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Gastrointestinal System Cancers

Digestive and Gastrointestinal System cancers.

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Anal Cancer
Appendix Cancers - including PMP
Colorectal (Bowel) Cancer
Esophageal Cancer
Extra-hepatic Bile Duct Cancer
Gallbladder Cancer
Gastrointestinal Carcinoid Tumours
Gastrointestinal Stromal Tumours
Liver Cancer
Pancreatic Cancer
Stomach (Gastric) Cancer
Small Bowel Cancer
Medical Terminology - Gastrointestinal
General Resources for GI Cancer
Latest Research Publications

General Resources for GI Cancer (9 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Yuan GL, Liang LZ, Zhang ZF, et al.
Hospitalization costs of treating colorectal cancer in China: A retrospective analysis.
Medicine (Baltimore). 2019; 98(33):e16718 [PubMed] Related Publications
BACKGROUND: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China.
METHODS: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank-sum tests (for 2 groups) and the Kruskal-Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer.
RESULTS: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ± 13.28 years; male: 59.46%; mean age: 61.80 ± 13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001).
CONCLUSION: The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.

Lovasik BP, Wang VL, Point du Jour KS, et al.
Visceral Kaposi Sarcoma Presenting as Small Bowel Intussusception: A Rare Presentation and Call to Action.
Am Surg. 2019; 85(7):778-780 [PubMed] Related Publications
Surgical emergencies related to visceral involvement of Kaposi sarcoma (KS) are rare complications of the disease. In this report, we describe a case of visceral KS causing small bowel intussusception in a young, previously undiagnosed human immunodeficiency virus (HIV)-positive patient. Southern surgeons should be particularly attentive to HIV/AIDS-related disease as a cause of surgical pathology, particularly in the southeast, and can play a significant advocacy role for improved access to HIV/AIDS diagnostic and treatment services.

Seawell J, Sciarretta JD, Pahlkotter M, et al.
The Understated Malignancy Potential of Nonoperative Acute Appendicitis.
Am Surg. 2019; 85(7):712-716 [PubMed] Related Publications
Cancer of the appendix is rare and is most commonly found incidentally on pathology after an appendectomy for uncomplicated appendicitis (UA). The medical management alternative with antibiotics and observation remains an ongoing debate. The purpose of our study was to develop modern epidemiological data for adult patients completing an appendectomy for UA secondary to an appendiceal neoplasm (AN). ACS-NSQIP database was queried (2005-2016) to identify patients completing an appendectomy. Cohorts of patients who were diagnosed with UA and an AN were included in the study. Relevant perioperative clinical and outcomes data were collected. Type of AN, surgical procedure, and mortality were analyzed. A total of 239,615 UA patients were identified, of whom 2,773 (1.2%) met the inclusion criteria of AN. Patients with AN were predominantly white (79.5%), with a mean age of 54.5 ± 15.9 years, and 54.6 per cent were females. AN pathology findings included malignant neoplasm (64.5%), malignant carcinoid (17.3%), benign carcinoid (9.3%), and benign neoplasm (8.8%). The overall reported incidence was 1.2 per cent and the mortality rate was 0.7 per cent. Our study emphasizes surgical intervention in adult UA maintains a 1 per cent incidence of AN, and treatment with antibiotics alone will presumably lead to a delay in surgical treatment and progression of disease.

Shuwen H, Miao D, Quan Q, et al.
Protective effect of the "food-microorganism-SCFAs" axis on colorectal cancer: from basic research to practical application.
J Cancer Res Clin Oncol. 2019; 145(9):2169-2197 [PubMed] Related Publications
BACKGROUND: Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC).
AIMS: This study aims to elucidate the "food-microorganism-SCFAs" axis and to provide guidance for prevention and intervention in CRC.
METHODS: The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening.
RESULTS: The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The "food-microorganism-SCFAs" axis was constructed by summarizing the pertinent literature.
CONCLUSIONS: This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.

