Showing papers in "World Journal of Gastrointestinal Oncology in 2018"

Fusobacterium nucleatum and colorectal cancer: A review

Abstract: Fusobacterium nucleatum (F. nucleatum) is a Gram-negative obligate anaerobe bacterium in the oral cavity and plays a role in several oral diseases, including periodontitis and gingivitis. Recently, several studies have reported that the level of F. nucleatum is significantly elevated in human colorectal adenomas and carcinomas compared to that in adjacent normal tissue. Several researchers have also demonstrated that F. nucleatum is obviously associated with colorectal cancer and promotes the development of colorectal neoplasms. In this review, we have summarized the recent reports on F. nucleatum and its role in colorectal cancer and have highlighted the methods of detecting F. nucleatum in colorectal cancer, the underlying mechanisms of pathogenesis, immunity status, and colorectal cancer prevention strategies that target F. nucleatum.

Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review

Abstract: Colorectal carcinogenesis (CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APCmin/+ mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.

Risk of gastric cancer development after eradication of Helicobacter pylori.

Abstract: Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer (GC) development through the Correa's gastric carcinogenesis cascade. However, H. pylori eradication alone does not eliminate GC, as pre-neoplastic lesions (atrophic gastritis, intestinal metaplasia and dysplasia) may have already developed in some patients. It is therefore necessary to identify patients at high-risk for gastric cancer after H. pylori eradication to streamline the management plan. If the patients have not undergone endoscopy with histologic assessment, the identification of certain clinical risk factors and non-invasive testing (serum pepsinogen) can predict the risk of atrophic gastritis. For those with suspected atrophic gastritis, further risk stratification by endoscopy with histologic assessment according to validated histologic staging systems would be advisable. Patients with higher stages may require long-term endoscopic surveillance. Apart from secondary prevention to reduce deaths by diagnosing GC at an early stage, identifying medications that could potentially modify the GC risk would be desirable. The potential roles of a number of medications have been suggested by various studies, including proton pump inhibitors (PPIs), aspirin, statins and metformin. However, there are currently no randomized clinical trials to address the impact of these medications on GC risk after H. pylori eradication. In addition, most of these studies failed to adjust for the effect of concurrent medications on GC risk. Recently, large population-based retrospective cohort studies have shown that PPIs were associated with an increased GC risk after H. pylori eradication, while aspirin was associated with a lower risk. The roles of other agents in reducing GC risk after H. pylori eradication remain to be determined.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection

Abstract: This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required.

Inflammation-associated microsatellite alterations: Mechanisms and significance in the prognosis of patients with colorectal cancer.

Abstract: Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono- and di-nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI-H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to classify it as MSI-low/elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.

Ampulla of Vater carcinoma: Molecular landscape and clinical implications

Abstract: Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.

Conversion surgery for gastric cancer patients: A review.

Abstract: Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as "conversion surgery", which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.

Novel biomarkers for patient stratification in colorectal cancer: A review of definitions, emerging concepts, and data

Abstract: Colorectal cancer (CRC) treatment has become more personalised, incorporating a combination of the individual patient risk assessment, gene testing, and chemotherapy with surgery for optimal care. The improvement of staging with high-resolution imaging has allowed more selective treatments, optimising survival outcomes. The next step is to identify biomarkers that can inform clinicians of expected prognosis and offer the most beneficial treatment, while reducing unnecessary morbidity for the patient. The search for biomarkers in CRC has been of significant interest, with questions remaining on their impact and applicability. The study of biomarkers can be broadly divided into metabolic, molecular, microRNA, epithelial-to-mesenchymal-transition (EMT), and imaging classes. Although numerous molecules have claimed to impact prognosis and treatment, their clinical application has been limited. Furthermore, routine testing of prognostic markers with no demonstrable influence on response to treatment is a questionable practice, as it increases cost and can adversely affect expectations of treatment. In this review we focus on recent developments and emerging biomarkers with potential utility for clinical translation in CRC. We examine and critically appraise novel imaging and molecular-based approaches; evaluate the promising array of microRNAs, analyze metabolic profiles, and highlight key findings for biomarker potential in the EMT pathway.

