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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).

Dashti SG, Chau R, Ouakrim DA, et al.
Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome.
JAMA. 2015; 314(1):61-71 [PubMed] Related Publications
IMPORTANCE: Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).
OBJECTIVE: To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.
EXPOSURES: Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use.
MAIN OUTCOMES AND MEASURES: Self-reported diagnosis of endometrial cancer.
RESULTS: Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Endometrial cancer was diagnosed in 11% (n = 70) of women with age at menarche greater than or equal to 13 years compared with 12.6% (n = 57) of women with age at menarche less than 13 years (incidence rate per 100 person-years, 0.27 vs 0.31; rate difference, -0.04 [95% CI, -0.15 to 0.05]; hazard ratio per year, 0.85 [95% CI, 0.73 to 0.99]; P = .04). Endometrial cancer was diagnosed in 10.8% (n = 88) of parous women compared with 14.4% (n = 40) of nulliparous women (incidence rate per 100 person-years, 0.25 vs 0.43; rate difference, -0.18 [95% CI, -0.32 to -0.04]; hazard ratio, 0.21 [95% CI, 0.10 to 0.42]; P < .001). Endometrial cancer was diagnosed in 8.7% (n = 70) of women who used hormonal contraceptives greater than or equal to 1 year compared with 19.2% (n = 57) of women who used contraceptives less than 1 year (incidence rate per 100 person-years, 0.22 vs 0.45; rate difference, -0.23 [95% CI, -0.36 to -0.11]; hazard ratio, 0.39 [95% CI, 0.23 to 0.64]; P < .001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use.
CONCLUSIONS AND RELEVANCE: For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.

Meester RG, Doubeni CA, Lansdorp-Vogelaar I, et al.
Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model.
JAMA. 2015; 313(23):2349-58 [PubMed] Related Publications
IMPORTANCE: Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs.
OBJECTIVE: To estimate the lifetime benefits, complications, and costs of an initial colonoscopy screening program at different levels of adenoma detection.
DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling with data from a community-based health care system on ADR variation and cancer risk among 57,588 patients examined by 136 physicians from 1998 through 2010.
EXPOSURES: Using modeling, no screening was compared with screening initiation with colonoscopy according to ADR quintiles (averages 15.3%, quintile 1; 21.3%, quintile 2; 25.6%, quintile 3; 30.9%, quintile 4; and 38.7%, quintile 5) at ages 50, 60, and 70 years with appropriate surveillance of patients with adenoma.
MAIN OUTCOMES AND MEASURES: Estimated lifetime colorectal cancer incidence and mortality, number of colonoscopies, complications, and costs per 1000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis.
RESULTS: In simulation modeling, among unscreened patients the lifetime risk of colorectal cancer incidence was 34.2 per 1000 (95% CI, 25.9-43.6) and risk of mortality was 13.4 per 1000 (95% CI, 10.0-17.6). Among screened patients, simulated lifetime incidence decreased with lower to higher ADRs (26.6; 95% CI, 20.0-34.3 for quintile 1 vs 12.5; 95% CI, 9.3-16.5 for quintile 5) as did mortality (5.7; 95% CI, 4.2-7.7 for quintile 1 vs 2.3; 95% CI, 1.7-3.1 for quintile 5). Compared with quintile 1, simulated lifetime incidence was on average 11.4% (95% CI, 10.3%-11.9%) lower for every 5 percentage-point increase of ADRs and for mortality, 12.8% (95% CI, 11.1%-13.7%) lower. Complications increased from 6.0 (95% CI, 4.0-8.5) of 2777 colonoscopies (95% CI, 2626-2943) in quintile 1 to 8.9 (95% CI, 6.1-12.0) complications of 3376 (95% CI, 3081-3681) colonoscopies in quintile 5. Estimated net screening costs were lower from quintile 1 (US $2.1 million, 95% CI, $1.8-$2.4 million) to quintile 5 (US $1.8 million, 95% CI, $1.3-$2.3 million) due to averted cancer treatment costs. Results were stable across sensitivity analyses.
CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study, higher adenoma detection rates in screening colonoscopy were associated with lower lifetime risks of colorectal cancer and colorectal cancer mortality without being associated with higher overall costs. Future research is needed to assess whether increasing adenoma detection would be associated with improved patient outcomes.

Mastalier B, Deaconescu V, Elaiah W, et al.
Multiple Intestinal Lymphoma.
Rom J Intern Med. 2015 Jan-Mar; 53(1):73-8 [PubMed] Related Publications
Gastrointestinal tract is the most common location for extralymphonodular lymphomas. The small intestine is affected only in 9% of the cases. Intestinal lymphoma may have single or multiple location. This paper describes a case of multiple location in the small intestine of a non-Hodgkin B-cell in a 53 years old patient, who was initially diagnosed with bilateral pneumonia with pleurisy with E. coli, steeper on the right side, but the persistence of symptoms as fever, malaise, despite appropriate treatment, required further investigation. The CT exam observed fluid collection in the hypogastrium around a digestive loop. The patient underwent surgery, the intraoperative foundings being: a large mesenteric tumor - 5 cm in diameter, a terminal ileal mesenteric tumor, a mesenteric tumor - 6 cm in diameter, omentum with nodular formations, a tumor - 3.3/2.5.1 cm in the abdominal wall, pseudotumoral appendix. Segmental. enterectomy with entero-enterostomy, excision of mesenteric tumors, appendectomy and omentectomy were performed. Pathological diagnosis was non-Hodgkin marginal zone B-cell MALT type lymphoma of the small intestine with extension to the appendix, meso, omentum and abdominal wall. Postoperatively, the patient received chemotherapy for remission.

