Intraoperative Normal Saline Administration and Acute Kidney Injury in Patients Undergoing Liver Transplantation.

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.

Pulmonary artery catheter monitoring versus arterial waveform-based monitoring during liver transplantation: a retrospective cohort study.

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47-1.56), p = 0.229; EAD: 0.99 (0.38-1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).

Effect of driving pressure-guided positive end-expiratory pressure on postoperative pulmonary complications in patients undergoing laparoscopic or robotic surgery: a randomised controlled trial.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).

Low MST1/2 and negative LATS1/2 expressions are associated with poor prognosis of colorectal cancers.

Mammalian STe20-like protein kinase 1/2 (MST1/2) and large tumor suppressor homolog 1/2 (LATS1/2) are the core components of the tumor-suppressive Hippo pathway. Dysregulation of this pathway is associated with the progression and metastasis of various cancers. However, MST1/2 and LATS1/2 expressions have not been systematically evaluated in colorectal cancers. We evaluated the clinicopathologic correlation and prognostic significance of MST1/2 and LATS1/2 immunohistochemical expressions in 327 colorectal cancer patients. Low MST1/2 expression, identified in 235 (71.9 %) cases, was significantly associated with poor differentiation (P = 0.018) and large size (P < 0.001) of the tumor. Negative LATS1/2 expression, identified in 226 (69.1 %) cases, was significantly correlated with low MST1/2 expression (P = 0.044). Low MST1/2 and negative LATS1/2 expressions were significantly associated with poor overall survivals (P = 0.015 and P = 0.038, respectively). Furthermore, the combined MST1/2lowLATS1/2negative expression group showed significantly worse overall survival than other groups (P = 0.003), and considered as an independent poor prognostic factor for colorectal cancer patients (hazard ratio = 1.720; 95 % confidence interval, 1.143-2.588; P = 0.009). Low MST1/2 and negative LATS1/2 expressions may serve as prognostic indicators in patients with colorectal cancer.

Serum neutrophil gelatinase-associated lipocalin and lactate level during surgery predict acute kidney injury and early allograft dysfunction after liver transplantation.

Early allograft dysfunction (EAD) and acute kidney injury (AKI) are common and clinically important complications after liver transplantation. Serum lactate level at the end of surgery could predict EAD and neutrophil gelatinase-associated lipocalin (NGAL) is known as a biomarker for AKI after liver transplantation. The authors investigated whether the combination of these two laboratory tests could be used as an early predictor of these two complications of EAD and AKI. We reviewed cases undergoing living donor liver transplantation (n = 353). Lactate-adjusted NGAL level, a combination of these two predictors, was calculated as the sum of each value multiplied by the odds ratio for EAD or AKI. We evaluated whether this combined predictor at the end of surgery is significantly associated with both postoperative AKI or EAD. We compared the area under the receiver operating characteristic curve (AUC) between our multivariable regression models with and without NGAL, lactate, or lactate-adjusted NGAL. NGAL, lactate and lactate-adjusted NGAL are significant predictors for EAD and AKI. The regression model for EAD or AKI including lactate-adjusted NGAL showed a greater AUC (for EAD: odds ratio [OR] 0.88, 95% confidence interval [CI] 0.84-0.91; for AKI: OR 0.89, 95% CI 0.85-0.92) compared to the AUC of the models including lactate (for EAD: OR 0.84, 95% CI 0.81-0.88; for AKI: OR 0.79, 95% CI 0.74-0.83) or NGAL alone (for EAD: OR 0.82, 95% CI 0.77-0.86; for AKI: OR 0.84, 95% CI 0.80-0.88) or the model without lactate or NGAL (for EAD: OR 0.64, 95% CI 0.58-0.69, for AKI: OR 0.75, 95% CI 0.70-0.79). In conclusion, lactate-adjusted NGAL level at the end of surgery could be a reliable combined laboratory predictor for postoperative EAD or AKI after liver transplantation with a greater discriminative ability than lactate or NGAL alone.

Low HES-1 and positive DLL4 expression predicts poor prognosis of colorectal cancers.

