Poor Postoperative Survival Research Articles

Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma - A case-control study based on liver panoramic digital pathology.

The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research. This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10 × 10cm was used to panoramically assess the intrahepatic infiltration extent of PHCC. The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15,000 µm, 62.9% of PHCCs had DIHI greater than 1cm away from the main tumor in liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI (P＜0.0001, P=0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100, 100%, and 69% respectively. The presence of DIHI in most PHCCs was a significant predictor of poor postoperative recurrence and survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.

Extracellular vesicle-packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models.

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)-dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer.

A comparative study of surgical outcomes for secondary spontaneous pneumothorax and the postoperative survival prognostic factor: interstitial vs. non-interstitial pneumonia.

To investigate the surgical outcomes and postoperative survival prognostic factors of intractable secondary spontaneous pneumothorax. A total of 95 patients who underwent thoracoscopic surgery for intractable secondary spontaneous pneumothorax between April 2010 and March 2020 were included in this study. These patients were classified into interstitial pneumonia and non-interstitial pneumonia groups, and a comparative study was performed on surgical outcomes and postoperative survival prognostic factors. There was no difference in the 1-year overall survival rate between the two groups. However, the 3-year overall survival rate was significantly lower in the interstitial pneumonia group than in the non-interstitial pneumonia group. The differences in short-term surgical outcomes (persistent air leakage, postoperative complications, etc.) were not significant between the two groups. Univariate analysis revealed that the drainage period, the development of postoperative complications, and recurrence were significant independent postoperative survival prognostic factors for all cases. Postoperative complications were the only associated postoperative survival prognostic factor for interstitial pneumonia pneumothorax in the multivariate analysis. The development of postoperative complications can cause poor postoperative survival prognosis of intractable secondary spontaneous pneumothorax due to interstitial pneumonia.

Neutrophil Extracellular Trap is Surrogate Biomarker for Prognosis and Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms. We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3. NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial-mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response. NET was an independent prognostic factor in LARC that were associated with patients' survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.

Construction and validation of a novel prognostic model for intrahepatic cholangiocarcinoma based on a combined scoring system of systemic immune-inflammation index and albumin-bilirubin: a multicenter study.

The degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection. A retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves. Univariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model's predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance. The SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.

675 Are Postoperative Outcomes in Flap Operations Affected by Obesity?

Abstract Aim To explore the outcomes of flap surgeries and how obesity affects them. To find if there is a correlation between CBC indices (also inflammatory markers) with flap survival. Method All flap surgeries on adults in the collaborating departments in an Indian tertiary care hospital from 2021-2022 excluding finger flaps were prospectively analyzed. Data of 90 patients including postoperative complications, preoperative Neutrophil-Lymphocyte Ratio (NLR) were recorded.BMI is calculated to classify patients based on Asia-Pacific guidelines where BMI&amp;gt;25 is obese, 23-24.9 is overweight, &amp;lt;18 is underweight.Chi square tests were used to assess association between obesity, NLR and early (within 7 days of surgery) &amp;late (beyond 7 days) postoperative complications -flap loss, wound dehiscence, surgical site infection. Multiple regression model and ANOVA test were also done with these variables. Results There is significant association between patients’ obese or overweight habitus and postoperative surgical site complications. 38% early (p = 0.001) and 36% late (p = 0.044) complications happened in obese patients alone. There is significant association between NLR and early postoperative complications (p = 0.002).60% with high NLR values had severe early postoperative complications, compared to 16.7% of patients with normal NLR and 21.1% with mildly raised NLR. Obesity and high NLR [NLR 10-18 or moderate stress, NLR&amp;gt;18 or severe stress] independently have significant correlation (0.038 for obesity, 0.015 for NLR) with early postoperative complications. Conclusions Obesity combined with high preoperative NLR is a quick, inexpensive predictor of poor early postoperative flap survival.

