for PAAD treatment.

Pembrolizumab in Combination with Folfirinox for Treatment of Advanced Pancreatic Adenocarcinoma With MSI-H.

Pancreatic cancer is one of the four most common causes of cancer-related death in the United States. Our patient had metastatic pancreatic cancer with a high tumour burden. He was trialled on an unconventional treatment of combination immunotherapy and chemotherapy. It resulted in decreased cancer burden and decreased FDG activity on a PET scan. Further studies are needed for standard pancreatic cancer treatment. LEARNING POINTS: Very few patients survive pancreatic cancer, especially metastatic disease. Our patient is doing very well after a few years.There is little evidence for concurrent use of chemotherapy and immunotherapy. Our patient received it and has had no new lesions, and there has been an improvement on imaging.

Solitary metastasis to the head of the pancreas from lung adenocarcinoma mimicking pancreatic ductal adenocarcinoma: A case report.

Solitary pancreatic metastasis is a rare cause of pancreatic neoplasm. Pancreatic ductal adenocarcinoma is the primary differential consideration when a solitary pancreatic mass is diagnosed, as it is the most common solitary solid pancreatic neoplasm. A majority of pancreatic ductal adenocarcinomas arise in the region of the head of the pancreas; however, specific neoplastic and non-neoplastic lesions can occur at or adjacent to the pancreatic head, which can mimic a pancreatic ductal adenocarcinoma. Therefore, a histopathological diagnosis is essential for confirming pancreatic ductal adenocarcinoma. Isolated solitary metastasis from primary lung adenocarcinoma is a rare cause of a solitary pancreatic head mass. We report a case in which imaging and pathology were integral to the diagnosis of a solitary lung adenocarcinoma metastasis to the head of the pancreas, which ultimately guided appropriate patient management.

Curative intent treatment for pancreatic duct adenocarcinoma invade superior mesenteric vein.

Pancreatic duct adenocarcinoma (PDAC) accounts for about 85-90% of all solid pancreatic tumors, which is well-known for poor prognosis and high morbidity. Despite the massive advent of chemotherapy and radiotherapy in recent years, surgical removal is still considered the cornerstone management option in this situation. Pancreaticoduodenectomy or Whipple procedure is generally contraindicated in metastasis or tumors that encase more than 50% of vessels. Vascular reconstruction is a state-of-the-art technique which requires the remarkable involvement of vascular experts in the setting of PDAC-invading vessels. In this article, we present an exceptional case of a 38-year-old male patient who underwent radical resection for advanced pancreatic cancer with superior mesenteric vein reconstruction by a great saphenous vein.

Fibrolytic vaccination against ADAM12 reduces desmoplasia in preclinical pancreatic adenocarcinomas.

A hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.g., the disintegrin metalloprotease, ADAM12. Previous studies have shown that immunotherapeutic ablation of ADAM12+ cells reduces fibrosis in various organs. In preclinical mouse models of PDAC, we observe ADAM12 expression in CAFs as well as in tumor cells but not in healthy mouse pancreas. Therefore, we tested prophylactic and therapeutic vaccination against ADAM12 in murine PDAC and observed delayed tumor growth along with a reduction in CAFs and tumor desmoplasia. This is furthermore associated with vascular normalization and alleviated tumor hypoxia. The ADAM12 vaccine induces a redistribution of CD8+ T cells within the tumor and cytotoxic responses against ADAM12+ cells. In summary, vaccination against the endogenous fibroblast target ADAM12 effectively depletes CAFs, reduces desmoplasia and delays the growth of murine PDACs. These results provide proof-of-principle for the development of vaccination-based immunotherapies to treat tumor desmoplasia.

Chemotherapy-Induced Cutaneous Sclerosis: A Rare Clinical Finding.

Scleroderma-like cutaneous sclerosis has been reported as a rare adverse reaction to several drugs, including the chemotherapeutical agent paclitaxel, used in therapeutic regimens for several malignancies. The sclerosis is usually limited to the skin, most commonly presenting in the lower limbs after weeks to months of therapy but is often refractory to treatment and progresses even after discontinuation of the offending agents, with significant resulting morbidity. We report a rare case of severe cutaneous sclerosis secondary to chemotherapy with nab-paclitaxel and gemcitabine, which did not respond to treatment and led to discontinuation of chemotherapy.

MLPH regulates EMT in pancreatic adenocarcinoma through the PI3K-AKT signaling pathway.

Pancreatic adenocarcinoma (PAAD) is an extremely malignant tumor, and most patients develop postoperative metastases. Melanophilin (MLPH) is involved in the progression of various tumors, but its molecular mechanisms and role in pancreatic cancer progression are unknown. In this study, differential MLPH expression in cancer tissues and the adjacent tissues was evaluated using the Gene Expression Profiling Interaction Analysis 2 (GEPIA 2) and Human Protein Atlas (HPA) databases. The role of MLPH in PAAD proliferation, invasion, and migration in vitro was explored via clone formation, Cell Counting Kit-8 assay, Transwell assay, and western blot. The in vivo validation of function was performed using a metastatic nude mouse model. The result showed that the pancreatic cancer tissues had significantly higher MLPH expression levels than the noncancerous pancreatic tissues. MLPH expression changes were related to PAAD cell proliferation, invasion, and migration. The western blotting demonstrated that PAAD cells had reduced Epithelial-mesenchymal transition (EMT)-related marker expression. Furthermore, overexpressing MLPH enhanced cell proliferation, migration, and invasion, and increased EMT-related marker expression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the molecular mechanism underlying the effect of MLPH on PAAD was significantly related to the PI3K-AKT pathway. LY294002 blocked the MLPH overexpression-mediated enhanced cell invasion and migration and inhibited EMT-associated marker expression. Conversely, 740Y-P reversed the inhibitory effects of MLPH downregulation and led to cell migration, invasion, and EMT. MLPH regulated EMT to mediate PAAD cell invasive migration through the PI3K-AKT pathway. The results indicated that MLPH is a possible target for blocking PAAD metastasis.

