The role of resection in hepatocellular carcinoma BCLC stage B: A multi-institutional patient-level meta-analysis and systematic review.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. METHODS: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. RESULTS: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03-0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. CONCLUSION: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies.

Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Benchmark Outcomes in Deceased Donor Kidney Transplantation: A Multicenter Analysis of 80 996 Transplants From 126 Centers.

Background: We defined clinically relevant benchmark values in deceased donor kidney transplantation (KT), to assess the best achievable results in low-risk patient cohorts from experienced centers. Methods: We identified the "ideal" cases from the United Network for Organ Sharing Standard Transplant Analysis and Research files from centers performing ≥50 KT per year between 2010 and 2018. Cases have been selected based on the kidney donor profile index values (<35%), a cold ischemia time (CIT) ≤18 h, a HLA mismatch ≤4, and excluding blood group (ABO) incompatible, dual and combined transplants. The outcomes of the benchmark cohort have been compared with a group of patients excluded from the benchmark cohort because but not meeting 1 or more of the abovementioned criteria. Results: The 171 424 KT patients in the United Network for Organ Sharing Standard Transplant Analysis and Research files were screened and 8694 benchmark cases of a total of 80 996 KT (10.7%) from 126 centers meeting the selection criteria were identified. The benchmarks for 1-, 3-, and 5-y patient survival are ≥97%, ≥92.5%, and ≥86.7%, and ≥95.4%, ≥87.8%, and ≥79.6% for graft survival. Benchmark cutoff for hospital length of stay is ≤5 d, ≤23.6% for delayed graft function, and ≤7.5% and ≤9.1% for 6-mo and 1-y incidence of acute rejection. Overall 1-, 3-, and 5-y actuarial graft survivals were 96.6%, 91.1%, and 84.2% versus 93.5%, 85.4%, and 75.5% in the benchmark and comparison groups, respectively (P < 0.001). Overall 1-, 3-, and 5-y actuarial patient survivals were 98.1%, 94.8%, and 90.0% versus 96.6%, 91.1%, and 83.0% in the benchmark and comparison groups, respectively (P < 0.001). Conclusions: For the first time, we quantified the best achievable postoperative results in an ideal scenario in deceased donor KT, aimed at improving the clinical practice guided by the comparison of center performances with the ideal outcomes defined.

Robotic 8-mm trocar fascial wounds: To close or not to close?

BACKGROUND: The aim of this study was to investigate 8-mm robotic trocar site hernia (TSH) rate over the short and long term, providing aids to manage the related fascial wounds. METHODS: A retrospective analysis of 320 patients undergoing robotic surgery was conducted. The primary outcome was 8-mm TSH rate with a minimum follow-up of 12 months. The secondary outcome was the rate of haematomas and infections related to 8-mm wounds and their association with patient comorbidities and trocar position. RESULTS: One case of TSH was observed (0.31%). There were 15 cases of wound infection (4.68%) and 22 cases of wound haematoma (6.87%). Trocar related complications were significantly associated with patient comorbidities, not with trocar position. CONCLUSIONS: Our results do not justify the 8-mm fascial wound closure. Data concerning the association between trocar-related complications and patient comorbidities strengthen the need to implement the control of metabolic state and correct administration of perioperative therapy in high-risk patients.

Local recurrence risk factors and outcomes in minimally invasive thermal ablation for liver tumors: a single-institution analysis.

BACKGROUND: Minimally Invasive thermal ablation (MITA) of liver tumors is a commonly performed procedure, alone or in combination with liver resection. Despite being a first-option strategy for small lesions, it is technically demanding, and many concerns still exist about local disease control. METHODS: Consecutive patients undergoing MITA from 1-2019 to 12-2022 were retrospectively enrolled. Risk factors of local recurrence were investigated through univariate and multivariable cox regression analysis. RESULTS: At the multivariable analysis of the 207 nodules undergoing MITA, RFA was associated with worse local Recurrence Free Survival (lRFS) than MWA (HR 2.87 [95 % CI 0.96-8.66], p = 0.05), as well as a concomitant surgical resection (HR 3.89 [95 % CI 1.06-9.77], p = 0.02). A concomitant surgical resection showed worse lRFS in the subgroup analysis of both HCC (HR 3.98 [95 % CI 1.16-13.62], p = 0.02) and CRLM patients (HR 2.68 [95 % CI 0.66-5.92], p = 0.04). Interestingly, a tumor size between 30 and 40 mm was not associated to worse lRFS. CONCLUSION: MWA may reduce the risk of local recurrence in comparison to RFA, while MITA associated to liver resection may face an increased risk of local recurrence. Further prospective studies are needed to confirm such results.