Hairy and enhancer of split-1 (HES-1) is a downstream transcription factor and delta-like 4 (DLL4) is a ligand of the Notch signalling pathway. HES-1 and DLL4 expression are known to have an association with the progression and metastasis of cancers. We evaluated HES-1 and DLL4 expression and assessed their correlation with biological behaviour and prognostic significance of 327 colorectal cancers. Low HES-1 expression was identified in 210 (64.2%) cases and was significantly correlated with large tumour size, lymphovascular invasion, and distant metastasis. DLL4 was positive in 132 (40.4%) cases and significantly correlated with perineural invasion, distant metastasis, and involved resection margin. Patients with low HES-1 expression showed significantly worse overall survival than patients with high HES-1 expression [hazard ratio (HR)=3.017; 95% confidence interval (CI) 1.880-4.841; p<0.001]. The overall survival of patients with positive DLL4 expression was significantly worse than that of patients with negative DLL4 expression (HR=2.922; 95% CI 1.976-4.322; p<0.001). Furthermore, the combined HES-1lowDLL4positive expression group showed the worst overall survival compared to other groups (p<0.001) and was an independent poor prognostic factor of colorectal cancer patients. Thus, low HES-1 and positive DLL4 expression are associated with aggressive biological behaviour and can be used as prognostic factors in colorectal cancer patients.

Changes in Trunk Muscle Activity during Unilateral Weight Bearing and Abnormal Postural Gait in Healthy Individuals.

Background and Objectives: Many people tend to carry their bags or baggage on only one side of their body. Due to smartphone use, people also tend to walk bent forward in a kyphotic posture. In this study, we aimed to assess trunk muscle activity changes due to weight-bearing, carried in the left or right hand, and using three different gait postures. Materials and Methods: We recruited 27 healthy participants (aged 19−75 years) with no history of LBP within the last 6 months before study participation. Electromyographic activities of the lower back and the abdominal muscles of the participants were evaluated using four-channel surface electromyography (EMG). Surface EMG recordings were obtained from four trunk muscles, including the flexor (rectus abdominis (RA), external oblique (EO)) and extensor muscles (lumbar erector spinae (LE), and the superficial lumbar multifidus (LM)), during unilateral weight-bearing tasks and with different gait postures (normal gait, with a sway back, and thoracic kyphosis). Results: In the "unilateral weight-bearing task", there was a significant difference in the activity of all the trunk muscles between the weight-bearing limb side and the opposite side (p < 0.05). The activation of the left trunk muscle was greater than that of the right trunk muscle when the dumbbell was lifted using the right hand. The other side showed the same result. In the "gait posture task" performed by the participants using a sway-back posture, the RA and EO had a higher level of activity in the stance and swing phases compared with that in a neutral gait (p < 0.05). Moreover, in the participants with a thoracic kyphosis posture, the LE and LM had a higher level of activity compared with that in a neutral gait (p < 0.05). Conclusions: Our results indicate that abnormal gait posture and unilateral weight-bearing tasks may impair the balance of trunk muscles, increasing the incidence of LBP. However, further large-scale, prospective, controlled studies are warranted to corroborate our results.

Deep learning model to predict Epstein-Barr virus associated gastric cancer in histology.

The detection of Epstein-Barr virus (EBV) in gastric cancer patients is crucial for clinical decision making, as it is related with specific treatment responses and prognoses. Despite its importance, the limited medical resources preclude universal EBV testing. Herein, we propose a deep learning-based EBV prediction method from H&E-stained whole-slide images (WSI). Our model was developed using 319 H&E stained WSI (26 EBV positive; TCGA dataset) from the Cancer Genome Atlas, and 108 WSI (8 EBV positive; ISH dataset) from an independent institution. Our deep learning model, EBVNet consists of two sequential components: a tumor classifier and an EBV classifier. We visualized the learned representation by the classifiers using UMAP. We externally validated the model using 60 additional WSI (7 being EBV positive; HGH dataset). We compared the model's performance with those of four pathologists. EBVNet achieved an AUPRC of 0.65, whereas the four pathologists yielded a mean AUPRC of 0.41. Moreover, EBVNet achieved an negative predictive value, sensitivity, specificity, precision, and F1-score of 0.98, 0.86, 0.92, 0.60, and 0.71, respectively. Our proposed model is expected to contribute to prescreen patients for confirmatory testing, potentially to save test-related cost and labor.

Transverse abdominis plane block compared with patient-controlled epidural analgesia following abdominal surgery: a meta-analysis and trial sequential analysis.

