Hepatobiliary Tumors Research Articles

Survival outcomes according to the tumor mutation burden and PD-L1 expression in hepatobiliary tumors.

566 Background: Hepatobiliary (HB) tumors are aggressive tumors with emerging evidence for increasing sensitivity to immune checkpoint inhibitors (ICI). Tumor mutation burden (TMB) was found to be a quantitative biomarker associated with production of neoantigens within the tumor and predict the sensitivity to immune therapy. Herein, we explore the TMB, microsatellite instability (MSI) and PD-L1 expression as a potential biomarker of response to immune therapy in HB tumors. Methods: We retrospectively assessed all patients with hepatobiliary malignancies who have undergone next generation sequencing (NGS) between October 2009 and June 2019. We then analysed the tumor mutation burden and PD-L1 of these tumors and also identified frequency of patients with no clinically actionable mutations. Results: In our total 61 patients with HB tumors predominantly were male (62.3%) with mean age of 63 years. Thirty-four patients had hepatocellular carcinoma, 22 patients had cholangiocarcinoma and 5 patients had gallbladder carcinoma. The most common risk factors were smoking status, cirrhosis, alcohol consumption and hepatitis C virus. The mean TMB reported was 3.2 (1.16 – 7.35). MSI was identified in 13 patients and one was indeterminate. Only 17 patients had PD-L1 positive. At least, 37 patients had one clinically actionable mutation while 24 patients had no clinically actionable mutations. Mean overall survival was 16.6 months, but no statistically significant difference was found by high PD-L1 (3 vs 3.7 months, p=0.3) expression. Conclusions: Our data suggests the TMB in HB tumors is low in general irrespective of their underlying risk factors. We also noted more than half had microsatellite stable tumors and PD-L1 expression. Future larger studies are needed to evaluate TMB, MSI and PD-L1 as a potential biomarker in hepatobiliary tumors to help select patients that will benefit from immune therapy.

The aura of malignant tumor: Clinical analysis of malignant tumor-related pyogenic liver abscess.

The global incidence of pyogenic liver abscess (PLA) is increasing, but related reports of malignant tumor-related PLA are infrequent. Potential malignant tumors of PLA have been reported, but there is no relevant predictive model for this subsection of patients.To explore the risk factors of malignant tumor-related PLA.A retrospective analysis about a total of 881 patients who had been diagnosed with PLA from January 2005 to May 2018 was performed. The incidence of malignant tumor-related PLA in the study was 9.99% (88/881) out of all PLA cases. And that of potential malignant tumors with PLA was 4.65% (41/881). There were 62 patients with malignant tumor-related PLA in the observation group, while 146 cases without malignant tumor-related PLA were considered as control group. The data from 52 cases of malignant tumor and nonmalignant tumor-related PLA was verified.The malignant tumor type was mainly hepatobiliary malignant tumor, which occupies 72.3% (45/62) in all malignant tumor related PLA cases used to the model. Compared with nonmalignant tumor group, the rate of ineffective and mortality was higher in the malignant tumor group [19.4%(12/62) vs 7.5%(11/148), P = .01]. Multivariate analysis suggested that hepatobiliary interventional therapy or surgery, hepatitis B virus infection, multiple abscesses, portal embolism, and bile duct dilatation were independent risk factors for potential malignant tumors within the patients who combined with PLA.PLA could be considered as an early warning sign of potential malignant tumors. Malignant tumor-related PLA had a poor prognosis. Patients with PLA who have more than one independent risk factor or logit(P) > −1.694 may be considered as the high risk group for potential hepatobiliary or colorectal malignant tumors.

Platinum-based therapy of patients with gastrointestinal cancers that harbor homologous recombination DNA damage response (HR-DDR) mutations: A single institutional retrospective analysis.

