Medicaid expansion and palliative care for advanced-stage liver cancer.

BACKGROUND: Medicaid expansion (ME) has contributed to transforming the United States healthcare system. However, its effect on palliative care of primary liver cancers remains unknown. This study aimed to evaluate the association between ME and the receipt of palliative treatment in advanced-stage liver cancer. METHODS: Patients diagnosed with stage IV hepatocellular carcinoma or intrahepatic cholangiocarcinoma were identified from the National Cancer Database and divided into pre-expansion (2010-2013) and postexpansion (2015-2019) cohorts. Logistic regression identified predictors of palliative treatment. Difference-in-difference (DID) analysis assessed changes in palliative care use between patients living in ME states and patients living in non-ME states. RESULTS: Among 12,516 patients, 4582 (36.6%) were diagnosed before expansion, and 7934 (63.6%) were diagnosed after expansion. Overall, rates of palliative treatment increased after ME (18.1% [pre-expansion] vs 22.3% [postexpansion]; P < .001) and are more pronounced among ME states. Before expansion, only cancer type and education attainment were associated with the receipt of palliative treatment. Conversely, after expansion, race, insurance, location, cancer type, and ME status (odds ratio [OR], 1.23; 95% CI, 1.06-1.44; P = .018) were all associated with palliative care. Interestingly, the odds were higher if treatment involved receipt of pain management (OR, 2.05; 95% CI, 1.23-2.43; P = .006). Adjusted DID analysis confirmed increased rates of palliative treatment among patients living in ME states relative to non-ME states (DID, 4.4%; 95% CI, 1.2-7.7; P = .008); however, racial disparities persist (White, 5.6; 95% CI, 1.4-9.8; P = .009; minority, 2.6; 95% CI, -2.5 to 7.6; P = .333). CONCLUSION: The implementation of ME contributed to increased rates of palliative treatment for patients residing in ME states after expansion. However, racial disparities persist even after ME, resulting in inequitable access to palliative care.

Flow Cytometry Assessment of Lymphocyte Populations Infiltrating Liver Tumors.

Tissue-resident and recruited immune cells are essential mediators of natural and therapy-induced immunosurveillance of liver neoplasia. This idea has been recently reinforced by the clinical approval of immune checkpoint inhibitors for the immunotherapy of hepatocellular carcinoma and cholangiocarcinoma. Such research progress relies on the in-depth characterization of the immune populations that are present in pre-neoplastic and neoplastic hepatic lesions. A convenient technology for advancing along this path is high-dimensional cytometry.In this chapter, we present a protocol to assess the subtype and differentiation state of hepatic lymphocyte populations by multicolor immunofluorescence staining and flow cytometry. We detail the steps required for viability assessment and immune cell phenotyping of single-cell suspensions of liver cells by means of surface and intracellular staining of more than a dozen markers of interest. This protocol does not require prior removal of debris and dead cells and allows to process multiple samples in parallel. The procedure includes the use of a fixative-resistant viability dye that allows cell fixation and permeabilization after cell surface staining and before intracellular staining and data acquisition on a flow cytometer. Moreover, we provide a panel of fluorochrome-labeled antibodies designed for the characterization of lymphocytic subsets that can be adapted to distinct experimental settings. Finally, we present an overview of the post-staining pipeline, including data acquisition on a flow cytometer and tools for post-acquisition analyses.

Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016.

BACKGROUND AND AIMS: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHOD: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. RESULTS: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). CONCLUSION: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.

Comparison Between Contrast-Enhanced Computed Tomography and Contrast-Enhanced Magnetic Resonance Imaging With Magnetic Resonance Cholangiopancreatography for Resectability Assessment in Extrahepatic Cholangiocarcinoma.

