Low-abundance proteins-based label-free SERS approach for high precision detection of liver cancer with different stages.

BACKGROUND: Surface-enhanced Raman scattering (SERS) technology have unique advantages of rapid, simple, and highly sensitive in the detection of serum, it can be used for the detection of liver cancer. However, some protein biomarkers in body fluids are often present at ultra-low concentrations and severely interfered with by the high-abundance proteins (HAPs), which will affect the detection of specificity and accuracy in cancer screening based on the SERS immunoassay. Clearly, there is a need for an unlabeled SERS method based on low abundance proteins, which is rapid, noninvasive, and capable of high precision detection and screening of liver cancer. RESULTS: Serum samples were collected from 60 patients with liver cancer (27 patients with stage T1 and T2 liver cancer, 33 patients with stage T3 and T4 liver cancer) and 40 healthy volunteers. Herein, immunoglobulin and albumin were separated by immune sorption and Cohn ethanol fractionation. Then, the low abundance protein (LAPs) was enriched, and high-quality SERS spectral signals were detected and obtained. Finally, combined with the principal component analysis-linear discriminant analysis (PCA-LDA) algorithm, the SERS spectrum of early liver cancer (T1-T2) and advanced liver cancer (T3-T4) could be well distinguished from normal people, and the accuracy rate was 98.5% and 100%, respectively. Moreover, SERS technology based on serum LAPs extraction combined with the partial least square-support vector machine (PLS-SVM) successfully realized the classification and prediction of normal volunteers and liver cancer patients with different tumor (T) stages, and the diagnostic accuracy of PLS-SVM reached 87.5% in the unknown testing set. SIGNIFICANCE: The experimental results show that the serum LAPs SERS detection combined with multivariate statistical algorithms can be used for effectively distinguishing liver cancer patients from healthy volunteers, and even achieved the screening of early liver cancer with high accuracy (T1 and T2 stage). These results showed that serum LAPs SERS detection combined with a multivariate statistical diagnostic algorithm has certain application potential in early cancer screening.

Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients.

BACKGROUND: Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP). METHODS: Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP's prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging. RESULTS: Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages. CONCLUSION: The PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study.

BACKGROUND: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. METHODS: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. RESULTS: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation. 1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. CONCLUSIONS: The effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

Natural killer cells modified with a Gpc3 aptamer enhance adoptive immunotherapy for hepatocellular carcinoma.

INTRODUCTION: Natural killer cells can attack cancer cells without prior sensitization, but their clinical benefit is limited owing to their poor selectivity that is caused by the lack of specific receptors to target tumor cells. In this study, we aimed to endow NK cells with the ability to specifically target glypican-3+ tumor cells without producing cell damage or genetic alterations, and further evaluated their therapeutic efficiency. METHODS: NK cells were modified with a Gpc3 DNA aptamer on the cell surface via metabolic glycoengineering to endow NK cells with specific targeting ability. Then, the G-NK cells were evaluated for their specific targeting properties, cytotoxicity and secretion of cytokines in vitro. Finally, we investigated the therapeutic efficiency of G-NK cells against glypican-3+ tumor cells in vivo. RESULTS: Compared with NK cells modified with a random aptamer mutation and unmodified NK cells, G-NK cells induced significant apoptosis/necrosis of GPC3+ tumor cells and secreted cytokines to preserve the intense cytotoxic activities. Moreover, G-NK cells significantly suppressed tumor growth in HepG2 tumor-bearing mice due to the enhanced enrichment of G-NK cells at the tumor site. CONCLUSIONS: The proposed strategy endows NK cells with a tumor-specific targeting ability to enhance adoptive therapeutic efficiency in GPC3+ hepatocellular carcinoma.

Perioperative safety, oncologic outcome, and risk factors of salvage liver resection for initially unresectable hepatocellular carcinoma converted by transarterial chemoembolization plus tyrosine kinase inhibitor and anti-PD-1 antibody: a retrospective multicenter study of 83 patients.