Thoracic epidural analgesia (TEA) and transversus abdominis plane (TAP) block are used for pain control after abdominal surgery. Although there have been several meta-analyses comparing these two techniques, the conclusion was limited by a small number of studies and heterogeneity among studies. Our meta-analysis used the Medline, EMBASE, and Cochrane central library databases from their inception through September 2022. Randomized controlled trials (RCTs) comparing TEA and TAP block were included. The pre-specified primary outcome was the pain score at rest at 12 h postoperatively. Twenty-two RCTs involving 1975 patients were included. Pooled analyses showed the pain score at rest at 12 h postoperatively was significantly different between groups favoring TEA group (Mean difference [MD] 0.58, 95% confidence interval CI - 0.01, 1.15, P = 0.04, I2 = 94%). TEA group significantly reduced the pain score at 48 h at rest (MD 0.59, 95% CI 0.15, 1.03, P = 0.009, I2 = 86%) and at 48 h at movement (MD 0.53, 95% CI 0.07, 0.99, P = 0.03, I2 = 76%). However, there was no significant difference at other time points. Time to ambulation was shorter in TAP block but the incidence of hypotension at 24 h and 72 h was significantly lower in TAP block compared to TEA. Trial sequential analysis showed that the required information size has not yet been reached. Our meta-analysis demonstrated there was no significant or clinically meaningful difference in the postoperative pain scores between TEA and TAP block group. Given the insufficient information size revealed by TSA, the high risk of bias of our included studies, and the significant heterogeneity of our meta-analysis results, our results should be interpreted carefully but it is not likely that the addition of further studies could prove any clinically meaningful difference in pain score between these two techniques.

Determination of pharmacokinetics and tissue distribution of a novel lutetium-labeled PSMA-targeted ligand, 177Lu-DOTA-PSMA-GUL, in rats by using LC-MS/MS.

Prostate specific membrane antigen (PSMA) is known to be overexpressed in prostate cancer cells, providing as a diagnostic and therapeutic target for prostate cancer. A lutetium-labeled PSMA targeted ligand, 177Lu-DOTA-PSMA-GUL is a novel radiopharmaceutical, which has been developed for the treatment of prostate cancer. While the GUL domain of 177Lu-DOTA-PSMA-GUL binds to the antigen, the beta-emitting radioisotope, 177Lu-labeled DOTA, interacts with prostate cancer cells. However, the in vivo pharmacokinetics of intact 177Lu-DOTA-PSMA-GUL has never been characterized. This study aimed to evaluate the pharmacokinetics and tissue distribution of the radiopharmaceutical in rats by using its stable isotope-labeled analog, 175Lu-DOTA-PSMA-GUL. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of 175Lu-DOTA-PSMA-GUL was developed and validated. Following intravenous injection, the plasma concentration-time profiles of 175Lu-DOTA-PSMA-GUL showed a multi-exponential decline with the average elimination half-life of 0.30 to 0.33 h. Systemic exposure increased with the dose and renal excretion is the major elimination route. Tissue distribution of 175Lu-DOTA-PSMA-GUL was most substantial in kidneys, followed by the prostate. The developed LC-MS/MS assay and the in vivo pharmacokinetic data of 175Lu-DOTA-PSMA-GUL would provide helpful information for further clinical studies to be developed as a novel therapeutic agent for prostate cancer.

Intra-host diversity of drug-resistant cytomegalovirus: A case report of cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.

Long-term outcomes in patients with advanced and/or metastatic non-small cell lung cancer who completed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: Multicenter, real-world data (KCSG LU20-11).

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non-small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration. METHODS: This multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020. RESULTS: Ninety-six patients who completed 2 years of ICIs were reviewed. The median durations of treatment and follow-up were 24.0 and 33.9 months, respectively. The objective response rate (ORR) was 85.4%. The median progression-free survival (PFS) and overall survival (OS) periods were not reached. After completion, the PFS and OS rates were 81.1% and 96.4%, respectively, at 12 months. Forty-three patients were identified who discontinued ICIs without disease progression: 26 (60.5%) for adverse events and 17 (39.5%) for other causes. The median durations of treatment and follow-up were 10.5 and 21.2 months, respectively. The ORR was 90.7%. The median PFS and OS periods were not reached. After discontinuation, the PFS and OS rates were 71.0% and 90.0%, respectively, at 12 months. CONCLUSIONS: A significantly high proportion of patients who completed 2 years of ICI therapy continued to experience long-term PFS. Even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival. LAY SUMMARY: The optimal treatment duration for immune checkpoint inhibitors (ICIs) remains to be determined. This study reports the long-term outcomes of patients with non-small cell lung cancer who completed 2 years of ICI therapy or achieved a durable response after the discontinuation of ICIs without disease progression in real-world practice. A significantly high proportion of patients who completed 2 years of ICIs continued to experience long-term progression-free survival. In addition, even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival.

