Malignancy Of Pancreas Research Articles

1O The somatic mutation landscape of the normal and malignant pancreas

1O The somatic mutation landscape of the normal and malignant pancreas

Laparoscopic versus open pancreaticoduodenectomy: Long-term outcome from a tertiary care centre.

Laparoscopic Whipple's pancreaticoduodenectomy (WPD) is one of the most advanced minimally invasive procedures. In recent years, with advancements in minimally invasive surgery, laparoscopic WPD has been increasingly adopted as a safe and feasible technique. This study aims to compare the short-term and long-term outcomes of laparoscopic WPD to open WPD in resectable ampullary, periampullary and head of pancreas malignancies. A retrospective analysis of a prospectively maintained database of patients who underwent WPD from January 2015 to January 2021 at the department of surgical gastroenterology in a tertiary care medical college hospital was conducted. Patient demographics and pre-operative details, intraoperative parameters (operating time and blood loss), post-operative length of hospital stay, median intensive care unit (ICU) stay, time to resume oral diet, post-operative complications, interventional procedures, mortality, 3-year survival, 3 year recurrence-free survival and overall survival were analysed. Forty-two patients underwent WPD during our study period; 14 patients underwent laparoscopic WPD and 28 patients underwent open WPD. None required conversion. The majority of the patients had periampullary carcinoma in both the groups. Laparoscopic WPD showed a trend towards shorter ICU stays, hospital stays and surgical site infections (SSIs) compared to open WPD. The median operating time was significantly longer in the laparoscopic WPD group (380 min) compared to the open group (285 min). However, median blood loss was significantly lower in the laparoscopic group (250 mL vs. 300 mL). The pancreas-specific post-operative complications like delayed gastric emptying, post-operative pancreatic fistula or post-operative pancreatic haemorrhage did not differ significantly between the groups. All patients had R0 resection and the mean lymph node yield was comparable between the two groups (14.92 vs. 13.42). The reoperation rate or mortality rate did not show any statistical significance between the two groups. The overall survival was 46 months in the open group and 48 months in the laparoscopic group. Three-year survival was 74.1% in the open WPD group and 69.2% in the laparoscopic group. Three-year recurrence-free survival was 55.5% in the open group and 69.23% in the laparoscopic group. Laparoscopic WPD appears to be safe and feasible, with similar short-term and long-term survival outcomes. With a trend favouring laparoscopic WPD in terms of blood loss, hospital and ICU stay and post-operative SSIs, it should be offered to selected patients when the expertise is available.

Stabilized Window for Intravital Imaging of the Murine Pancreas.

The physiology and pathophysiology of the pancreas are complex. Diseases of the pancreas, such as pancreatitis and pancreatic adenocarcinoma (PDAC) have high morbidity and mortality. Intravital imaging (IVI) is a powerful technique enabling the high-resolution imaging of tissues in both healthy and diseased states, allowing for real-time observation of cell dynamics. IVI of the murine pancreas presents significant challenges due to the deep visceral and compliant nature of the organ, which make it highly prone to damage and motion artifacts. Described here is the process of implantation of the Stabilized Window for Intravital imaging of the murine Pancreas (SWIP). The SWIP allows IVI of the murine pancreas in normal healthy states, during the transformation from the healthy pancreas to acute pancreatitis induced by cerulein, and in malignant states such as pancreatic tumors. In conjunction with genetically labeled cells or the administration of fluorescent dyes, the SWIP enables the measurement of single-cell and subcellular dynamics (including single-cell and collective migration) as well as serial imaging of the same region of interest over multiple days. The ability to capture tumor cell migration is of particular importance as the primary cause of cancer-related mortality in PDAC is the overwhelming metastatic burden. Understanding the physiological dynamics of metastasis in PDAC is a critical unmet need and crucial for improving patient prognosis. Overall, the SWIP provides improved imaging stability and expands the application of IVI in the healthy pancreas and malignant pancreas diseases.

