Tumors Of Pancreas Research Articles

Endoscopic Ultrasound in Solid Pseudopapillary Tumor of the Pancreas: About two Clinical Cases

Background: Solid pseudopapillary tumor of the pancreas (SPPT) or Frantz's tumor is a rare exocrine pancreatic tumor, it generally occurs among females within the second or third decade of life. The clinical symptomatology is non-specific, frequently presenting as a slowly growing abdominal mass without any biological abnormalities. The imaging usually shows a well-limited mass with little vascularity. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) helps the diagnosis. The treatment of these tumors is surgical, and the prognosis is excellent after complete resection. We report two new cases of Frantz tumor, detailing the clinicopathological features of this rare neoplasm. Case presentation: Case 1: A 19-year-old woman presented with middle upper abdominal pain. Computed tomography (CT) scan showed a solitary encapsulated mass in the pancreatic body. Endoscopic ultrasound showed a regular, well-defined, heterogenous lesion, measuring 50 × 46 cm, in the pancreatic body. endoscopic ultrasound fine-needle aspiration was then performed with cytopathological analysis compatible with SPPT. Body computed tomography confirmed the absence of metastases and she underwent a central pancreatectomy. 12 months after the diagnosis, she remains asymptomatic, continuing regular follow-up. Case 2: A 22-year-old woman presented with epigastric pain and weight loss. CT scan revealed a single 5 cm well defined mass in the pancreatic head. EUS showed a well-defined heterogenous hypoechoic encapsulated mass in the pancreatic head, measuring 64 × 44 mm; EUS-FNA was performed and cytopathological analysis was suggestive of SPPT. She underwent conventional cephalic duodenopancreatectomy. She presented septic postoperative complications, with a favorable outcome after medical and surgical therapy. she remains asymptomatic, after 6 months follow-up. Conclusion: Solid pseudo papillary pancreatic tumor is a rare exocrine low-grade neoplasm. EUS is a sensitive tool in the diagnosis of SPPT, identifying and characterizing the pathologic lesions, and allowing EUS-FNA with cytomorphological recognition, making it an invaluable tool for establishing diagnosis, helping clinical management and surgical planning.

Toceranib phosphate in the management of canine insulinoma: A retrospective multicentre study of 30 cases (2009-2019).

BackgroundInsulinomas are the most common tumour of the endocrine pancreas in dogs. These malignant tumours have a high metastatic rate and limited chemotherapeutic options. The multi‐receptor tyrosine kinase inhibitor sunitinib malate has benefit in the treatment of metastatic insulinoma in people. Toceranib phosphate, an analogous veterinary agent, may provide benefit for dogs.MethodsA retrospective study describing the extent and duration of clinical outcomes and adverse events (AEs) in dogs diagnosed with insulinoma and receiving toceranib.ResultsRecords for 30 dogs diagnosed with insulinoma and having received toceranib were identified from a medical record search of five university and eight referral hospitals. The median progression‐free interval and overall survival time were 561 days (95% confidence interval (CI): [246, 727 days]) and 656 days (95% CI: [310, 1045 days]), respectively. Of the dogs for which the canine Response evaluation criteria for solid tumours tool could be applied, the majority (66.7%) showed either a complete response, partial response or stable disease. Time to clinical progression was associated with prior intervention and type of veterinary practice. Larger dogs were at increased risk for disease progression and death. No novel AEs were reported.ConclusionsMost dogs diagnosed with insulinoma and receiving toceranib appeared to have a clinical benefit. Randomised, prospective studies are needed to better elucidate and objectively quantify the potential effect and survival benefit of toceranib therapy for management of insulinoma in dogs.

Pancreatic cystic lesions: An 11 years (2010–2020) of experience at Usmanu Danfodiyo University teaching hospital, Sokoto

