Treatment Option Overview (Small Intestine Cancer)

MedlinePlus

... small bowel. X-rays are taken at different times as the barium travels through the upper GI tract and small bowel. CT scan (CAT scan) : A procedure that makes a series of detailed pictures of areas inside the body, ...

Guidelines for the management of iron deficiency anaemia.

PubMed

Goddard, Andrew F; James, Martin W; McIntyre, Alistair S; Scott, Brian B

2011-10-01

Iron deficiency anaemia (IDA) occurs in 2-5% of adult men and postmenopausal women in the developed world and is a common cause of referral to gastroenterologists. Gastrointestinal (GI) blood loss from colonic cancer or gastric cancer, and malabsorption in coeliac disease are the most important causes that need to be sought. DEFINING IRON DEFICIENCY ANAEMIA: The lower limit of the normal range for the laboratory performing the test should be used to define anaemia (B). Any level of anaemia should be investigated in the presence of iron deficiency (B). The lower the haemoglobin the more likely there is to be serious underlying pathology and the more urgent is the need for investigation (B). Red cell indices provide a sensitive indication of iron deficiency in the absence of chronic disease or haemoglobinopathy (A). Haemoglobin electrophoresis is recommended when microcytosis and hypochromia are present in patients of appropriate ethnic background to prevent unnecessary GI investigation (C). Serum ferritin is the most powerful test for iron deficiency (A). Upper and lower GI investigations should be considered in all postmenopausal female and all male patients where IDA has been confirmed unless there is a history of significant overt non-GI blood loss (A). All patients should be screened for coeliac disease (B). If oesophagogastroduodenoscopy (OGD) is performed as the initial GI investigation, only the presence of advanced gastric cancer or coeliac disease should deter lower GI investigation (B). In patients aged >50 or with marked anaemia or a significant family history of colorectal carcinoma, lower GI investigation should still be considered even if coeliac disease is found (B). Colonoscopy has advantages over CT colography for investigation of the lower GI tract in IDA, but either is acceptable (B). Either is preferable to barium enema, which is useful if they are not available. Further direct visualisation of the small bowel is not necessary unless there are symptoms suggestive of small bowel disease, or if the haemoglobin cannot be restored or maintained with iron therapy (B). In patients with recurrent IDA and normal OGD and colonoscopy results, Helicobacter pylori should be eradicated if present. (C). Faecal occult blood testing is of no benefit in the investigation of IDA (B). All premenopausal women with IDA should be screened for coeliac disease, but other upper and lower GI investigation should be reserved for those aged 50 years or older, those with symptoms suggesting gastrointestinal disease, and those with a strong family history of colorectal cancer (B). Upper and lower GI investigation of IDA in post-gastrectomy patients is recommended in those over 50 years of age (B). In patients with iron deficiency without anaemia, endoscopic investigation rarely detects malignancy. Such investigation should be considered in patients aged >50 after discussing the risk and potential benefit with them (C). Only postmenopausal women and men aged >50 years should have GI investigation of iron deficiency without anaemia (C). Rectal examination is seldom contributory, and, in the absence of symptoms such as rectal bleeding and tenesmus, may be postponed until colonoscopy. Urine testing for blood is important in the examination of patients with IDA (B). All patients should have iron supplementation both to correct anaemia and replenish body stores (B). Parenteral iron can be used when oral preparations are not tolerated (C). Blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia (C).

Laboratory test variables useful for distinguishing upper from lower gastrointestinal bleeding.

PubMed

Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2015-05-28

To distinguish upper from lower gastrointestinal (GI) bleeding. Patient records between April 2011 and March 2014 were analyzed retrospectively (3296 upper endoscopy, and 1520 colonoscopy). Seventy-six patients had upper GI bleeding (Upper group) and 65 had lower GI bleeding (Lower group). Variables were compared between the groups using one-way analysis of variance. Logistic regression was performed to identify variables significantly associated with the diagnosis of upper vs lower GI bleeding. Receiver-operator characteristic (ROC) analysis was performed to determine the threshold value that could distinguish upper from lower GI bleeding. Hemoglobin (P = 0.023), total protein (P = 0.0002), and lactate dehydrogenase (P = 0.009) were significantly lower in the Upper group than in the Lower group. Blood urea nitrogen (BUN) was higher in the Upper group than in the Lower group (P = 0.0065). Logistic regression analysis revealed that BUN was most strongly associated with the diagnosis of upper vs lower GI bleeding. ROC analysis revealed a threshold BUN value of 21.0 mg/dL, with a specificity of 93.0%. The threshold BUN value for distinguishing upper from lower GI bleeding was 21.0 mg/dL.

Laboratory test variables useful for distinguishing upper from lower gastrointestinal bleeding

PubMed Central

Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2015-01-01

AIM: To distinguish upper from lower gastrointestinal (GI) bleeding. METHODS: Patient records between April 2011 and March 2014 were analyzed retrospectively (3296 upper endoscopy, and 1520 colonoscopy). Seventy-six patients had upper GI bleeding (Upper group) and 65 had lower GI bleeding (Lower group). Variables were compared between the groups using one-way analysis of variance. Logistic regression was performed to identify variables significantly associated with the diagnosis of upper vs lower GI bleeding. Receiver-operator characteristic (ROC) analysis was performed to determine the threshold value that could distinguish upper from lower GI bleeding. RESULTS: Hemoglobin (P = 0.023), total protein (P = 0.0002), and lactate dehydrogenase (P = 0.009) were significantly lower in the Upper group than in the Lower group. Blood urea nitrogen (BUN) was higher in the Upper group than in the Lower group (P = 0.0065). Logistic regression analysis revealed that BUN was most strongly associated with the diagnosis of upper vs lower GI bleeding. ROC analysis revealed a threshold BUN value of 21.0 mg/dL, with a specificity of 93.0%. CONCLUSION: The threshold BUN value for distinguishing upper from lower GI bleeding was 21.0 mg/dL. PMID:26034359

Inflammatory gastrointestinal diseases associated with PD-1 blockade antibodies.

PubMed

Collins, M; Michot, J M; Danlos, F X; Mussini, C; Soularue, E; Mateus, C; Loirat, D; Buisson, A; Rosa, I; Lambotte, O; Laghouati, S; Chaput, N; Coutzac, C; Voisin, A L; Soria, J C; Marabelle, A; Champiat, S; Robert, C; Carbonnel, F

2017-11-01

Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1. this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016. Patients were recruited through a pharmacovigilance registry. Patients' data were reviewed by a multidisciplinary committee that included gastroenterologists, oncologists and a pathologist. Quantitative variables are described by median (range), qualitative variable by frequency (percentage). Forty-four patients were addressed to a Gastroenterology unit for a suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1, which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13, 65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7, 35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo-obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper gastrointestinal tract inflammation. Median time to resolution was 36 days (6-172) in acute colitis, and 98 days (42-226) in microscopic colitis. This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Gastrointestinal cancer risk in patients with a family history of gastrointestinal cancer.

PubMed

Chung, Joo Won; Park, Jae Jun; Lim, Yun Jeong; Lee, Jun; Kim, Sun Moon; Han, Joung Ho; Jeon, Seong Ran; Lee, Hong Sub; Kim, Yong Sung; Song, Si Young

2018-06-25

This study was performed to evaluate the relationship between family history of gastrointestinal (GI) cancers and incidence of any GI cancer in the Korean population. Between January 2015 and July 2016, 711 GI cancer patients and 849 controls in 16 hospitals in Korea were enrolled. Personal medical histories, life styles, and family history of GI cancers were collected via questionnaire. There was a significant difference in the incidence of family history of GI cancer between GI cancer patients and controls (p=0.002). Patients with family history of GI cancer tended to be diagnosed as GI cancer at younger age than those without family history (p=0.016). The family members of GI cancer patients who were diagnosed before 50 years of age were more frequently diagnosed as GI cancer before the age of 50 years (p=0.017). After adjusting for major confounding factors, age (adjusted odds ratio [AOR] 1.065, 95% confidence interval [CI]; 1.053-1.076), male gender (AOR 2.270, 95% CI; 1.618-3.184), smoking (AOR 1.570, 95% CI; 1.130-2.182), and sibling's history of GI cancer (AOR 1.973, 95% CI; 1.246-3.126) remained independently associated with GI cancers. GI cancer patients tended to have a first relative with a history of concordant GI cancer. Personal factors (old age and male) and lifestyle (smoking) contribute to the development of GI cancer, independently. Individuals with high risk for GI cancers may be advised to undergo screening at an earlier age.

Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells.

PubMed

Saeki, N; Kuwahara, Y; Sasaki, H; Satoh, H; Shiroishi, T

2000-09-01

Amplification of proto-oncogenes associated with their over-expression is one of the critical carcinogenic events identified in human cancer cells. In many cases of human gastric cancer, a proto-oncogene ERBB-2 is co-amplified with CAB1 genes physically linked to ERBB-2, and both genes are over-expressed. The amplified region containing ERBB-2 and CAB1 was named 17q12 amplicon from its chromosomal location. The syntenic region corresponding to the 17q12 amplicon is well conserved in mouse. In this study we isolated and characterized a novel mouse gene that locates telomeric to the mouse syntenic region. Northern blot analysis using the mouse cDNA and a cloned partial cDNA of human homolog disclosed a unique expression pattern of the genes. They are expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. Moreover, in the GI tract, the expression is highly restricted to the esophagus and stomach. Thus, we named the mouse gene Gasdermin (Gsdm). This is the first report of a mammalian gene whose expression is restricted to both upper GI tract and skin. Interestingly, in spite of its expression in normal stomach, no transcript was detected by Northern blot analysis in human gastric cancer cells. These data suggest that the loss of the expression of the human homolog is required for the carcinogenesis of gastric tissue and that the gene has an activity adverse to malignant transformation of cells.

Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Akira; Shibuya, Keiko, E-mail: kei@kuhp.kyoto-u.ac.jp; Matsuo, Yukinori

2012-10-01

Purpose: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. Methods and Materials: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm{sup 3} of the organ, and absolute volume receiving 10-50 Gy [V{sub 10-50}]) of the stomach, duodenum, small intestine, and a composite structure ofmore » the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. Results: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V{sub 50} of {>=}16 cm{sup 3} of the stomach was the best predictor, and the actual incidence in patients with V{sub 50} <16 cm{sup 3} of the stomach vs. those with V{sub 50} of {>=}16 cm{sup 3} was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V{sub 50} of {>=}33 cm{sup 3} of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V{sub 50} <33 cm{sup 3} of the StoDuo vs. those with V{sub 50} {>=}33 cm{sup 3} was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. Conclusion: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel techniques, such as intensity-modulated radiotherapy, for the treatment of pancreatic cancer.« less

Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients

PubMed Central

Yang, Ju-Yeh; Lee, Tsung-Chun; Montez-Rath, Maria E.; Paik, Jane; Chertow, Glenn M.; Desai, Manisha

2012-01-01

Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial. PMID:22266666

Upper Gastrointestinal Tract Motility Disorders in Women, Gastroparesis, and Gastroesophageal Reflux Disease.

PubMed

Zia, Jasmine K; Heitkemper, Margaret M

2016-06-01

This article reviews the sex differences in upper gastrointestinal (GI) motility for both healthy and common dysmotility conditions. It focuses on gastroesophageal reflux disease and other esophageal motor disorders for the esophagus and on gastroparesis and accelerated gastric emptying for the stomach. It also describes differences in upper GI motility signs and symptoms during each female hormonal stage (ie, menstrual cycle, pregnancy, perimenopause, menopause) for both healthy participants and those suffering from one of the aforementioned upper GI dysmotility conditions. More research still needs to be conducted to better understand sex differences in upper GI motility. Copyright © 2016 Elsevier Inc. All rights reserved.

Etiological and Endoscopic Profile of Middle Aged and Elderly Patients with Upper Gastrointestinal Bleeding in a Tertiary Care Hospital in North India: A Retrospective Analysis.

PubMed

Mahajan, Pranav; Chandail, Vijant Singh

2017-01-01

Upper gastrointestinal (GI) bleeding is a common medical emergency associated with significant morbidity and mortality. The clinical presentation depends on the amount and location of hemorrhage and the endoscopic profile varies according to different etiology. At present, there are limited epidemiological data on upper GI bleed and associated mortality from India, especially in the middle and elderly age group, which has a higher incidence and mortality from this disease. This study aims to study the clinical and endoscopic profile of middle aged and elderly patients suffering from upper GI bleed to know the etiology of the disease and outcome of the intervention. Out of a total of 1790 patients who presented to the hospital from May 2015 to August 2017 with upper GI bleed, and underwent upper GI endoscopy, data of 1270 patients, aged 40 years and above, was compiled and analyzed retrospectively. All the patients included in the study were above 40 years of age. Majority of the patients were males, with a male to female ratio of 1.6:1. The most common causes of upper GI bleed in these patients were portal hypertension-related (esophageal, gastric and duodenal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia GAVE), seen in 53.62% of patients, followed by peptic ulcer disease (gastric and duodenal ulcers) seen in 17.56% of patients. Gastric erosions/gastritis accounted for 15.20%, and duodenal erosions were seen in 5.8% of upper GI bleeds. The in-hospital mortality rate in our study population was 5.83%. The present study reported portal hypertension as the most common cause of upper GI bleeding, while the most common endoscopic lesions reported were esophageal varices, followed by gastric erosion/gastritis, and duodenal ulcer.

Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis.

PubMed

Anglin, Rebecca; Yuan, Yuhong; Moayyedi, Paul; Tse, Frances; Armstrong, David; Leontiadis, Grigorios I

2014-06-01

There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use. MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case-control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/- NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment. Fifteen case-control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42). SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.

[Usefulness of upper gastrointestinal series to detect leaks in the early postoperative period of bariatric surgery].

PubMed

Medina, Francisco J; Miranda-Merchak, Andrés; Martínez, Alonso; Sánchez, Felipe; Bravo, Sebastián; Contreras, Juan Eduardo; Alliende, Isabel; Canals, Andrea

2016-04-01

Postoperative leaks are the most undesirable complication of bariatric surgery and upper gastrointestinal (GI) series are routinely ordered to rule them out. Despite the published literature recommending against its routine use, it is still being customarily used in Chile. To examine the usefulness of routine upper GI series using water-soluble iodinated contrast media for the detection of early postoperative leaks in patients undergoing bariatric surgery. A cohort of 328 patients subjected to bariatric surgery was followed from October 2012 to October 2013. Most of them underwent sleeve gastrectomy. Upper GI series on the first postoperative day were ordered to 308 (94%) patients. Postoperative leaks were observed in two patients, with an incidence of 0.6%. The sensitivity for upper GI series detection of leak was 0% and the negative predictive value was 99%. Routine upper GI series after bariatric surgery is not useful for the diagnosis of postoperative leak, given the low incidence of this complication and the low sensitivity of the technique.

Optional Sub-study to Intraoperative Imaging With ICG Registry

ClinicalTrials.gov

2016-07-19

Lung, Prostate, Breast, Colon, Pancreatic, Renal, Bladder,Thyroid, Ovarian, Head and Neck,GI (Foregut - Esophagus),GI (Midgut) Cancer; Cancer of the Ovarian, Head and Neck,GI (Foregut - Esophagus),GI (Midgut), Sarcoma Cancer; Cancer of Neuro-onc, Parathyroid, Desmoid Tumors, Melanoma Cancer

Upper gastrointestinal bleeding - state of the art.

PubMed

Szura, Mirosław; Pasternak, Artur

2014-01-01

Upper gastrointestinal (GI) bleeding is a condition requiring immediate medical intervention, with high associated mortality exceeding 10%. The most common cause of upper GI bleeding is peptic ulcer disease, which largely corresponds to the intake of NSAIDs and Helicobacter pylori infection. Endoscopy is the essential tool for the diagnosis and treatment of active upper GI hemorrhage. Endoscopic therapy together with proton pump inhibitors and eradication of Helicobacter pylori significantly reduces rebleeding rates, mortality and number of emergency surgical interventions. This paper presents contemporary data on the diagnosis and treatment of upper gastrointestinal bleeding.

Upper Gastrointestinal Involvement in Crohn Disease: Histopathologic and Endoscopic Findings.

PubMed

Diaz, Liege; Hernandez-Oquet, Rafael Enrique; Deshpande, Amar R; Moshiree, Baharak

2015-11-01

Studies describing the prevalence of upper gastrointestinal (GI) Crohn disease (CD) and its histopathologic changes have been inconsistent as a result of different definitions used for upper GI involvement, diverse populations, and varying indications for endoscopy. We reviewed the literature describing endoscopic findings and histologic lesions in gastric and duodenal mucosa of patients with established CD. PubMed, EMBASE, and the Cochrane Library were searched for gastroduodenal biopsy findings in patients with CD from 1970 to 2014. We included all retrospective and prospective studies in adults. We calculated the prevalence of the most common endoscopic and histopathological findings among patients with overall CD and upper GI CD. Of the 385 articles identified, 20 eligible studies were included. A total of 2511 patients had CD and 815 had upper GI CD. In the CD group, the most common histopathological finding was nonspecific gastric inflammation in 32% of patients, followed by gastric granuloma in 7.9%. Focal gastritis was prevalent in 30.9% of patients. In the upper GI CD group, gastric inflammation was present in 84% of patients, followed by duodenal inflammation in 28.2% and gastric granuloma in 23.2%. The most common gastric endoscopic finding in patients with CD was erythema in 5.9%, followed by erosions in 3.7%. Duodenal endoscopic findings included ulcers and erythema in 5.3% and 3.0% of patients, respectively. We found a prevalence of 34% for CD involving the upper GI tract across these 20 studies. Routine upper endoscopy with biopsies of the upper GI tract in the diagnostic workup of patients with CD can correctly classify the distribution and extent of the disease.

Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus

PubMed Central

Zhao, Jing-Bo; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr; Ejskjaer, Niels

2006-01-01

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed. PMID:16718808

Hospital variation and the impact of postoperative complications on the use of perioperative chemo(radio)therapy in resectable gastric cancer. Results from the Dutch Upper GI Cancer Audit.

PubMed

Schouwenburg, M G; Busweiler, L A D; Beck, N; Henneman, D; Amodio, S; van Berge Henegouwen, M I; Cats, A; van Hillegersberg, R; van Sandick, J W; Wijnhoven, B P L; Wouters, M W J; Nieuwenhuijzen, G A P

2018-04-01

Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications. All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy. Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31-7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04-4.65). Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Outcome Following a Negative CT Angiogram for Gastrointestinal Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Victoria, E-mail: drvictoriac@gmail.com; Tse, Donald, E-mail: donald.tse@gmail.com; Dixon, Shaheen, E-mail: shaheen7noorani@gmail.com

2015-04-15

ObjectiveThis study was designed to evaluate the role of a negative computed tomography angiogram (CTA) in patients who present with gastrointestinal (GI) hemorrhage.MethodsA review of all patients who had CTAs for GI hemorrhage over an 8-year period from January 2005 to December 2012 was performed. Data for patient demographics, location of hemorrhage, hemodynamic stability, and details of angiograms and/or the embolization procedure were obtained from the CRIS/PACS database, interventional radiology database, secure electronic medical records, and patient’s clinical notes.ResultsA total of 180 patients had 202 CTAs during the 8-year period: 87 CTAs were performed for upper GI hemorrhage (18 positivemore » for active bleeding, 69 negative) and 115 for lower GI hemorrhage (37 positive for active bleeding, 78 negative); 58.7 % (37/63) of patients with upper GI bleed and 77.4 % (48/62) of patients with lower GI bleed who had an initial negative CTA did not rebleed without the need for radiological or surgical intervention. This difference was statistically significant (p = 0.04). The relative risk of rebleeding, following a negative CTA, in lower GI bleeding versus upper GI bleeding patients is 0.55 (95 % confidence interval 0.32–0.95).ConclusionsPatients with upper GI bleed who had negative CTAs usually require further intervention to stop the bleeding. In contrast, most patients presenting with lower GI hemorrhage who had a negative first CTA were less likely to rebleed.« less

Chemoprevention of Gastrointestinal Cancer: The Reality and the Dream

PubMed Central

Chun, Kyung-Soo; Kim, Eun-Hee; Lee, Sooyeon

2013-01-01

Despite substantial progress in screening, early diagnosis, and the development of noninvasive technology, gastrointestinal (GI) cancer remains a major cause of cancer-associated mortality. Chemoprevention is thought to be a realistic approach for reducing the global burden of GI cancer, and efforts have been made to search for chemopreventive agents that suppress acid reflux, GI inflammation and the eradication of Helicobacter pylori. Thus, proton pump inhibitors, statins, monoclonal antibodies targeting tumor necrosis factor-alpha, and nonsteroidal anti-inflammatory agents have been investigated for their potential to prevent GI cancer. Besides the development of these synthetic agents, a wide variety of the natural products present in a plant-based diet, which are commonly called phytoceuticals, have also sparked hope for the chemoprevention of GI cancer. To perform successful searches of chemopreventive agents for GI cancer, it is of the utmost importance to understand the factors contributing to GI carcinogenesis. Emerging evidence has highlighted the role of chronic inflammation in inducing genomic instability and telomere shortening and affecting polyamine metabolism and DNA repair, which may help in the search for new chemopreventive agents for GI cancer. PMID:23560148

Barium enema

MedlinePlus

Lower gastrointestinal series; Lower GI series; Colorectal cancer - lower GI series; Colorectal cancer - barium enema; Crohn disease - lower GI series; Crohn disease - barium enema; Intestinal blockage - lower GI series; Intestinal ...

Endoscopic management and outcomes of pregnant women hospitalized for nonvariceal upper GI bleeding: a nationwide analysis.

PubMed

Nguyen, Geoffrey C; Dinani, Amreen M; Pivovarov, Kevin

2010-11-01

Upper GI endoscopy has an important diagnostic and therapeutic role in the management of nonvariceal upper GI bleeding (NVUGB). To characterize nationwide patterns of utilization of upper GI endoscopy in pregnant women with NVUGB and to assess health outcomes. Retrospective cohort study. Participating hospitals from the Nationwide Inpatient Sample, 1998-2007. Pregnant and age-matched nonpregnant women admitted for NVUGB. The study population was classified as pregnant women with NVUGB (n = 1210) and nonpregnant women with NVUGB (n = 6050). Rate of upper GI endoscopy, maternal mortality, fetal death/complications, and premature delivery. Pregnant women were less likely than nonpregnant women to undergo upper GI endoscopy (26% vs 69%; P < .0001) even after adjustment for comorbidities, transfusion requirement, and the presence of hypovolemic shock (adjusted odds ratio, 0.19; 95% confidence interval, 0.16-0.22). Among those who underwent endoscopy, pregnant women were less likely to undergo the procedure within 24 hours of admission (50% vs 57%; P = .02). Mortality was lower among pregnant women compared with nonpregnant women (0% vs 0.6%; P = .006). In comparing outcomes between those who did and did not undergo endoscopy, there was no difference in fetal loss (0.2% vs 0.6%), fetal distress/complications (2.7% vs 2.6%), or premature delivery (7.3% vs 6.4%). The study was based on administrative data. A conservative nonendoscopic approach is common in the management of pregnant women with NVUGB and is not associated with worse maternal or fetal outcomes. Upper GI endoscopy is, however, safe when judiciously implemented in the actively bleeding patient. Copyright © 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding. A risk modelling analysis.

PubMed

Majeed, Ammar; Wallvik, Niklas; Eriksson, Joakim; Höijer, Jonas; Bottai, Matteo; Holmström, Margareta; Schulman, Sam

2017-02-28

The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the 'total risk', based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2-3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07-0.55) and death (HR 0.61; 95 % CI, 0.39-0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4-4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3-6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

Gastroparesis

MedlinePlus

... Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Hemorrhoids Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & ... Nerve Damage (Diabetic Neuropathies) Indigestion (Dyspepsia) Related Diagnostic Tests Upper GI Endoscopy Upper GI Series Related Research ...

Crohn's Disease

MedlinePlus

... Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Hemorrhoids Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & ... research into many diseases and conditions. Related Diagnostic Tests Colonoscopy Upper GI Series Upper GI Endoscopy Related ...

Upper Gastrointestinal (GI) Tract X-Ray (Radiography)

MedlinePlus

... to drinking barium, some patients are also given baking-soda crystals (similar to Alka-Seltzer) to further ... contrast upper GI series. The patient will swallow baking-soda crystals that create gas in the stomach ...

Accuracy of upper gastrointestinal swallow study in identifying strictures after laparoscopic gastric bypass surgery.

PubMed

Daylami, Rouzbeh; Rogers, Ann M; King, Tonya S; Haluck, Randy S; Shope, Timothy R

2008-01-01

Stricture at the gastrojejunal anastomosis after Roux-en-Y gastric bypass is a significant sequela that often requires intervention. The diagnosis of stricture is usually established by a recognized constellation of symptoms, followed by contrast radiography or endoscopy. The purpose of this report was to evaluate the accuracy of contrast swallow studies in excluding the diagnosis of gastrojejunal stricture. A retrospective analysis of the charts of 119 patients who had undergone laparoscopic Roux-en-Y gastric bypass, representing 41 upper gastrointestinal (GI) swallow studies, was conducted. Of those patients who underwent GI swallow studies, 30 then underwent definitive upper endoscopy to confirm or rule out stricture. The overall sensitivity, specificity, and negative predictive value of the swallow studies were calculated. Of the 30 patients who underwent upper endoscopic examination for symptoms of stricture after laparoscopic gastric bypass, 20 were confirmed to have a stricture. The sensitivity, specificity, and negative predictive value of the upper GI swallow study in this group was 55%, 100%, and 53%, respectively. The demographics of the patients with strictures were similar to those of the study group as a whole. The results of our study have shown that a positive upper GI swallow study is 100% specific for the presence of stricture. However, the sensitivity and negative predictive value of upper GI swallow studies were poor, making this modality unsatisfactory in definitively excluding the diagnosis of gastrojejunal stricture.

[Routine fluoroscopic investigations after primary bariatric surgery].

PubMed

Gärtner, D; Ernst, A; Fedtke, K; Jenkner, J; Schöttler, A; Reimer, P; Blüher, M; Schön, M R

2016-03-01

Staple line and anastomotic leakages are life-threatening complications after bariatric surgery. Upper gastrointestinal (GI) tract X-ray examination with oral administration of a water-soluble contrast agent can be used to detect leaks. The aim of this study was to evaluate the impact of routine upper GI tract fluoroscopy after primary bariatric surgery. Between January 2009 and December 2014 a total of 658 bariatric interventions were carried out of which 442 were primary bariatric operations. Included in this single center study were 307 sleeve gastrectomies and 135 Roux-en-Y gastric bypasses. Up to December 2012 upper GI tract fluoroscopy was performed routinely between the first and third postoperative days and the detection of leakages was evaluated. In the investigation period 8 leakages (2.6 %) after sleeve gastrectomy, 1 anastomotic leakage in gastrojejunostomy and 1 in jejunojejunostomy after Roux-en-Y gastric bypass occurred. All patients developed clinical symptoms, such as abdominal pain, tachycardia or fever. In one case the leakage was detected by upper GI fluoroscopy and in nine cases radiological findings were unremarkable. No leakages were detected in asymptomatic patients. Routine upper GI fluoroscopy is not recommended for uneventful postoperative courses after primary bariatric surgery.

Temporal trends and regional variations in gastrointestinal cancer mortality in Peru, 2005-2014.

PubMed

Hernández-Vásquez, Akram; Bendezú-Quispe, Guido; Azañedo, Diego; Huarez, Bertha; Rodríguez-Lema, Belén

2016-01-01

To estimate and analyze the evolution of mortality rates of gastrointestinal (GI) cancer in Peru and its regions between 2005-2014. We performed a nationwide secondary analysis of Peru's Health Ministry registry of deaths during the period 2005-2014, with a focus on regional differences. Deaths registered with codes C15 to C25 (malignant neoplasms of digestive organs) from the ICD-10 were included. Calculation of age-standarized mortality rates and years of life lost (YLL) due to GI cancer per 100,000 habitants were also performed. Data of 67,527 deaths from GI cancers was analyzed, 35,055 (51.91%) were women. In 2005, the number of GI cancer deaths was 6,484, for 2014, 7,532 cases were recorded. The GI cancer age-standarized mortality rates at the country level showed a decrease of 12.70% between 2005-2014. Stomach cancer presented the highest age-standarized mortality rate despite showing a downward trend in the last years, equal for gallbladder, liver and biliary tract, and esophagus cancer. Colorectal, small intestine and anus cancer show a progressive increase. In 2014, Callao (48.8), Huancavelica (48.5), La Libertad (39.6), Lambayeque (40.5) and Huanuco (38.9) had the highest rates. The three types of GI cancers with the highest rates of YLL in 2014 were stomach cancer (118.51), followed by liver and biliary tract cancer (58.68) and colorectal (44.86). GI cancer mortality in Peru is high and a priority issue in regions like Huancavelica, Huanuco, Callao, La Libertad and Lambayeque. Stomach cancer remains the most frequent GI cancer, but with a downward trend in the study period.

Evaluation of nasogastric tubes to enable differentiation between upper and lower gastrointestinal bleeding in unselected patients with melena.

PubMed

Kessel, Boris; Olsha, Oded; Younis, Aurwa; Daskal, Yaakov; Granovsky, Emil; Alfici, Ricardo

2016-02-01

Gastrointestinal (GI) bleeding is a common surgical problem. The aim of this study was to evaluate how insertion of the nasogastric tube may enable differentiation between upper and lower GI bleeding in patients with melena. A retrospective study involving patients admitted to our surgery division with a melena was carried out between the years 2010 and 2012. A total of 386 patients were included in the study. Of these, 279 (72.2%) patients had negative nasogastric aspirate. The sensitivity of examination of nasogastric aspirate to establish the upper GI as the source of bleeding was only 28% and the negative predictive value of a negative nasogastric aspirate was less than 1%. Most patients who initially presented with melena and were found to have upper GI bleeding had a negative nasogastric aspirate. Insertion of a nasogastric tube does not affect the clinical decision to perform upper endoscopy and should not be routinely carried out.

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

PubMed Central

Guo, Lixia; Fan, Dominic; Zhang, Fahao; Price, Janet E.; Lee, Ju-Seog; Marchetti, Dario; Fidler, Isaiah J.; Langley, Robert R.

2011-01-01

An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic potential is highly desirable. Here, we demonstrate that plating GI-101A human breast cancer cells on hard (0.9%) agar selects for the subpopulation of metastasis-initiating cells. The agar-selected cells, designated GI-AGR, were homogeneous for CD44+ and CD133+ and five times more invasive than the parental GI-101A cells. Moreover, mice injected with GI-AGR cells had significantly more experimental brain metastases and shorter overall survival than did mice injected with GI-101A cells. Comparative gene expression analysis revealed that GI-AGR cells were markedly distinct from the parental cells but shared an overlapping pattern of gene expression with the GI-101A subline GI-BRN, which was generated by repeated in vivo recycling of GI-101A cells in an experimental brain metastasis model. Data mining on 216 genes shared between GI-AGR and GI-BRN breast cancer cells suggested that the molecular phenotype of these cells is consistent with that of cancer stem cells and the aggressive basal subtype of breast cancer. Collectively, these results demonstrate that analysis of cell growth in a hard agar assay is a powerful tool for selecting metastasis-initiating cells in a heterogeneous population of breast cancer cells, and that such selected cells have properties similar to those of tumor cells that are selected based on their potential to form metastases in mice. PMID:21514446

Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice.

PubMed

Sostres, Carlos; Carrera-Lasfuentes, Patrica; Lanas, Angel

2017-10-01

The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case-control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32-5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms. The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.

Upper Gastrointestinal (GI) Series

MedlinePlus

... abdomen or ask you to change position several times to evenly coat your upper GI tract with the barium. If you are having a double-contrast study, you will swallow gas-forming crystals that mix with the barium coating your stomach. ...

Haemosuccus pancreaticus, an uncommon cause of upper gastro intestinal bleeding: Case report and review of the literature.

PubMed

Shah, Amir Ali; Charon, Jean Pierre

2015-06-01

Haemosuccus Pancreaticus is defined as upper gastro intestinal (GI) bleeding from the ampula of vater via the pancreatic duct. It is most commonly associated with pancreatic inflammation, erosion of the pancrease by aneurysm or pseudo-aneurysm of the splenic artery. We report a 69 year old man with previous history of acute pancreatitis who was admitted with recurrent haematemesis. Initial upper GI endocopy was normal, while admitted, he collapse with abdominal pain and hypotension. He was resuscitated with blood and intravenous fluid. Repeat upper GI endocopy showed fresh blood in the duodenum, but no active bleeding site was demonstrated. An urgent coeliac axis CT angiogram was done which showed an splenic artery pseudo-aneurysm, which was successfully embolized. Patient is well 9 months after the procedure. This case highlights the importance of considering coeliac axis CT angiogram as part of investigation for obscure GI bleeding.

Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery Through Protein Expression Database Mining.

PubMed

Strickland, Sarah; Wasserman, Jason K; Giassi, Ana; Djordjevic, Bojana; Parra-Herran, Carlos

2016-05-01

Immunohistochemistry is frequently used to identify ovarian mucinous neoplasms as primary or metastatic; however, there is significant overlap in expression patterns. We compared traditional markers (CK7, CK20, CDX2, PAX8, estrogen receptor, β-catenin, MUC1, MUC2, and MUC5AC) to 2 novel proteins identified through mining of the Human Protein Atlas expression database: SATB2 and POF1B. The study cohort included 49 primary gastrointestinal (GI) mucinous adenocarcinomas (19 colorectal, 15 gastric, 15 pancreatobiliary), 60 primary ovarian mucinous neoplasms (19 cystadenomas, 21 borderline tumors, 20 adenocarcinomas), and 19 metastatic carcinomas to the ovary (14 lower and 5 upper GI primaries). Immunohistochemistry was performed on tissue microarrays, scored and interpreted as negative (absent or focal/weak) or positive. Metastatic tumors were frequently unilateral (42.8% of tumors from lower and 40% of tumors from upper tract) and ≥10 cm (85.7% of tumors from lower and 80% of tumors from upper tract). CK7 was positive in 88.5% upper GI and 88.3% primary ovarian compared with 24.3% lower GI neoplasms. CK20 and CDX2 were positive in 84.8% and 100% of lower GI tumors, respectively; however, expression was also common in upper GI (CK20 42.8%, CDX2 50%) and primary ovarian neoplasms (CK20 65.7%, CDX2 38.3%). Conversely, SATB2 was more specific for lower GI origin, being positive in 78.8% lower GI but only 11.5% upper GI and 1.7% primary ovarian neoplasms. PAX8 expression was common in primary ovarian neoplasms (75% of all neoplasms, 65% of carcinomas); only 1 (1.5%) GI tumor was positive. MUC2 and β-catenin were frequently positive in lower GI tumors (96.9% and 51.5%, respectively). Estrogen receptor expression was only seen in primary ovarian neoplasms (13.3%). Nuclear premature ovarian failure 1B (POF1B) expression was seen in malignant tumors regardless of their origin. A panel including CK7, SATB2, and PAX8 separated primary from secondary GI neoplasms with up to 77.1% sensitivity and 99% specificity, outperforming tumor laterality and size. Second-line markers such as CDX2, MUC2, estrogen receptor, MUC1, and β-catenin increased the sensitivity of immunohistochemistry in excluding lower GI origin. Biomarker search using proteomic databases has a value in diagnostic pathology, as shown with SATB2; however, as seen with POF1B, expression profiles in these databases are not always reproduced in larger cohorts.

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract.

PubMed

Le Bars, Pierre; Matamoros, Sébastien; Montassier, Emmanuel; Le Vacon, Françoise; Potel, Gilles; Soueidan, Assem; Jordana, Fabienne; de La Cochetière, Marie-France

2017-06-01

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.

The therapeutic value of targeting inflammation in gastrointestinal cancers

PubMed Central

Sun, Beicheng; Karin, Michael

2014-01-01

Inflammation has been implicated in the initiation and progression of gastrointestinal (GI) cancers. Inflammation also plays important roles in subverting immune tolerance, escape from immune surveillance, and conferring resistance to chemotherapeutic agents. Targeting key regulators and mediators of inflammation represents an attractive strategy for GI cancer prevention and treatment. However, the targeting of inflammation in GI cancer is not straight-forward and sometimes inflammation may contribute to tumor regression. We discuss the origins and effects of inflammation in GI cancer and how to target it successfully. PMID:24881011

ENDOSCOPIC FINDINGS OF UPPER GASTROINTESTINAL BLEEDING IN PATIENTS WITH LIVER CIRROSIS.