Park YY, An CH, Oh ST, et al.
Expression of CD133 is associated with poor prognosis in stage II colorectal carcinoma.
Medicine (Baltimore). 2019; 98(32):e16709 [PubMed] Related Publications
CD133 is currently believed to be one of the best colorectal cancer stem cell markers. This study aimed to evaluate prognostic significance of CD133 expression in colorectal cancer patients.A total of 303 patients with stage I to III colorectal cancer who underwent curative surgical resection from 2003 to 2008 at a single institution were included. CD133 expression was evaluated using immunohistochemical staining, and clinicopathological data were retrospectively reviewed. The patients were dichotomized after scoring CD133 expression (0 to 2+: low CD133 expression vs 3+ to 4+: high CD133 expression) according to the extent of area of CD133 positive tumor cells (<50% vs ≥50%) and pattern of staining (membranous staining of the luminal surface and/or staining of cellular debris in the tumor glands and cytoplasm).The 5-year overall survival (OS) (61.9% vs 80.2%, P = .001) and disease-free survival (64.8% vs 75.8%, P = .026) were poorer in the high CD133 expression group than the low CD133 expression group. In the multivariate analysis for risk factors of OS in the whole population, higher nodal stage (N2 compared to N0: hazard ratio [HR] 3.141; 95% confidence interval [CI] 1.718-5.744, P < .001), perineural invasion (HR 2.262; 95% CI 1.347-3.798, P = .002) and high CD133 expression (HR 1.929; 95% CI 1.221-3.048, P = .005) were independent poor prognostic factors of OS. Subgroup analyses according to each TNM stage revealed that CD133 expression was associated with OS only within the stage II patients (HR 3.167 95% CI 1.221-8.216, P = .018). Furthermore, the stage II patients demonstrating the high CD133 expression showed survival benefit of adjuvant chemotherapy, regardless of high-risk feature positivity (HR 0.201 95% CI 0.054-0.750, P = .017).High CD133 expression is correlated with poor prognosis in colorectal cancer patients after radical resection. The CD133 expression may serve as a more potent and informative biomarker for prognosis than conventional high-risk features in the stage II colorectal cancer patients.

Wang R, Liu K, Chen XZ,
Associations between gastric cancer risk and virus infection other than Epstein-Barr virus: The protocol of a systematic review and meta-analysis based on epidemiological studies.
Medicine (Baltimore). 2019; 98(32):e16708 [PubMed] Related Publications
BACKGROUND: Gastric cancer is one of the infection associated malignancies. In addition to Helicobacter pylori and Epstein-Barr virus (EBV), other oncoviruses might play potential roles in the development of gastric cancer. Associations of oncoviruses other than EBV with gastric cancer risk are aimed to be comprehensively reviewed and assessed in this systematic review and meta-analysis, to identify any potentially causative oncovirus. It might be informative to identify or deny certain oncoviruses which are candidates of risk factor for gastric cancer. To our knowledge, there is no comprehensive review on oncoviruses other than EBV associated with gastric cancer risk. Positive findings might be helpful to suggest further mechanism investigation and high-risk subpopulation recommendation.
METHODS: PubMed database will be searched up to Dec 31, 2018. The studies, compared the positivity of any oncovirus other than EBV between cases with histologically proven gastric cancer and healthy or nonmalignant controls, are eligible. The detection of oncovirus either in tissue or blood is acceptable. Selection, quality assessment (Newcastle-Ottawa Scale), and data extraction of eligible studies will be performed by 2 independent reviewers. Pooled prevalence of any oncovirus will be combined by meta-analysis for rate. Pooled odds ratio between gastric cancer cases and controls will be estimated by meta-analysis. Heterogeneity and publication bias will be tested. In sensitivity analysis, the leave-one-out method and exclusion of low power studies will be applied where applicable.
RESULTS: This review was not submitted for any ethical approval due to the literature-based nature. The results will be published in a journal and presented at conferences for academic purposes.Registration number was CRD42015029703 in the PROSPERO International Prospective Register of Systematic Reviews.
CONCLUSIONS: To our knowledge, there is no comprehensive review on oncoviruses other than EBV associated with gastric cancer risk. Positive findings might be helpful to suggest further mechanism investigation and high-risk subpopulation recommendation.