OBJECTIVE: To compare the diagnostic performance and interobserver agreement between contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CE-MRI) with magnetic resonance cholangiopancreatography (MRCP) for evaluating the resectability in patients with extrahepatic cholangiocarcinoma (eCCA). MATERIALS AND METHODS: This retrospective study included treatment-naïve patients with pathologically confirmed eCCA, who underwent both CECT and CE-MRI with MRCP using extracellular contrast media between January 2015 and December 2020. Among the 214 patients (146 males; mean age ± standard deviation, 68 ± 9 years) included, 121 (56.5%) had perihilar cholangiocarcinoma. R0 resection was achieved in 108 of the 153 (70.6%) patients who underwent curative-intent surgery. Four fellowship-trained radiologists independently reviewed the findings of both CECT and CE-MRI with MRCP to assess the local tumor extent and distant metastasis for determining resectability. The pooled area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of CECT and CE-MRI with MRCP were compared using clinical, surgical, and pathological findings as reference standards. The interobserver agreement of resectability was evaluated using Fleiss kappa (κ). RESULTS: No significant differences were observed between CECT and CE-MRI with MRCP in the pooled AUC (0.753 vs. 0.767), sensitivity (84.7% [366/432] vs. 90.3% [390/432]), and specificity (52.6% [223/424] vs. 51.4% [218/424]) (P > 0.05 for all). The AUC for determining resectability was higher when CECT and CE-MRI with MRCP were reviewed together than when CECT was reviewed alone in patients with discrepancies between the imaging modalities or with indeterminate resectability (0.798 [0.754-0.841] vs. 0.753 [0.697-0.808], P = 0.014). The interobserver agreement for overall resectability was fair for both CECT (κ = 0.323) and CE-MRI with MRCP (κ = 0.320), without a significant difference (P = 0.884). CONCLUSION: CECT and CE-MRI with MRCP showed no significant differences in the diagnostic performance and interobserver agreement in determining the resectability in patients with eCCA.

Cost-effectiveness analysis of pembrolizumab in combination with chemotherapy compared with chemotherapy alone as first-line treatment for patients with advanced biliary tract cancer in China.

OBJECTIVE: The objective of this study is to evaluate the cost-effectiveness of adding pembrolizumab to the standard first-line therapy of advanced biliary tract cancer (BTC) with gemcitabine and cisplatin from the perspective of the Chinese healthcare system. METHODS: The partitioned survival model developed from clinical data obtained in The KEYNOTE-966 trial served as the basis for a simulation in the TreeAge Pro 2011 software. The objective of the research was to estimate the 10-year life expectancy and total healthcare costs of patients with BTC, utilizing primary outcomes that evaluated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). To establish the willingness-to-pay (WTP) threshold, the 2022 Chinese per capita gross domestic product (GDP) of $37304.346/QALY was adopted. Furthermore, sensitivity analysis was conducted to ascertain the study's results under varying levels of uncertainty. RESULTS: Compared to chemotherapy alone, the addition of pembrolizumab to chemotherapy has been shown to yield an incremental gain of 0.184 quality-adjusted life years (QALY) at an additional cost of $103940.706. This translates into an incremental cost-effectiveness ratio (ICER) of $564895.141/QALY, which exceeds the willingness-to-pay (WTP) threshold in China. One-way sensitivity analyses performed on the model recognize the utility of PD, subsequent cost, and the cost of Pembrolizumab 100 mg had a major influence on the outcomes. However, no parameter elicited an ICER lower than the willingness-to-pay (WTP) threshold. CONCLUSIONS: Based on the perspective of the Chinese healthcare system, the utilization of pembrolizumab in combination with chemotherapy as an first-line treatment option for BTC does not appear to be a cost-effective approach compared to chemotherapy as a standalone therapy.

Immune checkpoint inhibitor for patients with advanced biliary tract cancer: A cost-effectiveness analysis.