Background: Pancreatic cystic lesions are heterogeneous lesions that could be benign, borderline, or malignant. Neoplastic cystic lesions/tumours are rare tumours of the exocrine pancreas; difficult to diagnose preoperatively, and they account for 2%–10% of pancreatic tumours. Pancreatic pseudocyst is the most typical benign cystic pancreatic lesion arising from pancreatic ductal inflammation or ductal disruption. Both benign and malignant cystic pancreatic lesions are amenable to surgical treatments, with a good prognosis. Aim: The aim is to present our 11yrs of experience in the management of pancreatic cystic lesions. Materials and Methods: We conducted a retrospective review of pancreatic cystic lesions managed at the General Surgery Unit of Usmanu Danfodiyo University, Sokoto, Nigeria, from 2010 to 2020. A retrospective review of the case notes of patients was done with an emphasis on biodata, presentation, investigations treatment offered, complications, and follow-up were analysed using the Statistical Package for the Social Science (SPSS) version 22, Inc. (Chicago II, USA). Results: We managed 28 patients over 11 years. Three patients had pancreatic cystic tumours, whereas 25 patients had pancreatic pseudocysts. The age ranges of the patient with pancreatic cystic tumours are 29–50 years with a male-to-female ratio of 2:1. All the patients had tumour excision with histology revealing two pseudopapillary tumours of the pancreas and one serous cystadenoma. The age range of patients with pseudocyst is 27–42 years with a male-to-female ratio of 1:3.1, and most of the patient had internal drainage. Conclusion: Pancreatic cystic tumours are uncommon pancreatic neoplasms that are amenable to surgical interventions with a good prognosis. Pancreatic pseudocyst was seen mainly in females within the young age group. Both benign and neoplastic pancreatic cystic lesions are amenable to surgical intervention with a good prognosis.

Clinical outcomes of patients with pancreatic tumors discussed in Tumor Board.

the recommendations of the decisions made by the Tumor Board (TB) should be followed to identify barriers that may interfere with the execution of the previously decided, best care for the patient. The aim of this study is to assess whether the TB conduct decision was performed in patients with pancreatic tumors, their life status 90 days after the TB decision, and to analyze the reasons why the conduct was not performed. we conducted a retrospective study with patients with pancreas tumors, evaluated between 2017 and 2019. We collected data on epidemiological status, whether the TB procedure was performed, the reason for not performing it, life status 90 days after the TB decision, and how many times each patient was discussed at a meeting. We compared categorical variables using the chi square test, numerical variables were presented as means and standard deviation. we studied 111 session cases, in 95 patients, 86 (90.5%) diagnosed with cancer. After 90 days of TB, 83 patients (87.37%) remained alive, 9 had (9.47%) died, and 3 (3.16%) were lost to follow-up. The TB decision was not observed in 12 (10.8%) cases and the reasons were: 25% (3) for loss of follow-up, 8.33% (1) for patient refusal, and 66.67% (8) due to clinical worsening. The cases of patients with metastases had a lower rate of TB conduct compliance (p=0.006). the TB conduct was performed in most cases and the most evident reason for non-compliance with the conducts is the patient's clinical worsening.

Targeting protumor factor chitinase-3-like-1 secreted by Rab37 vesicles for cancer immunotherapy.

Background: Chitinase 3-like-1 (CHI3L1) is a secretion glycoprotein associated with the immunosuppressive tumor microenvironment (TME). The secretory mode of CHI3L1 makes it a promising target for cancer treatment. We have previously reported that Rab37 small GTPase mediates secretion of IL-6 in macrophages to promote cancer progression, whereas the roles of Rab37 in the intracellular trafficking and exocytosis of CHI3L1 are unclear.Methods: We examined the concentration of CHI3L1 in the culture medium of splenocytes and bone marrow derived macrophages (BMDMs) from wild-type or Rab37 knockout mice, and macrophage or T cell lines expressing wild type, active GTP-bound or inactive GDP-bound Rab37. Vesicle isolation, total internal reflection fluorescence microscopy, and real-time confocal microscopy were conducted. We developed polyclonal neutralizing-CHI3L1 antibodies (nCHI3L1 Abs) to validate the therapeutic efficacy in orthotopic lung, pancreas and colon cancer allograft models. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37 and CHI3L1, and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from cancer patients.Results: We demonstrate a novel secretion mode of CHI3L1 mediated by the small GTPase Rab37 in T cells and macrophages. Rab37 mediated CHI3L1 intracellular vesicle trafficking and exocytosis in a GTP-dependent manner, which is abolished in the splenocytes and BMDMs from Rab37 knockout mice and attenuated in macrophage or T cell lines expressing the inactive Rab37. The secreted CHI3L1 activated AKT, ß-catenin and NF-κB signal pathways in cancer cells and macrophages to foster a protumor TME characterized by activating M2 macrophages and increasing the population of regulatory T cells. Our developed nCHI3L1 Abs showed the dual properties of reducing tumor growth/metastases and eliciting an immunostimulatory TME in syngeneic orthotopic lung, pancreas and colon tumor models. Clinically, high plasma level or intratumoral expression of CHI3L1 correlated with poor survival in 161 lung cancer, 155 pancreatic cancer and 180 colon cancer patients.Conclusions: These results provide the first evidence that Rab37 mediates CHI3L1 secretion in immune cells and highlight nCHI3L1 Abs that can simultaneously target both cancer cells and tumor microenvironment.