BACKGROUND: To assess the perioperative safety, oncological outcomes, and determinants influencing the oncological outcomes of salvage liver resection for initially unresectable hepatocellular carcinoma (HCC) rendered resectable through transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies (α-PD-1). METHODS: We retrospectively reviewed data from 83 consecutive patients across six tertiary hospitals who underwent salvage liver resection for initially unresectable HCC following conversion by TACE combined with TKIs and α-PD-1, emphasizing perioperative and oncological outcomes. Multivariate Cox regression analysis was employed to discern independent risk factors for postoperative recurrence-free survival (RFS). RESULTS: The median operative duration was 200 min, with a median blood loss of 400 ml. Intraoperative blood transfusions were necessitated for 27 patients. The overall perioperative complication rate was 48.2%, with a major complication rate of 16.9%. One patient died during the perioperative period due to postoperative liver failure. During the median follow-up period of 15.1 months, 24 patients experienced recurrence, with early and intrahepatic recurrence being the most common. Seven patients died during follow-up. Median RFS was 25.4 months, with 1- and 2-year RFS rates of 68.2% and 61.8%, respectively. Median overall survival was not reached, with 1- and 2-year overall survival rates of 92.2% and 87.3%, respectively. Multivariate Cox regression analysis revealed that pathological complete response (pCR) and intraoperative blood transfusion served as independent prognostic determinants for postoperative RFS. CONCLUSIONS: Our study provides preliminary evidence suggesting that salvage liver resection may be an effective and feasible treatment option for patients with unresectable HCC who achieve resectability after conversion therapy with TACE, TKIs, and α-PD-1. The perioperative safety of salvage liver resection for these patients was manageable and acceptable. However, further research, particularly prospective comparative studies, is needed to better evaluate the potential benefits of salvage liver resection in this patient population.

Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures.

PURPOSE: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. METHODS: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS: The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.

Population Pharmacokinetic Modeling of Lenvatinib in Chinese Patients With Advanced Hepatocellular Carcinoma Using Real-World Data.

Lenvatinib is a novel oral angiogenesis inhibitor approved in China for the treatment of unresectable hepatocellular carcinoma (HCC) without prior systemic treatment. We described the population pharmacokinetics of lenvatinib in Chinese patients with advanced HCC and explore the potential patient characteristics associated with lenvatinib pharmacokinetics using real-world data. A total of 266 samples, provided by 127 Chinese patients with advanced HCC, were analyzed by nonlinear mixed-effects modeling. Monte Carlo simulation was conducted to assess impact of covariates on the exposure to lenvatinib. The clearance of lenvatinib in Chinese patients with advanced HCC was 5.3 L/h, and alkaline phosphatase, total bilirubin, and sex were identified as important covariates associated with it. The clearance of Child-Pugh class B patients (4.82L/h) was significantly lower than that of Child-Pugh class A patients (5.53 L/h), and the systemic exposure increased with the increase of alkaline phosphatase and total bilirubin. There were sex differences in the pharmacokinetic characteristics of lenvatinib. The clearance of women was significantly lower than that of men (4.61 vs 5.6 L/h; P < .001), and the area under the plasma concentration-time curve of women was ≈20% higher than that of men. In this study, a population pharmacokinetic model of lenvatinib was established, which can be used to simulate clinical trials or various dosing scenarios. Our findings provide important new insights for optimizing the use of lenvatinib in patients with advanced HCC.

Label-free determination of liver cancer stages using surface-enhanced Raman scattering coupled with preferential adsorption of hydroxyapatite microspheres.