BACKGROUND AND AIMS: The increasingly widespread of immune checkpoint inhibitors (ICIs) in the field of antitumors has brought a new dawn for patients with advanced biliary tract cancer (aBTC). However, the choice of treatment needs to be supported by economic evaluation. Therefore, the cost-effectiveness comparison of first-line durvalumab or pembrolizumab plus gemcitabine and cisplatin (GemCis) treatment of aBTC was explored from the perspective of American and Chinese healthcare systems. METHODS: Ground on the TOPAZ-1 and KEYNOTE-966 trials, the Markov model with a 15-year horizon including three health states to imitate cost and effective outcomes was established. Incremental cost-effectiveness ratio (ICER) at willingness-to-pay (WTP) thresholds of $100 000/QALY and $37 408/ALY in the USA and China was used as the most important indicator. Other endpoint indexes included total cost, life years (LYs), quality-adjusted life years (QALYs) and incremental net-health benefit (INHB). To verify the robustness, sensitivity and subgroup analyses were performed. RESULTS: Durvalumab plus GemCis ($322 211 [2.94 QALYs] and $35 695 [2.76 QALYs]) increased cost (effectiveness) by $63 777 (.22 QALYs) and $5234 (.20 QALYs) than pembrolizumab plus GemCis ($258 434 [2.72 QALYs] and $30 461 [2.56 QALYs]) in the USA and China, respectively. The corresponding ICER was $288 725/QALY and $26 401/QALY, with INHB of -.42 and .06 QALYs, respectively. The cost of ICIs was the most important factor influencing results. CONCLUSIONS: In China, first-line durvalumab plus GemCis versus pembrolizumab plus GemCis was a cost-effective option for patients with aBTC, but not in the USA.

Early portal vein thrombosis after hepatectomy for perihilar cholangiocarcinoma: Incidence, risk factors, and management.

AIM: To study the incidence, risk factors and management of portal vein thrombosis (PVT) after hepatectomy for perihilar cholangiocarcinoma (PHCC). PATIENTS AND METHOD: Single-center retrospective analysis of 86 consecutive patients who underwent major hepatectomy for PHCC, between 2012 and 2019, with comparison of the characteristics of the groups with (PVT+) and without (PVT-) postoperative portal vein thrombosis. RESULTS: Seven patients (8%) presented with PVT diagnosed during the first postoperative week. Preoperative portal embolization had been performed in 71% of patients in the PVT+ group versus 34% in the PVT- group (P=0.1). Portal reconstruction was performed in 100% and 38% of PVT+ and PVT- patients, respectively (P=0.002). In view of the gravity of the clinical and/or biochemical picture, five (71%) patients underwent urgent re-operation with portal thrombectomy, one of whom died early (hemorrhagic shock after surgical treatment of PVT). Two patients had exclusively medical treatment. Complete recanalization of the portal vein was achieved in the short and medium term in the six survivors. After a mean follow-up of 21 months, there was no statistically significant difference in overall survival between the two groups. FINDINGS: Post-hepatectomy PVT for PHCC is a not-infrequent and potentially lethal event. Rapid management, adapted to the extension of the thrombus and the severity of the thrombosis (hepatic function, signs of portal hypertension) makes it possible to limit the impact on postoperative mortality. We did not identify any modifiable risk factor. However, when it is oncologically and anatomically feasible, left±extended hepatectomy (without portal embolization) may be less risky than extended right hepatectomy, and portal vein resection should only be performed if there is strong suspicion of tumor invasion.

Impact of Food Insecurity on Outcomes Following Resection of Hepatopancreaticobiliary Cancer.

