Arteriocolonic fistula of inferior mesenteric artery aneurysm: A case with lower gastrointestinal and intra-abdominal hemorrhage.

Introduction: Arteriocolonic fistula of Inferior Mesenteric Artery Aneurysm (IMAA) refers to a spontaneous formation of pathological communication between the artery and the adjacent gastrointestinal tract. It is a rare, life-threatening condition primarily manifesting as abdominal pain, gastrointestinal bleeding, abdominal pulsating masses. However, its clinical manifestations are usually atypical with a difficult diagnosis and treatment. Case presentation: We report a rare case of a 50-year-old male with a hemorrhagic shock due to primary arteriocolonic fistula of IMAA. Instead of sigmoidectomy, super selective transcatheter arterial embolization (TAE) was performed after diagnostic angiography. Postoperatively, dynamic contrast-enhanced abdominal computed tomography (CT) demonstrated no recanalization of the aneurysm, absence of abnormal collateral vessels, no active hemorrhage. The patient was discharged uneventfully after 2 weeks without abdominal pain or tension. Discussion: Colorectal tumor rupture is a major cause of lower gastrointestinal bleeding (LGIB), with IMAA being an uncommon etiology. Because of the high mortality of explorative laparotomy with an unclear bleeding site, diagnostic angiography and therapeutic TAE are viable options for diagnosing hemodynamic instability. Conclusion: Arteriocolonic fistulas commonly occur secondary to a pseudoaneurysm formed at the anastomosis of the transplanted blood vessel after an artery surgery, which ruptures and penetrates into the intestine. We reported a unique case of primary arteriocolonic fistula of IMAA: aneurysm rupture and bleeding from the abdomen into the hematochezia. After multidisciplinary consultations, our patient obtained the best outcome using the most minimally invasive surgical methods. With an abdominal artery aneurysm presenting with colorectal hemorrhage, arteriocolonic fistula of IMAA should be suspected.

MiR-29c-3p represses gastric cancer development via modulating MEST.

Gastric cancer (GC) triggers a great number of deaths worldwide. Although great efforts have been made in treating this cancer, GC patients' survival rate remains unsatisfactory. An increasing amount of evidence indicates that miR-29c-3p inhibits cancer progression. However, the mechanism of miR-29c-3p in GC remains to be fully defined. Hence, this work aimed to analyze the underlying mechanism of miR-29c-3p in GC. Outcomes showed marked downregulation of miR-29c-3p in GC tissue and cell lines. Functional experiments exhibited that miR-29c-3p repressed GC cell malignant behaviors. Moreover, bioinformatics analysis and dual-luciferase reporter gene detection indicated that MEST was targeted by miR-29c-3p. Rescue assay further proved that MEST participated in functions of miR-29c-3p in GC. To sum up, miR-29c-3p/MEST signaling pathway suppressed formation of malignant phenotypes of GC, and targeting the signaling pathway may be a new method for treating GC.

The role of long non-coding RNAs in mediating chemoresistance by modulating autophagy in cancer.

Cancer is a complex process in which protein-coding and non-coding genes play essential roles. Long noncoding RNAs (lncRNAs), as a subclass of noncoding genes, are implicated in various cancer processes including growth, proliferation, metastasis, and angiogenesis. Due to presence in body fluids such as blood and urine, lncRNAs have become novel biomarkers in cancer detection, diagnosis, progression, and therapy response. Remarkably, increasing evidence has verified that lncRNAs play essential roles in chemoresistance by targeting different signalling pathways. Autophagy, a highly conserved process in response to environmental stresses such as starvation and hypoxia, plays a paradoxical role in inducing resistance or sensitivity to chemotherapy agents. In this regard, we reviewed chemoresistance, the role of lncRNAs in cancer, and the role of lncRNAs in chemoresistance by modulating autophagy.

Immune-mediated adverse effects of immune-checkpoint inhibitors and their management in cancer.