PubMed

Hadayat, Rania; Jehangiri, Attique-ur-Rehman; Gul, Rahid; Khan, Adil Naseer; Said, Khalid; Gandapur, Asadullah

2015-01-01

Acute upper gastrointestinal (GI) bleeding is a common medical emergency. A common risk factor of upper GI bleeding is cirrhosis of liver, which can lead to variceal haemorrhage. 30-40% of cirrhotic patients who bleed may have non-variceal upper GI bleeding and it is frequently caused by peptic ulcers, portal gastropathy, Mallory-Weiss tear, and gastroduodenal erosions. The objective of this study was to determine the frequency of upper gastrointestinal endoscopic findings among patients presenting with upper gastrointestinal bleeding with liver cirrhosis. This descriptive cross-sectional study was carried out in Gastroenterology & Hepatology Department of Ayub Teaching Hospital, Abbottabad from February 2012 to June 2013. 252 patients diagnosed with cirrhosis, presenting with upper GI bleed, age 50 years of either gender, and were included in the study. Non-probability consecutive sampling was used, Endoscopy was performed on each patient and the findings documented. The mean age was 57.84 +/- 6.29 years. There were 158 (62.7%) males and 94 (37.3%) females. The most common endoscopic finding was oesophageal varices (92.9%, n=234) followed by portal hypertensive gastropathy (38.9%, n=98) with almost equal distribution among males and females. Gastric varices were found in 33.3% of patients (n=84). Among other non-variceal lesions, peptic ulcer disease was seen in 26 patients (10.3%) while gastric erosions were found in 8 patients (3.2%). In patients with acute upper GI bleeding and liver cirrhosis, the most common endoscopic finding is oesophageal varices, with a substantially higher value in our part of the country, apart from other non-variceal causes.

A prospective evaluation of undiagnosed joint hypermobility syndrome in patients with gastrointestinal symptoms.

PubMed

Fikree, Asma; Grahame, Rodney; Aktar, Rubina; Farmer, Adam D; Hakim, Alan J; Morris, Joan K; Knowles, Charles H; Aziz, Qasim

2014-10-01

The Joint Hypermobility Syndrome (JHS) is a common connective tissue disorder characterized by joint hyperflexibility, dysautonomia, and chronic pain. Gastrointestinal (GI) symptoms are reported in JHS patients attending rheumatology clinics, but the prevalence and symptom pattern of previously undiagnosed JHS in GI clinics are unknown. By using validated questionnaires, a prospective cross-sectional study in secondary care GI clinics estimated the prevalence of JHS in new consecutively referred patients, compared GI symptoms in patients with and without JHS, and by using multiple regression determined whether the burden of GI symptoms in JHS patients was dependent on chronic pain, autonomic, psychological, and medication related factors. A positive control group consisted of JHS patients referred from rheumatology clinics with GI symptoms (JHS-Rh). From 552 patients recruited, 180 (33%) had JHS (JHS-G) and 372 did not (non-JHS-G). Forty-four JHS-Rh patients were included. JHS-G patients were more likely to be younger, female with poorer quality of life (P = .02) than non-JHS-G patients. After age and sex matching, heartburn (odds ratio [OR], 1.66; confidence interval [CI], 1.1-2.5; P = .01), water brash (OR, 2.02; CI, 1.3-3.1; P = .001), and postprandial fullness (OR, 1.74; CI, 1.2-2.6; P = .006) were more common in JHS-G vs non-JHS-G. Many upper and lower GI symptoms increased with increasing severity of JHS phenotype. Upper GI symptoms were dependent on autonomic and chronic pain factors. JHS is common in GI clinics, with increased burden of upper GI and extraintestinal symptoms and poorer quality of life. Recognition of JHS will facilitate multidisciplinary management of GI and extra-GI manifestations. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Find a Gastroenterologist

MedlinePlus

... Province Select Country Zip/Postal Code Sort By GI Health Centers Colorectal Cancer Hepatitis C Inflammatory Bowel ... GI Symptoms Gastroparesis See All Topics (A-Z) GI Procedures Colonoscopy Colorectal Cancer Screening See All Procedures ( ...

Upper gastrointestinal bleeding.

PubMed

Feinman, Marcie; Haut, Elliott R

2014-02-01

Upper gastrointestinal (GI) bleeding remains a commonly encountered diagnosis for acute care surgeons. Initial stabilization and resuscitation of patients is imperative. Stable patients can have initiation of medical therapy and localization of the bleeding, whereas persistently unstable patients require emergent endoscopic or operative intervention. Minimally invasive techniques have surpassed surgery as the treatment of choice for most upper GI bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

Epidemiological Trends of GI Cancers in Patients Visiting a Tertiary Care Hospital in Chandigarh, North India.

PubMed

Sharma, Munesh K; Singh, Tarundeep; Pandey, Avdesh K; Kankaria, Ankita

2015-01-01

Cancer has become an epidemic disease. Nearly ten million new cancer cases are diagnosed annually in the world and out of these about half are from the developing world. To appropriately plan for treatment, management and prevention of the disease, it becomes necessary to study the trends about morbidity caused by cancers. Data for patients diagnosed with any form of gastrointestinal (GI) cancers was extracted from records maintained in the outpatient department registers of the Oncology Department of Government Medical College and Hospital in Chandigarh from 1999 to 2012. Trends were analysed for different categories of GI cancers for the period of 12 years. In present study GI cancers accounted for 23 % of all registered cases (n-9603) of carcinomas. Males predominated for all GI cancers except in the gall bladder. Gastrointestinal cancers as a proportion of total cancers increased from 21% in 1999 to 25.9% in 2012 with a significant increasing trend in our series (χ2 for linear trend=9.36, p<0.003). Cancers of the tonsil, oral cavity and pharynx taken together showed an increasing trend over the years (χ2 for trend=55.2, p<0.001) whereas cancers of the lower GI (χ2=19.6, p<0.0001) and gall bladder (χ2=19.5, p<0.0001) showed a declining trend in our series. GI cancers form a significant proportion of all cancers reporting to our data. In depth studies to ascertain the reasons for the changing trends are required to design intervention programs. Further information is necessary from cancer registries and from the hospital records of oncology departments.

The risk of gastrointestinal bleeding in patients receiving dabigatran etexilate: a systematic review and meta-analysis of the literature.

PubMed

Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Di Minno, Alessandro; Tremoli, Elena; Di Minno, Giovanni

2017-06-01

Evidence on the risk of gastrointestinal (GI) bleeding associated with dabigatran etexilate (DE) is contrasting. We performed a meta-analysis of literature to address this issue. Studies on GI bleeding risk in patients receiving DE or vitamin-K antagonists (VKA) were systematically searched. Twenty-three studies (26 datasets) showed no difference in the GI bleeding risk between the 250,871 patients treated with DE and the 460,386 receiving VKA (OR: 1.052, 95% CI: 0.815, 1.359). Similar results were obtained when pooling together adjusted ORs/HRs, obtained by means of multivariate analysis (OR: 1.06, 95% CI: 0.914, 1.222). Compared with VKA, DE use was associated with a significantly lower risk of upper GI (OR: 0.742, 95% CI: 0.569, 0.968), but not of lower GI bleedings (OR: 1.208, 95% CI: 0.902, 1.619). Furthermore, no significant difference in the GI bleeding risk was found when data on DE 110 mg and DE 150 mg twice-daily were separately compared with VKA. No difference in GI bleeding risk was found between DE and VKA. These results were confirmed for both dosages of DE and when specifically analyzing lower GI bleeding. In contrast, the risk of upper GI bleeding was lower with DE than with VKA. KEY MESSAGES No difference in the risk of gastrointestinal (GI) bleeding can be found between dabigatran etexilate (DE) and vitamin K-antagonists (VKA). These results are confirmed for both dosages of DE. The risk of upper GI bleeding is lower with DE than with VKA.

Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

PubMed

Chan, Francis K L; Kyaw, Moe; Tanigawa, Tetsuya; Higuchi, Kazuhide; Fujimoto, Kazuma; Cheong, Pui Kuan; Lee, Vivian; Kinoshita, Yoshikazu; Naito, Yuji; Watanabe, Toshio; Ching, Jessica Y L; Lam, Kelvin; Lo, Angeline; Chan, Heyson; Lui, Rashid; Tang, Raymond S Y; Sakata, Yasuhisa; Tse, Yee Kit; Takeuchi, Toshihisa; Handa, Osamu; Nebiki, Hiroko; Wu, Justin C Y; Abe, Takashi; Mishiro, Tsuyoshi; Ng, Siew C; Arakawa, Tetsuo

2017-01-01

It is not clear whether H 2 -receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Associations among binge eating behavior patterns and gastrointestinal symptoms: a population-based study

PubMed Central

Cremonini, F; Camilleri, M; Clark, MM; Beebe, TJ; Locke, GR; Zinsmeister, AR; Herrick, LM; Talley, NJ

2009-01-01

Background The psychological symptoms associated with binge eating disorder (BED) have been well documented. However, the physical symptoms associated with BED have not been explored. Gastrointestinal (GI) symptoms such as heartburn and diarrhea are more prevalent in obese adults, but the associations remain unexplained. Patients with bulimia have increased gastric capacity. The objective of the study was to examine if the severity of binge eating episodes would be associated with upper and lower GI symptoms. Methods Population-based survey of community residents through a mailed questionnaire measuring GI symptoms, frequency of binge eating episodes and physical activity level. The association of GI symptoms with frequency of binge eating episodes was assessed using logistic regression models adjusting for age, gender, body mass index (BMI) and physical activity level. Results In 4096 subjects, BED was present in 6.1%. After adjusting for BMI, age, gender, race, diabetes mellitus, socioeconomic status and physical activity level, BED was independently associated with the following upper GI symptoms: acid regurgitation (P < 0.001), heartburn (P < 0.001), dysphagia (P < 0.001), bloating (P < 0.001) and upper abdominal pain (P < 0.001). BED was also associated with the following lower GI symptoms: diarrhea (P < 0.001), urgency (P < 0.001), constipation (P < 0.01) and feeling of anal blockage (P = 0.001). Conclusion BED appears to be associated with the experience of both upper and lower GI symptoms in the general population, independent of the level of obesity. The relationship between increased GI symptoms and physiological responses to increased volume and calorie loads, nutritional selections and rapidity of food ingestion in individuals with BED deserves further study. PMID:19139750

Review of the gastrointestinal tract: from macro to micro.

PubMed

Reed, Kathleen K; Wickham, Rita

2009-02-01

To review the normal anatomy and physiology of the gastrointestinal (GI) tract, the malignant transformations in GI cancers, and the rationale for targeted therapy for these cancers. Published articles, book chapters and web sources. Oncology nurses require an understanding of normal GI anatomy and physiology, along with an understanding of malignant transformations at the cellular and molecular level, to effectively educate and care for the patient with a diagnosis of a GI cancer. Challenges for the oncology nurse include continuing education related to GI cancer, the development of effective patient education skills, ensuring safe administration of oral agents and remaining current regarding GI clinical trial opportunities. Education of nursing colleagues, development of an area of expertise through specialization, and development of leadership skills are opportunities associated with practicing in the dynamic environment of oncology nursing.

A national survey on the initial management of upper gastrointestinal bleeding.

PubMed

Liang, Peter S; Saltzman, John R

2014-01-01

To evaluate the initial management of upper gastrointestinal (GI) bleeding in the United States. Various guidelines have addressed the initial management of upper GI bleeding, but the extent to which these guidelines are followed in clinical practice is unknown. We conducted a national survey of emergency physicians, internists, and gastroenterologists practicing in hospitals affiliated with an ACGME-accredited gastroenterology fellowship. Participants rated their agreement and adherence to 9 preendoscopic quality indicators for the initial management of upper GI bleeding. Awareness, use, and barriers to the use of early prognostic risk scores were also assessed. A total of 1402 surveys were completed, with an estimated response rate of 11.3%. Gastroenterologists and trainees agreed with the quality indicators more than nongastroenterologists and attending physicians, respectively. There was no difference in the application of the quality indicators by specialty or clinical position. Among all physicians, 53% had ever heard of and 30% had ever used an upper GI bleeding risk score. More gastroenterologists than nongastroenterologists had heard of (82% vs. 44%, P<0.001) and used (51% vs. 23%, P<0.001) a risk score. There was no difference between attending physicians and trainees. Gastroenterologists and attending physicians more often cited lack of utility as a reason to not use risk scores, whereas nongastroenterologists and trainees more often cited lack of knowledge. Among emergency physicians, internists, and gastroenterologists in the United States, agreement with upper GI bleeding initial management guidelines was high but adherence--especially pertaining to the use of risk scores--was low.

Trifluridine/tipiracil: an emerging strategy for the management of gastrointestinal cancers.

PubMed

Peeters, Marc; Cervantes, Andrés; Moreno Vera, Shanti; Taieb, Julien

2018-04-27

Fluoropyrimidines are currently the backbone of treatment for gastrointestinal (GI) cancers but development of resistance to these agents remains a major problem. Trifluridine/tipiracil is an oral chemotherapeutic agent recently approved for third-line treatment of chemorefractory metastatic colorectal cancer. This article reviews the clinical value of trifluridine/tipiracil as a monotherapy, including recent trials in GI cancers, and the potential benefit of combining it with other agents in patients with GI cancers, including the preclinical rationale for combination therapy and recently completed and ongoing clinical trials. Data gathered so far suggest that trifluridine/tipiracil has the potential to form the chemotherapeutic backbone in the continuum of care for GI cancers in the future.

Gastrointestinal events in at-risk patients starting non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatic diseases: the EVIDENCE study of European routine practice.

PubMed

Lanas, Angel; Boers, Maarten; Nuevo, Javier

2015-04-01

Data concerning rates of gastrointestinal (GI) events in non-steroidal anti-inflammatory drug (NSAID) users derive mainly from clinical trials. The EVIDENCE study quantified the incidence of symptomatic uncomplicated and/or complicated GI events in at-risk European patients treated with NSAIDs in real-life practice. This non-interventional study assessed 4144 adults with at least one GI risk factor who recently initiated NSAID therapy for osteoarthritis (85%), rheumatoid arthritis (11%), ankylosing spondylitis (3%) or a combination (1%). Patient characteristics and medical history were collected from medical records. GI events (upper and lower) were recorded at in-clinic visits during 6 months' follow-up. Mean time on index NSAID at enrolment was 33 days. The incidence (per 100 person-years) was 18.5 per 100 person-years for uncomplicated GI events and 0.7 per 100 person-years for complicated GI events. Upper GI events were far more common (12%) than lower GI events (1%) during study follow-up (median 182 days (range 61-320)). Other reported rates for cardiovascular, anaemia or non-GI events were much less frequent. A minority (28%) of patients had ongoing proton pump inhibitor use at enrolment, with strong variation by practice and country. EVIDENCE is the largest prospective study of the real-life management of European patients treated with NSAIDs for rheumatic diseases and at increased GI risk. It shows that GI events from the upper GI tract are far more common than those from the lower GI tract. It also shows adherence to guidelines for gastroprotection is generally low. NCT01176682. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Immunotherapy for Gastrointestinal Malignancies

PubMed Central

Toomey, Paul G.; Vohra, Nasreen A.; Ghansah, Tomar; Sarnaik, Amod A.; Pilon-Thomas, Shari A.

2016-01-01

Background Gastrointestinal (GI) cancers are the most common human tumors encountered worldwide. The majority of GI cancers are unresectable at the time of diagnosis, and in the subset of patients undergoing resection, few are cured. There is only a modest improvement in survival with the addition of modalities such as chemotherapy and radiation therapy. Due to an increasing global cancer burden, it is imperative to integrate alternative strategies to improve outcomes. It is well known that cancers possess diverse strategies to evade immune detection and destruction. This has led to the incorporation of various immunotherapeutic strategies, which enable reprogramming of the immune system to allow effective recognition and killing of GI tumors. Methods A review was conducted of the results of published clinical trials employing immunotherapy for esophageal, gastroesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. Results Monoclonal antibody therapy has come to the forefront in the past decade for the treatment of colorectal cancer. Immunotherapeutic successes in solid cancers such as melanoma and prostate cancer have led to the active investigation of immunotherapy for GI malignancies, with some promising results. Conclusions To date, monoclonal antibody therapy is the only immunotherapy approved by the US Food and Drug Administration for GI cancers. Initial trials validating new immunotherapeutic approaches, including vaccination-based and adoptive cell therapy strategies, for GI malignancies have demonstrated safety and the induction of antitumor immune responses. Therefore, immunotherapy is at the forefront of neoadjuvant as well as adjuvant therapies for the treatment and eradication of GI malignancies. PMID:23302905

Lobular Metastatic Breast Cancer Patients With Gastrointestinal Involvement: Features and Outcomes.

PubMed

Montagna, Emilia; Pirola, Sara; Maisonneuve, Patrick; De Roberto, Giuseppe; Cancello, Giuseppe; Palazzo, Antonella; Viale, Giuseppe; Colleoni, Marco

2017-07-10

Metastatic breast cancer typically involves the lungs, bones, brain, and liver and only occasionally affects the gastrointestinal (GI) tract. The relevant published data have been limited to case reports and small series of patients. The present study focused on the treatment and outcomes of breast cancer patients with GI involvement diagnosed at the European Institute of Oncology. We analyzed the clinicopathologic features of the GI metastases and compared them with those of the primary tumors according to their histologic type (ductal or lobular carcinoma). From the database of the Department of Pathology, 40 patients who had undergone endoscopy or GI surgery with a final diagnosis of metastatic breast cancer from 2000 to 2014 were identified. The greatest proportion of patients (75%) had had primary invasive lobular carcinoma. Of the 40 patients, 82% had hormone receptor-positive disease in the metastatic lesion; 34 patients were candidates for systemic therapy. The median length of observation after GI metastasis was 18 months (range, 0.6-79 months). The overall survival from the diagnosis of GI involvement was 33 months (95% confidence interval, 16.8-38.3 months). Lobular breast carcinoma has a greater propensity to metastasize to the GI tract compared with other breast cancer subtypes. In the presence of GI symptoms, even if nonspecific, the GI tract should be thoroughly studied. Systemic treatment, including hormonal therapy, should be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: novel targets for prevention and intervention.

PubMed

Cathcart, Mary-Clare; O'Byrne, Kenneth J; Reynolds, John V; O'Sullivan, Jacintha; Pidgeon, Graham P

2012-01-01

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE(2), which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA(2) in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD(2) and its metabolite 15d-PGJ2, PGF(1α) and PGI(2). Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity. A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. Copyright © 2011 Elsevier B.V. All rights reserved.

Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries.

PubMed

Mo, Chen; Sun, Gang; Lu, Ming-Liang; Zhang, Li; Wang, Yan-Zhi; Sun, Xi; Yang, Yun-Sheng

2015-05-07

To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA. The preventive effects of PPIs were compared with the control group [taking placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA-associated upper GI injuries. The meta-analysis was performed using RevMan 5.1 software. We evaluated 8780 participants in 10 RCTs. The meta-analysis showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16; 95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with control. For patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36; 95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding (OR = 0.32; 95%CI: 0.13-0.79). PPIs are effective in preventing LDA-associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the risk of MACE.

Gastrointestinal cancer and brain metastasis: a rare and ominous sign.

PubMed

Go, Pauline H; Klaassen, Zachary; Meadows, Michael C; Chamberlain, Ronald S

2011-08-15

Metastatic brain tumors represent 20% to 40% of all intracranial neoplasms and are found most frequently in association with lung cancer (50%) and breast cancer (12%). Although brain metastases occur in <4% of all tumors of the gastrointestinal (GI) tract, the incidence of GI brain metastasis is rising in part due to more effective systemic treatments and prolonged survival of patients with GI cancer. Data were collected from 25 studies (11 colorectal, 7 esophageal, 2 gastric, 1 pancreatic, 1 intestinal, 3 all-inclusive GI tract cancer) and 13 case reports (4 pancreatic, 4 gallbladder, and 5 small bowel cancer). Brain metastases are found in 1% of colorectal cancer, 1.2% of esophageal cancer, 0.62% of gastric cancer, and 0.33% of pancreatic cancer cases. Surgical resection with whole brain radiation therapy (WBRT) has been associated with the longest median survival (38.4-262 weeks) compared with surgery alone (16.4-70.8 weeks), stereotactic radiosurgery (20-38 weeks), WBRT alone (7.2-16 weeks), or steroids (4-7 weeks). Survival in patients with brain metastasis from GI cancer was found to be diminished compared with metastases arising from the breast, lung, or kidney. Prolonged survival and improvement in clinical symptoms has been found to be best achieved with surgical resection and WBRT. Although early treatment has been linked to prolonged survival and improved quality of life, brain metastases represent a late manifestation of GI cancers and remain an ominous sign. Copyright © 2011 American Cancer Society.

Acute upper gastrointestinal bleeding (UGIB) - initial evaluation and management.

PubMed

Khamaysi, Iyad; Gralnek, Ian M

2013-10-01

Acute upper gastrointestinal bleeding (UGIB) is the most common reason that the 'on-call' gastroenterologist is consulted. Despite the diagnostic and therapeutic capabilities of upper endoscopy, there is still significant associated morbidity and mortality in patients experiencing acute UGIB, thus this is a true GI emergency. Acute UGIB is divided into non-variceal and variceal causes. The most common type of acute UGIB is 'non-variceal' and includes diagnoses such as peptic ulcer (gastric and duodenal), gastroduodenal erosions, Mallory-Weiss tears, erosive oesophagitis, arterio-venous malformations, Dieulafoy's lesion, and upper GI tract tumours and malignancies. This article focuses exclusively on initial management strategies for acute upper GI bleeding. We discuss up to date and evidence-based strategies for patient risk stratification, initial patient management prior to endoscopy, potential causes of UGIB, role of proton pump inhibitors, prokinetic agents, prophylactic antibiotics, vasoactive pharmacotherapies, and timing of endoscopy. Copyright © 2013 Elsevier Ltd. All rights reserved.

YH12852, a potent and highly selective 5-HT4 receptor agonist, significantly improves both upper and lower gastrointestinal motility in a guinea pig model of postoperative ileus.

PubMed

Hussain, Z; Lee, Y J; Yang, H; Jeong, E J; Sim, J Y; Park, H

2017-10-01

Postoperative ileus (POI) is a transient gastrointestinal (GI) dysmotility that commonly develops after abdominal surgery. YH12852, a novel, potent and highly selective 5-hydroxytryptamine 4 (5-HT 4 ) receptor agonist, has been shown to improve both upper and lower GI motility in various animal studies and may have applications for the treatment of POI. Here, we investigated the effects and mechanism of action of YH12852 in a guinea pig model of POI to explore its therapeutic potential. The guinea pig model of POI was created by laparotomy, evisceration, and gentle manipulation of the cecum for 60 seconds, followed by closure with sutures under anesthesia. Group 1 received an oral administration of vehicle or YH12852 (1, 3, 10 or 30 mg/kg) only, while POI Group 2 was intraperitoneally pretreated with vehicle or 5-HT 4 receptor antagonist GR113808 (10 mg/kg) prior to oral dosing of vehicle or YH12852 (3 or 10 mg/kg). Upper GI transit was evaluated by assessing the migration of a charcoal mixture in the small intestine, while lower GI transit was assessed via measurement of fecal pellet output (FPO). YH12852 significantly accelerated upper and lower GI transit at the doses of 3, 10, and 30 mg/kg and reached its maximal effect at 10 mg/kg. These effects were significantly blocked by pretreatment of GR113808 10 mg/kg. Oral administration of YH12852 significantly accelerates and restores delayed upper and lower GI transit in a guinea pig model of POI. This drug may serve as a useful candidate for the treatment of postoperative ileus. © 2017 John Wiley & Sons Ltd.

Small bowel obstruction from distant metastasis of primary breast cancer: a case report.

PubMed

Oh, Seung Jae; Park, Seon Young; Kim, Ji Young; Yim, Hyunee; Jung, Yongsik; Han, Sae Hwan

2018-02-01

Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.

Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries

PubMed Central

Mo, Chen; Sun, Gang; Lu, Ming-Liang; Zhang, Li; Wang, Yan-Zhi; Sun, Xi; Yang, Yun-Sheng

2015-01-01

AIM: To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. METHODS: We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA. The preventive effects of PPIs were compared with the control group [taking placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA-associated upper GI injuries. The meta-analysis was performed using RevMan 5.1 software. RESULTS: We evaluated 8780 participants in 10 RCTs. The meta-analysis showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16; 95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with control. For patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36; 95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding (OR = 0.32; 95%CI: 0.13-0.79). CONCLUSION: PPIs are effective in preventing LDA-associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the risk of MACE. PMID:25954113

[How frequent is the diagnosis of GI metastasis in an endoscopic patient sample in general internal medicine clinics> Results of a questionnaire survey of 34 medical clinics].

PubMed

Madeya, S; Börsch, G; Greiner, L; Hahn, H J

1993-03-01

With the aim of analysing the frequency of gastrointestinal (GI) metastases identified by endoscopic procedures, a survey was conducted by questionnaire, which was completed by 34 of 127 medical departments. Peritoneal carcinosis and direct tumor extension were disregarded. One GI metastasis (duodenum) was verified among 3477 upper GI tract endoscopies. Primary site was cutaneous melanoma. In another case metastatic origin is discussed (esophagus). Considering the average frequency of 102 upper GI tract endoscopies performed by the collaborating centers, one case of gastroduodenal metastasis could be expected every 17 (34) months in these institutions. 1634 examinations of the colon and rectum did not reveal any metastatic tumor growth. A longterm study is planned to provide further statistically reliable prevalence data.

Human papillomavirus and gastrointestinal cancer in Iranian population: A systematic review and meta-analysis.

PubMed

Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima

2017-01-01

Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.

MicroRNAs (miRNAs) as biomarker(s) for prognosis and diagnosis of gastrointestinal (GI) cancers.

PubMed

Macha, Muzafar A; Seshacharyulu, Parthasarathy; Krishn, Shiv Ram; Pai, Priya; Rachagani, Satyanarayana; Jain, Maneesh; Batra, Surinder K

2014-01-01

Gastrointestinal (GI) cancers remain one of the most common malignancies and are the second common cause of cancer deaths worldwide. The limited effectiveness of therapy for patients with advanced stage and recurrent disease is a reflection of an incomplete understanding of the molecular basis of GI carcinogenesis. Major advancements have improved our understanding of pathology and pathogenesis of GI cancers, but high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate new sensitive and specific diagnostic and prognostic markers for GI cancers. MicroRNAs (miRNAs) are short (19-24 nucleotides) noncoding RNA molecules that regulate gene expression at the posttranscriptional level thus playing an important role in modulating various biological processes including, but not limited to developmental processes, proliferation, apoptosis, metabolism, differentiation, epithelial-mechenchymal transition and are involved in the initiation and progression of various human cancers. Unique miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor-specific and tissue-specific expression profiles, stability, robust clinical assays for detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic and prognostic tools for GI cancers.

MicroRNAs (miRNAs) as Biomarker(s) for Prognosis and Diagnosis of Gastrointestinal (GI) Cancers

PubMed Central

Macha, Muzafar A.; Seshacharyulu, Parthasarathy; Krishn, Shiv Ram; Pai, Priya; Rachagani, Satyanarayana; Jain, Maneesh; Batra, Surinder K.

2014-01-01

Gastrointestinal (GI) cancers remain one of the most common malignancies and are the second common cause of cancer deaths worldwide. The limited effectiveness of therapy for patients with advanced stage and recurrent disease is a reflection of an incomplete understanding of the molecular basis of GI carcinogenesis. Major advancements have improved our understanding of pathology and pathogenesis of GI cancers, but high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate new sensitive and specific diagnostic and prognostic markers for GI cancers. MicroRNAs (miRNAs) are short (19–24 nucleotides) noncoding RNA molecules that regulate gene expression at the posttranscriptional level thus playing an important role in modulating various biological processes including, but not limited, to developmental processes, proliferation, apoptosis, metabolism, differentiation, epithelial-mechenchymal transition and are involved in the initiation and progression of various human cancers. Unique miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor-specific and tissue-specific expression profiles, stability, robust clinical assays for detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic and prognostic tools for GI cancers. PMID:24479799

Exosomal microRNAs as potential circulating biomarkers in gastrointestinal tract cancers: a systematic review protocol.

PubMed

Gheytanchi, Elmira; Madjd, Zahra; Janani, Leila; Rasti, Arezoo; Ghods, Roya; Atyabi, Fatemeh; Asadi-Lari, Mohammad Hossein; Babashah, Sadegh

2017-11-17

Metastasis is the most frequent type of recurrence in gastrointestinal (GI) cancers, and there is an emerging potential for new diagnostic and therapeutic approaches, especially in the cases of metastatic GI carcinomas. The expression profiles of circulating exosomal microRNAs are of particular interest as novel non-invasive diagnostic and prognostic biomarkers for improved detection of GI cancers in body fluids, especially in the serum of patients with recurrent cancers. The aim of this study is to systematically review primary studies and identify the miRNA profiles of serum exosomes of GI cancers. This systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidance. Relevant studies will be identified through a comprehensive search of the following main electronic databases: PubMed, Web of Science, Embase, Scopus, and Google Scholar, with no language restrictions (up to July 2017). Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against pre-defined criteria. The quality assessment of the included studies will be performed by the Newcastle-Ottawa Scale (NOS). Data will be analyzed using Stata software V.12. Publication bias will be assessed by funnel plots, Beggs' and Eggers' tests. The levels of evidence for primary outcomes will be evaluated using the GRADE criteria. The analysis of circulating exosomal miRNA profiles provides attractive screening and non-invasive diagnostic tools for the majority of solid tumors including GI cancers. There is limited information regarding the relationship between serum exosomal miRNA profiles and the pathological condition of patients with different GI cancers. Since there is no specific biomarker for GI cancers, we aim to suggest a number of circulating exosomal miRNA candidates as potential multifaceted GI cancer biomarkers for clinical utility. PROSPERO CRD42017057129.

Role of enhanced multi-detector-row computed tomography before urgent endoscopy in acute upper gastrointestinal bleeding.

PubMed

Miyaoka, Youichi; Amano, Yuji; Ueno, Sayaka; Izumi, Daisuke; Mikami, Hironobu; Yazaki, Tomotaka; Okimoto, Eiko; Sonoyama, Takayuki; Ito, Satoko; Fujishiro, Hirofumi; Kohge, Naruaki; Imaoka, Tomonori

2014-04-01

Multi-detector-row computed tomography (MDCT) has been reported to be a potentially useful modality for detection of the bleeding origin in patients with acute upper massive gastrointestinal (GI) bleeding. The purpose of this study is to investigate the efficacy of MDCT as a routine method for detecting the origin of acute upper GI bleeding prior to urgent endoscopy. Five hundred seventy-seven patients with acute upper GI bleeding (514 nonvariceal patients, 63 variceal patients) who underwent urgent upper GI endoscopy were retrospectively analyzed. Patients were divided into three groups: enhanced MDCT, unenhanced MDCT, and no MDCT before endoscopy. The diagnostic accuracy of MDCT for detection of the bleeding origin was evaluated, and the average procedure times needed to endoscopically identify the bleeding origin were compared between groups. Diagnostic accuracy among endoscopists was 55.3% and 14.7% for the enhanced MDCT and unenhanced MDCT groups, respectively. Among nonvariceal patients, accuracy was 50.2% in the enhanced MDCT group, which was significantly better than that in the unenhanced MDCT group (16.5%). In variceal patients, accuracy was significantly better in the enhanced MDCT group (96.4%) than in the unenhanced MDCT group (0.0%). These accuracies were similar to those achieved by expert radiologists. The average procedure time to endoscopic detection of the bleeding origin in the enhanced MDCT group was significantly faster than that in the unenhanced MDCT and no-MDCT groups. Enhanced MDCT preceding urgent endoscopy may be an effective modality for the detection of bleeding origin in patients with acute upper GI bleeding. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

[The validity of the sentinel node concept in gastrointestinal cancers].

PubMed

Kitagawa, Y; Fujii, H; Mukai, M; Ando, N; Kubota, T; Ikeda, T; Ohgami, M; Watanabe, M; Otani, Y; Ozawa, S; Hasegawa, H; Furukawa, T; Nakahara, T; Kubo, A; Kumai, K; Kitajima, M

2000-03-01

Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.

Endoscopic Optical Coherence Tomography

NASA Astrophysics Data System (ADS)

Zhou, Chao; Fujimoto, James G.; Tsai, Tsung-Han; Mashimo, Hiroshi

New gastrointestinal (GI) cancers are expected to affect more than 290,200 new patients and will cause more than 144,570 deaths in the United States in 2013 [1]. When detected and treated early, the 5-year survival rate for colorectal cancer increases by a factor of 1.4 [1]. For esophageal cancer, the rate increases by a factor of 2 [1]. The majority of GI cancers begin as small lesions that are difficult to identify with conventional endoscopy. With resolutions approaching that of histopathology, optical coherence tomography (OCT) is well suited for detecting the changes in tissue microstructure associated with early GI cancers. Since the lesions are not endoscopically apparent, however, it is necessary to survey a relatively large area of the GI tract. Tissue motion is another limiting factor in the GI tract; therefore, in vivo imaging must be performed at extremely high speeds. OCT imaging can be performed using fiber optics and miniaturized lens systems, enabling endoscopic OCT inside the human body in conjunction with conventional video endoscopy. An OCT probe can be inserted through the working channel of a standard endoscope, thus enabling depth-resolved imaging of tissue microstructure in the GI tract with micron-scale resolution simultaneously with the endoscopic view (Fig. 68.1).

Glycemic index, glycemic load and invasive breast cancer incidence in postmenopausal women: The PREDIMED study.

PubMed

Castro-Quezada, Itandehui; Sánchez-Villegas, Almudena; Martínez-González, Miguel Á; Salas-Salvadó, Jordi; Corella, Dolores; Estruch, Ramón; Schröder, Helmut; Álvarez-Pérez, Jacqueline; Ruiz-López, María D; Artacho, Reyes; Ros, Emilio; Bulló, Mónica; Sorli, Jose V; Fitó, Montserrat; Ruiz-Gutiérrez, Valentina; Toledo, Estefanía; Buil-Cosiales, Pilar; García Rodríguez, Antonio; Lapetra, José; Pintó, Xavier; Salaverría, Itziar; Tur, Josep A; Romaguera, Dora; Tresserra-Rimbau, Anna; Serra-Majem, Lluís

2016-11-01

The objective of this study was to evaluate the prospective associations between dietary glycemic index (GI) and glycemic load (GL) and the risk for invasive breast cancer incidence in postmenopausal women at high cardiovascular disease (CVD) risk. This study was conducted within the framework of the PREvención con DIeta MEDiterránea (PREDIMED) study, a nutritional intervention trial for primary cardiovascular prevention. We included 4010 women aged between 60 and 80 years who were initially free from breast cancer but at high risk for CVD disease. Dietary information was collected using a validated 137-item food frequency questionnaire. We assigned GI values using the International Tables of GI and GL values. Cases were ascertained through yearly consultation of medical records and through consultation of the National Death Index. Only cases confirmed by results from cytology tests or histological evaluation were included. We estimated multivariable-adjusted hazard ratios for invasive breast cancer risk across tertiles of energy-adjusted dietary GI/GL using Cox regression models. We repeated our analyses using yearly repeated measures of GI/GL intakes. No associations were found between baseline dietary GI/GL and invasive breast cancer incidence. The multivariable hazard ratio and 95% confidence interval (CI) for the top tertile of dietary GI was 1.02 (95% CI: 0.42-2.46) and for dietary GL was 1.00 (95% CI: 0.44-2.30) when compared with the bottom tertile. Repeated-measures analyses yielded similar results. In sensitivity analyses, no significant associations were observed for women with obesity or diabetes. Dietary GI and GL did not appear to be associated with an increased risk for invasive breast cancer in postmenopausal women at high CVD risk.

Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013).

