The liquid-to-solid transition of FUS is promoted by the condensate surface.

A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions in biological systems. Crucially, however, a further liquid-to-solid transition of the condensates can lead to irreversible pathological aggregation and cellular dysfunction associated with the onset and development of neurodegenerative diseases. Despite the importance of this liquid-to-solid transition of proteins, the mechanism by which it is initiated in normally functional condensates is unknown. Here we show, by measuring the changes in structure, dynamics, and mechanics in time and space, that single-component FUS condensates do not uniformly convert to a solid gel, but rather that liquid and gel phases coexist simultaneously within the same condensate, resulting in highly inhomogeneous structures. Furthermore, our results show that this transition originates at the interface between the condensate and the dilute continuous phase, and once initiated, the gelation process propagates toward the center of the condensate. To probe such spatially inhomogeneous rheology during condensate aging, we use a combination of established micropipette aspiration experiments together with two optical techniques, spatial dynamic mapping and reflective confocal dynamic speckle microscopy. These results reveal the importance of the spatiotemporal dimension of the liquid-to-solid transition and highlight the interface of biomolecular condensates as a critical element in driving pathological protein aggregation.

Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex.

The cytoskeleton of eukaryotic cells is primarily composed of networks of filamentous proteins, F-actin, microtubules, and intermediate filaments. Interactions among the cytoskeletal components are important in determining cell structure and in regulating cell functions. For example, F-actin and microtubules work together to control cell shape and polarity, while the subcellular organization and transport of vimentin intermediate filament (VIF) networks depend on their interactions with microtubules. However, it is generally thought that F-actin and VIFs form two coexisting but separate networks that are independent due to observed differences in their spatial distribution and functions. In this paper, we present a closer investigation of both the structural and functional interplay between the F-actin and VIF cytoskeletal networks. We characterize the structure of VIFs and F-actin networks within the cell cortex using structured illumination microscopy and cryo-electron tomography. We find that VIFs and F-actin form an interpenetrating network (IPN) with interactions at multiple length scales, and VIFs are integral components of F-actin stress fibers. From measurements of recovery of cell contractility after transient stretching, we find that the IPN structure results in enhanced contractile forces and contributes to cell resilience. Studies of reconstituted networks and dynamic measurements in cells suggest direct and specific associations between VIFs and F-actin. From these results, we conclude that VIFs and F-actin work synergistically, both in their structure and in their function. These results profoundly alter our understanding of the contributions of the components of the cytoskeleton, particularly the interactions between intermediate filaments and F-actin.

Combination of novel oncolytic herpesvirus with paclitaxel as an efficient strategy for breast cancer therapy.

BACKGROUND: New strategies are needed to improve the treatment of patients with breast cancer (BC). Oncolytic virotherapy is a promising new tool for cancer treatment but still has a limited overall durable antitumor response. A novel replicable recombinant oncolytic herpes simplex virus type 1 called VG161 has been developed and has demonstrated antitumor effects in several cancers. Here, we explored the efficacy and the antitumor immune response of VG161 cotreatment with paclitaxel (PTX) which as a novel oncolytic viral immunotherapy for BC. METHODS: The antitumor effect of VG161 and PTX was confirmed in a BC xenograft mouse model. The immunostimulatory pathways were tested by RNA-seq and the remodeling of tumor microenvironment was detected by Flow cytometry analysis or Immunohistochemistry. Pulmonary lesions were analyzed by the EMT6-Luc BC model. RESULTS: In this report, we demonstrate that VG161 can significantly represses BC growth and elicit a robust antitumor immune response in a mouse model. The effect is amplified when combined with PTX treatment. The antitumor effect is associated with the infiltration of lymphoid cells, including CD4+ T cells, CD8+ T cells, and NK cells (expressing TNF and IFN-γ), and myeloid cells, including macrophages, myeloid-derived suppressor cells, and dendritic cell cells. Additionally, VG161 cotreatment with PTX showed a significant reduction in BC lung metastasis, which may result from the enhanced CD4+ and CD8+ T cell-mediated responses. CONCLUSIONS: The combination of PTX and VG161 is effective for repressing BC growth by inducing proinflammatory changes in the tumor microenvironment and reducing BC pulmonary metastasis. These data will provide a new strategy and valuable insight for oncolytic virus therapy applications in primary solid or metastatic BC tumors.