Within the past decade, immune-checkpoint inhibitors (ICPIs), including anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, are undoubtfully the most remarkable advances in cancer therapy. The immune responses are modulated by these ICPIs via blocking the inhibitory PD-1/PD-L1 path and result in immune activation in the suppressive microenvironment of the tumor. While ICPIs result in benefits for numerous patients with malignancy and lead to disease control and survival, toxicity and safety problems have emerged as well. Although immune mediated adverse effects due to ICPIs could involve any organ system, skin, endocrine glands, and gastrointestinal tract, are one of the most commonly affected. Fortunately, in most of the cases, these immune­mediated adverse effects (imAEs) are manageable, while in some cases these toxicities are fulminant and fatal and lead to the withdrawal of treatment. Numerous attempts have been started and are continuing to reduce the incidence rate of imAEs. Further studies are required for a better understanding of these imAEs, decrease the occurrence, and lighten the severity. In this work, we overview the imAEs and also, highlight the most important aspects of the imAEs management.

Integrated characterisation of cancer genes identifies key molecular biomarkers in stomach adenocarcinoma.

AIMS: Gastric cancer is one of the leading causes for cancer mortality. Recent studies have defined the landscape of genomic alterations of gastric cancer and their association with clinical outcomes. However, the pathogenesis of gastric cancer has not been completely characterised. METHODS: Driver genes were detected by five computational tools, MutSigCV, OncodriveCLUST, OncodriveFM, dendrix and edriver, using mutation data of stomach adenocarcinoma (STAD) from the cancer genome altas database, followed by an integrative investigation. RESULTS: TTN, TP53, LRP1B, CSMD3, OBSCN, ARID1A, FAT4, FLG, PCLO and CSMD1 were the 10 most frequently mutated genes. PIK3CD, NLRC3, FMNL1, TRAF3IP3 and CR1 were the top five hub genes of the blue coexpression module positively correlated with pathological tumour stage and lymph node stage (p values <0.05 for all cases). Hierarchical clustering analysis of copy number variations of driver genes revealed three subgroups of STAD patients, and cluster 2 tumours were significantly associated with lower lymph node stage, less number of positive lymph nodes and higher microsatellite instability and better overall survival than cluster 1 and cluster 3 tumours (p values <0.05 for all cases, Wilcoxon rank-sum test or log rank test). High expression in one or more of DNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29 and ZNF568 genes was associated with increased mortality (p values <0.05 for all cases, log rank test). CONCLUSIONS: The driver genes shed insights into the tumourigenesis of gastric cancer and the genes DNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29 and ZNF568 pave the way for developing prognostic biomarkers for the disease.

Dual-targeting strategy using trastuzumab and lapatinib in a patient with HER2 gene amplification in recurrent metachronous metastatic gallbladder carcinoma.

Gallbladder carcinoma (GBC) is a rare and highly aggressive tumor. Early diagnosis is challenging, which results in a poor prognosis using systemic therapy. Recent studies have identified a subset of GBC patients with HER2 gene (ERBB2) amplification that could benefit from HER2-targeted therapy. Here, we report one patient with recurrent metachronous GBC with metastasis, who received the combination of trastuzumab and lapatinib. This approach achieved a partial response for both the brain and the lung metastases. This study demonstrated that HER2 inhibition is a promising therapeutic strategy for GBC with HER2 amplification and, combined with lapatinib, it can effectively target brain metastasis.

UBASH3B promotes tamoxifen resistance and could be negatively regulated by ESR1.