836 Background: HR-DDR deficiencies have been described across cancer types and associated with response to specific therapies, including platinum (Pt)-based drugs and poly ADP-ribose polymerase (PARP) inhibitors. We sought to estimate the frequency of HR-DDR gene mutations in gastrointestinal (GI) cancers and determine if these patients (pts) benefit from Pt-based therapy. Methods: A retrospective chart review was performed on 421 pts with GI cancers treated at our institution. Tumors were categorized as colorectal (CRC), gastroesophageal (GE), pancreatic (PDA), hepatobiliary (HB), or other. All had next-generation sequencing with mutations in one or more of the following HR-DDR genes: BRCA1, BRCA2, PALB2, CHEK2, ATM, ARID1A, MRE11A, NBN, BARD1, and BL M. Overall survival (OS) of pts was analyzed using Log-rank test. Results: Of those analyzed, 127 pts (84 women and 43 men) met the inclusion criteria. Forty-eight percent had primary CRC tumors, and the remainder had primary GE (17%), PDA (14%), HB (10%), and other GI (11%) tumors. Fifty-four percent had stage IV disease. Sixty-five percent received Pt-based therapy at some point during their disease course. HR-DDR analysis revealed the following mutation rates: 34% ARID1A; 16% ATM; 19% BRCA2; and 9% BRCA1. OS analysis showed no significant survival advantage based on stage or mutation type for any of the disease-specific cohorts. There was no significant OS benefit in pts who received Pt-based therapy vs. those who did not, although pts with ARID1A-mutated tumors did show a trend towards improved OS (P = 0.09). Conclusions: Despite our limited cohort, our data suggest that pts with GI tumors harboring certain HR-DDR gene mutations might benefit from Pt-based therapy, supporting the development of mutation-specific Pt-based clinical trials.

Primary Gallbladder Adenocarcinoma in a Cat

Background: Biliary tumors have low incidence in cats and are more common in elderly animals. Hepatobiliary tumors have different classifications and their etiology is difficult to interpret. In most cases, the diagnosis is only possible in advanced stages, which clouds the precursor factors. The late diagnosis is explained by the absence or specificity of clinical manifestations and laboratory changes. The majority of hepatobiliary neoplasms in cats are incidental findings in surgeries or necropsies. This study aimed to report clinical, laboratory, pathological and immunohistochemical results in a feline case of gall bladder adenocarcinoma.Case: A cat, male, neutered, mixed breed, 4 years, was admitted at a veterinary clinic with a history of polyuria / polydipsia, anorexia, apathy, jaundice and emesis for 60 days. The animal had been treated in another clinic with silymarin, famotidine and cyanocobalamin, and fed by esophageal tube based on the presumptive clinical diagnosis of cholangitis. The clinical examination revealed jaundice, abdominal pain, weight loss, enlargement of the liver and gallbladder and the presence of a structure in the epigastric region. Based on clinical signs, blood tests (complete blood count and liver enzymes), abdominal ultrasound and thoracic radiography were requested. In the exam results, eosinophilia, bilirubinemia and increased alkaline phosphatase, glutamic pyruvic transaminase and gamma glutamyl transferase were observed, in addition to the presence of icteric and hemolyzed serum. Ultrasound exam revealed thickened and dilated cystic and common ducts, large and thick gallbladder, bile with bile mud, hypoechogenic liver, thickening in the duodenal papilla and enlarged pancreatic and duodenal lymph nodes. There were no alterations in thoracic radiography. Based on the findings, the diagnosis of extrahepatic biliary obstruction was suggested. In celiotomy, dilated gallbladder with a thick blackened wall was observed. Bile puncture was performed for analysis, and total cholecystectomy and removal of obstructive content was performed. The patient suffered cardiorespiratory arrest after the procedure. A fragment of gallbladder and liver were sent to evaluation with histopathology and immunohistochemistry, and results were compatible with gallbladder adenocarcinoma.Discussion: Hepatobiliary neoplasms in cats are uncommon, apart from lymphoma. The incidence is higher in elderly cats and in males, which did not match the animal in this case. The clinical presentation of the condition is quite nonspecific, corroborating with other reports, in which changes are often only evident in advanced stages of the disease. Laboratory and imaging findings pointed to a biliary tree disorder, and cholangitis was suggested. However, the lack of clinical improvement and examination findings of exams lead to an exploratory laparotomy for better inspection of the organs and identification of possible causes. One of the differential diagnoses that should be considered in cats with extrahepatic biliary obstruction is gallbladder adenocarcinoma, especially in animals with an unsatisfactory response in clinical treatment. Tests such as histopathology and immunohistochemistry are essential for the definitive diagnosis of this neoplasm. Surgical resection is indicated in cases of malignant masses, providing longevity and better quality of life. Hypotension is a common complication in hepatobiliary surgeries, which can result in death.