INTRODUCTION: Food insecurity (FI) may predispose individuals to suboptimal nutrition, leading to chronic disease and poor health outcomes. We sought to assess the impact of county-level FI on postoperative outcomes among patients undergoing resection of hepatopancreaticobiliary (HPB) cancer. METHODS: Patients who were diagnosed with HPB cancer between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Data on annual county-level FI were obtained from the Feeding America: Mapping the Meal Gap report and were categorized into tertiles. Textbook outcome was defined as no extended length of stay, perioperative complications, 90-day readmission, and 90-day mortality. Multiple logistic regression and Cox regression models were used to assess outcomes and survival relative to FI. RESULTS: Among 49,882 patients (hepatocellular: n = 11,937, 23.9%; intrahepatic cholangiocarcinoma: n = 2111, 4.2%; extrahepatic cholangiocarcinoma: n = 4047, 8.1%; gallbladder: n = 2853, 5.7%; pancreatic: n = 28,934, 58.0%), 6702 (13.4%) patients underwent a surgical resection. Median age was 75 years (interquartile range 69-82), and most patients were male (n = 25,767, 51.7%) and self-identified as White (n = 36,381, 72.9%). Overall, 5291 (10.6%) and 39,664 (79.5%) individuals resided in low or moderate FI counties, respectively, while 4927 (9.8%) patients resided in high FI counties. Achievement of textbook outcome (TO) was 56.3% (n = 6702). After adjusting for competing risk factors, patients residing in high FI counties had lower odds to achieve a TO versus individuals living in low FI counties (odds ratio 0.69, 95% confidence interval [CI] 0.54-0.88, p = 0.003). In addition, patients residing in moderate and high FI counties had a greater risk of mortality at 1- (referent, low, moderate: hazard ratio [HR] 1.09, 95% CI 1.05-1.14; high: HR 1.14, 95% CI 1.08-1.21), 3- (referent, low, moderate: HR 1.09, 95% CI 1.05-1.14; high: HR 1.14, 95% CI 1.08-1.21), and 5- (referent, low, moderate: HR 1.05, 95% CI 1.01-1.09; high: HR 1.07, 95% CI 1.02-1.13) years versus individuals from low FI counties. CONCLUSIONS: FI was associated with adverse perioperative outcomes and long-term survival following resection of an HPB malignancy. Interventions directed towards mitigating nutritional inequities are needed to improve outcomes among vulnerable HPB populations.

NRAS-mutated oncocytic benign liver lesion in an organ donor: Pitfalls and troubles in frozen section diagnosis and risk assessment.

BACKGROUND: In the transplant setting, the definition of the risk of neoplastic transmission from donor to recipient often requires intraoperative pathological evaluation on frozen sections. Although most lesions can be easily classified into acceptable or unacceptable risk according to the Italian National Guidelines, there are cases in which unusual histologic features cannot be further investigated because of the lack of ancillary techniques on frozen sections. CASE PRESENTATION: Here we present a case of a liver lesion in a 51-year-old male donor, subjected to histopathological on-call examination. The frozen sections showed a well-demarcated lesion consisting of epithelioid cells disposed in laminar structures and intermingled with a dense lymphocytic population: this led to organ discard with interruption of the donation process. The definitive histological analysis required an extensive immunohistochemical (IHC) investigation: the final diagnosis was "bile duct adenoma with oncocytic features", eventually confirmed by a strongly positive anti-mitochondrial IHC. Finally, an NGS panel analysis was performed, which revealed NRAS mutation. DISCUSSION: To the best of our knowledge, this is the first case of oncocytic bile duct adenoma confirmed by anti-mitochondrial IHC and with NRAS mutation. The most challenging aspect of this case was represented by the transplant setting. In fact, the oncocytic features and the dense lymphocytic infiltrate represented concomitant unusual histological features that led to the halt of the organ donation procedures.

Clinical and cost effectiveness of endoscopic bipolar radiofrequency ablation for the treatment of malignant biliary obstruction: a systematic review.

Background: Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction. Objectives: To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research. Data sources: Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021. Review methods: The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters. Results: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency. Limitations: Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted. Conclusions: Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication. Future work: Future work investigating radiofrequency ablation must collect quality-of-life data. High-quality randomised controlled trials in secondary radiofrequency ablation are needed, with appropriate outcomes recorded. Study registration: This study is registered as PROSPERO CRD42020170233. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 7. See the NIHR Journals Library website for further project information.

The bile and pancreatic ducts transport fluids to the intestines to help people digest their food properly. Some types of cancer can cause these ducts to become totally or partially blocked. We wanted to know if endoscopic radiofrequency ablation is safe and works well to treat people who have one of these blockages that cannot be removed by surgery. Radiofrequency ablation burns away a blockage by hitting it with radio waves. Endoscopic means that the radio waves are directed to the blockage using a thin, tube-like wire with a camera at the end. During radiofrequency ablation, a person might have a small tube called a stent put into their bile or pancreatic duct to keep it open or to replace an already blocked stent.