Total gastrectomy as a risk factor for postoperative loss of skeletal muscle in minimally invasive surgery for patients with gastric cancer.

Loss of skeletal muscle mass after gastrectomy for gastric cancer leads to decreased quality of life and poor postoperative survival. However, few studies have examined the postoperative loss of skeletal muscle mass following minimally invasive gastrectomy. This study investigated the impact of minimally invasive total gastrectomy (MI-TG) on changes in skeletal muscle mass during the early postoperative period. Patients who underwent MI-TG or minimally invasive distal or proximal gastrectomy (MI-nonTG) for cStage I-III gastric cancer were retrospectively analyzed (n = 58 vs. 182). Their body composition was measured before surgery and 2 months after surgery. Multivariable linear regression analysis was performed to clarify the impact of the surgical procedure on skeletal muscle index changes using clinically relevant covariates. Skeletal muscle mass decreased more in the MI-TG group than in the MI-nonTG group (median [interquartile range]; -5.9% [-10.6, -3.7] vs -4.5% [-7.3, -1.9], P = 0.004). In multivariable linear regression analysis using clinically relevant covariates, MI-TG was an independent risk factor for postoperative loss of skeletal muscle mass (coefficient - 2.6%, 95% CI -4.5 to -0.68, P = 0.008). Total gastrectomy was a risk factor for loss of skeletal muscle mass during the early postoperative period. If oncologically feasible, proximal or distal gastrectomy with a small remnant stomach should be considered.

Tumor-suppressive role of microfibrillar associated protein 4 and its clinical significance as prognostic factor and diagnostic biomarker in hepatocellular carcinoma.

Revealing microfibrillar-associated protein 4 (MFAP4)'s function and its clinical significance in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate MFAP4 mRNA and protein expression in paired HCC and paracarcinoma tissues, respectively. MFAP4 serum concentration was detected using enzyme-linked immunosorbent assays in healthy people (n = 30), cirrhosis (n = 15) and HCC patients (n = 80). MFAP4 protein expression was detected in two tissue microarrays (n = 60 and n = 90). Plasmids were transfected into human HCC cell line Bel-7402, and MFAP4 function was determined in vitro in cell experiments. Furthermore, tumorigenicity studies in nude mice served to assess the function of MFAP4 for HCC. Both MFAP4 mRNA and protein expression were significantly downregulated in HCC tissue compared with paracarcinoma tissue (P < 0.05). Decreased MFAP4 expression in paracarcinoma tissue was associated with poor postoperative survival in HCC patients (P = 0.027). MFAP4 was also downregulated in HCC sera compared with healthy people (P < 0.05). In vitro, MFAP4 upregulation in Bel-7402 cells induced S phase arrest, promoted apoptosis, and inhibited migration and invasion. Western blotting indicated MFAP4 overexpression increased CDK4, CDK6, pRB, P27, and BCL-XS expression. Tumorigenicity study showed that the upregulation of MFAP4 inhibited the proliferation of Bel-7402 cells in nude mice. MFAP4 expression was significantly lower both in sera and tissue of HCC patients. MFAP4 can serve as molecular marker for HCC diagnosis and prognosis. Additionally, MFAP4 acted as an important HCC tumor suppressor by inducing S phase arrest, and promoting apoptosis, cell migration, and invasion.

Prognostic analysis of m6A-related lncRNAs as potential biomarkers in intrahepatic cholangiocarcinom.