VG161 activates systemic antitumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes.

The VG161 represents the first recombinant oncolytic herpes simplex virus type 1 carrying multiple synergistic antitumor immuno-modulating factors. Here, we report its antitumor mechanisms and thus provide firm theoretical foundation for the upcoming clinical application in pancreatic cancer. Generally, the VG161-mediated antitumor outcomes were analyzed by a collaboration of techniques, namely the single-cell sequencing, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADSI-MSI) and nanostring techniques. In vitro, the efficacy of VG161 together with immune checkpoint inhibitors (ICIs) has been successfully shown to grant a long-term antitumor effect by altering tumor immunity and remodeling tumor microenvironment (TME) metabolisms. Cellular functional pathways and cell subtypes detected from patient samples before and after the treatment had undergone distinctive changes including upregulated CD8+ T and natural killer cells. More importantly, significant antitumor signals have emerged since the administration of VG161 injection. In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong antitumor potential. The more robusting antitumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials.

Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny.

OBJECTIVE: Hepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified. DESIGN: A highly multiplexed imaging mass cytometry (IMC) panel was designed to simultaneously quantify 36 biomarkers of tissues from 134 patients with HCC and 7 healthy donors to generate 562 highly multiplexed histology images at single-cell resolution. Different function units were defined by topological analysis of TME. CN relevant to the patients' prognosis was identified as specific target for HCC therapy. Transgenic mouse models were used to validate the novel immunotherapy target for HCC. RESULTS: Three major types of intratumour areas with distinct distribution patterns of tumorous, stromal and immune cells were identified. 22 cellular metaclusters and 16 CN were defined. CN composed of various types of cells formed regional function units and the regional immunity was regulated reversely by resident Kupffer cells and infiltrating macrophages with protumour and antitumour function, respectively. Depletion of Kupffer cells in mouse liver largely enhances the T cell response, reduces liver tumour growth and sensitises the tumour response to antiprogrammed cell death protein-1 treatment. CONCLUSION: Our findings reveal for the first time the various topological function units of HCC TME, which also presents the largest depository of pathological landscape for HCC. This work highlights the potential of Kupffer cell-specific targeting rather than overall myeloid cell blocking as a novel immunotherapy for HCC treatment.

Critical evaluation of web-based prediction tools for human protein subcellular localization.

Human protein subcellular localization has an important research value in biological processes, also in elucidating protein functions and identifying drug targets. Over the past decade, a number of protein subcellular localization prediction tools have been designed and made freely available online. The purpose of this paper is to summarize the progress of research on the subcellular localization of human proteins in recent years, including commonly used data sets proposed by the predecessors and the performance of all selected prediction tools against the same benchmark data set. We carry out a systematic evaluation of several publicly available subcellular localization prediction methods on various benchmark data sets. Among them, we find that mLASSO-Hum and pLoc-mHum provide a statistically significant improvement in performance, as measured by the value of accuracy, relative to the other methods. Meanwhile, we build a new data set using the latest version of Uniprot database and construct a new GO-based prediction method HumLoc-LBCI in this paper. Then, we test all selected prediction tools on the new data set. Finally, we discuss the possible development directions of human protein subcellular localization. Availability: The codes and data are available from http://www.lbci.cn/syn/.

Line optical tweezers as controllable micromachines: techniques and emerging trends.

In the past three decades, the technology of optical tweezers has made significant contributions in various scientific areas, including optics, photonics, and nanosciences. Breakthroughs include manipulating particles in both static and dynamic ways, particle sorting, and constructing controllable micromachines. Advances in shaping and controlling the laser beam profile enable control over the position and location of the trap, which has many possible applications. A line optical tweezer (LOT) can be created by rapidly moving a spot optical tweezer using a tool such as a galvanometer mirror or an acousto-optic modulator. By manipulating the intensity profile along the beam line to be asymmetric or non-uniform, the technique can be adapted to various specific applications. Among the many exciting applications of line optical tweezers, in this work, we discuss in detail applications of LOT, including probing colloidal interactions, transporting and sorting of colloidal microspheres, self-propelled motions, trapping anisotropic particles, exploring colloidal interactions at fluid-fluid interfaces, and building optical thermal ratchets. We further discuss prospective applications in each of these areas of soft matter, including polymeric and biological soft materials.

Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods.

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.

Effects of Vimentin Intermediate Filaments on the Structure and Dynamics of In Vitro Multicomponent Interpenetrating Cytoskeletal Networks.

We investigate the rheological properties of interpenetrating networks reconstituted from the main cytoskeletal components: filamentous actin, microtubules, and vimentin intermediate filaments. The elastic modulus is determined largely by actin, with little contribution from either microtubules or vimentin. However, vimentin dramatically impacts the relaxation, with even small amounts significantly increasing the relaxation time of the interpenetrating network. This highly unusual decoupling between dissipation and elasticity may reflect weak attractive interactions between vimentin and actin networks.

A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: a multicenter retrospective study.

BACKGROUND: Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking. METHODS: We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell's C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers. RESULTS: Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30-50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management. CONCLUSIONS: The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram.

Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis.

BACKGROUND: Debate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria. METHODS: Patients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed. RESULTS: 100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116-9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281-6.589; P=0.011) were independently associated with favorable RFS after HCC resection. CONCLUSION: Preoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.

Effect of Divalent Cations on the Structure and Mechanics of Vimentin Intermediate Filaments.

Divalent cations behave as effective cross-linkers of intermediate filaments (IFs) such as vimentin IF (VIF). These interactions have been mostly attributed to their multivalency. However, ion-protein interactions often depend on the ion species, and these effects have not been widely studied in IFs. Here, we investigate the effects of two biologically important divalent cations, Zn2+ and Ca2+, on VIF network structure and mechanics in vitro. We find that the network structure is unperturbed at micromolar Zn2+ concentrations, but strong bundle formation is observed at a concentration of 100 µM. Microrheological measurements show that network stiffness increases with cation concentration. However, bundling of filaments softens the network. This trend also holds for VIF networks formed in the presence of Ca2+, but remarkably, a concentration of Ca2+ that is two orders higher is needed to achieve the same effect as with Zn2+, which suggests the importance of salt-protein interactions as described by the Hofmeister effect. Furthermore, we find evidence of competitive binding between the two divalent ion species. Hence, specific interactions between VIFs and divalent cations are likely to be an important mechanism by which cells can control their cytoplasmic mechanics.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

BACKGROUND: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required. PURPOSE: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice. STUDY TYPE: Retrospective. POPULATION: We enrolled 303 patients from two medical centers. Patients with a disease-free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126). FIELD STRENGTH/SEQUENCE: 3.0T axial T1 -weighted (T1 -w), T2 -weighted (T2 -w), contrast-enhanced T1 -weighted (CET1 -w). ASSESSMENT: ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19-9, and radiomic-related features of ER were assessed. In addition, to determine the intra- and interobserver reproducibility of radiomic features extraction, the intra- and interclass correlation coefficients (ICC) were calculated. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit. RESULTS: The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19-9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19-9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort). DATA CONCLUSION: The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;52:231-245.

Oncolytic virus combined with traditional treatment versus traditional treatment alone in patients with cancer: a meta-analysis.