We searched for research studies that looked at (1) whether or not radiofrequency ablation was able to remove blockages from the ducts, (2) if radiofrequency ablation allowed people to live longer, (3) if patients had a better quality of life after radiofrequency ablation, (4) if radiofrequency ablation caused any side effects and (5) how much it costs to treat people with radiofrequency ablation.

We found that treatment with radiofrequency ablation before giving a person a stent helped them to live a little longer with their cancer. We did not find any evidence that radiofrequency ablation increased pain or swelling in the bile duct or pancreatic duct. Radiofrequency ablation might cause more swelling in the gall bladder than having a stent without radiofrequency ablation, but there was not enough research available for us to be certain of this.

Radiofrequency ablation before inserting a stent could be a safe option to add to treatment of bile and pancreatic duct blockages caused by cancer. There is limited research evidence and so we are unable to recommend radiofrequency ablation as a treatment for standard clinical practice.

Accuracy and limitations of preoperative assessment of longitudinal spread of perihilar cholangiocarcinoma.

OBJECTIVE: Although surgical resection offers the only chance of cure of perihilar cholangiocarcinoma and R1 resection has a poor prognosis, there is no consensus on optimal preoperative assessment of its longitudinal spread. We aimed to establish the optimal means of achieving this goal. METHODS: This was a retrospective, single-center study of 61 patients who had undergone multi-detector row computed tomography, endoscopic retrograde cholangiography, intraductal ultrasonography, and mapping biopsy prior to resection of perihilar cholangiocarcinomas in our institute from January 2010 and December 2021. RESULTS: The most accurate single methods for assessing longitudinal spread were intraductal ultrasonography and mapping biopsy (both 72.1%). A combination of all four assessment methods was accurate in 51 (83.6%) of our patients. Independent risk factors for inaccuracy were Bismuth-Corlette Type IV and high histologic-grade tumors. The R0 resection rate was higher with accurate than inaccurate assessments (90.2% vs. 30.0%, P < 0.001). R0 resection was associated with significantly better relapse-free survival than R1 resection (P = 0.006). However, overall survival did not differ between these groups. CONCLUSION: Preoperative assessment of longitudinal spread of perihilar cholangiocarcinomas by four different modalities is optimal, achieving 83.6% accuracy and a 90.2% R0 resection rate.

Impact of Medicaid Expansion on the Treatment and Outcomes of Intrahepatic Cholangiocarcinoma.

INTRODUCTION: The Affordable Care Act increased insurance coverage for patients residing in states that expanded Medicaid coverage, but its impact on the outcomes of intrahepatic cholangiocarcinoma (ICC) is not clear. Therefore, we examine the impact of Medicaid expansion (ME) on access to treatment and outcomes of ICC. METHODS: We queried the National Cancer Database (NCDB) data for patients with a diagnosis of ICC (2010-2018). Difference-in-difference (DID) analysis was performed to assess the impact of January 2014 ME on curative-intent surgical resection, multimodal therapy, neoadjuvant chemotherapy, 30-day mortality, and overall survival (OS). RESULTS: Of the 2150 patients included in the study,1574 (73.2%) and 576 (26.8%) patients lived in non-ME and ME states, respectively. On adjusted DID, ME was independently associated with receipt of curative-intent surgical resection (DID coefficient: 0.05, 95% confidence interval [95% CI]: 0.04-0.06, p = 0.002) and multimodal therapy (DID coefficient: 0.08, 95% CI: 0.06-0.10, p = 0.004). In addition, ME was associated with improved OS in ME states (hazard ratio [HR]: 0.73, 95% CI: 0.62-0.87, p = 0.001) but not in non-ME states (HR: 0.95, 95% CI: 0.80-1.12, p = 0.536). CONCLUSION: ME status consistently predicted increased utilization of care processes that improved ICC outcomes, including greater rates of curative-intent surgery and multimodal therapy.

Systematic review of cholangiocarcinoma in Africa: epidemiology, management, and clinical outcomes.