Preoperative planning and intraoperative real-time navigation with indocyanine green fluorescence in robotic liver surgery.

PURPOSE: We aimed at exploring indocyanine green (ICG) fluorescence wide spectrum of applications in hepatobiliary surgery as can result particularly useful in robotic liver resections (RLR) in order to overcome some technical limitations, increasing safety, and efficacy. METHODS: We describe our experience of 76 RLR performed between March 2020 and December 2022 exploring all the possible applications of pre- and intraoperative ICG administration. RESULTS: Hepatocellular carcinoma and colorectal liver metastases were the most common indications for RLR (34.2% and 26.7% of patients, respectively), and 51.3% of cases were complex resections with high IWATE difficulty scores. ICG was administered preoperatively in 61 patients (80.3%), intraoperatively in 42 patients (55.3%) and in both contexts in 25 patients (32.9%), with no observed adverse events. The most frequent ICG goal was to achieve tumor enhancement (59 patients, 77.6%), with a success rate of 94.9% and the detection of 3 additional malignant lesions. ICG facilitated evaluation of the resection margin for residual tumor and perfusion adequacy in 33.9% and 32.9% of cases, respectively, mandating a resection enlargement in 7.9% of patients. ICG fluorescence allowed the identification of the transection plane through negative staining in the 25% of cases. Vascular and biliary structures were visualized in 21.1% and 9.2% of patients, with a success rate of 81.3% and 85.7%, respectively. CONCLUSION: RLR can benefit from the routine integration of ICG fluoresce evaluation according to each individual patient and condition-specific goals and issues, allowing liver functional assessment, anatomical and vascular evaluation, tumor detection, and resection margins assessment.

Role of preoperative 3D rendering for minimally invasive parenchyma sparing liver resections.

BACKGROUND: 3D rendering (3DR) represents a promising approach to plan surgical strategies. The study aimed to compare the results of minimally invasive liver resections (MILS) in patients with 3DR versus conventional 2D CT-scan. METHODS: We performed 118 3DR for various indications; the patients underwent a preoperative tri-phasic CT-scan and rendered with Synapse3D® Software. Fifty-six patients undergoing MILS with pre-operative 3DR were compared to a similar cohort of 127 patients undergoing conventional pre-operative 2D CT-scan using the propensity score matching (PSM) analysis. RESULTS: The 3DR mandated pre-operative surgical plan variations in 33.9% cases, contraindicated surgery in 12.7%, providing a new surgical indication in 5.9% previously excluded cases. PSM identified 39 patients in both groups with comparable results in terms of conversion rates, blood loss, blood transfusions, parenchymal R1-margins, grade ≥3 Clavien-Dindo complications, 90-days mortality, and hospital stay respectively in 3DR and conventional 2D. Operative time was significantly increased in the 3DR group (402 vs. 347 min, p = 0.020). Vascular R1 resections were 25.6% vs 7.7% (p = 0.068), while the conversion rate was 0% vs 10.2% (p = 0.058), respectively, for 3DR group vs conventional 2D. CONCLUSION: 3DR may help in surgical planning increasing resectability rate while reducing conversion rates, allowing the precise identification of anatomical landmarks in minimally invasive parenchyma-preserving liver resections.

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome.

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Systematic review, meta-analysis and single-centre experience of the diagnostic accuracy of intraoperative near-infrared indocyanine green-fluorescence in detecting pancreatic tumours.

