Intrahepatic Bile Duct Carcinoma Research Articles

Genetic issues in ICP.

Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disorder with variable global incidence. Genetic susceptibility, combined with hormonal and environmental influences, contributes to ICP aetiology. Adverse pregnancy outcomes linked to elevated serum bile acids highlight the importance of comprehensive risk assessment. ABCB4 and ABCB11 gene variants play a significant role in about 20% of severe ICP cases. Several other genes including ATP8B1, NR1H4, ABCC2, TJP2, SERPINA1, GCKR and HNF4A have also been implicated with ICP. Additionally, ABCB4 variants elevate the risk of drug-induced intrahepatic cholestasis, gallstone disease, gallbladder and bile duct carcinoma, liver cirrhosis and abnormal liver function tests. Genetic variations, both rare and common, intricately contribute to ICP susceptibility. Leveraging genetic insights holds promise for personalised management and intervention strategies. Further research is needed to elucidate variant-specific phenotypic expressions and therapeutic implications, advancing precision medicine in ICP management.

Adenosquamous carcinoma of the liver: The challenge of diagnosis.

Adenosquamous carcinoma of the liver is extremely rare. We report a case of adenosquamous carcinoma in the intrahepatic bile duct of a 56-year-old woman who complained of persistent abdominal pain, shivering and hyperthermia. Computed tomography demonstrated a solid-cystic neoplasm in segment 5/6/8 of the liver with a gradual enhancement pattern in the solid area. However, postoperative pathological examination showed adenosquamous carcinoma of intrahepatic bile duct.

Median liver resection in a patient with intrahepatic bile duct carcinoma

Median liver resection in a patient with intrahepatic bile duct carcinoma

Outcome of Localized Bile Duct Carcinoma in Six Dogs Treated with Liver Lobectomy.

The prognosis for bile duct carcinoma in dogs is generally believed to be poor. However, only a few studies have evaluated the postoperative outcomes in such cases. The objective of this case series was to describe the postoperative outcomes of localized intrahepatic bile duct carcinoma in dogs. The electronic medical records of 16 dogs with bile duct carcinoma were reviewed, and 6 dogs were included in the study. All cases were diagnosed as bile duct carcinoma using postoperative pathology, and five of them had already been diagnosed using preoperative core biopsy. The tumors in all of the dogs were confirmed as completely resected on histopathological examination. Two dogs received toceranib following the surgery. The median follow-up time was 693 days (range, 420-1386 days), with a median survival time of 894 days (range, 420-1386 days). Local recurrence or distant metastases were detected in two of the six dogs (33%) on 354 and 398 days following surgery, respectively. The median progression-free survival was 492 days (range, 354-1386 days). In conclusion, dogs with localized intrahepatic bile duct carcinoma had a good prognosis following complete surgical resection.

Pancreatic, Gastric, and other Gastrointestinal Cancers

According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index. This review contains 9 figures, 39 tables, and 173 references. Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

Pancreatic, Gastric, and other Gastrointestinal Cancers

According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index. This review contains 9 figures, 39 tables, and 173 references. Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

Correlation between Expression Differences of Epithelial-Mesenchymal Transition (EMT) in Cholangiocarcinoma Tissue

Background: By studying the expression of epithelial-mesenchymal transition regulators in cholangiocarcinoma and intrahepatic duct stones, the correlation between the expression of epithelial-mesenchymal transition regulators and cholangiocarcinoma was revealed. Objective: The objective is to investigate the correlation between the expression of epithelial-mesenchymal transition (EC) regulatory factors and cholangiocarcinoma in patients with intrahepatic duct stones and cholangiocarcinoma, to investigate the relationship between clinicopathological features and prognosis, and to observe the expression of molecular markers of epithelial-mesenchymal transition (EMT) in intrahepatic duct stones and bile duct carcinoma. Methods: Twenty cases of primary cholangiocarcinoma, 20 cases of intrahepatic cholangiolithiasis complicated with cholangiocarcinoma, and 20 cases of intrahepatic cholangiolithiasis specimens were collected from the Fourth People’s Hospital and the friendly medical unit of Haikou. Immunohistochemistry was used to detect the expression differences of EMT-related molecular markers Twisit1, Twisit2, E-cadherin, N-cadherin, and Vimentin in paraffin sections of normal intrahepatic bile duct tissues and patients with intrahepatic duct stones and cholangiocarcinoma. Results: Immunohistochemical staining revealed epithelial-mesenchymal transition (EMT) in intrahepatic cholangiocarcinoma tissue, intrahepatic cholangiolithiasis with cholangiocarcinoma, intrahepatic cholangiolithiasis with normal intrahepatic cholangiolithiasis, such as Sit1, Twisit2, E-cadherin, N-cadherin, and Vimentin proteins were different. The expression of E-cadherin was decreased in cholangiocarcinoma tissue and intrahepatic cholangiolithiocarcinoma combined with cholangiocarcinoma (P 0.05). There was no difference in the expression of intrahepatic bile duct stones and EMT (P > 0.05). Conclusion: The expression of E-cadherin, the molecular marker of EMT, was down-regulated, while the expression of N-cadherin and Vimentin was up-regulated. Age, gender, depth of tumor invasion, degree of tumor differentiation and lymph node metastasis were correlated with the expression of EMT in intrahepatic cholangiocarcinoma.

