Hepatobiliary Carcinoma Research Articles

S2022 Hepatobiliary Carcinoma - Analyzing Current Mortality Trends and Developing an Advanced Long Short-Term Memory (LSTM)-Based Predictive Model for Projecting Future Trends

S2022 Hepatobiliary Carcinoma - Analyzing Current Mortality Trends and Developing an Advanced Long Short-Term Memory (LSTM)-Based Predictive Model for Projecting Future Trends

Resection or Ablation for Early Hepatobiliary Carcinoma: A Meta-Analysis of Treatment Outcomes

Introduction: The optimal treatment for early hepatobiliary carcinoma (EHBC) remains controversial, with surgical resection and ablation offering distinct advantages and disadvantages. This meta-analysis aimed to compare the long-term outcomes of these two modalities in patients with EHBC. Methods: A systematic search of PubMed, Scopus, and Google Scholar was conducted for studies published between 2018 and 2024 that reported on the outcomes of resection or ablation in EHBC. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The secondary outcomes included complication rates and length of hospital stay. Results: A total of 25 studies (n=4,512 patients) were included in the meta-analysis. The pooled analysis showed that resection was associated with significantly better OS (HR 0.62, 95% CI 0.51-0.75, p<0.001) and RFS (HR 0.58, 95% CI 0.47-0.71, p<0.001) compared to ablation. However, resection was also associated with a higher risk of complications (OR 1.83, 95% CI 1.32-2.54, p<0.001) and a longer hospital stay (MD 3.2 days, 95% CI 2.1-4.3, p<0.001). Conclusion: Resection offers superior long-term oncological outcomes compared to ablation in patients with EHBC. However, the choice of treatment should be individualized based on patient factors and tumor characteristics, considering the higher risk of complications and longer hospital stay associated with resection.

220P Treatment outcomes of amrubicin monotherapy for patients with advanced hepatobiliary and pancreatic neuroendocrine carcinoma

220P Treatment outcomes of amrubicin monotherapy for patients with advanced hepatobiliary and pancreatic neuroendocrine carcinoma

Emerging need of molecular profiling in hepatobiliary cancer

: Gallbladder cancer is a rare malignancy but represents almost 50% of all biliary tract cancer. Biliary cancers are highly fatal malignancies with a 5-year survival rate of approximately 20%. The prognosis of gallbladder cancer is poor due to the aggressive tumor biology, late presentation, complicated anatomic position, and advanced stage at diagnosis. Locally advanced and metastatic disease treatment is with palliative chemotherapy. Alarming sign of gallbladder cancer is overall decreased in incidence in older patients but increased in the younger population. So many mutations have been reported for the gall bladder cancer till date. : A prospective observational study was conducted over a period of 1 year at Asian Institute of Medical Sciences Faridabad which includes hepatobiliary carcinoma patients who are at stage III and stage IV of cancer. After getting the consent formalin fixed paraffin embedded biopsy samples, and 5 ml serum sample was collected in serum separator tube (SST). A whole genome sequencing was performed using Illumina HiSEQ, Illumina (NGS) technology, allows for high-throughput sequencing of DNA and RNA. Illumina's NGS is based on "sequencing by Synthesis" to detect the mutations.: Most common mutation found was in the P53 gene. TP53 (p.Arg175His), TP53 (p.Arg306Ter), TP53 (p.Cys238Tyr), TP53 (p.Leu43Ter), TP53 (p.Glu339Ter), TP53 (p.Pro190Leu). Mutations in the TP53 gene are a common feature of carcinoma of the gallbladder, and are associated with a more aggressive tumor phenotype, resistance to chemotherapy, and poorer overall survival.