Shariff U, Seretis C, Youssef H
Management of colorectal cancer patients at high risk of peritoneal metastases.
J BUON. 2015; 20 Suppl 1:S71-9 [PubMed] Related Publications
PURPOSE: Colorectal cancer (CRC) has potential to spread within the peritoneal cavity, and this transcoelomic dissemination is termed "peritoneal metastases" (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical strategy to treat selected CRC patients with PM. Studies suggest that identification of CRC patients at high risk of PM may lead to earlier treatment strategies and improve survival in this subset of patients. The aim of this article was to summarise the current evidence regarding CRC patients at high risk of PM.
METHODS: A retrospective review of articles on CRC patients with high risk of PM published up to December 2014 in PubMed, Medline, Embase, and Ovid search engines was conducted. The following combination of search terms were used: "intraperitoneal chemotherapy", "HIPEC", "colorectal cancer", "peritoneal carcinomatosis", "peritoneal metastases", "high risk", "peritoneal recurrence".
RESULTS: Although opinions differ, CRC patients identified as "high risk" of PM included: limited, synchronous PM completely resected with the primary tumor, ovarian metastases (synchronous or metachronous) and spontaneous or iatrogenic perforation of the bowel by the primary tumor. Aggressive early treatment strategies currently used are: CRS and HIPEC for high-risk primary tumors and second-look CRS and HIPEC often following systematic chemotherapy for the primary resection. Positive results have been shown with both approaches in a number of studies. With CRS/HIPEC for the primary tumor, the overall survival in the two groups (25 patients treated with CRS/HIPEC vs 50 treated with conventional surgery) was significantly improved (p<0.03), as was disease-free survival (p<0.04). For second look surgery, in 29 patients treated with CRS and HIPEC, this resulted in 14% morbidity and 0% mortality and a 2-year disease-free survival rate in excess of 50%.
CONCLUSIONS: We are progressively moving to an era of individualised treatment strategies. The management of CRC patients with high risk of PM is ever evolving, with early detection and early treatment strategies showing promising results. The optimal timing of early surgery remains unclear and requires further evaluation. Should current and future randomized trials demonstrate long-term survival benefit, we may potentially see a change in treatment paradigm from current conventional surgery to a more aggressive, early radical approach as the standard of care.

Erdling A, Johansson A
Core temperature--the intraoperative difference between esophageal versus nasopharyngeal temperatures and the impact of prewarming, age, and weight: a randomized clinical trial.
AANA J. 2015; 83(2):99-105 [PubMed] Related Publications
Unplanned perioperative hypothermia is a well-known complication to anesthesia. This study compares esophageal and nasopharyngeal temperature measured in the same patient for a period of 210 minutes of anesthesia. Forty-three patients undergoing colorectal surgery were randomly assigned in 2 groups, with or without a prewarming period (group A = prewarming [n = 21] or group B = no prewarming [n = 22]). Demographics were similar in both groups. Mean temperatures at 210 minutes were statistically different between the groups at both sites of measurement. Esophageal temperature in group A was 36.5 ± 0.6 vs 35.8 ± 0.7 in group B (P = .001), and nasopharyngeal temperature was 36.7 ± 0.6 and 36.0 ± 0.6 in group A and group B, respectively (P = .002). A negative correlation was found between esophageal temperature and age (r2 = -.381, P < .012). Esophageal temperature was different with respect to BMI below or above 25. The temperatures were 35.81 ± 0.66 in the lower BMI group vs 36.46 ± 0.59 (P < .001). These results demonstrate a difference between the 2 measurement techniques and that prewarming, age and BMI have an impact on measured temperatures.

Li B, Liu HY, Guo SH, et al.
The postoperative clinical outcomes and safety of early enteral nutrition in operated gastric cancer patients.
J BUON. 2015 Mar-Apr; 20(2):468-72 [PubMed] Related Publications
PURPOSE: This study investigated the impact of early enteral nutrition (EEN) on the clinical outcomes of gastric cancer patients after radical gastrectomy.
METHODS: Four hundred gastric cancer patients undergoing radical gastrectomy of any extend with D2 nodal dissection were randomly divided into an experimental and a control group with 200 cases in each group. Patients in the control group received postoperative parenteral nutrition (PN), while patients in the experimental group received postoperative EEN. After treatment, the clinical outcomes, postoperative immune function, and nutritional status of the two groups were evaluated.
RESULTS: The postoperative fever time, intestinal function recovery time, anal exhaust time, and the length of hospital stay for patients in the experimental group were significantly shorter than those of the control group. We did not find significant differences in anastomotic leak, postoperative ileus and regurgitation between the two groups. The activities of multiple immune cell types, including CD3⁺, CD4⁺, CD4⁺/CD8⁺, and natural killer (NK) cells, were significantly lower in both groups on postoperative day 1 when compared with the preoperative levels (p<0.05). The level of CD8⁺ was not significantly different between the two groups (p>0.05). After treatment, levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells in the experimental group patients were 35.6 ± 4.2, 42.2 ± 3.0, 1.7 ± 0.3, and 27.3 ± 5.3%, respectively, on postoperative day 7, which were similar to the preoperative levels. The immune cell levels from the control group patients remained significantly lower when compared with preoperative values; in addition, these values were also significantly lower when compared with the EEN patients (p<0.05) CONCLUSION: For gastric cancer patients undergoing radical gastrectomy, the clinical outcome, immune function and nutritional status after EEN were significantly improved. These data suggest the widespread use of EEN in clinical practice.