Pathology of liver tumors

Based on recent advances in morphological and molecular research, tissue-based diagnostics of liver tumors exhibit a substantial dynamic. New clinically relevant tumor subtypes have been defined and the diagnostic criteria have been improved; examples are the new morphomolecular classifications of hepatocellular carcinoma and adenoma as well as intrahepatic cholangiocarcinoma. Therefore, molecular pathological diagnostics are gaining relevance in the identification of tumor types and therapeutic stratification. These developments are reflected in the new World Health Organization (WHO) classification of hepatobiliary tumors and the respective clinical practice guidelines.

MELD score does not increase after hepatectomy in cirrhotic patients

Presenter: Maria Baimas-George MD, MPH | Carolinas HealthCare System Background: With prevalence of hepatic cirrhosis increasing, there is a subsequent increase in patients needing liver resections as it is the mainstay of treatment for many hepatobiliary neoplasms. However, because of the reduced ability of a cirrhotic liver to tolerate surgical insult and mass reduction, resection requires consideration between oncologic benefit and risk of impaired hepatic reserve as liver function is expected to deteriorate post-operatively. To quantify this risk, we evaluated change in MELD and MELD-Na scores in cirrhotic patients with hepatocellular carcinoma (HCC) after liver resection. Methods: A retrospective review identified all cirrhotic patients with HCC who underwent a hepatic resection between 2010 to 2017 at a single tertiary-care institute. The MELD scores for each patient were calculated pre-operatively, immediately post-operative, and the first time point 3 months after surgery. Patients were stratified by major (>3 segment resection) and minor hepatectomy and by MELD/MELD-Na score (MELD: < 10 and 10; MELD-Na < 12 and 12) and the change after 3 months was evaluated. Results: Thirty-five patients were identified. Of these, 20 patients underwent a minor hepatectomy and 15 underwent a major hepatectomy. In the minor hepatectomy cohort, low-MELD patients (n=14) demonstrated an increase of 0.6 in MELD score 3 months post-operatively whereas the high-MELD cohort (n=6) demonstrated a decrease of 0.9. When stratified by MELD-Na, low-MELD-Na (n=14) demonstrated an increase of 0.2 whereas the high-MELD-Na (n=6) had a decrease of 1.0 after 3 months. In the major hepatectomy cohort, low-MELD patients (n=13) demonstrated an increase in MELD of 3.9 whereas high-MELD (n=2) had a decrease of 0.5 after 3 months. When stratified by MELD-Na, low-MELD-Na (n=9) demonstrated an increase of 4.9 whereas high-MELD-Na (n=6) had a decrease of 1.0. Conclusion: Liver function is expected to deteriorate post-operatively in cirrhotic patients undergoing hepatic resection. We demonstrate that MELD and MELD-Na scores either stay the same or mildly improve after 3 months post-operatively in patients undergoing minor hepatectomies, suggesting that either there is a adequate hepatic reserve present or the liver may repopuluate healthy hepatocytes.