Intrahepatic cholangiocarcinoma (iCCA) patients had no obvious symptoms at early stage and poor postoperative survival. Therefore, the establishment of an iCCA prognostic prediction model to carry out refined management of iCCA patients is expected to improve the survival of the iCCA patient population. In this paper, we analyzed the expression profiling data of patients from 32 iCCA tissues and eight paracancerous tissues in The Cancer Genome Atlas (TCGA) database. Perl software was used to separate M6A-related genes and lncRNAs from expression matrix files obtained from the TCGA database. The differentially expressed lncRNAs in the iCCA samples and the normal samples were screened out by differential analysis using the R package limma, and the m6A-related lncRNAs were further screened by Pearson correlation analysis. WGCNA clustering analysis constructs a random network to extract the module genes most related to iCCA, and take the intersection of differentially expressed lncRNAs related to m6A. Univariate Cox screening was performed for the intersection lncRNAs that had significant influence on the prognosis of iCCA patients, and further screening was performed by LASSO method and multivariate Cox regression analysis. Risk model was constructed and prognostic ability was evaluated according to risk score. In conclusion, we identified four m6A-related lncRNAs with potential prognostic value in iCCA, and established a novel m6A-related lncRNA-based prognostic model, which can be used as an independent prognostic factor to predict the prognosis of clinical patients.

Clinicopathologic and genomic features of high-grade pattern and their subclasses in lung adenocarcinoma

IntroductionRecent lung adenocarcinoma (LUAD) grading system proposed by the International Association for the Study of Lung Cancer (IASLC) has emphasized the proportion of high-grade patterns (HGPs). We aimed to evaluate the clinicopathologic and genomic characteristics associated with HGP which has not yet been fully investigated. MethodsTissue samples from 174 patients who underwent surgical resection of LUAD from January to December 2015 were histologically evaluated. Proportions of HGPs, including solid, micropapillary, cribriform, and complex glandular patterns, were individually quantified. Prognostic implications of HGP proportion, both as a continuous variable and as subclasses divided by cutoffs of 20%, 50%, and 90% (low-intermediate grade [LIG], HGP <20%; high grade 1 [HG1], 20-<50%, HG2, 50-<90%; HG3, ≥90%) were evaluated. Different clinicopathologic factors and genomic alterations according to the HGP subclasses were assessed. ResultsRelative hazards of the HGP gradually elevated as its proportion increased over 20%, the cut-off value established by the IASLC grading system, and the cancer-specific overall survival (OS) of HG1 subclass was not significantly decreased compared to the LIG subclass on univariate analysis. However, further subgrouping showed significantly increased frequencies of male, advanced stage tumors, lymphovascular invasion, and spread through alveolar space in higher HGP subclasses. Also, common LUAD driver mutations, particularly EGFR mutations, were less frequent, whereas alterations in TP53 and cell cycle pathway-related genes were more frequent. Higher HGP subclasses and TP53 gene alteration were associated with shorter cancer-specific OS and RFS in multivariate survival analysis. ConclusionsHGP subclasses of LUAD displayed distinct clinicopathological characteristics and genomic alterations, including TP53 and cell cycle pathway, emphasizing the clinical value of these subclasses in LUAD. Higher HGP subclass and alteration in TP53 may be markers of poor post-operative survival.

Prognostic significance of preoperative hyaluronic acid level in patients with hepatocellular carcinoma.

Serum hyaluronic acid (HA) levels are increased in patients with solid tumors, and may predict outcomes. However, as HA levels also correlate with the degree of liver fibrosis, the prognostic significance of serum HA levels in patients with hepatocellular carcinoma (HCC) is unclear. A total of 656 consecutive patients who underwent hepatic resection for HCC were divided into two groups by serum HA level (high HA [≥200ng/mL], n=248; low HA [<200ng/mL], n=408). Clinicopathological characteristics and postoperative survival were compared between groups. Moreover, 1:1 propensity score matching analysis was applied to adjust characteristics between groups. Both the 5-year overall and relapse-free survival rates (OSR and RFSR) in the low HA group were significantly better than those in the high HA group (59.8% vs. 38.6%, respectively, p<0.001 and 24.5% vs. 13.1%, respectively, p<0.001). After propensity score matching, two comparable groups of 124 patients each were obtained. However, both the 5-year OSR and RFSR in the low HA group remained significantly better than those in the high HA group (57.4% vs. 38.3%, respectively, p=0.006 and 22.5% vs. 14.7%, respectively, p=0.003). High preoperative HA level predicts poor postoperative survival of patients with HCC. undergoing hepatic resection.