Emerging role of long non-coding RNA in the development of gastric cancer.

Abstract: Gastric cancer is a common, worldwide malignancy and has a poor prognosis due to late diagnosis. Long non-coding RNAs (lncRNAs) are a significant subtype of RNA molecules with a length longer than 200 nucleotides (nt) that rarely encode proteins. In recent decades, deregulation of lncRNAs has been shown to be involved in tumorigenesis and tumor progression in various human carcinomas, including gastric cancer. Accumulating evidence has shown that some lncRNAs may function as diagnostic biomarkers or therapeutic targets for gastric cancer. Thus, exploring the specific functions of lncRNAs will help both gain a better understanding of the pathogenesis and develop novel treatments for gastric cancer. In this review, we highlight the expression and functional roles of lncRNAs in gastric cancer, and analyze the potential applications of lncRNAs as diagnostic markers and therapeutic targets.

Prediction of malignancy and adverse outcome of solid pseudopapillary tumor of the pancreas

Abstract: Since solid pseudopapillary tumor of the pancreas (SPTP) was officially classified by the World Health Organization in 1996, SPTP has recently received special attention in the literature. Studies have shown that SPTP is a heterogeneous tumor, with a small percentage of patients harboring aggressive behaviors. However, criteria for malignancy grade in SPTP have not been well established. The prognosis of SPTP is generally good, with cases having a chance for long-term survival even with recurrence and/or metastasis after surgical resection. The current American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis staging system is not specific to SPTP. The lack of a predictive staging classification that accurately describes the heterogeneity of this disease hinders meaningful research into optimal individualized therapy. Here we summarize and discuss the associated factors proposed for appraisal of the malignant potential and adverse outcome of SPTP.

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

Abstract: Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

Histo-molecular oncogenesis of pancreatic cancer: From precancerous lesions to invasive ductal adenocarcinoma

Abstract: Pancreatic cancer is a lethal malignancy, whose precursor lesions are pancreatic intraepithelial neoplasm, intraductal papillary mucinous neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm. To better understand the biology of pancreatic cancer, it is fundamental to know its precursors and to study the mechanisms of carcinogenesis. Each of these precursors displays peculiar histological features, as well as specific molecular alterations. Starting from such pre-invasive lesions, this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer, with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

Abstract: Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

Sessile serrated adenoma detection rate is correlated with adenoma detection rate.

Abstract: AIM To investigated the association between adenoma detection rate (ADR) and sessile serrated ADR (SSADR) and significant predictors for sessile serrated adenomas (SSA) detection. METHODS This study is a retrospective, single-center analysis. Total colonoscopies performed by the gastroenterologists at the University of Tokyo Hospital between January and December 2014 were retrospectively identified. Polyps were classified as low-grade or high-grade adenoma, cancer, SSA, or SSA with cytological dysplasia, and the prevalence of each type of polyp was investigated. Predictors of adenoma and SSA detection were examined using logistic generalized estimating equation models. The association between ADR and SSADR for each gastroenterologist was investigated by calculating a correlation coefficient weighted by the number of each gastroenterologist's examination. RESULTS A total of 3691 colonoscopies performed by 35 gastroenterologists were assessed. Overall, 978 (26.5%) low- and 84 (2.2%) high-grade adenomas, 81 (2.2%) cancers, 66 (1.8%) SSAs, and 2 (0.1%) SSAs with cytological dysplasia were detected. Overall ADR was 29.5% (men 33.2%, women 23.8%) and overall SSADR was 1.8% (men 1.7%, women 2.1%). In addition, 672 low-grade adenomas (68.8% of all the detected low-grade adenomas), 58 (69.9%) high-grade adenomas, 29 (34.5%) cancers, 52 (78.8%) SSAs, and 2 (100%) SSAs with cytological dysplasia were found in the proximal colon. Adenoma detection was the only significant predictor of SSA detection (adjusted OR: 2.53, 95%CI: 1.53-4.20; P < 0.001). The correlation coefficient between ADR and SSADR weighted by the number of each gastroenterologist's examinations was 0.606 (P < 0.001). CONCLUSION Our results demonstrated that ADR is correlated to SSADR. In addition, patients with adenomas had a higher prevalence of SSAs than those without adenomas.