Pathological and immunohistochemical aspects of primary hepatobiliary neoplasms in cats

ABSTRACT: Primary hepatobiliary neoplasms (PHN) are uncommon in cats, and originate in hepatocytes, intra- and extrahepatic bile ducts, mesenchymal cells, and cells of neuroendocrine origin. The aim of this study was to determine the frequency of PHN in cats diagnosed in the metropolitan region of Porto Alegre (RS), Brazil, for a period of 17 years, determining their epidemiological, anatomopathological and immunohistochemical aspects. Necropsy reports of 2.090 cats were analyzed, 125 were diagnosed with primary hepatobiliary diseases, of which 15 were cases of PHN, representing 12% of the specific hepatobiliary conditions and 0.7% of the necropsies. All PHN were malignant, of which 93.3% had epithelial origin and 6.7% presented mesenchymal origin. Cholangiocarcinoma was the most commonly diagnosed neoplasm, followed by hepatocellular carcinoma and hemangiosarcoma. In general, cats with no defined breed were the most affected. Concerning sex, 60% were females and 40% males. Age ranged from five to 18 years, with a mean age of 10.5 years (median of ten years). Grossly, cholangiocarcinoma and hemangiosarcoma were multinodular and hepatocellular carcinoma was massive. Microscopically, cholangiocarcinomas were arranged in acini and ducts, whereas hepatocellular carcinomas were arranged in solid sheets or trabeculae. On immunohistochemistry, cholangiocarcinomas, hepatocellular carcinomas, and hemangiosarcomas were positive for the antibodies CK 7, Hep Par-1, and vimentin and von Willebrand factor, respectively.

Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry (SweLiv)

Background: Complete national registry data on hepatocellular carcinoma (HCC) treatment patterns and long-term survival are not available. The aim was to describe treatment provided and survival in patients diagnosed with HCC in Sweden. Methods: Since 2009, Sweden has a national registry of hepatobiliary tumours (SweLiv), where all patients with malignancy in the liver are registered including provided treatments. Patient characteristics, treatment patterns and survival in HCC patients registered between 1 January 2009 and 31 December 2016 were analysed in the study. Kaplan-Meier analysis was used to estimate survival conditional on treatment group. Register completeness for 2009-2016 was 95.6%. Results: 3376 HCC patients were registered. Five hundred-one (14.8%) were resected, 390 (11.6%) ablated and 246 (7.2%) transplanted, as the primary treatment. 476 (14.1%) were offered transarterial chemoembolization (TACE) and 426 (12.6%) systemic sorafenib treatment, the remaining 1337 patients (40.0%) were offered the best supportive care (BSC). Median survival was 1.44 (95% CI: 1.31 - 1.63), 0.48 (95% CI: 0.45 - 0.58) and 0.25 (95% CI: 0.23 - 0.28) years for the TACE, sorafenib and BSC groups, respectively. Overall 5-year survival rates were 75% for transplanted, 50% for resected, and 28% for ablated treated patients. In the 20% of patients with ECOG score 2 offered curative treatment, median survival was not reached during 3 year follow up after transplantation or resection and was 28 months after ablation. After the introduction of national guidelines in 2013, median survival for the entire cohort was 17 months, which is 6 months longer compared with the time-period before. Simultaneously, treatment shifted from BSC towards ablation and resection. Conclusions: The majority of patients with HCC are given active treatment in Sweden. Survival may have improved with the introduction of national guidelines. Selected patients with low performance status seem to benefit from curative treatment.

Pattern of use of positron emission tomography/computed tomography (PET/CT) scan in non-colorectal gastrointestinal cancers at KFSHRC, Riyadh, Saudi Arabia