Wen Y, Zhang ZJ, Huang YP, et al.
Application of the Ethyl Acetate Extract of
J Biomed Nanotechnol. 2019; 15(9):1867-1880 [PubMed] Related Publications
The present study aims to evaluate the effect of the ethyl acetate extract of

Yoon JK, Byun C, Jo KS, et al.
Clinicopathologic parameters associated with the FDG-avidity in staging of early gastric cancer using 18F-FDG PET.
Medicine (Baltimore). 2019; 98(31):e16690 [PubMed] Related Publications
This study investigated the clinicopathologic factors associated with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) uptake of early gastric cancer (EGC) and used them to design a clinical scoring method to predict FDG-avidity of EGC.Two hundred twenty-nine retrospectively enrolled patients underwent preoperative F-FDG positron emission tomography/computed tomography (PET/CT). Histologic information was obtained by gastrectomy (n = 195) or endoscopic mucosal dissection (n = 34). The association between clinicopathologic factors and F-FDG uptake by the primary tumor was determined. The results were used to develop a clinical scoring method.F-FDG uptake was detected in 49 (17.5%) patients. According to univariate analysis, location, gross type, World Health Organization classification, Lauren classification, size, depth of invasion, and lymphatic invasion were significant variables affecting F-FDG uptake (all P < .05). According to multivariate analysis, location (lower 3rd, P = .035), gross type (0-I, 0-IIa, P < .001), size (≥2.5 cm, P = .026), and depth of invasion (submucosa, P = .007) were significantly associated with FDG-avidity. A clinical scoring system, ranged from 0 to 4, was developed by giving one score to 4 independent variables. A cut-off value of 2.5 showed good prediction of FDG-avidity in EGCs, with a sensitivity and specificity of 65.0% and 85.2%, respectively.F-FDG uptake by EGC depends on location, gross type, size, and depth of invasion of the primary tumor. A clinical scoring system based on clinicopathologic variables can predict the FDG-avidity of primary tumors in patients with EGC.

Zhou Q, Chen YG, Xiao J, et al.
Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy: Study protocol for a randomized controlled trial.
Medicine (Baltimore). 2019; 98(31):e16680 [PubMed] Related Publications
BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy.
METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years.
DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy.
TRIAL REGISTRATION: NCT03616444.

Xie M, Rao W, Zhang P, et al.
Endoscopic full-thickness resection for a gastrointestinal stromal tumor in a liver transplant recipient: A case report.
Medicine (Baltimore). 2019; 98(31):e16669 [PubMed] Related Publications
RATIONALE: With the development of endoscopic technique and the improvement of available accessories, endoscopic therapy became to play an important role in the management of gastrointestinal submucosal tumors (SMTs).
PATIENTS CONCERNS: A gastric SMT which was suspected to be gastrointestinal stroma tumor (GIST) was diagnosed in a liver transplant recipient who received transplanted operation 11 months ago.
DIAGNOSIS: gastric SMT, post-liver transplantation INTERVENTIONS:: Endoscopic full-thickness resection (EFR) was preformed to remove the tumor. The operation time was 50 minutes and oral immunosuppressant drug was not interrupted in the postoperative period.
OUTCOMES: The clinical course was uneventful and slightly elevated liver enzyme was observed on the fourth day after operation. The pathological diagnosis was GIST with complete capsule.
LESSONS: Our successful experience showed that EFR is a feasible, safe and efficacious treatment for small (<2 cm) gastric GIST in liver transplant recipients, providing the advantages of little damage, short operative time, stable graft function, without compromising postoperative outcomes.

Yang F, Xu YL, Zhu RF
Helicobacter pylori infection and the risk of colorectal carcinoma: a systematic review and meta-analysis.
Minerva Med. 2019; 110(5):464-470 [PubMed] Related Publications
INTRODUCTION: Helicobacter pylori is a gram-negative bacterium that is colonized in the stomach. H. pylori infection can lead to a series of stomach diseases. However, the relationship between H. pylori infection and colorectal cancer is currently controversial. Therefore, we performed this meta-analysis to further understand the relationship between H. pylori infection and colorectal cancer.
EVIDENCE ACQUISITION: We conducted a comprehensive retrieval from electronic databases, included the PubMed, Medline, China National Knowledge Infrastructure (CNKI), and China Wanfang Data Knowledge Service Platform databases (Wanfang Databases) through May 1st, 2018. We used the search terms H. pylori and colorectal cancer or colorectal carcinoma and collected all relevant studies to explore the association between H. pylori infection and colorectal cancer.
EVIDENCE SYNTHESIS: Twenty-seven studies including 14357 cases were included. H. pylori infection was associated with an increased risk of colorectal cancer. A pooled odds ratio (OR) of 1.27 with a 95% CI of 1.17-1.37 (P<0.001) was calculated by using a fixed-effects model (I2=45.5%, P=0.006). The subgroup analysis revealed that H. pylori infection was associated with an increased risk of colorectal cancer in the subgroups of Western countries (OR=1.34, 95% CI: 1.14-1.57) (P<0.001), serological testing (OR=1.20, 95% CI: 1.08-1.34) (P=0.001), multiple methods of testing (OR=2.63, 95% CI: 1.09-6.31) (P=0.031), cross-sectional studies (OR=1.92, 95% CI: 1.17-3.16) (P=0.010) and case-control studies (OR 1.26, 95% CI: 1.16-1.36) (P<0.001).
CONCLUSIONS: The present meta-analysis provides evidence suggests that a positive association between H. pylori infection and the risk of colorectal cancer.