Vedat Bayoglu I, Yildiz I, Varol U, et al.
Comparison of first-line bevacizumab in combination with mFOLFOX6 or XELOX in metastatic colorectal cancer.
J BUON. 2015 Mar-Apr; 20(2):460-7 [PubMed] Related Publications
PURPOSE: Currently, there are several oxaliplatin combination regimens for first-line therapy of metastatic colorectal cancer (mCRC). In this study, we compared the survival outcomes of mCRC patients treated with bevacizumab in combination with either modified 5-FU/FA/oxaliplatin (mFOL- FOX6) or capecitabine/oxaliplatin (XELOX).
METHODS: We designed a two-arm retrospective study of mCRC patients with adenocarcinoma of the colon or rectum who were treated with bevacizumab and either mFOLFOX6 or XELOX and who had complete clinical and treatment data. We analysed their therapeutic responses, adverse events, progression-free survival (PFS), and overall survival (OS), and then determined whether there were any statistically significant differences.
RESULTS: A total of 131 patients (85 male; 65% and 46 female; 35%) were evaluated. Fifty-seven patients (43.5%) were treated with bevacizumab and mFOLFOX6 and 74 (56.5%) with bevacizumab and XELOX. The median PFS was 9.1 months (95% CI, 4.9-13.1) and 10 months (95% CI, 4.2-15.9) in the mFOLFOX6 and XELOX arms, respectively (p=0.610). The median OS was 29 months (95% CI, 21.6- 34.3) and 27.5 months (95% CI 20-38) in the mFOLFOX6 and XELOX arms (p=0.812), respectively. The most common reason for treatment withdrawal was disease progression (102 patients; 91%) and the most common grade 3-4 toxicity was neuropathy (≤14%).
CONCLUSION: Our results show that XELOX is a safe and effective alternative to mFOLFOX6 when combined with bevacizumab as first-line treatment for mCRC patients.

Teker F, Demirag G, Erdem D, et al.
Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies.
J BUON. 2015 Mar-Apr; 20(2):443-51 [PubMed] Related Publications
PURPOSE: Colorectal cancer (CRC) survivors are currently living longer due to better therapies but they also need to maintain their quality of life (QoL). QoL is increasingly being used as primary outcome measure in clinical studies. This study was designed to gain knowledge about QoL during chemotherapy across different lines and different regimens.
METHODS: The study comprised 101 CRC out patients receiving chemotherapy who completed the EORTC QLQ-C30 questionnaire. The Shapiro-Wilk, Kruskal-Wallis, and Mann-Whitney U tests were used for statistical analyses.
RESULTS: The demographics of the patients were evaluated for QoL. Prior surgery, prior radiotherapy, working status, stage, comorbidity and sex had no effect on global health status in CRC patients, although some other demographics such as education, monthly income, age and type of chemotherapy regimen did have an effect on global health status. Role functioning was worse in older than in younger ones (p<0.05). Adjuvant chemotherapy did not affect the QoL scores negatively but palliative chemotherapy negatively affected the cognitive function, appetite loss and nausea/vomiting scores (p<0.05). According to chemotherapy regimen, the best QoL was observed with adjuvant FUFA regimen. In the palliative setting FOLFOX/Bevacizumab was associated with the best QoL scores whereas FOLFIRI/Cetuximab were associated with the worst QoL scores.
CONCLUSIONS: Palliative chemotherapy maintained QoL irrespective of the chemotherapy line in metastatic CRC (mCRC) patients. Some demographics affect QoL and different chemotherapy regimens showed different QoL scores.

Chen H, Wu Q
Expression of GW112 and GRIM-19 in colorectal cancer tissues.
J BUON. 2015 Mar-Apr; 20(2):438-42 [PubMed] Related Publications
PURPOSE: To investigate the expression of GW112 and GRIM-19 in colorectal cancer tissues.
METHODS: Immunohistochemistry and semi-quantitative PCR were used to simultaneously detect the levels of expression of GW112 and GRIM-19 in colorectal cancer tissues and normal colorectal tissues in 39 cases.
RESULTS: Expression of GW112 protein and mRNA were significantly higher in colorectal cancer tissues than in normal tissues (p<0.05). Expression of GRIM-19 protein and mRNA were significantly lower in colorectal cancer tissues than in normal tissues (p<0.05). GW112 gene mRNA copy number(GAPDH gene mRNA copy number were 0.53 ± 0.21 and 1.81 ± 0.65 in normal colorectal tissues and colorectal cancer tissues respectively, and GRIM-19 gene mRNA copy number/GAPDH gene mRNA copy number were 1.15 ± 0.29 and 1.74 ± 0.0.44 in colorectal cancer tissues and normal colorectal tissues, respectively. Expression of GW112 gene mRNA was significantly higher in colorectal cancer tissues than in normal tissues (p<0.05), and expression of GRIM- 19 gene mRNA was significantly lower in colorectal cancer tissues than in normal tissues (p<0.05).
CONCLUSION: High expression of GW112 in colorectal cancer tissues and reduced expression of GRIM-19 in colorectal cancer tissues may be associated with abnormal proliferation of cancer cells and are possibly one of the reasons for development of colorectal cancer, which can provide effective targets for clinical treatment of this disease.

Glinski K, Wasilewska-Tesluk E, Rucinska M, et al.
Clinical outcome and toxicity of 3D-conformal radiotherapy combined with chemotherapy based on the Intergroup SWOG 9008/INT0116 study protocol for gastric cancer.
J BUON. 2015 Mar-Apr; 20(2):428-37 [PubMed] Related Publications
PURPOSE: To retrospectively evaluate the efficacy and toxicity of adjuvant radio-chemotherapy in patients with gastric cancer and to relate them to the outcome of the landmark INT0116 study that is criticized because of the high toxicity and poor treatment compliance.
METHODS: A total of 102 patients who underwent postoperative fluorouracil (5-FU)-based radio-chemotherapy in our institution between 2004 and 2010 for stage IB-IV (AJCC 6th Edn.) gastric cancer were selected. Radiotherapy to 45 Gy was defined individually and delivered with 3D conformal technique. Chemotherapy was carried out during the first 4 and the last 3 days of radiotherapy with continuous infusion of 5-FU (400mg/m²/day) and leucovorin. Patients received an additional 3 cycles of chemotherapy of 5-FU (425mg/m²/day), mostly 1 before and 2 after radio-chemotherapy. Acute hematological and gastrointestinal toxicities were evaluated according to the CTC v3.0 scale.
RESULTS: Stage distribution was as follows: IB-5 (5%), II-32 (31%), III-49 (48%), and IV-14 (14%). There were 96% R0 resections; 15% of the patients had a D2 resection. Seventy-four patients (72.5%) received all 5 planned cycles and 98 (96%) completed radiotherapy. The 3- and 5-year overall survival (OS) rates were 57% and 48%, respectively. Multivariate analysis showed that variables significantly affecting OS were pT3-T4, pN2-3, R1 resection and female gender. Only 2% of the patients experienced grade 3 gastrointestinal toxicity; 7% had grade 3 or higher hematological toxicity.
CONCLUSIONS: We demonstrated better treatment tolerance, compliance, OS of adjuvant radio-chemotherapy for gastric cancer in comparison with INT0116 study. Conformal radiation techniques might have contributed to this improvement.