PubMed

Makarem, Nour; Bandera, Elisa V; Lin, Yong; Jacques, Paul F; Hayes, Richard B; Parekh, Niyati

2017-06-01

Higher carbohydrate intake, glycaemic index (GI), and glycaemic load (GL) are hypothesised to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms, but epidemiological evidence is inconsistent. This prospective cohort study investigates carbohydrate quantity and quality in relation to risk of adiposity-related cancers, which represent the most commonly diagnosed preventable cancers in the USA. In exploratory analyses, associations with three site-specific cancers: breast, prostate and colorectal cancers were also examined. The study sample consisted of 3184 adults from the Framingham Offspring cohort. Dietary data were collected in 1991-1995 using a FFQ along with lifestyle and medical information. From 1991 to 2013, 565 incident adiposity-related cancers, including 124 breast, 157 prostate and sixty-eight colorectal cancers, were identified. Cox proportional hazards models were used to evaluate the role of carbohydrate nutrition in cancer risk. GI and GL were not associated with risk of adiposity-related cancers or any of the site-specific cancers. Total carbohydrate intake was not associated with risk of adiposity-related cancers combined or prostate and colorectal cancers. However, carbohydrate consumption in the highest v. lowest quintile was associated with 41 % lower breast cancer risk (hazard ratio (HR) 0·59; 95 % CI 0·36, 0·97). High-, medium- and low-GI foods were not associated with risk of adiposity-related cancers or prostate and colorectal cancers. In exploratory analyses, low-GI foods, were associated with 49 % lower breast cancer risk (HR 0·51; 95 % CI 0·32, 0·83). In this cohort of Caucasian American adults, associations between carbohydrate nutrition and cancer varied by cancer site. Healthier low-GI carbohydrate foods may prevent adiposity-related cancers among women, but these findings require confirmation in a larger sample.

Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchino, Keita, E-mail: uchino13@intmed1.med.kyushu-u.ac.jp; Hirano, Gen; Hirahashi, Minako

2012-09-10

There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 proteinmore » to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.« less

Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients

PubMed Central

Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

2015-01-01

Abstract Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups. We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors. Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P < 0.05) higher symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P < 0.05) associated with candida esophagitis in non-HIV-infected patients. However, heartburn and acid regurgitation were independently (P < 0.05) associated with erosive esophagitis in both patient groups. The internal consistency test using Cronbach's α revealed that the 9 symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients (α, 0.85). This large-scale endoscopy-based study showed that HIV-infected patients have greater GI symptom scores compared with non-HIV-infected patients even after excluding GI-organic diseases. None of the upper GI symptoms predict candida esophagitis in HIV-infected patients, but dysphagia and odynophagia predict candida esophagitis in non-HIV-infected patients. Heartburn and acid regurgitation predict erosive esophagitis in both patient groups. PMID:26632738

Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients.

PubMed

Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

2015-11-01

Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups.We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors.Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P < 0.05) higher symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P < 0.05) associated with candida esophagitis in non-HIV-infected patients. However, heartburn and acid regurgitation were independently (P < 0.05) associated with erosive esophagitis in both patient groups. The internal consistency test using Cronbach's α revealed that the 9 symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients (α, 0.85).This large-scale endoscopy-based study showed that HIV-infected patients have greater GI symptom scores compared with non-HIV-infected patients even after excluding GI-organic diseases. None of the upper GI symptoms predict candida esophagitis in HIV-infected patients, but dysphagia and odynophagia predict candida esophagitis in non-HIV-infected patients. Heartburn and acid regurgitation predict erosive esophagitis in both patient groups.

Ethnic Variations in Gastric cancer in a tertiary care centre of Sikkim in North-East India.

PubMed

Lamtha, Sangey Chhophel; Tripathi, Manish Kumar; Bhutia, Karma Doma; Karthak, Caroline

2016-01-01

The etiology of gastric cancer is multifactorial. Marked differences in the incidence of gastric cancer among different ethnic groups living in the same geographical area have been observed. This study looked at ethnic and dietary factors in patients with gastric cancer diagnosed at a tertiary referral centre in Sikkim over a period of one year. Patients of 60 years and above were included in the study and divided into four ethnic groups : Bhutias, Lepchas, Rais and other groups. 211 cases underwent upper GI endoscopy and 32 were diagnosed to have gastric cancer. Gastric cancer incidence was highest in Bhutia ethnic group. A trend towards higher intake of smoked meats, fermented vegetables, salt tea, and H.pylori positivity in the Bhutia ethnic group was associated with higher incidence of gastric cancer as compared to other ethnic groups. The study with a referral centre bias showed that Bhutia ethnic group had a higher incidence of gastric cancer as compared to other ethnic groups.

Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy.

PubMed

Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S; Wunderlich, John R; Dudley, Mark E; Rosenberg, Steven A

2013-09-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3(+) T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8(+) cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ~50 × 10(9) T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3(+)CD8(+) cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I-mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I-mediated up-regulation of CD137 (4-1BB) expression on CD8(+) cells suggested that 0-3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.

Phenotype and Function of T Cells Infiltrating Visceral Metastases from Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell Transfer Therapy

PubMed Central

Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S.; Wunderlich, John R.; Dudley, Mark E.

2013-01-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3+ T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8+ cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ∼50 × 109 T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3+CD8+ cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I–mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I–mediated up-regulation of CD137 (4-1BB) expression on CD8+ cells suggested that 0–3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells. PMID:23904171

Bleeding after expandable nitinol stent placement in patients with esophageal and upper gastrointestinal obstruction: incidence, management, and predictors.

PubMed

Oh, Se Jin; Song, Ho-Young; Nam, Deok Ho; Ko, Heung Kyu; Park, Jung-Hoon; Na, Han Kyu; Lee, Jong Jin; Kang, Min Kyoung

2014-11-01

Placement of self-expandable nitinol stents is useful for the treatment of esophageal and upper gastrointestinal (GI) obstruction. However, complications such as stent migration, tumor overgrowth, and bleeding occur. Although stent migration and tumor overgrowth are well documented in previous studies, the occurrence of bleeding has not been fully evaluated. To evaluate the incidence, management strategies, and predictors of bleeding after placement of self-expandable nitinol stents in patients with esophageal and upper GI obstruction. We retrospectively reviewed the medical records and results of computed tomography and endoscopy of 1485 consecutive patients with esophageal and upper GI obstructions who underwent fluoroscopically guided stent placement. Bleeding occurred in 25 of 1485 (1.7%) patients 0 to 348 days after stent placement. Early stent-related bleeding occurred in 10 patients (40%) and angiographic embolization was used for 5/10. Late bleeding occurred in 15 patients (60%) and endoscopic hemostasis was used for 7/15. Twenty-two of 25 (88%) patients with bleeding had received prior radiotherapy and/or chemotherapy. Bleeding is a rare complication after placement of expandable nitinol stents in patients with esophageal and upper GI obstruction, but patients with early bleeding may require embolization for control. Care must be exercised on placing stents in patients who have received prior radiotherapy or chemotherapy. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Synthesis and Anticancer Activity of 2-(Alkyl-, Alkaryl-, Aryl-, Hetaryl-)-[1,2,4]triazolo[1,5-c]quinazolines

PubMed Central

Kovalenko, Sergiy I.; Antypenko, Lyudmyla M.; Bilyi, Andriy K.; Kholodnyak, Sergiy V.; Karpenko, Olexandr V.; Antypenko, Olexii M.; Mykhaylova, Natalya S.; Los, Tetyana I.; Kolomoets, Olexandra S.

2013-01-01

The combinatorial library of novel potential anticancer agents, namely, 2-(alkyl-, alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-c]quinazolines, was synthesized by the heterocyclization of the alkyl-, alkaryl-, aryl-, hetarylcarboxylic acid (3H-quinazoline-4-ylidene)hydrazides by oxidative heterocyclization of the 4-(arylidenehydrazino)quinazolines using bromine, and by the heterocyclization of N-(2-cyanophenyl)formimidic acid ethyl ester. The optimal method for synthesis of the s-triazolo[1,5-c]quinazolines appeared to be cyclocondensation of the corresponding carboxylic acid (3H-quinazoline-4-ylidene)hydrazides. The compounds’ structures were established by 1H, 13C NMR, LC- and EI-MS analysis. The in vitro screening of anticancer activity determined the most active compound to be 3,4,5-trimethoxy-N′-[quinazolin-4(3H)-ylidene]benzohydrazide (3.20) in micromolar concentrations with the GI50 level (MG_MID, GI50 is 2.29). Thus, the cancer cell lines whose growth is greatly inhibited by compound 3.20 are: non-small cell lung cancer (NCI-H522, GI50=0.34), CNS (SF-295, GI50=0.95), ovarian (OVCAR-3, GI50=0.33), prostate (PC-3, GI50=0.56), and breast cancer (MCF7, GI50=0.52), leukemia (K-562, GI50=0.41; SR, GI50=0.29), and melanoma (MDA-MB-435, GI50=0.31; SK-MEL-5, GI50=0.74; UACC-62, GI50=0.32). SAR-analysis is also discussed. PMID:23833709

Impact of laparoscopic sleeve gastrectomy on upper gastrointestinal symptoms.

PubMed

Carabotti, Marilia; Silecchia, Gianfranco; Greco, Francesco; Leonetti, Frida; Piretta, Luca; Rengo, Marco; Rizzello, Mario; Osborn, John; Corazziari, Enrico; Severi, Carola

2013-10-01

Altered gastric anatomy following laparoscopic sleeve gastrectomy (LSG) is likely to induce upper gastrointestinal (GI) symptoms. Published studies, however, have focused mainly on gastroesophageal reflux disease (GERD). This study aims to evaluate LSG's impact on the prevalence of upper GI symptoms and to assess the effects of time from surgery, weight loss, and proton pump inhibitor (PPI) therapy. The validated Rome III Criteria symptom questionnaire for upper GI symptoms, including quality of life items, has been self-administered to 97 patients who underwent LSG. Symptoms were analyzed either separately or altogether to classify patients in GERD or dyspepsia, subdivided in epigastric pain (EPS) and post-prandial distress (PDS) syndromes. Before LSG, 52.7% of the patients were asymptomatic, 27.0% had GERD, and 8.1% had dyspepsia (2.7% EPS, 5.4% PDS). After a median follow-up of 13 months, 91.9% of the patients complained of upper GI symptoms, the most prevalent being PDS (59.4 %). GERD prevalence did not differ before and after LSG. The only symptom strongly related to LSG was dysphagia (OR 4.7, 95% CI 1.3-20.4, p = 0.015), which was present in 19.7% of the patients and mainly associated with PDS rather than GERD. GI symptoms, however, did not have a great impact on quality of life. Time from surgery, weight loss after surgery, as well as concomitant PPI, did not influence the symptoms. After a median follow-up of 13 months, PDS-like dyspepsia, rather than GERD, was the main complaint, both poorly responding to PPI therapy. A longer follow-up will be necessary to evaluate their future persistency.

The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study.

PubMed

Hannouf, Malek B; Winquist, Eric; Mahmud, Salaheddin M; Brackstone, Muriel; Sarma, Sisira; Rodrigues, George; Rogan, Peter K; Hoch, Jeffrey S; Zaric, Gregory S

2018-01-01

The purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS). We used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have "occult" primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as "obvious." We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment. Eighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences. GI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

Novel Holistic Approaches for Overcoming Therapy Resistance in Pancreatic and Colon Cancers.

PubMed

Sarkar, Fazlul H

2016-01-01

Gastrointestinal (GI) cancers, such as of the colon and pancreas, are highly resistant to both standard and targeted therapeutics. Therapy-resistant and heterogeneous GI cancers harbor highly complex signaling networks (the resistome) that resist apoptotic programming. Commonly used gemcitabine or platinum-based regimens fail to induce meaningful (i.e. disease-reversing) perturbations in the resistome, resulting in high rates of treatment failure. The GI cancer resistance networks are, in part, due to interactions between parallel signaling and aberrantly expressed microRNAs (miRNAs) that collectively promote the development and survival of drug-resistant cancer stem cells with epithelial-to-mesenchymal transition (EMT) characteristics. The lack of understanding of the resistance networks associated with this subpopulation of cells as well as reductionist, single protein-/pathway-targeted approaches have made 'effective drug design' a difficult task. We propose that the successful design of novel therapeutic regimens to target drug-resistant GI tumors is only possible if network-based drug avenues and agents, in particular 'natural agents' with no known toxicity, are correctly identified. Natural agents (dietary agents or their synthetic derivatives) can individually alter miRNA profiles, suppress EMT pathways and eliminate cancer stem-like cells that derive from pancreatic cancer and colon cancer, by partially targeting multiple yet meaningful networks within the GI cancer resistome. However, the efficacy of these agents as combinations (e.g. consumed in the diet) against this resistome has never been studied. This short review article provides an overview of the different challenges involved in the understanding of the GI resistome, and how novel computational biology can help in the design of effective therapies to overcome resistance. © 2015 S. Karger AG, Basel.

Cost effectiveness of surveillance for GI cancers.

PubMed

Omidvari, Amir-Houshang; Meester, Reinier G S; Lansdorp-Vogelaar, Iris

2016-12-01

Gastrointestinal (GI) diseases are among the leading causes of death in the world. To reduce the burden of GI diseases, surveillance is recommended for some diseases, including for patients with inflammatory bowel diseases, Barrett's oesophagus, precancerous gastric lesions, colorectal adenoma, and pancreatic neoplasms. This review aims to provide an overview of the evidence on cost-effectiveness of surveillance of individuals with GI conditions predisposing them to cancer, specifically focussing on the aforementioned conditions. We searched the literature and reviewed 21 studies. Despite heterogeneity of studies in terms of settings, study populations, surveillance strategies and outcomes, most reviewed studies suggested at least some surveillance of patients with these GI conditions to be cost-effective. For some high-risk conditions frequent surveillance with 3-month intervals was warranted, while for other conditions, surveillance may only be cost-effective every 10 years. Further studies based on more robust effectiveness evidence are needed to inform and optimise surveillance programmes for GI cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

PubMed

Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

2016-07-03

Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

Gastrointestinal cancers in India: Treatment perspective

PubMed Central

Ghadyalpatil, Nikhil Suresh; Supriya, Chopra; Prachi, Patil; Ashwin, Dsouza; Avanish, Saklani

2016-01-01

GI cancer is not one cancer but is a term for the group of cancers that affect the digestive system including gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), esophageal cancer (EC), and pancreatic cancer (PC). Overall, the GI cancers are responsible for more cancers and more deaths from cancer than any other organ. 5 year survival of these cancers remains low compared to western world. Unlike the rest of the world where organ based specialities hepatobiliary, pancreatic, colorectal and esophagogastric exist, these cancers are managed in India by either a gastrointestinal surgeons, surgical oncologist, or a general surgeon with varying outcomes. The aim of this review was to collate data on GI cancers in indian continent. In colorectal cancers, data from tertiary care centres identifies the unique problem of mucinous and signet colorectal cancer. Results of rectal cancer resection in terms of technique (intersphincteric resection, extralevator aper, minimal invasive approach) to be comparable with world literature. However long term outcome and data regarding colon cancers and nationally is needed. Gastric cancer at presentation are advanced and in surgically resected patients, there is need for a trial to compare chemoradiation vs chemotherapy alone to prevent loco regional recurrence. Data on minimal invasive gastric cancer surgery may be sparse for the same reason. Theree is a lot of data on surgical techniques and perioperatve outcomes in pancreatic cancer. There is a high volume of locally advanced gallbladder cancers with efforts on to decide whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is better for down staging. Considering GI cancers, a heterogeneous disease with site specific treatment options and variable outcomes, the overall data and outcomes are extremely variable. Young patients with pathology unique to the Indian subcontinent (for example, signet ring rectal cancer, GBCs) need focussed attention. Solution for such pathology needs to come from the Indian continent itself. Joint efforts to improve outcomes for GI cancer can be integrated under the national cancer grid program. PMID:27606298

Gastrointestinal cancers in India: Treatment perspective.

PubMed

Ghadyalpatil, Nikhil Suresh; Supriya, Chopra; Prachi, Patil; Ashwin, Dsouza; Avanish, Saklani

2016-01-01

GI cancer is not one cancer but is a term for the group of cancers that affect the digestive system including gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), esophageal cancer (EC), and pancreatic cancer (PC). Overall, the GI cancers are responsible for more cancers and more deaths from cancer than any other organ. 5 year survival of these cancers remains low compared to western world. Unlike the rest of the world where organ based specialities hepatobiliary, pancreatic, colorectal and esophagogastric exist, these cancers are managed in India by either a gastrointestinal surgeons, surgical oncologist, or a general surgeon with varying outcomes. The aim of this review was to collate data on GI cancers in indian continent. In colorectal cancers, data from tertiary care centres identifies the unique problem of mucinous and signet colorectal cancer. Results of rectal cancer resection in terms of technique (intersphincteric resection, extralevator aper, minimal invasive approach) to be comparable with world literature. However long term outcome and data regarding colon cancers and nationally is needed. Gastric cancer at presentation are advanced and in surgically resected patients, there is need for a trial to compare chemoradiation vs chemotherapy alone to prevent loco regional recurrence. Data on minimal invasive gastric cancer surgery may be sparse for the same reason. Theree is a lot of data on surgical techniques and perioperatve outcomes in pancreatic cancer. There is a high volume of locally advanced gallbladder cancers with efforts on to decide whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is better for down staging. Considering GI cancers, a heterogeneous disease with site specific treatment options and variable outcomes, the overall data and outcomes are extremely variable. Young patients with pathology unique to the Indian subcontinent (for example, signet ring rectal cancer, GBCs) need focussed attention. Solution for such pathology needs to come from the Indian continent itself. Joint efforts to improve outcomes for GI cancer can be integrated under the national cancer grid program.

In Vivo and Ex Vivo Imaging Reveals a Long-Lasting Chlamydial Infection in the Mouse Gastrointestinal Tract following Genital Tract Inoculation

PubMed Central

Zhang, Qi; Huang, Yumeng; Gong, Siqi; Yang, Zhangsheng; Sun, Xin; Schenken, Robert

2015-01-01

Intravaginal infection with Chlamydia muridarum in mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected with C. trachomatis. Here, we utilized in vivo imaging of C. muridarum infection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. Unexpectedly, the C. muridarum-derived signal was still detectable in the abdominal area 100 days after inoculation. Ex vivo imaging of the mouse organs revealed that the long-lasting presence of the chlamydial signal was restricted to the gastrointestinal (GI) tract, which was validated by directly measuring the chlamydial live organisms and genomes in the same organs. The C. muridarum organisms spreading from the genital to the GI tracts were detected in different mouse strains and appeared to be independent of oral or rectal routes. Mice prevented from orally taking up excretions also developed the long-lasting GI tract infection. Inoculation of C. muridarum directly into the upper genital tract, which resulted in a delayed vaginal shedding of live organisms, accelerated the chlamydial spreading to the GI tract. Thus, we have demonstrated that the genital tract chlamydial organisms may use a systemic route to spread to and establish a long-lasting infection in the GI tract. The significance of the chlamydial spreading from the genital to GI tracts is discussed. PMID:26099591

Gastrointestinal toxicity and its relation to dose distributions in the anorectal region of prostate cancer patients treated with radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heemsbergen, Wilma D.; Hoogeman, Mischa S.; Hart, Guus A.M.

2005-03-15

Purpose: To study the correlations between the dose distributions in the anorectal region and late GI symptoms in patients treated for localized prostate carcinoma. Methods and materials: Data from a randomized study were analyzed. In this trial, patients were treated with either rectangular or conformal fields with a dose of 66 Gy. Data concerning GI symptoms were collected from questionnaires of 197 patients. The distributions of the anorectal region were projected on maps, and the dose parameters were calculated. The incidences of complaints were studied as a function of the dose-area parameters and clinical parameters, using a proportional hazard regressionmore » model. Finally, we tested a series of dose parameters originating from different parts of the anorectal region. Results: Analyzing the total region, only a statistically significant dose-area effect relation for bleeding was found (p < 0.01). Defining subareas, we found effect relations for bleeding, soiling, fecal incontinence, and mucus loss. For bleeding and mucus loss, the strongest correlation was found for the dose received by the upper 70-80% of the anorectal region (p < 0.01). For soiling and fecal incontinence, we found the strongest association with the dose to the lower 40-50% (p < 0.05). Conclusion: We found evidence that complaints originate from specific regions of the irradiated lower GI tract. Bleeding and mucus loss are probably related to irradiation of the upper part of the rectum. Soiling and fecal incontinence are more likely related to the dose to the anal canal and the lower part of the rectum.« less

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine.

PubMed

Lou, Wenhui; Xia, Ying; Xiang, Peng; Zhang, Liangqing; Yu, Xiangyou; Lim, Sam; Xu, Mo; Zhao, Lina; Rydholm, Hans; Traxler, Barry; Qin, Xinyu

2018-04-20

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control. ClinicalTrials.gov identifier NCT02157376.

Controlling nutritional status score, a promising prognostic marker in patients with gastrointestinal cancers after surgery: A systematic review and meta-analysis.

PubMed

Zhang, Yi; Zhang, Xu

2018-05-18

Controlling nutritional status (CONUT) score has been reported to correlate with gastrointestinal (GI) cancer prognosis, but the results remain inconsistent. This study was to synthetically determine the associations between CONUT score and prognosis in GI cancers. Online databases PubMed, Web of Science, Cochrane library, Embase, Google scholar, Wanfang and National Knowledge Infrastructure (CNKI) were searched for eligible articles published prior to March 10, 2018. Pooled Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the prognostic potential of CONUT score in patients with GI cancers using Stata SE 12.0. A total of 9 articles comprising 2400 patients were included in the analysis. Overall, CONUT score greater than the cutoff predicted poor 5-year overall survival for patients with GI cancers (HR = 2.39, 95% CI: 1.84-2.95, p < 0.001) and 5-year cancer-specific survival (HR: 3.47, 95% CI: 1.75-5.19, p < 0.001). And patients with high CONUT score were at significantly greater risk of relapse/recurrence (HR = 1.64, 95% CI: 1.30-1.98, p < 0.001). CONUT could be a noninvasive prognostic indicator that useful for predicting long-term survival in GI cancer patients after surgery. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

[Indications, diagnoses and quality markers in upper and lower endoscopies in 2010 and 2011 at the 1st Department of Medicine, Semmelweis University, Budapest].

PubMed

Gönczi, Lóránt; Kürti, Zsuzsanna; Golovics, Petra; Végh, Zsuzsanna; Lovász, Barbara; Dorkó, Andrea; Seres, Anna; Sümegi, Liza; Menyhárt, Orsolya; Kiss, Lajos; Papp, János; Gecse, Krisztina; Lakatos, Péter László

2016-12-01

The aim was to assess the incidence of endoscopic findings based on the indication of the procedures in upper/lower endoscopies, and measuring quality indicators of colonoscopies at the 1st Department of Medicine, Semmelweis University, Budapest. Data of 2987 patients (male/female:1361/1626, mean age: 60.7 years(y), SD: 16.7y) between 01.01.2010 and 31.12.2011 were analyzed. Both inpatient and outpatient records were collected. Incidence of peptic ulcer disease, esophageal varices, gastric polyps and gastric cancer were 10.8%, 4.5%, 6.1%, 2.9% in upper endoscopies, respectively. In colonoscopies colorectal polyps, diverticulosis, colorectal cancer and IBD were found in 29.9%, 22.4%, 6.9%, 9.7%, respectively. In patients having upper endoscopy with GI bleeding indication, older age (p<0.001), male gender (p<0.001, OR: 1.64), acenocoumarol/heparin use (p<0,001, peptic ulcers and esophageal varices were more frequent (p<0.001, OR: 2.83 and p<0.001, OR: 2.79), while in colonoscopies colorectal cancer had higher incidence (p<0.001, OR:3.27). 81% of colonoscopies were complete. Causes of incomplete procedures were ineffective bowel preparation (38.2%), technical difficulties (25.1%) and strictures (20.5%). The endoscopic findings and quality indicators (adenoma detection rate, coecal intubation rate) were in line with that reported in published series. Orv. Hetil., 2016, 157(52), 2074-2081.

[Home parenteral nutrition for terminal stage of cancer patient].

PubMed

Takamura, S; Sakuyama, T; Nakamura, Y; Takahashi, N; Hattori, M

1997-12-01

In the last 6 years, we have experienced 20 cancer patients who received home parenteral nutrition for terminal stage. The patients had 13 gastric cancers, 3 esophageal cancers and 5 others. The prognosis of upper G-I cancer is known to be poorer than that of colon cancer. The home care of our cases, the gastric cancer lasted 25 days on average, which was shorter than others. So the home care for patients in the terminal stage of gastric cancer is very short. Therefore we decide the home care for the terminal stage of gastric cancer as soon as possible. We conducted a questionnaire survey of our cases and family. We finally found that the most important thing is the safety of patient for the maintenance of home care. Our home care system is made up of a 3-way relationship among the patient, support system and doctor. The doctor is on call for the problems of the patient for 24 hours. Therefore, we believe that this system is comfortable for both the patient and family.

Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses.

PubMed

Tözün, Nurdan; Vardareli, Eser

Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virus-related chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.

Polycyclic Aromatic Hydrocarbons and digestive tract cancers - a perspective

PubMed Central

Diggs, Deacqunita L.; Huderson, Ashley C.; Harris, Kelly L.; Myers, Jeremy N.; Banks, Leah D.; Rekhadevi, Perumalla V.; Niaz, Mohammad S.; Ramesh, Aramandla

2011-01-01

Cancers of the colon are most common in the Western world. In majority of these cases, there is no familial history and sporadic gene damage seems to play an important role in the development of tumors in the colon. Studies have shown that environmental factors, especially diet, play an important role in susceptibility to GI tract cancers. Consequently, environmental chemicals that contaminate food or diet during its preparation becomes important in the development of GI cancers. Polycyclic aromatic hydrocarbons (PAHs) are one such family of ubiquitous environmental toxicants. These pollutants enter the human body through consumption of contaminated food, drinking water, inhalation of cigarette smoke, automobile exhausts, and contaminated air from occupational settings. Among these pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs and their ability to cause toxicity and breast or lung cancer have been published, aspects on contribution of diet, smoking and other factors towards development of digestive tract cancers and strategies to assess risk from exposure to PAHs have received much less attention. This review, therefore, focuses on dietary intake of PAHs in humans, animal models, and cell cultures used for GI cancer studies along with epidemiological findings. Bioavailability and biotransformation processes, which influence the disposition of PAHs in body and the underlying causative mechanisms of GI cancers, are also discussed. The existing data gaps and scope for future studies is also emphasized. This information is expected to stimulate research on mechanisms of sporadic GI cancers caused by exposure to environmental carcinogens. PMID:22107166

Digestive cancer management in Asia: position statements: a report on GI Oncology Summit in 2011.

PubMed

Sung, Joseph J Y; Ng, Enders K W; Lin, Jaw-Town; Ho, K Y; Ji, Jia-Fu; Sugano, Kentaro; Poon, Ronnie T P; Chan, Anthony T C; Goh, Khean-Lee; Han, Kwang-Hyub; Chen, Leo L T; Wu, Kai-Chun; Ng, Simon S M; Bresalier, Robert S; Chan, Francis K L

2012-09-01

With the rising incidence of digestive cancers in the Asia Pacific region and the advancement in diagnosis, management and palliation in these conditions, the clinical burden on oncologists is ever increasing. This Summit meeting was called to discuss the optimal management of digestive cancers and the role of Gastroenterologists. Experts from Asia Pacific countries in the fields of medical, oncologic, surgical and endoscopic management of cancers in the esophagus, stomach, colon/rectum and the liver reviewed the literature and their practice. 18 position statements were drafted, debated and voted. It was agreed that the burden on GI cancer is increasing. More research will be warranted on chemotherapy, chemoprevention, cost-effectiveness of treatment and nutrition. Cancer management guidelines should be developed in this region when more clinical data are available. In order to improve care to patients, a multi-disciplinary team coordinated by a "cancer therapist" is proposed. This cancer therapist can be a gastroenterologist, a surgeon or any related discipline who have acquired core competence training. This training should include an attachment in a center-of-excellence in cancer management for no less than 12 months. The management of GI cancer should be an integrated multi-disciplinary approach and training for GI cancer therapists should be provided for. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Nonvariceal upper gastrointestinal bleeding: differences in outcome for patients admitted to internal medicine and gastroenterological services.

PubMed

Sandel, M H; Kolkman, J J; Kuipers, E J; Cuesta, M A; Meuwissen, S G

2000-09-01

It has been suggested that admission to a gastroenterology service (GAS) is associated with a better prognosis and lower cost for treatment of gastrointestinal (GI) diseases, such as upper GI bleeding (UGB). However, a large potential bias by higher comorbidity on internal medicine services (MED) could not be excluded from these studies. We therefore compared patients with upper GI bleeding admitted to a gastroenterology or internal medicine department, with special emphasis on prognostic factors, such as comorbidity, and outcome. Between 1991 and 1995, 322 patients were admitted to our hospital for UGB. Forty-five patients had variceal and 277 patients had nonvariceal upper GI bleeding (NUGB). Of 232 patients with primary NUGB, 125 were admitted to GAS and 93 to MED. The charts of these patients were revised, comorbidity was carefully recorded, and the Rockall risk score was calculated. All deaths were individually classified as unavoidable, mostly due to severe underlying illness, or potentially avoidable. No differences in delay for endoscopy or treatment were observed between GAS and MED. The rebleeding, surgery, and mortality rates in GAS and MED patients were 11.6% versus 11.5% (NS), 7.8% versus 7.3% (NS), and 2.4% versus 10.8% (p = 0.02), respectively. Rockall scores differed between GAS and MED patients (3.1 +/- 1.8 vs 3.7 +/- 1.7, p = 0.02). The mortality rate stratified by Rockall score was lower for the GAS patients. However, individual analysis revealed that only three of 13 deaths were potentially avoidable: two of 10 at the MED and one of three at the GAS. The lower mortality among nonvariceal upper GI bleeding patients admitted to a gastroenterological service compared to an internal medicine service was mainly due to lesser comorbidity. This effect was not detected by stratification according to Rockall, but shown with analysis of individual patient charts only. The latter underscores the potential pitfalls when comparing outcome or cost of treatment between different medical services.

Impact of homeobox genes in gastrointestinal cancer.

PubMed

Joo, Moon Kyung; Park, Jong-Jae; Chun, Hoon Jai

2016-10-07

Homeobox genes, including HOX and non- HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal (GI) cancers, most studies have focused on the function of non- HOX genes including caudal-related homeobox transcription factor 1 (CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.

A prospective outcomes analysis of palliative procedures performed for malignant intestinal obstruction due to recurrent ovarian cancer.

PubMed

Chi, Dennis S; Phaëton, Rebecca; Miner, Thomas J; Kardos, Steven V; Diaz, John P; Leitao, Mario M; Gardner, Ginger; Huh, Jae; Tew, William P; Konner, Jason A; Sonoda, Yukio; Abu-Rustum, Nadeem R; Barakat, Richard R; Jaques, David P

2009-08-01

To obtain prospective outcomes data on patients (pts) undergoing palliative operative or endoscopic procedures for malignant bowel obstruction due to recurrent ovarian cancer. An institutional study was conducted from July 2002 to July 2003 to prospectively identify pts who underwent an operative or endoscopic procedure to palliate the symptoms of advanced cancer. This report focuses on pts with malignant bowel obstruction due to recurrent ovarian cancer. Procedures performed with an upper or lower gastrointestinal (GI) endoscope were considered "endoscopic." All other cases were classified as "operative." Following the procedure, the presence or absence of symptoms was determined and followed over time. All pts were followed until death. Palliative interventions were performed on 74 gynecologic oncology pts during the study period, of which 26 (35%) were for malignant GI obstruction due to recurrent ovarian cancer. The site of obstruction was small bowel in 14 (54%) cases and large bowel in 12 (46%) cases. Palliative procedures were operative in 14 (54%) pts and endoscopic in the other 12 (46%). Overall, symptomatic improvement or resolution within 30 days was achieved in 23 (88%) of 26 patients, with 1 (4%) postprocedure mortality. At 60 days, 10 (71%) of 14 pts who underwent operative procedures and 6 (50%) of 12 pts who had endoscopic procedures had symptom control. Median survival from the time of the palliative procedure was 191 days (range, 33-902) for those undergoing an operative procedure and 78 days (range, 18-284) for those undergoing an endoscopic procedure. Patients with malignant bowel obstructions due to recurrent ovarian cancer have a high likelihood of experiencing relief of symptoms with palliative procedures. Although recurrence of symptoms is common, durable palliation and extended survival are possible, especially in those patients selected for operative intervention.

Conditionally replicative adenovirus for gastrointestinal cancers.

PubMed

Yamamoto, Masato

2004-08-01

The clinical outcome of advanced gastrointestinal (GI) cancers (especially pancreatic and oesophageal cancers) is dismal, despite the advance of conventional therapeutic strategies. Cancer gene therapy is a category of new therapeutics, among which conditionally replicative adenovirus (CRAd) is one promising strategy to overcome existing obstacles of cancer gene therapy. Various CRAds have been developed for GI cancer treatment by taking advantage of the replication biology of adenovirus. Some CRAds have already been tested in clinical trials, but have fallen short of initial expectations. Concerns for clinical applicability include therapeutic potency, replication selectivity and interval end points in clinical trials. In addition, improvement of experimental animal models is needed for a deeper understanding of CRAd biology. Despite these obstacles, CRAds continue to be an exciting area of investigation with great potential for clinical utility. Further virological and oncological research will eventually lead to full realisation of the therapeutic potential of CRAds in the field of GI cancers.

Tenure Track Investigator | Center for Cancer Research

Cancer.gov

This position, which is supported with stable financial resources, is the equivalent of Assistant Professor/Associate Professor in an academic department. The Thoracic and Gastrointestinal Oncology Branch (TGIB) is looking for a candidate who will complement our current group of principal investigators focused on thoracic and gastrointestinal (GI) cancers. The candidate is expected to develop a translational research program focused on GI cancers. As such, the candidate will conduct both laboratory-based investigations, as well as develop a clinical program related to work being conducted in his or her laboratory. We encourage outstanding physician scientists investigating any area of GI research to apply. Areas of interest include, but are not limited to, hepatobiliary and colon rectal cancer, and development of novel therapeutics. Candidates may be eligible to join the NCI Liver Cancer Program.

Perioperative Administration of Traditional Japanese Herbal Medicine Daikenchuto Relieves Postoperative Ileus in Patients Undergoing Surgery for Gastrointestinal Cancer: A Systematic Review and Meta-analysis.

PubMed

Ishizuka, Mitsuru; Shibuya, Norisuke; Nagata, Hitoshi; Takagi, Kazutoshi; Iwasaki, Yoshimi; Hachiya, Hiroyuki; Aoki, Taku; Kubota, Keiichi

2017-11-01

Although it has been widely demonstrated that administration of Daikenchuto (DKT), a traditional Japanese herbal medicine, improves gastrointestinal (GI) motility in patients undergoing abdominal surgery, few studies have investigated the efficacy of perioperative DKT administration for relief of postoperative ileus (PI) in patients undergoing surgery for GI cancer. Therefore, the aim of this study was to investigate whether perioperative administration of DKT relieves PI in patients with GI cancer. We performed a comprehensive electronic search of the literature (Cochrane Library, PubMed, the Web of Science and ICHUSHI) up to December 2016 to identify studies that had shown the efficacy of perioperative DKT administration for relief of PI in patients with GI cancer. To integrate the individual effect of DKT, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I 2 statistics. Seven studies involving a total of 1,134 patients who had undergone GI cancer surgery were included in this meta-analysis. Among 588 patients who received DKT perioperatively, 67 (11.4%) had PI, whereas among 546 patients who did not receive DKT perioperatively, 87 (15.9%) had PI. Perioperative administration of DKT significantly reduced the occurrence of PI (RR=0.58, 95% CI=0.35-0.97, p=0.04, I 2 =48%) in comparison to patients who did not receive DKT or received placebo. The result of this meta-analysis suggests that perioperative administration of DKT relieves PI in patients undergoing surgery for GI cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Emerging Role of MicroRNAs as Liquid Biopsy Biomarkers in Gastrointestinal Cancers

PubMed Central

Shigeyasu, Kunitoshi; Toden, Shusuke; Zumwalt, Timothy J.; Okugawa, Yoshinaga; Goel, Ajay

2017-01-01

Cancer has emerged as a leading cause of mortality worldwide, claiming over 8 million lives annually. Gastrointestinal (GI) cancers account for ~35% of these mortalities. Recent advances in diagnostic and treatment strategies have reduced mortality among GI cancer patients, yet a significant number of patients still develop late-stage cancer, where treatment options are inadequate. Emerging interests in ‘liquid biopsies’ have encouraged investigators to identify and develop clinically-relevant noninvasive genomic and epigenomic signatures that can be exploited as biomarkers capable of detecting premalignant and early-stage cancers. In this context, microRNAs (miRNAs), which are small non-coding RNAs that are frequently dysregulated in cancers, have emerged as promising entities for such diagnostic purposes. Albeit the future looks promising, current approaches for detecting miRNAs in blood and other biofluids remain inadequate. This review summarizes existing efforts to exploit circulating miRNAs as cancer biomarkers, evaluates their potential and challenges as liquid biopsy-based biomarkers for GI cancers. PMID:28143873

One hundred and one over-the-scope-clip applications for severe gastrointestinal bleeding, leaks and fistulas.