PURPOSE: To explore the prognostic value of UBASH3B in ER+ breast cancer patients and explore potential molecular mechanisms. MATERIALS AND METHODS: Datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were re-analyzed to explore the association between UBASH3B and the progression of ER+ breast cancer. Kaplan-Meier plot analysis with a total of 734 ER+ samples and Gene Set Enrichment Analysis with 632 samples were used in the study. RESULTS: High expression of UBASH3B is negatively correlated with distant metastasis free survival (DMFS, P = 0.01, P = 0.045, P = 0.04 in 2 independent datasets and a merged dataset, respectively), disease specific survival (DSS, P = 0.028) and disease free survival (DFS, P = 0.0052, P = 0.011, P = 0.016 in 3 independent datasets, respectively) in ER+ breast cancer patients. Subset analysis found that UBASH3B also has prognostic value on both lymph node positive and negative sub-populations with ER+ breast cancer. This study also demonstrates that UBASH3B expression is tightly associated with tamoxifen resistance and TP53 mutation, which explains the association between UBASH3B and poor prognosis of ER+ breast cancer. Further analyses show that the expression of UBASH3B is affected by promoter methylation and copy number loss. Besides, UBASH3B is inversely correlated with ER and down-regulated by ER. Importantly, we find cisplatin could be a therapeutic option targeting on UBASH3B in clinical settings. CONCLUSIONS: UBASH3B is negatively regulated by ER and confers poor outcome in ER+ breast cancer patients. Cisplatin is a potential therapeutic option for the management of breast cancer patients with high expression of UBASH3B.

Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality. Although advances have been made in understanding the pathogenesis of PDAC, the outcome still remains poor. The aim of this study is to conduct a meta-analysis to evaluate the precise association between SMAD4 loss and clinicopathological significance in PDAC. A literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, Odds Ratio or Hazard Ratio with corresponding confidence intervals was calculated and summarized. 12 relevant articles were included for full review in detail and meta-analysis. The frequency of SMAD4 protein loss was significantly increased in PDAC than in nonmalignant pancreatic tissue, Odd Ratio was 0.05 with 95% confidence interval 0.01-0.23, p<0.0001. SMAD4 loss was significantly associated with poor overall survival in patients with PDAC, Hazard Ratio was 0.61 with 95% confidence interval 0.38-0.99, p=0.05. SMAD4 loss was not correlated with the size, grades, and lymph node metastasis of PDAC. In conclusion, SMAD4 is a biomarker for the diagnosis of PDAC. SMAD4 loss is significantly related to poor prognosis in patients with PDAC.

Genetic heterogeneity in hepatocellular carcinoma and paired bone metastasis revealed by next-generation sequencing.

Although bone involvement is reported as uncommon in hepatocellular carcinoma (HCC), its incidence has significantly increased in the last decade due to the longer survival of HCC patients related to recent progresses made both in the diagnosis and treatment of the disease. A better understanding of the pathogenic mechanisms underlying the spread of bone metastases in HCC is important. The primary tumor and its corresponding metastases are different at the molecular marker expression or gene status levels and that these differences may affect the clinical outcome of anticancer therapy, particularly in molecularly targeted therapies for the treatment of cancer. No study has investigated the genetic heterogeneity between HCC and paired bone metastasis. In this study, we investigated the genetic heterogeneity in HCC and paired metastasis using a next generation sequencing (NGS) platform to illustrate the molecularly targeted therapy related genes mutations.