A238 BEST APPROACH TO SURVEILLANCE COLONOSCOPY FOR COLORECTAL CANCER IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease and it has been recognized as a risk factor for hepatobiliary and colorectal carcinoma (CRC). Inflammatory bowel disease (IBD) is associated with a 6-fold increased risk of CRC as compared to the general population but with co-existing PSC, this risk rises to 30-fold and hence CRC surveillance is critical in these patients. Aims We performed a systematic review of the literature on surveillance colonoscopy for CRC in patients with PSC-IBD, with the aim of identifying the most effective approach. Methods The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under ID 472215. The search was executed in the databases Medline, EMBASE, Cochrane, Web of science, Scopus and Google Scholar databases from 1947 to May 2023. Observational or randomized controlled studies were included if patients had PSC-IBD (paediatric or adult) undergoing surveillance colonoscopy. There was no restriction for language. We used a modified version of the Newcastle–Ottawa Quality Assessment Scale to assess the risk of bias. Neoplasia was defined as the presence of low-grade dysplasia, high grade dysplasia or colorectal carcinoma. Results Amongst 2900 studies identified, 7 studies met the inclusion criteria with a total number of 379 PSC-IBD patients and 1884 IBD patients (all adult). The median frequency of surveillance colonoscopy was every 0-2 years. The most common endoscopic presentation of dysplasia in PSC-IBD was a normal appearing mucosa or subtle abnormalities such as mild inflammation. Three studies performed random and targeted biopsies and only one study did quadruple random biopsy (every 10 cm of the colon). Two studies used chromoendoscopy and high-definition endoscopy whereas another two studies used white light colonoscopy. Studies varied in terms of the number of biopsies taken and timing for the frequency and initiation of surveillance. Outcomes included intensive surveillance, resection, and colectomy. Our meta-analysis of 2 studies that reported the prevalence of colorectal dysplasia in PSC-IBD patients revealed a pooled prevalence of 21% (95% CI 1.4%-28%, I2 = 0%, Pampersand:003C0.597, shown in Figure 1) Conclusions Colorectal dysplasia is prevalent in patients with PSC-IBD and is associated with worse disease outcomes. As a result, PSC-IBD patients should be screened annually from the diagnosis of PSC. However, there is variation in practice, and no clear consensus on the best approach to perform screening colonoscopy in this population. Literature comparing various approaches is very sparse. Additional high-quality studies on this subject are needed to guide practice, particularly in paediatrics where data are non-existent. Figure 1: Forest plot for meta-analysis of CRC dysplasia prevalence in PSC-IBD Funding Agencies None

Nutritional assessment and following nutritional intervention during drug therapy for patients with hepatobiliary carcinoma

Nutritional assessment and following nutritional intervention during drug therapy for patients with hepatobiliary carcinoma

Recombinant protein EBI3 attenuates Clonorchis sinensis-induced liver fibrosis by inhibiting hepatic stellate cell activation in mice

BackgroundChronic infection with Clonorchis sinensis can cause hepatobiliary fibrosis and even lead to hepatobiliary carcinoma. Epstein-Barr virus-induced gene 3 protein (EBI3) is a subunit of interleukin 35, which can regulate inflammatory response and the occurrence of fibrotic diseases. Previous studies have reported that the expression of EBI3 in the serum of patients with liver cirrhosis is reduced. The present study aims to investigate the biological effects of EBI3 on liver fibrosis caused by C. sinensis and the underlying molecular mechanisms.MethodsWe first established a mouse model of liver fibrosis induced by C. sinensis infection and then measured the serum expression of EBI3 during the inflammatory and fibrotic phase. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed to investigate the potential role of EBI3 in liver fibrosis by regulating the extracellular matrix structural constituent and collagen catabolic process. Recombinant protein EBI3 (rEBI3) was added to hepatic stellate cells (HSCs) in vitro with C. sinensis antigen to explore its function. Finally, the therapeutic effect of rEBI3 was verified by intravenous injection into C. sinensis-infected mice.ResultsThe results showed that the serum expression of EBI3 increased in the inflammatory response phase but decreased in the fibrotic phase. The excretory-secretory products of C. sinensis (Cs.ESP) were able to stimulate HSC activation, while rEBI3 reduced the activation of HSCs induced by Cs.ESP. Also, the protein expression of gp130 and downstream protein expressions of JAK1, p-JAK1, STAT3 and p-STAT3 in HSCs were increased after rEBI3 incubation. Finally, intravenously injected rEBI3 inhibited hepatic epithelial-mesenchymal transition in C. sinensis-infected mice by inhibiting HSC activation and reducing liver injury.ConclusionThis study confirms that rEBI3 can attenuate C. sinensis-induced liver fibrosis by inhibiting HSC activation and may be one of the potential treatments for liver fibrosis.Graphical

