Upper Gastrointestinal Malignancies Research Articles

Pattern of Upper Gastrointestinal Malignancies as Seen at Endoscopy in Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria

Aims and Objective: Gastrointestinal malignancies are among the most lethal of all malignancies and are equally notorious for rapidly progressing to advanced stages even in the absence of serious symptoms, thus leading to delayed diagnoses and dismal pro...

Upper gastrointestinal diseases in patients for endoscopy in South-Western Uganda.

There is a paucity of published data regarding upper gastrointestinal diseases in Ugandans with upper gastrointestinal symptoms referred for endoscopy. To study the presenting complaints, pathology and Helicobacter pylori prevalence among patients with upper gastrointestinal symptoms in South-Western Uganda. Patients presenting with upper gastrointestinal symptoms underwent upper endoscopy and a urease test for Helicobacter Pylori, all suspicious lesions were biopsied for histopathology review as appropriate. The most common presenting complaints were epigastric pain (51.6%), dysphagia (13.6%) and odynophagia (7.1%). The most common endoscopy finding was gastritis (40.2%), followed by normal examination (15.2%), oesophageal cancer (13.6%), gastric ulcer (7.6%) and gastric cancer (7.1%). Patients older than 40 years (n=110) had significant findings including gastritis (50.9%), oesophageal cancer (22.7%) and gastric cancer (11.8%). However in younger patients, with the age range of 18-40 years (n=74), most examinations were normal (92.9%). Of the 176 patients able to undergo Helicobacter pylori testing 75.6% were positive. Helicobacter pylori infection was associated with statistically significant increase in gastritis, oesophageal cancer, gastric ulcer, gastric cancer, and duodenal ulcers (p-values< 0.05). Gastritis, ulcerative disease, and upper gastrointestinal malignancies are common in South-Western Ugandans and are associated with a high prevalence of Helicobacter pylori.

PTU-312 Patients referred straight to test for suspected upper gastro intestinal malignancy and normal endoscopy need further investigation: Abstract PTU-312 Table 1

Introduction Straight to Test (STT) Oesophagogastroduodenoscopy (OGD) is a referral pathway for General Practitioners (GP) for suspected cancer (red flag) symptoms of the Upper Gastrointestinal (UGI) tract. Pathways vary between organisations, many of which discharge patients following a normal OGD. Here we report the outcome of further investigation of patients with a normal upper endoscopy. Method Data were gathered retrospectively from STT referrals over a 3 month period (January – March 2012) at Leeds Teaching Hospitals NHS Trust, UK. Patients with simple dyspepsia and a normal OGD were discharged; those with weight loss underwent CT scan and clinic review. Electronic records were reviewed for further investigations and outcomes. Data were compared to a similar audit in 2009 in the same hospital. Results Of 298 STT endoscopy referrals 16 were excluded, due to failure to attend for OGD (8) or incomplete or inappropriate procedure (8). 282 patients underwent STT OGD; age range: 20 to 91 yrs, mean: 66 yrs, 44% males. In comparison, in the previous audit 200 patients were referred over a 6 month period. Presenting symptoms included: dysphagia 114 (40%), dyspepsia 98 (34%) and unintentional weight loss 91 (32%). UGI and non-UGI cancer was identified in 17 (6.02%) and 16 (5.67%) of patients, respectively; the corresponding figures from the 2009 audit were 13 (6.5%) and 7 (4.0%). Of the 17 identified UGI cancers, 9 (52.9%) were oesophageal, 7 (41.2%) gastric and 1 (5.9%) gastro-oesophageal junction. Other findings included peptic ulcer 20 (7.1%) and oesophagitis 10 (3.5%). Patients with a normal OGD and alarm symptoms (84) underwent further investigation, usually CT (65). The 16 cancers identified outside the UGI tract were pancreatic (3), lung (3), lymphoma (2), CLL (1), renal (2), ampullary (1), liver- HCC (1), parathyroid (1), colorectal (1) and ovarian (1). The positive predictive value (PPV) of individual symptoms is shown in the table; the PPV of dysphagia plus weight loss for UGI cancer was 23.07%. Conclusion Since 2009, suspected UGI cancer referrals have tripled, yet detection of UGI and non-UGI malignancy combined remains over 10%. UGI malignancy was identified in 1 in 4 patients presenting with the combination of dysphagia and weight loss. For patients referred with suspected UGI cancer and no significant finding on endoscopy, further targeted investigation is recommended. Disclosure of interest None Declared.