BackgroundPositron emission tomography/computed tomography (PET/CT) scan is useful if clinically indicated. It is not for conventional routine use due to its high cost. Moreover, it can be confusing if ordered in non-indicated conditions. We evaluate if the pattern of PET/CT ordered in gastrointestinal cancers (non-colorectal origin) has followed evidence-based guidelines and whether it helped in the improvement of patient’s outcome. This study included non-colorectal gastrointestinal cancer patients from 2007 to 2008 who had one or more PET/CT scans done during their management. In each case, data collected revealed whether PET/CT affected the management or the stage or not. Patients were identified through the hospital tumor registry software CNExT (C/NET Solutions, Berkeley, CA). Tabulation and statistical data analysis were done using JMP-SAS statistical software application (version 9.4: SAS Institute, Cary, NC, USA). The scan report quality and use indications were outlined.ResultsSeventy-seven patients were identified, with 107 PET/CT scans done. Their median age is 59 (21–86) years. Males were 45 (58.5%). Tumor origin was 46.8% esophageal and gastroesophageal junction cancer, 15.6% gastric cancer, 11.7% pancreatic cancer, 11.7% hepatobiliary tumors, 10.4% neuroendocrine tumors, 2.6 % gastrointestinal stromal tumors, and 1.3% small bowel cancer. Indications of the PET/CT were as follows: staging in 59.8%, follow-up after finishing treatment in 14.9%, restaging at relapse in 8.4%, assessing response after/during treatment in 3.7%, follow-up of previous PET/CT in 12.1%, and others in 0.9%. PET/CT changed the stage in 19.6% and affected the management plan in 11.2% only. Fifty-two scans needed pathological pursuit as decided by investigators; of them, PET/CT for the lesions that could have changed the stage reported indeterminate/equivocal results in 32 (29.9%) of all scans. The pathological pursuit for the equivocal lesions on PET/CT scans was done in only 12 of 52 (23.1%) scans.ConclusionsLocal guidelines for ordering PET/CT scan are suggested because overuse was documented, and an evidence-based approach should be respected before its use.

Enhancement pattern mapping technique for improving contrast-to-noise ratios and detectability of hepatobiliary tumors on multiphase computed tomography.

Currently, radiologists use tumor-to-normal tissue contrast across multiphase computed tomography (MPCT) for lesion detection. Here, we developed a novel voxel-based enhancement pattern mapping (EPM) technique and investigated its ability to improve contrast-to-noise ratios (CNRs) in a phantom study and in patients with hepatobiliary cancers. The EPM algorithm is based on the root mean square deviation between each voxel and a normal liver enhancement model using patient-specific (EPM-PA) or population data (EPM-PO). We created a phantom consisting of liver tissue and tumors with distinct enhancement signals under varying tumor sizes, motion, and noise. We also retrospectively evaluated 89 patients with hepatobiliary cancers who underwent active breath-hold MPCT between 2016 and 2017. MPCT phases were registered using a three-dimensional deformable image registration algorithm. For the patient study, CNRs of tumor to adjacent tissue across MPCT phases, EPM-PA and EPM-PO were measured and compared. EPM resulted in statistically significant CNR improvement (P<0.05) for tumor sizes down to 3mm, but the CNR improvement was significantly affected by tumor motion and image noise. Eighty-two of 89 hepatobiliary cases showed CNR improvement with EPM (PA or PO) over grayscale MPCT, by an average factor of 1.4, 1.6, and 1.5 for cholangiocarcinoma, hepatocellular carcinoma, and colorectal liver metastasis, respectively (P<0.05 for all). EPM increases CNR compared with grayscale MPCT for primary and secondary hepatobiliary cancers. This new visualization method derived from MPCT datasets may have applications for early cancer detection, radiomic characterization, tumor treatment response, and segmentation. We developed a voxel-wise enhancement pattern mapping (EPM) technique to improve the contrast-to-noise ratio (CNR) of multiphase CT. The improvement in CNR was observed in datasets of patients with cholangiocarcinoma, hepatocellular carcinoma, and colorectal liver metastasis. EPM has the potential to be clinically useful for cancers with regard to early detection, radiomic characterization, response, and segmentation.

Application and mechanism of manganese-coated caramelization nanospheres for active targeting in hepatobiliary tumors.