Abstract 1241: A single cell landscape of malignant pancreas cancer ascites

Abstract Despite advancement in surgical and medical management of pancreatic ductal adenocarcinoma (PDAC), this tumor type is currently the 3rd leading cause of cancer-related death in the United States and expected to become the 2nd by 2030. The development of ascites in PDAC patients generally indicates a poor prognosis although the reasons for this largely remain unknown. The exact mechanism of peritoneal spread of the cancer is still largely unknown. Herein, we collected and processed sterile ascites samples of 20 PDAC samples from 19 patients and performed single-cell RNA-seq analysis. Sixteen ascites samples were obtained from abdominal paracentesis and two cases in the postmortem period. For one patient ascites was collected both pre and postmortem. All but one patient received chemotherapy prior to ascites collection. Routine clinical cytology evaluation of ascites samples from 17 patients indicated it was malignant in 11 patients and nonmalignant in six patients. All ascites samples were purified by gradient centrifuge using Ficoll-Paque Plus to remove erythrocytes and necrotic debris. DAPI negative and Calcein positive cells were selected to enrich live cells from the cell suspension by flow sorting. We adopted the 10x Genomics Chromium Single Cell Gene Expression platform for single-cell RNA-seq library preparation. Scanpy was used for computational analysis of expression data after Cell Ranger pipelines. After QC check, normalization and doublet elimination, a total of 248,263 cells were analyzed. UMAP projection accurately clustered cells from each patient. Cell type annotation identified large numbers of immune cells compared to cancer cells and mesothelial cells with the most dominant population being macrophages. A subpopulation (0.23% of all cells) representing plasmacytoid dendritic cells was also found. Cancer cells were detected in twelve samples whereas no cancer cells were detected in eight samples after exhaustive marker gene exploration, and these findings largely matched the clinical diagnoses for each sample. In the ongoing period we will compare malignant versus non-malignant ascites by differential gene expression analysis, gene set enrichment analysis and trajectory inference to determine a) the extent the immunological clusters are enriched in malignant versus benign ascites, b) the distinct phenotypes and cell states of PDAC cells in immune rich versus immune poor ascites, c) role of plasmacytoid dendritic cells or mesothelial cells contribution to formation of malignant ascites. We believe our results will shed light on the dynamics of ascites formation and in turn identify novel targets for intervention. Citation Format: Shigeaki Umeda, Elias- Ramzey Karnoub, Etay Ziv, Jean Wu, Cristian Cruz, Wungki Park, Fiyinfolu Balogun, Alejandro Jiménez- Sánchez, Ronan Chaligné, Eileen M. O'Reilly, Christine A. Iacobuzio- Donahue. A single cell landscape of malignant pancreas cancer ascites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1241.

Molecular Research in Pancreatic Cancer: Small Molecule Inhibitors, Their Mechanistic Pathways and Beyond.

Pancreatic enzymes assist metabolic digestion, and hormones like insulin and glucagon play a critical role in maintaining our blood sugar levels. A malignant pancreas is incapable of doing its regular functions, which results in a health catastrophe. To date, there is no effective biomarker to detect early-stage pancreatic cancer, which makes pancreatic cancer the cancer with the highest mortality rate of all cancer types. Primarily, mutations of the KRAS, CDKN2A, TP53, and SMAD4 genes are responsible for pancreatic cancer, of which mutations of the KRAS gene are present in more than 80% of pancreatic cancer cases. Accordingly, there is a desperate need to develop effective inhibitors of the proteins that are responsible for the proliferation, propagation, regulation, invasion, angiogenesis, and metastasis of pancreatic cancer. This article discusses the effectiveness and mode of action at the molecular level of a wide range of small molecule inhibitors that include pharmaceutically privileged molecules, compounds under clinical trials, and commercial drugs. Both natural and synthetic small molecule inhibitors have been counted. Anti-pancreatic cancer activity and related benefits of using single and combined therapy have been discussed separately. This article sheds light on the scenario, constraints, and future aspects of various small molecule inhibitors for treating pancreatic cancer-the most dreadful cancer so far.