BACKGROUND: During pancreatic resections assessing tumour boundaries and identifying the ideal resection margins can be challenging due to the associated pancreatic gland inflammation and texture. This is particularly true in the context of minimally invasive surgery, where there is a very limited or absent tactile feedback. Indocyanine green (ICG) fluorescence imaging can assist surgeons by simply providing valuable real-time intraoperative information at low cost with minimal side effects. This meta-analysis summarises the available evidence on the use of near-infrared fluorescence imaging with ICG for the intraoperative visualization of pancreatic tumours (PROSPERO ID: CRD42021247203). METHODS: MEDLINE, Embase, and Web Of Science electronic databases were searched to identify manuscripts where ICG was intravenously administered prior to or during pancreatic surgery and reporting the prevalence of pancreatic lesions visualised through fluorescence imaging. RESULTS: Six studies with 7 series' reporting data on 64 pancreatic lesions were included in the analysis. MINOR scores ranged from 6 to 10, with a median of 8. The most frequent indications were pancreatic adenocarcinoma and neuroendocrine tumours. In most cases (67.2%) ICG was administered during surgery. ICG fluorescence identified 48/64 lesions (75%) with 81.3% accuracy, 0.788 (95%CI 0.361-0.961) sensitivity, 1 (95%CI 0.072-1) specificity and positive predictive value of 0.982 (95%CI 0.532-1). In line with the literature, ICG fluorescence identified 5/6 (83.3%) of pancreatic lesions during robotic pancreatic resections performed at our Institution. CONCLUSION: This meta-analysis is the first summarising the results of ICG immunofluorescence in detecting pancreatic tumours during surgery, showing good accuracy. Additional research is needed to define optimal ICG administration strategies and fluorescence intensity cut-offs.

Artificial intelligence in the diagnosis and management of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the third most common malignancy worldwide, with approximately 50% of patients developing colorectal cancer liver metastasis (CRLM) during the follow-up period. Management of CRLM is best achieved via a multidisciplinary approach and the diagnostic and therapeutic decision-making process is complex. In order to optimize patients' survival and quality of life, there are several unsolved challenges which must be overcome. These primarily include a timely diagnosis and the identification of reliable prognostic factors. Furthermore, to allow optimal treatment options, a precision-medicine, personalized approach is required. The widespread digitalization of healthcare generates a vast amount of data and together with accessible high-performance computing, artificial intelligence (AI) technologies can be applied. By increasing diagnostic accuracy, reducing timings and costs, the application of AI could help mitigate the current shortcomings in CRLM management. In this review we explore the available evidence of the possible role of AI in all phases of the CRLM natural history. Radiomics analysis and convolutional neural networks (CNN) which combine computed tomography (CT) images with clinical data have been developed to predict CRLM development in CRC patients. AI models have also proven themselves to perform similarly or better than expert radiologists in detecting CRLM on CT and magnetic resonance scans or identifying them from the noninvasive analysis of patients' exhaled air. The application of AI and machine learning (ML) in diagnosing CRLM has also been extended to histopathological examination in order to rapidly and accurately identify CRLM tissue and its different histopathological growth patterns. ML and CNN have shown good accuracy in predicting response to chemotherapy, early local tumor progression after ablation treatment, and patient survival after surgical treatment or chemotherapy. Despite the initial enthusiasm and the accumulating evidence, AI technologies' role in healthcare and CRLM management is not yet fully established. Its limitations mainly concern safety and the lack of regulation and ethical considerations. AI is unlikely to fully replace any human role but could be actively integrated to facilitate physicians in their everyday practice. Moving towards a personalized and evidence-based patient approach and management, further larger, prospective and rigorous studies evaluating AI technologies in patients at risk or affected by CRLM are needed.

The Role of Robotic Visceral Surgery in Patients with Adhesions: A Systematic Review and Meta-Analysis.

Abdominal adhesions are a risk factor for conversion to open surgery. An advantage of robotic surgery is the lower rate of unplanned conversions. A systematic review was conducted using the terms "laparoscopic" and "robotic". Inclusion criteria were: comparative studies evaluating patients undergoing laparoscopic and robotic surgery; reporting data on conversion to open surgery for each group due to adhesions and studies including at least five patients in each group. The main outcomes were the conversion rates due to adhesions and surgeons' expertise (novice vs. expert). The meta-analysis included 70 studies from different surgical specialities with 14,329 procedures (6472 robotic and 7857 laparoscopic). The robotic approach was associated with a reduced risk of conversion (OR 1.53, 95% CI 1.12-2.10, p = 0.007). The analysis of the procedures performed by "expert surgeons" showed a statistically significant difference in favour of robotic surgery (OR 1.48, 95% CI 1.03-2.12, p = 0.03). A reduced conversion rate due to adhesions with the robotic approach was observed in patients undergoing colorectal cancer surgery (OR 2.62, 95% CI 1.20-5.72, p = 0.02). The robotic approach could be a valid option in patients with abdominal adhesions, especially in the subgroup of those undergoing colorectal cancer resection performed by expert surgeons.

Robotic pancreaticoduodenectomy with biodegradable ductal stenting (Archimedes BPS®).