Long non-coding RNA linc00921 suppresses tumorigenesis and epithelial-to-mesenchymal transition of triple-negative breast cancer via targeting miR-9-5p/LZTS2 axis

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Dysregulation of long non-coding RNAs (lncRNAs) plays crucial roles in the initiation and progression of TNBC. In this study, we analyzed public GEO profiles to verify the key lncRNAs in TNBC. Linc00921 was selected for further study. Low expression of linc00921 was observed in 49 of 95 TNBC tissues. Low expression of linc00921 was correlated with poor postoperative disease-free survival (DFS) and overall survival (OS) of TNBC patients. Overexpression of linc00921 with lentivirus suppressed the proliferation, migration and invasion of TNBC cells. A luciferase reporter assay showed that linc00921 could sponge miR-9-5p in TNBC. Moreover, linc00921 and miR-9-5p occupied the same Argonaute-2 (Ago2) protein in TNBC cells. Leucine zipper tumor suppressor 2 (LZTS2) was recognized as a target gene of miR-9-5p, and thereby a linc00921/miR-9-5p/LZTS2 axis was identified in TNBC cells. Overexpression of linc00921 promoted nuclear export of β-catenin, neutralized its function, and subsequently promoted epithelial-to-mesenchymal transition (EMT) in TNBC. A xenograft tumor mouse model showed that the miR-9-5p inhibitor upregulates LZTS2 expression and induce nuclear export of β-catenin in TNBC. Thus, linc00921 upregulates LZTS2 by sponging miR-9-5p to suppress tumorigenesis and EMT of TNBC. Linc00921/miR-9-5p/LZTS2 axis may be a novel biomarker and therapeutic target for TNBC patients.

Combination of C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio as a Novel Prognostic Index in Patients With Bladder Cancer After Radical Cystectomy.

BackgroundInflammation is widely considered an important hallmark of cancer and associated with poor postoperative survival. The objective of this study is to assess the significance of preoperative C-NLR, a new inflammation-based index that includes preoperative C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), on therapeutic outcomes for bladder cancer (BC) patients after radical cystectomy (RC).Materials and MethodsBC patients who underwent RC between 2010 and 2019 were retrospectively analyzed from our medical center. The predictive effect of CRP, NLR, and C-NLR on the survival of BC patients were analyzed by the receiver operating characteristic (ROC) curves. The relationship between C-NLR and postoperative survival was investigated by Cox regression. The corresponding nomograms were built based on the Cox regression results of overall survival (OS) and disease-free survival (DFS), which were further validated by ROC curves, decision curve analysis (DCA) curves, and calibration curves.ResultsOf the 199 eligible patients, 83 (41.70%) were classified as high C-NLR group and the remaining 116 (58.30%) were classified as low C-NLR group. ROC analysis showed that C-NLR had the largest area under curve (AUC) compared to CRP and NLR. Multivariate analysis revealed that T-stage and C-NLR [high C-NLR vs. low C-NLR, hazard ratio (HR) = 2.478, 95% confidence interval (CI), 1.538–3.993, p < 0.001] were independent predictors of OS, whereas T-stage, M-stage, and C-NLR (high C-NLR vs. low C-NLR, HR = 2.817, 95% CI, 1.667–4.762, p < 0.001) were independent predictors of DFS. ROC and DCA analysis demonstrated better accuracy and discrimination of 3- and 5-year OS and DFS with C-NLR-based nomogram compared to TNM stage. The calibration curve reconfirmed the accurate predicting performance of nomograms.ConclusionC-NLR is a reliable predictor of long-term prognosis of BC patients after RC and will contribute to the optimization of individual therapy for BC patients.