Hisaka T, Ishikawa H, Sakai H, et al.
Sinusoidal Obstruction Syndrome and Postoperative Complications Resulting from Preoperative Chemotherapy for Colorectal Cancer Liver Metastasis.
Anticancer Res. 2019; 39(8):4549-4554 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications.
PATIENTS AND METHODS: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab.
RESULTS: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups.
CONCLUSION: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

Fukuoka E, Yamashita K, Tanaka T, et al.
Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8
Anticancer Res. 2019; 39(8):4539-4548 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP).
PATIENTS AND METHODS: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8
RESULTS: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8
CONCLUSION: NAC-FP induced PD-L1 expression on ICs and CD8

Takimoto R, Kamigaki T, Okada S, et al.
Prognostic Factors for Colorectal Cancer Patients Treated With Combination of Immune-cell Therapy and First-line Chemotherapy: A Retrospective Study.
Anticancer Res. 2019; 39(8):4525-4532 [PubMed] Related Publications
BACKGROUND/AIM: In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cells vaccination (DCs), in combination with 1st-line chemotherapies in terms of the survival of patients with advanced colorectal cancer (CRC).
PATIENTS AND METHODS: A total of 198 patients who were diagnosed with advanced CRC and administered 1st-line chemotherapies were enrolled in this study. The correlation between overall survival (OS) and various clinical factors was examined by univariate and multivariate analyses.
RESULTS: Univariate analyses revealed that the prognosis was improved in CRC patients who received immune-cell therapy with PS 0, bevacizumab (BV), and capecitabine-including regimens (Cap). Finally, multivariate analysis demonstrated that PS=0, and the combination of immune-cell therapy and Cap provided a survival benefit in patients with advanced CRC.
CONCLUSION: The survival benefit could be potentially obtained with better PS by the combination of immune-cell therapy and Cap as a 1st-line setting in patients with CRC.

Tanaka Y, Ueno T, Yoshida N, et al.
Is Oral Mucositis Occurring During Chemotherapy for Esophageal Cancer Patients Correctly Judged? EPOC Observational Cohort Study.
Anticancer Res. 2019; 39(8):4441-4448 [PubMed] Related Publications
BACKGROUND/AIM: Oral mucositis (OM) is one of the frequent adverse events experienced by patients receiving chemotherapy. Most diagnoses of OM are based on complaints from patients. The aim of this study was to develop a tool to diagnose OM accurately.
MATERIALS AND METHODS: A central review system (CRS) was created to allow judgment when the patient background is completely unknown. The primary endpoint was the rate of grade 2 or higher OM, and the secondary endpoint was the difference in grade between each institution's clinician judgement and that of the CRS.
RESULTS: In total, 53 patients were registered from four institutions. CRS successfully detected grade 2 or higher OM in 16 (30.2%) of the 53 patients. The detection rate of all grades of OM was 41.5% (22 of 53 patients) by each institution's clinician judgement and 84.9% (45 of 53 patients) by CRS judgement (p<0.0001).
CONCLUSION: OM during chemotherapy may be underestimated.

Ashizawa N, Shimizu H, Sudo M, et al.
Clinical Significance of NADPH Oxidase 5 in Human Colon Cancer.
Anticancer Res. 2019; 39(8):4405-4410 [PubMed] Related Publications
BACKGROUND/AIM: Recent studies have reported the involvement of NADPH oxidases (NOXs) in tumor progression. However, the role of NOX5 in colon cancer is unclear. We examined the clinical significance of NOX5 expression in colon cancer.
PATIENTS AND METHODS: NOX5 expression was evaluated by immunohistochemistry in 119 patients with stage II or III colon cancer, and the relationship between NOX5 expression and clinicopathological data was analyzed.
RESULTS: Of all tissues, 39.5% were negative and 60.5% were positive for NOX5 expression. Positive expression was significantly associated with undifferentiated histology (p=0.037) and lymph node metastasis (p=0.023). The 5-year progression-free survival rate of NOX5-positive patients was significantly worse than that of NOX5-negative patients (p=0.046). The rates of local recurrence observed in NOX5-positive patients were higher than that in NOX5-negative patients.
CONCLUSION: NOX5 expression may be related to poor prognostic factors and could be useful as a prognostic biomarker.