Wen J, Linghu EQ, Yang YS, et al.
Associated risk factor analysis for positive resection margins after endoscopic submucosal dissection in early-stage gastric cancer.
J BUON. 2015 Mar-Apr; 20(2):421-7 [PubMed] Related Publications
PURPOSE: To investigate the associated risk factors and the prognostic impact of positive resection margins after endoscopic submucosal dissection (ESD) of early-stage gastric cancer.
METHODS: A retrospective analysis of prospectively collected data was performed on 319 consecutive lesions in 316 patients who underwent ESD. Age, gender, surgeons, lesion location, maximum diameter of resected specimens, macroscopic type, depth of tumor invasion and tumor differentiation were evaluated as potential risk factors.
RESULTS: A total of 27 (8.5%) patients exhibited positive resection margins after ESD. Among 25 successfully followed-up patients 13 were subjected to gastrectomy, 1 was administered chemotherapy, 2 underwent additional endoscopic resection and 9, who were initially followed-up during a median period of 11.7 months (range 1-40), had neither recurrence nor metastasis. Univariate analysis revealed that age, lesion location, depth of tumor invasion, macroscopic type and tumor differentiation were correlated with positive resection margin. By contrast, multivariate logistic regression analysis showed that only age, tumor differentiation and depth of tumor invasion were independent risk factors of positive resection margins.
CONCLUSION: Age, tumor differentiation and depth of tumor invasion were independent risk factors for post-ESD positive resection margins. This result suggests that older patients, undifferentiated lesions and a greater depth of invasion increase the risk for post-ESD positive resection margins.

Tsvetanova Dimova R, Dimitrova Dimitrova D, Angelova Levterova B, et al.
Feasibility of immunochemical faecal occult blood testing for colorectal cancer screening in Bulgaria.
J BUON. 2015 Mar-Apr; 20(2):413-20 [PubMed] Related Publications
PURPOSE: Colorectal carcinoma (CRC) is the second most common cancer in Europe. Screening guidelines recommend a range of screening options that include faecal occult blood tests (FOBTs). The efficacy of FOBT-based CRC screening is dependent on the participation rate, thus emphasizing the importance of the latter. This study aimed at analysing the feasibility of CRC screening with immunochemical FOBT (iFOBT).
METHODS: A cross-sectional study of 600 asymptomatic persons at average risk, aged ≥45years from urban and rural municipalities was performed. An educational brochure, iFOBT kit with translated colored leaflet, informed consent form and questionnaire were administered to participants by 30 general practitioners. Faecal samples were analysed for occult blood using point-of-care rapid iFOBT (cut off 10 ng(GPs)Hb/ml) by the patients themselves at home. The questionnaire aimed to establish if they encountered difficulties in self-testing and self-analysing. Direct and indirect measures of test feasibility were used difficulties for reported study participation rate.
RESULTS: The participation rate was 78.8% (473 participants). Patients < 65 years (x² =70.8, Р<0.001), those with lower education level (x² =82.1, p<0.001), and patients living in villages (x² =4.3, p<0.05) reported difficulties more frequently and they needed help for self-testing by iFOBT. Positive test was found in 8.5% of all participants. Of them 19 persons (48.7%) had haemorrhoids, 8 (20.0%) benign neoplasms, and 3 (7.5%) had CRC.
CONCLUSIONS: CRC screening study by means of iFOBT as a point-of-care test proved to be feasible, since a high participation rate was obtained.

Papadimitriou G, Manganas D, Phedias Georgiades C, et al.
Emergency surgery for obstructing colorectal malignancy: prognostic and risk factors.
J BUON. 2015 Mar-Apr; 20(2):406-12 [PubMed] Related Publications
PURPOSE: Emergency surgery for colorectal malignant obstruction is thought to correlate with poor outcome. The main aim of our study was to identify possible factors that could predict obstruction, and risk factors of poor postoperative outcome. The second aim was to determine any differences between primary anastomosis and stoma creation in the obstruction population, especially in left-sided tumors.
METHODS: A retrospective review of 212 patients who underwent surgery for colorectal malignancy between January 2008 and January 2013 was performed. Fifty-five patients (26%) underwent emergency surgery for completely obstructing colorectal carcinoma, and 157 (74%) underwent elective surgery.
RESULTS: The groups were comparable for age, gender, ASA score, tumor location, tumor stage, lymph node metastasis and mortality. Advanced tumor stage was recorded as the only prognostic factor of obstruction (p=0.001). Postoperative mortality rate was 9.1% in the obstruction group and 6.4% in the elective group (p=0.498). Analysis didn't reveal any risk factors for poor early outcome in the obstruction group. All patients with right-sided obstructive cancer were treated with resection and primary anastomosis, while the same procedure was performed in almost 61% of operations for left-sided tumors with no anastomotic failure.
CONCLUSIONS: Obstructive colorectal malignancy presents at a more advanced stage compared with non-obstructive cancer, with, interestingly, no statistically significant differences in postoperative mortality. Risk factors of poor early outcome couldn't be identified. Resection and primary restitution of continuity is the surgical approach of choice for right-sided obstructive cancers, but it can be, also, safely performed in left-sided cancers.