Anaesthetic Management of a Patient with Von-Hippel-Lindau Syndrome: A Conglomeration of Perplexities

Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease with multisystem involvement. Tumours associated with VHL include, hemangioblastomas of the spine and brain, retinal capillary hemangioblastomas, renal cell carcinoma, pheochromocytoma, and neuroendocrine tumours of pancreas. We present a case of a 54 year old female second-degree uterovaginal prolapse scheduled for laparoscopic assisted vaginal hysterectomy. She was diagnosed with adult polycystic kidney disease, pheochromocytoma, parathyroid adenoma, vertebral hemangioma and multiple renal and hepatic cysts. Though genetic testing was not feasible, the co-existing systemic manifestations in this patient were strongly suggestive of Von Hippel Lindau syndrome. Owing to the multi-morbidities, central neuraxial block was deemed appropriate as opposed to general anaesthesia. In concert with the surgeons, it was decided to change the surgical plan to vaginal hysterectomy and avoid adrenaline infiltration at the surgical site, as it is known to precipitate arrythmias. We placed an intra-arterial catheter for continuous blood pressure monitoring before administration of the subarachnoid block and co-loaded the patient with fluids to avoid any drastic hypotension. The patient remained hemodynamically stable throughout the procedure, which could be attributed to extensive pre-operative work-up multi-disciplinary pre-operative optimization and synergistic management with surgical team. Providing anaesthesia to patients with multisystem involvement such as Von Hippel Lindau syndrome can be very challenging. Meticulous pre-anaesthetic evaluation and pre-operative optimization are often crucial. A multidisciplinary approach is often employed to achieve the best possible pre-operative functional status of these patients. Well-coordinated team with flexibility in management tailored to the patient helps achieve the best possible outcomes. Disclaimer: Informed consent was obtained from the patient prior to publication Main Points • Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease with multisystem involvement; associated tumours include hemangioblastomas of the CNS, retinal capillary hemangioblastomas, renal cell carcinoma, pheochromocytoma, endolymphatic sac tumours of the middle ear, serous cystadenomas and neuroendocrine tumours of pancreas. • Providing anaesthesia to patients with multisystem involvement such as Von Hippel Lindau syndrome can be very challenging. Meticulous pre-anaesthetic evaluation and pre-operative optimization are often crucial. • A detailed anaesthetic plan, tailored to each patient, has to be formulated in elective cases, after an extensive work-up of the associated tumours. • Extensive pre-operative work-up, a multi-disciplinary approach towards pre-operative optimization and synergistic management with surgical team remains vital in minimizing peri-operative complications. • Anaesthetic implications are often at the nexus of surgical outcomes, hence, proper communication with the surgical team and arrival at a joint plan is crucial.

Laparoscopic Parenchymal Sparing Multiple Metastatectomy Combined with Left Lateral Segmentectomy for Long Term Hepatic Recurrence from Resected Solid Pseudopapillary Tumor of Pancreas

Introduction: Solid pseudopapillary neoplasm(SPN) of the pancreas are rare tumors that occurs in young women. SPN can metastasizes in 5–15% of all cases and the common site is the liver. The management of metastatic tumors of SPN is unclear. We report a case of Laparoscopic Parenchymal Sparing Multiple Metastatectomy Combined with Left Lateral Segmentectomy for long term Hepatic Recurrence from Resected Solid Pseudopapillary tumor of Pancreas. Case/methods: A 26-year-old lady underwent distal pancreatectomy with splenectomy on 30/3/2015 for solid pseudopapillary tumor of pancreas. Patient was on routine follow up and a PET CT done on 14/10/2020 showed Multiple Bilobar Liver Metastasis in Segments 2/3, 6, 7, 8. Patient underwent of Laparoscopic Parenchymal Sparing Multiple Metastatectomy Combined with Left Lateral Segmentectomy on 22/10/2020. Intra operatively, metastasis was noted at segment 6,7,8 sub capsular. Intraoperative USG showed deep seated segment 2 metastasis for which Laparoscopic left lateral Segmentectomy was done. Results: Postoperative period was uneventful. Histopathology confirmed the 4 metastasis with adequate margins. She was discharged on post-operative day 2. Post 10 months of surgery patient is having a disease-free survival. Conclusion: Long term hepatic recurrence in SPN is rare. Aggressive management of Liver Metastasis ensures a long term disease free survival. In our case we were able to manage the multiple liver metastasis using a combination of Laparoscopic Parenchymal sparing hepatic metastatectomy and Left Lateral Segmentectomy to achieve a R0 resection and this reinforces the role of laparoscopic liver surgery even in such rare tumors.

