Conventional three-port laparoscopic appendectomy versus transumbilical and suprapubic single-incision laparoscopic appendectomy using only conventional laparoscopic instruments.

PURPOSE: Single-incision laparoscopic appendectomy (SILA) is usually performed using single-port instruments, which may restrict its development and application. This study explored the performance of transumbilical SILA (TSILA) and suprapubic SILA (SSILA) using only conventional laparoscopic instruments and compared them with conventional three-hole/port laparoscopic appendectomy (CLA). METHODS: This retrospective study included 174 patients who underwent CLA, TSILA, or SSILA for acute appendicitis at our hospital between June 2019 and July 2021. Demographic data and clinical outcomes were compared among the three groups. RESULTS: Compared with CLA, TSILA was associated with significant reductions in postoperative pain, length of hospital stay, and hospital cost, while SSILA was associated with significant reductions in length of hospital stay and hospital cost (all P < 0.05). Significantly more patients in the two SILA groups were cosmetically satisfied than those in the CLA group (all P < 0.05). However, compared with CLA, SSILA required a significantly longer operative time (65.3 ± 24.1 vs 56.5 ± 20.9, P = 0.039). Besides, compared with TSILA, SSILA showed significantly higher postoperative pain score (2 ± 2 vs 3 ± 2, P = 0.006). Mild incisional or intraabdominal infections were noticed in 2 (3.0%) patients in the CLA group, 3 (5.1%) in the TSILA group, and 3 (6.3%) in the SSILA group (P = 0.69). CONCLUSION: SILA performed with only conventional laparoscopic instruments was associated with reduced hospital stay and cost and higher cosmetic satisfaction in comparison to CLA. However, it is technically demanding and may increase operative time.

Molecular characterization of circulating tumor cells-from bench to bedside.

Circulating tumor cells (CTCs) are cancer cells discovered in cancer patients' peripheral blood that successfully escape from the primary tumor site and/or metastases, struggle to survive in the bloodstream, and have potential for seeding metastases. Numerous methods have been proposed to capture CTCs. The value of CTCs as a means of understanding cancer metastasis and a major form of 'liquid biopsy' has been widely demonstrated. Recently, single-cell molecular analyses of CTCs have provided profound biological insights into tumor heterogeneity, mechanism of metastasis and tumor evolution. In addition, because CTC analysis is non-invasive, CTCs exhibit great potential as biomarkers for assessment of cancer prognosis and therapy response. In this review, we summarize modern technologies for CTC detection and isolation, single-cell genomic/transcriptomic characterization of CTCs, and prospective clinical applications of CTCs. We expect that, after further technical improvements in methods of detection and sequencing, CTC analyses will shed new light on the mechanisms driving cancer metastasis and benefit many cancer patients.

Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis and the Effect of Octreotide Combined with Nonsteroidal Anti-Inflammatory Drugs on Preventing Its Occurrence.

BACKGROUND The aim of this study was to explore the risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and investigate the effect of octreotide combined with nonsteroidal anti-inflammatory drugs on preventing its occurrence. MATERIAL AND METHODS A total of 139 patients undergoing ERCP in our hospital from May 2016 to April 2017 were retrospectively analyzed, and divided into an observation group (n=67) (octreotide + indomethacin) and a control group (n=72) (no preventive drugs). The preoperative and postoperative inflammatory cytokines such as tumor necrosis factor-α (TNF)-α, interleukin-6 (IL-6) and IL-8, and serum amylase levels were measured, and the incidence of pancreatitis and hyper amylasemia were monitored. RESULTS Serum amylase level was increased significantly 3 hours after operation in both groups with significantly higher level in the control group compared to the observation group. After 24 hours, serum amylase in the observation group was decreased to preoperative level, whereas it was still higher than preoperative in the control group (P<0.05). Regarding the levels of TNF-α, IL-6, IL-8, and visual analogue scale, they were significantly increased in both groups after operation with significantly higher levels in the control group compared to the observation group (P<0.05). Furthermore, logistic regression analysis showed that difficult intubation, pancreatic duct angiography, surgery for a long time, and the history of previous pancreatitis were risk factors for post-ERCP pancreatitis (P<0.05). CONCLUSIONS Difficult intubation, pancreatic duct angiography, surgery for a long time, and the history of previous pancreatitis were risk factors for post-ERCP pancreatitis. Octreotide combined with non-steroidal anti-inflammatory drugs can reduce the pain of patients with abdominal pain as well as the incidence of postoperative pancreatitis, indicating that they might be effective preventative approaches for pancreatitis.

miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFß-mediated epithelial to mesenchymal transition.