OC-087 Randomised trial of enteral feeding in patients discharged from hospital following surgical resection of an upper gastrointestinal malignancy

Introduction Patients undergoing upper gastrointestinal surgery often eat poorly post operatively, despite dietetic input. The benefit of nutritional supplementation following hospital discharge is unknown. We examined the benefit of 6 weeks nutritional supplementation via the patients feeding jejunostomy on fatigue, quality of life and independent living. Method Patients undergoing oesophagectomy or total gastrectomy for cancer had a feeding jejunostomy placed routinely at surgery. Jejunal feeding was started postoperatively and if tolerated at discharge consenting patients were randomly allocated (stratified by gastric/oesophageal) to nutritional supplementation (600 Kcal/day) via their feeding jejunostomies or no jejunal supplement. All patients received oral supplements and dietetic input. Patients were assessed at discharge and 3, 6, 12 and 24 weeks following discharge for fatigue (MFI-20), quality of life (EORTC QLQ-OES18), health economic analysis (independent living: EQ5D) as well as completing 2 day dietary diaries. Results were analysed non-parametrically (Mann-Whitney) and data presented as medians with interquartile ranges. Results 44 patients (M:F 29:15) were randomised, 23 received jejunal supplements. There was no difference between the groups in age, sex, neo-adjuvant chemotherapy, ASA grade, type of operation, operative time, blood loss, length of hospital stay, and inpatient complications. Percentage of calculated energy requirement actually received was greater in the supplemented group at weeks 3 and 6 (p Conclusion Dietary intake following hospital discharge after oesophageal or gastric surgery is poor. Addition of jejunal feeding over and above dietary advice and sip feeds is effective in providing patients with an adequate energy intake. Increased energy intake however, produced no obvious improvement in measures of fatigue, quality of life or health economics. Interestingly improvement in fatigue and independence plateaued by 12 weeks whilst there was little evidence of improvement in quality of life at 24 week. Disclosure of interest None Declared.

Exceptional responses in patients with upper gastrointestinal malignancies enrolled in first-in-man studies: 2002-2012.

311 Background: First-in-man (FIM) studies test the efficacy and safety of novel therapeutic agents with proven in vitro activity when used for the first time in humans. Patients with advanced upper gastrointestinal malignancies (UGIM) have limited systemic treatment options. We established a database of FIM studies published from 2002-2012 to identify exceptional responders in patients with UGIM. Methods: Using a Scopus search, we compiled a database of published FIM studies enrolling patients with UGIM between 2002 and 2012. We identified exceptional responders to therapy among these patients as a complete response or a partial response lasting at least 6 months. Results: We identified 84 FIM studies enrolling at least one patient with UGIM. In total 554 patients with UGIM were enrolled including 290 pancreatic adenocarcinomas (52.3%), 110 gastric adenocarcinomas (19.9%), 83 esophageal carcinomas (15.0%), 41 hepatocellular carcinomas (7.4%), and 30 cholangiocarcinomas/gallbladder carcinomas (5.4%). One patient with pancreatic cancer treated with bosutinib, a src kinase inhibitor, had a complete response with a progression-free survival (PFS) of 42 months. Four partial responses were reported including one pancreatic cancer patient treated with CHR-3996, a histone deacetylase inhibitor (PFS 12 mo); two pancreatic cancer patients treated with trametinib, a MEK inhibitor (10 and 11.75 mo); and one cholangiocarcinoma patient treated with SB-743921, a kinesin inhibitor (11 mo). Two additional partial responses were noted without available PFS data including one pancreatic cancer patient treated with KOS-1584, a second generation epothilone, and one gastric cancer patient treated with apatinib, a VEGFR-2 inhibitor. Conclusions: Exceptional responses are seen in patients with UGIM enrolled in FIM studies. Actionable genetic aberrations may be driving disease in these patients. Further studies are needed to understand these responses at the molecular level. These molecular studies could open new treatment opportunities for patients with advanced UGIM.