Could DOAC Be a Better Choice Than Warfarin in Low Compliance Patients with Fontan Procedure?

Background and Objectives: After the Fontan procedure, thromboembolic events need to be prevented. We present a young patient with a history of Fontan procedure and poor adherence to warfarin who developed systemic thromboembolism. He was changed to maintenance dabigatran, which is one of the available direct oral anticoagulants (DOACs). Case presentation: A 20-year-old man was diagnosed with cerebral infarct, pulmonary thromboembolism (PTE), and renal infarcts. He was prescribed warfarin to prevent thromboembolic events after the Fontan procedure. Based on his poor adherence to warfarin, we decided to change the anticoagulant therapy from warfarin to dabigatran 150 mg bid. One month later, his pulmonary thromboembolism regressed. Conclusion: Our case report showed a young adult with low compliance to warfarin who developed cerebral, pulmonary, and renal thromboembolic events. Thus, in our opinion, the change from warfarin to a DOAC was necessary for further prevention and treatment of PTE. A change from warfarin to a DOAC should be considered in patients with poor compliance who are at high risk of thromboembolic events, for example, after the Fontan procedure.

Increased expression levels of AURKA and KIFC1 are promising predictors of progression and poor survival associated with gastric cancer.

Increased cell proliferation is a critical hallmark of cancer development and progression. The proliferation of tumor cells depends on mitotic deregulation. Here, we identified the differentially expressed genes (DEGs) in gastric cancer (GC) through RNA sequencing data and bioinformatics analysis. Subsequent functional and pathway enrichment analyses showed that the screened DEGs were enriched in the mitosis-associated pathway. Based on the analysis results, we selected two signatures (aurora kinase A [AURKA] and kinesin family member C1 [KIFC1]) to determine their clinicopathological significance. The results showed a significant positive correlation between AURKA and KIFC1 expression both at the mRNA and protein levels. AURKA expression was positively correlated with distant metastases (p = 0.032) and tumor-node-metastasis (TNM) stage (p = 0.001). Elevated KIFC1 expression was significantly associated with tumor size (p = 0.029), depth of invasion (p < 0.001), lymph node metastasis (p < 0.001), distant metastasis (p = 0.023), and TNM stage (p < 0.001). Higher AURKA (hazard ratio [HR] = 1.3, p < 0.001) and KIFC1 (HR = 1.41, p < 0.001) mRNA levels were also significantly correlated with poor overall survival. Thus, AURKA and KIFC1 could serve as potential prognostic markers and therapeutic targets for GC.

Landscape of epigenetically regulated lncRNAs and DNA methylation in smokers with lung adenocarcinoma.

In this study, we identified long non-coding RNAs (lncRNAs) associated with DNA methylation in lung adenocarcinoma (LUAD) using clinical and methylation/expression data from 184 qualified LUAD tissue samples and 21 normal lung-tissue samples from The Cancer Genome Atlas (TCGA). We identified 1865 differentially expressed genes that correlated negatively with the methylation profiles of normal lung tissues, never-smoker LUAD tissues and smoker LUAD tissues, while 1079 differentially expressed lncRNAs were identified using the same criteria. These transcripts were integrated using ingenuity pathway analysis to determine significant pathways directly related to cancer, suggesting that lncRNAs play a crucial role in carcinogenesis. When comparing normal lung tissues and smoker LUAD tissues, 86 candidate genes were identified, including six lncRNAs. Of the 43 candidate genes revealed by comparing never-smoker LUAD tissues and smoker LUAD tissues, 13 were also different when compared to normal lung tissues. We then investigated the expression of these genes using the Gene Expression of Normal and Tumor Tissues (GENT) and Methylation and Expression Database of Normal and Tumor Tissues (MENT) databases. We observed an inverse correlation between the expression of 13 genes in normal lung tissues and smoker LUAD tissues, and the expression of five genes between the never-smoker and smoker LUAD tissues. These findings were further validated in clinical specimens using bisulfite sequencing, revealing that AGR2, AURKB, FOXP3, and HMGA1 displayed borderline differences in methylation. Finally, we explored the functional connections between DNA methylation, lncRNAs, and gene expression to identify possible targets that may contribute toward the pathogenesis of cigarette smoking-associated LUAD. Together, our findings suggested that differentially expressed lncRNAs and their target transcripts could serve as potential biomarkers for LUAD.