BACKGROUND: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. METHODS: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGFß pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. RESULTS: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGFß signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/Smad7/TGFß in vitro and in vivo. CONCLUSION: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGFß signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.

Overexpression of DBC1, correlated with poor prognosis, is a potential therapeutic target for hepatocellular carcinoma.

Deleted in Breast Cancer 1 (DBC1) is a regulatory protein involved in cell metabolism and cancer progression. Nevertheless, the expression and prognostic values of DBC1 in hepatocellular carcinoma (HCC) are still not well understood. The following study investigated the clinical significance and biological function of DBC1 in HCC. Briefly, overexpression of DBC1 at transcriptional and translational levels in human HCC tissues compared to adjacent normal tissues was observed using quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) approach. Furthermore, upregulated DBC1 was significantly correlated with tumor size (p = 0.005), N stage (p = 0.016), M stage (p = 0.011), tumor differentiation (p < 0.001), and American Joint Committee on Cancer (AJCC) stage (p = 0.001). Moreover, Kaplan-Meier survival analysis revealed that DBC1 was an independent prognosis predictor for disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). In addition, by using Cell Counting Kit-8 (CCK8) assays and colony formation assays, we found that the knockdown of DBC1 significantly suppressed the proliferation of HCC cells in vitro. To conclude, these findings demonstrated that DBC1 was essential in tumorigenesis and proliferation. Moreover, it was identified as a potential therapeutic target for HCC.

Up-Regulated Maternal Embryonic Leucine Zipper Kinase Predicts Poor Prognosis of Hepatocellular Carcinoma Patients in a Chinese Han Population.

BACKGROUND Maternal embryonic leucine zipper kinase (MELK) has been implicated in various types of tumors, but its expression profile and clinicopathologic significance in hepatocellular carcinoma (HCC) in Chinese Han people remains unknown. Therefore, this study attempted to investigate the expression pattern of MELK in HCC tissues obtained from a Chinese Han population. MATERIAL AND METHODS The expression of MELK, from RNA to protein levels, in HCC or disease-free human liver tissues was evaluated using quantitative real-time polymerase chain reaction assays and immunohistochemistry staining, and its prognostic significance was determined based on its impact on HCC patients' survival. RESULTS We found that HCC tissues expressed a higher level of MELK RNA than non-tumor tissues in tumor-related public databases (P<0.001). Hence, we assessed MELK mRNA expression within 32 HCC samples and their adjacent non-tumorous liver tissues in our center. Subsequently, MELK protein expression was evaluated within 101 HCC specimens and 40 disease-free liver tissues. Notably, it revealed that high MELK protein expression was significantly related with tumor number, tumor size, higher pathological tumor-nodule-metastasis stage, vascular invasion, and recurrence (P<0.05, all). Furthermore, elevated MELK protein expression was correlated with decreased overall survival and disease-free survival (P=0.004 and P=0.002, respectively). Univariate and multivariate analysis results show that MELK protein may serve as an independent prognostic indicator for determining prognosis of HCC patients. CONCLUSIONS We found that, in a Chinese Han population, MELK was highly expressed within HCC tissues from RNA to protein levels, and may be a potential independent prognostic biomarker for HCC patients.

Influence of TLR4 rs1927907 locus polymorphisms on tacrolimus pharmacokinetics in the early stage after liver transplantation.