BACKGROUND: The prevalence, management, and clinical outcomes of cholangiocarcinoma in Africa are unknown. The aim is to conduct a comprehensive systematic review on the epidemiology, management, and outcomes of cholangiocarcinoma in Africa. METHODS: We searched PubMed, EMBASE, Web of Science and CINHAL from inception up to November 2019 for studies on cholangiocarcinoma in Africa. The results reported follow PRISMA guidelines. Quality of studies and risk of bias were adapted from a standard quality assessment tool. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values < 0.05 were considered significant. RESULTS: A total of 201 citations were identified from the four databases. After excluding duplicates, 133 full texts were reviewed for eligibility, and 11 studies were included. The 11 studies are reported from 4 countries only: 8 are from North Africa (Egypt 6 and Tunisia 2), and 3 in Sub-Saharan Africa (2 in South Africa, 1 in Nigeria). Ten studies reported management and outcomes, while one study reported epidemiology and risk factors. Median age for cholangiocarcinoma ranged between 52 and 61 years. Despite the proportion with cholangiocarcinoma being higher among males than females in Egypt, this gender disparity could not be demonstrated in other African countries. Chemotherapy is mainly used for palliative care. Surgical interventions are curative and prevent cancer progression. Statistical analyses were performed with Stata 15.1. CONCLUSION: The known global major risk factors such as primary sclerosing cholangitis, Clonorchis sinensis and Opisthorchis viverrini infestation are rare. Chemotherapy treatment was mainly used for palliative treatment and was reported in three studies. Surgical intervention was described in at least 6 studies as a curative modality of treatment. Diagnostic capabilities such as radiographic imaging and endoscopic are lacking across the continent which most likely plays a role in accurate diagnosis.

Role of Intraoperative Assessment of Proximal Bile Duct Margin Status and Additional Resection of Perihilar Cholangiocarcinoma: Can Local Clearance Trump Tumor Biology? A Retrospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate the clinical implications of the proximal bile duct margin status in resection of perihilar cholangiocarcinoma (PHCC). Intraoperative frozen section (IFS) analysis to assess the bile duct margin status is commonly used during PHCC resection. However, the impact of additional resection after obtaining a positive margin on the long-term outcome remains unclear. PATIENTS AND METHODS: Among the 257 patients who underwent PHCC resection, 190 patients with a negative distal margin were included and analyzed. IFS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of either invasive cancer, or carcinoma, in situ. RESULTS: IFS analysis revealed an initial positive margin in 69 (36%) patients. Among 20 patients who underwent re-resection, only 11 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes: recurrence-free survival (RFS) and overall survival (OS) were 16 and 25 months for patients with an initial positive margin, but 47 and 63 months for patients with an initial negative margin, respectively (p < 0.0001). In contrast, there was no difference in RFS or OS between patients with a secondary R0 margin, and those with a final R1 margin (14 vs. 16 months for RFS, p = 0.98, and 23 versus 25 months for OS, p = 0.63, respectively). CONCLUSION: An IFS-positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable PHCC. Additional resection has minimal impact on survival, even when negative margin is achieved.

Methods of tissue preparation after EUS-guided tissue acquisition without rapid on-site assessment: Results of a randomized study.

In the absence of rapid on-site evaluation (ROSE), it is not clear which method of tissue preparation is best to process tissue obtained from EUS guidance. Cytological smearing (CS), cell block (CB), and direct histology (DH) are the available techniques. AIM: To compare the diagnostic yield of three techniques of tissue preparation for EUS-guided tissue acquisition without ROSE. METHODS: Patients who were referred for EUS-FNA of peri-gastrointestinal masses were recruited. Without ROSE, each lesion was biopsied with three needle passes, and the order in which tissue is prepared was randomized to either (i) CS + CB, (ii) CB only, or (iii) DH only. The prepared specimens were reviewed. RESULTS: A total of 243 specimens were taken from 81 patients. Tissue diagnosis was achieved in 78/81 (96.3%) of patients, including 63 neoplasms (PDAC [n = 45], pancreatic neuroendocrine tumors [PNET; n = 4], cholangiocarcinoma [n = 5], metastatic disease [n = 4], lymphoma [n = 1], linitis plastica [n = 2], leiomyoma [n = 2]) and 15 benign pathologies (chronic pancreatitis [n = 8], reactive nodes [n = 5], inflammatory biliary stricture [n = 1], and pancreatic rest [n = 1]). The three non-diagnostic cases were found to be PDAC (n = 2) and PNET (n = 1). Sensitivity and diagnostic accuracy was highest with DH (94 and 95%), which was significantly better than that by CS + CB (43 and 54%; P = 0.0001) and CB-only preparations (32 and 48.6%; P < 0.0001). There was no significant difference between the CS + CB and CB-only arms (P > 0.22). CONCLUSION: Without ROSE, our findings suggest that with just a single pass, DH should be the tissue preparation method of choice given its significantly higher diagnostic accuracy compared with CS and/or CB techniques.