Simultaneous targeting of mitochondrial Kv1.3 and lysosomal acid sphingomyelinase amplifies killing of pancreatic ductal adenocarcinoma cells in vitro and in vivo

Pancreas ductal adenocarcinoma (PDAC) remains a malignant tumor with very poor prognosis and low 5-year overall survival. Here, we aimed to simultaneously target mitochondria and lysosomes as a new treatment paradigm of malignant pancreas cancer in vitro and in vivo. We demonstrate that the clinically used sphingosine analog FTY-720 together with PAPTP, an inhibitor of mitochondrial Kv1.3, induce death of pancreas cancer cells in vitro and in vivo. The combination of both drugs results in a marked inhibition of the acid sphingomyelinase and accumulation of cellular sphingomyelin in vitro and in vivo in orthotopic and flank pancreas cancers. Mechanistically, PAPTP and FTY-720 cause a disruption of both mitochondria and lysosomes, an alteration of mitochondrial bioenergetics and accumulation of cytoplasmic Ca2+, events that collectively mediate cell death. Our findings point to an unexpected cross-talk between lysosomes and mitochondria mediated by sphingolipid metabolism. We show that the combination of PAPTP and FTY-720 induces massive death of pancreas cancer cells, thereby leading to a substantially delayed and reduced PDAC growth in vivo.Key messagesFTY-720 inhibits acid sphingomyelinase in pancreas cancer cells (PDAC).FTY-720 induces sphingomyelin accumulation and lysosomal dysfunction.The mitochondrial Kv1.3 inhibitor PAPTP disrupts mitochondrial functions.PAPTP and FTY-720 synergistically kill PDAC in vitro.The combination of FTY-720 and PAPTP greatly delays PDAC growth in vivo.

Etiological Spectrum of Obstructive Jaundice: "Our Experience in Two University Hospitals in Yemen"

Background: Obstructive jaundice is a surgical emergency with preoperatively uncertain diagnosis. Its early diagnosis and treatment is important to avoid fatal complications.
 Objective: to determine the etiology of obstructive jaundice.
 Patients and methods: The data of patients, who were operated for obstructive jaundice at department of Surgery in Sana'a University Hospital and Thamar University Hospital between January 2004 and December 2008, were prospectively analyzed in relation to the causes of obstructive jaundice. The study included 134 patients (91 females and 43 males). Their ages varied from 8-90 years. 
 Results: Among 9 underlying causes of obstructive jaundice, the common bile duct stones were the most common cause, 68 patients (50.7%). Malignancies of pancreas and hepatobiliary tract came in the second place, 33 patients (24.6%), followed by 13 patients with stenosis of papilla of Vater (9.7%) and benign strictures of extrahepatic biliary ducts, 10 patients (7.4%).
 Ascaris in common bile duct was found in 3 patients. Mirrizi's syndrome was found in 2 patients. Obstruction due to ruptured hydatid cyst was found in 2 patients. Two patients had amoebic liver abscesses One patient had pancreatic pseudocyst. 
 Conclusion: Obstructive jaundice of Yemeni patients in our series was most often due to common bile duct stones followed by malignancy of pancreas and hepatobiliary tract. Cancer of the pancreas was the most common malignant cause. Rare causes such as ascaris in common bile duct was detected. Cooperation between surgeon and radiologist is highly recommended 

Abstract B023: RHAMMB promotes pancreatic cancer metastasis

Abstract Pancreatic cancer is a leading cause of cancer-related death. The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), and pancreatic neuroendocrine tumor (PNET) is the second common malignancy of pancreas. Pancreatic cancer patients are often diagnosed with metastatic diseases. The 5-year survival is lowest for pancreatic cancer among all cancers. There is an urgent need to understand the key regulators for pancreatic cancer metastasis and develop new therapeutic strategies. We found that Receptor for hyaluronan-mediated motility (RHAMM) is overexpressed in pancreatic cancer, but it is absent or limited in normal human tissues and not expressed in adult pancreas. RHAMM was initially identified as a protein that binds to hyaluronic acid (HA). RHAMM promotes HA-induced motility, modulates cytoskeletal organization, and activates extracellular-regulated kinase (Erk). RHAMM encodes 18 exons and alternative splicing yields different isoforms, RHAMMv1-4. We found that RHAMMB (known as RHAMMv3) is the most prominent alternative splicing isoform in PDAC and PNET, and high RHAMMB mRNA levels correlate with inferior survival of pancreatic cancer patients in TCGA cohort. We demonstrated that RHAMMB overexpression promotes metastasis of pancreatic cancer in mouse models and knockdown of RHAMM by shRNA suppresses migration and metastasis. Given RHAMM’s tumor-specific overexpression patten, we developed nanoparticles to target RHAMMB-overexpressing pancreatic cancer. We demonstrated that RHAMM-targeting nanoparticles loaded with multiple therapeutics can be used as a systemic therapy to suppress RHAMMB-overexpressing tumors in immunocompetent mice. Taken together, RHAMMB plays an important role for pancreatic cancer metastasis and serves as a therapeutic gateway for pancreatic cancer treatment. Citation Format: Xiang Chen, Tiantian Zhang, Seung Koo Lee, Dunrui Wang, Zhengming Chen, Ching-Hsuan Tung, Yao-Tseng Chen, Yi-Chieh Nancy Du. RHAMMB promotes pancreatic cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B023.