PubMed

Wedi, Edris; Gonzalez, Susana; Menke, Detlev; Kruse, Elena; Matthes, Kai; Hochberger, Juergen

2016-02-07

To investigate the efficacy and clinical outcome of patients treated with an over-the-scope-clip (OTSC) system for severe gastrointestinal hemorrhage, perforations and fistulas. From 02-2009 to 10-2012, 84 patients were treated with 101 OTSC clips. 41 patients (48.8%) presented with severe upper-gastrointestinal (GI) bleeding, 3 (3.6%) patients with lower-GI bleeding, 7 patients (8.3%) underwent perforation closure, 18 patients (21.4%) had prevention of secondary perforation, 12 patients (14.3%) had control of secondary bleeding after endoscopic mucosal resection or endoscopic submucosal dissection (ESD) and 3 patients (3.6%) had an intervention on a chronic fistula. In 78/84 patients (92.8%), primary treatment with the OTSC was technically successful. Clinical primary success was achieved in 75/84 patients (89.28%). The overall mortality in the study patients was 11/84 (13.1%) and was seen in patients with life-threatening upper GI hemorrhage. There was no mortality in any other treatment group. In detail OTSC application lead to a clinical success in 35/41 (85.36%) patients with upper GI bleeding and in 3/3 patients with lower GI bleeding. Technical success of perforation closure was 100% while clinical success was seen in 4/7 cases (57.14%) due to attendant circumstances unrelated to the OTSC. Technical and clinic success was achieved in 18/18 (100%) patients for the prevention of bleeding or perforation after endoscopic mucosal resection and ESD and in 3/3 cases of fistula closure. Two application-related complications were seen (2%). This largest single center experience published so far confirms the value of the OTSC for GI emergencies and complications. Further clinical experience will help to identify optimal indications for its targeted and prophylactic use.

Evaluating compliance to a low glycaemic index (GI) diet in women with polycystic ovary syndrome (PCOS).

PubMed

Egan, Nicola; Read, Anna; Riley, Paddy; Atiomo, William

2011-03-08

A low Glycaemic Index (GI) diet may decrease some long-term health risks in Polycystic Ovary Syndrome (PCOS) such as endometrial cancer. This study was performed to assess compliance to a low GI diet in women with PCOS. Food diaries prospectively collected over 6 months from women on a low GI diet or healthy eating diet were analysed retrospectively. The women were recruited for a pilot randomised control trial investigating whether a low GI diet decreased the risk of Endometrial Cancer. Nine women with PCOS completed 33 food diaries (17 from women on a low GI diet and 16 from women on a healthy eating diet) recording 3023 food items (low GI group:n = 1457; healthy eating group:n = 1566). Data was analysed using Foster-Powell international values inserted into an SPSS database as no scientifically valid established nutrition software was found. The main outcome measures were mean item GI and Glyacemic Load (GL), mean meal GL, percentage high GI foods and mean weight loss. Women allocated the low GI diet had a statistically significant lower GI of food items (33.67 vs 36.91, p < 0.05), lower percentage of high GI foods (4.3% vs 12.1%, p < 0.05) and lower GL of food items and meals. Women with PCOS on a low GI diet consumed food items with a significantly lower mean GI and GL compared to the healthy eating diet group. Longer term compliance needs evaluation in subsequent studies to ascertain that this translates to reduced long term health risks. ISRCTN: ISRCTN86420258.

Peptide YY, neuropeptide Y and corticotrophin-releasing factor modulate gastrointestinal motility and food intake during acute stress.

PubMed

Forbes, Sarah C; Cox, Helen M

2014-11-01

Peripheral neuropeptide Y (NPY) provides protection against the endocrine, feeding and gastrointestinal (GI) responses to stress; however, it is not yet established how it interacts with corticotrophin-releasing factor (CRF) to mediate these effects. Peptide YY (PYY) also has significant roles in GI motility and food intake but little is known about its role in stress responses. Upper GI transit, fecal pellet output (FPO) and feeding responses, and the role of CRF1 receptors, during restraint or a novel environment stress, were ascertained in PYY-/-, NPY-/- and wild type (WT) mice, with CRF and the CRF1 antagonist, antalarmin, injected intraperitoneally. Upper GI transit and FPO were significantly increased in PYY-/- mice during restraint stress. Exogenous CRF increased defecation during placement in a novel environment in WT mice through CRF1 , while CRF1 blockade reduced defecation in WT and NPY-/- mice but had no effect in PYY-/- mice. In addition, CRF1 blockade had no effect on upper GI transit in WT mice, or on food intake in PYY-/- or NPY-/- mice, but it significantly increased food intake in WT mice. Endogenous NPY appears to inhibit the colonic motor response induced by CRF1 activation, unlike PYY, while both peptides are required for CRF1 modulation of feeding behavior during stress. Overall, these results provide new insights into the mechanism by which PYY and NPY affect stress responses. © 2014 John Wiley & Sons Ltd.

Use of gastroprotection in patients discharged from hospital on nonsteroidal anti-inflammatory drugs.

PubMed

Coté, Gregory A; Norvell, John P; Rice, John P; Bulsiewicz, William J; Howden, Colin W

2008-01-01

Gastrointestinal (GI) hemorrhage is responsible for 200-400,000 hospitalizations in the United States annually. Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for > or =30% of admissions due to GI hemorrhage. Misoprostol reduces the number of NSAID-related upper GI events while proton pump inhibitors (PPIs) reduce the incidence of endoscopic ulcers. To measure the utilization of GI prophylaxis in patients discharged from hospital on ulcerogenic medicines. We performed a medical record review of all 480 patients discharged from the medical service over a 3-month period on aspirin or nonaspirin NSAIDs. Use of gastroprotection was recorded, particularly among those patients not previously prescribed a PPI or misoprostol. Patients with a different indication for PPI therapy were excluded. In all, 480 patients were identified, and 142 were excluded. Of the 338 remaining patients, 154 (46%) were prescribed GI prophylaxis. In particular, 240 patients had not been receiving a PPI or misoprostol at the time of admission (gastroprotection naive). Of these, 23.3% received a new prescription for GI prophylaxis at discharge. Use of gastroprotection increased among patients older than 60 years compared with those 60 years and younger (P = 0.008), but there was no difference among patients with higher baseline comorbidity or those receiving multiple agents of interest. Although hospitalization offers an opportunity to recognize patients at high risk of developing upper GI complications from NSAIDs, utilization of appropriate gastroprotection seemed suboptimal. Educational efforts directed at physicians may help them recognize risk factors for GI hemorrhage and current indications for prophylaxis.

Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona.

PubMed

Baraniskin, Alexander; Van Laethem, Jean-Luc; Wyrwicz, Lucjan; Guller, Ulrich; Wasan, Harpreet S; Matysiak-Budnik, Tamara; Gruenberger, Thomas; Ducreux, Michel; Carneiro, Fatima; Van Cutsem, Eric; Seufferlein, Thomas; Schmiegel, Wolff

2017-11-01

In the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use. Opinion leaders and experts from diverse nationalities selected on scientific merit were asked to answer to a prepared set of questions about the current status of molecular diagnostics in different GI cancers. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. Preselected molecular genetic biomarkers that are described and disputed in the current medical literature in different GI cancers were debated, and recommendations for clinical routine practice were made whenever possible. Furthermore, the preanalytical variations were commented and proposals for quality controls of biospecimens were made. The current article summarises the recommendations of the expert committee regarding prognostic and predictive molecular genetic biomarkers in different entities of GI cancers. The briefly and comprehensively formulated guidelines should assist clinicians in the process of decision making in daily clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Formulation and optimization of zinc-pectinate beads for the controlled delivery of resveratrol.

PubMed

Das, Surajit; Ng, Ka-Yun; Ho, Paul C

2010-06-01

Preventive and therapeutic efficacies of resveratrol on several lower gastrointestinal (GI) diseases (e.g., colorectal cancer, colitis) are well documented. To overcome the problems due to its rapid absorption and metabolism at the upper GI tract, a delayed release formulation of resveratrol was designed to treat these lower GI diseases. The current study aimed to develop a delayed release formulation of resveratrol as multiparticulate pectinate beads by varying different formulation parameters. Zinc-pectinate (Zn-pectinate) beads exhibited better delayed drug release pattern than calcium-pectinate (Ca-pectinate) beads. The effects of the formulation parameters were investigated on shape, size, Zn content, moisture content, drug encapsulation efficiency, swelling-erosion, and resveratrol retention pattern of the formulated beads. Upon optimization of the formulation parameters in relative to the drug release profiles, the optimized beads were further subjected to morphological, chemical interaction, enzymatic degradation, and stability studies. Almost all prepared beads were spherical with approximately 1 mm diameter and efficiently encapsulated resveratrol. The formulation parameters revealed great influence on resveratrol retention and swelling-erosion behavior. In most of the cases, the drug release data more appropriately fitted with zero-order equation. This study demonstrates that the optimized Zn-pectinate beads can encapsulate very high amount of resveratrol and can be used as delayed release formulation of resveratrol.

Primary aortoduodenal fistula associated with abdominal aortic aneurysm with presentation of gastrointestinal bleeding: a case report.

PubMed

Lin, Tzu-Chieh; Tsai, Chung-Lin; Chang, Yao-Tien; Hu, Sung-Yuan

2018-06-07

Primary aortoduodenal fistula (ADF) is a rare cause of gastrointestinal (GI) bleeding and is difficult to diagnose as the clinical presentation is subtle. Clinicians should keep a high level of suspicion for an unknown etiology of GI bleeding, especially in older patients with or without abdominal aortic aneurysm (AAA). Computed tomographic angiography (CTA) can be used to detect primary ADF. Open surgery or endovascular aortic repair (EVAR) for ADF with bleeding will improve the survival rate. We report a rare case of AAA complicating ADF with massive GI bleeding in a 73-year-old Taiwanese man. He presented with abdominal pain and tarry stool for 5 days and an initial upper GI endoscopy at a rural hospital showed gastric ulcer only, but hypotension with tachycardia and a drop in hemoglobin of 9 g/dl from 12 g/dl occurred the next day. He was referred to our hospital for EVAR and primary closure of fistula defect due to massive GI bleeding with shock from ADF caused by AAA. Diagnosis was made by CTA of aorta. A timely and accurate diagnosis of primary ADF may be challenging due to insidious episodes of GI bleeding, which are frequently under-diagnosed until the occurrence of massive hemorrhage. Clinical physicians should keep a high index of awareness for primary ADF, especially in elderly patients with unknown etiology of upper GI bleeding with or without a known AAA.

Neurostimulation of the Gastrointestinal Tract: Review of Recent Developments

PubMed Central

Abell, Thomas L.; Chen, Jiande; Emmanuel, Anton; Jolley, Christopher; Sarela, Abeezar I.; Törnblom, Hans

2015-01-01

Neurostimulation is one manifestation of neuromodulation of the gastrointestinal (GI) tract. This manuscript reviews the history of neurostimulation of the GI tract with emphasis on current methods of stimulation. Upper GI disorders can be modulated with both temporary (placed endoscopically or surgically) or permanent (placed surgically) gastric electrical stimulation (GES) devices. The current gastrointestinal (GI) neurostimulation of stomach (GES) devices have been used in both children and adults and some patients have been followed in excess of 15 years with good long-term results. Similar GES devices have also been used for a variety of lower GI disorders, including constipation and fecal incontinence, for a number of years. Based on these recent developments, the future uses of neurostimulation in the GI tract are discussed with an emphasis on new applications and innovations. PMID:25581846

Contrast-enhanced endoscopic ultrasonography in digestive diseases.

PubMed

Hirooka, Yoshiki; Itoh, Akihiro; Kawashima, Hiroki; Ohno, Eizaburo; Itoh, Yuya; Nakamura, Yosuke; Hiramatsu, Takeshi; Sugimoto, Hiroyuki; Sumi, Hajime; Hayashi, Daijiro; Ohmiya, Naoki; Miyahara, Ryoji; Nakamura, Masanao; Funasaka, Kohei; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi

2012-10-01

Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early 1990s. The concept of the injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) led to "endoscopic ultrasonographic angiography". After the arrival of the first-generation contrast agent, high-frequency (12 MHz) EUS brought about the enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning endosonoscope with both radial and linear probes enabled the use of high-end ultrasound machines and depicted the enhancement of both color/power Doppler flow-based imaging and harmonic-based imaging using second-generation contrast agents. Many reports have described the usefulness of the differential diagnosis of pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE-EUS images was an objective method of diagnosis using the time-intensity curve (TIC), but it was limited to the region of interest. Recently developed Inflow Time Mapping™ can be generated from stored clips and used to display the pattern of signal enhancement with time after injection, offering temporal difference of contrast agents and improved tumor characterization. On the other hand, three-dimensional CE-EUS images added new information to the literature, but lacked positional information. Three-dimensional CE-EUS with accurate positional information is awaited. To date, most reports have been related to pancreatic lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in other organs: upper GI cancer diagnosis, submucosal tumors, and biliary disorders, and it might also provide functional information. Studies of CE-EUS in diseases in many other organs will increase in the near future.

Annual Trends of Gastrointestinal Cancers Mortality in Iran During 1990-2015; NASBOD Study.

PubMed

Salimzadeh, Hamideh; Delavari, Farnaz; Sauvaget, Catherine; Rezaee, Negar; Delavari, Alireza; Kompani, Farzad; Rezaei, Nazila; Sheidaei, Ali; Modirian, Mitra; Haghshenas, Rosa; Chegini, Maryam; Gohari, Kimiya; Zokaiee, Hossein; Farzadfar, Farshad; Malekzadeh, Reza

2018-02-01

Gastrointestinal (GI) neoplasms are among the most common cancers in Iran. This study aimed to measure annual trends in mortality rates from GI cancers in Iran between 1990 and 2015. This study was part of an ongoing study termed the 'National and Subnational Burden of Diseases' study in Iran. Data used in this study was obtained from the Iranian Death Registration System (1995 to 2010) and from 2 major cemeteries in Tehran (1995 to 2010) and Isfahan (2007 to 2010). All-cause mortality rates were estimated using the spatio-temporal model and the Gaussian process regression model. Age-standardized mortality rates (ASMR) per 100 000 person-years was calculated using data from Iran and the standard world population for comparison. Among GI cancers, gastric cancer represented the leading cause of mortality followed by cancers of the esophagus, liver, and colorectal cancers with the ASMR of 20.5, 5.8, 4.4, and 4.0 per 100 000 persons-years, respectively, between 1990 and 2015. While a decreasing trend occurred in mortality of esophageal, gastric, and colorectal cancers, particularly in the recent decade, we recorded an upward pattern and steady rise in mortality rates from liver, pancreatic, and gallbladder cancers during the study period. The ASMR of all studied causes were enhanced by advancing age and were found to be more prominent in adults aged 50 or older. Among all age-groups, higher death rates were detected in males versus females for all studied cancers except for gallbladder and biliary tract cancers. Gastric cancer mortality is still high and death rates from several other GI cancers are increasing in the nation. Interventions for cancer prevention, early detection, and access to high quality cancer treatment services are needed to reduce GI cancer burden and death rates in Iran and in the region. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Is cancer history really an exclusion criterion for clinical trial of lung cancer? Influence of gastrointestinal tract cancer history on the outcomes of lung cancer surgery.

PubMed

Aokage, Keiju; Okada, Morihito; Suzuki, Kenji; Nomura, Shogo; Suzuki, Shigeki; Tsubokawa, Norifumi; Mimae, Takahiro; Hattori, Aritoshi; Hishida, Tomoyuki; Yoshida, Junji; Tsuboi, Masahiro

2017-02-15

Exclusion of patients with a history of other cancer treatment except in situ situation has been considered to be inevitable for clinical trials investigating survival outcome. However, there have been few reports confirming these influences on surgical outcome of lung cancer patients ever. Multi-institutional, individual data from patients with non–small cell lung cancer resected between 2000 and 2013 were collected. The patients were divided into two groups: those with a history of gastrointestinal tract cancer (GI group) and those without any history (non-GI group). We compared the outcomes with well-matched groups using propensity scoring to minimize bias related to the nonrandomness. The influence of gastrointestinal tract cancer stage, disease-free interval, and treatment method for gastrointestinal tract cancer on the surgical outcome of non–small cell lung cancer was examined. We analyzed 196 patients in the GI group and 3732 in the non-GI group. In unmatched cohort, multivariate analyses showed that a history of gastrointestinal tract cancer did not affect overall survival or recurrence-free survival. Independent predictors of poor prognosis included older age, male sex, high carcinoembryonic antigen levels and advanced clinical stage of non–small cell lung cancer. The two groups in the matched cohort demonstrated equivalent overall survival and recurrence-free survival, even in patients with clinical stage I. Gastrointestinal tract cancer stage, disease-free interval and treatment method for gastrointestinal tract cancer were not associated with outcomes. History of early gastrointestinal tract cancer completely resected is not always necessary for exclusion criteria in clinical trial of lung cancer.

Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer.

PubMed

Alsubai, Jelal; Matters, Gail L; McGovern, Christopher O; Liao, Jiangang; Gilius, Evan L; Smith, Jill P

2016-01-07

Today, genetic biomarkers have been demonstrated to play an important role in identifying at-risk subjects for familial or inherited cancers. We have identified a single-nucleotide polymorphism (SNP) that results in missplicing of the cholecystokinin (CCK) receptor gene and expressing a larger mutated receptor in pancreatic cancer. The purpose of this study was to evaluate the significance and specificity of this SNP as a potential biomarker in patients with pancreatic cancer compared with other gastrointestinal (GI) cancers that also have CCK receptors. DNA was isolated and genotyped for the CCK receptor SNP from frozen tumor tissue from banked specimens of patients with pancreas, gastric, or colon cancer and from human cancer cell lines. Genotype and allelic frequencies were compared between the cancer cohort and two normal control databases using Fisher's exact test and odds ratio (OR). The Kaplan-Meier method was used to estimate the survival for patients with the CCK-B receptor SNP compared with those with the wild-type genotype. Immunohistochemical staining of cancer cells was done to detect the mutated receptor. Colon and gastric cancer patients had similar genotype frequencies for the CCK receptor SNP as that reported in the normal population. In contrast, the prevalence of the SNP in subjects with pancreatic cancer was twice that of controls and other GI cancers. Survival was adversely affected by the presence of the SNP only in those with pancreatic cancer. Immunoreactivity for the mutated receptor was positive in pancreatic cancer tissues with the SNP but absent in other GI cancers. A SNP of the CCK receptor is significantly increased in patients with pancreatic cancer but not in those with other GI malignancies. Therefore, this SNP may be a potential biomarker for pancreatic cancer.

Ethnic variations in upper gastrointestinal hospitalizations and deaths: the Scottish Health and Ethnicity Linkage Study.

PubMed

Cezard, Genevieve I; Bhopal, Raj S; Ward, Hester J T; Bansal, Narinder; Bhala, Neeraj

2016-04-01

Upper gastrointestinal (GI) diseases are common, but there is a paucity of data describing variations by ethnic group and so a lack of understanding of potential health inequalities. We studied the incidence of specific upper GI hospitalization and death by ethnicity in Scotland. Using the Scottish Health and Ethnicity Linkage Study, linking NHS hospitalizations and mortality to the Scottish Census 2001, we explored ethnic differences in incidence (2001-10) of oesophagitis, peptic ulcer disease, gallstone disease and pancreatitis. Relative Risks (RRs) and 95% confidence intervals were calculated using Poisson regression, multiplied by 100, stratified by sex and adjusted for age, country of birth (COB) and socio-economic position. The White Scottish population (100) was the reference population. Ethnic variations varied by outcome and sex, e.g. adjusted RRs (95% confidence intervals) for oesophagitis were comparatively higher in Bangladeshi women (209; 124-352) and lower in Chinese men (65; 51-84) and women (69; 55-88). For peptic ulcer disease, RRs were higher in Chinese men (171; 131-223). Pakistani women had higher RRs for gallstone disease (129; 112-148) and pancreatitis (147; 109-199). The risks of upper GI diseases were lower in Other White British and Other White [e.g. for peptic ulcer disease in men, respectively (74; 64-85) and (81; 69-94)]. Risks of common upper GI diseases were comparatively lower in most White ethnic groups in Scotland. In non-White groups, however, risk varied by disease and ethnic group. These results require consideration in health policy, service planning and future research. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Transcatheter arterial embolization for endoscopically unmanageable non-variceal upper gastrointestinal bleeding.

PubMed

Lee, Han Hee; Park, Jae Myung; Chun, Ho Jong; Oh, Jung Suk; Ahn, Hyo Jun; Choi, Myung-Gyu

2015-07-01

Transcatheter arterial embolization (TAE) is a therapeutic option for endoscopically unmanageable upper gastrointestinal (GI) bleeding. We aimed to assess the efficacy and clinical outcomes of TAE for acute non-variceal upper GI bleeding and to identify predictors of recurrent bleeding within 30 days. Visceral angiography was performed in 66 patients (42 men, 24 women; mean age, 60.3 ± 12.7 years) who experienced acute non-variceal upper GI bleeding that failed to be controlled by endoscopy during a 7-year period. Clinical information was reviewed retrospectively. Outcomes included technical success rates, complications, and 30-day rebleeding and mortality rates. TAE was feasible in 59 patients. The technical success rate was 98%. Rebleeding within 30 days was observed in 47% after an initial TAE and was managed with re-embolization in 8, by endoscopic intervention in 5, by surgery in 2, and by conservative care in 12 patients. The 30-day overall mortality rate was 42.4%. In the case of initial endoscopic hemostasis failure (n = 34), 31 patients underwent angiographic embolization, which was successful in 30 patients (96.8%). Rebleeding occurred in 15 patients (50%), mainly because of malignancy. Two factors were independent predictors of rebleeding within 30 days by multivariate analysis: coagulopathy (odds ratio [OR] = 4.37; 95% confidence interval [CI]: 1.25-15.29; p = 0.021) and embolization in ≥2 territories (OR = 4.93; 95% CI: 1.43-17.04; p = 0.012). Catheterization-related complications included hepatic artery dissection and splenic embolization. TAE controlled acute non-variceal upper GI bleeding effectively. TAE may be considered when endoscopic therapy is unavailable or unsuccessful. Correction of coagulopathy before TAE is recommended.

Feasibility and safety of a novel magnetic-assisted capsule endoscope system in a preliminary examination for upper gastrointestinal tract.

PubMed

Lien, Gi-Shih; Wu, Ming-Shun; Chen, Chun-Nan; Liu, Chih-Wen; Suk, Fat-Moon

2018-04-01

Current capsule endoscopy procedures are ineffective for upper gastrointestinal (GI) tract examination because they do not allow for operator-controlled navigation of the capsule. External controllability of a capsule endoscope with an applied magnetic field is a possible solution to this problem. We developed a novel magnetic-assisted capsule endoscope (MACE) system to visualize the entire upper GI tract. The present study evaluated the safety and feasibility of the MACE system for the examination of the upper GI tract, including the esophagus, stomach, and duodenum. The present open clinical study enrolled ten healthy volunteers. All participants swallowed a MACE, and an external magnetic field navigator was used for magnetic capsule manipulation in the upper GI tract. We assessed the maneuverability of the magnetic capsule and completeness of the MACE examination as well as the safety and tolerability of the procedure. The present study enrolled ten healthy volunteers with a mean age and body mass index of 47.7 years and 25.6 kg/m 2 , respectively. One volunteer withdrew because of difficulty in swallowing the capsule. In total, nine volunteers underwent the MACE examination. The average examination time was 27.1 min. The maneuverability of the capsule was assessed as good and fair in 55.6 and 44.4% of the participants, respectively. The overall completeness of the examination in the esophagus, stomach, and duodenum was 100, 85.2, and 86.1%, respectively. No severe adverse events occurred during this study. All participants exhibited satisfactory tolerance of the MACE examination. The MACE system has satisfactory maneuverability and visualization completeness with excellent acceptance and tolerance.

Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of cancer anorexia.

PubMed

Yavuzsen, Tugba; Walsh, Declan; Davis, Mellar P; Kirkova, Jordanka; Jin, Tao; LeGrand, Susan; Lagman, Ruth; Bicanovsky, Lesley; Estfan, Bassam; Cheema, Bushra; Haddad, Abdo

2009-12-01

Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms. A 22-item GI questionnaire assessed the severity of anorexia and the prevalence of concurrent GI symptoms, including taste changes, food aversions, altered sense of smell, and diurnal food intake changes. The relationship between anorexia severity and anticancer therapy and prior menstrual or pregnancy-related appetite changes was also assessed. Ninety-five of 101 patients with anorexia surveyed had complete data. Seventy-eight percent of them had moderate or severe anorexia. Abnormal diurnal appetite variation, taste changes, and food aversions were present in over 50% of all those with anorexia. Judged by the numerical rating scale, the worse the anorexia, the more prevalent were early satiety, constipation, vomiting, and food aversions. Those with more severe anorexia had greater weight loss, and worse performance status. Anorexia severity did not correlate with that during prior menses/pregnancy or antitumor therapy. Evaluation of multiple other GI symptoms is important in understanding the total experience of cancer anorexia. Early satiety, taste changes, food aversions, and altered sense of smell are important accompanying GI symptoms. Most validated anorexia tools do not assess these commonly associated GI symptoms. Future research should develop a comprehensive anorexia symptom questionnaire.

Magnetic resonance imaging with k-means clustering objectively measures whole muscle volume compartments in sarcopenia/cancer cachexia.

PubMed

Gray, Calum; MacGillivray, Thomas J; Eeley, Clare; Stephens, Nathan A; Beggs, Ian; Fearon, Kenneth C; Greig, Carolyn A

2011-02-01

Sarcopenia and cachexia are characterized by infiltration of non-contractile tissue within muscle which influences area and volume measurements. We applied a statistical clustering (k-means) technique to magnetic resonance (MR) images of the quadriceps of young and elderly healthy women and women with cancer to objectively separate the contractile and non-contractile tissue compartments. MR scans of the thigh were obtained for 34 women (n = 16 young, (median) age 26 y; n = 9 older, age 80 y; n = 9 upper gastrointestinal cancer patients, age 65 y). Segmented regions of consecutive axial images were used to calculate cross-sectional area and (gross) volume. The k-means unsupervised algorithm was subsequently applied to the MR binary mask image array data with resultant volumes compared between groups. Older women and women with cancer had 37% and 48% less quadriceps muscle respectively than young women (p < 0.001). Application of k-means subtracted a significant 9%, 14% and 20% non-contractile tissue from the quadriceps of young, older and patient groups respectively (p < 0.001). There was a significant effect of group (i.e., cancer vs healthy) when controlling for age as a covariate (p = 0.003). K-means objectively separates contractile and non-contractile tissue components. Women with upper GI cancer have significant fatty infiltration throughout whole muscle groups which is maintained when controlling for age. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Up-regulation of 5-lipoxygenase by inhibition of cathepsin G enhances TRAIL-induced apoptosis through down-regulation of survivin

PubMed Central

Woo, Seon Min; Min, Kyoung-Jin; Seo, Seung Un; Kim, Shin; Park, Jong-Wook; Song, Dae Kyu; Lee, Hyun-Shik; Kim, Sang Hyun; Kwon, Taeg Kyu

2017-01-01

Cathepsin G is a serine protease secreted from activated neutrophils, it has important roles in inflammation and immune response. Moreover, cathepsin G promotes tumor cell-cell adhesion and migration in cancer cells. In this study, we investigated whether inhibition of cathepsin G could sensitize TRAIL-mediated apoptosis in cancer cells. An inhibitor of cathepsin G [Cathepsin G inhibitor I (Cat GI); CAS 429676-93-7] markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), lung cancer (A549) and cervical cancer (Hela) cells. In contrast, combined treatment with Cat GI and TRAIL had no effect on apoptosis in normal cells [mesangial cell (MC) and human skin fibroblast (HSF)]. Cat GI induced down-regulation of survivin expression at the post-translational level, and overexpression of survivin markedly blocked apoptosis induced by combined treatment with Cat GI plus TRAIL. Interestingly, Cat GI induced down-regulation of survivin via 5-lipoxygenase (5-LOX)-mediated reactive oxygen species (ROS) production. Inhibition of 5-LOX by gene silencing (siRNA) or a pharmacological inhibitor of 5-LOX (zileuton) markedly attenuated combined treatment-induced apoptosis. Taken together, our results indicate that inhibition of cathepsin G sensitizes TRAIL-induced apoptosis through 5-LOX-mediated down-regulation of survivin expression. PMID:29290980

Epidermolysis bullosa

MedlinePlus

... Blood test for anemia Culture to check for bacterial infection if wounds are healing poorly Upper endoscopy or an upper GI series if symptoms include swallowing problems Growth rate will be checked often for a baby ...

Reactive oxygen species formation and bystander effects in gradient irradiation on human breast cancer cells.

PubMed

Zhang, Dongqing; Zhou, Tingyang; He, Feng; Rong, Yi; Lee, Shin Hee; Wu, Shiyong; Zuo, Li

2016-07-05

Ionizing radiation (IR) in cancer radiotherapy can induce damage to neighboring cells via non-targeted effects by irradiated cells. These so-called bystander effects remain an area of interest as it may provide enhanced efficacy in killing carcinomas with minimal radiation. It is well known that reactive oxygen species (ROS) are ubiquitous among most biological activities. However, the role of ROS in bystander effects has not been thoroughly elucidated. We hypothesized that gradient irradiation (GI) has enhanced therapeutic effects via the ROS-mediated bystander pathways as compared to uniform irradiation (UI). We evaluated ROS generation, viability, and apoptosis in breast cancer cells (MCF-7) exposed to UI (5 Gy) or GI (8-2 Gy) in radiation fields at 2, 24 and 48 h after IR. We found that extracellular ROS release induced by GI was higher than that by UI at both 24 h (p < 0.001) and 48 h (p < 0.001). More apoptosis and less viability were observed in GI when compared to UI at either 24 h or 48 h after irradiation. The mean effective doses (ED) of GI were ~130% (24 h) and ~48% (48 h) higher than that of UI, respectively. Our results suggest that GI is superior to UI regarding redox mechanisms, ED, and toxic dosage to surrounding tissues.

Chauliodites niedzwiedzkii sp. n. (Grylloblattida: Chaulioditidae) from Triassic sediments of Poland.

PubMed

Aristov, Danil S; Zyła, Dagmara; Wegierek, Piotr

2013-01-01

A new representative of the family Chaulioditidae (Insecta, Grylloblattida), Chauliodites niedzwiedzkii sp. n., is described from the Upper Olenekian-Lower Anisian sediments of Pałęgi in Holy Cross Mountains, Poland. This is the first formal description of any fossil insect from Pałęgi area.

HIV-Associated Gastrointestinal Cancer.

PubMed

Jensen, Björn E-O; Oette, Mark; Haes, Johannes; Häussinger, Dieter

2017-01-01

People living nowadays with HIV and AIDS may be treated effectively regarding virus replication and immunology. However, non-AIDS-defining cancer is of growing relevance due to high incidence and unfavorable outcome. The aim of this review is to summarize current knowledge on gastrointestinal (GI) carcinoma. Although literature on GI cancer is rare, an increased incidence of esophageal, gastric, pancreatic, hepatocellular, and colorectal carcinoma has been demonstrated. However, there are only few reports on therapy strategies and outcome, so that, despite increased occurrence of many GI carcinomas, only little is known about individualized treatment options and outcome in HIV-positive patients. More efforts have to be undertaken to close this gap. © 2017 S. Karger GmbH, Freiburg.

Design of a multicentre randomized controlled trial to evaluate the effectiveness of a tailored clinical support intervention to enhance return to work for gastrointestinal cancer patients.

PubMed

Zaman, AnneClaire G N M; Tytgat, Kristien M A J; Klinkenbijl, Jean H G; Frings-Dresen, Monique H W; de Boer, Angela G E M

2016-05-10

Gastrointestinal (GI) cancer is frequently diagnosed in people of working age, and many GI cancer patients experience work-related problems. Although these patients often experience difficulties returning to work, supportive work-related interventions are lacking. We have therefore developed a tailored work-related support intervention for GI cancer patients, and we aim to evaluate its cost-effectiveness compared with the usual care provided. If this intervention proves effective, it can be implemented in practice to support GI cancer patients after diagnosis and to help them return to work. We designed a multicentre randomized controlled trial with a follow-up of twelve months. The study population (N = 310) will include individuals aged 18-63 years diagnosed with a primary GI cancer and employed at the time of diagnosis. The participants will be randomized to the intervention or to usual care. 'Usual care' is defined as psychosocial care in which work-related issues are not discussed. The intervention group will receive tailored work-related support consisting of three face-to-face meetings of approximately 30 min each. Based on the severity of their work-related problems, the intervention group will be divided into groups receiving three types of support (A, B or C). A different supportive healthcare professional will be available for each group: an oncological nurse (A), an oncological occupational physician (B) and a multidisciplinary team (C) that includes an oncological nurse, oncological occupational physician and treating oncologist/physician. The primary outcome measure is return to work (RTW), defined as the time to a partial or full RTW. The secondary outcomes are work ability, work limitations, quality of life, and direct and indirect costs. The hypothesis is that tailored work-related support for GI cancer patients is more effective than usual care in terms of the RTW. The intervention is innovative in that it combines oncological and occupational care in a clinical setting, early in the cancer treatment process. METC protocol number NL51444.018.14/Netherlands Trial Register number NTR5022 . Registered 6 March 2015.

Diagnosing and Managing IBD

MedlinePlus

... of your abdomen. Newer scanners have an open design to minimize claustrophobia. A CT of the abdomen ... CE) Upper tract Crohn’s disease EGD-Upper GI Series (UGIS) Perianal Crohn’s disease MRI-EUS PSC (primary ...

Discrepancies between upper GI symptoms described by those who have them and their identification by conventional medical terminology: a survey of sufferers in four countries.

PubMed

Heading, Robert C; Thomas, Edward C M; Sandy, Phil; Smith, Gary; Fass, Ronnie; Hungin, Pali S

2016-04-01

The objective of this study was to develop a self-administered questionnaire for upper gastrointestinal (GI) symptoms using lay vocabulary uninfluenced by established medical terminology or concepts and to conduct a survey of symptom occurrence among sufferers in four countries. The questionnaire was designed by integrating information gained from the vocabulary used by 38 upper GI symptom sufferers. There was no medical input to its development. The questionnaire was then used, after appropriate translation, in Brazil, Russia, the UK and the USA. Details of 10 659 symptom episodes were obtained from 2665 individuals. Nine symptoms described in lay vocabulary were identified during questionnaire development. Of these, one corresponded to regurgitation, whereas two that were distinguished by survey participants might both be interpreted as heartburn. One chest symptom for which a corresponding medical term was uncertain occurred in ∼30% of the respondents. Five different 'stomach' or abdominal symptoms were identified. The predominant symptom and the pattern of concurrent symptoms often varied from one symptom episode to another. Use of the terms 'heartburn', 'reflux', 'indigestion' and 'burning stomach' to describe symptoms varied between countries. Some common upper GI symptoms described by those who suffer them have no clear counterpart in conventional medical terminology. Inadequacy of the conventional terminology in this respect deserves attention, first, to characterize it fully, and thereafter to construct enquiry that delivers more precise symptom identification. Our results suggest that improvement may require the use of vocabulary of individuals suffering the symptoms without imposing conformity with established symptom concepts.