Here, we explored a label-free albumin targeted analysis method by utilizing hydroxyapatite (HAp) to adsorb-release serum albumin, in conjunction with surface-enhanced Raman scattering (SERS) for screening liver cancer (LC) at different tumor (T) stages. Excitingly, albumin can be preferentially adsorbed by HAp as compared with other serum proteins. Moreover, we developed a novel strategy using a high concentration of PO43- solution as the albumin-release agent. This method overcomes the shortcomings of the traditional purification technology of serum albumin, which requires acid to release protein, and ensures that the structure and properties of albumin are not damaged. The SERS spectra of serum albumin obtained from three sample groups were analyzed to verify the feasibility of this new method: healthy volunteers (n = 35), LC patients with T1 stage (n = 25) and LC patients with T2-T4 stage (n = 23). Furthermore, principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to classify the early T (T1) stage LC vs. normal group and advanced T (T2-T4) stage LC vs. normal group, yielding high diagnostic accuracies of 90.00% and 96.55%, respectively, which showed a 10% improvement in diagnostic accuracy for the early stage detection of cancer as compared with previous studies. The results of this exploratory work demonstrated that HAp-adsorbed-released serum albumin combined with SERS analysis has great potential for label-free, noninvasive and sensitive detection of different T stages of liver cancer.

A microsphere nanoparticle based-serum albumin targeted adsorption coupled with surface-enhanced Raman scattering for breast cancer detection.

The serum albumin level is inseparable associated with survival in patients with breast cancer, and simultaneously serve as a good indicator of prognosis of cancer. Here, we proposed a novel extraction-isolation analysis method of albumin for breast cancer detection utilizing hydroxyapatite particles (HAp) to targeted adsorb albumin from serum relying on its specific adsorption capacity. An ideal protein-release reagent was used for isolating albumin from the surface of HAp, and meanwhile ensuring that the structure and property of albumin was not suffered damage. The surface-enhanced Raman scattering (SERS) signal of extracted albumin was obtained, and partial least squares (PLS) and linear discriminant analysis (LDA) analysis approach were employed to analyze SERS spectra data, with the aim to assess the capability of HAp method for identifying breast cancer, yielding an ideal diagnostic accuracy of 98.6%, demonstrating promising potential as a non-invasive and sensitive nanotechnology for breast cancer screening.

Developing a risk prediction model for multidrug-resistant bacterial infection in patients with biliary tract infection.

BACKGROUND/AIMS: The aim of this study was to develop a tool to predict multidrug-resistant bacteria infections among patients with biliary tract infection for targeted therapy. PATIENTS AND METHODS: We conducted a single-center retrospective descriptive study from January 2016 to December 2018. Univariate and multivariable logistic regression analysis were used to identify independent risk factors of multidrug-resistant bacterial infections. A nomogram was constructed according to multivariable regression model. Moreover, the clinical usefulness of the nomogram was estimated by decision curve analysis. RESULTS: 121 inpatients were randomly divided into a training cohort (n = 79) and validation cohort (n = 42). In multivariate analysis, 5 factors were associated with biliary tract infections caused by multidrug-resistant bacterial infections: aspartate aminotransferase (Odds ratio (OR), 13.771; 95% confidence interval (CI), 3.747-64.958; P < 0.001), previous antibiotic use within 90 days (OR, 4.130; 95% CI, 1.192-16.471; P = 0.032), absolute neutrophil count (OR, 3.491; 95% CI, 1.066-12.851; P = 0.046), previous biliary surgery (OR, 3.303; 95% CI, 0.910-13.614; P = 0.079), and hemoglobin (OR, 0.146; 95% CI, 0.030-0.576; P = 0.009). The nomogram model was constructed based on these variables, and showed good calibration and discrimination in the training set [area under the curve (AUC), 0.86] and in the validation set (AUC, 0.799). The decision curve analysis demonstrated the clinical usefulness of our nomogram. Using the nomogram score, high risk and low risk patients with multidrug-resistant bacterial infection could be differentiated. CONCLUSIONS: This simple bedside prediction tool to predict multidrug-resistant bacterial infection can help clinicians identify low versus high risk patients as well as choose appropriate, timely initial empirical antibiotics therapy. This model should be validated before it is widely applied in clinical settings.

Surface-enhanced Raman scattering analysis of serum albumin via adsorption-exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening.

Combining serum albumin via adsorption-exfoliation on hydroxyapatite particles (HAp) with surface-enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS-SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp-adsorbed-exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.