Increased HOXC6 mRNA expression is a novel biomarker of gastric cancer.

In this study, we aimed to investigate the molecular biomarkers that are pivotal for the development and progression of gastric cancer (GC). We analyzed clinical specimens using RNA sequencing to identify the target genes. We found that the expression of HOXC6 mRNA was upregulated with the progression of cancer, which was validated by quantitative real time PCR and RNA in-situ hybridization. To compare the protein expression of HOXC6, we evaluated GC and normal gastric tissue samples using western blot analysis and immunohistochemistry. We detected significantly higher levels of HOXC6 in the GC tissues than in the normal controls at both mRNA and protein levels. The expression levels of HOXC6 mRNA in patients with advanced gastric cancer (AGC) were significantly higher than those in patients with early gastric cancer (EGC). Kaplan-Meier curves showed that high expression of HOXC6 mRNA is significantly associated with poor clinical prognosis. Our findings suggest that HOXC6 mRNA may be a novel biomarker and can be potentially valuable in predicting the prognosis of GC patients. Especially, HOXC6 mRNA in-situ hybridization may be a diagnostic tool for predicting prognosis of individual GC patients.

Ultrasound assessment of gastric content in fasted patients before elective laparoscopic cholecystectomy: a prospective observational single-cohort study.

BACKGROUND: Patients with symptomatic gallbladder diseases exhibit delayed gastric emptying. We evaluated the residual gastric content in fasted patients scheduled for elective laparoscopic cholecystectomy because of symptomatic gallbladder disease using ultrasonography. METHODS: This prospective observational single-cohort study was approved by the Institutional Review Board, and written informed consent was obtained from all included patients. Before anesthesia induction, the gastric antrum was examined by ultrasound. Once the presence of solid content was excluded, the patients were classified using a three-point grading system (grade 0: no fluid; grade 1: fluid in the right lateral decubitus position; grade 2: fluid in both the supine and right lateral decubitus positions), and the fluid volume was measured. A stomach was considered empty if it had no contents or ≤ 1.5 mL·kg-1 of fluid, and was considered full if solid content or > 1.5 mL·kg-1 of fluid was detected. RESULTS: Among 138 patients, 18 patients (13%) presented with a full stomach, 12 (9%) of whom had solid content, and six (4%) of whom had >1.5 mL·kg-1 of fluid in their stomach. Among the remaining 120 patients with an empty stomach, 65 patients presented with a grade 0 antrum, and 55 patients with a grade 1 or 2 antrum with ≤ 1.5 mL·kg-1 of fluid. CONCLUSION: The gastric ultrasound assessment revealed that 13% of patients scheduled for elective cholecystectomy because of symptomatic gallbladder disease had a full stomach despite following the fasting guidelines. This was higher than the reported incidence of a full stomach among the general surgical population. Further studies are required to delineate the clinical implications of our findings. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03259841); registered 4 August, 2017.

RéSUMé: CONTEXTE: Les patients atteints de maladies vésiculaires symptomatiques souffrent de retard de la vidange gastrique. Nous avons évalué par échographie le contenu gastrique résiduel chez des patients à jeun devant subir une cholécystectomie non urgente par laparoscopie en raison de maladie vésiculaire symptomatique. MéTHODE: Cette étude prospective observationnelle sur une cohorte unique a été approuvée par le Comité d'éthique indépendant et le consentement éclairé écrit a été obtenu de tous les patients inclus. Avant l'induction de l'anesthésie, l'antre gastrique a été examiné par échographie. Une fois la présence de solides exclue, les patients ont été catégorisés selon un système de notation de 3 grades (0 : aucun liquide; 1 : liquides détectés en position de décubitus latéral droit; 2 : liquides détectés en décubitus dorsal et en décubitus latéral droit), et le volume liquidien a été mesuré. Un estomac était considéré comme vide s'il n'avait aucun contenu solide et ≤ 1,5 mL·kg−1 de liquides, et considéré comme plein si du contenu solide ou > 1,5 mL·kg−1 de liquides était détecté. RéSULTATS: Parmi 138 patients, 18 (13 %) se sont présentés avec un estomac plein, parmi lesquels 12 (9 %) avaient du contenu solide, et six (4 %) avaient > 1,5 mL·kg−1 de liquides dans l'estomac. Parmi les 120 patients restants avec un estomac vide, 65 présentaient un antre gastrique de grade 0 et 55 présentaient un antre de grade 1 ou 2 avec ≤ 1,5 mL·kg−1 de liquides. CONCLUSION: L'évaluation gastrique par échographie a révélé que 13 % des patients devant subir une cholécystectomie non urgente en raison de maladie vésiculaire symptomatique avaient un estomac plein tout en ayant respecté les directives de jeûne. Ce chiffre était plus élevé que l'incidence rapportée d'estomac plein parmi la population chirurgicale générale. Des études supplémentaires sont nécessaires pour déterminer les implications cliniques de nos résultats. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03259841); enregistrée le 4 août 2017.