Evidence-based Value of Prophylactic Drainage in Gastrointestinal Surgery

PubMed Central

Petrowsky, Henrik; Demartines, Nicolas; Rousson, Valentin; Clavien, Pierre-Alain

2004-01-01

Objective: To determine the evidence-based value of prophylactic drainage in gastrointestinal (GI) surgery. Methods: An electronic search of the Medline database from 1966 to 2004 was performed to identify articles comparing prophylactic drainage with no drainage in GI surgery. The studies were reviewed and classified according to their quality of evidence using the grading system proposed by the Oxford Centre for Evidence-based Medicine. Seventeen randomized controlled trials (RCTs) were found for hepato-pancreatico-biliary surgery, none for upper GI tract, and 13 for lower GI tract surgery. If sufficient RCTs were identified, we performed a meta-analysis to characterize the drain effect using the random-effects model. Results: There is evidence of level 1a that drains do not reduce complications after hepatic, colonic, or rectal resection with primary anastomosis and appendectomy for any stage of appendicitis. Drains were even harmful after hepatic resection in chronic liver disease and appendectomy. In the absence of RCTs, there is a consensus (evidence level 5) about the necessity of prophylactic drainage after esophageal resection and total gastrectomy due to the potential fatal outcome in case of anastomotic and gastric leakage. Conclusion: Many GI operations can be performed safely without prophylactic drainage. Drains should be omitted after hepatic, colonic, or rectal resection with primary anastomosis and appendectomy for any stage of appendicitis (recommendation grade A), whereas prophylactic drainage remains indicated after esophageal resection and total gastrectomy (recommendation grade D). For many other GI procedures, especially involving the upper GI tract, there is a further demand for well-designed RCTs to clarify the value of prophylactic drainage. PMID:15570212

Upper gastrointestinal issues in athletes.

PubMed

Waterman, Jason J; Kapur, Rahul

2012-01-01

Gastrointestinal (GI) complaints are common among athletes with rates in the range of 30% to 70%. Both the intensity of sport and the type of sporting activity have been shown to be contributing factors in the development of GI symptoms. Three important factors have been postulated as contributing to the pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood flow, and neuroendocrine changes. As a result of those factors, gastroesophageal reflux disease (GERD), nausea, vomiting, gastritis, peptic ulcers, GI bleeding, or exercise-related transient abdominal pain (ETAP) may develop. GERD may be treated with changes in eating habits, lifestyle modifications, and training modifications. Nausea and vomiting may respond to simple training modifications, including no solid food 3 hours prior to an athletic event. Mechanical trauma, decreased splanchnic blood flow during exercise, and non-steroidal anti-inflammatory drugs (NSAID) contribute to gastritis, GI bleeding, and ulcer formation in athletes. Acid suppression with proton-pump inhibitors may be useful in athletes with persistence of any of the above symptoms. ETAP is a common, poorly-understood, self-limited acute abdominal pain which is difficult to treat. ETAP incidence increases in athletes beginning a new exercise program or increasing the intensity of their current exercise program. ETAP may respond to changes in breathing patterns or may resolve simply with continued training. Evaluation of the athlete with upper GI symptoms requires a thorough history, a detailed training log, a focused physical examination aimed at ruling out potentially serious causes of symptoms, and follow-up laboratory testing based on concerning physical examination findings.

Evaluation of miRNA-196a2 and apoptosis-related target genes: ANXA1, DFFA and PDCD4 expression in gastrointestinal cancer patients: A pilot study

PubMed Central

Toraih, Eman A.; Ibrahiem, Afaf; Abdeldayem, Hala; Mohamed, Amany O.; Abdel-Daim, Mohamed M.

2017-01-01

Previous reports have suggested the significant association of miRNAs aberrant expression with tumor initiation, progression and metastasis in cancer, including gastrointestinal (GI) cancers. The current preliminary study aimed to evaluate the relative expression levels of miR-196a2 and three of its selected apoptosis-related targets; ANXA1, DFFA and PDCD4 in a sample of GI cancer patients. Quantitative real-time PCR for miR-196a2 and its selected mRNA targets, as well as immunohistochemical assay for annexin A1 protein expression were detected in 58 tissues with different GI cancer samples. In addition, correlation with the clinicopathological features and in silico network analysis of the selected molecular markers were analyzed. Stratified analyses by cancer site revealed elevated levels of miR-196a2 and low expression of the selected target genes. Annexin protein expression was positively correlated with its gene expression profile. In colorectal cancer, miR-196a over-expression was negatively correlated with annexin A1 protein expression (r = -0.738, p < 0.001), and both were indicators of unfavorable prognosis in terms of poor differentiation, larger tumor size, and advanced clinical stage. Taken together, aberrant expression of miR-196a2 and the selected apoptosis-related biomarkers might be involved in GI cancer development and progression and could have potential diagnostic and prognostic roles in these types of cancer; particularly colorectal cancer, provided the results experimentally validated and confirmed in larger multi-center studies. PMID:29091952

Airway Management During Upper GI Endoscopic Procedures: State of the Art Review.

PubMed

Goudra, Basavana; Singh, Preet Mohinder

2017-01-01

With the growing popularity of propofol mediated deep sedation for upper gastrointestinal (GI) endoscopic procedures, challenges are being felt and appreciated. Research suggests that management of the airway is anything but routine in this setting. Although many studies and meta-analyses have demonstrated the safety of propofol sedation administered by registered nurses under the supervision of gastroenterologists (likely related to the lighter degrees of sedation than those provided by anesthesia providers and is under medicolegal controversy in the United States), there is no agreement on the optimum airway management for procedures such as endoscopic retrograde cholangiopancreatography. Failure to rescue an airway at an appropriate time has led to disastrous consequences. Inability to evaluate and appreciate the risk factors for aspiration can ruin the day for both the patient and the health care providers. This review apprises the reader of various aspects of airway management relevant to the practice of sedation during upper GI endoscopy. New devices and modification of existing devices are discussed in detail. Recognizing the fact that appropriate monitoring is important for timely recognition and management of potential airway disasters, these issues are explored thoroughly.

Hematemesis: Unusual presentation of isolated gastric tuberculosis.

PubMed

Nasa, Mukesh; Kumar, Arvind; Phadke, Aniruddha; Sawant, Prabha

2016-01-01

A 25-year-old male presented with hematemesis, epigastric pain, and melena. He had dyspepsia with significant weight loss for 3 months period. On clinical examination, he was pale with no organomegaly or lymphadenopathy. The X-ray chest was normal, and ultrasound abdomen was normal. Upper GI endoscopy revealed nodularity and ulceration along proximal part of lesser curvature of the stomach. CT scan abdomen showed thickening of lesser curvature just below gastro-esophageal junction. The biopsies were negative for malignancy. Repeat upper GI endoscopy showed a nonhealing ulcer, on repeat well biopsies taken from the base of ulcer primary gastric tuberculosis was diagnosed. It showed many epithelioid cell granulomas and multinucleated giant cells with caseous necrosis on histology. Acid-fast bacilli on Zeil Neelsen staining and TB PCR were positive for Mycobacterium tuberculosis. He was put on four-drug anti-tuberculous treatment. On follow-up, the patient gradually improved and regained weight. Repeat upper GI endoscopy done after 8 weeks showed healing of the ulcer with decrease in nodularity. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Viable Cancer Cells in the Remnant Stomach are a Potential Source of Peritoneal Metastasis after Curative Distal Gastrectomy for Gastric Cancer.

PubMed

Murata, Satoshi; Yamamoto, Hiroshi; Yamaguchi, Tsuyoshi; Kaida, Sachiko; Ishida, Mitsuaki; Kodama, Hirokazu; Takebayashi, Katsushi; Shimizu, Tomoharu; Miyake, Toru; Tani, Tohru; Kushima, Ryoji; Tani, Masaji

2016-09-01

The mechanisms underlying peritoneal metastasis (PM) after curative gastrectomy for gastric cancer (GC) are not well elucidated. This study assessed whether viable cancer cells, including cancer stemlike cells (CSCs), were present in the remnant stomach immediately before gastrointestinal (GI) tract reconstruction because these could be a source of PM after gastrectomy. Saline fluid used for remnant stomach lumen irrigation before GI reconstruction was prospectively collected from 142 consecutive patients undergoing distal gastrectomy for GC and cytologically examined. Proliferative activity (Ki67 staining) and stemness (expression of the CSC surface markers CD44s or CD44v6) were evaluated in detected cancer cells. Viable cancer cells were detected in 33 (23.2 %) of the 142 remnant stomachs. These cells formed clusters and stained positively for Ki67, indicating proliferation. Cancer cells in remnant stomachs and surface cancer cells in primary GCs from 10 (30.3 %) of these 33 cases also stained positively for CD44s or CD44v6. In a multiple logistic regression analysis, advanced cancer (odds ratio [OR], 4.65; 95 % confidence interval [CI], 1.32-16.4; P = 0.017), tumor size of 40 mm or larger (OR, 3.78; 95 % CI, 1.12-12.8; P = 0.033), and histologic differentiation (OR, 3.10; 95 % CI, 1.30-7.40; P = 0.011) were associated independently with the presence of cancer cells in the remnant stomach. Viable, proliferative, and clustered cancer cells, including CSCs, were found in remnant gastric lumens immediately before GI reconstruction, indicating a possible cellular source of PM after curative gastrectomy for GC. Dissemination of gastric contents into the peritoneal cavity should be avoided during GI reconstruction.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneummore » plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.« less

Emergency pancreatoduodenectomy (whipple procedure) for massive upper gastrointestinal bleeding caused by a diffuse B-cell lymphoma of the duodenum: report of a case.

PubMed

Stratigos, Panagiotis; Kouskos, Efstratios; Kouroglou, Maria; Chrisafis, Ioannis; Fois, Lucia; Mavrogiorgis, Anastasios; Axiotis, Efthimios; Zamtrakis, Sotirios

2007-01-01

We herein report a rare case of a massive upper gastrointestinal (GI) bleeding, caused by high-grade diffuse B-cell lymphoma of the duodenum, secondary to immunoproliferative small intestinal disease (IPSID) and treated with an emergency partial pancreatoduodenectomy. A 42-year-old man was admitted to our hospital because of hematemesis. Upper GI endoscopy was unrevealing because of the copious bleeding. Initially, the patient underwent conservative treatment, thus resulting in the temporary cessation of the bleeding. Later, the hemorrhage massively relapsed. An urgent abdominal ultrasound raised the suspicion of a large, possibly bleeding, neoplasm of the duodenum, which was finally confirmed by abdominal computed tomography. The patient underwent an emergency laparotomy, during which a partial pancreatoduodenectomy was performed (Whipple procedure). Histologically, the tumor was a high-grade B-cell lymphoma of the duodenum. The nearby small intestinal mucosa was suggestive of IPSID. A massive upper GI hemorrhage from a high-grade B-cell non-Hodgkin lymphoma of the duodenum, which develops secondary to IPSID, is a very rare clinical demonstration of this disease. Our case is one of the few reports in the English literature, for which the Whipple procedure has been performed as a curative treatment.

Glycemic index, glycemic load and endometrial cancer risk: results from the Australian National Endometrial Cancer study and an updated systematic review and meta-analysis.

PubMed

Nagle, Christina M; Olsen, Catherine M; Ibiebele, Torukiri I; Spurdle, Amanda B; Webb, Penelope M

2013-03-01

The relationship between habitual consumption of foods with a high glycemic index (GI) and/or a diet with a high glycemic load (GL) and risk of endometrial cancer is uncertain, and relatively few studies have investigated these associations. The objectives of this study were to examine the association between GI/GL and risk of endometrial cancer using data from an Australian population-based case-control study and systematically review all the available evidence to quantify the magnitude of the association using meta-analysis. The case-control study included 1,290 women aged 18-79 years with newly diagnosed, histologically confirmed endometrial cancer and 1,436 population controls. Controls were selected to match the expected Australian state of residence and age distribution (in 5-year bands) of cases. For the systematic review, relevant studies were identified by searching PubMed and Embase databases through to July 2011. Random-effects models were used to calculate the summary risk estimates, overall and dose-response. In our case-control study, we observed a modest positive association between high dietary GI (OR 1.43, 95 % CI 1.11-1.83) and risk of endometrial cancer, but no association with high dietary GL (OR 1.15, 95 % CI 0.90-1.48). For the meta-analysis, we collated information from six cohort and two case-control studies, involving a total of 5,569 cases. The pooled OR for the highest versus the lowest intake category of GI was 1.15 (0.95-1.40); however, there was significant heterogeneity (p 0.004) by study design (RR 1.00 [95 % CI 0.87-1.14] for cohort studies and 1.56 [95 % CI 1.21-2.02] for case-control studies). There was no association in the dose-response meta-analysis of GI (RR per 5 unit/day increment of GI 1.00, 95 % CI 0.97-1.03). GL was positively associated with endometrial cancer. The pooled RR for the highest versus the lowest GL intake was 1.21 (95 % CI 1.09-1.33) and 1.06 (95 % CI 1.01-1.11) per 50 unit/day increment of GL in the dose-response meta-analysis. The pooled results from observational studies, including our case-control results, provide evidence of a modest positive association between high GL, but not GI, and endometrial cancer risk.

Gastrointestinal metastases from breast cancer: report of two cases.

PubMed

Gerova, Vanya A; Tankova, Ludmila T; Mihova, Anna A; Drandarska, Ivanka L; Kadian, Hilda O

2012-01-01

Metastatic involvement of the gastrointestinal (GI) tract secondary to breast cancer (BC) is rare and usually occurs in patients with lobular BC. We report 2 cases with GI presentations of metastatic BC. In the first case endoscopy and endoscopic ultrasonography because of abdominal discomfort, tenesmus and rectal bleeding demonstrated liver, gastric and rectal metastases with histological and immunohistological patterns of metastatic lobular BC. In the second case gastric involvement, endoscopically presented as a solid nodular lesion in the gastric body and fundus with involvement of the gastro-esophageal junction, was established with clinical symptoms of solid food dysphagia and dyspepsia; the metastatic infiltration from ductal BC was proven histologically and immunohistochemically. The GI metastases were presented 5 and 7 years after radical mastectomy because of lobular and ductal BC respectively. The cases are of interest with a feature of liver and GI metastases in double sites (stomach and rectum) from lobular BC, as well as solid gastric metastasis from ductal BC. They illustrate the need for special attention to GI metastatic disease in patients with invasive BC who present with non-specific GI symptoms.

Synchronous gastric and colonic metastases of invasive lobular breast carcinoma: case report and review of the literature.

PubMed

Critchley, Adam Charles; Harvey, James; Carr, Michael; Iwuchukwu, Obi

2011-07-01

Breast cancer is the most common malignancy in women and the main cause of cancer death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from primary breast cancer are rare but breast cancer is the second most common primary malignancy to metastasise to the GI tract after malignant melanoma. The metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain metastases are more common in IDC. Most series report a greater prediliction for lobular carcinoma to metastasise to the GI tract, gynaecological organs or peritoneum. The presentation of GI metastasis due to breast cancer is typically vague and the clinical, radiological, endoscopic and histopathologic findings are often difficult to distinguish from primary gastric carcinoma. Such a patient is more likely to present to a luminal surgeon or gastroenterologist than a breast surgeon. Therefore a high index of clinical suspicion with early endoscopy in those with non-specific symptoms and a past history of breast cancer, particularly ILC, are recommended. It is imperative to differentiate between metastatic breast cancer and primary gastric carcinoma as treatment strategies differ hugely. Therefore, correlation of endoscopic biopsy histology with the primary breast cancer histology is essential. Treatment modalities are limited to appropriate systemic therapy, which may have a palliative effect in up to 50%. Surgical intervention is nearly always limited to palliative bypass only. Prognosis is consistent with the median survival of all women with metastatic disease secondary to breast cancer.

Bromelain-induced apoptosis in GI-101A breast cancer cells.

PubMed

Dhandayuthapani, Sivanesan; Perez, Honey Diaz; Paroulek, Alexandra; Chinnakkannu, Panneerselvam; Kandalam, Umadevi; Jaffe, Mark; Rathinavelu, Appu

2012-04-01

Bromelain is a proteolytic enzyme extracted from the stems and the immature fruits of pineapple that was found to be antitumorigenic in different in vitro models. Bromelain has been reported to promote apoptosis, particularly in breast cancer cells, with the up-regulation of c-Jun N-terminal kinase and p38 kinase. Our study was designed to determine if bromelain could induce apoptosis in GI-101A breast cancer cells. GI-101A cells were treated with increasing concentrations of bromelain for 24 hours. The effect of bromelain for inducing cell death via activation of the apoptosis mechanism in GI-101A cells was further determined by using caspase-9 and caspase-3 assays along with the M30-Apoptosense assay to measure cytokeratin 18 (CK18) levels in the cytoplasm of the cultured cancer cells. A dose-dependent increase in the activities of caspase-9 and caspase-3 coinciding with elevation of CK18 levels was found in bromelain-treated cells compared with control cells. Furthermore, the apoptosis induction by bromelain was confirmed by DNA fragmentation analysis and 4,6'-diamino-2-phenylindole dihydrochloride fluorescence staining of the nucleus. Our results indicate an increase in apoptosis-related cell death in breast cancer cells with increasing concentrations of bromelain.

Rare upper gastrointestinal hemorrhage of cetuximab: A case report.

PubMed

Duan, Shi-Jie; Gao, Zi-Ming; Wang, Peng-Liang; Gong, Bao-Cheng; Huang, Han-Wei; Luo, Lei; Wang, Xin; Xing, Ya-Nan; Xu, Hui-Mian; Liu, Fu-Nan

2017-12-01

cetuximab, an epidermal growth factor receptor inhibitor, is a targeted therapeutic regimen of colorectal cancers. Several common adverse effects have been found, such as cutaneous or gastrointestinal toxicity. However, according to the articles had been published, upper gastrointestinal bleeding (UGIB) is considered to be rare and its mechanism remains unclear. In this report, we presented a 42-year-old male patient with advanced recto-sigmoid cancer. After palliative operation, the patient suffered from complete upper gastrointestinal (GI) obstruction, which was induced by extensive abdominal metastasis of the tumor. Considering his poor condition, we chose the targeted drug, cetuximab, as his further treatment. But after the application of cetuximab, the UGIB immediately happened twice in this patient. UGIB, as a rare complication of cetuximab, occured to the patient. We stopped the bleeding with thrombin, hemocoagulase and somatostatin and suspended the subsequent treatment plan of cetuximab. At the same time, anti-shock treatment was given immediately. He was died of respiratory and circulatory failure caused by UGIB and advanced tumor eventually. UGIB should be considered as a rare but severe complication of cetuximab. When cetuximab is applied for patients with advanced colon tumors, more cautions should be required if the patients are accompanied by upper gastrointestinal obstruction. In addition, for those patients who suffered from UGIB recently, cetuximab should be prohibited if the Rockall score ranged > 5 points. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tang, Qinggong; Frank, Aaron; Wang, Jianting; Chen, Chao-wei; Jin, Lily; Lin, Jon; Chan, Joanne M.; Chen, Yu

2016-03-01

Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is unable to detect those subsurface lesions. Since cancer development is associated with both morphological and molecular alterations, imaging technologies that can quantitative image tissue's morphological and molecular biomarkers and assess the depth extent of a lesion in real time, without the need for tissue excision, would be a major advance in GI cancer diagnostics and therapy. In this research, we investigated the feasibility of multi-modal optical imaging including high-resolution optical coherence tomography (OCT) and depth-resolved high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. APC (adenomatous polyposis coli) mice model were imaged using OCT and FLOT and the correlated histopathological diagnosis was obtained. Quantitative structural (the scattering coefficient) and molecular imaging parameters (fluorescence intensity) from OCT and FLOT images were developed for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 87.4% (87.3%) for sensitivity (specificity) which gives the most optimal diagnosis (the largest area under receiver operating characteristic (ROC) curve). This project results in a new non-invasive multi-modal imaging platform for improved GI cancer detection, which is expected to have a major impact on detection, diagnosis, and characterization of GI cancers, as well as a wide range of epithelial cancers.

Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers.

PubMed

Brücher, Björn L D M; Li, Yan; Schnabel, Philipp; Daumer, Martin; Wallace, Timothy J; Kube, Rainer; Zilberstein, Bruno; Steele, Scott; Voskuil, Jan L A; Jamall, Ijaz S

2016-03-01

One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications. In order to achieve these goals, it is necessary to understand the key issues in different aspects of biotechnology to anticipate future directions of personalized and individualized diagnosis and multimodal treatment strategies. Providing an overview of translational data in cancers proved to be a challenge as different methods and techniques used to obtain molecular data are used and studies are based on different tumor entities with different tumor biology and prognoses as well as vastly different therapeutic approaches. The pros and cons of the available methodologies and the potential response data in genomics, microRNA, epigenetics and proteomics with a focus on upper gastrointestinal cancers are considered herein to allow for an understanding of where these technologies stand with respect to cancer diagnosis, prognosis and treatment.

Discrepancies between upper GI symptoms described by those who have them and their identification by conventional medical terminology: a survey of sufferers in four countries

PubMed Central

Thomas, Edward C.M.; Sandy, Phil; Smith, Gary; Fass, Ronnie; Hungin, Pali S.

2016-01-01

Objective The objective of this study was to develop a self-administered questionnaire for upper gastrointestinal (GI) symptoms using lay vocabulary uninfluenced by established medical terminology or concepts and to conduct a survey of symptom occurrence among sufferers in four countries. Methods The questionnaire was designed by integrating information gained from the vocabulary used by 38 upper GI symptom sufferers. There was no medical input to its development. The questionnaire was then used, after appropriate translation, in Brazil, Russia, the UK and the USA. Details of 10 659 symptom episodes were obtained from 2665 individuals. Results Nine symptoms described in lay vocabulary were identified during questionnaire development. Of these, one corresponded to regurgitation, whereas two that were distinguished by survey participants might both be interpreted as heartburn. One chest symptom for which a corresponding medical term was uncertain occurred in ∼30% of the respondents. Five different ‘stomach’ or abdominal symptoms were identified. The predominant symptom and the pattern of concurrent symptoms often varied from one symptom episode to another. Use of the terms ‘heartburn’, ‘reflux’, ‘indigestion’ and ‘burning stomach’ to describe symptoms varied between countries. Conclusion Some common upper GI symptoms described by those who suffer them have no clear counterpart in conventional medical terminology. Inadequacy of the conventional terminology in this respect deserves attention, first, to characterize it fully, and thereafter to construct enquiry that delivers more precise symptom identification. Our results suggest that improvement may require the use of vocabulary of individuals suffering the symptoms without imposing conformity with established symptom concepts. PMID:26735161

A score card for upper GI endoscopy: Evaluation of interobserver variability in examiners with various levels of experience.

PubMed

Neumann, M; Friedl, S; Meining, A; Egger, K; Heldwein, W; Rey, J F; Hochberger, J; Classen, M; Hohenberger, W; Rösch, T

2002-10-01

In most European countries, training in GI endoscopy has largely been based on hands-on acquisition of experience in patients rather than on a structured training programme. With the development of training models systematic hands-on training in a variety of diagnostic and therapeutic endoscopy techniques was achieved. Little, however, is known about methods of objectively assessing trainees' performance. We therefore developed an assessment 'score card' for upper GI endoscopy and tested it in endoscopists with various levels of experience. The aim of the study was therefore to assess interobserver variations in the evaluation of trainees. On the basis of textbook and expert opinions a consensus group of eight experienced endoscopists developed a score card for diagnostic upper GI endoscopy with biopsy. The score card includes an assessment of the single steps of the procedure as well as of the times needed to complete each step. This score card was then evaluated in a further conference including ten experts who blindly assessed videotapes of 15 endoscopists performing upper GI endoscopy in a training bio-simulation model (the 'Erlangen Endo-Trainer'). On the basis of their previous experience (i. e. the number of endoscopies performed) these 15 endoscopists were classified into four groups: very experienced, experienced, having some experience and inexperienced. Interobserver variability (IOV) was tested for the various score card parameters (Kendall's rank-correlation coefficient 0.0-0.5 poor, 0.5-1.0 good agreement). In addition, the correlation between the score card assessment and the examiners' experience levels was analysed. Despite poor IOV results for all the parameters tested (Kendall coefficient < 0.3), the assessment parameters correlated well when the examiners' different experience levels were taken into account (correlation coefficient 0.59-0.89, p < 0.05). The score card parameters were suitable for differentiating between the four groups of examiners with different levels of endoscopic experience. As expected with scores involving subjective assessment of performance, the variability between reviewers was substantial. Nevertheless, the assessment score was capable of distinguishing reliably between different experience levels in terms of a good individual observer consistency. The score card can therefore be used to document both training status and progress during endoscopy training courses using bio-simulation models, and this might be able to provide improved quality assurance in GI endoscopy training.

Use of a specially designed partially covered self-expandable metal stent (PSEMS) with a 40-mm diameter for the treatment of upper gastrointestinal suture or staple line leaks in 11 cases.

PubMed

Fischer, Andreas; Bausch, Dirk; Richter-Schrag, Hans-Juergen

2013-02-01

The use of self-expandable stents to treat postoperative leaks and fistula in the upper gastrointestinal (GI) tract is an established treatment for leaks of the upper GI tract. However, lumen-to-stent size discrepancies (i.e., after sleeve gastrectomy or esophageal resection) may lead to insufficient sealing of the leaks requiring further surgical intervention. This is mainly due to the relatively small diameter (≤30 mm) of commonly used commercial stents. To overcome this problem, we developed a novel partially covered stent with a shaft diameter of 36 mm and a flare diameter of 40 mm. From September 2008 to September 2010, 11 consecutive patients with postoperative leaks were treated with the novel large diameter stent (gastrectomy, n = 5; sleeve gastrectomy, n = 2; fundoplication after esophageal perforation, n = 2; Roux-en-Y gastric bypass, n = 1; esophageal resection, n = 1). Treatment with commercially available stents (shaft/flare: 23/28 mm and 24/30 mm) had been unsuccessful in three patients before treatment with the large diameter stent. Due to dislocation, the large diameter stent was anchored in four patients (2× intraoperatively with transmural sutures, 2× endoscopically with transnasally externalized threads). Treatment was successful in 11 of 11 patients. Stent placement and removal was easy and safe. The median residence time of the stent was 24 (range, 18-41) days. Stent dislocation occurred in four cases (36 %). It was treated by anchoring the stent. Mean follow-up was 25 (range, 14-40) months. No severe complication occurred during or after intervention and no patient was dysphagic. Using the novel large diameter, partially covered stent to seal leaks in the upper GI tract is safe and effective. The large diameter of the stent does not seem to injure the wall of the upper GI tract. However, stent dislocation sometimes requires anchoring of the stent with sutures or transnasally externalized threads.

The incidence of upper extremity injuries in endoscopy nurses working in the United States.

PubMed

Drysdale, Susan A

2013-01-01

Numerous studies have addressed musculoskeletal disorders in the international working population. The literature indicates that injuries exist at astounding rates with significant economic impact. Attempts have been made by government, private industry, and special interest groups to address the issues related to the occurrence and prevention of musculoskeletal injuries. Because of the limited research on the gastrointestinal (GI) endoscopy nursing sector, this descriptive, correlational study explored the incidence of upper extremity injuries in GI endoscopy nurses and technicians in the United States. A total of 215 subjects were included in the study. Findings show that upper extremity injuries exist among nurses working in GI endoscopy. Twenty-two percent of respondents missed work for upper extremity injuries. The findings also show that the severity of disability is related to the type of work done, type of assistive aids available at work, and whether or not ergonomic or physiotherapy assessments were provided at the place of employment. In reference to rate of injury and the availability of ergonomics and physiotherapy assessments, those who had ergonomic assessments available to them had scores on the Disabilities of the Arm, Shoulder, and Hand (DASH) inventory (indicating upper extremity disability) that were significantly lower (DASH score, 9.96) than those who did not have the assessments available (DASH score, 14.66). The results suggest that there are a significant number of subjects who are disabled to varying degrees and the majority of these are employed in full-time jobs.

Dose-Volume Histogram Predictors of Chronic Gastrointestinal Complications After Radical Hysterectomy and Postoperative Concurrent Nedaplatin-Based Chemoradiation Therapy for Early-Stage Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isohashi, Fumiaki, E-mail: isohashi@radonc.med.osaka-u.ac.jp; Yoshioka, Yasuo; Mabuchi, Seiji

2013-03-01

Purpose: The purpose of this study was to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in cervical cancer patients who underwent radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy. Methods and Materials: This study analyzed 97 patients who underwent postoperative concurrent chemoradiation therapy. The organs at risk that were contoured were the small bowel loops, large bowel loop, and peritoneal cavity. DVH parameters subjected to analysis included the volumes of these organs receiving more than 15, 30, 40, and 45 Gy (V15-V45) and their mean dose. Associations between DVH parameters or clinical factors andmore » the incidence of grade 2 or higher chronic GI complications were evaluated. Results: Of the clinical factors, smoking and low body mass index (BMI) (<22) were significantly associated with grade 2 or higher chronic GI complications. Also, patients with chronic GI complications had significantly greater V15-V45 volumes and higher mean dose of the small bowel loops compared with those without GI complications. In contrast, no parameters for the large bowel loop or peritoneal cavity were significantly associated with GI complications. Results of the receiver operating characteristics (ROC) curve analysis led to the conclusion that V15-V45 of the small bowel loops has high accuracy for prediction of GI complications. Among these parameters, V40 gave the highest area under the ROC curve. Finally, multivariate analysis was performed with V40 of the small bowel loops and 2 other clinical parameters that were judged to be potential risk factors for chronic GI complications: BMI and smoking. Of these 3 parameters, V40 of the small bowel loops and smoking emerged as independent predictors of chronic GI complications. Conclusions: DVH parameters of the small bowel loops may serve as predictors of grade 2 or higher chronic GI complications after postoperative concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer.« less

Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome

PubMed Central

Katz, Lior H.; Burton-Chase, Allison M.; Advani, Shailesh; Fellman, Bryan; Polivka, Katrina M.; Yuan, Ying; Lynch, Patrick M.; Peterson, Susan K.

2016-01-01

Background Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Methods Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Results Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper GI endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for endometrial cancer and only one-third advised relatives to have genetic counseling. Conclusions Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of non-diagnostic germline mutation testing among patients with LLS. PMID:26272410

Characterization of the effects of opiorphin and sialorphin and their analogs substituted in position 1 with pyroglutamic acid on motility in the mouse ileum.

PubMed

Kamysz, Elżbieta; Sałaga, Maciej; Sobczak, Marta; Kamysz, Wojciech; Fichna, Jakub

2013-03-01

Opiorphin and sialorphin are two recently discovered endogenous enkephalin-degrading enzyme inhibitors. Our aim was to characterize their effect on the mouse ileum motility and to investigate the role of glutamine in position 1. Opiorphin, sialorphin, and their analogs substituted in position 1 with pyroglutamic acid (pGlu) were synthesized by the solid-phase method using Fmoc chemistry. The effect of peptides on gastrointestinal (GI) motility was characterized using in vitro assays and in mouse model of upper GI transit. Opiorphin and sialorphin, but not their analogs, significantly increased electrical field-stimulated contractions in the mouse ileum in a δ-opioid receptor-dependent manner. Opiorphin, sialorphin, and their analogs did not influence the effect of [Met(5)]enkephalin on smooth muscle contractility in the mouse ileum in vitro. [Met(5)]enkephalin and sialorphin, but not opiorphin injected intravenously (1 mg/kg), significantly inhibited the upper GI transit. The intraperitoneal administration of peptides (3 mg/kg) did not change the mouse upper GI transit. In conclusion, this is the first study investigating the effect of opiorphin and sialorphin on the mouse ileum motility and demonstrating that glutamine in position 1 is crucial for their pharmacological action. Our results may be important for further structure-activity relationship studies on opiorphin and sialorphin and future development of potent clinical therapeutics aiming at the enkephalinergic system. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors.

PubMed

Scheiman, James M

2002-01-01

Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

PubMed

Arana-Guajardo, Ana Cecilia; Barrera-Torres, Gustavo; Villarreal-Alarcón, Miguel Ángel; Vega-Morales, David; Esquivel-Valerio, Jorge Antonio

2017-12-16

The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Aspirin and proton pump inhibitor combination therapy for prevention of cardiovascular disease and Barrett's esophagus.

PubMed

Peura, David A; Wilcox, C Mel

2014-01-01

Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.

The risk of cancer as a result of elevated levels of nitrate in drinking water and vegetables in Central India.

PubMed

Taneja, Pinky; Labhasetwar, Pawan; Nagarnaik, Pranav; Ensink, Jeroen H J

2017-08-01

The objective of the present study was to determine the effect of nitrates on the incidence of gastrointestinal (GI) cancer development. Nitrate converted to nitrite under reducing conditions of gut results in the formation of N-nitrosamines which are linked to an increased gastric cancer risk. A population of 234 individuals with 78 cases of GI cancer and 156 controls residing at urban and rural settings in Nagpur and Bhandara districts of India were studied for 2 years using a case-control study. A detailed survey of 16 predictor variables using Formhub software was carried out. Nitrate concentrations in vegetables and primary drinking water supplies were measured. The logistic regression model showed that nitrate was statistically significant in predicting increasing risk of cancer when potential confounders were kept at base level (P value of 0.001 nitrate in drinking water; 0.003 for nitrate in vegetable) at P < 0.01. Exposure to nitrate in drinking water at >45 mg/L level of nitrate was associated with a higher risk of GI cancers. Analysis suggests that nitrate concentration in drinking water was found statistically significant in predicting cancer risk with an odds ratio of 1.20.

Metastatic breast cancer to the gastrointestinal tract: report of five cases and review of the literature.

PubMed

Ambroggi, Massimo; Stroppa, Elisa Maria; Mordenti, Patrizia; Biasini, Claudia; Zangrandi, Adriano; Michieletti, Emanuele; Belloni, Elena; Cavanna, Luigi

2012-01-01

Luminal gastrointestinal (GI) metastases from breast cancer are rare, reports are fragmentary and poor. The purposes of this study are to assess the gastrointestinal involvement from breast cancer in a retrospective study at a single institution and reviewing the related literature. Between January 2007 and December 2011 a total of 980 patients with breast cancer were treated at our institution, patients' records and report database were analysed. Institutional Review Board approval was obtained for this study. A search of the literature using PubMed, CancerLit, Embase, was performed. Selected for the present review were papers published in English before June 2012. Five of 980 patients (0.5%) showed gastrointestinal metastases from breast cancer, 3 patients had gastric involvement, 1 jejunum, and 1 rectum. Reviewing the literature, 206 patients affected by gastrointestinal metastasis from breast cancer were identified: the most frequent site of metastasis was the stomach (60%). The majority of the patients underwent chemotherapy and endocrine therapy, someone surgery and radiotherapy. GI metastases from breast cancer are rare, but possible, and a very late recurrence can also occur. Cyto-histological diagnosis is mandatory, to differentiate GI metastases from breast cancer to other diseases and to allow an adequate treatment.

Novel intervention with acupuncture for anorexia and cachexia in patients with gastrointestinal tract cancers: a feasibility study.

PubMed

Yoon, Saunjoo L; Grundmann, Oliver; Williams, Joseph J; Carriere, Gwen

2015-03-01

To investigate the feasibility of using acupuncture as a complementary intervention to existing treatments and to evaluate the efficacy of acupuncture in improving appetite and slowing weight loss with patients with gastrointestinal (GI) tract cancers. 
 One-group pre- and postintervention feasibility study. 
 Outpatient clinic for patients with cancer and a community setting, both in Florida. 
 A convenience sample of seven adults with GI cancer.
 Eight acupuncture sessions were provided during eight weeks. Data were collected using the visual analog scale (VAS) for appetite, Simplified Nutritional Appetite Questionnaire (SNAQ), Karnofsky Performance Status, and bioelectrical impedance analysis. 
 Appetite, weight, attrition rate.
 Seven patients with a mean age of 61 years completed the intervention. Acupuncture was well accepted, feasible, and safe without any reported side effects. Appetite showed improvement, with an average score of 3.04 on the VAS and 4.14 on SNAQ compared to the preintervention scores. The average weight loss was 1.32% compared to the baseline during an eight-week period. 
 The acupuncture intervention was feasible and indicated positive outcomes. Because of the small sample size and lack of a control group, statistical significance of effectiveness was not determined. Acupuncture seemed to improve appetite and slow weight loss in patients with GI cancers, so additional studies with a larger sample size and a variety of cancers are warranted. 
 Oncology nurses are uniquely able to equip patients with information about complementary therapy modalities, such as acupuncture, which is a promising way to improve appetite and slow weight loss in patients with GI cancers.