Robotic total meso-rectal excision for rectal cancer: A systematic review following the publication of the ROLARR trial

Abstract: Robotic total meso-rectal excision for rectal cancer: A systematic review following the publication of the ROLARR trial

Role of pre-transplant 18F-FDG PET/CT in predicting hepatocellular carcinoma recurrence after liver transplantation.

Abstract: The last two decades have seen a paradigm shift in the selection of patients with hepatocellular carcinoma (HCC) for liver transplantation. Microvascular invasion and differentiation have been the most significant factors affecting post-transplant recurrence; however, because of inherent disadvantages of pre-transplant biopsy, histological criteria never gained popularity. Recently, the selection criteria evolved from morphological to biological criteria, such as biomarkers and response to loco-regional therapy. With the introduction of multimodality imaging, combination of computed tomography with nuclear medicine imaging, particularly, 18F-fluorodeoxyglucose positron emission tomography fulfilled an unmet need and rapidly became a critical component of HCC management. This review article will focus on the use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the pre-transplant evaluation of HCC patients with special discussion on its ability to predict HCC recurrence after liver transplantation.

Targeted therapy or immunotherapy? Optimal treatment in hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality in the United States and the second leading cause of cancer mortality worldwide. Sorafenib is the only food and drug administration (FDA) approved as first line systemic treatment in HCC. Regorafenib and nivolumab are the only FDA approved second line treatment after progression on sorafenib. We will discuss all potential first and second line options in HCC. In addition, we also will explore sequencing treatment options in HCC, and examine biomarkers that can potentially predict benefits from treatments such as immune checkpoint inhibitor. This minireview summarizes potential treatments in HCC based on clinical trials that have been published in manuscript or abstract format from 1994-2018.

Shattering the castle walls: Anti-stromal therapy for pancreatic cancer.

Abstract: Despite the availability of potent chemotherapy regimens, such as 5-fluorouracil, folinic acid, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel plus gemcitabine, treatment outcomes in metastatic pancreatic cancer (PC) remain unsatisfactory. The presence of an abundant fibrous stroma in PC is considered a crucial factor for its unfavorable condition. Apparently, stroma acts as a physical barrier to restrict intratumoral cytotoxic drug penetration and creates a hypoxic environment that reduces the efficacy of radiotherapy. In addition, stroma plays a vital supportive role in the development and progression of PC, which has prompted researchers to assess the potential benefits of agents targeting several cellular (e.g., stellate cells) and acellular (e.g., hyaluronan) elements of the stroma. This study aims to briefly review the primary structural properties of PC stroma and its interaction with cancer cells and summarize the current status of anti-stromal therapies in the management of metastatic PC.

miR-122-5p as a novel biomarker for alpha-fetoprotein-producing gastric cancer

Abstract: AIM To investigate the clinical utility of alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC)-specific microRNA (miRNA) for monitoring and prognostic prediction of patients. METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC. We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility. We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples. Moreover, we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels, and also investigated the correlation of the selected miRNA expression levels and malignant potential. RESULTS Among the five miRNAs selected from the miRNA array results, the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients (P < 0.05). In tissue samples, miR-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa. Conversely, in the AFPGC tissue, miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the non-AFPGC tissue samples (P < 0.05). Plasma miR-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the non-AFPGC patients (P < 0.05) and were strongly correlated with plasma AFP levels (r = 0.7975, P < 0.0001). Moreover, the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients. In contrast, no correlation was found between miR-122-5p expression levels and liver metastasis in the non-AFPGC patients. CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.