BACKGROUND: Oncolytic virus therapy has shown benefits for multiple cancers, while limitations remain for traditional treatment. However, few studies have concentrated on comparing whether oncolytic virus combined with traditional treatment is better than traditional treatment alone in patients with cancer. We conducted a meta-analysis of the curative effect and safety of oncolytic virus combination therapy. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases comprehensively for articles comparing oncolytic virus combined with traditional treatment to traditional treatment alone in patients with cancer. A meta-analysis and trial sequential analysis were performed. RESULTS: A total of 12 studies involving 1494 patients (combination therapy group, 820 patients; traditional treatment group, 674 patients) were included in the study. Compared with traditional treatment alone, combination therapy was significantly associated with high objective response rate [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82, p = 0.04]. There were no significant differences for other outcomes such as 1- and 2-year survival rate, and 4- and 12-month progression-free survival rate. Combination therapy was significantly associated with high incidence of grade ≥ 3 adverse effects (OR 1.47, 95% CI 1.06-2.05, p = 0.02) and high incidence of grade ≥ 3 neutropenia (OR 1.65, 95% CI 1.13-2.43, p = 0.01). There were no significant differences for other grade ≥ 3 adverse effects, e.g., gastrointestinal adverse effects, influenza-like illness, fatigue, anemia, and thrombocytopenia. CONCLUSION: Despite partially increased toxicity, the combination therapy improves the effectiveness of cancer treatment. However, high-quality, large-scale studies are needed to evaluate its effectiveness and safety.

A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65-0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66-0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85-1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03-1.39); P = 0.002]. CONCLUSION: This meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population.

LESSONS LEARNED: Modification of FOLFIRINOX significantly improves safety and tolerability in Chinese patients with locally advanced pancreatic cancer.Patients with locally advanced pancreatic cancer benefit from neoadjuvant therapy and experience a much better survival than patients with upfront surgery. BACKGROUND: The objective of this study was to evaluate the efficacy of modified-FOLFIRINOX (mFOLFIRINOX) regimens in Chinese patients with locally advanced pancreatic cancer (LAPC) and to compare outcomes between patients with LAPC treated with mFOLFIRINOX-based neoadjuvant therapy (LAPC-N) and patients with LAPC who underwent upfront surgery (LAPC-S). METHODS: Forty-one patients with LAPC-N were enrolled prospectively. Imaging features, chemotherapy response, adverse events, perioperative complications, histology, and survival were analyzed. Seventy-four patients with resectable pancreatic cancer (RPC) (from April 2012 to November 2017) and 19 patients with LAPC-S (from April 2012 to March 2014) were set as observational cohorts, and data were collected retrospectively. LAPC-N patients with adequate response underwent surgical treatment, whereas continuous chemotherapy was given to LAPC-N patients who were not deemed resectable after treatment, and the response was re-evaluated every 2 months. RESULTS: Forty-one patients with LAPC received mFOLFIRINOX with a response rate of 37.1%. The most common severe adverse events were neutropenia and anemia. mFOLFIRINOX-based neoadjuvant therapy contributed to a remarkable decrease in CA19-9 level and tumor diameter. Fourteen LAPC-N patients underwent surgery (LAPC-N-S) after downstaging. Compared with LAPC-N-S cases, LAPC-S patients had longer operative time, more blood loss, and a higher risk of grade 5 complications. The median overall survival (OS) and progression-free survival (PFS) of LAPC-N-S patients were 27.7 months and 19.3 months, respectively, which were similar to those of patients with RPC (30.0 months and 23.0 months) and much longer than those of patients with LAPC-S (8.9 months and 7.6 months), respectively. CONCLUSION: Neoadjuvant chemotherapy such as the mFOLFIRINOX regimen can be recommended for Chinese patients with LAPC after dose modification. Patients with LAPC-N who underwent surgery obtained significantly improved survival compared with patients in the observational LAPC-S cohort, who did not undergo neoadjuvant therapy.

Identification of protein subcellular localization via integrating evolutionary and physicochemical information into Chou's general PseAAC.

Identifying the location of proteins in a cell plays an important role in understanding their functions, such as drug design, therapeutic target discovery and biological research. However, the traditional subcellular localization experiments are time-consuming, laborious and small scale. With the development of next-generation sequencing technology, the number of proteins has grown exponentially, which lays the foundation of the computational method for identifying protein subcellular localization. Although many methods for predicting subcellular localization of proteins have been proposed, most of them are limited to single-location. In this paper, we propose a multi-kernel SVM to predict subcellular localization of both multi-location and single-location proteins. First, we make use of the evolutionary information extracted from position specific scoring matrix (PSSM) and physicochemical properties of proteins, by Chou's general PseAAC and other efficient functions. Then, we propose a multi-kernel support vector machine (SVM) model to identify multi-label protein subcellular localization. As a result, our method has a good performance on predicting subcellular localization of proteins. It achieves an average precision of 0.7065 and 0.6889 on two human datasets, respectively. All results are higher than those achieved by other existing methods. Therefore, we provide an efficient system via a novel perspective to study the protein subcellular localization.