Investigation of body image as a mediator of the effects of bowel and GI symptoms on psychological distress in female survivors of rectal and anal cancer.

PubMed

Benedict, Catherine; Rodriguez, Vivian M; Carter, Jeanne; Temple, Larissa; Nelson, Christian; DuHamel, Katherine

2016-04-01

Treatment for rectal and anal cancer (RACa) can result in persistent bowel and gastrointestinal (GI) dysfunction. Body image problems may develop over time and exacerbate symptom-related distress. RACa survivors are an understudied group, however, and factors contributing to post-treatment well-being are not well understood. This study examined whether poorer body image explained the relation between symptom severity and psychological distress. Participants (N = 70) completed the baseline assessment of a sexual health intervention study. Bootstrap methods tested body image as a mediator between bowel and GI symptom severity and two indicators of psychological distress (depressive and anxiety symptoms), controlling for relevant covariates. Measures included the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-CR38) Diarrhea, GI Symptoms, and Body Image subscales and Brief Symptom Index Depression and Anxiety subscales. Women averaged 55 years old (SD = 11.6), White (79 %), and were 4 years post-treatment. Greater Depression was related to poorer Body Image (r = -.61) and worse Diarrhea (r = .35) and GI Symptoms (r = .48). Greater Anxiety was related to poorer Body Image (r = -.42) and worse GI Symptoms (r = .45), but not Diarrhea (r = .20). Body Image mediated the effects of bowel and GI symptoms on Depression, but not on Anxiety. Long-term bowel and GI dysfunction are distressing and affect how women perceive and relate to their bodies, exacerbating survivorship difficulties. Interventions to improve adjustment post-treatment should address treatment side effects, but also target body image problems to alleviate depressive symptoms. Reducing anxiety may require other strategies. Body image may be a key modifiable factor to improve well-being in this understudied population. Longitudinal research is needed to confirm findings.

Risk Factors for GI Adverse Events in a Phase III Randomized Trial of Bevacizumab in First-Line Therapy of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study

PubMed Central

Burger, Robert A.; Brady, Mark F.; Bookman, Michael A.; Monk, Bradley J.; Walker, Joan L.; Homesley, Howard D.; Fowler, Jeffrey; Greer, Benjamin E.; Boente, Matthew; Fleming, Gini F.; Lim, Peter C.; Rubin, Stephen C.; Katsumata, Noriyuki; Liang, Sharon X.

2014-01-01

Purpose To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Patients and Methods Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. Results Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). Conclusion History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy. PMID:24637999

Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis.

PubMed

Tse, Genevieve; Eslick, Guy D

2016-02-01

Evidence suggests that soy foods have chemoprotective properties that may reduce the risk of certain cancers such as breast and prostate cancer. However, data involving gastrointestinal (GI) have been limited, and the evidence remains controversial. This study aims to determine the potential relationship between dietary soy intake and GI cancer risk with an evaluation of the effects of isoflavone as an active soy constituent. Relevant studies were identified after literature search via electronic databases through May 2014. Subgroup analysis for isoflavone intake (studies n = 10) was performed. Covariants including gender types, anatomical subsites and preparation methods were also evaluated. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated using a random effects model. Twenty-two case-control and 18 cohort studies were included for meta-analysis, which contained a total of 633,476 participants and 13,639 GI cancer cases. The combined OR was calculated as 0.93 (95% CI 0.87-0.99; p value heterogeneity = 0.01), showing only a slight decrease in risk, the association was stronger for colon cancer (OR 0.92; 95% CI 0.96-0.99; p value heterogeneity = 0.163) and colorectal cancer (CRC) (OR 0.92; 95% CI 0.87-0.97; p value heterogeneity = 0.3). Subgroup analysis for isoflavone intake showed a statistically significant risk reduction with a risk estimate of 0.73 (95% CI 0.59-0.92; p value heterogeneity = 0), and particularly for CRC (OR 0.76; 95% CI 0.59-0.98; p value heterogeneity = 0). This study provides evidence that soy intake as a food group is only associated with a small reduction in GI cancer risk. Separate analysis for dietary isoflavone intakes suggests a stronger inverse association.

Upper GI Endoscopy

MedlinePlus

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Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

PubMed Central

McQuade, Rachel M.; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C.; Nurgali, Kulmira

2016-01-01

Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers. PMID:27857691

Radiation-induced complications in prostate cancer patients treated with radiotherapy

NASA Astrophysics Data System (ADS)

Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

2014-09-01

The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

Classification and functions of enteroendocrine cells of the lower gastrointestinal tract

PubMed Central

Gunawardene, Ashok R; Corfe, Bernard M; Staton, Carolyn A

2011-01-01

With over thirty different hormones identified as being produced in the gastrointestinal (GI) tract, the gut has been described as ‘the largest endocrine organ in the body’ (Ann. Oncol., 12, 2003, S63). The classification of these hormones and the cells that produce them, the enteroendocrine cells (EECs), has provided the foundation for digestive physiology. Furthermore, alterations in the composition and function of EEC may influence digestive physiology and thereby associate with GI pathologies. Whilst there is a rapidly increasing body of data on the role and function of EEC in the upper GI tract, there is a less clear-cut understanding of the function of EEC in the lower GI. Nonetheless, their presence and diversity are indicative of a role. This review focuses on the EECs of the lower GI where new evidence also suggests a possible relationship with the development and progression of primary adenocarcinoma. PMID:21518048

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

ClinicalTrials.gov

2018-03-29

Colorectal Adenocarcinoma; Gastric Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer; Unresectable Pancreatic Carcinoma

Fluorophore-conjugated antibodies for imaging and resection of GI tumors

NASA Astrophysics Data System (ADS)

Bouvet, Michael; Hoffman, Robert M.

2016-03-01

Negative surgical margins are critical to prevent recurrence in cancer surgery. This is because with current technology in many cases negative margins are impossible due the inability of the surgeon to detect the margin. Our laboratory has developed fluorophore-labeled monoclonal antibodies to aid in cancer visualization in orthotopic nude mouse models of human gastrointestinal (GI) cancer in order to achieve negative margins in fluorescence-guided surgery (FGS). The technologies described herein have the potential to change the paradigm of surgical oncology to engender significantly improved outcomes.

Gastro-oesophageal cancer: facts, myths and surgical folk lore.

PubMed

Park, K G M

2002-12-01

The prognosis of patients with gastric and oesophageal cancers remains poor but increased knowledge of the factors involved in carcinogenesis and a better understanding of the disease process has led to strategies to improve outcomes. These are discussed under the following headings: (1) Prevention of the disease, (2) early detection of tumours, (3) treatment selection and (4) treatment. The likely impact of developments in each of these areas is considered in relation to population-based data from the Scottish Audit of Gastro-Oesophageal Cancer (SAGOC). Although there are a number of novel developments in the management of gastric and oesophageal cancer it is only by the conduct of controlled trials that the value of these will be determined. More immediate improvements in patient care may be derived from rationalisation of existing resources to ensure that all patients benefit from early diagnosis, the appropriate selection and delivery of treatment. One model of care, which may ensure this is the development of managed clinical networks, would maintain the involvement of all units in the management and treatment of upper GI cancers to a level that is possible with the facilities available. At the same time the patients requiring more specialised treatment would benefit from established referral networks

Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu; Moughan, Jennifer; Myerson, Robert

Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structuremore » receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.« less

Dietary fiber and the glycemic index: a background paper for the Nordic Nutrition Recommendations 2012

PubMed Central

Øverby, Nina Cecilie; Sonestedt, Emily; Laaksonen, David E.; Birgisdottir, Bryndis Eva

2013-01-01

The aim of this study is to review recent data on dietary fiber (DF) and the glycemic index (GI), with special focus on studies from the Nordic countries regarding cardiometabolic risk factors, type 2 diabetes, cardiovascular disease, cancer, and total mortality. In this study, recent guidelines and scientific background papers or updates on older reports on DF and GI published between 2000 and 2011 from the US, EU, WHO, and the World Cancer Research Fund were reviewed, as well as prospective cohort and intervention studies carried out in the Nordic countries. All of the reports support the role for fiber-rich foods and DF as an important part of a healthy diet. All of the five identified Nordic papers found protective associations between high intake of DF and health outcomes; lower risk of cardiovascular disease, type 2 diabetes, colorectal and breast cancer. None of the reports and few of the Nordic papers found clear evidence for the GI in prevention of risk factors or diseases in healthy populations, although association was found in sub-groups, e.g. overweight and obese individuals and suggestive for prevention of type 2 diabetes. It was concluded that DF is associated with decreased risk of different chronic diseases and metabolic conditions. There is not enough evidence that choosing foods with low GI will decrease the risk of chronic diseases in the population overall. However, there is suggestive evidence that ranking food based on their GI might be of use for overweight and obese individuals. Issues regarding methodology, validity and practicality of the GI remain to be clarified. PMID:23538683

Methodological Challenges in the Application of the Glycemic Index in Epidemiological Studies Using Data from the European Prospective Investigation into Cancer and Nutrition1–3

PubMed Central

van Bakel, Marit M. E.; Slimani, Nadia; Feskens, Edith J. M.; Du, Huaidong; Beulens, Joline W. J.; van der Schouw, Yvonne T.; Brighenti, Furio; Halkjaer, Jytte; Cust, Anne E.; Ferrari, Pietro; Brand-Miller, Jennie; Bueno-de-Mesquita, H. Bas; Peeters, Petra; Ardanaz, Eva; Dorronsoro, Miren; Crowe, Francesca L.; Bingham, Sheila; Rohrmann, Sabine; Boeing, Heiner; Johansson, Ingegerd; Manjer, Jonas; Tjonneland, Anne; Overvad, Kim; Lund, Eiliv; Skeie, Guri; Mattiello, Amalia; Salvini, Simonetta; Clavel-Chapelon, Françoise; Kaaks, Rudolf

2009-01-01

Associations between the glycemic index (GI) or glycemic load (GL) and diseases are heterogeneous in epidemiological studies. Differences in assigning GI values to food items may contribute to this inconsistency. Our objective was to address methodological issues related to the use of current GI and GL values in epidemiological studies. We performed ecological comparison and correlation studies by calculating dietary GI and GL from country-specific dietary questionnaires (DQ) from 422,837 participants from 9 countries participating in the European Prospective Investigation into Cancer and Nutrition study and single standardized 24-h dietary recalls (24-HDR) obtained from a representative sample (n = 33,404) using mainly Foster Powell's international table as a reference source. Further, 2 inter-rater and 1 inter-method comparison were conducted, comparing DQ GI values assigned by independent groups with values linked by us. The ecological correlation between DQ and 24-HDR was good for GL (overall r = 0.76; P < 0.005) and moderate for GI (r = 0.57; P < 0.05). Mean GI/GL differences between DQ and 24-HDR were significant for most centers. GL but not GI from DQ was highly correlated with total carbohydrate (r = 0.98 and 0.15, respectively; P < 0.0001) and this was higher for starch (r = 0.72; P < 0.0001) than for sugars (r = 0.36; P < 0.0001). The inter-rater and inter-method variations were considerable for GI (weighted κ coefficients of 0.49 and 0.65 for inter-rater and 0.25 for inter-method variation, respectively) but only mild for GL (weighted κ coefficients > 0.80). A more consistent methodology to attribute GI values to foods and validated DQ is needed to derive meaningful GI/GL estimates for nutritional epidemiology. PMID:19158224

Endoscopic management of foreign bodies in the upper-GI tract: experience with 1088 cases in China.

PubMed

Li, Zhao-Shen; Sun, Zhen-Xing; Zou, Duo-Wu; Xu, Guo-Ming; Wu, Ren-Pei; Liao, Zhuan

2006-10-01

Reports on endoscopic management of ingested foreign bodies of the upper-GI tract in China are scarce. To report our experience and outcome in the management of ingestion of foreign bodies in Chinese patients. Between January 1980 and January 2005, a total of 1088 patients (685 men and 403 women; age range, 1 day to 96 years old) with suspected foreign bodies were admitted to our endoscopy center. All patients underwent endoscopic procedure after admission. Demographic and endoscopic data, including age, sex, and referral sources of patients, types, number and location of foreign bodies, associated upper-GI diseases, endoscopic methods, and accessory devices for removal of foreign bodies were collected and analyzed. A total of 1090 foreign bodies were found in 988 (90.8%) patients. The types of foreign bodies varied greatly: mainly food boluses, coins, fish bones, dental prostheses, or chicken bones. The foreign bodies were located in the pharynx (n = 12), the esophagus (n = 577), the stomach (n = 441), the duodenum (n = 50), and the surgical anastomosis (n = 10). The associated GI diseases (n = 88) included esophageal carcinoma (33.0%), stricture (23.9%), diverticulum (15.9%), postgastrectomy (11.4%), hiatal hernia (10.2%), and achalasia (5.7%). A rat-tooth forceps and a snare were the most frequently used accessory devices. The success rate for foreign-body removal was 94.1% (930/988). Ingestion of foreign bodies is a common clinic problem in China. Endoscopy procedures are frequently performed, and a high proportion of patients with foreign bodies require endoscopic intervention.

Factitious disorder: a rare cause of haematemesis.

PubMed

McFarlane, Michael; Eaden, Jayne; Burch, Nicola; Disney, Ben

2017-10-01

Acute upper gastrointestinal (GI) bleeding is a common condition in the UK with 50-70,000 admissions per year. In 20% of cases no cause can be found on endoscopy. Here, we present the case of a young female patient who was admitted on three occasions with large volume haematemesis and bleeding from other sites. She was extensively investigated and underwent multiple endoscopic procedures. She was eventually diagnosed with factitious disorder after concerns were raised about the inconsistent nature of her presentations. She was found to be venesecting herself from her intravenous cannula, and ingesting the blood to simulate upper GI bleeding. This is a rare cause of 'haematemesis' but perhaps not as rare as is thought.

Diets/dietary habits and certain gastrointestinal disorders in the tropics: a review.

PubMed

Nneli, R O; Nwafia, W C; Orji, J O

2007-01-01

Against the background that what one eats affects the gastrointestinal tract (G.I T), the role of diet and dietary habits including fibres, food additives and preservatives on the aetiology of gastric cancers, colorectal cancers and other G.I disorders in the tropics are herein reviewed. Carcinomas of the gut believed to be on the decline in the developed countries have plateaued and increasing cases are being reported in the tropics. Africa and Nigeria in particular, with little or no cases previously are currently experiencing patterns of incidence similar to those of the Western Hemisphere. All these developments are premeditated by the nature of diets and dietary factors contained therein. Some of these factors contain chemical carcinogens, irritants as additives or preservatives, high cholesterol, highly spiced foods, alcohol, nicotine, xanthines, caffeine, most of which provoke gastric acid secretions dyspepsia and heartburn, and they lack vegetables and dietary fibres known to protect the G.I tract against various diseases. The roles of dietary hygiene implicating certain microorganisms associated with G.I diseases like Helicobacter Pylori are also discussed. It presupposes that well articulated diet and proper dietary manipulations remain the cure for all diet induced G.I disorders while avoidance of such habits that predispose to them must be encouraged to ensure proper and healthy G.I T.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the targetmore » volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.« less

Evaluation of Anticancer Activity of Curcumin Analogues Bearing a Heterocyclic Nucleus.

PubMed

Ahsan, Mohamed Jawed; Ahsan, Mohamed Jawed

2016-01-01

We report herein an in vitro anticancer evaluation of a series of seven curcumin analogues (3a-g). The National Cancer Institute (NCI US) Protocol was followed and all the compounds were evaluated for their anticancer activity on nine different panels (leukemia, non small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer) represented by 60 NCI human cancer cell lines. All the compounds showed significant anticancer activity in one dose assay (drug concentration 10 μM) and hence were evaluated further in five dose assays (0.01, 0.1, 1, 10 and 100 μM) and three dose related parameters GI50, TGI and LC50 were calculated for each (3a-g) in micro molar drug concentrations (μM). The compound 3d (NSC 757927) showed maximum mean percent growth inhibition (PGI) of 112.2%, while compound 3g (NSC 763374) showed less mean PGI of 40.1% in the one dose assay. The maximum anticancer activity was observed with the SR (leukemia) cell line with a GI50 of 0.03 μM. The calculated average sensitivity of all cell lines of a particular subpanel toward the test agent showed that all the curcumin analogues showed maximum activity on leukemia cell lines with GI50 values between 0.23 and 2.67 μM.

Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer

PubMed Central

Prasad, Sahdeo; Tyagi, Amit K.

2015-01-01

Gastrointestinal (GI) cancer, a cancer of different organs of the digestive system, is one of the most common cancers around the world. The incidence and death rate of some of these cancers are very high. Although a large variety of chemotherapeutic agents have been introduced since the last few decades to combat GI cancer, most of them are very expensive and have side effects. Therefore, the compounds derived from natural sources, which are considered to be safe and cost effective, are needed. Ginger (Zingiber officinale) is one of the most widely used natural products consumed as a spice and medicine for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, cough, and bronchitis. Experimental studies showed that ginger and its active components including 6-gingerol and 6-shogaol exert anticancer activities against GI cancer. The anticancer activity of ginger is attributed to its ability to modulate several signaling molecules like NF-κB, STAT3, MAPK, PI3K, ERK1/2, Akt, TNF-α, COX-2, cyclin D1, cdk, MMP-9, survivin, cIAP-1, XIAP, Bcl-2, caspases, and other cell growth regulatory proteins. In this review, the evidences for the chemopreventive and chemotherapeutic potential of ginger extract and its active components using in vitro, animal models, and patients have been described. PMID:25838819

Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is Dynamic and Associated with Genomic Instability in a Barrett’s Esophagus Cohort

PubMed Central

Gall, Alevtina; Fero, Jutta; McCoy, Connor; Claywell, Brian C.; Sanchez, Carissa A.; Blount, Patricia L.; Li, Xiaohong; Vaughan, Thomas L.; Matsen, Frederick A.; Reid, Brian J.; Salama, Nina R.

2015-01-01

Background The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett’s esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear. Methodology The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett’s Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett’s esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort. Results/Significance Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett’s esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett’s esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC. PMID:26076489

Incidence and mitigation of gastrointestinal events in patients with relapsing-remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE).

PubMed

Gold, Ralf; Schlegel, Eugen; Elias-Hamp, Birte; Albert, Christian; Schmidt, Stephan; Tackenberg, Björn; Xiao, James; Schaak, Tom; Salmen, Hans Christian

2018-01-01

Gastrointestinal (GI) events are common adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing-remitting multiple sclerosis (RRMS). The objective of the TOLERATE study was to evaluate GI tolerability and GI mitigation via symptomatic therapies in patients initiating DMF in a real-world clinical setting in Germany. TOLERATE was a multicentre, open-label, single-arm study performed at 25 German sites. Endpoints were frequency, severity, duration (all primary) and mitigation of GI-related events (secondary). Patients were instructed to take DMF according to the prescribing information for up to 12 weeks and to document GI events and intake of GI-symptomatic therapy on numerical rating scales, using eDiaries. A total of 211 patients were included in the safety population (71% female; mean age 40 ± 11 years). Of these, 185 patients (87.7%) reported GI-related events, out of which nearly half received GI-symptomatic therapy (84/185; 45.4%). The most frequently reported GI events were upper abdominal pain, flatulence and nausea. GI-related events peaked during the first 3 weeks of therapy and rapidly decreased thereafter. The severity of GI events over 12 weeks according to the Modified Overall Gastrointestinal Symptom Scale were mild to moderate in the majority of patients reporting GI-related events and taking symptomatic GI medication (53.6%). Only 10% of all patients discontinued study treatment due to AEs in general, while 6.6% discontinued due to GI-related events. The severity of GI-related events decreased over time in patients who received symptomatic treatment with one or more medications (e.g. acid secretion blockers, antidiarrhoeals or antiemetics). Gastrointestinal events associated with delayed-release DMF were mainly mild to moderate in severity. Prevalence of GI events peaked during the first 3 weeks of therapy and rapidly faded thereafter. Although 44.9% of patients experiencing GI events used common GI symptomatic therapies, only 6.6% of patients discontinued DMF because of GI events, suggesting that GI events could be managed well with common symptomatic therapy.

Incidence of Esophageal Carcinomas After Surgery for Achalasia: Usefulness of Long-Term and Periodic Follow-up.

PubMed

Ota, Masaho; Narumiya, Kosuke; Kudo, Kenji; Yagawa, Yohsuke; Maeda, Shinsuke; Osugi, Harushi; Yamamoto, Masakazu

2016-11-14

BACKGROUND Patients with esophageal achalasia are considered to be a high-risk group for esophageal carcinoma, and it has been reported that this cancer often arises at a long interval after surgery for achalasia. However, it is unclear whether esophageal carcinoma is frequent when achalasia has been treated successfully and the patient is without dysphagia. In this study, we reviewed patients with esophageal carcinoma who were detected by regular follow-up after surgical treatment of achalasia.   CASE REPORT Esophageal cancer was detected by periodic upper GI endoscopy in 6 patients. Most of them had early cancers that were treated by endoscopic resection. All 6 patients had undergone surgery for achalasia and the outcome had been rated as excellent or good. Annual follow-up endoscopy was done and the average duration of follow-up until cancer was seen after surgery was 14.3 years (range: 5 to 40 years). Five patients had early cancer. Four cases had multiple lesions.   CONCLUSIONS In conclusion, surgery for achalasia usually improves passage symptoms, but esophageal cancer still arises in some cases and the number of tumors occurring many years later is not negligible. Accordingly, long-term endoscopic follow-up is needed for detection of malignancy at an early stage.

Serum albumin level in the management of postoperative enteric fistula for gastrointestinal cancer patients.

PubMed

Lu, Chien-Yu; Wu, Deng-Chyang; Wu, I-Chen; Chu, Koung-Shing; Sun, Li-Chu; Shih, Ying-Ling; Chen, Fang-Ming; Hsieh, Jan-Sing; Wang, Jaw-Yuan

2008-01-01

Postoperative enteric fistula is a serious complication and cause of death following gastrointestinal (GI)-tract surgery. Many reports have demonstrated the effectiveness of parenteral nutrition in the spontaneous closure of enteric fistula. Our study was aimed at analyzing the prognostic factors of parenteral nutritional support in the treatment of enteric fistula for patients with GI-tract cancer following surgery. GI-tract cancer patients receiving surgical interventions, which then unfortunately developed enteric fistula, were included in our study. All of them had to have received parenteral nutrition soon after leakages were recognized, and they were subsequently divided into successful and unsuccessful (classified as "failure") groups according to spontaneous closure of fistula or not, respectively. The studied patients' laboratory data were collected to identify the clinically relevant prognostic factors. Fifty-three primary GI-tract cancer patients with postoperative enteric fistulas were enrolled into our study. Of these, 33 patients were considered as successful parenteral nutritional therapy (successful group) and the other 20 patients (failure group) were not. After a period of parenteral nutritional therapy, serum total bilirubin, creatinine, C-reactive protein (CRP), hemoglobin, and albumin were significantly different between these two groups (all p < .05). Using a multivariate logistic regression analysis, it was determined that increased serum albumin level was an independent predictive factor of successful management for enteric fistula (p = .029), in addition to the well-known lower drainage amount (< 500 mL/day) from the enteric fistula (p = .013). Our observations show that both serum albumin levels and drainage amounts from the enteric fistula can be potentially used as important prognostic predictors of healing enteric fistula under total parenteral nutrition in patients following surgery for GI-tract malignancies.

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

PubMed

Uygun, Kazim; Kocak, Zafer; Altaner, Semsi; Cicin, Irfan; Tokatli, Fusun; Uzal, Cem

2006-08-31

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

Perioperative nutritional status changes in gastrointestinal cancer patients.

PubMed

Shim, Hongjin; Cheong, Jae Ho; Lee, Kang Young; Lee, Hosun; Lee, Jae Gil; Noh, Sung Hoon

2013-11-01

The presence of gastrointestinal (GI) cancer and its treatment might aggravate patient nutritional status. Malnutrition is one of the major factors affecting the postoperative course. We evaluated changes in perioperative nutritional status and risk factors of postoperative severe malnutrition in the GI cancer patients. Nutritional status was prospectively evaluated using patient-generated subjective global assessment (PG-SGA) perioperatively between May and September 2011. A total of 435 patients were enrolled. Among them, 279 patients had been diagnosed with gastric cancer and 156 with colorectal cancer. Minimal invasive surgery was performed in 225 patients. PG-SGA score increased from 4.5 preoperatively to 10.6 postoperatively (p<0.001). Ten patients (2.3%) were severely malnourished preoperatively, increasing to 115 patients (26.3%) postoperatively. In gastric cancer patients, postoperative severe malnourishment increased significantly (p<0.006). In univariate analysis, old age (>60, p<0.001), male sex (p=0.020), preoperative weight loss (p=0.008), gastric cancer (p<0.001), and open surgery (p<0.001) were indicated as risk factors of postoperative severe malnutrition. In multivariate analysis, old age, preoperative weight loss, gastric cancer, and open surgery remained significant as risk factors of severe malnutrition. The prevalence of severe malnutrition among GI cancer patients in this study increased from 2.3% preoperatively to 26.3% after an operation. Old age, preoperative weight loss, gastric cancer, and open surgery were shown to be risk factors of postoperative severe malnutrition. In patients at high risk of postoperative severe malnutrition, adequate nutritional support should be considered.

Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek

Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence ofmore » modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.« less

Investigation of Body Image as a Mediator of the Effects of Bowel and GI Symptoms on Psychological Distress in Female Survivors of Rectal and Anal Cancer

PubMed Central

Benedict, Catherine; Rodriguez, Vivian M.; Carter, Jeanne; Temple, Larissa; Nelson, Christian; DuHamel, Katherine

2016-01-01

Purpose Treatment for rectal and anal cancer (RACa) can result in persistent bowel and gastrointestinal (GI) dysfunction. Body image problems may develop over time and exacerbate symptom-related distress. RACa survivors are an understudied group, however, and factors contributing to post-treatment well-being are not well understood. This study examined whether poorer body image explained the relation between symptom severity and psychological distress. Methods Participants (N=70) completed the baseline assessment of a sexual health intervention study. Bootstrap methods tested body image as a mediator between bowel and GI symptom severity and two indicators of psychological distress (depressive and anxiety symptoms), controlling for relevant covariates. Measures included the EORTC-QLQ-CR38 Diarrhea, GI Symptoms, and Body Image subscales and Brief Symptom Index Depression and Anxiety subscales. Results Women averaged 55 years old (SD=11.6), White (79%), and 4-years post-treatment. Greater Depression related to poorer body image (r=−.61) and worse diarrhea (r=.35) and GI symptoms (r=.48). Greater Anxiety related to poorer body image (r=−.42) and worse GI symptoms (r=.45), but not diarrhea (r=.20). Body image mediated the effects of bowel and GI symptoms on Depression, but not on Anxiety. Conclusions Long-term bowel and GI dysfunction are distressing and affect how women perceive and relate to their bodies, exacerbating survivorship difficulties. Interventions to improve adjustment post-treatment should address treatment side effects, but also target body image problems to alleviate depressive symptoms. Reducing anxiety may require other strategies. Body image may be a key modifiable factor to improve well-being in this understudied population. Longitudinal research is needed to confirm findings. PMID:26446699

CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine.

PubMed

Ohnishi, Nobuhiko; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sato, Yasuharu; Tari, Akira; Gion, Yuka; Noujima-Harada, Mai; Taniguchi, Kohei; Tabata, Tetsuya; Nagakita, Keina; Omote, Shizuma; Takahata, Hiroyuki; Iwamuro, Masaya; Okada, Hiroyuki; Maeda, Yoshinobu; Yanai, Hiroyuki; Yoshino, Tadashi

2016-11-01

Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10 down ) GI-FL. The diagnosis of CD10 down FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10 down GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs 3.5%, P < 0.001). Compared to CD10 + GI-FL, CD10 down GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10 down group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa-associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10 down GI-FL, and an identical clone was found between CD10 down follicles and CD10 + BCL2 + neoplastic follicles. In the diagnosis of cases with CD10 down BCL2 + follicles, careful examination with molecular studies should be carried out. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

PubMed Central

Hasenoehrl, Carina; Taschler, Ulrike; Storr, Martin; Schicho, Rudolf

2016-01-01

Background and Purpose In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract. Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced cannabinoids and their receptors. After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity. In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARα) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of cannabinoids in the gut and critically determine the course of bowel inflammation and colon cancer. The following review summarizes important and recent findings on the role of cannabinoid receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease and colon cancer. PMID:27561826

Intestinal leiomyoma

MedlinePlus

... most often found when a person has an upper gastrointestinal (GI) endoscopy or colonoscopy for another reason. Rarely, these tumors can cause bleeding, blockage or rupture of the intestines If this ...

Upper gastrointestinal bleeding in a patient with depression receiving selective serotonin reuptake inhibitor therapy.

PubMed

Kumar, Deepak; Saaraswat, Tanuj; Sengupta, S N; Mehrotra, Saurabh

2009-02-01

Serotonin plays an important role in the normal clotting phenomenon and is released by platelets. Platelets are dependent on a serotonin transporter for the uptake of serotonin, as they cannot synthesize it themselves. Selective serotonin reuptake inhibitors (SSRIs) block the uptake of serotonin into platelets and can cause problems with clotting leading to bleeding. This case report highlights the occurrence of upper gastrointestinal bleeding in the index case on initiating SSRI therapy for depression and the prompt resolution of the same on its discontinuation on two separate occasions. SSRIs may cause upper gastrointestinal (GI) bleeding. Physicians should be aware of the same and should try to rule out previous episodes of upper GI bleed or the presence of other risk factors which might predispose to it before prescribing SSRIs; they should also warn the patients about this potential side effect. Also, the presence of thalassemia trait in the index patient deserves special attention and needs to be explored to see if it might in any way contribute in potentiating this side effect of SSRIs.

Telomeres and telomere dynamics: relevance to cancers of the gastrointestinal tract

PubMed Central

Basu, Nivedita; Skinner, Halcyon G.; Litzelman, Kristin; Vanderboom, Russell; Baichoo, Esha; Boardman, Lisa A.

2013-01-01

Summary Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to GI tract cancer. Peripheral blood telomeres are shorter in patients with many types of GI tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres (ALT) is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and ALT activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere related phenotypes, and its relationship to carcinogenesis increases. PMID:24161135

Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy?

PubMed

Phillips, F; Muls, A C G; Lalji, A; Andreyev, H J N

2015-08-01

Gastrointestinal (GI) symptoms during and after cancer therapy can significantly affect quality of life and interfere with treatment. This study assessed whether bile acid malabsorption (BAM) or bile acid diarrhoea (BAD) are important causes of diarrhoea associated with cancer treatment. A retrospective analysis was carried out of consecutive patients assessed for BAM using ((75) Se) Selenium homocholic acid taurocholate (SeHCAT) scanning, after reporting any episodes of loose stool, attending a gastroenterology clinic in a cancer centre. Between 2009 and 2013, 506 consecutive patients (54.5% male; age range: 20-91 years), were scanned. BAM/BAD was diagnosed in 215 (42.5%). It was mild in 25.6%, moderate in 29.3% and severe in 45.1%. Pelvic chemoradiation had induced BAM in > 50% of patients. BAM was also frequent after treatment for conditions not previously associated with BAM, such as anal and colorectal cancer, and was present in > 75% of patients referred after pancreatic surgery. It was also unexpectedly frequent in patients who were treated for malignancy outside the GI tract, such as breast cancer and haematological malignancy. BAM/BAD are very common and under-appreciated causes of GI symptoms after cancer treatment. Health professionals should have a low threshold in suspecting this condition, as diagnosis and treatment can significantly improve quality of life. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Late gastrointestinal effects of pelvic radiation: a nurse-led service.

PubMed

Ludlow, Helen; Green, John; Turner, Jeff

2017-02-23

There are currently at least 2 million people in the UK living with and following a cancer diagnosis. Typically four out of every ten people with cancer will receive radiotherapy, but a large proportion of people who have pelvic radiotherapy may go on to develop gastrointestinal (GI) symptoms. This includes rectal bleeding and faecal incontinence, which can have a huge impact on quality of life. These problems often go under-reported by patients and are also under-recognised or under-treated by health professionals. Cancer survivorship is a growing topic that is likely to have a major impact on the NHS, with increasing numbers of patients presenting. A late GI effects of pelvic radiotherapy clinic was set up to address these growing needs of patients with GI symptoms following radiotherapy. This article also shares insights from a doctoral study that is underway looking at people's experiences of living with symptoms following their treatment, in order to improve awareness of the major impact that this can have.

pH-Responsive Hydrogels with Dispersed Hydrophobic Nanoparticles for the Oral Delivery of Chemotherapeutics

PubMed Central

Schoener, Cody A.; Hutson, Heather N.; Peppas, Nicholas A.

2012-01-01

Amphiphilic polymer carriers were formed by polymerizing a hydrophilic, pH-responsive hydrogel composed of poly(methacrylic – grafted – ethylene glycol) (P(MAA-g-EG)) in the presence of hydrophobic PMMA nanoparticles. These polymer carriers were varied in PMMA nanoparticle content to elicit a variety of physiochemical properties which would preferentially load doxorubicin, a hydrophobic chemotherapeutic, and release doxorubicin locally in the colon for the treatment of colon cancers. Loading levels ranged from 49% to 64% and increased with increasing nanoparticle content. Doxorubicin loaded polymers were released in a physiological model where low pH was used to simulate the stomach and then stepped to more neutral conditions to simulate the upper small intestine. P(MAA-g-EG) containing nanoparticles were less mucoadhesive as determined using a tensile tester, polymer samples, and fresh porcine small intestine. The cytocompatibility of the polymer materials were assessed using cell lines representing the GI tract and colon cancer and were non-cytotoxic at varying concentrations and exposure times. PMID:23281185

Jejunal varices diagnosed by capsule endoscopy in patients with post-liver transplant portal hypertension.

PubMed

Bass, Lee M; Kim, Stanley; Superina, Riccardo; Mohammad, Saeed

2017-02-01

Portal hypertension secondary to portal vein obstruction following liver transplant occurs in 5%-10% of children. Jejunal varices are uncommon in this group. We present a case series of children with significant GI blood loss, negative upper endoscopy, and jejunal varices detected by CE. Case series of patients who had CE for chronic GI blood loss following liver transplantation. Three patients who had their initial transplants at a median age of 7 months were identified at our institution presenting at a median age of 8 years (range 7-16 years) with a median Hgb of 2.8 g/dL (range 1.8-6.8 g/dL). Upper endoscopy was negative for significant esophageal varices, gastric varices, and bleeding portal gastropathy in all three children. All three patients had significant jejunal varices noted on CE in mid-jejunum. Jejunal varices were described as large prominent bluish vessels underneath visualized mucosa, one with evidence of recent bleeding. The results led to venoplasty of the portal vein in two patients and a decompressive shunt in one patient with resolution of GI bleed and anemia. CE is useful to diagnose intestinal varices in children with portal hypertension and GI bleeding following liver transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Indigestion

MedlinePlus

... Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Hemorrhoids Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & ... Bowel Syndrome (IBS) Peptic Ulcer Disease Related Diagnostic Tests Upper GI Endoscopy Your Digestive System and How ...