Experience in the diagnosis and treatment of mesenteric lymphangioma in adults: A case report and review of literature

Abstract: Experience in the diagnosis and treatment of mesenteric lymphangioma in adults: A case report and review of literature

Inhibiting focal adhesion kinase: A potential target for enhancing therapeutic efficacy in colorectal cancer therapy.

Abstract: Inhibiting focal adhesion kinase: A potential target for enhancing therapeutic efficacy in colorectal cancer therapy

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Abstract: Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogenous metastasis from GC, such as vascular invasion, advanced age, differentiation, Borrmann type 1 or 2 and expansive growth. Recently, molecular mechanisms that contribute to metastatic site determination have been elucidated by advanced molecular biological techniques. Investigating the molecules that specifically participate in metastasis establishment in distinct secondary organs will lead to the development of novel biomarkers for patient stratification according to their metastatic risk and strategies for preventing and treating distinct metastases. We reviewed articles related to the molecular landscape of hematogenous metastasis from GC.

Laparoscopic and endoscopic cooperative surgery for gastric tumors: Perspective for actual practice and oncological benefits

Abstract: Laparoscopic and endoscopic cooperative surgery (LECS) is a surgical technique that combines laparoscopic partial gastrectomy and endoscopic submucosal dissection. LECS requires close collaboration between skilled laparoscopic surgeons and experienced endoscopists. For successful LECS, experience alone is not sufficient. Instead, familiarity with the characteristics of both laparoscopic surgery and endoscopic intervention is necessary to overcome various technical problems. LECS was developed mainly as a treatment for gastric submucosal tumors without epithelial lesions, including gastrointestinal stromal tumors (GISTs). Local gastric wall dissection without lymphadenectomy is adequate for the treatment of gastric GISTs. Compared with conventional simple wedge resection with a linear stapler, LECS can provide both optimal surgical margins and oncological benefit that result in functional preservation of the residual stomach. As technical characteristics, however, classic LECS involves intentional opening of the gastric wall, resulting in a risk of tumor dissemination with contamination by gastric juice. Therefore, several modified LECS techniques have been developed to avoid even subtle tumor exposure. Furthermore, LECS for early gastric cancer has been attempted according to the concept of sentinel lymph node dissection. LECS is a prospective treatment for GISTs and might become a future therapeutic option even for early gastric cancer. Interventional endoscopists and laparoscopic surgeons collaboratively explore curative resection. Simultaneous intraluminal approach with endoscopy allows surgeons to optimizes the resection area. LECS, not simple wedge resection, achieves minimally invasive treatment and allows for oncologically precise resection. We herein present detailed tips and pitfalls of LECS and discuss various technical considerations.

Small intestinal hemangioma: Endoscopic or surgical intervention? A case report and review of literature

Abstract: Small intestinal hemangioma: Endoscopic or surgical intervention? A case report and review of literature

Comparison between laparoscopic and open surgery for large gastrointestinal stromal tumors: A meta-analysis

Abstract: Comparison between laparoscopic and open surgery for large gastrointestinal stromal tumors: A meta-analysis

Upgraded role of autophagy in colorectal carcinomas.

Abstract: Autophagy is a basic catabolic process closely associated with degradation of cellular components. The role of autophagy in colorectal cancer (CRC) remains controversial. The mechanism of autophagy has been identified as protecting mechanism against tumorigenesis by isolation of damaged organelles or as cytoprotective provides energy in hypoxic regions of CRC tumors. Mutations in proto-oncogenes, such as RAS and BRAF, have been associated with autophagy initiation through signaling pathways of BRAF/MEK/ERK and PI3K/AKT/mTOR. A combination therapy of chemotherapeutic agents and autophagy inhibitors such as hydroxychloroquine or immunotherapy might represent a major step that could be evaluated as a putative novel therapeutic strategy in CRC patients.