Ohsawa M, Hamai Y, Ibuki Y, et al.
Long-term Esophageal Cancer Survivor Treated by Bypass for Esophagobronchial Fistula After Chemoradiotherapy: A Case Report.
Anticancer Res. 2019; 39(8):4399-4403 [PubMed] Related Publications
BACKGROUND: An esophagorespiratory fistula (ERF) is a fatal complication for patients with tracheobronchial invasion by esophageal cancer. We report the case of a long-term esophageal cancer survivor treated by esophageal bypass operation for ERF after chemoradiotherapy (CRT).
CASE REPORT: A 44-year-old man was treated with definitive CRT (i.e. 66 Gy radiotherapy, chemotherapy with cisplatin, and 5-fluorouracil) for unresectable locally advanced esophageal cancer with massive invasion of the left main bronchus. Although a complete clinical response was obtained, the patient developed pneumonia due to an ERF. Esophageal bypass operation was performed for symptomatic relief. The patient's symptoms improved and oral ingestion became possible. No recurrence has been seen for 12 years.
CONCLUSION: Esophageal bypass surgery can help in relieving symptoms and might be associated with long-term survival for esophageal cancer patients with ERF after good response to CRT. Thus, bypass surgery is a useful option in the treatment for esophageal cancer with ERF.

Nayeri M, Iskander O, Tabchouri N, et al.
Low Tie Compared to High Tie Vascular Ligation of the Inferior Mesenteric Artery in Rectal Cancer Surgery Decreases Postoperative Complications Without Affecting Overall Survival.
Anticancer Res. 2019; 39(8):4363-4370 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to determine the clinical impact of low tie ligation (LT) of the inferior mesenteric artery (IMA) below the left colic artery versus high tie ligation (HT) at the origin of the IMA in patients undergoing rectal cancer surgery.
PATIENTS AND METHODS: Between January 2005 and December 2017, all consecutive patients who underwent rectal resection for non-metastatic cancer were retrospectively included. Patients who had LT were compared to those who had HT.
RESULTS: Overall, 200 patients were identified (101 HT and 99 LT). Postoperative 30-day mortality rate was nil in both groups. There were significantly higher severe postoperative complications in HT versus LT patients (Clavien-Dindo III-IV) (18.8% vs. 9.1%, p=0.048). Median follow-up was 38.5 months and overall survival at 5 years was 91.5% and there was no difference between the two groups (90.1% vs. 92.9%; HT vs. LT p=0.640).
CONCLUSION: LT ligation of IMA significantly decreased the severe postoperative complication rate without affecting recurrence-free or overall survival.

Matsuda A, Yamada T, Matsumoto S, et al.
Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival After TAS-102 Treatment of Patients With Metastatic Colorectal Cancer.
Anticancer Res. 2019; 39(8):4343-4350 [PubMed] Related Publications
BACKGROUND/AIM: TAS-102 is recommended as salvage-line therapy for metastatic colorectal cancer (mCRC), but practical predictors for its efficacy are lacking.
PATIENTS AND METHODS: In a single-institutional retrospective study of 33 patients treated with TAS-102, we investigated the predictive value of the pretreatment neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios for progression-free (PFS) and overall (OS) survival. Predictive ability using cut-offs of the median value (3.14) and 5 for NLR were compared.
RESULTS: In univariate analysis, Eastern Cooperative Oncology Group performance score, NLR, and PLR were negatively significantly associated with PFS and OS. The number of treatment lines was negatively associated with PFS. The NLR cut-off of 5 was superior to the median value. Multivariate analyses showed a significant prognostic impact for NLR at cut-off 5 (hazard ratio(HR)=6.26, p=0.02 for PFS; HR=6.97, p=0.07 for OS).
CONCLUSION: The pretreatment NLR is a prognostic biomarker for patients with mCRC who receive TAS-102 treatment.