Jin NY, Wang K, Wei SQ, et al.
Diagnostic value of autofluorescence imaging combined with narrow band imaging in intraepithelial neoplasia of Barrett's esophagus.
J BUON. 2015 Mar-Apr; 20(2):399-405 [PubMed] Related Publications
PURPOSE: To evaluate the diagnostic values of Auto Fluorescence Imaging (AFI) combined with Narrow Band Imaging (NBI) in the diagnosis of the intraepithelial neoplasia of Barrett's esophagus (BE).
METHODS: Seventy four suspicious BE intraepithelial lesions were assessed in 50 patients by AFI, who were further subjected to NBI mode to observe the changes of gastric mucosal capillaries and gastric pits. The corresponding lesions were biopsied for pathological examination.
RESULTS: Among the 74 AFI-diagnosed cases of suspicious lesions, 44 (59.5%) were high-grade intraepithelial neoplasias (BEHGIN), while the remaining 30 cases (40.5%) were false-positive. The NBI-diagnostic results of these 44 BEHGIN lesions were as follows: 39 cases were confirmed and 5 were suspicious; among the 30 false-positive BEHGIN cases, NBI gave 7 false-positive cases. The false-positive rates decreased from 40.5% of AFI to 9.5% (7/74) of NBI-AFI (p<0.05). The positive predictive value of AFI in BEHGIN was 59.5% (44/74), while that of AFI-NBI combination was 84.8% (39/46; p<0.05).
CONCLUSIONS: The AFI-NBI combination technology could significantly improve (p<0.05) the detection rate of BEHGIN.

Vyas D, Castro P, Saadeh Y, Vyas A
The role of nanotechnology in gastrointestinal cancer.
J Biomed Nanotechnol. 2014; 10(11):3204-18 [PubMed] Related Publications
The rising interest in the utilization of nanoparticles for diagnosis and treatment in all cancers including gastrointestinal cancer has increased research interest, and funding in the area of medical nanotechnology. Interesting outcomes of research studies on different applications are published every day, and it include approaches such as molecular targeting, photodynamic therapy, and magnetic localization. The discoveries being made by research teams and the hypothesized applications are thus far very promising. There are limitations that must be researched and overcome, but the increasing evidence for the use of nanoparticles in cancer treatment cannot be ignored. In this review, several recent techniques are discussed on the development of more effective and targeted cellular/molecular techniques in the diagnosis and treatment of gastrointestinal cancer.

Maffione AM, Marzola MC, Capirci C, et al.
Value of (18)F-FDG PET for Predicting Response to Neoadjuvant Therapy in Rectal Cancer: Systematic Review and Meta-Analysis.
AJR Am J Roentgenol. 2015; 204(6):1261-8 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to assess the predictive value of (18)F-FDG PET/ CT for pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
MATERIALS AND METHODS: A systematic search was performed (PubMed and Cochrane databases) for potentially relevant studies up to January 2014. Pooled sensitivity and specificity were calculated. The AUCs of the global cohort and for "major response," "complete response," "only PET after chemoradiotherapy," "ad interim PET," "major response excluding ad interim studies," "complete response excluding ad interim studies," "response index (RI)," "posttreatment maximum standardized uptake value (SUV(max) post)," "visual response analysis (VRA)," "percentage reduction of the total lesion glycolysis (ΔTLG)," and "percentage reduction of the metabolic tumor volume (ΔMTV)" were analyzed. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% CI were calculated.
RESULTS: Thirty-four of 131 (26%) initial articles met the inclusion criteria. Those articles included 1526 patients. PET/CT showed good pooled accuracy both in the global cohort (pooled sensitivity, 73%; pooled specificity, 77%; pooled AUC, 0.83) and for subgroups. Pooled accuracy was similar for early PET restaging and at 1 and 2 weeks after beginning chemoradiotherapy (pooled sensitivity, 84%; pooled specificity, 81%; pooled AUC, 0.89). The major response group showed similar sensitivity to the complete response group (74% and 71%, respectively). RI, SUV(max), and VRA were the most frequent parameters used. Pooled RI and SUV(max) postcutoff values were 63% and 4.4. Pooled time to PET during and after chemoradiotherapy was 1.5 and 6.5 weeks, respectively.
CONCLUSION: This meta-analysis supports the use of FDG PET for restaging locally advanced rectal cancer.

Altini C, Niccoli Asabella A, Di Palo A, et al.
18F-FDG PET/CT role in staging of gastric carcinomas: comparison with conventional contrast enhancement computed tomography.
Medicine (Baltimore). 2015; 94(20):e864 [PubMed] Related Publications
The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT).This retrospective study included 45 patients who underwent performed whole body CECT and F-FDG PET/CT before any treatment. We calculated CECT and F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy, PPV and NPV of CECT, and F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases.The F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with F-FDG PET/CT permits a more valid staging in these patients.

Hou PY, Teng CJ, Chung CS, et al.
Aortic pseudoaneurysm formation following concurrent chemoradiotherapy and metallic stent insertion in a patient with esophageal cancer.
Medicine (Baltimore). 2015; 94(20):e862 [PubMed] Related Publications
Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT) for esophageal cancer patient with esophageal metallic stent insertion is a rare condition.A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was treated with concurrent weekly cisplatin (30 mg/m) and 5-Fluorouracil (500 mg/m) as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During the treatment regimen, the platelet count dropped to less than 200 × 10 /μL. One month after the completion of CCRT, chest CT revealed the presence of an aortic pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic endografting was performed and the patient responded well to surgery. However, the patient died 2 months later due to a nosocomial infection.Multimodality treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal metallic stent placement near a great vessel may increase the risk of pseudoaneurysm formation.