Total Pancreatectomy for Head of the Pancreas Tumor - Surprising Findings

Introduction: Pancreatic adenocarcinoma (PAC) is one of the leading causes of cancer deaths with rising prevalence in recent years. Surgical resection is the only potentially curative treatment for PAC. Pancreatic leak is a major complication of pancreaticoduodenectomy (PD), while total pancreatectomy (TP) can result in brittle insulin-dependent diabetes mellitus and cachexia-like syndrome with previously high mortality rates that rendered TP impractical and largely abandoned. However, recent advancements in the treatment of DM, drop-in mortality rate, and reduced pancreatic leak risk has led the surgical community to retrospectively review TP cases in comparison to PD.

Analysis of safety and efficacy of laparoscopic distal pancreatectomy in the treatment of left pancreatic malignant tumors.

ObjectiveDistal pancreatectomy is the most extensive operation to treat malignant tumors of the left pancreas; however, malignant pancreatic tumors are prone to early invasion and metastasis.MethodsThe clinical data of 80 patients undergoing surgical treatment for malignant tumors of the pancreatic body or tail from January 2013 to December 2017 were retrospectively analyzed. The main clinical variables were compared between patients undergoing laparoscopic distal pancreatectomy (LDP) vs. open distal pancreatectomy (ODP).ResultsThere were no significant differences in general patient characteristics, complications, and postoperative survival (χ2 = 0.09) between the groups. The operation time in the LDP group was significantly longer than that in the ODP group; however, the LDP group was superior to the ODP group regarding the length of postoperative hospital stay, diet recovery, and rectal exhaust and ambulation times.ConclusionLDP is a safe and feasible treatment for left pancreatic malignancies, with the same surgical efficacy as ODP. LDP also has the advantages of minimally invasive surgery, such as minimal trauma and enhanced recovery after surgery.

Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis.

Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in noncancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64 026 controls (odds ratio [OR]: 3.80 [1.92-7.51], P=.0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases vs 77 of 64 026 gnomAD controls (OR: 2.4 [0.88-6.58], P=.087), and variants in CPB1 were detected in 5 of 1385 cases vs 33 of 64 026 controls (OR: 7.02 [2.74-18.01], P=.0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58-8.39], P < .023) and CPB1 (OR: 9.51 [3.46-26.15], P < .001). Rare variants in CPB1 and CPA1 that induce ER stress are associated with increased odds of developing pancreatic cancer.

Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype\u2013phenotype correlation and gene therapy perspective

BackgroundClassical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both.MethodsIn this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome.ResultsWe reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy.ConclusionsCombined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

Diet high in branched-chain amino acid promotes PDAC development by USP1-mediated BCAT2 stabilization.

BCAT2-mediated branched-chain amino acid (BCAA) catabolism is critical for pancreatic ductal adenocarcinoma (PDAC) development, especially at an early stage. However, whether a high-BCAA diet promotes PDAC development in vivo, and the underlying mechanism of BCAT2 upregulation, remain undefined. Here, we find that a high-BCAA diet promotes pancreatic intraepithelial neoplasia (PanIN) progression in LSL-KrasG12D/+; Pdx1-Cre (KC) mice. Moreover, we screened with an available deubiquitylase library which contains 31 members of USP family and identified that USP1 deubiquitylates BCAT2 at the K229 site. Furthermore, BCAA increases USP1 protein at the translational level via the GCN2-eIF2α pathway both in vitro and in vivo. More importantly, USP1 inhibition recedes cell proliferation and clone formation in PDAC cells and attenuates pancreas tumor growth in an orthotopic transplanted mice model. Consistently, a positive correlation between USP1 and BCAT2 is found in KC; LSL-KrasG12D/+; p53flox/+; Pdx1-Cre mice and clinical samples. Thus, a therapeutic targeting USP1-BCAT2-BCAA metabolic axis could be considered as a rational strategy for treatment of PDAC and precisive dietary intervention of BCAA has potentially translational significance.