SWIP-a stabilized window for intravital imaging of the murine pancreas.

Pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are grave illnesses with high levels of morbidity and mortality. Intravital imaging (IVI) is a powerful technique for visualizing physiological processes in both health and disease. However, the application of IVI to the murine pancreas presents significant challenges, as it is a deep, compliant, visceral organ that is difficult to access, easily damaged and susceptible to motion artefacts. Existing imaging windows for stabilizing the pancreas during IVI have unfortunately shown poor stability for time-lapsed imaging on the minutes to hours scale, or are unable to accommodate both the healthy and tumour-bearing pancreata. To address these issues, we developed an improved stabilized window for intravital imaging of the pancreas (SWIP), which can be applied to not only the healthy pancreas but also to solid tumours like PDAC. Here, we validate the SWIP and use it to visualize a variety of processes for the first time, including (1) single-cell dynamics within the healthy pancreas, (2) transformation from healthy pancreas to acute pancreatitis induced by cerulein, and (3) the physiology of PDAC in both autochthonous and orthotopically injected models. SWIP can not only improve the imaging stability but also expand the application of IVI in both benign and malignant pancreas diseases.

Palliative management of terminal stage hepatobiliary pancreas malignancy: Hospice care perspective in the era of POLST

Palliative management of terminal stage hepatobiliary pancreas malignancy: Hospice care perspective in the era of POLST

Mucin 5AC Serves as the Nexus for β-Catenin/c-Myc Interplay to Promote Glutamine Dependency During Pancreatic Cancer Chemoresistance

A major clinical challenge for patients with pancreatic cancer (PC) is metabolic adaptation. Neoplastic cells harboring molecular perturbations suffice for their increased anabolic demand and nucleotide biosynthesis to acquire chemoresistance. The mucin 5AC expressed de novo in malignant pancreas promotes cancer cell stemness and is significantly associated with poor patient survival. Identification of MUC5AC-associated drivers of chemoresistance through metabolic alterations may facilitate the sculpting of a new combinatorial regimen. The contributions of MUC5AC to glutaminolysis and gemcitabine resistance were examined by The Cancer Genome Atlas data analysis, RNA sequencing, and immunohistochemistry analysis on pancreatic tissues of KrasG12D;Pdx1-Cre (KC) and KrasG12D;Pdx1-Cre;Muc5ac-/- mice. These were followed by metabolite flux assays as well as biochemical and xenograft studies on MUC5AC-depleted human and murine PC cells. Murine and human pancreatic 3-dimensional tumoroids were used to evaluate the efficacy of gemcitabine in combination with β-catenin and glutaminolysis inhibitors. Transcriptional analysis showed that high MUC5AC-expressing human and autochthonous murine PC tumors exhibit higher resistance to gemcitabine because of enhanced glutamine use and nucleotide biosynthesis. Gemcitabine treatment led to MUC5AC overexpression, resulting in disruption of E-cadherin/β-catenin junctions and the nuclear translocation of β-catenin, which increased c-Myc expression, with a concomitant rise in glutamine uptake and glutamate release. MUC5AC depletion and glutamine deprivation sensitized human PC cells to gemcitabine, which was obviated by glutamine replenishment in MUC5AC-expressing cells. Coadministration of β-catenin and glutaminolysis inhibitors with gemcitabine abrogated the MUC5AC-mediated resistance in murine and human tumoroids. The MUC5AC/β-catenin/c-Myc axis increases the uptake and use of glutamine in PC cells, and cotargeting this axis along with gemcitabine may improve therapeutic efficacy in PC.