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 3627: Comparison of genetic profiles of small and large duct type intrahepatic cholangiocarcinoma with distal extrahepatic cholangiocarcinoma

Abstract Cholangiocarcinoma comprises epithelial malignancy that occurs in various sites in the biliary tree. Cholangiocarcinoma is categorized into intrahepatic, perihilar, and distal bile duct carcinomas according to its anatomical position. According to the fifth edition of World Health Organization Classification of Tumors, intrahepatic cholangiocarcinoma (ICC) is further classified into small- and large duct types on histopathological basis. We analyzed molecular profiles of different types of cholangiocarcinoma by next-generation sequencing (NGS). We utilized the Oncomine Comprehensive Assay (OCA) panel v2 on the IonTorrent™ NGS platform to explore genetic differences among the two histologic types of ICC and distal extrahepatic cholangiocarcinoma (DEC). Formalin-fixed paraffin-embedded tumor tissues were obtained from 25 patients who underwent surgical resection of cholangiocarcinoma in Korea University Guro Hospital between 2010 and 2018. We analyzed 7 and 8 small- and large duct type ICCs and 10 DECs. NGS assay of the included cases showed distinct genetic alterations between ICC and DEC, which were enriched in different biological pathways. Unsupervised hierarchical clustering analysis showed two distinct groups. The first group consisted of 12 cases (9 DECs and 3 large duct type ICCs). The second group included 13 cases (7 large duct type and 6 small duct type ICCs). Molecular alteration patterns of a subset of large duct type ICCs were more closely related to DECs than small duct type ICCs. All included small duct type ICCs were considered genetically distinct from DECs. Our study suggested an association between anatomical and histopathological classifications of intra- and extrahepatic cholangiocarcinomas. Citation Format: Hayeon Kim, Soo Yeon Lee, Aeree Kim, Baek-hui Kim, Chung-yeul Kim. Comparison of genetic profiles of small and large duct type intrahepatic cholangiocarcinoma with distal extrahepatic cholangiocarcinoma [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 3627.

Hepatitis B virus infection and the risk of cancer among the Chinese population.

The relationship between hepatitis B virus (HBV) and nonhepatocellular cancers remains inconclusive. This large case-control study aimed to assess the associations between HBV infection status and multiple cancers. Cases (n = 50 392) and controls (n = 11 361) were consecutively recruited from 2008 to 2016 at the First Affiliated Hospital of Nanjing Medical University. Multivariable adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression by adjusting age and gender. A meta-analysis based on published studies was also performed to verify the associations. Of these, 12.1% of cases and 5.5% of controls were hepatitis B surface antigen (HBsAg) seropositive. We observed significant associations between HBsAg seropositivity and esophagus cancer (aOR [95% CI] = 1.32 [1.13-1.54]), stomach cancer (1.46 [1.30-1.65]), hepatocellular carcinoma (HCC; 39.11 [35.08-43.59]), intrahepatic and extrahepatic bile duct carcinoma (ICC and ECC; 3.83 [2.58-5.67] and 1.72 [1.28-2.31]), pancreatic cancer (PaC; 1.37 [1.13-1.65]), non-Hodgkin lymphoma (NHL; 1.88 [1.61-2.20]) and leukemia (11.48 [4.05-32.56]). Additionally, compared to participants with HBsAg-/anti-HBs-/anti-HBc-, participants with HBsAg-/anti-HBs-/anti-HBc+, indicating past HBV-infected, had an increased risk of esophagus cancer (aOR [95% CI] = 1.46 [1.24-1.73]), stomach cancer (1.20 [1.04-1.39]), HCC (4.80 [3.95-5.84]) and leukemia (15.62 [2.05-119.17]). Then the overall meta-analysis also verified that HBsAg seropositivity was significantly associated with stomach cancer (OR [95% CI] = 1.23 [1.14-1.33]), ICC (4.05 [2.78-5.90]), ECC (1.73 [1.30-2.30]), PaC (1.26 [1.09-1.46]), NHL (1.95 [1.55-2.44]) and leukemia (1.54 [1.26-1.88]). In conclusion, both our case-control study and meta-analysis confirmed the significant association of HBsAg seropositivity with stomach cancer, ICC, ECC, PaC, NHL and leukemia. Of note, our findings also suggested that the risk of stomach cancer elevated for people whoever exposed to HBV.

Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors.

109 Background: RET gene fusions are targetable oncogenic drivers in multiple tumor types, including up to 20% of papillary thyroid cancers (PTC). Pralsetinib is an investigational, highly potent, selective inhibitor of oncogenic RET alterations. In the registration-enabling Phase 1/2 ARROW study (NCT03037385), pralsetinib demonstrated an overall response rate (ORR; response-evaluable patients [REP], central review) of 73% (19/26) in treatment-naïve patients and 61% (49/80; 2 pending confirmation) in platinum-exposed patients with RET fusion+ non-small cell lung cancer (NSCLC) and was well tolerated (data cut-off November 18, 2019). We provide an update on the clinical activity of pralsetinib in other RET fusion+ solid tumor types. Methods: ARROW consists of a phase 1 dose escalation (30–600 mg once [QD] or twice daily) followed by a phase 2 expansion (400 mg QD) in patients with advanced RET-altered solid tumors. Primary objectives were ORR and safety. Results: As of November 18, 2019, 29 patients with metastatic solid tumor types other than NSCLC (16 PTC, 1 undifferentiated thyroid, 3 pancreatic, 3 colon, 6 other) bearing a RET fusion have received pralsetinib. Efficacy data are presented for REP enrolled by July 11, 2019. In patients with thyroid cancer that is RET fusion+, ORR (investigator assessment) was 75% (9/12; all confirmed). Median (range) duration of response (DOR) was 14.5 (3.7+, 16.8) months (mo), with 67% of responding patients continuing treatment. Two patients with stable disease were continuing treatment at 11.5+ and 19.3+ mo. In other RET fusion+ cancers, ORR was 60% (3/5; all confirmed) with partial responses in 2/2 patients with pancreatic cancer (DOR 5.5, 7.4+ mo) and 1 patient with intrahepatic bile duct carcinoma (DOR 7.5 mo). Two patients with colon cancer had stable disease for 7.3 and 9.3 mo. Responses were observed across multiple fusion genotypes. In the entire safety population (all patients treated with 400 mg QD pralsetinib, regardless of diagnosis; n = 354), most treatment-related adverse events (TRAEs) were grade 1-2, and included increased aspartate aminotransferase (31%), anemia (22%), increased alanine aminotransferase (21%), constipation (21%) and hypertension (20%). Only 4% of patients in the safety population discontinued due to TRAEs. Conclusions: Pralsetinib demonstrated broad and durable antitumor activity across multiple advanced solid tumor types, regardless of RET fusion genotype, and was well tolerated. The study is ongoing and still enrolling patients in this cohort. Clinical trial information: NCT03037385.

Mixed adenoneuroendocrine carcinoma of the liver: A rare case report.

A 55-year-old woman presented with chest and back pain of unknown cause. Contrast-enhanced computed tomography revealed two low-density tumors, sized 4.6 and 4.4 cm, in the hepatic caudate and left inner lobes, respectively. There are multiple enlarged lymph nodes around the abdominal aorta, hepatogastric ligament and gastrosplenic ligament. At the same time, there were multiple enlarged lymph nodes between the portal vein and the vena cava. Upper gastrointestinal endoscopy revealed chronic non-atrophic gastritis and esophagitis (grade B). Endoscopic examination of the lower digestive tract revealed polyps of the colon, diagnosed as tubular adenomas following biopsy and histopathological examination. The patient underwent left three hepatic resection (including left inner lobe, left outer lobe and right anterior lobe resection), abdominal lymph node dissection, right liver tumor radiofrequency ablation, hepatic caudate lobe resection, intestinal adhesion release, vena cava formation, portal vein repair and hilar cholangioplasty. The pathological examination of the resected specimens revealed intrahepatic bile duct carcinoma and hepatic parenchymal neuroendocrine tumor (NET). In addition, liver solid portions consisted of tumor cells with characteristic salt-and-pepper nuclei. Immunohistochemical examination revealed expression of the neuroendocrine marker synaptophysin in this solid component, confirming the diagnosis of NET. Furthermore, the MIB-1 proliferation index of the NET was higher compared with that of the adenocarcinoma, and lymph node invasion by the NET component was detected, indicating a neuroendocrine carcinoma (NEC, or NET G3). The diagnosis of mixed adenoneuroendocrine carcinoma of the liver was confirmed based on the World Health Organization 2010 criteria. Taking into consideration the patient's poor general condition, only symptomatic supportive treatment was administered postoperatively, without chemotherapy. Contrast-enhanced computed tomography at 45 days postoperatively revealed disease progression, with metastases in the liver stump, abdominal lymph nodes, spine and pelvis. The patient remained on symptomatic supportive treatment and succumbed to disease progression 3 months after surgery.