PURPOSE: The aim of this study was to assess the potential influence of single nucleotide polymorphisms (SNPs) in the TLR4 gene on tacrolimus pharmacokinetics in the early stage after liver transplantation. METHODS: A total of 96 liver transplant patients receiving tacrolimus-based immunosuppressive regimens were enrolled in this study. The SNPs of CYP3A5 rs776746 and TLR4 rs1927907 were genotyped in both donors and recipients. Trough tacrolimus concentration (ng/mL) and tacrolimus daily doses (mg/day) were recorded for the first 4 weeks post-transplantation. The tacrolimus dose-adjusted trough concentrations (C/D ratio) required to achieve target concentrations were compared among patients according to allele status for CYP3A5 rs776746 and TLR4 rs1927907 during the first 4 weeks post-transplantation. RESULTS: Both donor and recipient CYP3A5 rs776746 allele A and donor TLR4 rs1927907 allele A were associated with a lower C/D ratio during the early stage after transplantation. The difference was even more striking in patients with both the CYP3A5 and TLR4 genotypes. With increasing numbers of genotype AA/AG, patients were found to have increasingly lower tacrolimus C/D ratios at all time points between post-transplantation weeks 1 and 4. CONCLUSIONS: Collectively, donor TLR4 rs1927907 SNPs were closely associated with tacrolimus elimination in our Chinese Han patient population. The combination of the donor TLR4 rs1927907 SNP and both donor and recipient CYP3A5 rs776746 SNP might have a greater effect on tacrolimus elimination than each SNP separately. Screening for these SNPs prior to liver transplantation might be useful for determining adequate initial daily doses of immunosuppressive agents and achieving the desired immunosuppressive effect.

DDX21 functions as a potential novel oncopromoter in pancreatic ductal adenocarcinoma: a comprehensive analysis of the DExD box family.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with an ill-defined pathogenesis. DExD box (DDX) family genes are widely distributed and involved in various RNA metabolism and cellular biogenesis; their dysregulation is associated with aberrant cellular processes and malignancies. However, the prognostic significance and expression patterns of the DDX family in PDAC are not fully understood. The present study aimed to explore the clinical value of DDX genes in PDAC. METHODS: Differentially expressed DDX genes were identified. DDX genes related to prognostic signatures were further investigated using LASSO Cox regression analysis. DDX21 protein expression was analyzed using the UALCAN and human protein atlas (HPA) online tools and confirmed in 40 paired PDAC and normal tissues through Tissue Microarrays (TMA). The independent prognostic significance of DDX21 in PDAC was determined through the construction of nomogram models and calibration curves. The functional roles of DDX21 were investigated using gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Cell proliferation, invasion, and migration were assessed using Cell Counting Kit-8, colony formation, Transwell, and wound healing assays. RESULTS: Upregulation of genes related to prognostic signatures (DDX10, DDX21, DDX60, and DDX60L) was significantly associated with poor prognosis of patients with PDAC based on survival and recurrence time. Considering the expression profile and prognostic values of the signature-related genes, DDX21 was finally selected for further exploration. DDX21 was overexpressed significantly at both the mRNA and protein levels in PDAC compared to normal pancreatic tissues. DDX21 expression, pathological stage, and residual tumor were significant independent prognostic indicators in PDAC. Moreover, functional enrichment analysis revealed that Genes co-expressed with DDX21 are predominantly involved in RNA metabolism, helicase activity, ribosome biogenesis, cell cycle, and various cancer-related pathways, such as PI3K/Akt signaling pathway and TGF-ß signaling pathway. Furthermore, in vitro experiments confirmed that the knockdown of DDX21 significantly reduced MIA PaCa-2 cell viability, proliferation, migration, and invasion. CONCLUSIONS: Four signature-related genes could relatively precisely predict the prognosis of patients with PDAC. Specifically, DDX21 upregulation may signal an unfavorable prognosis by negatively affecting the biological properties of PDAC cells. DDX21 may be considered as a candidate therapeutic target in PDAC.

Phosphaturic Mesenchymal Tumor Along the Hallux side Inducing a Chronic non-Healing Wound: A Case Report with Literature Review.

Phosphaturic mesenchymal tumor (PMT) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, and bone calcification disorders. Complete surgical resection of the tumor is believed to be the most effective treatment measure. However, the diagnosis of PMT is very difficult because of its insidious and small size, especially, when it appears in subcutaneous tissue with a chronic non-healing wound. We report a rare case of a 38-year-old man with a chronic non-healing wound on the left hallux for approximately eight months. Plain radiographic images and magnetic resonance imaging (MRI) revealed a cystic radiolucent shadow in the left distal phalanx. Bone scan observations also showed increased uptake in the same location. Histologically, this tumor was composed of numerous spindle cells with clusters of giant cells. The serum FGF23 level was significantly higher before surgery, with higher FGF23 levels closer to the tumor. Reverse transcription polymerase chain reaction and immunohistochemistry further confirmed the high expression of FGF23 in tumors. These data suggest that FGF23 may be a potential causative factor of PMT. The serum FGF23 levels might be useful for the diagnosis of PMT and localization of the tumor. The tumor was CD56- and D2 to 40-positive and CD31-negative. The non-healing wound caused by PMT might be attributed to the invasive growth of the tumor, destruction of intercellular junctions, and decrease in the number of endothelial cells.