Stem Cell Markers CXCR-4 and CD133 Predict Aggressive Phenotype and Their Double Positivity Indicates Poor Prognosis of Oral Squamous Cell Carcinoma.

Simple SummaryOral cancer is one of the most frequent malignancies in the world, with a poor prognosis. The absence of accurate biomarkers for predicting oral cancer progression is the primary cause of treatment failures. Multiple studies have shown that cancer stem cells play a critical role in tumor growth and chemo resistance. We uncovered, for the first time, the importance of combinatorial expression of stem cell related molecules CXCR-4 and CD-133 as possible biomarkers to predict poor prognosis of oral squamous cell carcinoma. The findings will aid in the identification of high-risk cases in order to provide appropriate therapy.The activation of the SDF-1/CXCR-4 pathway is crucial for the invasion and metastasis of oral cancer cells. The CXCR-4 positive cells possess stem cell characteristics and express the cancer stem cell marker, CD133, in tumors of colon and pancreas. Despite several studies, the co-expression of CXCR-4 and CD133 and its significance is still largely unknown in oral cancer. Therefore, we aimed to investigate the impact of CXCR-4 and CD133 double positivity in the prognosis of oral cancer. The significance of PKC-δ, one of the key signaling molecules that regulates CXCR-4, was also analyzed. Immunohistochemistry and double immunofluorescence was used to investigate the co-localization of CXCR-4, PKC-δ and CD133 in the human tissues and cell lines of oral squamous cell carcinoma. The expression of CXCR-4, PKC-δ and CD133 were found to be higher in poorly differentiated and lymph node metastasis-positive cases. Interestingly, CXCR-4 positive cells showed positive staining for PKC-δ and CD133 in oral cancer tissue and cell lines. Moreover, CXCR-4+/CD133+ and CXCR-4+/PKC-δ+ double positive cases have the worst survival. We discovered, for the first time, that patients with expression of both CXCR-4 and CD133 have a lower survival rate, and CXCR-4+/CD133+, as well as CXCR-4+/PKC-δ+ double positivity, can be utilized to predict poor prognosis. CXCR-4, PKC-δ and CD133 might regulate aggressiveness and invasion of oral cancer cells.

Comparison of analysis methods for determination of dynamic tissue conductivity during microseconds-long pulsed electric fields

Objective: High-frequency irreversible electroporation (H-FIRE) is an emerging therapy which uses bursts of high-voltage, bipolar pulses to ablate tissue. This paper aims to quantify electric-field-dependent material properties of select tissues for computational models. The results show that tissues treated with 5 and 10 μs H-FIRE can be approximated as purely resistive, simplifying analysis and numerical modeling. Methods: Parallel-plate electrodes were used to apply H-FIRE waveforms (5-5-5 and 10-1-10) to samples of porcine pancreas, liver, prostate, brain, and patient-derived prostate tumor. Resistance of each sample during pulsing was calculated from captured current waveforms using two methods for comparison: one assuming a purely resistive response from tissue and the other assuming dispersion. Results: Conductivity versus electric field (EF) behavior is reported for all five tissue types. There was little dependence of conductivity on EF magnitude for most tissues except for prostate and prostate tumor tissue. Additionally, the study found that differences between the two resistance analysis methods were less than 10% except for prostate (<30%) and liver and pancreas at lower EF magnitudes. Conclusion: Prostate and prostate tumor tissues are expected to undergo more EF redistribution during H-FIRE as compared with the other tissues. Also, in most cases under study, the results suggest that frequency effects are minimal using these particular waveforms. Significance: Currently, high-frequency effects on tissue properties that occur during microseconds-long bipolar pulses are not yet clear and quantified. This work reports these properties while also assessing whether approximation of the tissue as resistive is appropriate.

Abstract PO-124: EZH2 blockade overcomes suppression of the proinflammatory senescence-associated secretory phenotype in the pancreas and drives NK cell-mediated pancreatic tumor responses

Abstract T cell-targeting immunotherapies that produce durable and sometimes curative responses in other malignancies have failed in pancreatic ductal adenocarcinoma (PDAC) due to poor T cell infiltration and tumor immunogenicity. We and others have demonstrated that cellular senescence and its associated secretory phenotype (SASP), which leads to production of proinflammatory cytokines, chemokines, and growth factors, can be a powerful way to reactivate a different type of Natural Killer (NK) cell immunity. Recently, we found that RAS pathway targeting MEK and CDK4/6 inhibitors can induce senescence in KRAS mutant lung tumor and PDAC models; however, therapy-induced senescence (TIS) led to NK cell-mediated tumor regressions only in the lungs. Here we set out to understand how the pancreas tumor microenvironment (TME) suppresses NK immunity and develop strategies to harness NK cell surveillance for PDAC immunotherapy. Syngeneic murine KRAS-driven lung tumor and PDAC cells were transplanted into lungs, pancreas, or liver of C57BL/6 mice. Following 2-week treatment with the MEK inhibitor trametinib and CDK4/6 inhibitor palbociclib (T/P) to induce senescence, immune responses were assessed by flow cytometry, and the SASP profile assessed by RNA- and ATAC-seq analysis. An NK1.1-targeted antibody was also used to deplete NK cells and evaluate treatment efficacy. shRNA-mediated EZH2 knockdown and treatment with EZH2 methyltransferase inhibitors in murine and human PDAC cells and mouse models was used to determine the role of EZH2 in SASP regulation by qPCR and cytokine array. The effects of EZH2 blockade on NK cell immunity were determined in co-culture migration and cytotoxicity assays in vitro and in PDAC transplant models in vivo by flow cytometry. The efficacy of T/P treatment in combination with EZH2-targeting shRNAs or inhibitors was measured by ultrasound tumor measurements and survival in PDAC-bearing animals. Tumors propagated in the pancreas TME display transcriptional repression and reduced chromatin accessibility of SASP transcriptional activators (NF-KB, IRFs) and factors necessary for NK cell activity (IL-15,-18) and chemotaxis (CCL2,-7,-8; CXCL9,-10) following TIS, and do not undergo anti-tumor NK immune surveillance as compared to tumors grown in the lungs and liver. We identified induction of EZH2 and repression of its targets, including key SASP factors and regulators, specifically in tumor cells grown in the pancreas TME. Genetic or pharmacological inhibition of EZH2 enhanced proinflammatory SASP signaling and resulted in NK cell infiltration and anti-tumor cytotoxicity in PDAC models. Remarkably, EZH2 knockdown in combination with T/P treatment led to complete tumor regressions in PDAC-bearing mice that were reversed following NK cell depletion. These results demonstrate that EZH2 mediates transcriptional repression of the proinflammatory SASP in the pancreas TME, and that EZH2 blockade in combination with TIS could be a powerful means to reactivate absent NK cell surveillance in PDAC to achieve immune-mediated tumor control. Citation Format: Loretah Chibaya, Yvette Lopez-Diaz, Haibo Liu, Katherine C. Murphy, John P. Morris IV, Yu-jui Ho, Janelle Simon, Wei Luan, Amanda Kulick, Lakhena Leang, Elisa de Stanchina, Lihua J. Zhu, Scott W. Lowe, Marcus Ruscetti. EZH2 blockade overcomes suppression of the proinflammatory senescence-associated secretory phenotype in the pancreas and drives NK cell-mediated pancreatic tumor responses [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-124.

Solid pseudopapillary tumors of the pancreas in young women: Case report.

Introduction and importanceSolid pseudopapillary tumor of the pancreas (SPTP) is a rare tumor of the exocrine pancreas, with undetermined etiopathogeny, which most often affects young women. The clinical and physical signs are non-specific and despite the progress of complementary examinations, Confirmation is usually anatomopathological. Surgical resection is the only curative treatment.Case presentationWe report the case of a 17-year-old girl, consulted for a left hypochondrium mass which imaging concluded to be a corporal-caudal tumor mass of the pancreas for which a complete surgical excision was performed and whose anatomopathological study confirmed a pseudo-papillary and solid tumor of the pancreas. The positive diagnosis of SPTP remains difficult and is usually made on pathological analysis with immunohistochemical study.DiscussionSolid pseudopapillary tumor of the pancreas is a rare anatomic-clinical entity, first described by Frantz in 1959. The clinical manifestations of SPTP are not specific. Biologically, no signs are predictive of SPTP and imaging usually shows a well encapsulated mass with both solid and cystic components. The curative treatment of SPTP is exclusively surgical and consists of a complete removal of the tumor with its capsule because of its degenerative potential SPTP has a good prognosis with a recurrence rate of 10–15% and 95% survival at 5 years.ConclusionSolid pseudopapillary tumor of the pancreas is a rare tumor of the exocrine pancreas. Its evolution is slow. Preoperative diagnosis remains difficult despite the progress of complementary examinations. Surgical resection is the only curative treatment. Its prognosis remains excellent.