Statin use and risk of liver cancer: Evidence from two population-based studies.

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case-control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43-0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24-0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45-2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.

Hospitalization outcomes between intrahepatic bile duct carcinoma versus extrahepatic biliary cholangiocarcinoma

Background: Cholangiocarcinoma is an uncommon cancer with a very bad prognosis despite advances made in treatment. The location of the tumor (intrahepatic versus extrahepatic) determines surgical options. In our study, we examine variations in outcomes between patients admitted to the hospital with intrahepatic versus extrahepatic disease. Methods: Data from the NIS, a database developed for the healthcare Cost and Utilization project (HCUP) was used for our analysis. We identified patients who were 18 years and older with intrahepatic or extrahepatic biliary duct carcinoma who underwent a procedure (biliary stent, resection, bypass, pancreatic resection, liver resection and transplantation) during a hospitalization. Our primary aim was to describe outcomes in terms of inpatient mortality, length of stay and hospitalization cost based on tumor location. We used multivariable logistic regression to calculate adjusted odd ratios and mean differences for each cohort. We controlled for patient level characteristics (age, race, sex, comorbidity burden), hospital level characteristics (hospital region, size and teaching status), insurance type and procedure received during hospitalization using multivariable analysis. Results: We identified a total of 18,840 admissions in 2014 with a discharge diagnosis of cholangiocarcinoma (intrahepatic or extrahepatic). Of these, 13,930 (73.1%) were intrahepatic while 4,930 (26.1%) were extrahepatic. Inpatient mortality amongst patents with extrahepatic bile duct carcinoma was 5.5% while that for intrahepatic bile duct carcinoma was 7.69%. After controlling for confounders, including treatment received during hospitalization, patients with extrahepatic disease were 30% less likely (Adjusted Odds Ratio 0.70, 95 % CI 0.512-0.966) to die during hospitalization compared to patients admitted for intrahepatic bile duct carcinoma. Length of stay was similar between the two groups (Adjusted Mean Difference -0.10, 95 % CI -0.64 -0.44) as was average cost of hospitalization (Adjusted Mean Difference. -4126, 95% CI -1.0986.5 - 2733.16). Conclusion: The location of biliary duct carcinoma predicts inpatient mortality, even after controlling for treatment received. Intrahepatic cholangiocarcinoma has a worse prognosis than extrahepatic tumors, although length of stay and average cost of hospitalization are similar across the two cohorts. The two carcinomas have different histology, molecular characteristics, and associated genetic abnormalities. Intrahepatic cholangiocarcinoma is more likely to be associated with cirrhosis due to underlying viral hepatitis or non alcoholic fatty liver disease. It is unclear if these pathological characteristics or underlying chronic inflammation influence outcomes. We recommend prospective studies to better understand reasons for variation in hospitalization mortality seen in patients with intrahepatic cholangiocarcinoma.

Multicentric intrahepatic cholangiocellular carcinoma in a budgerigar (Melopsittacus undulatus): a case report