Combination of Total Psoas Index and Albumin-Globulin Score for the Prognosis Prediction of Bladder Cancer Patients After Radical Cystectomy: A Population-Based Study.

BackgroundSarcopenia as the loss of skeletal muscle mass is related with poor postoperative survival. This work purposed to evaluate the prognostic prediction of the total psoas index (TPI), albumin–globulin score (AGS), and the combination of TPI and AGS (CTA) in bladder cancer (BCa) patients after radical cystectomy.MethodsBCa patients that received radical cystectomy between 2012 and 2020 were retrieved from our medical center. The calculation of TPI was based on the plain computed tomography images. The predictive effects of TPI, AGS, and CTA grade on survival of BCa patients were analyzed and compared with the albumin–globulin ratio (AGR) through the receiver operating characteristic (ROC) curves. A nomogram was further established based on the Cox regression results from CTA grade and clinicopathological characteristics, which are verified by the decision curve analysis (DCA).ResultsA total of 112 eligible patients diagnosed as BCa were included in this study for retrospective analysis. The patients with lower TPI or higher AGS grade (1/2) contained poorer overall survival (OS) and disease-free survival (DFS). Divided by CTA grade, there were 35 (31.25%) patients in grade 1 associated with the best postoperative prognosis, which was accompanied with increased TPI and decreased AGS. The CTA grade could better predict postoperative outcomes compared with TPI, AGR, and AGS for the highest area under the curve (AUC; 0.674 of OS and 0.681 of DFS). The 3- and 5-year OS and DFS nomograms were conducted based on CTA grade and clinical variables, with a higher predictive performance than the TNM stage.ConclusionThis study revealed that the novel index CTA functioned as an effective prognostic predictor for postoperative OS and DFS of BCa patients after radical cystectomy. Preoperative assessment of CTA would contribute to optimizing clinical therapies.

The expression of the alpha1 subunit of Na+/K+-ATPase is related to tumor development and clinical outcomes in gastric cancer.

The Na+/K+-ATPase alpha1 subunit (ATP1A1) is a critical component of Na+/K+-ATPase (NKA), a membrane pump that maintains a low intracellular Na+/K+ ratio and retains cellular volume and osmolarity. ATP1A1 was recently implicated in tumor behavior. Therefore, the present study investigated the role of ATP1A1 in patients with gastric cancer (GC). Knockdown experiments were conducted on human GC cell lines using ATP1A1 siRNA, and its effects on proliferation, the cell cycle, apoptosis, and cellular movement were examined. Gene expression profiling was performed by a microarray analysis. Primary tumor samples from 192 GC patients who underwent gastrectomy were subjected to an immunohistochemical analysis. High ATP1A1 expression levels were observed in NUGC4 and MKN74 cells. Cell proliferation was suppressed and apoptosis was induced by the siRNA-induced knockdown of ATP1A1. The microarray analysis showed that knockdown of ATP1A1 leads to the up-regulated expression of genes involved in the interferon (IFN) signaling pathway, such as STAT1, STAT2, IRF1, and IRF9. Furthermore, the depletion of ATP1A1 altered the phosphorylation of the MAPK pathway. The immunohistochemical analysis revealed that the expression of ATP1A1 was associated with the histological type, venous invasion, and the pathological T stage. Furthermore, the prognostic analysis showed a relationship between high ATP1A1 expression levels and poor postoperative survival. ATP1A1 appears to regulate tumor progression by altering IFN signaling, and high ATP1A1 expression levels were associated with poor postoperative survival in GC patients. The present results provide novel insights into the function of ATP1A1 as a mediator and/or biomarker of GC.