Basyigit S, Ozkan S, Uzman M, et al.
Should screening for colorectal neoplasm be recommended in patients at high risk for coronary heart disease: a cross-sectional study.
Medicine (Baltimore). 2015; 94(20):e793 [PubMed] Related Publications
Colorectal neoplasm (CRN) and coronary heart disease (CHD) share common risk factors. We aimed to assess the risk for CRN in patients who are at high risk for developing CHD determined by measurements, which are independent from the risk factors for CRN.This study was conducted on individuals who underwent total colonoscopic examination and were without history of CHD. Two-hundred thirty-five subjects (82 with CRN and 153 with normal colonoscopic findings) participated in the study. Colorectal carcinoma (CRC) was defined as the presence of adenocarcinoma. We measured carotid intima media thickness (CIMT), flow-mediated dilation (FMD), and calculated Framingham risk score (FRS) for all participants. An increased CIMT (≥1.0 mm), a decreased FMD (<10%), and a high FRS (>20%) were defined as high risks for developing CHD. The risk and the prevalence of CRN were analyzed in relation to the risk for developing CHD.The ratio of the patients with overall-CRN and CRC was significantly higher in individuals who are at high risk for developing CHD compared with individuals who are at low risk for developing CHD by each 3 risk estimation method (P < 0.05 for all). An increased CIMT, a decreased FMD, and a high FRS score were significantly associated with the high risk for the presence of CRC (odds ratio [OR]: 6.018, OR: 3.699, and OR: 4.120, respectively). An increased CIMT, a decreased FMD, and an intermediate FRS were significantly associated with the risk for the presence of overall-CRN (OR: 3.607, OR: 1.866 and OR: 2.889, respectively).The risk for CRN increases as the risk for developing CHD increases. It can be suggested that screening for CRN can be recommended for individuals who are at high risk for developing CHD.

Chen XZ, Chen H, Castro FA, et al.
Epstein-Barr virus infection and gastric cancer: a systematic review.
Medicine (Baltimore). 2015; 94(20):e792 [PubMed] Related Publications
Epstein-Barr virus (EBV) infection is found in a subset of gastric cancers. Previous reviews have exclusively focused on EBV-encoded small RNA (EBER) positivity in gastric cancer tissues, but a comprehensive evaluation of other type of studies is lacking.We searched the PubMed database up to September, 2014, and performed a systematic review.We considered studies comparing EBV nucleic acids positivity in gastric cancer tissue with positivity in either adjacent non-tumor tissue of cancer patients or non-tumor mucosa from healthy individuals, patients with benign gastric diseases, or deceased individuals. We also considered studies comparing EBV antibodies in serum from cancer patients and healthy controls.Selection of potentially eligible studies and data extraction were performed by 2 independent reviewers. Due to the heterogeneity of studies, we did not perform formal meta-analysis.Forty-seven studies (8069 cases and 1840 controls) were identified. EBER positivity determined by in situ hybridization (ISH) was significantly higher in cancer tissues (range 5.0%-17.9%) than in adjacent mucosa from the same patients or biopsies from all control groups (almost 0%). High EBV nuclear antigen-1 (EBNA-1) positivity by PCR was found in gastric cancer tissues, but most were not validated by ISH or adjusted for inflammatory severity and lymphocyte infiltration. Only 4 studies tested for EBV antibodies, with large variation in the seropositivities of different antibodies in both cases and controls, and did not find an association between EBV seropositivity and gastric cancer.In summary, tissue-based ISH methods strongly suggest an association between EBV infection and gastric cancer, but PCR method alone is invalid to confirm such association. Very limited evidence from serological studies and the lack of novel antibodies warrant further investigations to identify potential risk factors of EBV for gastric cancer.

Zhao Q, Li Y, Wang J, et al.
Concurrent Neoadjuvant Chemoradiotherapy for Siewert II and III Adenocarcinoma at Gastroesophageal Junction.
Am J Med Sci. 2015; 349(6):472-6 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: This study was conducted to investigate the efficacy and safety of using a concurrent neoadjuvant chemoradiotherapy (a XELOX regimen) to treat adenocarcinoma of the gastroesophageal junction.
METHODS: Seventy-six patients having resectable adenocarcinoma at the gastroesophageal junction (T3/4, N+, M0) were recruited to participate and randomly assigned to either a chemoradiotherapy group or a surgery group. Patients in the chemoradiotherapy group were orally given capecitabine (1,000 mg/m2, twice daily for 14 days, days 1-14) and intravenous oxaliplatin (130 mg/m2 on day 1) for 2 cycles. Radiotherapy was performed with a total of 45 Gy administered in 25 sessions for 5 weeks. Patients in the surgery group received only surgical intervention.
RESULTS: In the concurrent chemoradiotherapy group, the overall response rate was 55.6% (20/36), tumor control rate was 100% and a pathological complete response was achieved in 16.7% (6/36). The entire chemoradiotherapy group had R0 resections as did 80% of the surgery group (32/40) (P < 0.05). In the concurrent chemoradiotherapy group, 6 patients developed grade 3 side effects. Treatment was either discontinued or the dose adjusted. Major hematological side effects in the chemoradiotherapy group included leukopenia, neutropenia, anemia and thrombocytopenia. Nonhematological side effects included nausea, vomiting and appetite loss. Chemoradiotherapy-related death was not observed.
CONCLUSIONS: Concurrent neoadjuvant chemoradiotherapy administration increased the rate of R0 resection and demonstrated favorable safety in patients with Siewert II or III adenocarcinoma at the gastroesophageal junction. These results support the use of neoadjunctive chemoradiotherapy in the treatment of adenocarcinoma of the gastroesophageal junction.

Jung JH, Choi KD, Koh YW, et al.
Risk factors of lymph node metastasis in patients with gastric neuroendocrine tumor with normal serum gastrin level.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):207-13 [PubMed] Related Publications
BACKGROUND/AIMS: Locoregional gastric carcinoids with normal serum gastrin level have been recommended radical resection regardless of tumor size or depth of invasion. However, there have been some reports which showed small sporadic gastric carcinoids could be treated with local resection. The aim of this study was to elucidate risk factors of lymph node metastasis in patients with gastric carcinoids with normal serum gastrin level and determine the indications for limited resection such as endoscopic treatment.
METHODOLOGY: We performed clinicopathologic reviews of thirty gastric carcinoids with normal serum gastrin level from January 1996 to December 2010.
RESULTS: One case show distant metastasis and two cases showed lymph node metastasis at the time of diagnosis. For twenty seven cases which showed no regional lymph node or distant metastasis initially no additional lymph node or distant metastasis were diagnosed throughout the follow up period. Large tumor size (>10 mm), proper muscle infiltration, WHO classification grade 2 and lymphovascular invasion was noted risk factor of lymph node metastasis by univariate logistic regression analysis.
CONCLUSIONS: Small (≤10 mm) gastric carcinoids with normal serum gastrin level confined to submucosa can be treated with endoscopic or local resection unless lymphovascular invasion.