Current strategies for malignant pedunculated colorectal polyps.

Abstract: Despite significant advances in imaging techniques, the incidence of colorectal cancer has been increasing in recent years, with many cases still being diagnosed in advanced stages. Early detection and accurate staging remain the main factors that lead to a decrease in the cost and invasiveness of the curative techniques, significantly improving the outcome. However, the diagnosis of pedunculated early colorectal malignancy remains a current challenge. Data on the management of pedunculated cancer precursors, apart from data on nonpolypoid lesions, are still limited. An adequate technique for complete resection, which provides the best long-term outcome, is mandatory for curative intent. In this context, a discussion regarding the diagnosis of malignancy of pedunculated polyps, separate from non-pedunculated variants, is necessary. The purpose of this review is to provide a critical review of the most recent literature reporting the different features of malignant pedunculated colorectal polyps, including diagnosis and management strategies.

Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms

Abstract: Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms

Stents combined with iodine-125 implantation to treat main portal vein tumor thrombus

Abstract: AIM To evaluate the efficacy of main portal vein stents combined with iodine-125 (125I) to treat main portal vein tumor thrombus. METHODS From January 1, 2010 to January 1, 2015, 111 patients were diagnosed with liver cancer combined with main portal vein tumor thrombus. They were non-randomly assigned to undergo treatment with transarterial chemoembolization (TACE)/transarterial embolization (TAE) + portal vein stents combined with 125I implantation (Group A) and TACE/TAE + portal vein stents only (Group B). After the operation, scheduled follow-up was performed at 6, 12 and 24 mo. The recorded information included clinical manifestations, survival rate, and stent restenosis rate. Kaplan-Meier curves, log-rank test and Cox regression were used for data analyses. RESULTS From January 1, 2010 to January 1, 2015, 54 and 57 patients were allocated to Groups A and B, respectively. The survival rates at 6, 12 and 24 mo were 85.2%, 42.6% and 22.2% in Group A and 50.9%, 10.5% and 0% in Group B. The differences were significant [log rank P < 0.05, hazard ratio (HR): 0.37, 95%CI: 0.24-0.56]. The rates of stent restenosis were 18.5%, 55.6% and 83.3% in Group A and 43.9%, 82.5% and 96.5% in Group B. The differences were significant (log rank P < 0.05, HR: 0.42, 95%CI: 0.27-0.63). Cox regression identified that treatment was the only factor affecting survival rate in this study. CONCLUSION Main portal vein stents combined with 125I can significantly improve survival rate and reduce the rate of stent restenosis.

HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer.

Abstract: Human epidermal growth factor receptor 2 (HER2)-inhibition is an important therapeutic strategy in HER2-amplified gastro-oesophageal cancer (GOC). A significant proportion of GOC patients display HER2 amplification, yet HER2 inhibition in these patients has not displayed the success seen in HER2 amplified breast cancer. Much of the current evidence surrounding HER2 has been obtained from studies in breast cancer, and we are only recently beginning to improve our understanding of HER2-amplified GOC. Whilst there are numerous licensed HER2 inhibitors in breast cancer, trastuzumab remains the only licensed HER2 inhibitor for HER2-amplified GOC. Clinical trials investigating lapatinib, trastuzumab emtansine, pertuzumab and MM-111 in GOC have demonstrated disappointing results and have not yet changed the treatment paradigm. Trastuzumab deruxtecan may hold promise and is currently being investigated in phase II trials. HER2 amplified GOC differs from breast cancer due to inherent differences in the HER2 amino-truncation and mutation rate, loss of HER2 expression, alterations in HER2 signalling pathways and differences in insulin-like growth factor-1 receptor and MET expression. Epigenetic alterations involving different microRNA profiles in GOC as compared to breast cancer and intrinsic differences in the immune environment are likely to play a role. The key to effective treatment of HER2 amplified GOC lies in understanding these mechanisms and tailoring HER2 inhibition for GOC patients in order to improve clinical outcomes.