Protein expression profiles and prognostic value of E2F family members in clear cell renal cell carcinoma.

The derangement of the cell cycle facilitates uncontrolled cell proliferation and acquisition of genetic alterations favorable for malignancy. However, the protein expression profiles of E2 F family cell cycle regulators in clear cell renal cell carcinoma (ccRCC) have not yet been thoroughly investigated. In this study, we aimed to examine the protein expression profiles and prognostic value of E2 F1, E2 F3, and E2 F4 in ccRCC cases. The immunohistochemical expression of E2 F1, E2 F3, and E2 F4 was quantitatively scored in 180 ccRCC tumor tissues and 79 normal kidney tissues. The prognostic implications of these E2 F members were determined. We found that ccRCC tumor cells showed higher nuclear expression of E2 F1, E2 F3 and E2 F4 than normal kidney samples. High E2 F1 and E2 F3 expression in tumor cells was associated with poor prognostic factors of ccRCC, whereas high E2 F4 correlated with beneficial prognostic factors. High expression of E2 F1 and E2 F3 in tumor cells was correlated with a poor overall and recurrence-free survival, while high E2 F4 expression did not. In conclusion, E2 F1, E2 F3 and E2 F4 may function as oncogenes during tumorigenesis of ccRCC, although they contribute to the progression of ccRCC in different ways. Additional studies are required to clarify the conflicting role of E2 F4 in the tumor evolution of ccRCC.

High Membranous Expression of Fatty Acid Transport Protein 4 Is Associated with Tumorigenesis and Tumor Progression in Clear Cell Renal Cell Carcinoma.

The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell carcinoma (RCC) in comparison with 80 specimens of the normal kidney. We also examined the clinical implication of these three fatty acid transporters in RCC, which was validated by an open-access The Cancer Genome Atlas data analysis. Both CD36 and FATP4 revealed higher membranous expressions in RCC tumor cells than in normal cells. In contrast, ACSL1 expression was remarkably reduced in RCC tumor cells compared to normal cells. CD36, FATP4, and ACSL1 showed high expressions in 74 (41.1%), 85 (47.2%), and 72 (40.0%) out of 180 RCC cases, respectively. Clinically, high FATP4 in tumor cells was associated with female gender (p = 0.05), high TNM stage (p = 0.039), tumor necrosis (p = 0.009), and tumor recurrence (p = 0.037), while high ACSL1 was only related to female gender (p = 0.023). CD36 expression revealed no correlation with the clinicopathologic parameters of RCC. Increased FATP4 expression displayed an association with short recurrence-free survival (p = 0.003). In conclusion, the high FATP4 expression was clinically associated with poor prognostic factors of RCC. Overexpression of membranous FATP4 and CD36 combined with reduced cytoplasmic expression of ACSL1 might be a tumor-specific feature of RCC, contributing to the tumorigenesis and tumor progression.

Prognostic Characteristics of MACC1 Expression in Epithelial Ovarian Cancer.

Recent studies have shown that overexpression of metastasis-associated in colon cancer 1 (MACC1) is significantly associated with adverse prognoses of patients with different kinds of cancer. However, the exact survival effect of MACC1 on epithelial ovarian cancer (EOC) patients has not yet been established. Thus, the objective of this study was to explore the prognostic role of MACC1 mRNA in EOC by using Kaplan-Meier (KM) plotter and ONCOMINE database. Our results indicated that MACC1 mRNA high expression was significantly associated with unfavorable overall survival (hazard ratio (HR) = 1.51 (95% confidence interval (CI): 1.21 - 1.88), P = 0.00025) and progression-free survival (HR = 1.53 (95% CI: 1.24 - 1.89), P = 5.8e-05) in EOC patients. We also found that the expression of MACC1 mRNA in EOC was 2.5 times higher than that in normal surface ovarian epithelium, which was statistically significant (P = 2.86e-7). Our results suggest that MACC1 expression might be a biomarker for poor prognosis in individual EOC patients.