Jorgensen B, Knudtson J
Stop cancer colon. Colorectal cancer screening--updated guidelines.
S D Med. 2015; Spec No:82-7 [PubMed] Related Publications
Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers in the U.S. Its incidence and mortality have shown a decreasing trend over the last several decades. The greatest contribution to this trend has been colorectal cancer screening. Colonoscopy continues to be the preferred screening modality. However, recommendations for the use of screening tests other than colonoscopy have generated much interest. Guidelines regarding current screening and surveillance recommendations have recently been updated by expert panels, such as the U.S. Multi-Society Task Force, National Comprehensive Cancer Network and National Institute of Health. A review of the updated guidelines as well as a PubMed search for articles dating 2006 to present relating to colorectal cancer screening and surveillance was performed. We discuss the importance of colorectal screening and highlight updates to current colorectal cancer screening and surveillance guidelines.

Bogaards JA, Wallinga J, Brakenhoff RH, et al.
Direct benefit of vaccinating boys along with girls against oncogenic human papillomavirus: bayesian evidence synthesis.
BMJ. 2015; 350:h2016 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To assess the reduction in the vaccine preventable burden of cancer in men if boys are vaccinated along with girls against oncogenic human papillomavirus (HPV).
DESIGN: Bayesian evidence synthesis approach used to evaluate the impact of vaccination against HPV types 16 and 18 on the burden of anal, penile, and oropharyngeal carcinomas among heterosexual men and men who have sex with men. The reduced transmission of vaccine-type HPV from vaccination of girls was assumed to lower the risk of HPV associated cancer in all men but not to affect the excess risk of HPV associated cancers among men who have sex with men.
SETTING: General population in the Netherlands.
INTERVENTION: Inclusion of boys aged 12 into HPV vaccination programmes.
MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs) and numbers needed to vaccinate.
RESULTS: Before HPV vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men were lost to vaccine preventable cancers associated with HPV in the Netherlands. This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among girls remains at the current level of 60%. To prevent one additional case of cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and 1975, respectively. The burden of HPV related cancer in men would be reduced by 66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case, 1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2593, 29107, and 6484, respectively.
CONCLUSIONS: Men will benefit indirectly from vaccination of girls but remain at risk of cancers associated with HPV. The incremental benefit of vaccinating boys when vaccine uptake among girls is high is driven by the prevention of anal carcinomas, which underscores the relevance of HPV prevention efforts for men who have sex with men.

Aurello P, Magistri P, D'Angelo F, et al.
Treatment of esophagojejunal anastomosis leakage: a systematic review from the last two decades.
Am Surg. 2015; 81(5):450-3 [PubMed] Related Publications
Esophagojejunal anastomosis leakage is one of the major complications after total gastrectomy for gastric cancer and is an independent predictor of survival. Our aim is to systematically review the literature and discuss the reported therapeutic approaches to identify the best therapeutic approach. Pubmed, EMbase, Cochrane Library, CILEA Archive, BMJ Clinical Evidence, and Up ToDate databases were screened limiting the research to articles written in English from January 1992 through December 2013. This way a total of 474 manuscripts were retrieved for furthermore evaluation. Eleven manuscripts were considered eligible and the study is focused on those works. We analyzed a total of 3,893 patients and 114 cases of esophagojejunal anastomosis leakage. Different treatments were grouped into three main categories: conservative approach (66 cases), endoscopic approach (21 cases), and surgical approach (27 cases). The overall mortality rate is 26.32 per cent and surgical approach showed the higher rate. According to the reported data, a complete resolution of the leakage can be achieved in an interval ranging from 7 to 28 days in the group treated conservatively. Conservative approach should always be considered as the treatment of choice. Reoperation may be necessary in case of wide dehiscence or when other treatments fail; therefore, the high mortality rate related to this procedure is due to the comorbidities of patients undergoing relaparotomy. Finally, endoscopic approach with endoclips seems promising but needs furthermore studies.

Anderson BJ, Hill EG, Sweeney RE, et al.
The impact of surgical diversion before neoadjuvant therapy for rectal cancer.
Am Surg. 2015; 81(5):444-9 [PubMed] Related Publications
Up-front fecal diversion can palliate emergent symptoms related to locally advanced rectal cancer (LARC) allowing patients to receive neoadjuvant chemoradiation therapy (nCRT). We analyzed outcomes of pretreatment-diverted LARC patients relative to nondiverted patients to define the impact of this management strategy. We retrospectively collected data on 103 LARC patients treated with nCRT and surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Thirteen LARC patients underwent pretreatment diversion for urgent symptoms and 90 LARC patients proceeded directly to nCRT. In all, 50 per cent of diverted patients presented with T4 tumor compared with 14 per cent in the nondiverted patients (P = 0.003). Diverted patients experienced a delay in time-to-treatment initiation of 12 days, although this difference was not statistically significant. Similar rates of chemoradiation and surgical toxicities were observed. Even though diverted patients demonstrated less pathologic response to nCRT compared with nondiverted patients (P = 0.04), there was no significant difference in overall survival. In conclusion, our study demonstrates the effectiveness of up-front fecal diversion at managing emergent obstructive symptoms related to advanced rectal cancer without additional complications, allowing patients to proceed with nCRT followed by radical surgery.