Aim: To elucidate the MRI mechanisms of manganese oxide-coated carbohydration nanosphere (Mn@CNS) for active targeting in hepatobiliary tumors. Materials & methods: The cytotoxicity, internalization pathway, metabolism and excretion pathway of Mn@CNS were assessed by several cell types. The MRI of Mn@CNS was verified via rat models bearing hepatobiliary tumors. Results: Mn@CNS showed no obvious cytotoxicity. Mice macrophage and hepatocellular Mn content significantly differed between pre- and post-uptake levels (p<0.01). The animal experiment revealed fine T1 imaging of hepatobiliary tumors with peak enhancement at 3h. Mn@CNS was metabolized within the cells and excreted mainly via feces. Conclusion: Mn@CNS is safe, biodegradable, and may serve as a new strategy for active target imaging and treatment applications.

Contrast-enhanced ultrasonography features of hepatobiliary neoplasms in cats

BackgroundContrast-enhanced ultrasonography (CEUS) features of primary hepatobiliary neoplasms have been reported in dogs but no information is available in cats.MethodsQualitative and quantitative features of bile duct adenomas (BDAs, n=20), bile...

Axitinib Plus Toripalimab as Second-line Treatment in Hepatobiliary Malignant Tumors

Axitinib Plus Toripalimab as Second-line Treatment in Hepatobiliary Malignant Tumors

Colangiocarcinoma primario con metástasis duodenal y bazo en felino con virus de leucemia: reporte de un caso

Primary hepatobiliary neoplasms are rare in cats. They can differentiate according to their form of expansion in nodular, massive or diffuse. The definitive diagnosis is with histopathological examination, however, in the majority, the diagnosis turns out to be in postmortem. Due to its aggressive biological behavior, the prognosis becomes unfavorable. The objective of the present study was to report the case of a nine-year-old female feline with chronic renal disease and feline leukemia virus, who was diagnosed with a fast evolutionary cholangiocarcinoma (30 days) that evolved to metastasis in the duodenum and spleen.

CT finding in neoplasms of Hepatobiliary system

The orginal and extent of mass lesion could be defined better the ultrasonography. Moving further currently multiphasic contrast enhariced dynamic CT has shown promise in better characterization of the morphology of hepato-biliary tumors with its multiplanar reformats, and phasic study. The prospective study will include 50 patients of hepato-biliary malignancies being treated at Tertiary care Hospital. Before commencing for CT examination all procedure, historical, clinical, laboratory data was recorded. Most common primary was from colorectal malignancy constituting 11 cases (39%), followed by gastric carcinoma (6 cases, 21%), pancreatic malignancy (3 cases, 11%). Majority of the heptic metastasic nodules appear illdefined irregular iso to hypodense (21 out of 28 patients; 785%) on NCCT scan. And no/minimal enhancement noted after contrast study (17 out of 28 patients: 61%). Majority of the metastatic nodules are solitary (64%), and right lobe is most commonly involved (20 out of 28 patients (72%). The mean size of metastatic lesions encountered in our study was 4.2cm.

Differentiation of hypervascular primary hepatic tumors showing hepatobiliary hypointensity on gadoxetic acid-enhanced magnetic resonance imaging.

To determine the imaging features that help differentiate hypervascular primary hepatic tumors showing hepatobiliary hypointensity on gadoxetic acid MRI. This study comprised 148 patients with pathologically proven hypervascular hepatic tumors who underwent gadoxetic acid MRI. Tumors included 23 atypical focal nodular hyperplasias (FNHs), 11 hepatocellular adenomas (HCAs), 15 neuroendocrine tumors (NETs), 25 intrahepatic cholangiocarcinomas (ICCs), and 74 hepatocellular carcinomas (HCCs). MRIs were analyzed for morphologic features, signal intensity, and enhancement pattern of the tumors to determine the differential features using multivariate logistic regression analysis. We evaluated the diagnostic performance of the MRI features for differentiating the five tumor types upon review by two observers. Multivariate analysis revealed that reverse target sign on hepatobiliary phase in FNHs (p = 0.009), iso or hyperintensity on ADC map in FNHs and HCAs (p = 0.009, < 0.001, respectively), central hypointensity on arterial phase in NETs (p = 0.001), hepatobiliary target sign in ICCs (p = 0.002), the presence of septum and capsule in HCCs (all p < 0.001) were significant independent features of each tumor group over other tumor groups. Diagnostic accuracy for both observers was 98-98.6% for FNHs, 96.6-98% for HCAs, 97.3-98.6% for NETs, 90.5-94.6% for ICCs, and 85.8-93.2% for HCCs. Ancillary MRI features established in our study can be helpful in the differentiation of hypervascular and hepatobiliary hypointense primary hepatic tumors on gadoxetic acid MRI.

Outcomes of extended hepatectomy for hepatobiliary tumors. Initial experience from a non-university hepatobiliary center

IntroductionHepatectomy is the gold standard curative treatment for hepatic neoplasms in patients with preserved liver function. Many large tumors require extended hepatectomy (EH). Possibility of developing major postoperative complications including liver failure is feared by many surgeons. We aim to describe our outcomes of EH for large hepatobiliary tumors. Material and methodsAll patients undergoing hepatectomy between 2012 and 2017 were prospectively followed. Results91 patients underwent hepatectomy with ten patients underwent EH. The majority of patients were women, age of 63, BMI of 24, and MELD score of 11. Six patients underwent an extended right hepatectomy, while four patients underwent extended left hepatectomy. Operative time was 224 min with estimated blood loss of 500 ml. No intraoperative complications were seen. Two patients experienced postoperative complications (pleural effusion in one patient and respiratory failure in another). Length of ICU stay was 2 days, and hospital stay was 5 days. 80% of the patients are currently alive with median follow-up of 41.2 months. ConclusionEH can be undertaken safely with acceptable morbidity and mortality in our center.

Comparison of biomarkers among 34,855 GI cancer samples show heterogeneity of tumor types.

e14287 Background: Recent data indicate that biomarker driven use of targeted therapy and I/O-therapy among patients with GI cancer is associated with improved outcome. The presence of biomarkers varies broadly between different GI tumor types, highlighting the importance of comprehensive molecular profiling.To analyze the presence of various alterations in GI cancer samples of a large database, comparing congruency between various tumor types. Methods: A retrospective data analysis of 34855 GI cancer patients profiled at CARIS Life Sciences obtained from Jan 1st2010 till Sep 14th2018 was performed. GI tumors were classified as : CRC, esophageal/gastric/GIST, small intestine, pancreatic/hepatobiliary/liver. Technologies used to analyze the biomarkers: IHC for PD-L1, MMR and Her2, and DNA-NGS for EGFR, BRAF, KRAS, NRAS, MET-CNV, TMB, MSI, POLE and BRCA1/2. Results: Median age was 61 (range 18-89 years). 51.5% was CRC (n = 18047), 15.5 % was esophageal /Gastric/GIST (n = 5470), 3% was small intestinal cancer (n = 886) and 30% was pancreatic/hepatobiliary/liver cancer (n = 10452). Information on biomarkers was available from 2931 cases for MET amplification to 28536 for RAS information. Overall, the most common finding was a pathogenic RAS-mutation (either KRAS or NRAS) in 7650 cases (26.81%), the rarest one was a mutation in EGFR in 12 cases (0.06%). Higher rate of HER2 amplification was observed among pts with esophageal/gastric/GIST tumors (6.5%) in comparison to tumors at other GI sites ( ~1.5%). High TMB was seen among patient with CRC and small intestine tumors (~7%) while it was lowest among pancreatic cancer (1.8%). Compared to other GI sites lower MSI /MMR deficiency rates were observed in pancreatic /hepatobiliary tumors, significantly higher PD-L1 positivity was observed in gastrooesophageal cancer types, increased MET-amplifications in gastrooesophageal and small intestinal cancer types and lower RAS-mutation rate in gastrooesophageal cancer. Conclusions: Molecular profiling analyzing druggable biomarkers can help identify patients with increased likelihood for benefit from immune-checkpoint-inhibitors and targeted therapies. Further investigations are needed to evaluate the different findings in various GI cancer types.