Accuracy of the Emotion Thermometers (ET) Screening Tool in Patients Undergoing Surgery for Upper Gastrointestinal Malignancies

Distress is common in patients with gastrointestinal cancers. Most conventional scales are too long for routine clinic use. We tested the Emotion Thermometers (ET) tool, a brief visual-analogue scale. There are four emotional upset thermometers: distress, anxiety, depression, and anger. Sixty-nine surgical patients were recruited from an academic hospital clinic in 2012; 64 had complete data for Beck depression inventory and ET. The sample size was modest due to the specialist nature of the sample. We examined sensitivity, specificity, and area under the receiver-operator-curve. A dimensional multi-domain approach to screening for emotional disorders is preferable to using the distress thermometer alone and can be achieved with little extra time burden to clinicians. The ET is a diagnostic tool that is primarily designed for screening to identify cancer patients who would benefit by enhanced psychosocial care.

Targeting c-MET/HGF signaling pathway in upper gastrointestinal cancers: rationale and progress.

Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement. However several important questions remain to be answered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including uppergastrointestinal- cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/ environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers.

Correlation of Fiducial Motion in 4D-CT Planning Scans With Real-Time Fiducial Tracking During Fractionated SBRT of Upper Gastrointestinal Malignancies

Correlation of Fiducial Motion in 4D-CT Planning Scans With Real-Time Fiducial Tracking During Fractionated SBRT of Upper Gastrointestinal Malignancies

The role of ¹⁸F-FDG PET imaging in upper gastrointestinal malignancies.

Cancers of the upper gastrointestinal tract form a prevalent and highly morbid group of malignancies. Specifically, median survival for patients with esophagus, gastric, and pancreatic cancers is less than 1 year, and although there has been progress in therapeutic strategies, the vast majority of newly diagnosed patients with these cancers will die of their disease. (18)F-FDG PET ((18)f-fluorodeoxyglucose positron emission tomography) is a useful but underutilized resource for identifying metastatic disease in the upper gastrointestinal tract. While prevalent in the United States, worldwide, (18)F-FDG PET is underutilized especially in countries with a growing emergence of gastroesophageal cancers, despite evidence of clear benefit in cancer staging, and in some cases response assessment and surveillance.

Clinical significance of incidental findings on staging positron emission tomography for oesophagogastric malignancies.

The aim of this retrospective study was to determine the clinical significance of incidental findings detected on positron emission tomography (PET) in patients undergoing staging of oesophagogastric malignancies. Patients with oesophagogastric malignancies who underwent PET between June 2007 and May 2012 were included in the study. PET was performed according to hospital protocol. All imaging was interpreted by two consultant radiologists in nuclear medicine. Incidental findings that were unrelated to the primary malignancy were recorded and patients were recommended to have further investigations (imaging, endoscopy and biopsy). Overall, 333 patients (240 male, 93 female; mean age: 67 years) with upper gastrointestinal malignancies were eligible for inclusion in the study. Eighty-nine of these patients had PET demonstrating one or more incidental findings. Two patients were found to have a second primary malignancy. One patient had a distant metastasis of his primary cancer and six patients had a premalignant lesion. In this study, incidental findings were discovered in 26.7% of patients with known oesophagogastric cancer. A second primary cancer or premalignant lesion was found in 8.4% of patients with incidental findings. Patients with these findings should be investigated to rule out further malignancy. There were a high proportion of false positive results in our study. It is recommended that each patient is considered on an individual basis and assessed with simultaneous PET and computed tomography.