Cholangiocarcinoma or intrahepatic bile duct carcinoma is a malignant neoplasm of biliary epithelium which occurs mainly in wild animals rather than domestic ones. An adult 4-year-old male budgerigar was referred with symptoms of lethargy, decreased activity, and vomiting with undigested food in feces. Supportive care was tried for 3 months, but the bird did not show any signs of recovery and was finally euthanized. Necropsy revealed hepatomegaly in one lobe of the liver while the other lobe was dwindled. The remaining large lobe had a multinodular appearance with white to gray, non-umbilicated foci ranging from 2 mm to 3 cm in diameter which was scattered throughout the parenchyma. The histopathological examination revealed multiple foci or masses of less differentiated cholangiocellular carcinoma. The large tumor masses had tubular, acinar, and solid arrangements with a center of necrosis. The masses were composed of neoplastic cells of biliary epithelium similar to the normal cuboidal ductal lining cells with moderate eosinophilic cytoplasm and round to oval vesicular nuclei. Multinuclear tumor giant cells were not seen; however, karyomegaly was rarely observed and infrequently in some foci. Based on histopathological characteristics, multicentric intrahepatic cholangiocellular carcinoma was confirmed. It seems that the probable cause of the tumor in this bird was chronic exposure to toxins such as aflatoxins.

Trends in Incidence of Primary Liver Cancer in the Elderly (Aged 65+ Years) in England, 1971-2010

Background: About 45% of the cases of liver cancer in England are diagnosed in the elderly. Since the 1990s, there has been a substantial increase in the incidence of liver cancer, and it has been projected that the incidence of rates will continue to increase to 15/100,000 by 2035. Aim: To determine the trends of incidence of liver cancer in the elderly in England during the period 1971-2010. Methods: Population-based national cancer registration data (obtained from the Office for National Statistics) were analyzed to determine the incidence of liver cancer (ICD-9 code: 155, ICD-10 code: C22) by age, gender, morphologic subtype and level of deprivation. Microsoft Excel and SPSS software were used for the analysis. Results: During the 40-year period, a total of 42,800 cases of liver cancer in the elderly were registered in England (58% male, 42% female). The number of cases increased by 462% - from 2,019 in 1971-75 (404 cases/year) to 11,345 in 2006-10 (2269 cases/year). The incidence rate (per 100,000) increased from 9.0 in 1971-75 to 37.4 in 2006-10 in males (316% increase); and from 4.6 to 19.6 in females (326% increase). In males, the incidence rates of liver cell carcinoma (ICD-10 code: C22.0) increased by 140% and the intrahepatic bile duct carcinoma (ICD-10 code: C22.1) by 2467%; whereas in females the incidence rates increased by 22% and 2260%, respectively. As for level of deprivation, the largest increase in incidence was observed in the least deprived population (721% in males, 690% in females). Conclusion: During the past four decades, there has been a remarkable increase in the incidence of liver cancer in the elderly in England. The relatively large increase in liver cell carcinoma in males, those in the least deprived category, and substantial increase in intrahepatic bile duct carcinoma in both genders warrant further investigation. These findings are also relevant for the planning of oncology services, resource allocation, screening for early diagnosis and public health education for primary prevention of liver cancer.

Management of Choledochal Cysts: An Institutional Review

Introduction: Choledochal cysts are congenital abnormalities characterized by cyst formation and dilation of the biliary tree. They are a rare condition more common in females with the highest incidence in the United States estimated at 1 in 13,500 live births (1). They can be clinically silent, cause biliary obstruction and/or transform to malignancy. Management is controversial because statistics regarding malignant transformation vary widely. Estimates from select studies vary from 10% (2) to 26% (3). This study was performed to review the natural history and management of choledochal cysts at our institution. Methods: Patient charts from 2009-2017 were obtained with the following ICD9 and ICD10 codes: Choledochal cyst (Q44.4); biliary cyst (K83.5); other specified disorders of the biliary tract (576.8); anomalies of gallbladder, bile ducts, and liver (751.69); biliary atresia (751.61); other congenital malformations of bile ducts (Q44.5); and intrahepatic bile duct carcinoma (155.1, C22.1). A total of 2,546 charts were identified. Charts were then reviewed for the presence of choledochal cysts. Results: Eleven patients with choledochal cysts were found. Ten out of the 11 were female. Five had Type I cysts (one of these patients also had a Type II cyst). Five had Type II cysts. There was only one patient with a Type III cyst and only one with a Type IV cyst. Five out of the 11 patients with choledochal cysts were managed with surgical removal with either a Roux-en-Y hepaticojejunostomy, Roux-en-Y choledochojejunostomy or Whipple procedure depending on other patient factors. The patient with the Type III cyst was lost to follow-up after diagnosis of the cyst. Conclusion: Management of choledochal cysts at our institution varied with about half opting for surgical removal and half opting for serial follow-up with imaging. Given the rarity of the disease and varied results regarding transformation to malignancy, an individualized patient approach should be taken. Future research aims could include creation of a database of patients with choledochal cysts, given that malignant transformation and management will likely vary by type of cyst, patient characteristics, and patient preference.