Association between F-box-only protein 43 overexpression and hepatocellular carcinoma pathogenesis and prognosis.

BACKGROUND: Despite great advances in the prevention, diagnosis, treatment, and management regarding hepatocellular carcinoma (HCC), the overall prognosis of HCC remains unfavorable. The expression profile, prognostic role, and biological functions of F-box-only protein 43 (FBXO43) in HCC remain unclear. Here, we determine the expression profile and prognostic value of FBXO43 in patients with HCC. MATERIALS AND METHODS: A total of 467 HCC patients and their clinicopathological data were collected from the Second Affiliated Hospital of Jiaxing University, the Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. The expression profile, prognostic value, biological functions, and underlying mechanism of its involvement of FBXO43 were explored based on TCGA, Gene Expression Omnibus (GEO), LinkedOmics, and Cancer Dependency Map (DepMap). The expression of FBXO43 in 93 paired liver tissues was investigated via immunohistochemical staining, tissue microarray analysis, and Western blot. The prognostic value was assessed using survival analysis. RESULTS: FBXO43 RNA was upregulated in HCC liver tissues and was associated with an unfavorable prognosis (p < 0.05). Furthermore, FBXO43 protein was overexpressed in HCC liver tissues compared with that in paired normal liver tissues. Overexpression of FBXO43 protein was significantly associated with advanced TNM stage, large tumor size, lymphatic invasion, distant metastasis, earlier cancer recurrence, and decreased overall survival after radical surgery (p < 0.05). Cox regression analysis showed that FBXO43 had significant prognostic value in HCC. Importantly, FBXO43 and its co-expressed genes were mainly involved in cell cycle regulation, DNA replication, metabolic regulation, and so on. FBXO43 knockdown could significantly affect the HCC cell lines growth and proliferation. CONCLUSIONS: We first revealed that FBXO43 was overexpressed in liver HCC tissues at the RNA and protein levels and served as an independent prognostic factor for HCC patients. Therefore, FBXO43 is worth investigating as a potential HCC treatment target.

CircZFR promotes pancreatic cancer progression through a novel circRNA-miRNA-mRNA pathway and stabilizing epithelial-mesenchymal transition protein.

Pancreatic cancer (PC) ranks third in incidence and seventh in mortality among cancers worldwide. CircZFR has been implicated in various human cancers. Yet, how they affect PC progression is understudied. Herein, we demonstrated that circZFR was upregulated in PC tissues and cells, a feature that was correlated with the poor performance of patients with PC. Functional analyses elucidated that circZFR facilitated cell proliferation and enhanced tumorigenicity of PC. Moreover, we found that circZFR facilitated cell metastasis by differentially regulating the levels of proteins related to epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that circZFR sponged miR-375, thereby upregulating the downstream target gene, GREMLIN2 (GREM2). Additionally, circZFR knockdown resulted in attenuation of the JNK pathway, an effect that was reversed by GREM2 overexpression. Collectively, our findings implicate circZFR as a positive regulator of PC progression through the miR-375/GREM2/JNK axis.

Hernioscopy Revealing Rare Abdominal Cocoon Syndrome in an Elderly Patient: A Novel Technique for Abdominal Pathology.

BACKGROUND Incarcerated inguinal hernias (IGHs) combined with abdominal cocoons (ACs) are uncommon in adults. Abdominal cavity exploration using laparoscopy via the hernial sac (hernioscopy) has rarely been reported. Here, an elderly man with unilateral IGH complicated by a contralateral inguinal hernia and AC was found using hernioscopy. We present the surgical decision-making points in an elderly patient with IGH, enrich the diversity of AC, and propose a relatively novel hernioscopy approach. CASE REPORT A 90-year-old man presented with chronic constipation and reducible right inguinal masses. A lump in the right groin was strangulated for 2 days, accompanied with progressive abdominal pain, distension, and vomiting. The levels of inflammatory markers were elevated. Abdominal computed tomography revealed a dilated small bowel and a large mass in the right groin. Subsequently, the patient's condition quickly deteriorated. Therefore, he underwent surgical repair of bilateral hernias. Additionally, in our hospital, a total of 46 patients underwent hernioscopy because of IGH. No intraoperative or postoperative complications were observed. According to our clinical practice, hernioscopy via the bilateral hernial sacs was performed in this elderly patient. We found that almost the entire small bowel and colon were encapsulated in a fibrous and cocoon-like membrane, which postoperative pathological results revealed as AC. CONCLUSIONS This is the first report to reveal that AC complicated with IGH could occur in a 90-year-old man. Hernioscopy is a relatively novel and safe surgical approach to abdominal pathology associated with incarcerated or strangulated inguinal hernias. It is rarely used in adults with IGH.