Satiety - early

MedlinePlus

... check for anemia Esophagogastroduodenoscopy (EGD) Stool tests for bleeding X-rays studies of the stomach, esophagus, and small intestine (abdominal x-ray and an upper GI and small bowel series ) Stomach-emptying studies

Perioperative Nutritional Status Changes in Gastrointestinal Cancer Patients

PubMed Central

Shim, Hongjin; Cheong, Jae Ho; Lee, Kang Young; Lee, Hosun; Noh, Sung Hoon

2013-01-01

Purpose The presence of gastrointestinal (GI) cancer and its treatment might aggravate patient nutritional status. Malnutrition is one of the major factors affecting the postoperative course. We evaluated changes in perioperative nutritional status and risk factors of postoperative severe malnutrition in the GI cancer patients. Materials and Methods Nutritional status was prospectively evaluated using patient-generated subjective global assessment (PG-SGA) perioperatively between May and September 2011. Results A total of 435 patients were enrolled. Among them, 279 patients had been diagnosed with gastric cancer and 156 with colorectal cancer. Minimal invasive surgery was performed in 225 patients. PG-SGA score increased from 4.5 preoperatively to 10.6 postoperatively (p<0.001). Ten patients (2.3%) were severely malnourished preoperatively, increasing to 115 patients (26.3%) postoperatively. In gastric cancer patients, postoperative severe malnourishment increased significantly (p<0.006). In univariate analysis, old age (>60, p<0.001), male sex (p=0.020), preoperative weight loss (p=0.008), gastric cancer (p<0.001), and open surgery (p<0.001) were indicated as risk factors of postoperative severe malnutrition. In multivariate analysis, old age, preoperative weight loss, gastric cancer, and open surgery remained significant as risk factors of severe malnutrition. Conclusion The prevalence of severe malnutrition among GI cancer patients in this study increased from 2.3% preoperatively to 26.3% after an operation. Old age, preoperative weight loss, gastric cancer, and open surgery were shown to be risk factors of postoperative severe malnutrition. In patients at high risk of postoperative severe malnutrition, adequate nutritional support should be considered. PMID:24142640

Burden of Gastrointestinal and Liver Diseases in Iran: Estimates Based on the Global Burden of Disease, Injuries, and Risk Factors Study, 2010.

PubMed

Malekzadeh, Fatemeh; Sepanlou, Sadaf Ghajarieh; Poustchi, Hossein; Naghavi, Mohsen; Forouzanfar, Mohammad Hossein; Shahraz, Saeid; Moradi-Lakeh, Maziar; Malekzadeh, Reza

2015-07-01

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries is necessary for improving the accuracy of future updates of GBD in these countries.

Resource Utilization in Ambulatory Primary Care at Darnall Army Community Hospital, Fort Hood, Texas

DTIC Science & Technology

1991-07-23

population: gastroenteritis (GI), otitis media (OM), and upper respiratory infection (URI). These resources will be thc- dependent variables of the study...1991. The children ranged in age from 3 to 5 years old and were diagnosed with otitis media , upper respiratory tract infection, and gastroenteritis. A...x-rays wer-e rarely ordered to confirm the diagnoses of otitis media , gastroeinteritis. and upper respiratory tract infection. Only eight, laboratory

Potential role of gastrointestinal microbiota composition in prostate cancer risk

PubMed Central

2013-01-01

Background Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk. Presentation of the hypothesis The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents. Testing the hypothesis Because very little preliminary data exist on this potential association, a case–control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time. Implications of the hypothesis Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host’s risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies. PMID:24180596

Celiac Disease

MedlinePlus

... Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Hemorrhoids Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & ... Defects Dermatitis Herpetiformis Reproductive Problems Osteoporosis Related Diagnostic Tests Upper GI Endoscopy For Health Care Professionals Dermatitis ...

Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic session for diagnosis and staging of gastric neoplastic lesions.

PubMed

Gheorghe, C; Iacob, R; Dumbrava, Mona; Becheanu, G; Ionescu, M

2009-01-01

Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic technique which allows subsurface in vivo histological assessment during ongoing endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in staging upper GI malignant lesions. We describe for the first time the use of both techniques during the same endoscopic session, in a pilot study, in order to increase the diagnostic yield of histological assessment and provide the staging of the gastric neoplastic lesions thus decreasing the time to therapeutic decision. CLE has been performed with the Pentax EG-3870CIK confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS has been performed subsequently, during the same endoscopic Propofol sedation session, using a standard radial EUS-scope. Eleven patients have been investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion of gastric cancer recurrence after resection 9% and infiltrating type gastric cancer 9%. Histological assessment after targeted biopsy has established the diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2 patients - one case with suspected recurrent gastric cancer after surgery and one case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in one case. The EUS evaluation showed in one gastric lymphoma patient a lesion interesting the mucosa and submucosa with regional adenopathy and a submucosal lesion with regional adenopathy in the other gastric lymphoma case. The therapeutic decision was surgery in 73% of cases, chemotherapy and follow-up in 18% of cases and follow-up in 9% of cases. No complications were registered during the CLE/EUS explorations. CLE and EUS can be successfully associated during the same endoscopic session, for upper GI neoplastic lesions allowing targeted biopsies for histological assessment and disease staging for optimal therapeutic decision.

Valentino's syndrome a perforated peptic ulcer mimicking acute appendicitis.

PubMed

Wijegoonewardene, Sandeep Indika; Stein, Joel; Cooke, David; Tien, Alan

2012-06-28

The authors present a case of a 30-year-old female who presented with symptoms and signs suggestive of appendicitis accompanied by elevated inflammatory markers. The patient was consented and taken to theatre for laparoscopic apendicectomy. At operation, the appendix was found to be normal but with surrounding turbid fluid in the right paracolic gutter and subhepatic space. On further inspection, a perforated pre pyloric ulcer was discovered. This was managed laparoscopically with a peritoneal lavage and falciform ligament patch repair. The patient made a good recovery and was discharged 2 days later. At 6 week follow-up the patient had an upper gastrointestinal (GI) endoscopy which showed complete healing of the ulcer. At 6 week follow-up the patient had an upper GI endoscopy which showed complete healing of the ulcer.

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

PubMed Central

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events. PMID:27490468

Surgical process improvement tools: defining quality gaps and priority areas in gastrointestinal cancer surgery.

PubMed

Wei, A C; Devitt, K S; Wiebe, M; Bathe, O F; McLeod, R S; Urbach, D R

2014-04-01

Surgery is a cornerstone of cancer treatment, but significant differences in the quality of surgery have been reported. Surgical process improvement tools (spits) modify the processes of care as a means to quality improvement (qi). We were interested in developing spits in the area of gastrointestinal (gi) cancer surgery. We report the recommendations of an expert panel held to define quality gaps and establish priority areas that would benefit from spits. The present study used the knowledge-to-action cycle was as a framework. Canadian experts in qi and in gi cancer surgery were assembled in a nominal group workshop. Participants evaluated the merits of spits, described gaps in current knowledge, and identified and ranked processes of care that would benefit from qi. A qualitative analysis of the workshop deliberations using modified grounded theory methods identified major themes. The expert panel consisted of 22 participants. Experts confirmed that spits were an important strategy for qi. The top-rated spits included clinical pathways, electronic information technology, and patient safety tools. The preferred settings for use of spits included preoperative and intraoperative settings and multidisciplinary contexts. Outcomes of interest were cancer-related outcomes, process, and the technical quality of surgery measures. Surgical process improvement tools were confirmed as an important strategy. Expert panel recommendations will be used to guide future research efforts for spits in gi cancer surgery.

Surgical process improvement tools: defining quality gaps and priority areas in gastrointestinal cancer surgery

PubMed Central

Wei, A.C.; Devitt, K.S.; Wiebe, M.; Bathe, O.F.; McLeod, R.S.; Urbach, D.R.

2014-01-01

Background Surgery is a cornerstone of cancer treatment, but significant differences in the quality of surgery have been reported. Surgical process improvement tools (spits) modify the processes of care as a means to quality improvement (qi). We were interested in developing spits in the area of gastrointestinal (gi) cancer surgery. We report the recommendations of an expert panel held to define quality gaps and establish priority areas that would benefit from spits. Methods The present study used the knowledge-to-action cycle was as a framework. Canadian experts in qi and in gi cancer surgery were assembled in a nominal group workshop. Participants evaluated the merits of spits, described gaps in current knowledge, and identified and ranked processes of care that would benefit from qi. A qualitative analysis of the workshop deliberations using modified grounded theory methods identified major themes. Results The expert panel consisted of 22 participants. Experts confirmed that spits were an important strategy for qi. The top-rated spits included clinical pathways, electronic information technology, and patient safety tools. The preferred settings for use of spits included preoperative and intraoperative settings and multidisciplinary contexts. Outcomes of interest were cancer-related outcomes, process, and the technical quality of surgery measures. Conclusions Surgical process improvement tools were confirmed as an important strategy. Expert panel recommendations will be used to guide future research efforts for spits in gi cancer surgery. PMID:24764704

Improved synthesis of ADAM10 inhibitor GI254023X.

PubMed

Hoettecke, Nicole; Ludwig, Andreas; Foro, Sabine; Schmidt, Boris

2010-01-01

The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations. 2010 S. Karger AG, Basel.

Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

PubMed Central

Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

2012-01-01

Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

Proteinase-activated receptor 2 (PAR-2) in gastrointestinal and pancreatic pathophysiology, inflammation and neoplasia.

PubMed

Søreide, Kjetil

2008-08-01

Of all the body systems, the gastrointestinal (GI) tract is the most exposed to proteinases. Proteolytic activity must thus be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological GI conditions. The protease-activated receptor-2 (PAR-2) is expressed in numerous cell types within the GI tract, suggesting both multiple functions and numerous modes of receptor activation. Although best known as a pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers. Of interest, trypsin and PAR-2 act together in an autocrine loop that promotes proliferation, invasion and metastasis in neoplasia through various mechanisms. Trypsin and PAR-2 seem to act both directly and indirectly through activation of other proteinase cascades, including metalloproteinases. PAR-2 activation can participate in inflammatory reactions, be protective to mucosal surfaces, send or inhibit nociceptive messages, modify gut motility or secretory functions, and stimulate cell proliferation and motility. Several studies point to a role for the PARs in disease processes of the GI tract and pancreas ranging from inflammatory bowel disease, symptoms associated with irritable bowel syndrome, pain in pancreatitis, development of colon and other GI cancers, and even infectious colitis. Proteinases should not only be considered from the traditional view as digestive or degradative enzymes in the gut, but additionally as signalling molecules that actively participate in the spectrum of physiology and diseased states of the GI tract.

Treatment of vascular malformation of the gastrointestinal tract

NASA Astrophysics Data System (ADS)

Waldschmidt, Juergen; Stroedter, L.; Doede, T.; Kischkel, A.

2000-06-01

Vascular malformations of the gastrointestinal tract are rare phenomenon. They are generally manifested by upper or lower GI - bleeding and do not resolve spontaneously. Emergency intervention is necessary. This paper reports on 10 cases, treated in the Dept. of Pediatric surgery of the FU Berlin, recorded from 1981 to 1999. We use the Nd:YAG laser 1064 nm, Fibertom 5100, Dornier, Germany, with a 600nm barefiber. Reduction in size of the hemangiomas and stop of the GI-bleeding was achieved in all cases.

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Carbohydrate, dietary glycaemic index and glycaemic load, and colorectal cancer risk: a case-control study in China.

PubMed

Huang, Jing; Fang, Yu-Jing; Xu, Ming; Luo, Hong; Zhang, Nai-Qi; Huang, Wu-Qing; Pan, Zhi-Zhong; Chen, Yu-Ming; Zhang, Cai-Xia

2018-04-01

A carbohydrate-rich diet results in hyperglycaemia and hyperinsulinaemia; it may further induce the carcinogenesis of colorectal cancer. However, epidemiological evidence among Chinese population is quite limited. The aim of this study was to investigate total carbohydrate, non-fibre carbohydrate, total fibre, starch, dietary glycaemic index (GI) and glycaemic load (GL) in relation to colorectal cancer risk in Chinese population. A case-control study was conducted from July 2010 to April 2017, recruiting 1944 eligible colorectal cancer cases and 2027 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. There was no clear association between total carbohydrate intake and colorectal cancer risk. The adjusted OR was 0·85 (95 % CI 0·70, 1·03, P trend=0·08) comparing the highest with the lowest quartile. Total fibre was related to a 53 % reduction in colorectal cancer risk (adjusted ORquartile 4 v. 1 0·47; 95 % CI 0·39, 0·58). However, dietary GI was positively associated with colorectal cancer risk, with an adjusted ORquartile 4 v. 1 of 3·10 (95 % CI 2·51, 3·85). No significant association was found between the intakes of non-fibre carbohydrate, starch and dietary GL and colorectal cancer risk. This study indicated that dietary GI was positively associated with colorectal cancer risk, but no evidence supported that total carbohydrate, non-fibre carbohydrate, starch or high dietary GL intake were related to an increased risk of colorectal cancer in a Chinese population.

Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial.

PubMed

Sherwood, Matthew W; Nessel, Christopher C; Hellkamp, Anne S; Mahaffey, Kenneth W; Piccini, Jonathan P; Suh, Eun-Young; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hankey, Graeme J; Berkowitz, Scott D; Fox, Keith A A; Patel, Manesh R

2015-12-01

Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cancer risk in patients with alopecia areata: a nationwide population-based matched cohort study.

PubMed

Chen, Chih-Chiang; Chang, Yun-Ting; Liu, Han-Nan; Chen, Yi-Ju

2018-05-01

Alopecia areata (AA) is an organ-specific autoimmune disorder. Defective immune system related disorders are prone to increase the risk of cancer formation. However, the association among AA and variety of cancer types had never been studied. A nationwide population-based matched cohort study was conducted to evaluate the cancer risk in patients with AA. Records from Taiwan National Health Insurance Research Database were analyzed. Cases of AA from 1997 to 2013 and cancers registered in the catastrophic illness profile from the same time period were collected. The standard incidence ratio (SIR) of each cancer was calculated. In total, 2099 cancers among 162,499 patients with AA and without prior cancers were identified. The overall cancer risks in AA patients were slightly decreased, especially among male subjects (SIR: 0.89). Refer to individual cancer, the cancer risk of nonmelanoma skin cancer (NMSC) (SIR: 0.59), upper GI cancer (SIR: 0.70), liver cancer (SIR: 0.82), uterine, and cervix cancer (SIR: 0.84) were significantly lower in patients with AA. In contrast, AA patients were inclined to have lymphoma, breast cancer, kidney, and urinary bladder cancer with the SIR of 1.55, 2.93, and 2.95, respectively. Age stratified analyses revealed female AA patients younger than 50 years old have even higher risk of breast cancer (SIR: 3.37). Further sensitivity analysis showed similar results after excluding major autoimmune disorders. Cancer risk in AA patients is organ specific, and it is not associated with the underlying autoimmune disorders in patients with AA. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Perceived stress and gastrointestinal symptoms in nursing students in Korea: A cross-sectional survey

PubMed Central

2011-01-01

Background Although nursing students experience a high level of stress during their training, there has been limited research on stress and its impact on the student's physical responses, such as gastrointestinal symptoms. The aims of this study are to assess the prevalence of GI symptoms in nursing students in Korea and to examine the association between the perceived stress and GI symptoms. Methods A cross-sectional descriptive study design was used. A total of 715 students of a three-year associate degree nursing program in a Korean college participated. The Perceived Stress Scale and a GI Symptoms Questionnaire were administered through a self-reported system. Chi-square tests, Fisher's exact test, and logistic regression analysis were performed using SPSS 17.0. Results Sixty-five percent of the nursing students experienced more than one GI symptom, with 31.1% of students reporting more than three GI symptoms. Most of the nursing students complained of upper dysmotility and bowel symptoms. In addition, students who reported higher perceived stress were significantly more likely to complain of GI symptoms. Compared to nursing students with the lowest perceived stress level, the adjusted odds ratio (OR) for GI symptoms in students with the highest perceived stress level was 3.52 times higher (95% CI = 2.05-6.06). Conclusions GI symptoms that are highly prevalent among nursing students are significantly associated with the perceived stress level. High perceived stress should be considered a risk factor for GI symptoms. To reduce perceived stress, stress management programs including cognitive reappraisal training are needed in nursing curriculum. PMID:22067441

Gastrointestinal Bleeding Due to Gastrointestinal Tract Malignancy: Natural History, Management, and Outcomes.

PubMed

Schatz, Richard A; Rockey, Don C

2017-02-01

Gastrointestinal (GI) tumor bleeding can vary from occult bleeding to massive hemorrhage and can be the presenting sign of malignancy. Our primary aims were to: (1) characterize the natural history, treatment, and outcomes in patients with GI tumor bleeding and (2) compare and contrast bleeding in upper GI (UGI)/small bowel (SB) and lower GI malignancies. Patients with endoscopically confirmed tumor bleeding were identified through search of consecutive electronic medical records: Bleeding was determined by the presence of melena, hematochezia, hematemesis, or fecal occult blood. Comprehensive clinical and management data were abstracted. A total of 354 patients with GI tumors were identified: 71 had tumor bleeding (42 UGI/SB and 29 colonic). GI bleeding was the initial presenting symptom of malignancy in 55/71 (77%) of patients; 26/71 patients had widely metastatic disease at presentation. Further, 15 of 26 patients with metastatic disease presented with GI bleeding. Visible bleeding was present in 14/42 (33%) and 4/29 (14%) of UGI/SB and colonic tumors, respectively. Endoscopic hemostasis was attempted in 10 patients, and although initial control was successful in all, bleeding recurred in all of these patients. The most common endoscopic lesion was clean-based tumor ulceration. Overall mortality at 1 year was 57% for esophageal/gastric, 14% for SB, and 33% for colonic tumors. When patients with GI malignancy present with GI bleeding, it is often the index symptom. Initial endoscopic hemostasis is often successful, but rebleeding is typical. Esophageal and gastric tumors carry the poorest prognosis, with a high 1-year mortality rate.

Chronic Diarrhea in Children

MedlinePlus

... Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Hemorrhoids Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & ... Disease IBS in Children Lactose Intolerance Related Diagnostic Tests Colonoscopy Flexible Sigmoidoscopy Upper GI Endoscopy Your Digestive ...

The fourth space surgery: endoscopic subserosal dissection for upper gastrointestinal subepithelial tumors originating from the muscularis propria layer.

PubMed

Liu, Fei; Zhang, Song; Ren, Wei; Yang, Tian; Lv, Ying; Ling, Tingsheng; Zou, Xiaoping; Wang, Lei

2018-05-01

We developed a novel method of endoscopic subserosal dissection (ESSD) for removal of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the upper gastrointestinal (GI) tract. The aim of this study was to evaluate the efficacy, safety, and clinical outcome of this method. Eleven patients with upper GI SETs originating from the MP layer were treated by ESSD between October 2016 and March 2017. ESSD technique consists of six major procedures: (1) incising the mucosal and submucosal layer around the lesion and exposing MP layer; (2) continuous injection was performed while the injection needle slowly moved from the MP layer toward the subserosal layer; (3) incising MP layer; (4) subserosal injection was performed to further separate the serosa from the MP layer; (5) the mucosa, submucosa, and MP layer including SET were carefully dissected en bloc; and (6) closure of the gastric-wall defect with endoscopic techniques. Primary outcome including clinical procedural success and procedure-related adverse events were documented. ESSD was successfully performed in 11 patients. The complete resection rate was 100%, and the mean operation time was 51 (range 22-76) min. The mean resected lesion size was 27 (range 15-40) mm. Pathological diagnosis of these lesions included gastrointestinal stromal tumors (8/11), heterotopic pancreas (1/11), hamartoma (1/11), and leiomyoma (1/11). The small perforations occurred in two patients (4 × 4 and 5 × 5 mm, respectively) during the operation. All perforations and defects were closed successfully by endoscopic techniques. No GI bleeding, peritonitis, abdominal abscess, and other adverse events were observed. No lesion residual or recurrence was found during the follow-up period (mean 18 weeks; range 10-29 weeks). ESSD seems to be an efficacious, safe, and minimally invasive treatment for patients with upper GI SETs originating from the MP layer, making it possible to resect deep lesions, provide precise pathological diagnosis, and maintain the integrity of serosa.

A comparison of cost effectiveness using data from randomized trials or actual clinical practice: selective cox-2 inhibitors as an example.

PubMed

van Staa, Tjeerd-Pieter; Leufkens, Hubert G; Zhang, Bill; Smeeth, Liam

2009-12-01

Data on absolute risks of outcomes and patterns of drug use in cost-effectiveness analyses are often based on randomised clinical trials (RCTs). The objective of this study was to evaluate the external validity of published cost-effectiveness studies by comparing the data used in these studies (typically based on RCTs) to observational data from actual clinical practice. Selective Cox-2 inhibitors (coxibs) were used as an example. The UK General Practice Research Database (GPRD) was used to estimate the exposure characteristics and individual probabilities of upper gastrointestinal (GI) events during current exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs. A basic cost-effectiveness model was developed evaluating two alternative strategies: prescription of a conventional NSAID or coxib. Outcomes included upper GI events as recorded in GPRD and hospitalisation for upper GI events recorded in the national registry of hospitalisations (Hospital Episode Statistics) linked to GPRD. Prescription costs were based on the prescribed number of tables as recorded in GPRD and the 2006 cost data from the British National Formulary. The study population included over 1 million patients prescribed conventional NSAIDs or coxibs. Only a minority of patients used the drugs long-term and daily (34.5% of conventional NSAIDs and 44.2% of coxibs), whereas coxib RCTs required daily use for at least 6-9 months. The mean cost of preventing one upper GI event as recorded in GPRD was US$104k (ranging from US$64k with long-term daily use to US$182k with intermittent use) and US$298k for hospitalizations. The mean costs (for GPRD events) over calendar time were US$58k during 1990-1993 and US$174k during 2002-2005. Using RCT data rather than GPRD data for event probabilities, the mean cost was US$16k with the VIGOR RCT and US$20k with the CLASS RCT. The published cost-effectiveness analyses of coxibs lacked external validity, did not represent patients in actual clinical practice, and should not have been used to inform prescribing policies. External validity should be an explicit requirement for cost-effectiveness analyses.

PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy.

PubMed

Long, Junyu; Lin, Jianzhen; Wang, Anqiang; Wu, Liangcai; Zheng, Yongchang; Yang, Xiaobo; Wan, Xueshuai; Xu, Haifeng; Chen, Shuguang; Zhao, Haitao

2017-08-03

Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

A Fibreoptic endoscopic study of upper gastrointestinal bleeding at Bugando Medical Centre in northwestern Tanzania: A retrospective review of 240 cases

PubMed Central

2012-01-01

Background Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. Findings A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Conclusion Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding. PMID:22537571

A fibreoptic endoscopic study of upper gastrointestinal bleeding at Bugando Medical Centre in northwestern Tanzania: a retrospective review of 240 cases.

PubMed

Jaka, Hyasinta; Koy, Mheta; Liwa, Anthony; Kabangila, Rodrick; Mirambo, Mariam; Scheppach, Wolfgang; Mkongo, Eliasa; McHembe, Mabula D; Chalya, Phillipo L

2012-07-03

Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding.

Prevalence of Helicobacter pylori prevalence and upper gastrointestinal endoscopy in HIV/AIDS patients with gastrointestinal symptoms in the University Teaching Hospitals in Cameroon.

PubMed

Andoulo, F A; Kowo, M; Ngatcha, G; Ndam, A N; Awouoyiegnigni, B; Sida, M B; Tzeuton, C; Ndjitoyap Ndam, E C

2016-08-01

To determine the prevalence of Helicobacter pylori (H. pylori) infection and of various upper gastrointestinal (GI) lesions in HIV + patients with GI symptoms and the relation of H. pylori infection to CD4 cell counts. In all, 56 HIV + patients and 56 age- and sex-matched HIV - controls, all with upper GI symptoms, were evaluated by an upper endoscopy examination and gastric biopsy. H. pylori status was assessed with a urease test and histology. HIV was diagnosed with the rapid test and enzyme-linked immunosorbent assay (ELISA). The prevalence of H. pylori was 50% (28/56 [95%CI 36.3-63.7]) in HIV + subjects and 55% (31/56 [95%CI 41.5-68.7]) in HIV - controls (p = 0.57). H. pylori infection rates did not differ significantly in HIV + patients between those with a CD4 count ≥200/mm 3 (52%) and those with a CD4 count <200/mm 3 (42%) (p = 0.62). The prevalence on endoscopy of specific lesions in HIV + patients and controls were compared: esophageal candidiasis (61%, 34/56 vs. 7%; p<0.0001), esophageal ulcers (18%, 10/56 vs 2%; p = 0.01), corpus gastritis (41%; 23/56 vs 5%; p<0.0001), and duodenitis (20%, 11/56, vs 0%; p = 0.001). The prevalence rate of H. pylori did not differ significantly between HIV + and HIV - subjects. Prevalence of H. pylori was also lower, although not significantly, among HIV + patients with CD4 T-cell counts below 200/mm 3 . On endoscopy, esophageal candidiasis was the most common finding in HIV + patients, discovered by dysphagia.

Prospective Study of Glycemic Load, Glycemic Index, and Carbohydrate Intake in Relation to Risk of Biliary Tract Cancer.

PubMed

Larsson, Susanna C; Giovannucci, Edward L; Wolk, Alicja

2016-06-01

Diets that induce a high glycemic response might increase the risk of biliary tract cancer (BTC). We evaluated the hypothesis that diets with high glycemic load (GL) and high glycemic index (GI), which are measures of the glycemic effect of foods, are associated with an increased incidence of BTC. We used data from a population-based prospective study of 76,014 Swedish adults (age 45-83 years; 57% men) who were free of cancer and had completed a food-frequency questionnaire in the autumn of 1997. Incident cancer cases were ascertained by linkage with the Swedish Cancer Registry. Data were analyzed using Cox proportional hazards regression models. During a mean follow-up of 13.3 years (1,010,777 person-years), we identified 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases. A high dietary GL was associated with an increased risk of BTC. The multivariable relative risks for the highest versus lowest quartile of dietary GL were 1.63 (95% confidence interval (95% CI), 1.01-2.63) for extrahepatic BTC, 2.14 (95% CI, 1.06-4.33) for gallbladder cancer, and 3.46 (95% CI, 1.22-9.84) for intrahepatic BTC. Dietary GI was statistically significantly positively associated with risk of extrahepatic BTC and gallbladder cancer. We observed no statistically significant association between carbohydrate intake and BTC risk, although all associations were positive. Although these data do not prove a causal relationship, they are consistent with the hypothesis that high-GL and high-GI diets are associated with an increased risk of BTC.

Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

PubMed

Rice, Thomas W; Gress, Donna M; Patil, Deepa T; Hofstetter, Wayne L; Kelsen, David P; Blackstone, Eugene H

2017-07-08

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society. © 2017 American Cancer Society.

[Interface bond and compatibility between GI-II glass/alumina composite and Vitadur alpha veneering porcelain].

PubMed

Meng, Yukun; Chao, Yonglie; Liao, Yunmao

2002-01-01

Multiple layer techniques were commonly employed in fabricating all-ceramic restorations. Bond and compatibility between layers were vitally important for the clinical success of the restorations. The purposes of this study were to investigate the bond of the interface between the GI-II glass/alumina composite and Vitadur alpha veneering porcelain, and to study the thermal compatibility between them. Prepared a bar shaped specimen of GI-II glass/alumina composite 25 mm x 5 mm x 1 mm in size, with bottom surface pre-notched. The upper surface was veneered with Vitadur alpha veneering porcelain (0.2 mm opaque dentin and 0.6 mm dentin porcelain), then fractured and the fracture surface were examined under scanning electron microscope (SEM) and electron microprobe analyzer (EMPA) with electron beam of 10 micrometer in diameter; ten all-ceramic single crowns for an upper right central incisor were fabricated and the temperatures of thermal shock resistance were tested. SEM observation showed tight bond between the composite and the porcelain; The results of EMPA showed that penetration of Na, Al elements from glass/alumina into veneering porcelain and Si, K, Ca elements from veneering porcelain into glass/alumina occurred after sintering baking; The temperature of thermal shock resistance for anterior crowns in this study was 158 +/- 10.3 degrees C, cracks were mainly distributed in veneering porcelain with thicker layer. Chemical bond exists between the GI-II glass/alumina composite and Vitadur alpha veneering porcelain, and there is good thermal compatibility between them.

Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ronald C.; Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

2012-07-15

Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associationsmore » between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.« less

Gastroparesis

MedlinePlus

... emptying study (using isotope labeling) Upper GI series Treatment People with diabetes should always control their blood sugar levels. Better ... digestive tract more easily (gastroenterostomy) Outlook (Prognosis) ... imbalances Malnutrition People with diabetes may have serious complications from poor blood sugar ...

Mucoadhesive microspheres for gastroretentive delivery of acyclovir: in vitro and in vivo evaluation.

PubMed

Dhaliwal, Sumeet; Jain, Subheet; Singh, Hardevinder P; Tiwary, A K

2008-06-01

The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as mucoadhesive polymers. Microsphere formulations were prepared using emulsion-chemical crosslinking technique and evaluated in vitro, ex-vivo and in-vivo. Gelatin capsules containing drug powder showed complete dissolution (90.5 +/- 3.6%) in 1 h. The release of drug was prolonged to 12 h (78.8 +/- 3.9) when incorporated into mucoadhesive microspheres. The poor bioavailability of acyclovir is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract to duodenum and jejunum). The results of mucoadhesion study showed better retention of thiolated chitosan microspheres (8.0 +/- 0.8 h) in duodenal and jejunum regions of intestine. The results of qualitative and quantitative GI distribution study also showed significant higher retention of mucoadhesive microspheres in upper GI tract. Pharmacokinetic study revealed that administration of mucoadhesive microspheres could maintain measurable plasma concentration of acyclovir through 24 h, as compared to 5 h after its administration in solution form. Thiolated chitosan microsphere showed superiority over the other formulations as observed with nearly 4.0-fold higher AUC(0-24) value (1,090 +/- 51 ng h/ml) in comparison to drug solution (281 +/- 28 ng h/ml). Overall, the result indicated prolonged delivery with significant improvement in oral bioavailability of acyclovir from mucoadhesive microspheres due to enhanced retention in the upper GI tract.

Upper gastrointestinal bleeding in patients with hepatic cirrhosis: clinical course and mortality prediction.

PubMed

Afessa, B; Kubilis, P S

2000-02-01

We conducted this study to describe the complications and validate the accuracy of previously reported prognostic indices in predicting the mortality of cirrhotic patients hospitalized for upper GI bleeding. This prospective, observational study included 111 consecutive hospitalizations of 85 cirrhotic patients admitted for GI bleeding. Data obtained included intensive care unit (ICU) admission status, Child-Pugh score, the development of systemic inflammatory response syndrome (SIRS), organ failure, and inhospital mortality. The performances of Garden's, Gatta's, and Acute Physiology and Chronic Health Evaluation (APACHE) II prognostic systems in predicting mortality were assessed. Patients' mean age was 48.7 yr, and the median APACHE II and Child-Pugh scores were 17 and 9, respectively. Their ICU admission rate was 71%. Organ failure developed in 57%, and SIRS in 46% of the patients. Nine patients had acute respiratory distress syndrome, and three patients had hepatorenal syndrome. The inhospital mortality was 21%. The APACHE II, Garden's, and Gatta' s predicted mortality rates were 39%, 24%, and 20%, respectively, and their areas under the receiver operating characteristic curve (AUC) were 0.78, 0.70, and 0.71, respectively. The AUC for Child-Pugh score was 0.76. SIRS and organ failure develop in many patients with hepatic cirrhosis hospitalized for upper GI bleeding, and are associated with increased mortality. Although the APACHE II prognostic system overestimated the mortality of these patients, the receiver operating characteristic curves did not show significant differences between the various prognostic systems.

Chronic gastritis in China: a national multi-center survey

PubMed Central

2014-01-01

Background Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. Methods A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Results Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. Conclusions The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy. PMID:24502423

Chronic gastritis in China: a national multi-center survey.

PubMed

Du, Yiqi; Bai, Yu; Xie, Pei; Fang, Jingyuan; Wang, Xiaozhong; Hou, Xiaohua; Tian, Dean; Wang, Chengdang; Liu, Yandi; Sha, Weihong; Wang, Bangmao; Li, Yanqing; Zhang, Guoliang; Li, Yan; Shi, Ruihua; Xu, Jianming; Li, Youming; Huang, Minghe; Han, Shengxi; Liu, Jie; Ren, Xu; Xie, Pengyan; Wang, Zhangliu; Cui, Lihong; Sheng, Jianqiu; Luo, Hesheng; Wang, Zhaohui; Zhao, Xiaoyan; Dai, Ning; Nie, Yuqiang; Zou, Yiyou; Xia, Bing; Fan, Zhining; Chen, Zhitan; Lin, Sanren; Li, Zhao-Shen

2014-02-07

Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

Survivorship after lower gastrointestinal cancer: Patient-reported outcomes and planning for care.

PubMed

Frick, Melissa A; Vachani, Carolyn C; Hampshire, Margaret K; Bach, Christina; Arnold-Korzeniowski, Karen; Metz, James M; Hill-Kayser, Christine E

2017-05-15

There is significant need for quality follow-up care to optimize long-term outcomes for the growing population of lower gastrointestinal (GI) cancer survivors. Patient-reported outcomes (PROs) provide valuable information regarding late and long-term effects (LLTEs). A convenience sample from 1129 colon, rectal, and anal cancer survivors (n = 792; 218, and 119, respectively) who participated in an Internet-based survivorship care plan (SCP) tool between May 2010 and October 2014 was used to examine patient-reported demographics, treatment, and toxicity data. Responses from a follow-up survey were reviewed. The median age of diagnosis was 51 years, and 81% of survivors were Caucasian. The most commonly reported LLTEs for all survivors were neuropathy, fatigue, cognitive changes, changes in GI function, urogenital and sexual dysfunction, and dermatologic effects. The prevalence of these effects varied with time since diagnosis, treatment modality, and treatment center. Individuals who had survived anal cancer reported a high prevalence of sexual dysfunction and radiation-induced dermatologic effects. Over 87% of users reported satisfaction levels of good to excellent using the SCP tool, and 69% reported that they intend to share the SCP with their health care team. For lower GI cancer survivors, it is feasible to obtain PROs from an Internet-based survivorship tool. Survivors report a wide spectrum of LLTEs, and these can be used to inform counseling at the time of diagnosis and to help anticipate and respond to disease-related and treatment-related sequelae during follow-up. The authors are among the first to report on PROs in anal cancer survivors. Further investigation on the impact of SCPs on health care communication and use is needed. Cancer 2017;123:1860-1868. © 2017 American Cancer Society. © 2017 American Cancer Society.

Failure-to-rescue in patients undergoing surgery for esophageal or gastric cancer.

PubMed

Busweiler, L A; Henneman, D; Dikken, J L; Fiocco, M; van Berge Henegouwen, M I; Wijnhoven, B P; van Hillegersberg, R; Rosman, C; Wouters, M W; van Sandick, J W

2017-10-01

Complex surgical procedures such as esophagectomy and gastrectomy for cancer are associated with substantial morbidity and mortality. The purpose of this study was to evaluate trends in postoperative morbidity, mortality, and associated failure-to-rescue (FTR), in patients who underwent a potentially curative resection for esophageal or gastric cancer in the Netherlands, and to investigate differences between the two groups. All patients with esophageal or gastric cancer who underwent a potentially curative resection, registered in the Dutch Upper GI Cancer Audit (DUCA) between 2011 and 2014, were included. Primary outcomes were (major) postoperative complications, postoperative mortality and FTR. To investigate groups' effect on the outcomes of interest a mixed model was used. Overall, 2644 patients with esophageal cancer and 1584 patients with gastric cancer were included in this study. In patients with gastric cancer, postoperative mortality (7.7% in 2011 vs. 3.8% in 2014) and FTR (38% in 2011 and 19% in 2014) decreased significantly over the years. The adjusted risk of developing a major postoperative complication was lower (OR 0.54; 95% CI 0.42-0.70), but the risk of FTR was higher (OR 1.85; 95% CI 1.05-3.27) in patients with gastric cancer compared to patients with esophageal cancer. Once a postoperative complication occurred, patients with gastric cancer were more likely to die compared to patients with esophageal cancer. Underlying mechanisms like patient selection, and differences in structure and organization of care should be investigated. Next to morbidity and mortality, failure-to-rescue should be considered as an important outcome measure after esophagogastric cancer resections. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Cardiac muscle wasting in individuals with cancer cachexia.