BACKGROUND: Postoperative Pancreatic Fistula (POPF) development remains a challenge after pancreaticoduodenectomy, occurring in 3-45% of cases [1]. The placement of a trans-anastomotic Wirsung stent is usually done in high-risk patients to decrease incidence and severity of POPF. METHODS: Herein, we present a fully robotic pancreaticoduodenectomy with a biodegradable ductal stent interposition in a 47 y.o. female with a main duct IPMN of the pancreatic head and a fistula risk score of 6 (Moderate-risk). VIDEO: After gastrocolic ligament division and hepatic flexure and duodenum mobilization, the loco-regional lymphadenectomy was performed. Following gastric transection with endo-GIA, the bile duct and gastroduodenal artery have been divided, and the cholecystectomy performed. The neck of the pancreas has been transected, the jejunum divided with endo-GIA and mobilized from the Treitz ligament, and the uncinate process dissected from the mesenteric vessels. A Blumgart anastomosis has been performed between the soft-texture pancreatic stump and the jejunal loop with the interposition of a 6 Fr/60 mm long, medium degrading stent (20 days) in the 2 mm duct (Archimedes BPS®, AMG Int., Winsen-Germany). The hepatico-jejunostomy and gastro-jejunostomy have been performed distally on the same loop. Three abdominal drains have been positioned. RESULTS: Surgery lasted 480 min, with 175 mls blood loss. The patient postoperatively developed a biochemical leak and was discharged home by day 12. She was readmitted a month later for an amylase-negative intra-abdominal abscess that was successfully treated with percutaneous drainage. CONCLUSION: Biodegradable pancreatic stent positioning could be an effective strategy in reducing POPF occurrence in high-risk patients.

Robotic central pancreatectomy: a systematic review and meta-analysis.

BACKGROUND: Central pancreatectomy is usually performed to excise lesions of the neck or proximal body of the pancreas. In the last decade, thanks to the advent of novel technologies, surgeons have started to perform this procedure robotically. This review aims to appraise the results and outcomes of robotic central pancreatectomies (RCP) through a systematic review and meta-analysis. METHODS: A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of RCP. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modelling. RESULTS: Thirteen series involving 265 patients were included. In all cases but one, RCP was performed to excise benign or low-grade tumours. Clinically relevant post-operative pancreatic fistula (POPF) occurred in 42.3% of patients. While overall complications were reported in 57.5% of patients, only 9.4% had a Clavien-Dindo score ≥ III. Re-operation was necessary in 0.7% of the patients. New-onset diabetes occurred postoperatively in 0.3% of patients and negligible mortality and open conversion rates were observed. CONCLUSION: RCP is safe and associated with low perioperative mortality and well preserved postoperative pancreatic function, although burdened by high overall morbidity and POPF rates.

Robotic versus Laparoscopic Surgery for Spleen-Preserving Distal Pancreatectomies: Systematic Review and Meta-Analysis.

BACKGROUND: When oncologically feasible, avoiding unnecessary splenectomies prevents patients who are undergoing distal pancreatectomy (DP) from facing significant thromboembolic and infective risks. METHODS: A systematic search of MEDLINE, Embase, and Web Of Science identified 11 studies reporting outcomes of 323 patients undergoing intended spleen-preserving minimally invasive robotic DP (SP-RADP) and 362 laparoscopic DP (SP-LADP) in order to compare the spleen preservation rates of the two techniques. The risk of bias was evaluated according to the Newcastle-Ottawa Scale. RESULTS: SP-RADP showed superior results over the laparoscopic approach, with an inferior spleen preservation failure risk difference (RD) of 0.24 (95% CI 0.15, 0.33), reduced open conversion rate (RD of -0.05 (95% CI -0.09, -0.01)), reduced blood loss (mean difference of -138 mL (95% CI -205, -71)), and mean difference in hospital length of stay of -1.5 days (95% CI -2.8, -0.2), with similar operative time, clinically relevant postoperative pancreatic fistula (ISGPS grade B/C), and Clavien-Dindo grade ≥3 postoperative complications. CONCLUSION: Both SP-RADP and SP-LADP proved to be safe and effective procedures, with minimal perioperative mortality and low postoperative morbidity. The robotic approach proved to be superior to the laparoscopic approach in terms of spleen preservation rate, intraoperative blood loss, and hospital length of stay.

Liquid biopsy in cholangiocarcinoma: Current status and future perspectives.

Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.