New Vascular Disrupting Agents in Upper Gastrointestinal Malignancies

Antivascular approaches aim to cause rapid and catastrophic shutdown in the vascular function of the tumour, leading to extensive tumour cell death. Tumour vascular disrupting agents (VDAs) are a new class of cancer therapies that target the existing vasculature of tumours, taking advantage of the relative instability of tumour vasculature and its supporting structures. Treatment with VDAs induces a rapid collapse and regression of tumour vessels, with a consequent deprivation of blood and oxygen which leads to ischemic or hemorrhagic necrosis of the tumour. In this review, an overview of the most recently developed vascular disrupting agents is reported, focusing on the biological effects exerted by these compounds on endothelial cells and tumour vasculature, potentially effective in the treatment of several malignancies including upper gastrointestinal tumours. In particular, we have focused on the antimitotic agent combretastatin and its numerous synthetic analogues such as combretastatin A-4-phosphate, OXI4503, and AVE8062, and on the colchicine analogue ZD6126.

Editorial (Thematic Issue: Targeted Therapies in Upper Gastrointestinal Malignancies)

Editorial (Thematic Issue: Targeted Therapies in Upper Gastrointestinal Malignancies)

Histopathological Varieties of Upper Gastro Intestinal Malignancies with Prior Endoscopic Examination Followed by Biopsy

Histopathological Varieties of Upper Gastro Intestinal Malignancies with Prior Endoscopic Examination Followed by Biopsy

Cell-Free DNA for the Detection of Pancreatic, Liver and Upper Gastrointestinal Cancers: Has Progress Been Made?

Detecting alterations in blood cell-free DNA (cfDNA) is hoped to be a novel, noninvasive method for diagnosing, prognosing and monitoring cancer patients. Several studies have assessed the usefulness of measuring tumor-specific genetic and epigenetic changes of cfDNA, such as loss of heterozygosity, frequency of mutations, alterations of microsatellites and the methylation of genes in patient blood samples. However, few well-designed trials have been carried out to translate these findings effectively. In this review, we have assessed the clinical utility of cfDNA in pancreatic, liver and upper gastrointestinal malignancies.

Endoscopic evaluation of patients with dyspepsia in a secondary referral hospital in Egypt

BackgroundDyspepsia is a common clinical problem. More than half of patients presenting with dyspepsia have no detectable lesion for their symptoms. The common organic causes of dyspepsia include peptic ulcer, esophagitis and cancer. The diagnostic test of choice is endoscopy. Age specific thresholds to trigger endoscopic evaluation may differ by gender, availability of resources and regional disease specific risks. AimThe aim of the study was to determine the prevalence of significant endoscopic lesions in Egyptian patients presenting with dyspepsia in relation to age. Materials and methodsThis was a retrospective study. Data on patients presenting with dyspepsia and scheduled for upper gastrointestinal (UGI) endoscopy between January 2000 and January 2013 were collected. ResultsOne thousand four hundred patients with dyspepsia (31% of all endoscopies) were assessed by UGI endoscopy. Fifty-one percent were male. The mean age was 43±15years. Four hundred and fifty patients (32%) had a history of smoking, 388 (32%) were taking aspirin or non-steroidal anti-inflammatory drugs and 22 (2%) were consuming alcohol. Endoscopy revealed normal findings or miscellaneous irrelevant findings in 913 patients (65%). Significant endoscopic findings were diagnosed in 487 (35%). These included peptic ulcers in 245 patients (18%), esophagitis in 191 (14%), erosive gastroduodenitis in 112 (8%) and UGI malignancy in 16 (1%). Significant endoscopic findings were associated with increasing age. ConclusionDyspepsia is a common indication for endoscopy in Egypt. Endoscopy revealed normal findings or miscellaneous irrelevant findings in the majority of patients. The most frequent significant pathologies included peptic ulcer, esophagitis and erosive gastroduodenitis. These were associated with increasing age. UGI malignancy was uncommon and found in older age groups.