Yamamoto K, Hirao M, Nishikawa K, et al.
Sarcopenia Is Associated With Impaired Overall Survival After Gastrectomy for Elderly Gastric Cancer.
Anticancer Res. 2019; 39(8):4297-4303 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to evaluate the impact of sarcopenia diagnosed by the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm on long-term outcome after gastrectomy.
PATIENTS AND METHODS: A total of 90 elderly gastric cancer patients without distant metastasis aged 65 years or older who underwent gastrectomy at the Osaka National Hospital between July 2012 and January 2015 were included in the current analysis.
RESULTS: The sarcopenic group (n=19) had a poorer overall survival (OS) (p<0.0001) compared to the non-sarcopenic group (n=79). OS after recurrence was also worse in the sarcopenic group. Multivariate analysis indicated that sarcopenia was an independent risk factor for worse OS after gastrectomy (hazard ratio(HR)=2.92; 95% confidence interval(CI)=1.15-7.75; p=0.025), along with N stage ≥2, age ≥75 years, and presence of severe postoperative complications.
CONCLUSION: Sarcopenia is a potential target for preoperative intervention in elderly gastric cancer patients to improve prognosis after gastrectomy. (UMIN-CTR: R000041532).

Sdralis EK, Davakis S, Syllaios A, et al.
Prognostic Value of Subcarinal Lymph Nodes in Minimally Invasive Esophagectomy for Cancer.
Anticancer Res. 2019; 39(8):4291-4295 [PubMed] Related Publications
BACKGROUND/AIM: Surgical resection for esophageal cancer has remained the gold-standard therapy provided worldwide. Subcarinal lymph-nodes are classified as peri-esophageal nodes and their dissection may be performed during a 2- or 3-stage esophagectomy. The necessity and prognostic value of subcarinal lymphadenectomy is still debatable. The purpose of this study was to investigate the rate of invaded subcarinal lymph-nodes out of the total lymph-nodes resected. Detection of invaded nodes was correlated with clinical staging and tumor differentiation.
PATIENTS AND METHODS: This is a retrospective analysis of consecutive esophagectomies for cancer, performed in a UK tertiary center. The study was conducted over a 3-year period.
RESULTS: The rate of subcarinal lymph-node invasion was extremely low according to the results of our analysis.
CONCLUSION: Lymphadenectomy is not devoid of clinical impact on patients and therefore, the decision should actually be the outcome of a dynamic balance between complications and survival benefit.

Jingu K, Takahashi N, Murakami Y, et al.
Is Concurrent Chemotherapy With Radiotherapy for Esophageal Cancer Beneficial in Patients Aged 80 Years or Older?
Anticancer Res. 2019; 39(8):4279-4283 [PubMed] Related Publications
BACKGROUND/AIM: To determine whether concurrent chemotherapy with radiotherapy should be performed in elderly patients with esophageal cancer.
PATIENTS AND METHODS: A total of 185 patients aged 80 years or older who were treated with definitive radiotherapy alone or combined with chemoradiotherapy for esophageal cancer at seven institutions were enrolled. In order to compare survival rates of patients treated with chemoradiotherapy with those of patients treated with radiotherapy alone, propensity score matching was performed to homogenize the two populations.
RESULTS: For the whole patient cohort, the 3-year overall survival (OS) rate was 52.6% and the median survival was 42.5 months. After propensity score matching, the 3-year OS rate for the chemoradiotherapy group was not significantly better than that for the group treated with radiotherapy alone (53.7% vs. 59.9%, p=0.876).
CONCLUSION: Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older did not have significant OS benefit over radiotherapy alone.

Rubio CA, Schmidt PT
Dissecting the Microscopic Anatomy of Colon Crypts in Non-dysplastic Sessile Serrated Polyps.
Anticancer Res. 2019; 39(8):4259-4263 [PubMed] Related Publications
BACKGROUND/AIM: Sessile serrated polyps (SSP) are characterized by crypts with corrupted shapes (CCS).
MATERIALS AND METHODS: The number of CCS and the lateral size of 60 non-dysplastic SSP (NDSSP) were investigated.
RESULTS: Out of 60 NDSSP, 34 were small (≤9 mm) and 26, large (≥10 mm). In total, 1,101 CCS were recorded: 547 CCS were connected to the lumen (CCSL) and 554 CCS were not (CCSNL). The lateral size of NDSSP, the total number of CCS and the number of CCSNL were significantly higher in large NDSSP than in small NDSSP. Conversely, the number of CCS connected to the lumen/mm (CCSL/mm) and of crypts with normal shapes connected to the lumen/mm (CCSNL/mm), were significantly lower in large NDSSP than in small NDSSP.
CONCLUSION: The lateral expansion of large NDSSP ensues via increased numbers of CCS at the expense of a decreased number of both CCSL/mm and CCSNL/mm.