Hepatitis B Virus Reactivation Potential Risk Factors in Hepatocellular Carcinoma via Transcatheter Arterial Chemoembolization: A Retrospective Research.

Background: To explore the clinical characteristics of reactivation of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The pathological correlation of prognosis and hepatitis B virus reactivation has been given detailed analyses in our research. Methods: A total of 108 related TACE-treated HCC clinical data from January 2008 to January 2016 was gleaned and involved in this retrospective analysis. To lucubrate the nuance of survival rates between HBV reactivated group and HBV nonreactivated group, clinical data of each patient was analyzed in detail and refined the retrospective studies. Results: HBV reactivation occurred in 42 patients with a proportion of 38.9%. The detected HBV DNA level ≥104 in patients showed a reactivation rate of 65.8% (25/38), which was significantly higher than the HBV DNA < 104 cases (24.3%, 17/70). Research data revealed a conspicuous lower cellular immunity (P < 0.01) and better 2-year survival rate (P=0.03) in the HBV-reactivated group when compared to the nonreactivated group. Conclusion: Some of the patients with primary hepatocellular carcinoma possibly had HBV reactivation at post-TACE-therapy. And the predominant risk factors of HBV reactivation are positive HBV test and immunosuppression. Our study suggested that HBV reactivation at post-TACE-therapy is an independent predictor of poor prognosis and low survival rate as well as a crucial reason for poor prognosis and lower survival rate, which indirectly proved that it is urgent to necessitate the antiviral therapy and immune enhancer in improving the curative effect and prognosis of HCC patients.

Hirschsprung's Disease-Related Giant Sigmoid Volvulus Complicated by Refractory Hypertension in an Elderly Man.

BACKGROUND Sigmoid volvulus (SV) is a life-threatening condition occasionally seen in adults. Adult Hirschsprung's disease (HD)-related SV is rarely complicated by difficult-to-control hypertension. In this report we present the case of an elderly man with a rare constellation of HD, SV, and refractory hypertension. CASE REPORT An 82-year-old man had long-term constipation, moderate abdominal pain, and progressive abdominal distension. A CT scan revealed the typical "coffee bean sign". Blood pressure was abnormal high. Subsequently, the patient's condition deteriorated. Therefore, he underwent a Hartmann's procedure. A giant and redundant sigmoid colon (length more than 60 cm, maximal diameter about 15 cm) was demonstrated to be the cause of SV during the process of surgery. Moreover, abdominal compartment syndrome caused by SV resulted in his high and refractory blood pressure (BP). Postoperative pathological results revealed HD in his sigmoid colon. CONCLUSIONS SV is rarely combined with conditions like refractory hypertension or HD among the elderly. Clinical features of SV typically present with long-term constipation, severe abdominal pain, and progressive abdominal distension. The "coffee bean sign" could be observed in imaging examinations. It is important to note that the management of SV is to relieve the obstruction and prevent recurrence, no matter which therapy is used in elderly patients with Hirschsprung's disease.

Keratin 80 promotes migration and invasion of colorectal carcinoma by interacting with PRKDC via activating the AKT pathway.

Little is known about the function of Keratin 80 (KRT80), an epithelial keratin, in cancer. This study investigated the role of KRT80 in the prognosis of colorectal carcinoma (CRC) and the underlying mechanisms involved in CRC migration and invasion. We analyzed the expression of KRT80 using The Cancer Genome Atlas and Oncomine databases. Higher expression of KRT80 was found to be significantly associated with multiple pathological parameters, lower disease-free survival, and overall survival in CRC patients. Also, KRT80 was an independent prognostic indicator for CRC. Furthermore, altered KRT80 expression impacted migration and invasion of CRC cells, as well as the expression of epithelial-mesenchymal transition (EMT)-related markers and cell morphology via the AKT pathway. Inhibiting the expression of AKT could reverse these phenomena. Liquid Chromatograph Mass Spectrometer/Mass Spectromete, Co-immunoprecipitation, and laser scanning confocal microscopy techniques showed that KRT80 could interact with protein kinase, DNA-activated, catalytic polypeptide (PRKDC). Suppressing PRKDC could inhibit the expression of AKT and EMT, as well as the migration and invasion of CRC cells. Taken together, these results demonstrated that KRT80 was an independent prognostic biomarker for CRC and promoted CRC migration and invasion by interacting with PRKDC via activation of the AKT pathway.