Impact of the Affordable Care Act on Presentation, Treatment, and Outcomes of Intrahepatic Cholangiocarcinoma.

BACKGROUND: The Affordable Care Act (ACA) transformed the US healthcare system, expanding healthcare insurance coverage. However, its impact on rare malignancies that lack an established screening strategy such as intrahepatic cholangiocarcinoma (ICC) remains ill-defined. METHODS: Patients diagnosed with ICC were identified from the National Cancer Database and divided relative to ACA implementation. Multivariate logistic regression analyses were performed to evaluate association with stage at diagnosis, receipt of surgical and multimodal treatments, and survival. RESULTS: Among the 9095 patients, 5636 (62.0%) were diagnosed before and 3459 (38.0%) after the implementation of the ACA. Across US regions, rates of early-stage diagnosis increased in the post-ACA era (Northeast, 62.9% vs. 85.2%; South, 63.7% vs. 78.5%; Midwest, 62.1% vs. 83.4%; West, 55.5% vs. 75.4%; p < 0.001). On multivariate analyses, the post-ACA era was associated with increased early-stage diagnosis (OR = 2.19; 95% CI 1.79-2.69), and receipt of surgical treatment (OR = 1.19, 95% CI 1.03-1.38) (both p < 0.01). Furthermore, the ACA's Medicaid expansion (ME) was also associated with improved overall survival (HR = 0.89, 95% CI 0.80-0.99, p = 0.038). Of note, although the odds of receiving surgical treatment increased after ACA for non-Hispanic White patients (OR = 1.34; 95% CI 1.20-1.49; p < 0.001), no such effect was observed in non-Hispanic Black (OR = 1.01, 95% CI 0.71-1.45), Hispanic (OR = 1.44, 95% CI 0.99-2.09), or others (OR = 1.43, 95% CI 0.98-2.10) (all p > 0.05). CONCLUSIONS: The implementation of the ACA increased rates of early diagnosis and receipt of surgical treatment. Additionally, ME improved short- and long-term outcomes. However, racial and socioeconomic disparities persist, resulting in inequitable access to care and outcomes for patients with ICC.

Validation of the Thai Version of the Memorial Symptom Assessment Scaled - Short Form Among Cholangiocarcinoma Patients.

BACKGROUND: The Memorial Symptom Assessment Scale-Short Form (MSAS-SF), a standard instrument for assessing cancer patients' symptoms, has been validated in numerous languages. However, it has not been validated in Thai. OBJECTIVES: The purpose of this study was to translate the MSAS-SF into Thai and determine its psychometric properties in Cholangiocarcinoma (CCA) patients. METHODS: The MSAS-SF was translated into Thai, and 231 CCA patients completed the questionnaires, which included baseline characteristics, T-MSAS-SF, Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep), and the Hospital Anxiety and Depression Scale (HADS). Cronbach's alpha coefficient was used to assess reliability for internal consistency. For convergent validity, Pearson's correlation coefficient was used to calculate the relationship between the T-MSAS-SF and the T-CaSUN, HADS, and FACT-Hep subscales. RESULTS: Subscale and total T-MSAS-SF internal consistency reliability was moderately high, with Cronbach alpha coefficients ranging from 0.76 to 0.87. For convergent validity, the majority of T-MSAS-SF scores had moderate to low inverse correlation with FACT-Hep, HADS T-CaSUN subscales with the correlation coefficients-0.10 to -0.68 (p<0.05), reflecting that they were measuring a similar construct. CONCLUSION: Our findings showed that the T-MSAS-SF has acceptable validity and reliability to assess the psychometric properties of early to advance stage CCA patients during treatment and early post-treatment stage.