Indications and Complication of Laparoscopic Cholecystectomy at a Tertiary Care Setting in Sindh Province: A Cross Sectional Survey

Objective: The study was aimed to-evaluate the indications and-complications-of the laparoscopic cholecystectomy at a tertiary care setting in sindh province. Background: The-hepato-biliary-system is affected by a wide range of illnesses known as gall bladder diseases, each of which has a unique clinical presentation and degree of morbidity. The majority of adult populations in Western nations are affected by cholelithiasis, which affects 5% to 25% of the adult population. Initially, people from developing nations had little access to the advantages of laparoscopic cholecystectomy. Materials and Methods: A cross sectional study was carried out at the surgical dept Chandka Medical College Hospital Larkana for a period of 6 months in 2020 which included patients who went through laparoscopic cholecystectomy were included in the study, however, the patients having a history of previous abdominal surgery, hepatobiliary carcinoma , challenges ejection fraction, patients with coagulopathies and those reactive for HbsAg or HCV antibodies were excluded from the study. Results: The mean age of the subjects was 43.8± 9.67 years. There were 93.7% of study participants were females, 18.6% were diabetic and 26.5%) were hypertensive. 41.81% patients were aged between 30 to 40 years. The indications for the cholecystectomy included Symptomatic cholelithiasis for 148 (83.62%) cases, acute cholecystitis for 24(13.56%) cases and gall bladder polyp for 5 (2.82%) cases. There were 11 (6.21%) cases which needed to be converted to open cholecystectomy. Bile leaking was reported in 8 (4.52%) cases and injury to liver/intestine were reported for 3 (1.69%) cases. Conclusion: In a setting of a developing country, -laparoscopic-cholecystectomy-looks to be a safe and-effective treatment with few complications. Keywords: Laparoscopic cholecystectomy, Indications, Complications, cholelithiasis.

DISEASE PROCESSES IDENTIFIED IN CAPTIVE ARABIAN SAND CATS (FELIS MARGARITA HARRISONI).

The objective of this retrospective study is to identify common and significant causes of mortality and disease processes in the Arabian sand cat (Felis margarita harrisoni) captive population at Al Ain Zoo (Abu Dhabi, United Arab Emirates). Complete postmortem records of 25 Arabian sand cats, dead between 2009 and 2022, were reviewed retrospectively. A complete postmortem examination was done in all cases, and information was recorded in the Al Ain Zoo database and files. Out of 25 animals dead, 11 were adults (4-12 yr) and 12 were classified as geriatric animals (>12 yr), with only two neonatal (0-4 mon) deaths and no recorded deaths in juveniles (4 mon to 4 yr). Interestingly, but also expected because of the age range, 24% of the cases had concurrent pathologies at the time of death. As expected in adult and geriatric felines, more than half of the cases (60%) developed nephropathies that were either one of the most important contributors or the main cause of death of the animal. Different neoplastic lesions were described in four cases and reported for the first time in this subspecies: benign peripheral nerve sheath tumor, hepatobiliary carcinoma, and two different thyroid neoplasia. A vasculoproliferative disorder of the liver, peliosis hepatis, was described in one of the cases. Additionally, in at least four cases, hyperthyroidism was strongly suspected in connection with thyroid neoplasia and hyperplasia, clinical signs, and other observed postmortem lesions. Traumatic causes of death also were reported in six cases, including the only two neonates recorded dead. This information will contribute to Arabian sand cat improved veterinary care by identifying common pathologies in this species, potentially allowing earlier diagnosis and, ultimately, improving their management and husbandry in the captive breeding populations.