Weight Loss as an Untapped Early Detection Marker in Pancreatic and Periampullary Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival of common cancers, partly because there are no reliable early detection tests. Unintentional weight loss (≥ 5% decrease from baseline) has been linked to PDAC, but the frequency and severity of weight loss using objective measures, and its relationship to prognosis, have not been well characterized. We identified 390 patients with PDAC (all stages) and two or more prediagnosis weights in the electronic medical record. Percentage weight loss in the 365 and 180days preceding diagnosis was calculated. Results were compared with raw weights of age- and sex-matched non-cancer controls (n=780). Odds ratios for PDAC were calculated using conditional logistic regression. Cox proportional hazards models were used for survival. Within 1year of diagnosis, more PDAC patients lost ≥ 5% weight relative to controls (74.9% vs. 11.2%; p<0.001), with a median weight loss of 14.2 versus 2.9lbs. The odds ratio for PDAC comparing weight loss within 1year of 5 to < 10% was 10.30 (p<0.001) and 77.82 for ≥ 10% (p<0.001), compared with stable weight. Weight loss prior to diagnosis was also associated with early-stage PDAC. PDAC cases with ≥ 10% prediagnosis weight loss had worse survival compared with stable weights (hazard ratio [HR] 1.60; p=0.01). Greater prediagnosis weight loss was associated with poor survival after pancreatectomy (5 to < 10% vs. < 5%, HR 2.40, p=0.03; ≥ 10% vs. < 5%, HR 2.59, p=0.03). Diagnosis of PDAC is preceded by unintentional weight loss in the majority of patients, even at an early stage. Greater prediagnosis weight loss severity is also associated with poor postoperative survival.

EB2 promotes hepatocellular carcinoma proliferation and metastasis via MAPK/ERK pathway by modulating microtubule dynamics.

Metastasis is the main cause of poor postoperative survival of hepatocellular carcinoma (HCC) patients. Cytoskeleton rearrangement is a key event in cancer metastasis. However, the significance of microtubule (MT), one of the core components of cytoskeleton, in this process is only beginning to be revealed. Here, we find that the MT dynamics regulator end-binding protein 2 (EB2) is highly expressed in HCC and predicts poor prognosis of HCC patients. Functional studies show that EB2 overexpression promotes HCC proliferation, invasion and metastasis in vitro and in vivo, while EB2 knockdown has opposite results. Mechanistically, EB2 mediates MTs destabilization, increases Src (Src proto-oncogene non-receptor tyrosine kinase) activity, and thus facilitates extracellular signal-regulated kinase (ERK) signaling activation, which could in turn promote EB2 expression in HCC, eventually resulting in enhanced HCC proliferation, invasion and metastasis. Furthermore, U0126, a specific ERK inhibitor, could effectively inhibit EB2-mediated HCC proliferation and metastasis in vitro and in vivo. In conclusion, EB2 coordinates MT cytoskeleton and intracellular signal transduction, forming an EB2-MT-ERK positive feedback loop, to facilitate HCC proliferation, invasion and metastasis. EB2 could serve as a promising prognostic biomarker and potential therapeutic target for HCC; HCC patients with high EB2 expression may benefit from treatment with ERK inhibitors.

Clinical Significance of Stanniocalcin2 mRNA Expression in Patients With Colorectal Cancer.

Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC). Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction. Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival. High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.

Frailty Is a Risk Factor for Postoperative Mortality in Patients With Cirrhosis Undergoing Diverse Major Surgeries.