Uncertain Beginnings: Acinar and Ductal Cell Plasticity in the Development of Pancreatic Cancer.

The pancreas consists of several specialized cell types that display a remarkable ability to alter cellular identity in injury, regeneration, and repair. The abundant cellular plasticity within the pancreas appears to be exploited in tumorigenesis, with metaplastic, dedifferentiation, and transdifferentiation processes central to the development of pancreatic intraepithelial neoplasia and intraductal papillary neoplasms, precursor lesions to pancreatic ductal adenocarcinoma. In the face of shifting cellular identity, the cell of origin of pancreatic cancer has been difficult to elucidate. However, with the extensive utilization of in vivo lineage-traced mouse models coupled with insights from human samples, it has emerged that the acinar cell is most efficiently able to give rise to both intraductal papillary neoplasms and pancreatic intraepithelial neoplasia but that acinar and ductal cells can undergo malignant transformation to pancreatic ductal adenocarcinoma. In this review, we discuss the cellular reprogramming that takes place in both the normal and malignant pancreas and evaluate the current state of evidence that implicate both the acinar and ductal cell as context-dependent origins of this deadly disease.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of pancreas: a rare entity

Introduction: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) comprise of both epithelial and neuroendocrine component in which each element has to comprise at least 30% of the tumor. MiNEN usually involve various gastrointestinal organs, however it is very infrequent in pancreas. Case Presentation: We encountered an 81-year-old male patient who presented with pain in upper abdomen since 3 months. He noticed jaundice with cholestatic features for last 15 days which was associated with anorexia and weight loss. Liver function test revealed: Bilirubin-3.8mg/dl; AST- 76 U/L; ALT- 163 U/L; Alkaline phosphatase- 826 IU/L, while carbohydrate antigen 19-9 was 46.9 U/ml. CECT abdomen reported a mass in the pancreatic head with dilated common bile duct and pancreatic duct. He underwent pancreatoduodenectomy (PD) with uneventful post-operative course. Histopathological examination revealed two different tumours: ductal adenocarcinoma admixed with neuroendocrine tumour of pancreas which was confirmed with immunohistochemistry (CK-7, Chromogranin and Synaptophysin positive). He received adjuvant chemotherapy and at the end of six months follow up, he has no recurrence. Conclusion: MiNEN is a rare malignancy of pancreas for which pancreatoduodenectomy was performed and diagnosis confirmed on histopathology with immunohistochemistry. It is important to share all individual experience-based information of such anecdotal cases to get knowledge about their clinical and biological behaviour and to standardize optimal therapy.

Palliative Management of Terminal Stage Hepatobiliary Pancreas Malignancy: Hospice Care Perspective in the Era of POLST

Palliative Management of Terminal Stage Hepatobiliary Pancreas Malignancy: Hospice Care Perspective in the Era of POLST

County-Level Variation in Utilization of Surgical Resection for Early-Stage Hepatopancreatic Cancer Among Medicare Beneficiaries in the USA

IntroductionGeographic variations in access to care exist in the USA. We sought to characterize county-level disparities relative to access to surgery among patients with early-stage hepatopancreatic (HP) cancer. MethodsData were extracted from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked database from 2004 to 2015 to identify patients undergoing surgery for early-stage HP cancer . County-level information was acquired from the Area Health Resources Files (AHRF). Multivariable logistic regression analysis was performed to assess factors associated with utilization of HP surgery on the county level. ResultsAmong 13,639 patients who met inclusion criteria, 66.9% (n = 9125) were diagnosed with pancreatic cancer and 33.1% (n = 4514) of patients had liver cancer. Among patients diagnosed with early-stage liver and pancreas malignancy, two-thirds (n = 8878, 65%) underwent surgery. Marked county-level variation in the utilization of surgery was noted among patients with early-stage HP cancer ranging from 57.1% to more than 83.3% depending on which county a patient resided. After controlling for patient and tumor-related characteristics, counties with the highest quartile of patients living below the poverty level had 35% lower odds of receiving surgery for early stage HP cancer compared patients who lived in a county with the lowest proportion of patients below the poverty line (OR 0.65, 95% CI 0.55–0.77). In addition, patients residing in counties with the highest surgeon-to-population ratio (OR 2.01, 95% CI 1.52–2.65), as well as the highest hospital bed-to-population ratio (OR 1.29, 95% CI 1.07–1.54), were more likely to undergo surgical treatment for an early-stage HP malignancy. ConclusionArea-level variations among patients undergoing surgery for early-stage HP cancer were mainly due to differences in structural measures and county-level factors. Policies targeting high-poverty counties and improvement in structural measures may reduce variations in utilization of surgery among patients diagnosed with early-stage HP cancer.

Bacteriemia por Vibrio cholerae (no-O1/no O139): reporte de caso

Vibrio cholerae (no-O1/no-O139) es un patógeno poco común que causa infecciones en humanos y que se encuentra en vida libre en ríos y en el mar, donde coloniza peces y moluscos, fuente principal de contagio para los humanos. Se presenta el caso de un paciente de 78 años con antecedente de diabetes mellitus y sospecha de neoplasia pancreática, quien consultó por síndrome febril asociado a dolor abdominal y se documentó bacteriemia por V. cholerae, por lo que se inició manejo antibiótico con posterior resolución del cuadro clínico. Como el caso se relacionó con el consumo de agua contaminada, se notificó a la autoridad competente para realizar el control de la fuente infecciosa, intervención que permitirá evitar la infección de la población que tiene contacto con ese pozo de agua.

Abstract 4698: Increased CHST15 expression follows declines in Arylsulfatase B (ARSB) and DKK3 and disinhibition of non-canonical WNT signaling

Abstract CHST15 (carbohydrate sulfotransferase 15; chondroitin 4-sulfate-6-sulfotransferase), is the sulfotransferase enzyme which adds 6-sulfate to chondroitin 4-sulfate to make chondroitin 4,6-sulfate, known as CSE. Increased CHST15 expression has been identified in malignant pancreas, renal, colon, ovary, and prostate tissues. We now report a pathway by which expression of CHST15 is increased following decline in the enzyme ARSB (arylsulfatase B; N-acetylgalactosamine-4-sulfatase), which is required for removal of 4-sulfate groups from chondroitin 4-sulfate (C4S). Previous work has shown that decline in ARSB and the resulting increase in C4S leads to decline in activity of SHP2, a ubiquitous non-receptor tyrosine phosphatase, due to enhanced binding of SHP2 with C4S when ARSB is reduced. Decline in SHP2 leads to enhanced ERK1/2 phosphorylation and subsequent downstream effects, including hypermethylation of the DKK (Dickkopf WNT signaling pathway inhibitor)3 promoter and suppressed DKK3 expression. Since DKK3 acts to inhibit Wnt signaling, Wnt signaling is enhanced in prostate epithelium when ARSB is reduced. Experiments were performed to identify the pathway by which CHST15 expression is up-regulated when ARSB is reduced and to assess the role of Wnt. The impact of ARSB silencing on CHST15 expression was determined in normal and malignant human prostate cells, in normal and malignant prostate tissue obtained by laser-capture microdissection, in HepG2 cells, and in prostate tissue of the ARSB-null mouse. Effects of selective inhibitors of Wnt and MAPK signaling pathways on CHST15 expression were evaluated. CHST15 expression was increased in malignant prostate epithelial tissue, in ARSB-null mouse prostate tissue, and following ARSB silencing in human prostate epithelial cells. The activation of Wnt signaling which followed declines in ARSB and DKK3 was required for increased CHST15 expression. Inhibition of Wnt3A blocked the increase in CHST15 expression in prostate epithelial cells co-cultured with prostate stromal cells, whereas DKK3 antibody increased CHST15. Inhibition of Rac-1 GTPase and of phospho-p38 MAPK signaling blocked the observed increase in CHST15 expression, whereas inhibition of JNK, Sp1, or of Rho kinase had no effect. These results indicate that the increase in epithelial CHST15 occurred in the malignant prostate cells and tissue due to effects of non-canonical Wnt signaling leading to enhanced phospho-p38 MAPK. The resultant increase in CHST15 when ARSB activity is reduced may contribute to determination of epithelial vs. stromal characteristics. Citation Format: Joanne Kramer Tobacman, Sumit Bhattacharyya, Leo Feferman. Increased CHST15 expression follows declines in Arylsulfatase B (ARSB) and DKK3 and disinhibition of non-canonical WNT signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4698.