Combing a novel device and negative pressure wound therapy for managing the wound around a colostomy in the open abdomen: A case report.

RATIONALE: An open abdomen complicated with small-bowel fistulae becomes a complex wound for local infection, systemic sepsis and persistent soiling irritation by intestinal content. While controlling the fistulae drainage, protecting surrounding skin, healing the wound maybe a challenge. PATIENT CONCERNS: In this paper we described a 68-year-old female was admitted to emergency surgery in general surgery department with severe abdomen pain. Resection part of the injured small bowel, drainage of the intra-abdominal abscess, and fashioning of a colostomy were performed. DIAGNOSES: She failed to improve and ultimately there was tenderness and lot of pus under the skin around the fistulae. The wound started as a 3-cm lesion and progressed to a 6 ×13  (78 cm) around the stoma. INTERVENTIONS: In our case we present a novel device for managing colostomy wound combination with negative pressure wound therapy. OUTCOMES: This tube allows for an effective drainage of small-bowel secretion and a safe build-up of granulation tissue. Also it could be a barrier between the bowel suction point and foam. LESSONS: Management of open abdomen wound involves initial dressing changes, antibiotic use and cutaneous closure. When compared with traditional dressing changes, the NPWT offers several advantages including increased granulation tissue formation, reduction in bacterial colonization, decreased of bowel edema and wound size, and enhanced neovascularization.

Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Orthotopic liver transplantation (OLT) improves the prognosis of patients with hepatocellular carcinoma (HCC). Moreover, the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis. However, studies correlating the complement system with tacrolimus metabolism after OLT are scarce. In this study, the role of single nucleotide polymorphisms (SNPs) associated with the sixth complement component (C6) in tacrolimus metabolism was investigated during the early stages of liver transplantation. METHODS: The study enrolled 135 adult patients treated with OLT for HCC between August 2011 and October 2013. Ten SNPs in C6 gene and rs776746 in cytochrome P450 3A5 (CYP3A5) gene were investigated. The tacrolimus levels were monitored daily during 4 weeks after transplantation. RESULTS: Both donor and recipient CYP3A5 rs776746 allele A were correlated with decreased concentration/dose (C/D) ratios. Recipient C6 rs9200 allele G and donor C6 rs10052999 homozygotes were correlated with lower C/D ratios. Recipient CYP3A5 rs776746 allele A (yielded median tacrolimus C/D ratios of 225.90 at week 1 and 123.61 at week 2), C6 rs9200 allele G (exhibited median tacrolimus C/D ratios of 211.31 at week 1, 110.23 at week 2, and 99.88 at week 3), and donor CYP3A5 rs776746 allele A (exhibited median C/D ratios of 210.82 at week 1, 111.06 at week 2, 77.49 at week 3, and 85.60 at week 4) and C6 rs10052999 homozygote (exhibited median C/D ratios of 167.59 at week 2, 157.99 at week 3, and 155.36 at week 4) were associated with rapid tacrolimus metabolism. With increasing number of these alleles, patients were found to have lower tacrolimus C/D ratios at various time points during the 4 weeks after transplantation. In multiple linear regression analysis, recipient C6 rs9200 group (AA vs. GG/GA) was found to be related to tacrolimus metabolism at weeks 1, 2, and 3 (P = 0.005, P = 0.045, and P = 0.033, respectively), whereas donor C6 rs10052999 group (CC/TT vs. TC) was demonstrated to be correlated with tacrolimus metabolism only at week 4 (P = 0.001). CONCLUSIONS: Recipient C6 gene rs9200 polymorphism and donor C6 gene rs10052999 polymorphism are new genetic loci that affect tacrolimus metabolism in patients with HCC after OLT.

STYK1 promotes epithelial-mesenchymal transition and tumor metastasis in human hepatocellular carcinoma through MEK/ERK and PI3K/AKT signaling.