Pyogenic Liver Abscess After Pancreaticoduodenectomy: A Single-Center Experience.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex procedure with a morbidity rate of 40%-50%. We evaluated the incidence, associated factors, etiologic characteristics, and outcome of pyogenic liver abscess (PLA), a rare infectious complication of PD. METHODS: We retrospectively assessed the data of patients who underwent PD (n = 326) between January 2012 and February 2017 at a single institution. Patients who developed PLA after PD were matched (1:3) for age, sex, and pathologic diagnosis with patients without PLA after PD. Patients who developed PLA without abdominal operation history (n = 77) were also reviewed in the same period. RESULTS: Eleven patients (3.4%) developed PLA after PD; diabetes (5/11, 45.5% versus 4/33, 12.1%; P = 0.031) increased the risk of PLA after PD. The preoperative and postoperative fasting blood glucose (FBG) was significantly higher in PLA+ group than PLA- group: preoperative FBG (median: 7.39 versus 4.49; P < 0.01), postoperative FBG (median: 8.98 versus 5.68; P < 0.01). The occurrence of multiple liver abscess was significantly higher in patients with PLA after PD than patients who developed PLA without abdominal operation history (7/11 versus 22/77; P = 0.036). Microbial pus culture was positive in eight patients with PLA after PD (n = 8/11) and in forty-one patients who developed PLA without abdominal operation history (n = 41/77). Klebsiella pneumoniae was the most commonly isolated microorganism in PLA patients with or without a history of PD (5/8, 62.5% versus 34/41, 82.9%; P = 0.333). CONCLUSIONS: Patients with diabetes (including impaired fasting plasma glucose) have a higher risk of developing PLA after PD. Multiple liver abscess was the most common type of PLA after PD; K pneumoniae should be covered when empirically treated patients with PLA.

Patients with pancreatic cystic neoplasms can benefit from management of multidisciplinary team: Experience from a Chinese academic center.

BACKGROUND: Pancreatic cystic neoplasms (PCNs) are a spectrum of neoplasms that can be benign or malignant. The accuracy of diagnosis is critical for this disease since different types of PCNs are treated differently using various modalities. The use of a multidisciplinary team (MDT) has been shown to improve the management and outcomes of various diseases. We aimed to determine the performance of MDT in the management of PCNs. METHODS: We retrospectively reviewed 167 pathologically-proven PCN patients and divided them among three groups according to their surgical data and treatment modalities: 1) historical control group (HC group); 2) concurrent control group (CC group); and 3) MDT group. The composition of subtypes of PCNs, preoperative diagnostic accuracy, postoperative complications, and postoperative hospital stay were compared among the three groups. RESULTS: The incidence of SCN reduced in the MDT group, while the incidence of IPMN was much higher (P < 0.05). MDT management significantly improved the accuracy of preoperative diagnosis (71.7%) and also increased the individual diagnostic accuracies of ultrasound, CT, and MRI/MRCP. Postoperative pancreatic fistula was significantly reduced in the MDT group (28.3%; P < 0.001). Furthermore, the mean hospital stay after surgery in the MDT group (10.37 days) was shorter than those of the other two groups (27.35 days in HC group, and 19.28 days in CC group; P < 0.05). CONCLUSION: For patients with PCN, MDT management was associated with an improvement in the overall accuracy of preoperative diagnosis, a lower incidence postoperative morbidity, and decreased length of hospital stay.

A preoperative nomogram predicts prognosis of up front resectable patients with pancreatic head cancer and suspected venous invasion.

BACKGROUND: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion. METHODS: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution. RESULTS: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort. CONCLUSIONS: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery.