Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted

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Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Importance Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. Objective To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. Data Sources The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. Study Selection Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. Data Extraction and Synthesis Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. Main Outcomes and Measures We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. Results Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). Conclusions and Relevance The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.

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Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma Systematic Review and Meta-analysis

Purpose A nomogram is a useful and convenient tool for individualized cancer prognoses. We sought to develop a clinical nomogram for predicting survival of patients with resected non–small-cell lung cancer (NSCLC). Patients and Methods On the basis of data from a multi-institutional registry of 6,111 patients with resected NSCLC in China, we identified and integrated significant prognostic factors for survival to build a nomogram. The model was subjected to bootstrap internal validation and to external validation with a separate cohort of 2,148 patients from the International Association for the Study of Lung Cancer (IASLC) database. The predictive accuracy and discriminative ability were measured by concordance index (C-index) and risk group stratification. Results A total of 5,261 patients were included for analysis. Six independent prognostic factors were identified and entered into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year overall survival (OS) showed optimal agreement...

https://ascopubs.org/doi/pdf/10.1200/JCO.2014.56.6661

Development and Validation of a Nomogram for Predicting Survival in Patients With Resected Non–Small-Cell Lung Cancer

Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review.Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943-62. ©2017 AACR.

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New Horizons for Precision Medicine in Biliary Tract Cancers

Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only potentially curative treatment, but the majority of patients present with advanced stage disease, and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has increased tremendously, diagnostic techniques have evolved, and novel therapeutic approaches have been established. This review discusses the changing epidemiologic trends and provides an overview of newly identified etiologic risk factors for CCA. Furthermore, the molecular pathogenesis is discussed as well as the influence of etiology and biliary location on the mutational landscape of CCA. This review provides an overview of the diagnostic evaluation of CCA and its staging systems. Finally, new therapeutic options are critically reviewed, and future therapeutic strategies discussed.

Cholangiocarcinoma: Current Knowledge and New Developments

Purpose This study aimed to establish an effective prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy. Patients and Methods The nomogram was based on a retrospectively study on 367 patients who underwent partial hepatectomy for ICC at the Eastern Hepatobiliary Surgery Hospital from 2002 to 2007. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve and compared with five currently used staging systems on ICC. The results were validated using bootstrap resampling and a prospective study on 82 patients operated on from 2007 to 2008 at the same institution. Results On multivariate analysis of the primary cohort, independent factors for survival were serum carcinoembryonic antigen, CA 19-9, tumor diameter and number, vascular invasion, lymph node metastasis, direct invasion, and local extrahepatic metastasis, which were all selected into the nomogram. The calibration curve for probability of ...

https://ascopubs.org/doi/pdf/10.1200/JCO.2012.41.5984

Prognostic Nomogram for Intrahepatic Cholangiocarcinoma After Partial Hepatectomy

Aims To observe the outcomes of various treatments for patients with early intrahepatic recurrent hepatocellular carcinoma (HCC) after partial hepatectomy. Methods A total of 629 patients with intrahepatic recurrent HCC within Milan criteria following hepatectomy were prospectively collected between November 2004 and May 2010. Overall survival (OS) and recurrence to death survival (RTDS) were analyzed by the Kaplan–Meier method and log-rank test. Cox regression analysis was used for multivariate analyses. Results The 5-year OS and RTDS rates were 64.5%, 43.0%; 37.0%, 26.7%; 27.7% and 8.3% for patients who received re-hepatectomy ( n  = 128), percutaneous radiofrequency ablation (PRFA, n  = 162) and transarterial chemoembolization (TACE, n  = 339) (re-hepatectomy vs. TACE, P P  = 0.005, 0.008; PRFA vs. TACE, P 20 ng/mL (1.64, 1.24–2.17; 1.66, 1.26–2.20), presence of varices (1.69, 1.28–2.22; 1.61, 1.23–2.10) and Edmondson-Steiner grade III–IV (1.66, 1.17–2.35; 1.70, 1.20–2.40) at the initial stage; and tumor number (1.34, 1.04–1.73; 1.32, 1.03–1.70), time to recurrence (TTR) (3.46, 2.58–4.65; 1.59, 1.19–2.14) and treatment for recurrence (TACE: 3.18, 2.16–4.66; 2.95, 2.02–4.31; PRFA: 1.49, 0.97–2.29; 1.44, 0.94–2.19). Conclusions For early intrahepatic recurrent HCC, re-hepatectomy achieved best outcome. It produced similar result as PRFA for patients with more invasive primary tumors and underlying cirrhosis/varices. TACE had worst prognosis which was only suitable for multifocal recurrence and TTR ≤1 year.

Early intrahepatic recurrence of hepatocellular carcinoma after hepatectomy treated with re-hepatectomy, ablation or chemoembolization: a prospective cohort study.

Background TikTok is the world’s fastest-growing video application, with 1.6 billion users in 2021. More and more patients are searching for information on genitourinary cancers via TikTok. We aim to evaluate the functional quality and reliability of genitourinary cancer-related videos on it and share our thoughts based on the results for better public health promotion. Materials and Methods We retrieved 167 videos on bladder, prostate, and kidney cancer from TikTok. Only 61 videos (36.53%) met the inclusion criteria and were eventually regarded as sample videos. Each video’s length and descriptions, hashtags, number of views/likes/comments, forms of expression, and the uploader’s profile were included. Three validated assessment instruments: the Hexagonal Radar Schema, the Health on the Net Code scale, and the DISCERN instrument, were used for evaluating the quality and reliability of the information. All misinformation was counted and categorized. Univariate analysis of variance was performed for analyzing the results. The Post-Hoc least significant difference test was conducted to explore further explanation. Results Amongst 61 sample videos, healthcare practitioners contributed the most content (n = 29, 47.54%). However, 22 posts (36.07%) were misinformative, and the most common type was using outdated data. More than half of the videos could provide good (> 1 point) content on the diseases’ symptoms and examinations. However, the definition and outcomes were less addressed (tied at 21%). The HONcode scale and the DISCERN instrument revealed a consistent conclusion that most videos (n = 59, 96.72%) on TikTok were of poor to mediocre quality. Videos published by media agencies were statistically better in terms of reliability and overall score (P = 0.003 and 0.008, respectively). Fifty-three videos (86.89%) had at least two unexplained medical terms. Healthcare professionals tend to use professional terms most (mean = 5.28 words). Conclusions Most videos on genitourinary cancers on TikTok are of poor to medium quality and reliability. However, videos posted by media agencies enjoyed great public attention and interaction. Medical practitioners could improve the video quality by cooperating with media agencies and avoiding unexplained terminologies.

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TikTok as an Information Hodgepodge: Evaluation of the Quality and Reliability of Genitourinary Cancers Related Content

Background and Aim

To study the change in serum alpha fetoprotein (AFP) of patients with recurrent hepatocellular carcinoma (HCC) after curative resection and to analyze its effect on the survival.



Methods

We prospectively collected 981 consecutive patients with post-resectional recurrent HCC between 2005 and 2010 at the Eastern Hepatobiliary Surgery Hospital. According to the change of AFP from the initial stage to recurrent stage, the patients were divided into stable-L (20 ng/mL to 20 ng/mL, n = 296), stable-M (20–400 ng/mL to 20–400 ng/mL, n = 102), stable-H (400 ng/mL to 400 ng/mL, n = 212), decreasing (n = 287), and increasing (n = 84) groups. The overall survival (OS) and recurrence to death survival (RTDS) were analyzed using Kaplan–Meier method. Multivariate analysis was performed by Cox proportional hazards regression.



Results

The stable-H/increasing and stable-L/decreasing groups had the lowest and highest 5-year OS and RTDS rates (10.8%/18.8% vs 56.3%/55.0%; 3.4%/5.1% vs 37.7%/33.2%; both P < 0.001), while the stable-M group had the lower rates, which were 29.8% and 23.6% (for OS and RTDS: vs stable-L, P < 0.001 and 0.002; vs deceasing, P = 0.001 and 0.012; vs increasing, P = 0.113 and 0.011; vs stable-H, both P < 0.001). Cox regression analysis showed that AFP inconsistency was an independent factor affecting RTDS (decreasing vs stable-L, hazard ratio: 1.10, 95% confidence interval: 0.79–1.54, P = 0.575; increasing vs stable-L, 2.93, 2.06–4.16, P < 0.001).



Conclusions

The AFP inconsistency was an important prognostic factor for recurrent HCC.

Changes in serum alpha fetoprotein in patients with recurrent hepatocellular carcinoma following hepatectomy.

Background Urinary stones usually start at a young age and tend to recur. Therefore, preventing stone occurrence and recurrence in young people is crucial. We aimed to investigate the association between subcutaneous adipose tissue, visceral adipose tissue, and stone episodes in young people. Methods We retrospectively studied patients aged below 40 years with kidney or ureteral stones. Data on demographic and metabolic characteristics, urolithiasis history, subcutaneous fat area (SFA), and visceral fat area (VFA) were collected. We evaluated the association between SFA or VFA and the occurrence or recurrence of stone episodes using binary logistic regression and Poisson regression analyses. Results In total, 120 patients were included. Abdominal obesity, overweight or obesity, dyslipidemia, metabolic syndrome, SFA, and VFA increased with the number of stone episodes (all p < 0.05). The increase in SFA was independently associated with episode occurrence (p = 0.015). Patients with an SFA > 97 cm2 had a higher risk of episode occurrence. SFA and VFA accumulation were independently associated with episode recurrence (all p < 0.05), and SFA had a stronger association than VFA did. Conclusions In young people, SFA accumulation is an independent and early risk factor for the occurrence and recurrence of stone episodes. Subcutaneous fat could be a convenient and effective indicator to assess the risk of stone episodes before the development of metabolic disorders.

Guanghua Liu

Papers

Prognostic Nomogram for Intrahepatic Cholangiocarcinoma After Partial Hepatectomy

Early intrahepatic recurrence of hepatocellular carcinoma after hepatectomy treated with re-hepatectomy, ablation or chemoembolization: a prospective cohort study.

TikTok as an Information Hodgepodge: Evaluation of the Quality and Reliability of Genitourinary Cancers Related Content

Changes in serum alpha fetoprotein in patients with recurrent hepatocellular carcinoma following hepatectomy.

Subcutaneous Adipose Tissue Accumulation Is an Independent Risk Factor of Urinary Stone in Young People