Engineering of recombinant Wisteria floribunda agglutinin specifically binding to GalNAcβ1,4GlcNAc (LacdiNAc).

Wisteria floribunda agglutinin (WFA) is a useful probe for distinguishing glycan structural alterations in diseases such as intrahepatic bile duct carcinoma and hepatic fibrosis; however, the gene encoding WFA has not been identified. Here, we identified the gene encoding WFA, and recombinant WFA (rWFA) was expressed in Escherichia coli and purified. The natural complementary DNA sequence obtained from wisteria seeds contained an open reading frame of 861 nucleotides encoding a WFA precursor, which included a hydrophobic signal peptide at the N-terminus, a propeptide at the C-terminus and a single cysteine (Cys) residue for dimer formation. We characterized the natural and rWFA by the glycoconjugate microarray and frontal affinity chromatography. rWFA exhibited glycan binding specificity similar to that of natural WFA: both bound to Gal- and N-acetylgalactosamine (GalNAc)-terminated glycans. Moreover, the engineered WFA with an amino acid substitution in Cys-272 yielded a recombinant monomeric lectin with limited binding specificity but wild-type affinity for GalNAc-terminated glycans, specifically GalNAcβ1,4GlcNAc. Thus, this engineered lectin may be applied to highly sensitive biomarker detection.

Radioembolization with 90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: final report of a prospective pilot study.

This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of radioembolization of liver-dominant metastatic gastrointestinal cancer using 90Y glass microspheres. Between June 2010 and October 2013, 42 adult patients (26 men, 16 women; median age 60 years) with metastatic chemotherapy-refractory unresectable colorectal (n=21), neuroendocrine (n=11), intrahepatic bile duct (n=7), pancreas (n=2), and esophageal (n=1) carcinomas underwent 60 lobar or segmental administrations of 90Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for up to 5.5 years after radioembolization. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Time to maximum response, response duration, progression-free survival (PFS) (hepatic and extrahepatic), and overall survival (OS) were measured. Median target dose and activity were 109.4 Gy and 2.6 GBq per treatment session, respectively. Majority of clinical AE were grade 1 or 2 in severity. Patients with colorectal cancer had hepatic objective response rate (ORR) of 25% and a hepatic disease control rate (DCR) of 80%. Median PFS and OS were 1.0 and 4.4 months, respectively. Patients with neuroendocrine tumors (NET) had hepatic ORR and DCR of 73% and 100%, respectively. Median PFS was 8.9 months for this cohort. DCR and median PFS and OS for patients with cholangiocarcinoma were 86%, 1.1 months, and 6.7 months, respectively. 90Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort.

Survival patterns in teenagers and young adults with cancer in the United Kingdom: Comparisons with younger and older age groups

AimsWe aimed to describe and compare survival in teenagers and young adults (TYAs) with cancer to that of younger children and older adults, to identify sub-populations at greater or lesser risk of death. MethodsWe compared survival in cancer patients diagnosed in the United Kingdom aged 13–24years (TYAs) to those aged 0–12 (children) and 25–49years (adults) using the National Cancer Data Repository. All cases had a first cancer diagnosis between 1st January 2001 and 31st December 2005 with censor date 31st December 2010 or death if earlier. ResultsWe found six distinct statistically significant survival patterns. In pattern 1, the younger the age-group the better the 1- and 5-year survival (acute lymphoid leukaemia, carcinoma of ovary and melanoma). In pattern 2, TYAs had a worse 5-year survival than both children and young adults (bone and soft tissues sarcomas). In pattern 3, TYAs had a worse 1-year survival but no difference at 5-years (carcinoma of cervix and female breast). In pattern 4, TYAs had better 1-year survival than adults, but no difference at 5years (carcinoma of liver and intrahepatic bile ducts, germ cell tumours of extra-gonadal sites). In pattern 5, the younger the age-group the better the 5-year survival, but the difference developed after 1-year (acute myeloid leukaemia, carcinoma of colon and rectum). In pattern 6, there was no difference in 1- and 5-year survival between TYAs and adults (testicular germ cell tumours, ovarian germ cell tumours and carcinoma of thyroid). ConclusionTYAs with specific cancer diagnoses can be grouped according to 1- and 5-year survival patterns compared to children and young adults. To further improve survival for TYAs, age-specific biology, pharmacology, proteomics, genomics, clinician and patient behaviour studies embedded within clinical trials are required.