A Cross-Sectional Study on Association between Metabolic Syndrome and Hepatobiliary Cancers

Background and Aim: Several studies have supported the idea that a metabolic abnormality contributes to expansion of hepatocellular carcinoma (HCC). To date, metabolic factors have not been shown to be associated with hepatocellular carcinoma (HCC). Therefore, the present study aimed to assess the metabolic syndrome association with hepatocellular carcinoma. Patients and Methods: This cross-sectional study was carried out on surgically treated and radiologically confirmed 360 HCC cases in Gastroenterology Department of Central Hospital, Sargodha and Hayatabad Medical Complex Peshawar, during the period from January 2022 June 2022. Study protocol was approved by the research and ethical committee. Informed written consents were taken from each individual. Body mass index, blood pressure, medical history, and other related information were gathered from medical records. Patients were categorized into different groups based on their BMI: i) <18.5 kg/m2, ii) 18.5-23.9 kg/m2, iii) 24-29.9 kg/m2, Fiv) 30-34.9 kg/m2 and ≥ 35 kg/m2. A routine biochemical or immunological analytic method was used to determine all metabolic parameters and liver function tests. The metabolic-associated factors were associated with HCC-related different liver function’s test and stratified for BMI, free fatty acids, and Glycated Albumin (GA). Chemical analysis was used to detect antioxidant capacity (TAOC) and malondialdehyde (MDA). Data analysis was done in SPSS version 27. Results: Of the total 360 HCC patients, there were 234 (65%) male and 126 (35%) females. The overall mean age was 68.62±6.4 years. The association between hepatobiliary cancer and body mass index (BMI), smoking, ischemic heart disease, hypertension, and diabetes was found in a univariate analysis of the data. Based on BMI, patients were categorized as follows: 35 (9.7%) in (<18.5 kg/m2), 70 (19.4%) in (18.5-23.5 kg/m2), 118 (32.8%) in (24-29.9 kg/m2), 88 (24.4%) in (30-34.9 kg/m2), and 49 (13.7%) in (≥ 35 kg/m2). The incidence of smokers, non-smokers, and ex-smokers were 146 (40.6%), 60 (16.7%), and 154 (42.8%) respectively. The prevalence of different risk factors such as hypertension, diabetes, ischemic heart disease, Aspirin use, and statin use was 188 (52.2%), 124 (34.4%), 66 (18.3%), 148 (41.1%), and 142 (39.4%) respectively. The HCC group had significantly higher mean body mass index, glucose level, and lipid level than controls (P <0.05). HCC patients showed a significant association between liver function and metabolic factors. A significant association between high level of GA and increased cancer risk were found between cases and control. Conclusion: The present study concluded that hepatobiliary carcinoma may be caused by metabolic syndrome, which includes dyslipidemia, a high body mass index, and high serum glucose levels as independent risk factors. This finding supports previous research and emphasizes that the connection between hapotabiliatry cancer and increased BMI remains for liver tumors, bile duct cancer, and gallbladder cancers. Keywords: Hepatobiliary carcinoma, metabolic syndrome, Obesity, Diabetes

Deficient Immune Response following SARS-CoV-2 Vaccination in Patients with Hepatobiliary Carcinoma: A Forgotten, Vulnerable Group of Patients

Introduction: Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment. Methods: In this prospective, longitudinal study, 101 patients were included, of whom 59 were patients with HBC under anticancer treatment. A cohort of patients with a past medical history of gastrointestinal cancer, of whom 28.6% had HBC without detectable active tumor disease having been off therapy for at least 12 months, served as control. Levels of SARS-CoV-2 anti-spike IgG, surrogate neutralization antibodies (sNABs), and cellular immune responses were compared. In uni- and multivariable subgroup analyses, risk factors for impaired immunogenicity were regarded. Data on rates and clinical courses of SARS-CoV-2 infections were documented. Results: In patients with HBC under active treatment, levels of SARS-CoV-2 anti-spike IgG were significantly lower (2.55 log10 BAU/mL; 95% CI: 2.33–2.76; p < 0.01) than in patients in follow-up care (3.02 log10 BAU/mL; 95% CI: 2.80–3.25) 4 weeks after two vaccinations. Antibody levels decreased over time, and differences between the groups diminished. However, titers of SARS-CoV-2 sNAB were for a longer time significantly lower in patients with HBC under treatment (64.19%; 95% CI: 55.90–72.48; p < 0.01) than in patients in follow-up care (84.13%; 95% CI: 76.95–91.31). Underlying CLD and/or liver cirrhosis Child-Pugh A or B (less than 8 points) did not seem to further impair immunogenicity. Conversely, chemotherapy and additional immunosuppression were found to significantly reduce antibody levels. After a third booster vaccination for SARS-CoV-2, levels of total and neutralization antibodies were equalized between the groups. Moreover, cellular response rates were balanced. Clinically, infection rates with SARS-CoV-2 were low, and no severe courses were observed. Conclusion: Patients with active HBC showed significantly impaired immune response rates to basic vaccinations for SARS-CoV-2, especially under chemotherapy, independent of underlying cirrhotic or non-cirrhotic CLD. Although booster vaccinations balanced differences, waning immunity was observed over time and should be monitored for further recommendations. Our data help clinicians decide on individual additional booster vaccinations and/or passive immunization or antiviral treatment in patients with HBC getting infected with SARS-CoV-2.