Cholangiocarcinoma in Young Cats

Background: Cholangiocellular carcinoma is a malignant tumor that occurs mainly in elderly dogs and cats. Primary hepatobiliary neoplasms are considered rare in felines, although cholangiocarcinoma is the most common tumor type among malignant liver tumors in the species. The objective of this work is to report two cases of cholangiocarcinoma in young domestic cats, with three years old, and to approach clinical and pathological aspects to promote awareness of this type of injury in young animals, with a focus on prevention of predisposing factors.Cases: A 3-year-old male domestic cat (cat 1) had a history of progressive weight loss, persistent vomiting, diarrhea, and episodes of seizure. At the clinical examination was noted moderate degree of jaundice. In the biochemical exams it was verified as alteration hypoproteinemia, increase of urea and hyponatremia. Abdominal ultrasonography revealed a formation in the left epigastric region measuring 8.0 x 5.0 cm, with a diffusely heterogeneous parenchyma, suggestive of hepatic neoplasia, in addition to the presence of free abdominal fluid. Cavity fluid analysis was suggestive of carcinoma. A 3-year-old male domestic cat (cat 2), with history of hyporexia, emaciation and vomiting was taken to care. Physical examination showed moderate dehydration, hypocorous mucosa and presence of abdominal mass on palpation. The animal's serum biochemical assessment were verified as changes, increasing AST. Ultrasonographic examination showed an abdominal mass, located caudally to the spleen, with irregular shape, measuring approximately 4.7 cm suggestive of hepatic neoplasia, in addition to the presence of abdominal fluid. The hepatic cytology performed by fine needle aspiration was suggestive of carcinoma. After the clinical worsening of two cats and due unfavorable prognosis, euthanasia and necropsy were performed. In the macroscopic analysis of cat 1, numerous nodules of whitish and sometimes "umbilicate" coloration were observed in the liver, measuring up to three cm in diameter, distributed randomly by the hepatic parenchyma and with a soft consistency at cut. An ovoid-wicking mass, measuring 6.0 x 7.0 x 5.0 cm in diameter and coloring ranging from white to light brown was checked together. In the macroscopic evaluation of cat 2, numerous coalescing masses of whitish coloring measuring up to 6.0 cm in diameter were observed covering almost every hepatic parenchyma and also affecting the pancreas, with a soft consistency at cut. The microscopic findings of both cats were compatible with the diagnosis of cholangiocarcinoma. Considering the immunohistochemical profile, in both cases there was positivity for the CK Pan antibody and CEA and negativity for the CK20, TTF-1, Hepatocyte specific antigen, CD10 and CD56 antibodies.Discussion: Cholangiocarcinomas usually occur in elderly animals, with a mean age of 9 years, so it may be suggested that the cause of the disease in cat 1 and 2 was possibly related to the early and continuous presence of carcinogens. The biliary duct trematod Platynosomum fastosum, the chemical agents plutonium and americium, intestinal parasites such as Ancylostoma spp. and Trichuris vulpis, as well as the occurrence of chronic inflammations independent of etiology are commonly involved in the occurrence of cholangiocarcinoma. Clinical and anatomopathological observations made evident that these two young cats, with three years old, had metastatic cholangiocarcinoma. Thus, veterinary providers should be aware that this tumor type can occur in young animals and is mindful of means of prevention and / or recommended treatment of predisposing factors.

Lymphadenectomy in oncological visceral surgery-Part1 : Hepatobiliary tumors and pancreatic cancer

Lymphadenectomy is an integral component of the oncological surgery of cancer of the gastrointestinal tract and the hepato-pancreato-biliary system. The lymph node dissection is mainly prognostic but may also offer therapeutic advantages in the treatment of most cancers. Moreover, lymphadenectomy enables an accurate TNM staging, which is essential for afurther stratification of the individual treatment as well as the inclusion in clinical trials on adjuvant therapy. This article gives an overview of the anatomy of the lymphatic drainage system of visceral organs and summarizes the current role of asystematic lymphadenectomy in oncological surgery (Part1: hepatobiliary tumors and pancreatic cancer).