Matsumoto A, Yuda M, Tanaka Y, et al.
Efficacy of Percutaneous Endoscopic Gastrostomy for Patients With Esophageal Cancer During Preoperative Therapy.
Anticancer Res. 2019; 39(8):4243-4248 [PubMed] Related Publications
BACKGROUND/AIM: This study aimed to clarify the benefits and disadvantages of percutaneous endoscopic gastrostomy (PEG) for patients with esophageal cancer (EC) during preoperative therapy.
MATERIALS AND METHODS: We retrospectively reviewed 92 patients who underwent esophagectomy for EC after preoperative therapy. Patients were divided into the PEG group (n=14) and the control group (n=78) and compared regarding patient characteristics, nutritional status, operative variables, and postoperative complications.
RESULTS: In the PEG group first nutritional status and tumor stage were significantly worse, but changes of nutritional status from first visit to operation were significantly better. According to the intraoperative thermal imaging, there was no patient with blood flow disturbance in the gastric conduit due to PEG. Short-term surgical outcomes did not significantly differ.
CONCLUSION: PEG has less adverse effects on gastric tube production in esophagectomy and may be considered in highly selective patients during preoperative therapy.

Ito Y, Kobuchi S, Takesada W, Takahashi C
Assessment of Oxaliplatin-induced Chronic Neuropathy and Anticancer Efficacy Through Pharmacokinetic and Toxicodynamic Evaluation of a Rat Model of Colorectal Cancer.
Anticancer Res. 2019; 39(8):4207-4213 [PubMed] Related Publications
BACKGROUND/AIM: Oxaliplatin-induced chronic neuropathy is a prominent factor for dose reduction and not completing all cycles of chemotherapy for patients with colorectal cancer (CRC). The aim of the study was to investigate the pharmacokinetics and toxicodynamics of oxaliplatin-induced chronic neuropathy in CRC rats to ensure effective management.
MATERIALS AND METHODS: A rat model of CRC was developed using 1,2-Dimethylhydrazine and dextran sulfate. Oxaliplatin (L-OHP) was administered intravenously to CRC rats every week. The pharmacokinetic profiles and tumor distribution of L-OHP and chronic neuropathies were investigated for over four weeks.
RESULTS: The mean values of the area under the concentration-time curve for L-OHP showed a dose-dependent increase. Chronic neuropathy occurred from Day 14 in the 8 mg/kg group and Day 19 in the 3 and 5 mg/kg groups.
CONCLUSION: These results provide preliminary information for the development of a pharmacokinetic and toxicodynamic model of L-OHP for CRC therapy cycles.

Ichikawa H, Nishie H, Yano S, et al.
Antitumor Effect of a Novel Photodynamic Therapy With Acetylated Glucose-conjugated Chlorin for Gastrointestinal Cancers.
Anticancer Res. 2019; 39(8):4199-4206 [PubMed] Related Publications
BACKGROUND/AIM: We previously synthesized a glucose-conjugated chlorin compound e6 (G-chlorin e6), and reported that it has very strong antitumor effects. The aim of the present study was to synthesize acetylated glucose-conjugated chlorin (AcN003HP) and evaluate its antitumor effect and excretion.
MATERIALS AND METHODS: To evaluate the antitumor effect of AcN003HP, its IC
RESULTS: AcN003HP showed stronger antitumor effects and accumulation into cancer cells compared to talaporfin sodium, a conventional photosensitizer. AcN003HP was localized in the endoplasmic reticulum. In a xenograft tumor mouse model, AcN003HP showed longer excretion time from the body than G-chlorin e6, and photodynamic therapy using AcN003HP showed very strong antitumor effects.
CONCLUSION: The safety, improved controllability, and robust antitumor effects suggest AcN003HP as a good next-generation photosensitizer.