Role of Resection of the Primary in Metastatic Well-Differentiated Neuroendocrine Tumors.

Resection of the primary (RP) in metastatic neuroendocrine tumor (NET) is controversial. The aim was to evaluate survival outcomes for RP in metastatic NET patients. Data were obtained from US hospitals at the National Cancer Database between 2004 and 2014. χ2, analysis of variance tests, univariate, and multivariate cox proportional hazards models were evaluated. Kaplan-Meier curves and log-rank tests conducted to compare the survival difference of patient characteristics. A total of 2361 patients were identified. The mean age was 62.1 years (standard deviation, 13 years), male-to-female ratio 1:1; 33% were small intestine, 26.3% pancreas, and 24.4% lung; 69.6% were well-differentiated; and 42.5% underwent RP. The 5-year overall survival (OS) was significantly improved for patients who underwent RP in small intestine (5-year OS, 63.9% vs 44.2%), lung (5-year OS, 65.4% vs 20.2%), and pancreas tumors (5-year OS, 75.6% vs 30.6%). On multivariate analysis, RP (hazard ratio, 0.46; 95% confidence interval, 0.29-0.73; P < 0.001), female, year of diagnosis 2010-2014, margin, Charlson-Deyo score less than 2, and age less than 51 years, were associated with better OS. Resection of the primary in metastatic well-differentiated NET is associated with improved OS compared with no RP.

70-Year-Old Man With Chronic Nausea and Vomiting

70-Year-Old Man With Chronic Nausea and Vomiting

How does the pancreatic solid pseudopapillary neoplasm confuse us: Analyzing from the point view of MRI-based radiomics?

ObjectivesTo construct MRI-based radiomics logistic model in differentiating solid pseudopapillary neoplasm (SPN) from three differential diseases containing adenocarcinoma, neuroendocrine tumor (NET), and cystadenoma of pancreas. Materials and methodsA total of 21 SPNs and 140 differential diseases were enrolled. The MRI images of T1WI, T2WI, DWI, and contrast-enhanced (CE) sequences were taken to delineate the volume of interest, and the corresponding radiomics features were calculated. After the preprocess of data balance and image standardize, the data was divided into training set (6 SPNs and 42 differential diseases) and validation set (15 SPNs and 98 differential diseases) with a proportion of 7:3, randomly. Then after feature selection, four MRI-based logistic models included T1WI, T2WI, DWI, CE, and sum logistic models (Log-T1WI, Log-T2WI, Log-DWI, Log-CE, and Log-sum) were established. The receiver operation curve (ROC) was depicted to evaluate the efficacy of each model. ResultsTo the single MRI sequence, the AUCs of Log-T1WI, Log-T2WI, Log-DWI, and Log-CE were similar. Seemingly the AUCs of Log-T2WI were slightly higher with 0. 876 (95%CI, 0.797–0.956) in the training set and 0.853 (95%CI, 0.708–0.998) in the validation set. The Log-sum of four MRI sequences displayed better differentiating efficiency, with AUCs of 0.929 (95%CI, 0.877–0.980) in the training set and 0.925 (95%CI, 0.845–1.000) in the validation set. The Log-Ra/Clin model combined clinical information and radiomics showed the highest AUC of 0.962 (95%CI, 0.919–0.985). ConclusionsMRI-based radiomics analysis helped to discern SPNs from radiologically misdiagnosed adenocarcinoma, neuroendocrine tumor, and cystadenoma of pancreas. The efficacy of single sequence logistic model was similar. The Log-sum combined four sequences and Log-Ra/Clin combined clinical information and radiomics demonstrated the better performance in distinction.

Сучасні можливості діагностики і лікування нейроендокринних пухлин шлунково-кишкового тракту і підшлункової залози

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