Eukaryotic Translation Initiation Factor 5A Independently Predicts Poor Prognosis of Cholangiocarcinoma Patients and Regulates the Ferroptosis and Mitochondrial Apoptosis.

Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma characterized by the differentiation of bile duct cells, and the patients with CCA often have a poor prognosis. Eukaryotic translation initiation factor 5A (eIF5A) is reported to have multiple biological activities. Targeted activation of ferroptosis may be a therapeutic strategy for cancer. Nevertheless, the effects of eIF5A and ferroptosis on CCA are still elucidated. Our study explored the effects of eIF5A in CCA, and the mechanisms also are studied. In this paper, TCGA database analysis suggested that eIF5A was upregulated in CCA, and high expression of eIF5A might predict a poor prognosis. Moreover, FANCD2, SLC7A11, and HSPB1 were significantly overexpressed in CCA. The results indicated that eIF5A was overexpressed in CCA tissues and cells. Further experiments demonstrated that eIF5A silencing decreased CCA cell activity and enhanced ferroptosis and mitochondrial apoptosis. In addition, upregulation of eIF5A showed the opposite effect on CCA cells compared with downregulation of eIF5A. Finally, the silencing of eIF5A could restrain the growth of xenografted tumors and promote ferroptosis. Overall, eIF5A enlarged CCA cell activity and attenuated ferroptosis and mitochondrial apoptosis. The results suggested that assessment of eIF5A might provide help for the diagnosis and treatment of CCA.

High expression of CCDC6 in relation to unfavorable outcome and immune cells infiltration in hepatobiliary carcinoma.

Background: The diagnosis of hepatobiliary carcinoma includes both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the first and the second most common hepatobiliary malignancies, respectively. CCDC6 (coiled-coil domain-containing protein 6) is a protein that interacts with apoptosis and DNA damage response elements and is commonly detected in cells. The prognostic and biological roles of CCDC6 in hepatobiliary carcinoma remain unknown.Methods: We used data from UALCAN, GEPIA, TIMER, GeneMANIA, STRING and HPA databases to determine the prognostic values and biological functions of CCDC6 in HCC and CCA. We downloaded the original online data from TCGA and GEO databases and analyzed them with R 3.2.2. We also gathered clinical records from patients with HCC (n = 94) and iCCA (n = 99) in our hospital to explore associations between CCDC6 expression and hepatobiliary carcinoma using immunohistochemistry detection. We used KEGG, GO and GESA analyses to explore relative pathways of CCDC6 in HCC and CCA. In addition, we assessed correlations between CCDC6 expression and tumor-infiltrating immune cells using data from the TIMER and GEPIA databases. Finally, we assessed associations between CCDC6 and marker genes of tumor-infiltrated immune cells in HCC to confirm some of our findings.Results: The mRNA and protein expressions of CCDC6 were noticeably upregulated in HCC and CCA tissues as compared with the expressions in healthy control tissues. The high CCDC6 expression levels were significantly correlated with advanced tumor grades as well as poor prognosis in patients with HCC, but not in patients with CCA. Our functional enrichment analysis revealed that CCDC6 is mainly involved in cell cycle processes, gene transcription, and immune cell-related pathways. Moreover, we found that the CCDC6 levels were positively correlated with the presence of tumor-infiltrating immune cells, including macrophages, CD4+T cells and dendritic cells.Conclusion: CCDC6 expression was increased in hepatobiliary carcinoma tissues. High expressions of CCDC6 were significantly associated with clinical severity variables (especially with advanced cancer stages and pathological tumor grades) and poor prognoses in patients with HCC. CCDC6 upregulation is associated with histone acetylation and immune infiltration in hepatobiliary carcinoma. In addition, CCDC6 has the potential to be used as a predictive biomarker during targeting therapy and immunotherapy.

