Advances and considerations in the use of immunotherapies for primary hepato-biliary malignancies.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) comprise the two most common primary liver malignancies. Curative treatment options often include hepatectomy or liver transplantation; however, many patients present with advanced disease that is not amenable to surgical management. In turn, many patients are treated with systemic or targeted therapy. The tumor microenvironment (TME) is a complex network of immune cells and somatic cells, which can foster an environment for disease development and progression, as well as susceptibility and resistance to systemic therapeutic agents. In particular, the TME is comprised of both immune and non-immune cells. Immune cells such as T lymphocytes, natural killer (NK) cells, macrophages, and neutrophils reside in the TME and can affect tumorigenesis, disease progression, as well as response to therapy. Given the importance of the immune system, there are many emerging approaches for cancer immunotherapy. We herein provide a review the latest data on immunotherapy for primary HCC and BTC relative to the TME.

One-tenth-activity total-body positron emission tomography versus full-activity imaging in patients with a complex of hepatic malignant tumors: a retrospective study.

Background: The value of ultra-low-activity 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging in patients with hepatic malignancies remains unclear. Methods: A cross-sectional study was conducted from April 2019 to May 2021 in Zhongshan Hospital, Fudan University. A total of 49 patients with hepatic malignancies, including hepatocellular carcinoma (HCC) (n=13) or intrahepatic cholangiocarcinoma (ICC) (n=36), underwent 60-min dynamic PET imaging, with 15 undergoing full-activity 18F-FDG and 34 undergoing ultra-low-activity 18F-FDG. The kinetic metrics (K1-k3, and Ki) of tumors were calculated and compared between the activity groups. Another 54 patients (27 each group) with hepatic malignancies, including HCC (n=9), ICC (n=34), and metastases (n=11), underwent static imaging. Image qualities were compared between the groups in terms of 5-point Likert scores (with a score ≥3 fulfilling the clinical requirement), the mean standardized uptake value (SUVmean), the standard deviation of standardized uptake value (SUVSD), and the signal-to-noise ratio (SNR) of the liver; the SUVmean of blood pool and muscle; and the tumor-to-liver ratio (TLR), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of lesions. Intergroup comparisons were performed using Chi-squared test for categorical variables and the Student's t-test or the Mann-Whitney test for continuous variables depending on the normality of variables. Results: There was a nonsignificant difference in the kinetic metrics (K1-k3 and Ki) of tumors between the activity groups. In static imaging, 1-min full-activity (F1) and 8-min ultra-low-activity (L8) images obtained image-quality scores >3 and were thus selected for intergroup comparisons. Nonsignificant differences in SUVmean of liver, blood pool, and muscle were identified between F1 and L8 images (P=0.641, P=0.542, and P=0.073, respectively) although the liver SNR was slightly higher in F1 (13.10 vs. 11.31; P=0.003). Lesion detectability was 98.5% and 100% for F1 and L8 images, respectively, but there were no significant differences in TLR, TBR, or TMR between the groups. Conclusions: The results of this single-center study indicate that the performance of ultra-low-activity PET imaging is comparable to that of full-activity imaging in patients with hepatic malignancies.

Peritumoral abnormalities on dynamic-enhanced CT after brachytherapy for hepatic malignancies: local progression or benign changes?