Nakazawa N, Ogata K, Yokobori T, et al.
Low IRBIT Levels Are Associated With Chemo-resistance in Gastric Cancer Patients.
Anticancer Res. 2019; 39(8):4111-4116 [PubMed] Related Publications
BACKGROUND/AIM: We investigated whether the expression of inositol 1, 4, 5-trisphosphate receptor-binding protein released with inositol 1, 4, 5-trisphosphate (IRBIT) in clinical gastric cancer (GC) patients could predict the therapeutic response to postoperative adjuvant chemotherapy.
MATERIALS AND METHODS: Immunohistochemistry was used to investigate IRBIT expression in 115 GC patients. To clarify whether IRBIT had a relationship with the therapeutic effects of chemotherapy, we compared two groups - 62 patients treated with postoperative adjuvant chemotherapy and 53 patients treated with postoperative adjuvant chemotherapy.
RESULTS: Regarding the postoperative adjuvant chemotherapy-free group, we did not find any statistically significant correlation between clinicopathological features and recurrence regardless of the expression of IRBIT. In contrast, in the group receiving postoperative adjuvant chemotherapy, a significant association was found between IRBIT expression and both overall and disease-free survival.
CONCLUSION: IRBIT may be used as a useful predictive marker for chemotherapy.

Yoon SN, Park JH, Lwin TM, et al.
Tumor-sealing Surgical Orthotopic Implantation of Human Colon Cancer in Nude Mice Induces Clinically-relevant Metastases Without Early Peritoneal Carcinomatosis.
Anticancer Res. 2019; 39(8):4065-4071 [PubMed] Related Publications
BACKGROUND: Surgical orthotopic implantation of human colon cancer tissue to the ceca of mice has been used to mimic behavior of cancer in human patients for the development of precision cancer medicine. However, with the current method of serosal surface implantation (SSI) of pieces of human colon cancer tissue, cancer cells are exposed to the peritoneum, which can artificially increase the rate of peritoneal carcinomatosis (PC) during the disease course. The objective of the present study was to introduce a tumor-sealing method (TSM) and compare it with SSI for the ability to produce clinically-relevant metastases without artificial PC.
MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm
RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001).
CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.

Virgilio E, Giarnieri E, Montagnini M, et al.
Advances in Intraluminal Exfoliative Cytology of Gastric Cancer: Oncologic Implication of the Sixth Metastatic Route (Metastasis VI).
Anticancer Res. 2019; 39(8):4019-4022 [PubMed] Related Publications
Historically, analysis of intragastric exfoliative cytology (IEC) of gastric cancer (GC) was used with a diagnostic intent only. With the successful advent of endoscopic biopsy, the rate of detection of GC has improved worldwide and, as a consequence, IEC has been progressively abandoned. Today, however, there is a renewed interest in this field of research, as witnessed by several pertinent publications. As discussed in this review, in fact, currently the importance of analyzing IEC in patients with early and advanced GC seems to reside in its clinicopathological and prognostic significance. In fact, compared to non-sloughing tumors, GC exhibiting intragastric exfoliation was recently associated with an aggressive tumor phenotype (characterized by deeper infiltration of the gastric wall, lymph nodal or distant metastases, angiolymphatic and perineural invasion) and poorer prognosis. Adoption of IEC examination in routine practice might help identify patients at higher risk of developing local recurrence and peritoneal metastasis from early and advanced GC, optimizing their treatment and improving quality of life and life expectancy.

Kang BW, Baek DW, Kang H, et al.
Novel Therapeutic Approaches for Epstein-Barr Virus Associated Gastric Cancer.
Anticancer Res. 2019; 39(8):4003-4010 [PubMed] Related Publications
Epstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is classified as one of four GC subtypes by comprehensive molecular characterization. Though the mechanism of tumorigenesis by EBV infection has not yet been fully clarified, EBV infection might contribute to the malignant transformation of GC cells by involving various cellular processes and signaling pathways. EBVaGC has shown the following distinct characteristics in contrast to other subtypes: extreme DNA hypermethylation, recurrent phosphatidylinositol 4,5-biphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) mutations, overexpression of programmed cell death ligand 1/2 (PD-L1/2), and occasional immune cell signaling activation. Therefore, using these molecular features as guides, targeted agents need to be evaluated in clinical trials for EBVaGC. Accordingly, this review uses the best available evidence to focus on novel therapeutic approaches using the distinct pathologic characteristics of EBVaGC patients.

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