Serine/threonine/tyrosine kinase 1 (STYK1) is known to be involved in tumor progression. However, its molecular role and mechanism in hepatocellular carcinoma (HCC) remains unknown. We evaluated the effect of STYK1 expression in HCC tissues and investigated the underlying mechanisms associated with progression. HCC tissues expressed greater levels of STYK1 than paired non-tumor tissues. Patients with HCC expressing low levels of STYK1 showed both, greater disease-free (p < 0.0001) and overall (p = 0.0004) survival than those expressing high levels of STYK1. Decreased expression of STYK1 was significantly associated with decreased cell proliferation, reduced migratory capability, and reduced invasive capability. Overexpression of STYK1 was significantly associated with increased cell proliferation, migratory capability, and invasive capability in vitro, as well as increased volume of tumor, weight of tumor, and number of pulmonary metastases in vivo. Furthermore, STYK1's mechanism of promoting cancer cell mobility and epithelial-mesenchymal transition (EMT) was found to be via the MEK/ERK and PI3K/AKT pathways, resulting in increased expression of mesenchymal protein markers: snail, fibronectin, and vimentin, and decreased E-cadherin expression. Our results suggest that STYK1 acts as an oncogene by inducing cell invasion and EMT via the MEK/ERK and PI3K/AKT signaling pathways and it therefore may be a potential therapeutic target in HCC.

Interleukin-6 and rs1800796 locus single nucleotide polymorphisms in response to hypoxia/reoxygenation in hepatocytes.

Ischemia-reperfusion injury due to hypoxia/reoxygenation (H/R) is one of the main causes of liver damage during liver surgery. Donor interleukin-6 (IL-6) rs1800796 single nucleotide polymorphisms (SNPs) affect the metabolism of tacrolimus following liver transplantation-related hepatic H/R. This study investigated the response of IL-6 and its promoter polymorphisms to hepatic H/R in liver parenchymal cells. The association between IL-6 rs1800796 SNPs and IL­6 expression was measured in 84 disease-free liver tissues using tissue microarrays and immunohistochemistry. Subsequently, LO2G, LO2C and NC-LO2 cells were successfully constructed via stable lentivirus-mediated transfection. The effects of IL-6 and its SNPs on the biological function of LO2 cells were examined using a cell model of H/R. Our results revealed that IL-6 was mainly expressed in hepatocytes. The intermediate IL-6 expression rate in genotype CC carriers was higher than that in genotype CG/GG carriers (P=0.006), which was subsequently verified at the IL-6 mRNA level (P=0.002). The concentrations of alanine aminotransferase in the LO2G cells were significantly higher than those in the LO2C cells following H/R for 6 h and H/R for 24 h (P<0.05). The viability of the LO2C cells was higher than that of the LO2G cells (P<0.05). Furthermore, the expression of IL-6 and its downstream molecules was significantly increased in the LO2C cells compared with the LO2G cells (P<0.05). Therefore, the sequence variants of rs1800796 SNPs (G→C) exhibit an increased IL-6 transcription efficiency in liver parenchymal cells. In addition, the increased expression of IL-6 protects the hepatocytes following hepatic H/R injury.

Donor IL-18 rs5744247 polymorphism as a new biomarker of tacrolimus elimination in Chinese liver transplant patients during the early post-transplantation period: results from two cohort studies.

AIM: This study evaluated the relationships between IL-18 polymorphisms and tacrolimus elimination in Chinese liver transplant patients. PATIENTS & METHODS: Eighty-four liver transplant patients from Shanghai (training set) and 50 patients from Shandong (validating set) were inculded. IL-18 polymorphisms (rs5744247, rs7106524, rs549908, rs187238 and rs1946518) and CYP3A5 rs776746 were genotyped. RESULTS: In training set, daily drug dose, total bilirubin, donor CYP3A5 rs776746 and IL-18 rs5744247 genotypes were screened to construct prediction model for tacrolimus elimination. This model was confirmed in validating set (p < 0.001). Donor IL-18 rs5744247 polymorphism was an independent predictor of tacrolimus elimination in the first week after transplantation in both training (p = 0.008) and validating cohorts (p = 0.033). CONCLUSION: Donor IL-18 rs5744247 polymorphism may influence on tacrolimus elimination. Original submitted 16 July 2014; Revision submitted 12 November 2014.