Zhang H, Zhang X, Wang J, et al.
Comparison of high-resolution melting analysis, Sanger sequencing and ARMS for KRAS mutation detection in metastatic colorectal cancer.
Clin Lab. 2015; 61(3-4):435-9 [PubMed] Related Publications
BACKGROUND: Treatment of metastatic colon carcinoma with the anti-epidermal growth factor receptor antibody cetuximab/panitumumab is reported to be ineffective in KRAS-mutant tumors; therefore, it is necessary to perform KRAS mutation analysis before cetuximab or panitumumab treatment is initiated.
METHODS: This study was designed to compare and evaluate the efficacy of three different methodologies--high resolution melting (HRM), Sanger sequencing, and Amplification Refractory Mutation System (ARMS)--for KRAS mutation detection in a clinical setting.
RESULTS: In total, 55 samples from patients with metastatic colorectal cancer were analyzed. Compared to Sanger sequencing, good consistency was found between the results of the ARMS (Kappa = 0.839) and HRM (Kappa = 0.839). The sensitivities of the methods were compared after a consensus was reached: if two of the three methodologies showed a similar result, it was considered as the consensus result. The frequency of KRAS mutations in our population was 34.5%, and discordant findings were observed in five samples. No significant difference in sensitivity was found among the three methodologies.
CONCLUSIONS: From the results, we can conclude that after careful in-laboratory validation, HRM is a good alternative to the ARMS and Sanger sequencing for KRAS mutation testing.

Kong W, Wang J, Ping X, et al.
Biomarkers for assessing mucosal barrier dysfunction induced by chemotherapy: Identifying a rapid and simple biomarker.
Clin Lab. 2015; 61(3-4):371-8 [PubMed] Related Publications
BACKGROUND: Chemotherapy-induced mucosal barrier dysfunction is of clinical interest. However, the assessment of mucosal barrier dysfunction still poses challenges. In this study, we compared several biomarkers with the dual sugar gut permeability test for assessing mucosal barrier dysfunction during chemotherapy.
METHODS: Forty-two patients with gastric or colorectal cancer underwent chemotherapy, including FAM or FOLFOX4 regimens. Patients were asked to grade and record their symptoms of gastrointestinal toxicity daily. The urinary lactulose-mannitol ratio was measured to assess the intestinal permeability. Plasma levels of citrulline, diamine oxidase (DAO), D-lactic acid, and endotoxin were also measured. Intestinal permeability was observed in the subgroup of patients with diarrhea or constipation.
RESULTS: The urinary lactulose-mannitol ratio and plasma citrulline levels increased on the third and sixth post-chemotherapy days, respectively. There were no significant differences in the plasma levels of D-lactic acid, endotoxin or DAO activity compared to their levels before chemotherapy. The urinary lactulose-mannitol ratio in diarrhea patients was significantly higher than in constipation patients.
CONCLUSIONS: These results indicate that the urinary lactulose-mannitol ratio and plasma citrulline level are appropriate biomarkers for assessing mucosal barrier dysfunction in patients receiving chemotherapy. Mucosal barrier dysfunction in diarrhea patients was greater than in constipation patients.

Wang F, Li S, Wang L, et al.
DATS suppresses growth of esophageal squamous cell carcinoma by regulation of ERK1/2.
Clin Lab. 2015; 61(3-4):315-22 [PubMed] Related Publications
BACKGROUND: It is well known that garlics contain a large number of organosulfur compounds including diallyl trisulfide (DATS), which possess anticancer properties. However, the effects of DATS on esophageal squamous cell carcinoma (ESCC) growth are still poorly understood. In this study, we investigated the effects of DATS on ESCC cell growth in vivo and in vitro, as well as the associated signaling pathways.
METHODS: Cell proliferation was measured using the crystal violet assay. The transwell method was used to evaluate the effect of DATS on ESCC cell migration. Also, Western blot was performed to detect the activation of ERK1/2 and AKT1 responds to DATS. Finally, the effect of DATS on ESCC xenografts in nude mice was also investigated.
RESULTS: Our results showed that DATS significantly inhibited ESCC cell proliferation in a time- and dose-dependent manner. DATS time-dependently (p < 0.05) increased phosphorylation of ERK1/2, but not AKT1. Suppression of ERK1/2 activation with PD9805 also completely blocked DATS-inhibited ESCC cell proliferation. Meanwhile, DATS also robustly suppressed ESCC xenograft growth and increased ERK1/2 activation in nude mice.
CONCLUSIONS: Our finding demonstrated that DATS inhibits the proliferation of ESCC cells by activation of ERK1/2 in vitro and in vivo. These findings revealed that DATS could be used for therapeutic intervention for human ESCC.

Gleeson FC, Kipp BR, Voss JS, et al.
Endoscopic ultrasound fine-needle aspiration cytology mutation profiling using targeted next-generation sequencing: personalized care for rectal cancer.
Am J Clin Pathol. 2015; 143(6):879-88 [PubMed] Related Publications
OBJECTIVES: In an era of precision medicine, our aim was to determine the frequency and theranostic potential of mutations identified in malignant lymph nodes (LNs) sampled by endoscopic ultrasound fine-needle aspiration (EUS FNA) of patients with rectal cancer by targeted next-generation sequencing (NGS).
METHODS: The NGS Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA) and MiSeq (Illumina, San Diego, CA) sequencers were used to sequence and assess for 2,800 or more possible mutations in 50 established cancer-associated genes.
RESULTS: Among 102 patients, 89% had 194 pathogenic alterations identified in 19 genes. The identification of KRAS, NRAS, or BRAF mutations suggests that 42% are likely nonresponders to anti-epidermal growth factor receptor therapy. Among KRAS, NRAS, or BRAF wild-type patients, alterations in eight genes linked to alternative therapies were identified in 44%.
CONCLUSIONS: Our data demonstrate the successful ability to apply a single multiplex test to allow multigene mutation detection from malignant LN cytology specimen DNA collected by EUS FNA.

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