A rare case of lipoprotein-X in cholestasis secondary to hepatobiliary carcinoma

Lead Author's Financial Disclosure: Nothing to disclose.

Anticancer Effect of Biodegradable Magnesium on Hepatobiliary Carcinoma: An In Vitro and In Vivo Study.

Biliary-stent implantation has become an effective treatment for patients with malignant obstructive jaundice caused by hepatobiliary carcinoma. Stent restenosis due to tumor ingrowth is a common problem. In this study, we assessed a biodegradable form of magnesium (Mg) for its anticancer effect on hepatobiliary carcinoma, compared to the conventional stent material of titanium (Ti). The results showed that a Mg extract inhibited proliferation and induced apoptosis in human cholangiocarcinoma cells, while a Mg plate inhibited cell adhesion and destroyed the cytoskeleton in the process of biodegradation. In animal experiments with H22 tumor-bearing mice, Mg wires implanted in tumors exhibited an inhibitory effect on their growth compared with Ti wires. Fifteen days after implantation of metal wires, the mean tumor volume and weight in the Mg group were significantly smaller than in the Ti group. We observed the dynamic-degradation process of Mg wires in tumors and generation of H2 gas via soft X-ray photography and scanning electron microscopy. Histopathological analyses showed that apoptosis of tumor cells around Mg wires significantly increased, expression of carbonic anhydrase 9 significantly decreased, and the upstream protein hypoxia-inducible factor 1-alpha also decreased to some extent. Taken together, these results indicated that biodegradable Mg had antitumor properties both in vitro and in vivo, suggesting its potential application as a novel material for biodegradable biliary stents.

Diagnostic and Prognostic Significance of CA 19-9 as Tumour Marker in Pancreatic, Hepatobiliary and Other Gastrointestinal Cancers

Introduction: The CA 19-9 antigen isolated by Koprowski and colleagues in 1979 is a lacto-N-fucopentaose II-like substance and one of the tumour-associated antigens present in serum in the mucin fraction. Close attention has been paid to the role CA 19-9 in the diagnosis of digestive tract tumours. In this study, serum analysis of CA 19-9 levels in 91 patients with gastrointestinal, hepatobiliary and pancreatic carcinoma was done. These data was used to evaluate the clinicians with adequate information on use of CA 19-9 as tumour marker- both diagnostic and prognostic. Aim: To study the role of tumour marker, CA 19-9 as a diagnostic and prognostic tool, and also to monitor the response of gastrointestinal, hepatobiliary and pancreatic cancer to treatment. Materials and Methods: This cross-sectional study was done on 91 cases of gastrointestinal, hepatobiliary and pancreatic carcinomas conducted in tertiary care hospital associated with medical college in Jamnagar, Gujarat, India were studied from September 2012 to March 2015 for two years and five months. The sample size was of 91 patients. Statistical method used was sensitivity, specificity, positive predictive value and negative predictive value. The material used was serum of the patient both pre as well as postoperatively and CalBiotech CA 19-9 Elisa Kit was used to determine the Value. The collected data were entered into Microsoft Excel spread sheet. The statistical methods used for variables were Mean and median along with Sensitivity and Specificity. Software used was “Epi Info”, version 7.0. Results: Total 91 cases of gastrointestinal, hepatobiliary and pancreatic carcinomas were studied. Enzyme Linked Immunosorbent Assay (ELISA) was used preoperatively and post operatively to determine the CA 19-9 values in patients of gastrointestinal, hepatobiliary and pancreatic carcinomas. It was found that CA 19-9 is an important tumour marker with sensitivity of 76.31% and specificity of 73.33% for diagnosis of the gastrointestinal, hepatobiliary and pancreatic carcinoma. When aided with Fine Needle Aspiration Cytology (FNAC) and histopathological findings it helps in giving a sure shot diagnosis. It also provides useful prognostic information for the same. Conclusion: This study helps to understand the role of CA 19-9 as diagnostic and prognostic marker for pancreatic, hepatobiliary and gastrointestinal carcinomas.