Facile phase transfer of hydrophobic Fe3O4@Cu2-xS nanoparticles by red blood cell membrane for MRI and phototherapy in the second near-infrared window.

The development of nanotheranostic agents integrating diagnosis and therapy has gained tremendous attention in the past few decades, but many of them are inherently hydrophobic and need complicated phase-transfer and tedious surface modifications. This work proposed a facile method of transferring hydrophobic Fe3O4@Cu2-xS nanoparticles from oil to water by using red blood cell membrane to create theranostic nanobeads for T2-weighted MRI and second near-infrared photothermal ablation. The obtained nanoplatform, namely SCS@RBCM, showed a core-shell structure with the inner core densely packed with Fe3O4@Cu2-xS nanoclusters and the surface coated with a layer of RBCM. SCS@RBCM displayed a stable nanostructure, high NIR II light absorption and photothermal conversion ability, T2-weighted MR imaging and magnetic field targeting ability. Meanwhile, the RBCM cloaking endowed SCS with reduced elimination by macrophages. With the navigation of an external magnetic field (MF), the tumor accumulation of SCS@RBCM was dramatically increased, thus achieving good performance of MR imaging and antitumor efficacy through the PTT effect under NIR II irradiation. Therefore, our strategy presents a new and desirable paradigm in the phase-transfer of hydrophobic nanotheranostics for optimizing their biomedical performance.

Ultrasound-induced reactive oxygen species generation and mitochondria-specific damage by sonodynamic agent/metal ion-doped mesoporous silica.

Designing tumor microenvironment (TME)-specific active nanoparticles with minimum side effects for synergistic cancer therapy has become a hot topic in the recent decades. Aiming at further enhancing the therapeutic efficacy, an in situ-induced mitochondrial dysfunction is a very promising strategy. To achieve these goals, a nano-sono-chemodynamic agent denoted as TPP-Cu@HMS, which integrated hematoporphyrin monomethyl ether (HMME), mPEG-NHS, triphenylphosphonium (TPP)-decorated mesoporous silica (MS) and coordinatively bound Cu2+ ions for mitochondria-specific sonodynamic-chemodynamic therapy (SDT-CDT) of cancer, was designed. Upon the ultrasound (US) treatment, TPP-Cu@HMS can specifically target mitochondria and in situ generate 1O2 against cancer cells. Specifically, to overcome the short lifespan of 1O2, the released Cu2+ ions from TPP-Cu@HMS could act as a Fenton-like agent to convert endogenous H2O2 to ·OH in the acidic environment of cancer cells, disrupt the mitochondrial membrane potential and lead to mitochondrial disintegration, which could systematically enhance the therapeutic efficiency of SDT. Therefore, we highlight the current strategy as a promising prospect for cancer therapy.

Somatostatin Octapeptide Inhibits Cell Invasion and Metastasis in Hepatocellular Carcinoma Through PEBP1.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a major threat to human health. The condition carries a high risk of death; 45% of new cases occur in China. Surgical resection is the first choice for treatment of HCC, but 30.9% of patients experience recurrence within 6 months after the operation. To improve patient survival, we must determine how to reduce the probability of recurrence and metastasis and elucidate the underlying mechanism of disease. We therefore studied the effect of somatostatin octapeptide (octreotide) on the invasion and metastasis of HCC. METHODS: The migration and invasion cytological tests were used to detect the effect of octreotide on liver cancer cells (SK-Hep-1 and HepG2). PEBP1 RNAi was used to knockdown expression. Invasion and metastasis were measured with transwell migration and wound-healing assays. Western blotting was used to detect changes in levels of PEBP1 and invasion pathway proteins after octreotide treatment. The effect of octreotide was studied in vivo by establishing a pulmonary metastasis model using SK-Hep-1 cells in nude mice. In-vivo bioluminescence imaging and hematoxylin and eosin staining of lung tissue were used to verify the results. RESULTS: Increasing concentrations of octreotide were progressively more effective in halting the invasion and metastasis of liver cancer cells. Octreotide may upregulate PEBP1, TIMP-2, and E-cadherin while downregulating MMP-2 and Twist to inhibit cell invasion and metastasis. And downregulation of PEBP1 would also change the expression of MMP-2, TIMP-2 and Twist. The in-vivo experiments showed no cancer cell metastasis in 4 of the 6 mice in the octreotide-treatment group, while all of the mice in the control group displayed pulmonary metastasis of human HCC cells. And the survival period of the mice in the octreotide-treatment group was significantly prolonged. CONCLUSIONS: Octreotide may weaken invasion and metastasis through the upregulation of PEBP1. Octreotide may reduce the risk of recurrence and metastasis after surgery for liver cancer.