Age and Alarm Symptoms Predict Upper Gastrointestinal Malignancy among Patients with Dyspepsia

Background : Upper gastrointestinal (UGI) malignancy is one of the major causes of cancer related death. Endoscopy in dyspeptic patients above 45 years, or those with alarm symptoms may detect this condition. There were only limited data in Indonesia about age and alarm symptoms to predict UGI malignancy. This study was aimed to determine the prevalence of UGI malignancy among dyspepsia patients and to develop a simple clinical prediction model. Method: A cross-sectional study to 390 patients with dyspepsia underwent endoscopy in Endoscopy Unit of Sanglah Hospital Denpasar between July 2012 and June 2013 was conducted. Demography and alarm symptoms were documented. Chi-square and logistic regression test analysis were conducted to analyze variables associated with UGI malignancy. Results: Twenty (5.13%) of 390 patients with dyspepsia had UGI malignancy. Of the 20 patients, 65% were gastric cancer and 30% were esophageal cancer. The mean age was 59 ± 12 years. Variables associated with UGI malignancy were weight loss (OR = 8.2), dysphagia (OR = 6.2), age > 45 years old (OR = 5.6), gastrointestinal bleeding (OR = 5.5), persistent vomiting (OR = 5.4), and anemia (OR = 4.9). Using a simplified rule of age >45 years and the presence of any alarm symptom, sensitivity was 85% and specificity was 67.57%. Conclusions: UGI malignancy was found in 5.13% of patients with dyspepsia who underwent endoscopy. Simple clinical prediction model states that age above 45 years and alarm symptoms may be used as a screening tool to predict UGI malignancy. Keywords: dyspepsia, alarm symptoms, upper GI malignancy, clinical prediction model

Met, IGF1R, and Other New Targets in Upper GI Malignancies

Upper gastrointestinal (GI) malignancies comprise some of the most aggressive human cancers. Expanding knowledge of molecular mechanisms is finally translating into clinical application, and this has occurred at a relatively rapid rate in the past several years. However, despite recent advances in targeted therapies in upper GI cancers our overall success with targeted therapeutics in this disease area remains dismal. This statement is particularly troubling given some sobering facts: upper GI malignancies are prevalent as well as aggressive with a high morbidity and mortality. Esophagus and gastric cancer combined have an annual global incidence of over 1.2 million new cases annually while median survival is less than 1 year for most patients with metastatic disease. Progress has been limited due to several factors including: disease heterogeneity and variance of phenotype across the globe, clinical trial design strategies that have not yet incorporated selective mechanisms to afford individualized matching of drug to tumor molecular profile and last, a lack of validated predictive markers. Nevertheless there is evidence that many targeted agents can be administered safely at doses that achieve the required effect at the protein level. Several drugs that have negative early trial results can be potentially vital therapeutic agents if patient selection is appropriate.

UPPER GASTROINTESTINAL MALIGNANCIES: 6976 ENDOSCOPY REVIEW IN A MULTINATIONAL STUDY

IntroductionThis is a multinational study to compare the prevalence of upper gastrointestinal malignant and pre-malignant conditions in three different populations. The populations involved in this study included British, Japanese and...

PTH-059 Upper Gastrointestinal Malignancies: 6976 Endoscopy Review in a Multinational Study

IntroductionTo compare the prevalence of upper gastrointestinal (UGI) malignant and premalignant conditions in three separate populations; British, Japanese and Arabian.Methods6976 Upper Gastrointestinal (UGI) endoscopies were retrospectively reviewed in a multinational...

Gastroesophageal Reflux Disease Questionnaire (GerdQ) in real‐world practice: A national multicenter survey on 8065 patients

Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China. A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure. Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3-18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8. The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.