RETROSPECTIVE EVALUATION OF HEPATOCELLULAR NEOPLASMS IN NILE LECHWE (KOBUS MEGACEROS) FROM TWO FLORIDA ZOOLOGICAL INSTITUTIONS.

This case series describes hepatocellular neoplasms in 10 Nile lechwe (Kobus megaceros) at two separate zoological institutions in Florida. Histologically, the neoplasms were classified as hepatocellular carcinoma (n = 7), hepatocellular adenoma (n = 2), and hepatobiliary carcinoma (n = 1). Common clinical signs were nonspecific and included thin body condition (n =7), lethargy (n =6), lameness (n =3), and acute recumbency (n =5). Four males and six females were affected, and the mean age at death was 12.7 yr with a range of 4-18 yr. All cases were diagnosed postmortem, and metastasis to various sites, including lung, lymph nodes, and omentum, was found in 40% of cases (n = 4). A single case of hepatocellular carcinoma in a Nile lechwe was described in 2007; however, this is the first reported series of neoplasms in Reduncinae. The pathogenesis behind the development of hepatocellular neoplasms in Nile lechwe has not yet been identified.

Cholangiocarcinoma miscoding in hepatobiliary centres

IntroductionCholangiocarcinoma (CCA) are sub-divided into intrahepatic (iCCA) or extrahepatic (eCCA). eCCA are further subdivided into perihilar (pCCA) and distal (dCCA). Current and previous versions of the WHO International Coding of Disease and Oncology classifications (ICD) have separate topography codes for iCCA and eCCA, but none for pCCA. Over recent decades, multiple studies report rising incidence rates of iCCA with declining rates of eCCA, without reference to pCCA. We hypothesised the lack of a specific code for pCCA has led to errors CCA coding, specifically with miscoding of pCCA as iCCA. MethodsClinical notes of cases coded as hepatobiliary carcinoma using ICD-10 criteria (C22.1/Intrahepatic Bile Duct carcinoma, C24.0/Extrahepatic Bile Duct carcinoma, C23X/Malignant Neoplasm Gall Bladder, C22.0/Malignant Neoplasm Liver Cell Carcinoma) over a 2 year period (2015–2017), were reviewed by two independent clinicians at three independent UK regional HepatoPancreatoBiliary centres. The agreed final diagnosis was compared to the originally allocated ICD-10 code. ResultsOf the 625 CCA cases fully reviewed, 226 were coded as C22.1/iCCA. 98 (43%) of these were true iCCA and coded correctly, while 76 cases (34%) were actually pCCA. 92% all pCCA cases were incorrectly coded as iCCA. ConclusionCCA coding misclassification in UK HPB centres is common, particularly the miscoding of pCCA, which is extrahepatic and the commonest form of CCA, as iCCA. This may be contributing to apparent rising incidence rates of iCCA. Our findings confirm the need to implement distinct topographical codes for iCCA, pCCA and dCCA in future iterations of ICD.