OBJECTIVES: To determine if dynamic CT can differentiate local progression from radioactive seed-induced peritumoral reaction (RSIPR) after brachytherapy with iodine-125 radioactive seeds (BIRS) for advanced hepatic malignancies. METHODS: Enhanced CT images of seed-implanted lesions between 2006 and 2018 were retrospectively evaluated. Hounsfield units of peritumoral parenchyma were measured and assessed quantitatively. The classification, conversion, consequences, and serological indicators during follow-up were recorded and quantified. Statistical differences were analyzed using a Pearson χ2 test. RESULTS: RSIPR was observed in 201 of 290 (69.3%) lesions (161 patients; median age, 55 years; range, 26-79 years), while local progression occurred in 53 lesions. The low density of local progression was much lower than that of RSIPR (p < 0.001), and the former did not exhibit iso-/high density in the portal or equilibrium phase. Ring-like enhancement in progressive lesions was also quite different from RSIPR. Local progression rate was lower for lesions with RSIPR than for those without RSIPR (14.9% vs 25.8%; p = 0.03), and their doses were different (397.2 Gy vs 120.3 Gy, p < 0.001). CONCLUSIONS: Radioactive seed-induced peritumoral reaction has characteristic manifestations on CT images, which is associated with a higher dose of lesions and lower local progression rate. Notably, the enhancement pattern of local progression was distinct from RSIPR and was clearly distinguishable on dynamic-enhanced CT. KEY POINTS: • Radioactive seed-induced peritumoral reaction after brachytherapy with 125I seeds for liver malignancies has characteristic manifestations on CT images, which is associated with a higher dose of lesions (397.2 Gy vs 120.3 Gy, p < 0.001), as a focal radiation injury. • Lesions with RSIPR were less likely to develop local progression, while those without RSIPR had a higher rate of local progression (14.9% vs 25.8%; p = 0.03). • The enhancement pattern of local progression after brachytherapy was distinct from radioactive seed-induced peritumoral reaction and was clearly distinguishable on dynamic-enhanced CT.

Low skeletal muscle mass and post-operative complications after surgery for liver malignancies: a meta-analysis.

PURPOSE: To assess the influence of low skeletal muscle mass (LSMM) on post-operative complications in patients with hepatic malignancies grade (Clavien Dindo ≥ 3) undergoing resection. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between sarcopenia and major post-operative complications (≥ grade 3 according to Clavien-Dindo classification) after resection of different malignant liver tumors. RevMan 5.3 software was used to perform the meta-analysis. The methodological quality of the included studies was assessed according to the QUIPS instrument. RESULTS: The analysis included 17 studies comprising 3157 patients. Subgroup analyses were performed for cholangiocarcinoma (CCC), colorectal cancer (CRC) liver metastases, and hepatocellular carcinoma (HCC). LSMM as identified on CT was present in 1260 patients (39.9%). Analysis of the overall sample showed that LSMM was associated with higher post-operative complications grade Clavien Dindo ≥ 3 (OR 1.56, 95% CI 1.25-1.95, p < 0.001). In the subgroup analysis, LSMM was associated with post-operative complications in CRC metastases (OR 1.60, 95% CI 1.11-2.32, p = 0.01). In HCC and CCC sub-analyses, LSMM was not associated with post-operative complications in simple regression analysis. CONCLUSION: LSMM is associated with major post-operative complications in patients undergoing surgery for hepatic metastases and it does not influence major post-operative complications in patients with HCC and CCC.

Results of Intrahepatic Cholangiocarcinoma Resections: a Single-Center Analysis.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary neoplasm of the liver after hepatocellular carcinoma (HCC). Although an underlying cause is not usually found, liver flukes, cirrhosis, primary sclerosing cholangitis, and viral hepatitis have been found to increase the risk in recent years. In this study, we aimed to present our experience on ICC and compare the outcomes of patients with a concomitant liver pathology and with incidentally detected ICC. PATIENTS AND METHODS: Thirty-three patients who underwent surgical resection for ICC were included in the study. Patients were divided into two groups, group one (with concomitant liver disease, n = 13) and group two (incidentally detected ICC, n = 18). Demographics, perioperative findings, pathological properties, recurrence rates, and survival rates were retrospectively analyzed and compared between the groups. RESULTS: The mean age of patients was 59.77 ± 9.81 years, of whom sixteen (51.6%) were males. Thirteen patients (41.9%) had concomitant liver disease, the most common being chronic hepatitis B infection. Eighteen patients (58.1%) had incidentally detected ICC. There were no significant differences between the groups except for follow-up time and recurrence rate. The recurrence rate was significantly higher in the incidentally detected ICC group (61.1% versus 7.7%, p = 0.003). Follow-up time was significantly higher in patients with concomitant liver disease (42 versus 17.5 months, p = 0.007). The mortality rate was higher in the incidentally detected ICC group (55.6 to 23.1%, p = 0.071) but the difference did not reach statistical significance. CONCLUSION: Surgical resection in ICC patients with underlying liver disease is associated with better prognosis than in incidentally detected ICC patients. Incidental ICC may be a different tumor with different biology, hence the high recurrence rates.

Clinical efficacy and safety of ex-vivo liver resection and liver auto-transplantation: a bayesian single-arm Meta-analysis / 中华肝胆外科杂志

Objective:To evaluate the clinical efficacy and safety of ex vivo liver resection and autotransplantation (ELRA) by using a Bayesian single-arm Meta-analysis.Methods:Databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from January 1, 1990 to December 30, 2021 on ELRA studies. The Bayesian one-arm Meta-analysis was performed by using the statistical software of R (V4.1.2) and the Markov chain-Monte Carlo method was used to simulate the posterior distribution. The mortality rate within 30 days after operation, 1-year survival rate, major postoperative complications, R 0 resection rate and other related indexes were analyzed. Results:A total of 20 studies with 436 patients were included. Bayesian single-arm Meta-analysis showed that the 1-year survival rate after ELRA was 83.24% [95% highest posterior density ( HPD): 72.40%-92.05%]. The 1-year survival rates after surgery were 88.66% (95% HPD: 81.52%-94.50%) for patients with hepatic alveolar echinococcosis and 61.29% (95% HPD: 38.53%-93.68%) for patients with hepatic malignancies, respectively. The mortality rate within 30 d after surgery, the incidence of significant postoperative complications, and the R 0 resection rate were 6.96% (95% HPD: 4.47%-10.15%), 27.91% (95% HPD: 19.00%-38.30%), and 99.84% (95% HPD: 37.61%-100.00%), respectively. Renal failure was the most frequent cause of death after ELRA. Conclusion:ELRA is indicated for hepatic malignancies and hepatic alveolar echinococcosis when intrahepatic resection cannot be accomplished in vivo. The greatest benefit is observed in patients with hepatic alveolar echinococcosis, while only some patients with hepatic malignancies can benefit. The indications for ELRA for hepatic malignancies need to be further studied to define the subgroup of patients who can benefit from this operation.

MRI-guided percutaneous thermoablation as first-line treatment of recurrent hepatic malignancies following hepatic resection: single center long-term experience.

PURPOSE: Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection. MATERIAL AND METHODS: Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method. RESULTS: A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1-4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months. CONCLUSION: MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.

Microwave Ablation of Small Hepatic Metastases Using MR Guidance and Monitoring: Clinical Safety and Efficacy.

BACKGROUND: To evaluate the technical success and clinical safety of magnetic resonance (MR)-guided microwave ablation (MWA) of small hepatic metastases. MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. A retrospective analysis of the patient data revealed 50 patients with small hepatic metastases (34 men, 16 women) who underwent MWA under MR guidance and monitoring. After the procedure, the intervention-related complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) and Society of Interventional Radiology (SIR) classification system. Furthermore, the overall survival (OS) and local tumor-free survival (LTP) of the patients were analyzed. RESULTS: The patients who underwent MR-guided MWA achieved technical success. The mean energy, ablation duration per tumor, and procedure duration were 55.3 ± 9.4 kJ, 11.7 ± 5.6 min and 89.5 ± 30.9 min, respectively. Most adverse events and complications were CTCAE grade 1 or 2 or SIR classification grade A or B. The 1-, 2-, and 3-year local tumor progression (LTP) rates were 65.9%, 31.5% and 18.5%, respectively, with a mean LTP of 19.216 months (95% CI: 16.208, 22.224); and the 1-, 2- and 3-year overall survival (OS) rates were 81.8%, 60.8% and 44.7%, respectively, with a mean OS of 26.378 months (95% CI: 23.485, 29.270). Multivariate Cox's regression analysis further illustrated that tumor location (challenging locations vs ordinary locations) and the anesthesia (general anesthesia VS local anesthesia) were important factors affecting LTP and OS. CONCLUSION: MR-guided MWA can successfully treat small hepatic metastases with potentially favorable safety and technical efficacy.

MR-guided microwave ablation in hepatic malignancies: clinical experiences from 50 procedures.

Purpose: To investigate technical success, technique efficacy, safety and outcome of MR-guided microwave ablation (MWA) in hepatic malignancies.Material and methods: In this prospective IRB-approved study, patients scheduled for percutaneous treatment of hepatic malignancies underwent MR-guided MWA in a closed-bore 1.5 T MR system. Technical success was assessed on post-procedural MR control imaging. Technique efficacy was evaluated 4 weeks after the procedure on multi-parametric MRI. Assessment of safety followed the Society of Interventional Radiology grading system. Kaplan-Meier survival estimates were calculated to evaluate overall survival (OS), time to local tumor progression (TLTP), and time to non-target progression (TNTP).Results: Between 2015 and 2019, 47 patients (60.5 ± 12.2 years; 39 male) underwent 50 procedures for 58 hepatic tumors (21 hepatocellular carcinomas; 37 metastases). Mean target tumor size was 16 ± 7mm (range: 6-39 mm). Technical success and technique efficacy were 100% and 98%, respectively. Lesions were treated using 2.6 applicator positions (range: 1-6). Mean energy, ablation duration per tumor, and procedure duration were 43.2 ± 23.5 kJ, 26.7 ± 13.1 min and 211.2 ± 68.7 min, respectively. 10 minor (20%) and 3 major (6%) complications were observed. Median post-interventional hospital admission was 1 day (range: 1-19 days). Median OS was 41.6 (IQR: 26.4-) months. Local recurrence occurred after 4 procedures (8%) with TLTP ranging between 3.1 and 41.9 months. Non-target recurrence was observed in 64% of patients after a median TNTP of 13.8 (IQR 2.3-) months.Conclusion: MR-guided MWA allows for safe and successful treatment of hepatic malignancies with a high technique efficacy however with relatively long procedure durations.

Cryoablation combined with radiotherapy for hepatic malignancy: Five case reports.

BACKGROUND: The survival of patients treated with monotherapy for hepatic malignancies is not ideal. A comprehensive program of cryoablation combined with radiotherapy for the treatment of hepatic malignancies results in less trauma to the patients. It may provide an option for the treatment of patients with advanced hepatic malignancies. CASE SUMMARY: We reported 5 cases of advanced-stage hepatic malignancies treated in our hospital from 2017-2018, including 3 cases of primary hepatocellular carcinoma and 2 cases of metastatic hepatic carcinoma. They first received cryoablation therapy on their liver lesions. The procedure consisted of 2 freeze-thaw cycles, and for each session, the duration of freezing was 13-15 min, and the natural re-warming period was 2-8 min. Depending on the tumor size, the appropriate cryoprobes were selected to achieve complete tumor ablation to the greatest extent possible. After cryoablation surgery, intensity-modulated radiotherapy (IMRT) for liver lesions was performed, and the radiotherapy regimen was 5400 cGy/18f and 300 cGy/f. None of the 5 patients had adverse events above grade II, and their quality of life was significantly improved. Among them, 4 patients were free of disease progression in the liver lesions under local control, and their survival was prolonged; 3 patients are still alive. CONCLUSION: Our clinical practice demonstrated that cryoablation combined with IMRT could be implemented safely. The definitive efficacy for hepatic malignancies needs to be confirmed in larger-size sample prospective studies.

Imaging of primary malignant tumors in non-cirrhotic liver.

Primary hepatic malignancies in non-cirrhotic liver include a wide spectrum of tumors, which are classified based on their cells of origin. Hepatocellular carcinoma is the most common primary malignant tumor, followed by intrahepatic cholangiocarcinoma. Beside these tumors, other primary malignancies in the non-cirrhotic liver are quite rare. Accurate diagnosis is often difficult with imaging alone and biopsy with further histopathological analysis is often necessary. However, many of these tumors exhibit suggestive or characteristic imaging features due to their different cellular components, allowing radiologists to suggest the correct diagnosis. Thus, the aim of this article is to provide an overview of imaging presentation of primary malignant liver tumors that develop in the non-cirrhotic liver, including potential differential diagnoses. Such knowledge is essential as it may contribute to accurate radiological diagnosis and improved patient outcome.

Multiclass Classification of Hepatic Anomalies with Dielectric Properties: From Phantom Materials to Rat Hepatic Tissues.

Open-ended coaxial probes can be used as tissue characterization devices. However, the technique suffers from a high error rate. To improve this technology, there is a need to decrease the measurement error which is reported to be more than 30% for an in vivo measurement setting. This work investigates the machine learning (ML) algorithms' ability to decrease the measurement error of open-ended coaxial probe techniques to enable tissue characterization devices. To explore the potential of this technique as a tissue characterization device, performances of multiclass ML algorithms on collected in vivo rat hepatic tissue and phantom dielectric property data were evaluated. Phantoms were used for investigating the potential of proliferating the data set due to difficulty of in vivo data collection from tissues. The dielectric property measurements were collected from 16 rats with hepatic anomalies, 8 rats with healthy hepatic tissues, and in house phantoms. Three ML algorithms, k-nearest neighbors (kNN), logistic regression (LR), and random forests (RF) were used to classify the collected data. The best performance for the classification of hepatic tissues was obtained with 76% accuracy using the LR algorithm. The LR algorithm performed classification with over 98% accuracy within the phantom data and the model generalized to in vivo dielectric property data with 48% accuracy. These findings indicate first, linear models, such as logistic regression, perform better on dielectric property data sets. Second, ML models fitted to the data collected from phantom materials can partly generalize to in vivo dielectric property data due to the discrepancy between dielectric property variability.

Liver transplantation for primary hepatic malignancies of childhood: The UNOS experience.

BACKGROUND/PURPOSE: The purpose of this study was to determine factors associated with patient and graft survival following orthotopic liver transplantation (OLT) in children and adolescents with primary hepatic malignancies. METHODS: The United Network for Organ Sharing (UNOS) database was queried for all patients <18years old who received an OLT with a primary malignant liver tumor between 1987 and 2012 (n=544). Five-year patient and graft survival were determined using Kaplan-Meier methodology, and independent predictors of survival were determined using multivariate Cox proportional hazards model. RESULTS: The majority of patients were diagnosed with hepatoblastoma (HB) (n=376, 70%) with 84 (15%) hepatocellular carcinoma (HCC) and 84 (15%) other. HCC patients were older, more often hospitalized at the time of transplant, and more likely to receive a cadaveric organ compared to HB patients. Five-year patient and graft survival for the entire cohort was 73% and 74%, respectively, with the majority of deaths owing to malignancy. On multivariate analysis, independent predictors of 5-year patient and graft survival included diagnosis, transplant era, and medical condition at transplant. CONCLUSIONS: In recent years, there has been significant improvement in posttransplant patient and graft survival for children and adolescents with primary hepatic malignancies. However, patients with HCC continue to have worse outcomes than those with other cancer types. TYPE OF STUDY: Case series with no comparison group. LEVEL OF EVIDENCE: IV.

Diagnostic accuracy of different magnetic resonance imaging sequences for detecting local tumor progression after radiofrequency ablation of hepatic malignancies.

OBJECTIVE: To evaluate the diagnostic accuracy of the individual sequences of a clinical routine liver MRI protocol for the detection of local tumour progression after radiofrequency (RF) ablation of hepatic malignancies. MATERIAL AND METHODS: A cohort of 93 patients treated for 140 primary and secondary hepatic malignancies with RF ablation was assembled for this retrospective study. The cohort contained 31 cases of local tumour progression, which occurred 8.3±6.2months (range: 4.0-28.2 months) after treatment. All patients underwent clinical routine follow-up MRI at 1.5T including following sequences: unenhanced T1-weighted fast low angle shot (FLASH-2D), T2-weighted turbo-spin-echo sequence, contrast-enhanced (CE) T1-weighted volume-interpolated breath-hold examination (VIBE), diffusion-weighted imaging (DWI). Follow-up was 32.7±22.5months (range: 4.0-138.3 months). Two readers independently evaluated the individual sequences separately for signs of local tumour progression. Diagnostic confidence was rated on a 4-point scale. Inter-reader agreement was assessed with Cohens kappa. Long-term follow-up and histological specimen served as standard of reference. RESULTS: Both readers reached the highest sensitivity for detection of local tumour progression with unenhanced T1-FLASH 2D (88.2% and 94.1%, respectively) and the highest specificity with CE T1-VIBE (96.2% and 97.2%, respectively). Highest inter-reader agreement was reached with T1-FLASH-2D (kappa=0.83). Typical pitfalls for false-positive diagnoses were focal cholestasis and vasculature adjacent to the ablation zone. Diagnostic confidence was highest with CE T1-VIBE for reader 1 and DWI for reader 2. CONCLUSION: Unenhanced T1-FLASH-2D is an essential sequence for follow-up imaging after tumour ablation with a high sensitivity for detection of local progression and a high inter-reader agreement.

Clinical curative effect and safety of Silybin-nanosuspension in the treatment of liver tumor / 中国生化药物杂志

Objective To study the clinical efficacy and safety of Silybin-nanosuspension in the treatment of liver cancer.Methods 56 patients with liver tumor were collected from February 2014 to May 2015 in our hospital,and all patients were randomly divided into treatment group(n=24)and control group(n=32).The treatment group was treated with oral Silybin-nanosuspension 360mg(Silybin)and control group was treated with Silybin capsule 360mg(Silybin),once a day.The treatment was over once the following conditions appear,the disease progression,or intolerable toxicity,or the lesion site can be treat with surgery,or patient death.Evaluating the efficacy through comparing the data of objective response rate,disease control rate, progression-free survival and overall survival,and record the adverse reactions through measuring the values of indicators of blood toxicity ( leukocytes, neutrophils,platelets and hemoglobin ) and the liver function parameters ( Valley alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) .Results The objective response rate, disease control rate, progression-free survival and overall survival of treatment group were significantly better than control group(P<0.05),and the parameters of blood toxicity and liver function were no significant differences.Conclusion The Silybin-nanosuspension is safe and effective for the treatment of liver malignancies.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review.

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Implantable arterial port-related bloodstream infection in patients with primary or metastatic hepatic malignancies.

The incidence of implantable arterial post-related bloodstream infections (IAP-RBSI) among patients with unresectable hepatic malignancies is not well defined. We reviewed the 9-year incidence of implantable arterial post-related bloodstream infections in patients with hepatic malignancies, at a tertiary care center in Japan. The incidence was 1.9 infections per 10,000 catheter-days.

Liver Resection for Primary Hepatic Neoplasms.

Subtotal hepatic resection was performed in 356 patients; 87 had primary hepatic malignancies, 108 had metastatic tumors, and 161 had benign lesions including 8 traumatic injuries. The global mortality was 4.2%. The experience has elucidated the role of subtotal hepatic resection both for benign and malignant neoplasms.