Impact of Abdominal Shape on Short-Term Surgical Outcome of Laparoscopy-Assisted Distal Gastrectomy for Gastric Cancer.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for gastric cancer. The aim of the present study was to explore the impact of abdominal shape parameters on gastric antrum cancer patients' short-term surgical outcomes of LADG with D2 lymph node dissection in both genders, including the number of lymph nodes retrieved and surgical safety index. METHODS: This was a retrospective analysis of 177 gastric antrum cancer patients, who underwent LADG between April 2009 and January 2016. The abdominal shape parameters, including abdominal anterior-posterior diameter (APD), transverse diameter (TD), xiphoid process of the sternum-navel distance (XND), and thickness of subcutaneous fat (SCF) at the umbilicus level, were calculated by preoperative abdominal computed tomography (CT) scans. The effects of abdominal shape parameters on the short-term surgical outcomes of LADG were analyzed. RESULTS: In male patients undergoing LADG and D2 lymph node dissection, the number of retrieved lymph nodes was significantly lower in patients with APD ≥17.3 cm (P = 0.005), TD ≥27.4 cm (P = 0.029), SCF ≥1.2 cm (P = 0.014), and BMI ≥22.2 (P = 0.008), whereas in female patients, these were statistically insignificant (P > 0.05). APD, TD, SCF, and BMI were negatively correlated with the number of retrieved lymph nodes in male patients. There was no significant difference in the number of lymph nodes retrieved between high-XND group and low-XND group in either gender. Operation time was significantly shorter in male patients with XND < 17.0 cm (P = 0.044) and in female patients with SCF < 2.15 cm (P = 0.013). Intraoperative blood loss and postoperative complication rate were not significantly different between high- and low-APD groups, high- and low-TD groups, high- and low-XND groups, and high- and low-SCF groups in either gender. Compared with male patients, SCF and TD were significantly higher in female patients. In addition, a higher incidence rate of hypertension was observed in patients of both genders with large APD and SCF, although statistically significant only in male patients. CONCLUSIONS: LADG with D2 lymph node dissection can effectively achieve the lymph node dissection requirement of radical distal gastrectomy for patients with various abdominal shapes. It is worth noting that APD, TD, and SCF can impact on lymph node dissection of LADG in male patients. Nevertheless, in female patients, abdominal shape do not impact on lymph node dissection of LADG. Moreover, LADG with D2 lymph node dissection is proved to be safe for various abdominal shape in both genders, even for abdominal obese patients.

The Clinical Evaluation of Tegafur Gimeracil Oteracil Combined with THP and DDP for Second-Line Treatment of Advanced Cardiac Carcinoma.

The aim of this study is to explore the clinical effect of tegafur gimeracil oteracil combined with pirarubicin hydrochloride (THP) and diamminedichloroplatinum (DDP) for second-line treatment of advanced cardiac carcinoma, and find the most effective method to improve its survival rate and decrease the adverse reactions. 70 patients with advanced cardiac carcinoma admitted during February 2010-March 2014 were selected and divided into two groups with 35 cases in each group. All patients were treated with THP and DDP, and tegafur gimeracil oteracil was added to the observation group. The differences of effective rate, life quality, and adverse reactions after treatment in observational group were observed. The result of total curative effect indicated that the occurrence rate of complete remission + partial remission (CR + PR) in the control group was 28.57 %, the total effective rate was 51.43 %, the occurrence rate of CR + PR in the observational group was 34.29 %, and the total effective rate was 57.15 %; there was no statistical difference between the two groups (P > 0.05). The result of KPS scoring indicated that the improvement rate in the control group was 28.57 %, the total effective rate was 62.86 %, the improvement rate in the observational group was 42.86 %, and the total effective rate was 80 %; there was statistical difference between two groups (P < 0.05); the occurrence rates of adverse reactions including leukocyte decrease, thrombocytopenia, anemia, nausea and vomiting, constipation, peripheral neurovirulence, hepatotoxicity, and renal toxicity were statistically different (P < 0.05). Tegafur gimeracil oteracil combined with THP and DDP in treating advanced cardiac carcinoma can improve the life quality and decrease the adverse reactions.

Clinical modalities for management of gastric cancer hepatic metastasis.

The best treatment for gastric cancer hepatic metastasis is still widely debated. Gastric cancer hepatic metastases has long been justified the indication of palliative chemotherapy. Inspired by the good results of the management of colorectal cancer hepatic metastases, surgeons have focused on the curative or palliative treatment of gastric cancer hepatic metastases. The current clinical modalities used for treatment of gastric cancer hepatic metastasis include liver resection, systemic chemotherapy, radiofrequency ablation (RFA), hepatic arterial infusion (HAI), and palliative gastrectomy. This article presents a review of the literature on hepatic resection, RFA, HAI, palliative gastrectomy, and systemic chemotherapy for the treatment of liver metastases in gastric carcinoma, and discusses the indications and long-term results.

Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer.

AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance. METHODS: We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed. RESULTS: Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival. CONCLUSION: The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.