The Evaluation of Clinical Status of Endoscopic Retrograde Cholangiography for the Placement of Metal and Plastic Stents in Cholangiocarcinoma Therapy.

Objective: Cholangiocarcinoma is a common malignant tumor that occurs in the bile duct system, which can be treated by using the endoscopic retrograde cholangiography (ERCP). This study was aimed at exploring the therapeutic effect of ERCP with metal stent and plastic stent for cholangiocarcinoma. Methods: The clinical data of 71 patients with cholangiocarcinoma treated by ERCP in our hospital from June 2020 to October 2021 were retrospectively analyzed. According to different stent types, the patients were divided into plastic stent group (n = 43) and metal stent group (n = 28). Patients in the plastic stent group and metal stent group were received with plastic stent and metal stent, respectively. The indexes of liver function (serum alkaline phosphatase (ALT), direct bilirubin (DBIL), glutamic oxaloacetic transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL)), postoperative complications, success rate of stent implantation, and survival time of patients in the two groups were determined. Logistic multivariate regression analysis was used to analyze the prognostic factors of postoperative cholangiocarcinoma. Results: The liver function indexes of the two groups were significantly improved after treatment with the stent, in which the ameliorative effect in the metal stent group was better than that in the plastic stent group (P < 0.05). The incidence of postoperative complications in the plastic stent group and the metal stent group was 53.49% and 14.29%, respectively, and the success rate of stent placement was 60.47% and 96.43%, respectively. The incidence of complications in the metal stent group was lower than that in the plastic stent group, and the success rate of stent placement was higher than that in the plastic stent group (P < 0.05). The median survival time of patients in the plastic stent group and the metal stent group was 8.15 and 11.83 months, respectively. The survival time of patients in the metal stent group was longer than that of the plastic stent group. The median survival time of patients with types I, II, III, and IV was 12.73, 11.54, 10.57, and 9.36 months, respectively. The survival time of patients with stage I was significantly higher than that of patients with types II, III, and IV. There was an inverse relationship between the disease type and the survival time of patients. Logistic multivariate regression analysis showed that tumor diameter ≥ 5 cm, portal vein invasion, lymph node metastasis, and classification of hilar cholangiocarcinoma were the risk factors (P < 0.05) and metal stent type was the protective factor (P < 0.05). Conclusion: In the clinical treatment of patients with cholangiocarcinoma, the placement of metal stent and plastic stent under ERCP plays an important role. The placement of the metal stent under ERCP has a higher success rate and better prognosis and can prolong the survival time of patients to a greater extent, but the price of the metal stent is relatively expensive. For patients with an expected survival period of more than 4-6 months, the metal stent should be considered; otherwise, the plastic stent can be used to maintain cost-effectiveness. Therefore, it is necessary to comprehensively analyze the patient's economic affordability, expected survival time, stent drainage time, and personal needs and then select an appropriate treatment method.

The Cytomorphologic and Molecular Assessment of Bile Duct Brushing Specimens.

Biliary duct brushing cytology is the standard of care for the assessment of bile duct strictures but suffers from low sensitivity for the detection of a high-risk stricture. Pathologic diagnosis of strictures is optimized by integration of cytomorphology and molecular analysis with fluorescence in situ hybridization or next-generation sequencing. Bile duct cancers are genetically heterogeneous, requiring analysis of multiple gene panels to increase sensitivity. Using molecular analysis as an ancillary test for bile duct brushing samples aids in the identification of mutations that support the diagnosis of a high-risk stricture as well as the identification of actionable mutations for targeted therapies currently in clinical trials for the treatment of patients with bile duct cancer.