Perendoscopic Placement of Palliative Stent for Obstructive Jaundice Caused by Head of Pancreas Malignancy in Dr Moewardi General Hospital-Surakarta

Pancreatic cancer is difficult to diagnose in early stage. Malignant bile duct obstruction is a severe complication of pancreatic cancer, which can lead to poor outcomes including cholangitis, delayed treatment, reduced quality of life, and increased mortality. Perendoscopic placement of stents is a method widely used in the management of various malignant and benign pancreatico-biliary abnormalities. A 70-year-old woman came to Dr Moewardi General Hospital in Surakarta with the chief complaint of yellowish skin and eyes since one month before hospital admission. Patient was diagnosed with obstructive jaundice due to suspected of advanced stage pancreatic cancer. Subsequently, patient underwent endoscopic retrograde cholangiopancreatography (ERCP) which revealed an intrahepatic and extrahepatic bile ducts dilatation due to pancreatic tumor which infiltrated common bile duct, thus self expandable metallic stent (SEMS) placement was performed. Furthermore, patients received palliative therapy due to inadequate chemotherapy requirement.

Diabetic mortality risk among cancer patients in the United State SEER population, 1975-2016.

The focus on diabetic mortality in cancer patients remains superficial. The objective of our study is to identify cancer patients with the highest risk of diabetic mortality compared with other cancer patients and the general US population. The representative data of cancer patients dying from diabetes between 1975 and 2016 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) and excess risks for multiple cancer sites were calculated. Cox regression analysis was performed to identify potential risk factors of death from diabetes. Among 9,043,788 cancer patients diagnosed between 1975 and 2016, 51,611 patients died from diabetes. the SMR of diabetic death was 2.15 compared with the general population. Malignancies of pancreas, liver, and brain had the highest SMR (>15) compared with the general population. The risk of death from diabetes was increasing in more recent years. The majority of deaths from diabetes occurred in those >45 years of age diagnosed with prostate, breast, colorectum, lung, or bladder cancer. Patients with older age, male sex, black race, higher histologic grade, unmarried status, and not undergoing surgery are at higher risk compared with other cancer survivors. Compared to the general population, cancer patients are at elevated risk of death from diabetes throughout the follow-up period. Elderly, black, unmarried males with distant metastases and without receiving surgery are recommended with earlier detection and more efficient diabetic care, especially for those with prostate, breast, colorectum, lung, or bladder cancer.

Dual malignancy: a rare presentation of synchronous periampullary carcinoma with renal cell carcinoma

The occurrence of synchronous pancreatic cancer and other primary cancer is not frequent and reaches about 5.6% as reported in autoptic studies. Double resections of the pancreas with another organ due to synchronous malignancies have been published only in quite sporadic sets of cases or individual case reports. We present a case report of a 40 years lady who presented with intermittent pain, fever and jaundice for 15 days. Examination revealed a palpable gall bladder, firm in consistency and tender to touch. She was admitted with a provisional diagnosis of cholangitis and started on intravenous antibiotics. Patient’s clinical condition improved and she was planned for a CECT and MRCP which revealed an heterogenously enhancing mass lesion in upper pole of left kidney, s/o of renal cell carcinoma (RCC) and an enhancing lesion in periampullary region s/o periampullary carcinoma with no evidence of free fluid or metastasis. ERCP guided biopsy revealed moderately differentiated adenocarcinoma and USG guided renal biopsy revealed clear cell carcinoma. Whipple’s procedure with left nephrectomy was performed. Intra operative findings revealed post-operative course and hospital stay was uneventful. Biopsy revealed poorly differentiated pancreaticobiliary adenocarcinoma with no lympho vascular or lymph nodal invasion (pT3aN0) and left sided clear cell renal carcinoma with no lympho vascular invasion (pT1N0). Synchronous malignancy of pancreas and kidney is a very rare presentation. Literature describes presence of RCC with periampullary metastasis and patients presenting with RCC post whipple’s procedure but only a handful of case reports describe presence of dual malignancy as reported above.