Abstract 1095: Comprehensive pan-cancer analyses of RAS genomic diversity

Abstract The RAS family of small GTPases represents the most commonly activated oncogenes and mutations in KRAS, NRAS and HRAS are found in approximately one third of all human cancers. To better understand the prevalence of somatic RAS mutations and the compendium of genes that have RAS-dependent co-mutation frequencies in an unbiased pan-cancer manner, we analyzed targeted next-generation sequence data from the AACR Project GENIE Registry (GENIE version 6.1-public). Our analyses utilized 644,757 mutations from 64,217 tumors in 97 cancer types. A Bayesian hierarchical model was implemented to estimate cancer-specific prevalence of RAS and non-RAS somatic mutations. To evaluate RAS co-mutations, we compared the observed co-mutation frequencies of RAS and non-RAS somatic mutations to posterior predictive distributions of their expected co-mutation frequencies under independence. The prevalence of RAS codon 12, 13 and 61 mutations varied among cancer types, ranging from 77.7% in pancreatic cancer-PAC, 44.8% in colorectal cancer-CRC, 31.2% in non-small cell lung cancer-NSCLC, 1.1% in breast cancer, and 0.5% in mesotheliomas. A cancer type-specific distribution was observed, such that KRAS was frequently mutated in &amp;gt;25% of the tumors, NRAS was frequently mutated in melanoma, hematologic malignancies and thyroid cancer, while HRAS was overall less frequently mutated. KRAS codon 12 mutations predominated in pancreatic cancers (69.8%), GI cancers (30.9-48.5%), NSCLC (26.3%), endometrial cancer (14.7%) and germ cell tumors (11.6%). KRAS G12C mutations were predominantly seen in NSCLC (12.4%, 95% CI: 11.8-13.1%) with lower frequencies in GI cancers (3.2% in CRC). RAS mutations co-occurred with mutations in STK11, ATM, KEAP1, RBM10 and EPHA5 in NSCLC, TERT in melanoma and PIK3CA in CRC. Patterns of mutual exclusivity emerged between RAS mutations and BRAF in melanoma, thyroid and NSCLC, EGFR and RB1 in NSCLC, GNA11 and GNAQ in melanoma, FGFR3 in bladder cancer, MEN1 in PAC, RNF43 in CRC, BAP1 in melanoma and BAP1 and TERT2 in hepatobiliary carcinoma. A cancer type-specific co-occurrence pattern was noted for RAS and TP53 genomic alterations, with a significant enrichment in TP53 mutations in RAS-mutant PAC but a significant under-representation of TP53 mutations in RAS-mutant endometrial cancer, NSCLC, ovarian cancer and CRC. Analysis of codon specific RAS variants revealed additional co-mutation patterns, including an enrichment in NTRK3 mutations in KRAS G12C-mutant NSCLC and mutual exclusivity between KRAS G12C mutations and EGFR and BRAF in NSCLC. The tissue-distinct differential enrichment in RAS mutations and co-mutation patterns may be reflective of selection of oncogenic RAS signaling under the tumor type-specific modifying effect of other driver mutations. The RAS genetic architecture points to tissue-specific therapeutic vulnerabilities that may be translated to targeted treatment strategies. Citation Format: Robert Scharpf, Gregory Riely, Mark Awad, Michele Lenoue-Newton, Biagio Ricciuti, Julia Rudolph, Leon Raskin, Andrew Park, Jocelyn Lee, Christine Lovly, Valsamo Anagnostou. Comprehensive pan-cancer analyses of RAS genomic diversity [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 1095.

Incidental pulmonary embolism in oncologic patients\u2014a systematic review and meta-analysis

PurposeIncidental pulmonary embolism (IPE) is a common finding on computed tomography (CT). IPE is frequent in oncologic patients undergoing staging CT. The aim of this analysis was to provide the pooled frequency of IPE and frequencies of IPE in different primary tumors.MethodsMEDLINE, SCOPUS, and EMBASE databases were screened for studies investigating frequency of IPE in oncologic staging CT up to February 2020. Overall, 12 studies met the inclusion criteria and were included into the present study.ResultsThe pooled analysis yielded a total of 28,626 patients. IPE was identified in 963 patients (3.36%, 95% CI = 3.15; 3.57). The highest frequency was found in prostate cancer (8.59%, 95%CI = 3.74; 13.44), followed by hepatobiliary carcinoma (6.07%, 95%CI = 3.09; 9.05) and pancreatic cancer (5.65%, 95%CI = 3.54; 7.76). The lowest frequencies were identified in tumors of male reproductive organs (0.79%, 95%CI = 0.21; 1.37) and hematological diseases (1.11% 95%CI = 0.74; 1.48).ConclusionThe overall frequency of IPE in oncologic patients was 3.36%. There are considerable differences in regard to primary tumors with the highest frequency in prostate cancer and pancreatic and hepatobiliary carcinomas.