Label-free detection of nasopharyngeal and liver cancer using surface-enhanced Raman spectroscopy and partial lease squares combined with support vector machine.

In this paper, we investigated the feasibility of using surface enhanced Raman spectroscopy (SERS) and multivariate analysis method to discriminate liver cancer and nasopharyngeal cancer from healthy volunteers. SERS measurements were performed on serum protein samples from 104 liver cancer patients, 100 nasopharyngeal cancer patients, and 95 healthy volunteers. Two dimensionality reduction methods, principal component analysis (PCA) and partial least square (PLS) were compared, and the results indicated that the performance of PLS is superior to that of PCA. When the number of components was compressed to 3 by PLS, support vector machine (SVM) with a Gaussian radial basis function (RBF) was employed to classify various cancers simultaneously. Based on the PLS-SVM algorithm, high diagnostic accuracies of 95.09% and 90.67% were achieved from the training set and the unknown testing set, respectively. The results of this exploratory work demonstrate that serum protein SERS technology combined with PLS-SVM diagnostic algorithm has great potential for the noninvasive screening of cancer.

[Clinical evaluation of laparoscopic hepatectomy for liver tumors in Couinaud â , â £a, â ¦, and â §].

OBJECTIVE: To summarize the clinical experience of laparoscopic hepatectomy (LH) for liver tumors in Couinaud Ⅰ, Ⅳa, Ⅶ, and Ⅷ segment. METHODS: Fifty-six patients with tumor in Couinaud Ⅰ, Ⅳa, Ⅶ, or Ⅷ segment underwent LH in Department of Hepatobiliary Surgery, the First Affiliated Hospital of Fujian Medical University from July 2009 to December 2014.The pathological diagnoses were hepatic hemangioma(5 patients), colorectal cancer metastasis to the liver(4 patients), hepatic adenoma (6 patients), hepatocellular carcinoma(32 patients), focal nodular hyperplasia(8 patients) and liver harmatoma(1 patient). The liver function of all patients was Child-Pugh class A. All patients were followed up by several kinds of methods which included outpatient or inpatient review, telephone and mail until January 2015. RESULTS: LH was converted to open hepatectomy in one patient, and tumor resection by LH was successful in other patients.The mean diameter of tumor was (5.7±3.4)cm (range 3-9 cm). The mean operative time was (115±46)min (range 55-260 min). And the mean estimated intraoperative blood loss was (181±135)ml (range 20-550 ml). The postoperative hospital stay was (7.1±1.5)days (range 5-10 days). Postoperative complications occurred in 4 patients(7.1 percent) and resolved with conservative management. There was no perioperative deaths. At the 1-month follow-up, 47 patients had returned to full-time work. A total of 9 patients had evidence of recurrence after operation. The one-year overall and disease-free survival rates of patients with malignant tumor were 100 percents and 87.5 percents, respectively. CONCLUSION: LH for tumors in segment Ⅰ, Ⅳa, Ⅶ, and Ⅷ is safe and effective.

Comparative mitochondrial proteomic analysis of hepatocellular carcinoma from patients.