Insulin receptor substrate 1 is a novel member of EGFR signaling in pancreatic cells.

Pancreatic ductal adenocarcinoma is an extremely incurable cancer type characterized by cells with highly proliferative capacity and resistance against the current therapeutic options. Our study reveals that IRS1 acts as a bridging molecule between EGFR and IGFR/InsR signalization providing a potential mechanism for the interplay between signaling pathways and bypassing EGFR-targeted or IGFR/InsR-targeted therapies. The analysis of IRS1 phosphorylation status in four pancreatic cell lines identified the impact of EGFR signaling on IRS1 activation in comparison with InsR/IGFR signaling. Significantly reduced viability was observed in IRS1-silenced cells even upon EGF stimulation showing the critical role of IRS1 in the EGFR signaling network in both malignant and normal pancreatic cells. This study also demonstrated that EGFR binds directly to IRS1 and at least on two tyrosine sites, Y612 and Y896, IRS1 becomes phosphorylated in response to EGF stimulation. Mechanistically, the EGFR-mediated phosphorylation of IRS1 can further activate the MAPK signaling pathway with the recruitment of GRB2 protein. Collectively, in this study, IRS1 was identified as a crucial regulator in the EGFR signaling suggesting IRS1 as a potential target for more durable responses to targeted PDAC therapy.

Expression, potential biological behaviour and clinical significance of MCM3 in pancreatic adenocarcinoma: a comprehensive study integrating high throughput sequencing, CRISPR screening and in-house immunohistochemistry.

BACKGROUND: Minichromosome maintenance complex component 3 (MCM3) plays a key role in various tumours. However, it remains largely unknown what the specific role and clinical significance of MCM3 in pancreatic adenocarcinoma (PAAD) are. MATERIALS AND METHODS: We integrated high-throughput data from PAAD worldwide to analyse the expression level of MCM3 mRNA. We used immunohistochemistry to analyse MCM3 protein expression levels in 145 cases in the PAAD group and 29 cases in the non-PAAD group. We also mainly analysed the necessity of MCM3 for PAAD growth based on CRISPR screen data. In addition, we used enrichment analysis and protein-protein interaction networks to explore the molecular mechanism of MCM3 in PAAD. We also analysed the correlation between MCM3 expression, components of the immune microenvironment in PAAD tissue and clinical prognosis. RESULTS: In PAAD, we observed for the first time that MCM3 was significantly highly expressed at both the mRNA (SMD = 0.67, 95% CI: 0.38 ∼ 0.96) and the protein level (p < 0.05). The mRNA (AUC = 0.78, 95% CI: 0.74 ∼ 0.81; sensitivity = 0.66, 95% CI: 0.55 ∼ 0.76; specificity = 0.76, 95% CI: 0.67 ∼ 0.84) and protein (AUC = 0.929) expression levels of MCM3 had a good ability to distinguish between PAAD and non-PAAD tissue. There was heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells. MCM3 played an essential role in PAAD growth, through abnormal DNA replication, p53 signalling and cell cycle checkpoints. PAAD with high MCM3 expression was sensitive to c-75, brivanib, flavopiridol and VNLG/124 drugs, with stable molecular docking models. CONCLUSION: MCM3 is likely to be a critical element in promoting the initiation and growth of PAAD. Flavopiridol may exert its anti-PAAD effect through the interaction between MCM3, classic CDK1 targets in the cell cycle checkpoint and p53 pathway as well as related molecules in other pathways.

MCM3 could potentially play a crucial role in promoting the onset and growth of PAAD.There is heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells.The interplay between MCM3, well-established CDK1 targets in the cell cycle checkpoint and p53 pathway, along with relevant molecules in other pathways, may mediate the anti-pancreatic adenocarcinoma (PAAD) effect of flavopiridol.

Comments and illustrations of the European Federation of Societies for Ultrasound in Medicine contrast-enhanced ultrasound guidelines. Rare pancreatic tumors, imaging features on transabdominal ultrasound and EUS with contrast enhancement: Rare epithelial pancreatic tumors: solid pseudopapillary neoplasm, acinar cell carcinoma, mixed neuroendocrine-non-neuroendocrine neoplasms, some rare subtypes of pancreatic adenocarcinoma and pancreatoblastoma.

Rare malignant pancreatic lesions are systematically reported in this review. The focus is on the imaging appearance of the rare epithelial pancreatic tumors such as the solid pseudopapillary neoplasm, acinar cell carcinoma, rare subtypes of adenocarcinoma, and pancreatoblastoma as seen on ultrasound, EUS, and contrast-enhanced ultrasound or EUS. The present overview summarizes the data and shows that not every pancreatic tumor is likely to be the most common entities of ductal adenocarcinoma or neuroendocrine tumor.