With a rising burden of cirrhosis surgeries, understanding risk factors for postoperative mortality is more salient than ever. The role of baseline frailty has not been assessed in this context. We evaluated the association between patient frailty and postoperative risk among diverse patients with cirrhosis and determined if frailty improves prognostication of cirrhosis surgical risk scores. This was a retrospective cohort study of U.S. veterans with cirrhosis identified between 2008 and 2016 who underwent nontransplant major surgery. Frailty was ascertained using the Hospital Frailty Risk Score (HFRS). Cox regression analysis was used to investigate the impact of patient frailty on postoperative mortality. Logistic regression was used to identify incremental changes in discrimination for postoperative mortality when frailty was added to the risk prediction models, including the Model for End-Stage Liver Disease (MELD), MELD-sodium (MELD-Na), Child-Turcotte-Pugh (CTP), Mayo Risk Score (MRS), and Veterans Outcomes and Costs Associated With Liver Disease (VOCAL)-Penn. A total of 804 cirrhosis surgeries were identified. The majority of patients (48.5%) had high-risk frailty at baseline (HFRS >15). In adjusted Cox regression models, categories of increasing frailty scores were associated with poorer postoperative survival. For example, intermediate-risk frailty (HFRS 5-15) conferred a 1.77-fold increased hazard relative to low-risk frailty (HFRS, <5; 95% confidence interval [CI], 1.06-2.95; P=0.03). High-risk frailty demonstrated a similarly increased hazard (hazard ratio, 1.74; 95% CI, 1.05-2.88; P=0.03), suggesting a threshold effect of frailty on postoperative mortality. The incorporation of frailty improved discrimination of MELD, MELD-Na, and CTP for postoperative mortality, but did not do so for the MRS or VOCAL-Penn score. Patient frailty was an additional important predictor of cirrhosis surgical risk. The incorporation of preoperative frailty assessments may help to risk stratify patients, especially in settings where the MELD-Na and CTP are commonly applied.

The safety and efficacy of combined hepatic artery resection in treatment of hilar cholangiocarcinoma: a meta-analysis

Objective: To evaluate the safety and effectiveness of combined hepatic artery resection for the treatment of hilar cholangiocarcinoma. Methods: We searched Pubmed, The Cochrane Library, Embase, Web of Science, China Knowledge Network, Wanfang Data Resource System, Vip-Chinese Sci-tech Journal System Database, and China Biomedical Literature Database, and collected the randomized controlled studies or retrospective studies on the safety and efficacy of combined hepatic artery resection and non-hepatic artery resection in the treatment of hilar cholangiocarcinoma. The search period is from January 1, 2006 to December 31, 2019. Review Manager 5.3 software was used to analyze the extracted data indicators. Results: A total of 14 articles were collected, and a total of 2 374 patients with hilar cholangiocarcinoma were included in the study. Meta-analysis results showed that the perioperative mortality in the hepatic artery resection (HAR) group was higher than that of the control group (OR=1.70, 95%CI=0.02-2.90, P=0.05), and the total postoperative morbidity rate was higher than that of the control group (OR=1.28, 95%CI= 0.93-1.76, P=0.13), both of which were not statistically significant compared with the control group. Subgroup analysis showed that the incidence of liver failure (OR=1.15, 95%CI= 0.73-1.82, P=0.54), biliary fistula (OR=1.20, 95%CI= 0.78-1.84, P=0.40), and abdominal infection in the two groups (OR=0.98, 95%CI= 0.53-1.83, P=0.95) was without significant difference. The R0 resection rate of the HAR group was higher than that of the control group, and the difference was not statistically significant (OR=1.08, 95%CI=0.66-1.75, P=0.77). The rates of lymph node metastasis in the HAR group were higher than that in the control group (OR= 2.48, 95%CI= 1.05-5.84, P=0.04). One-year(OR=0.48, 95%CI= 0.32-0.72, P=0.000 5), 3-year (OR= 0.51, 95%CI=0.36-0.72, P=0.000 1), and 5-year (OR=0.50, 95%CI=0.35-0.70, P<0.000 1) survival rates of HAR group were lower than those of the control group. The survival rates of patients in HAR group treated with combined chemotherapy drugs after operation were significantly improved (OR= 7.33, P=0.02). Conclusions: The safety of combined HAR treatment for hilar cholangiocarcinoma is acceptable, but poor postoperative survival may be related to the high lymph node metastasis rate. Therefore, it is still necessary to be cautious in carrying out this operation. Combined with adjuvant chemotherapy after surgery may improve survival.