PURPOSE: To define mitochondrial protein markers related to liver cancer. EXPERIMENTAL DESIGN: Mitochondrial subproteomes of 20 patient-derived liver carcinoma and tumor-free control tissues were performed by 2DE coupled with MALDI-TOF/TOF. The altered patterns of three identified proteins were validated by Western blot and immunohistochemistry. RESULTS: The results showed that compared with tumor-free control samples, nine proteins were downregulated and six proteins were upregulated in carcinoma samples. The increased expression of Arg1 mRNA and protein was validated by Western blot, Q-RT-PCR, paraffin tissue microarray and immunohistochemistry. Furthermore, a literature review shows that Heat shock protein 10 (Hsp10), single-stranded DNA-binding protein (SSBP1), and peptidyl-prolyl cis-trans isomerase A (PPIA), which were identified as being increased in the tumor samples in this study, may be closely related to protein folding and translation. CONCLUSIONS AND CLINICAL RELEVANCE: These results show that in addition to changes in the signaling pathways, such as the Ras-Raf-MEK-ERK pathway, altered mitochondrial DNA replication and protein folding in liver cancer are also worth studying further. Collectively, these results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in expression and carry implications for the investigation of their potential as therapeutic and prognostic markers. Further studies focusing on these proteins will be used to predict treatment response and reverse the apoptosis resistance.

Evaluation of the clinical features of HCC following hepatectomy for different stages of HCC.

BACKGROUND/AIMS: This study was to evaluate and compare the clinical and pathological characteristics and patient outcomes after hepatic resection for different stages of HCC according to the Barcelona Clinic Liver Cancer (BCLC) classification system. METHODOLOGY: Three hundred and sixteen primary hepatectomies for HCC were divided into stage 0-c, according to BCLC classification. The clinicopathological variables of the patients in each group were compared statistically. RESULTS: There were significant differences in the incidence of capsular invasion, α-fetoprotein, blood loss, blood transfusion and tumor related number among each of the stage 0-C, respectively (p<0.05). Disease-free survival was influenced by histopathological grade (p=0.000), tumor capsule (p=0.015), tumor related number (p=0.000) and BCLC (p=0.000). Overall survival was influenced by histopathological grade (p=0.000), tumor capsule (p=0.035), tumor related number (p=0.005), cirrhosis (p=0.000) and BCLC (p=0.000). CONCLUSIONS: HCC in stage 0 and A were closely correlated with a better prognosis, which reflected the relatively benign pathobiological features of HCC at an early developmental stage. In comparison, HCC in stages B and C exhibited a tendency towards a more aggressive phenotype. Our findings suggest that stage B classification is optimal for estimating the biological behavior and clinical prognosis of patients undergoing partial hepatectomy for early stage HCC.

[The effect of different hepatic vascular exclusion for massive hemorrhage in hepatectomy].

OBJECTIVE: To analyze the effect of different hepatic vascular exclusions for massive hemorrhage in hepatectomy. METHODS: The clinical data of 2238 cases with hepatectomy treated from January 1995 to August 2009 was analyzed retrospectively in the cause of massive hemorrhage (blood loss ≥ 1000 ml), blood loss during liver resection and massive hemorrhage incidence with different methods of hepatic vascular exclusion. RESULTS: Among 2238 cases received hepatectomy, 215 cases (9.6%) had massive hemorrhage because of portal vein tumor thrombus extraction (26.0%), extensive adhesions around the tumor (24.7%), section of liver hemorrhage (23.7%), hepatic vascular injury (15.8%), and tumor rupture (9.8%). Among 2182 cases received hepatectomy without portal vein tumor thrombus extraction, 159 cases (7.3%) had massive hemorrhage, 1257 cases (57.6%) which blood loss were less than 400 ml. Hepatectomy with different hepatic vascular exclusion methods had different blood loss and massive hemorrhage incidence. CONCLUSION: Pringle combined with clamping infrahepatic vena cava method and the liver double-hanging maneuver through the retrohepatic avascular tunnel on the right of the inferior vena cava method can reduce blood loss and massive hemorrhage incidence in hepatectomy more effectively, especially for huge liver tumor resection.