PubMed

Barkhudaryan, Anush; Scherbakov, Nadja; Springer, Jochen; Doehner, Wolfram

2017-11-01

Cachexia is a severe complication of cancer that adversely affects the course of the disease and is associated with high rates of mortality. Patients with cancer manifest symptoms, such as fatigue, shortness of breath, and impaired exercise tolerance, which are clinical signs of chronic heart failure. The aim of this study was to evaluate cardiac muscle wasting in cancer individuals. We retrospectively analysed 177 individuals who died of cancer, including 58 lung, 60 pancreatic, and 59 gastrointestinal (GI) cancers, and 42 cancer-free controls who died of other, non-cardiovascular reasons. Cancer cachexia (CC) was defined based on clinical and/or pathological diagnosis, body mass index (BMI) <20.0 kg/m 2 and/or oedema-free body weight loss of 5.0% during the previous year or less. The pathology reports were analysed for BMI, heart weight (HW), and left and right ventricular wall thicknesses (LVWT and RVWT, respectively). The analysis of clinical data included recording of biochemical parameters and medication data of study patients. CC was detected in 54 (30.5%) subjects. Individuals with CC had a significantly lower HW than non-cachectic subjects (363.1 ± 86.2 vs. 447.0 ± 128.9 g, P < 0.001) and control group (412.9 ± 75.8 g, P < 0.05). BMI correlated with HW in cases with GI cancer (r = 0.44, P < 0.001), lung cancer (r = 0.53, P < 0.0001), and pancreatic cancer (r = 0.39, P < 0.01). Body weight loss in individuals with lung, pancreatic, and GI cancers is accompanied by a decrease in HW. In patients with CC who receive cancer treatment, screening for cardiac muscle wasting may have clinical importance. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans.

PubMed

Fedirko, V; Lukanova, A; Bamia, C; Trichopolou, A; Trepo, E; Nöthlings, U; Schlesinger, S; Aleksandrova, K; Boffetta, P; Tjønneland, A; Johnsen, N F; Overvad, K; Fagherazzi, G; Racine, A; Boutron-Ruault, M C; Grote, V; Kaaks, R; Boeing, H; Naska, A; Adarakis, G; Valanou, E; Palli, D; Sieri, S; Tumino, R; Vineis, P; Panico, S; Bueno-de-Mesquita, H B; Siersema, P D; Peeters, P H; Weiderpass, E; Skeie, G; Engeset, D; Quirós, J R; Zamora-Ros, R; Sánchez, M J; Amiano, P; Huerta, J M; Barricarte, A; Johansen, D; Lindkvist, B; Sund, M; Werner, M; Crowe, F; Khaw, K T; Ferrari, P; Romieu, I; Chuang, S C; Riboli, E; Jenab, M

2013-02-01

The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage.

PubMed

Tuskey, Anne; Peura, David

2013-01-01

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage

PubMed Central

2013-01-01

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone. PMID:24267478

High preoperative ratio of blood urea nitrogen to creatinine increased mortality in gastrointestinal cancer patients who developed postoperative enteric fistulas.

PubMed

Lin, Hsing-Lin; Chen, Chao-Wen; Lu, Chien-Yu; Sun, Li-Chu; Shih, Ying-Ling; Chuang, Jui-Fen; Huang, Yu-Ho; Sheen, Maw-Chang; Wang, Jaw-Yuan

2012-08-01

Development of an enteric fistula after surgery is a major therapeutic complication. In this study, we retrospectively examined the potential relationship between preoperative laboratory data and patient mortality by collecting patient data from a tertiary medical center. We included patients who developed enteric fistulas after surgery for gastrointestinal (GI) cancer between January 2005 and December 2010. Patient demographics and data on preoperative and pre-parenteral nutritional statuses were compared between surviving and deceased patients. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to determine the predictors and cut-off values, respectively. Patients with incomplete data and preoperative heart, lung, kidney, and liver diseases were excluded from the study; thus, out of 65 patients, 43 were enrolled. Logistic regression analysis showed that blood urea nitrogen-to-creatinine (BUN/Cr) ratio [p = 0.007; OR = 0.443, 95% confidence interval (CI), 0.245-0.802] was an independent predictor of mortality in patients who developed enteric fistulas after surgery for GI cancer. In conclusion, the results of our study showed that a high preoperative BUN/Cr ratio increases the risk of mortality in patients who develop enteric fistulas after surgery for GI cancer. Copyright © 2012. Published by Elsevier B.V.

The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer.

PubMed

Kaczmarczyk, Melissa M; Miller, Michael J; Freund, Gregory G

2012-08-01

Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes mellitus, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions. Copyright © 2012 Elsevier Inc. All rights reserved.

The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes, cardiovascular disease and colon cancer

PubMed Central

Kaczmarczyk, Melissa M.; Miller, Michael J.; Freund, Gregory G.

2012-01-01

Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions. PMID:22401879

3-(4-chlorophenyl)-[1, 2, 3] oxadiazol-3-ium-5-olate and its 4-formyl analog-Ultrasound assisted synthesis and in-vitro anticancer evaluation against human tumor cell lines.

PubMed

Bhosale, Sachin K; Deshpande, Shreenivas R; Wagh, Rajendra D

2017-03-01

The title compound, 3-(4-chlorophenyl)-4-formyl-[1, 2, 3] oxadiazol-3-ium-5-olate 5 was synthesized under ultrasonication by formylation of 3-(4-chlorophenyl)-[1, 2, 3] oxadiazol-3-ium-5-olate 4 and characterized by spectral studies. The ultrasonic method of synthesis was found to be simple, ecofriendly, economical, reduces reaction time and gave good yield when compared with traditional methods of synthesis. Anticancer activity of the compounds were tested against 60 human tumor cell lines and compared with standard drug vincristine sulphate. Compound 5 was found to be active against CNS (SNB-75, %GI=46.71), renal (UO-31, %GI=31.52), non small cell lung (NCI-H522, %GI=25.65), leukemia (MOLT-4, %GI=23.02) human tumor cell lines whereas, compound 4 against breast (MDA-MB-231/ATCC, %GI=19.90, T-47D %GI=16.50, MCF-7 15.10) and ovarian (IGROV1 %GI=19.30, OVCAR-4 %GI=17.90) human tumor cell lines. Compound 5 showed higher cytotoxicity against NCI-H23 cells (non small lung cancer cell panel) as compared to standard drug vincristine sulphate. Further structural modification of these compounds may lead to potent anticancer activity.

The glycemic index: methodological aspects related to the interpretation of health effects and to regulatory labeling.

PubMed

Aziz, Alfred

2009-01-01

The glycemic index (GI) is an experimental system that classifies carbohydrates (CHO) and CHO-containing foods according to their blood glucose-raising potential. It is based on the glycemic response following the ingestion of a test food containing a defined amount of available CHO relative to that of an equi-carbohydrate portion of either white bread or glucose. The concept has been extended to mixed meals and whole diets where the GI of the meal/diet is expressed as the weighted average of the GI of each food, based on the percentage of the total mealldiet CHO provided by each food. Over the last few decades, a substantial number of epidemiological and interventional studies have reported beneficial associationsleffects of lower GI diets across a wide spectrum of pathophysiological conditions, including diabetes, cardiovascular disease, obesity, and certain forms of cancer. This has prompted proponents of the GI to recommend its use for dietary planning and labeling purposes. However, the currently recommended GI methodology is not well standardized and has several flaws, which brings into question the strength of evidence attributed to the health effects of low-GI diets. This review focuses exclusively on the methodological aspects of the GI, how they might impact the interpretation of data related to the purported health benefits of low GI diets, and the considerations for the use of the GI in food labeling. In addition, alternative systems for classifying the glycemic effects of CHO-containing foods are briefly discussed.

Managing pain and fatigue in people with spinal cord injury: a randomized controlled trial feasibility study examining the efficacy of massage therapy.

PubMed

Lovas, J; Tran, Y; Middleton, J; Bartrop, R; Moore, N; Craig, A

2017-02-01

A randomized controlled trial (RCT). To determine the efficacy of massage therapy (MT) as a treatment that could be implemented to reduce pain and fatigue in people with chronic spinal cord injury (SCI). Laboratory setting in Sydney, Australia. Participants included 40 people with SCI living in the community who were randomly assigned into one of two RCT arms: MT (Swedish massage to upper body) or an active concurrent control (guided imagery (GI) relaxation). All participants received 30 min once a week of either massage or GI over 5 consecutive weeks. In addition to sociodemographic and injury factors, assessments and reliable measures including the short-form McGill Pain Questionnaire and Chalder's Fatigue Scale were validated. Chronic pain and fatigue were significantly reduced in the massage group when assessed at the end of 5 weeks (P<0.05), with large effect sizes. Interestingly, GI was as effective as MT in reducing pain and fatigue. Pain scores were reduced significantly over time in both MT and GI groups (P=0.049 and P=0.032, respectively). Total fatigue scores were also reduced in both MT and GI groups (P=0004 and P=0.037, respectively.)Conclusions:Massage and GI are both active treatments that provide potential clinical benefits for adults with SCI. Future research should clarify the role of massage and GI in managing pain and fatigue in SCI and assess outcomes into the longer-term.

Abdominal rigidity

MedlinePlus

... other symptoms do you have at the same time? For example, do you have abdominal pain ? You may have the following tests: Barium studies of the stomach and intestines (such as an upper GI series ) Blood tests Colonoscopy Gastroscopy Peritoneal lavage Stool studies ...

Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis.

PubMed

Kuan, Renee; Holt, Robert J; Johnson, Kenneth E; Kent, Jeffrey D; Peura, David A; Malone, Dan

2013-03-01

Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID treatment, with a modest financial impact on total health care costs. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Dysregulation of Wnt/β-catenin Signaling in Gastrointestinal Cancers

PubMed Central

White, Bryan D.; Chien, Andy J.; Dawson, David W.

2012-01-01

Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal (GI) tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, APC (adenomatous polyposis coli), and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including crosstalk with other altered signaling pathways. A more complex view of Wnt/β-catenin signaling and its role in GI cancers is now emerging as divergent phenotypic outcomes are found to be dictated by temporospatial context and relative levels of pathway activation. This review summarizes the dysregulation of Wnt/β-catenin signaling in colorectal carcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, with particular emphasis on the latter two. We conclude by addressing some of the major challenges faced in attempting to target the pathway in the clinic. PMID:22155636

PET imaging in adaptive radiotherapy of gastrointestinal tumours.

PubMed

Bulens, Philippe; Thomas, Melissa; Deroose, Christophe M; Haustermans, Karin

2018-06-04

Radiotherapy is the standard of care in the multimodality treatment of a variety of gastrointestinal (GI) tumours, such as oesophageal cancer, gastric cancer, rectal cancer and anal cancer. Additionally, radiotherapy has served as an alternative for surgery in patients with liver cancer, cancer of the biliary tract and pancreatic cancer. Positron-emission tomography (PET), generally in combination with computed tomography (CT), has an established role in the diagnosis, response assessment and (re-)staging of several GI tumours. However, the additional value of PET in adaptive radiotherapy, i.e. during the radiation treatment course and in the delineation process, is still unclear. When performed during radiotherapy, PET aims at assessing treatment-induced variations in functional tumour volumes to reduce the radiation target volume. Moreover, in the radiation treatment planning, tumour delineation could be more accurate by incorporating PET to identify the metabolic tumour volume. This review focuses on the additional value of PET for adaptive radiotherapy protocols as well as for the target volume adaptation for individualised treatment strategies in oesophageal, gastric, pancreatic, liver, biliary tract, rectal and anal neoplasms.

RUNX1T1 Amplification Induces Small Cell Cancer

DTIC Science & Technology

and it is believed that the second, more differentiated component has transformed into a small cell cancer. Similarly, extra-pulmonary small cell...tumors have primary tumors that arise outside the lung, such as in the prostate or GI tract, and transform into a small cell cancer. So in reality the

Proton pump inhibitors alter the composition of the gut microbiota.

PubMed

Jackson, Matthew A; Goodrich, Julia K; Maxan, Maria-Emanuela; Freedberg, Daniel E; Abrams, Julian A; Poole, Angela C; Sutter, Jessica L; Welter, Daphne; Ley, Ruth E; Bell, Jordana T; Spector, Tim D; Steves, Claire J

2016-05-01

Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Validation and characterization of a novel method for selective vagal deafferentation of the gut.

PubMed

Diepenbroek, Charlene; Quinn, Danielle; Stephens, Ricky; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; de Lartigue, Guillaume

2017-10-01

There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate models. This method provides improved tissue specificity and superior separation of afferent and efferent signaling compared with vagotomy, capsaicin, and subdiaphragmatic deafferentation. NEW & NOTEWORTHY We develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons. This reliable approach provides superior tissue specificity and selectivity for vagal afferent over efferent targeting than traditional approaches. It can be used to address questions about the role of gut to brain signaling in physiological and pathophysiological conditions. Copyright © 2017 the American Physiological Society.

Rectal metastasis from breast cancer: an interval of 17 years.

PubMed

Amin, Aliasger A; Reddy, Anil; Jha, Madan; Prasad, Kolanu

2011-05-12

Metastasis to gastrointestinal (GI) tract from breast cancer is rare. Commonly affected organ in GI tract is stomach, followed by colon and then rectum. The authors report a case of a 61-year-old woman who had a mastectomy for lobular carcinoma of the breast 17 years ago and was referred to colorectal clinic with increased frequency of stools. Colonoscopy showed a stricture in the rectum, but biopsy was inconclusive. As she was symptomatic, she had a Hartmann's resection 5 months after she initially presented to the clinic. Histopathology of the resected specimen showed it to be metastasis from lobular carcinoma of the breast. Awareness of potential long delays in the presentation of metastatic breast cancer especially lobular carcinoma helps in the earlier diagnosis and clinical management.

NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu; Moughan, Jennifer; Garofalo, Michael C.

Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint ofmore » the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.« less

Associations of dietary carbohydrates, glycaemic index and glycaemic load with risk of bladder cancer: a case-control study.

PubMed

Augustin, Livia S A; Taborelli, Martina; Montella, Maurizio; Libra, Massimo; La Vecchia, Carlo; Tavani, Alessandra; Crispo, Anna; Grimaldi, Maria; Facchini, Gaetano; Jenkins, David J A; Botti, Gerardo; Serraino, Diego; Polesel, Jerry

2017-11-01

Carbohydrate foods with high glycaemic index (GI) and load (GL) may negatively influence cancer risk. We studied the association of dietary carbohydrates, GI, GL, intake of bread and pasta with risk of bladder cancer using data from an Italian case-control study. The study included 578 men and women with histologically confirmed bladder cancer and 608 controls admitted to the same hospitals as cases for acute, non-neoplastic conditions. OR were estimated by logistic regression models after allowance for relevant confounding factors. OR of bladder cancer for the highest v. the lowest quantile of intake were 1·52 (95 % CI 0·85, 2·69) for available carbohydrates, 1·18 (95 % CI 0·83, 1·67) for GI, 1·96 (95 % CI 1·16, 3·31, P trend<0·01) for GL, 1·58 (95 % CI 1·09, 2·29, P trend=0·03) for pasta and 1·92 (95 % CI 1·28, 2·86, P trend<0·01) for bread. OR for regular consumption of legumes and whole-grain products were 0·78 (95 % CI 0·60, 1·00) and 0·82 (95 % CI 0·63, 1·08), respectively. No heterogeneity in risks emerged across strata of sex. This case-control study showed that bladder cancer risk was directly associated with high dietary GL and with consumption of high quantity of refined carbohydrate foods, particularly bread. These associations were apparently stronger in subjects with low vegetable consumption.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

PubMed Central

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-01

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer.

PubMed

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-26

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

Crohn's Disease

MedlinePlus

... causes, such as infection. You may also undergo flexible sigmoidoscopy, colonoscopy, body CT, body MRI, MR enterography, upper GI, small ... Flexible sigmoidoscopy , performed by inserting a sigmoidoscope (a flexible tube ... can also sometimes be seen. Body CT scan , a special type of x-ray ...

Teaching peroral endoscopic myotomy (POEM) to surgeons in practice: an "into the fire" pre/post-test curriculum.

PubMed

Kishiki, Tomokazu; Lapin, Brittany; Wang, Chi; Jonson, Brandon; Patel, Lava; Zapf, Matthew; Gitelis, Matthew; Cassera, Maria A; Swanström, Lee L; Ujiki, Michael B

2018-03-01

With the increasing adoption of peroral endoscopic myotomy (POEM) as a first-line therapy for achalasia as well as a growing list of other indications, it is apparent that there is a need for effective training methods for both endoscopists in training and those already in practice. We present a hands-on-focused with pre- and post-testing methodology to teach these skills. Six POEM courses were taught by 11 experienced POEM endoscopists at two independent simulation laboratories. The training curriculum included a pre-training test, lectures and discussion, mentored hands-on instruction using live porcine and ex-plant models, and a post-training test. The scoring sheet for the pre- and post-tests assessed the POEM performance with a Likert-like scale measuring equipment setup, mucosotomy creation, endoscope navigation, visualization, myotomy, and closure. Participants were stratified by their experience with upper-GI endoscopy (Novices <100 cases vs. Experts ≥100 cases), and their data were analyzed and compared. Sixty-five participants with varying degrees of experience in upper-GI endoscopy and laparoscopic achalasia cases completed the training curriculum. Participants improved knowledge scores from 69.7 ± 17.1 (pre-test) to 87.7 ± 10.8 (post-test) (p < 0.01). POEM performance increased from 15.1 ± 5.1 to 25.0 ± 5.5 (out of 30) (p < 0.01) with the greatest gains in mucosotomy [1.7-4.4 (out of 5), p < 0.01] and equipment (3.4-4.7, p < 0.01). Novices had significantly lower pre-test scores compared with Experts in upper-GI endoscopy (overall pre-score: 11.9 ± 5.6 vs. 16.3 ± 4.6, p < 0.01). Both groups improved significantly after the course, and there were no differences in post-test scores (overall post-score: 23.9 ± 6.6 vs. 25.4 ± 5.1, p = 0.34) between Novices and Experts. A multimodal curriculum with procedural practice was an effective curricular design for teaching POEM to practitioners. The curriculum was specifically helpful for training surgeons with less upper-GI endoscopy experience.

Protective mechanism against cancer found in progeria patient cells

Cancer.gov

NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

Association Between Circular Stapler Diameter and Stricture Rates Following Gastrointestinal Anastomosis: Systematic Review and Meta-analysis.

PubMed

Allen, W; Wells, C I; Greenslade, M; Bissett, I P; O'Grady, G

2018-04-09

Stricture is a common complication of gastrointestinal (GI) anastomoses, associated with impaired quality of life, risk of malnutrition, and further interventions. This systematic review and meta-analysis aimed to determine the association between circular stapler diameter and anastomotic stricture rates throughout the GI tract. A systematic literature search of EMBASE, MEDLINE and Cochrane Library was performed. The primary outcome was the rate of radiologically or endoscopically confirmed anastomotic stricture. Pooled odds ratios (OR) were calculated using random-effects models to determine the effect of circular stapler diameter on stricture rates in different regions of the GI tract. Twenty-one studies were identified: seven oesophageal, twelve gastric, and three lower GI. Smaller stapler sizes were strongly associated with higher anastomotic stricture rates throughout the GI tract. The oesophageal anastomosis studies showed; 21 versus 25 mm circular stapler: OR 4.39 ([95% CI 2.12, 9.07]; P < 0.0001); 25 versus 28/29 mm circular stapler: OR 1.71 ([95% CI 1.15, 2.53]; P < 0.008). Gastric studies showed; 21 versus 25 mm circular stapler: OR 3.12 ([95% CI 2.23, 4.36]; P < 0.00001); 25 versus 28/29 mm circular stapler: OR 7.67 ([95% CI 1.86, 31.57]; P < 0.005). Few lower GI studies were identified, though a similar trend was found: 25 versus 28/29 mm circular stapler: pooled OR 2.61 ([95% CI 0.82, 8.29]; P = 0.100). The use of larger circular stapler sizes is strongly associated with reduced risk of anastomotic stricture in the upper GI tract, though data from lower GI joins are limited.

Acta Oncologica Lecture. Gastrointestinal consequences of cancer treatment and the wider context: a bad gut feeling.

PubMed

Muls, Ann Cecile

2014-03-01

The percentage of people living with a diagnosis of cancer is rising globally. Between 20% and 25% of people treated for cancer experience a consequence of cancer which has an adverse impact on the quality of their life. Gastrointestinal (GI) symptoms are the most common of all consequences of cancer treatment and have the greatest impact on daily activity. PATHOPHYSIOLOGY OF LONG-TERM BOWEL DAMAGE AFTER PELVIC RADIOTHERAPY: Long-term damage to the bowel after radiotherapy is mediated by ischaemic changes and fibrosis. Each fraction of radiotherapy causes a series of repetitive injuries to the intestinal tissue resulting in an altered healing process, which affects the integrity of the repair and changes the architecture of the bowel wall. THE NATURE OF GI SYMPTOMS THAT DEVELOP: Patient-reported outcome measures show that diarrhoea, urgency, increased bowel frequency, tenesmus and flatulence are the five most prevalent GI symptoms with a moderate or severe impact on patients' daily lives after treatment with pelvic radiotherapy. Many patients also experience fatigue, urinary problems and have sexual concerns. SYSTEMATIC ASSESSMENT AND MANAGEMENT: The complex nature of those symptoms warrants systematic assessment and management. The use of a tested algorithm can assist in achieving this. The most common contributing factors to ongoing bowel problems after pelvic radiotherapy are small intestinal bacterial overgrowth, bile acid malabsorption, pancreatic insufficiency, rectal bleeding and its impact on bone health. Symptom burden, socio-psychosocial impact, memory and cognitive function, fatigue, urinary problems and sexual concerns need to be taken into account when thinking about consequences of cancer treatment. As our understanding of consequences of cancer treatments continues to emerge and encompass a wide variety of specialties, a holistic, multifaceted and multidisciplinary approach is required to manage those consequences long-term.

Methodology for adding glycemic index and glycemic load values to 24-hour dietary recall database.

PubMed

Olendzki, Barbara C; Ma, Yunsheng; Culver, Annie L; Ockene, Ira S; Griffith, Jennifer A; Hafner, Andrea R; Hebert, James R

2006-01-01

We describe a method of adding the glycemic index (GI) and glycemic load (GL) values to the nutrient database of the 24-hour dietary recall interview (24HR), a widely used dietary assessment. We also calculated daily GI and GL values from the 24HR. Subjects were 641 healthy adults from central Massachusetts who completed 9067 24HRs. The 24HR-derived food data were matched to the International Table of Glycemic Index and Glycemic Load Values. The GI values for specific foods not in the table were estimated against similar foods according to physical and chemical factors that determine GI. Mixed foods were disaggregated into individual ingredients. Of 1261 carbohydrate-containing foods in the database, GI values of 602 foods were obtained from a direct match (47.7%), accounting for 22.36% of dietary carbohydrate. GI values from 656 foods (52.1%) were estimated, contributing to 77.64% of dietary carbohydrate. The GI values from three unknown foods (0.2%) could not be assigned. The average daily GI was 84 (SD 5.1, white bread as referent) and the average GL was 196 (SD 63). Using this methodology for adding GI and GL values to nutrient databases, it is possible to assess associations between GI and/or GL and body weight and chronic disease outcomes (diabetes, cancer, heart disease). This method can be used in clinical and survey research settings where 24HRs are a practical means for assessing diet. The implications for using this methodology compel a broader evaluation of diet with disease outcomes.

Can patients determine the level of their dysphagia?

PubMed Central

Ashraf, Hafiz Hamad; Palmer, Joanne; Dalton, Harry Richard; Waters, Carolyn; Luff, Thomas; Strugnell, Madeline; Murray, Iain Alexander

2017-01-01

AIM To determine if patients can localise dysphagia level determined endoscopically or radiologically and association of gender, age, level and pathology. METHODS Retrospective review of consecutive patients presenting to dysphagia hotline between March 2004 and March 2015 was carried out. Demographics, clinical history and investigation findings were recorded including patient perception of obstruction level (pharyngeal, mid sternal or low sternal) was documented and the actual level of obstruction found on endoscopic or radiological examination (if any) was noted. All patients with evidence of obstruction including oesophageal carcinoma, peptic stricture, Schatzki ring, oesophageal pouch and cricopharyngeal hypertrophy were included in the study who had given a perceived level of dysphagia. The upper GI endoscopy reports (barium study where upper GI endoscopy was not performed) were reviewed to confirm the distance of obstructing lesion from central incisors. A previously described anatomical classification of oesophagus was used to define the level of obstruction to be upper, middle or lower oesophagus and this was compared with patient perceived level. RESULTS Three thousand six hundred and sixty-eight patients were included, 42.0% of who were female, mean age 70.7 ± 12.8 years old. Of those with obstructing lesions, 726 gave a perceived level of dysphagia: 37.2% had oesophageal cancer, 36.0% peptic stricture, 13.1% pharyngeal pouches, 10.3% Schatzki rings and 3.3% achalasia. Twenty-seven point five percent of patients reported pharyngeal level (upper) dysphagia, 36.9% mid sternal dysphagia and 25.9% lower sternal dysphagia (9.5% reported multiple levels). The level of obstructing lesion seen on diagnostic testing was upper (17.2%), mid (19.4%) or lower (62.9%) or combined (0.3%). When patients localised their level of dysphagia to a single level, the kappa statistic was 0.245 (P < 0.001), indicating fair agreement. 48% of patients reporting a single level of dysphagia were accurate in localising the obstructing pathology. With respect to pathology, patients with pharyngeal pouches were most accurate localising their level of dysphagia (P < 0.001). With respect to level of dysphagia, those with pharyngeal level lesions were best able to identify the level of dysphagia accurately (P < 0.001). No association (P > 0.05) was found between gender, patient age or clinical symptoms with their ability to detect the level of dysphagia. CONCLUSION Patient perceived level of dysphagia is unreliable in determining actual level of obstructing pathology and should not be used to tailor investigations. PMID:28246477

Can patients determine the level of their dysphagia?

PubMed

Ashraf, Hafiz Hamad; Palmer, Joanne; Dalton, Harry Richard; Waters, Carolyn; Luff, Thomas; Strugnell, Madeline; Murray, Iain Alexander

2017-02-14

To determine if patients can localise dysphagia level determined endoscopically or radiologically and association of gender, age, level and pathology. Retrospective review of consecutive patients presenting to dysphagia hotline between March 2004 and March 2015 was carried out. Demographics, clinical history and investigation findings were recorded including patient perception of obstruction level (pharyngeal, mid sternal or low sternal) was documented and the actual level of obstruction found on endoscopic or radiological examination (if any) was noted. All patients with evidence of obstruction including oesophageal carcinoma, peptic stricture, Schatzki ring, oesophageal pouch and cricopharyngeal hypertrophy were included in the study who had given a perceived level of dysphagia. The upper GI endoscopy reports (barium study where upper GI endoscopy was not performed) were reviewed to confirm the distance of obstructing lesion from central incisors. A previously described anatomical classification of oesophagus was used to define the level of obstruction to be upper, middle or lower oesophagus and this was compared with patient perceived level. Three thousand six hundred and sixty-eight patients were included, 42.0% of who were female, mean age 70.7 ± 12.8 years old. Of those with obstructing lesions, 726 gave a perceived level of dysphagia: 37.2% had oesophageal cancer, 36.0% peptic stricture, 13.1% pharyngeal pouches, 10.3% Schatzki rings and 3.3% achalasia. Twenty-seven point five percent of patients reported pharyngeal level (upper) dysphagia, 36.9% mid sternal dysphagia and 25.9% lower sternal dysphagia (9.5% reported multiple levels). The level of obstructing lesion seen on diagnostic testing was upper (17.2%), mid (19.4%) or lower (62.9%) or combined (0.3%). When patients localised their level of dysphagia to a single level, the kappa statistic was 0.245 ( P < 0.001), indicating fair agreement. 48% of patients reporting a single level of dysphagia were accurate in localising the obstructing pathology. With respect to pathology, patients with pharyngeal pouches were most accurate localising their level of dysphagia ( P < 0.001). With respect to level of dysphagia, those with pharyngeal level lesions were best able to identify the level of dysphagia accurately ( P < 0.001). No association ( P > 0.05) was found between gender, patient age or clinical symptoms with their ability to detect the level of dysphagia. Patient perceived level of dysphagia is unreliable in determining actual level of obstructing pathology and should not be used to tailor investigations.

Redox-responsive microbeads containing thiolated pectin-doxorubicin conjugate inhibit tumor growth and metastasis: An in vitro and in vivo study.

PubMed

Cheewatanakornkool, Kamonrak; Niratisai, Sathit; Dass, Crispin R; Sriamornsak, Pornsak

2018-07-10

The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox-responsive microbeads containing thiolated pectin-doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract and allow redox-triggered drug release in the colon. Morphology, particle size, drug content, and in vitro drug release behavior of the microbeads were characterized; in vitro cytotoxicity was tested on mouse colon carcinoma, human colorectal adenocarcinoma, and human bone osteosarcoma cell lines. In vivo anticancer efficacy of coated microbeads was examined in BALB/c mice with murine colon carcinoma. These coated microbeads significantly inhibited the growth of all cell lines. The in vivo study confirmed delivery of DOX to the colorectal tumor site, redox-responsiveness, and anticancer efficacy of coated microbeads. Coated microbeads also effectively inhibited primary tumor growth and suppressed tumor metastases without gross toxicity to the non-target tissue. No noticeable damage was found in mouse GI tissues, indicating lack of DOX toxicity. These novel coated microbeads containing thiolated pectin-DOX conjugate may be a promising vehicle for targeted clinical delivery of DOX to the colorectal cancer site by oral administration. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

The frequency, risk factors, and complications of gastrointestinal dysfunction during enteral nutrition in critically ill patients.

PubMed

Atasever, Ayse Gulsah; Ozcan, Perihan Ergin; Kasali, Kamber; Abdullah, Taner; Orhun, Gunseli; Senturk, Evren

2018-01-01

Gastrointestinal (GI) motility disorders in intensive care patients remain relatively unexplored. Nowadays, the frequency, risk factors and complications of GI dysfunction during enteral nutrition (EN) become more questionable. To evaluate the frequency, risk factors and complications of GI dysfunction during EN in the first 2 weeks of the intensive care unit (ICU) stay and to identify precautions to prevent the development of GI dysfunction and avoid complications. In this prospective observational study, we deliberately targeted at-risk patients. A total of 137 patients who received nasogastric tube feeding in an ICU of a tertiary hospital were enrolled. The incidence of GI dysfunction that was found to be 63% which was associated mainly between MDR bacteria positivity and negative fluid balance. Diarrhea was observed in 36 patients (26%) and on 147 patient-days (incidence rate, 5.5 per 100 patient-days). The median day of diarrhea onset was 6 days after the initiation of EN. Forty patients (29%) presented with constipation (85% during the first week). Fifty patients (36%) exhibited upper digestive intolerance on 212 patient-days (incidence rate, 7.9 per 100 patient-days), after a median EN duration of 6 days (range, 2-14 days). Logistic regression analysis revealed MDR bacteria growth in the culture (OR, 1.75; 95% CI, 1.15-2.67; P =0.008) and negative fluid balance (OR, 0.57; 95% CI, 0.34-0.94; P =0.03) as the risk factors for GI dysfunction. We also showed that GI dysfunction was associated with high SOFA score, hypoalbuminemia, catecholamine use, and prolonged length of stay (LOS). GI dysfunction, on the other hand, can cause some complications including inadequate nutrition, and newly developed decubitus ulcers. GI dysfunction should be considered a clinical predictor of inadequate nutrition and prolonged LOS. In addition, the most dramatic risk for GI dysfunction was observed in patients with MDR bacteria growth in the culture and patients in negative fluid balance. Intensivists provide appropriate nutrition for patients, as well as prompt intervention and the development of treatment strategies in the event of GI dysfunction.

A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.

PubMed

Jørgensen, Silje F; Reims, Henrik M; Frydenlund, Didrik; Holm, Kristian; Paulsen, Vemund; Michelsen, Annika E; Jørgensen, Kristin K; Osnes, Liv T; Bratlie, Jorunn; Eide, Tor J; Dahl, Christen P; Holter, Ellen; Tronstad, Rune R; Hanevik, Kurt; Brattbakk, Hans-Richard; Kaveh, Fatemeh; Fiskerstrand, Torunn; Kran, Anne-Marte B; Ueland, Thor; Karlsen, Tom H; Aukrust, Pål; Lundin, Knut E A; Fevang, Børre

2016-10-01

The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation. In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed. The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests). In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene expression, and infections (including norovirus) are rarely a cause of the CVID enteropathy.

The effect of novel rhenium compounds on lymphosarcoma, PC-3 prostate and myeloid leukemia cancer cell lines and an investigation on the DNA binding properties of one of these compounds through electronic spectroscopy

PubMed Central

Parson, Carl; Smith, Valerie; Krauss, Christopher; Banerjee, Hirendra N.; Reilly, Christopher; Krause, Jeanette A.; Wachira, James M.; Giri, Dipak; Winstead, Angela; Mandal, Santosh K.

2014-01-01

Despite the tremendous success of cisplatin and other platinum-based anticancer drugs, severe toxicity and resistance to tumors limit their applications. It is believed that the coordination (formation of covalent bond) of the metal (platinum) to the nitrogen bases of DNA cause the ruptures of the cancer as well as normal cells. A search for anticancer drugs with different modes of action resulted in the synthesis of variety of novel compounds. Many of them are in clinical trials now. Recently we synthesized a series of novel rhenium pentylcarbonato compounds (PC1–PC6). The rhenium atom in each compound is coordinated (bonded) to a planar polypyridyl aromatic ligand, thereby forcing each compound to intercalate between the DNA bases. We have investigated the DNA binding properties of one of the PC-series of compounds (PC6) using electronic spectroscopy. The UV absorption titration of PC6 with DNA shows hypochromic effect with concomitant bathochromic shift of the charge transfer band at 290 nm. These results suggest that the compound PC6 binds to DNA through intercalation. It is therefore likely that the other PC-series of compounds will behave in a similar manner. Thus it is expected that these compounds will exhibit negligible or no side effect. We have observed that the PC-series of compounds are strong cytotoxic agents against lymphosarcoma (average GI50 ≈ 2±2.6 µM), PC-3 prostate (average GI50 ≈ 3±2.8 µM) and myeloid leukemia (average GI50 ≈ 3±2.8 µM) cancer cell lines. The average GI50 values of the PC-series of compounds are 2–3 less than the corresponding GI50 values of cisplatin. Also each of the PC-series of compounds exhibits less toxicity than cisplatin in the glomerular mesangial cells. PMID:25221731

Endoscopic stenting for benign upper gastrointestinal strictures and leaks.

PubMed

Sharaiha, Reem Z; Kim, Katherine J; Singh, Vikesh K; Lennon, Anne Marie; Amateau, Stuart K; Shin, Eun Ji; Canto, Marcia Irene; Kalloo, Anthony N; Khashab, Mouen A

2014-01-01

Self-expandable metal stents (SEMS) and self-expandable plastic stents (SEPS) maybe used for the treatment of benign upper gastrointestinal (GI) leaks and strictures. This study reviewed our experience with stent insertions in patients with benign upper GI conditions. Patients who underwent stent placement for benign upper GI strictures and leaks between March 2007 and April 2011 at a tertiary referral academic center were studied using an endoscopic database and electronic patient records. The technical success, complications, and clinical improvement after stent removal were compared according to type of stent. The outcomes measured were clinical response, adverse events, and predictors of stent migration. Thirty-eight patients (50 % male, mean age = 54 years, range = 12-82) underwent 121 endoscopic procedures. Twenty patients had stents placed for strictures, and 18 had stents placed for leaks. Stent placement was technically successful in all patients. The average duration of stent placement was 54 days (range = 18-118). Clinical improvement immediately after stent placement was seen in 29 of the 38 patients (76.3 %). Immediate post-procedure adverse events occurred in 8 patients. Late adverse events were seen in 18 patients. Evidence of stent migration occurred in 16 patients and was seen in 42 of the 118 successfully placed stents (35.5 %). Migration was more frequent with fully covered SEMS (p = 0.002). After stent removal, 27 patients were evaluable for long-term success (median follow-up time of 283 days, IQR 38-762). Resolution of strictures or leaks was seen in 11 patients (40.7 %). Predictors for long-term success included increasing age and if the stent did not cross the GE junction. Placement of SEPS and SEMS for benign refractory strictures and fistulas has modest long-term clinical efficacy and is limited by a significant migration rate. Stent migration is common and frequent with fully covered SEMS compared to other types of stents, regardless of indication or location.

Acute NSAID-related transmural duodenitis and extensive duodenal ulceration.

PubMed

Hashash, Jana G; Atweh, Lamya A; Saliba, Teddy; Chakhachiro, Zaher; Al-Kutoubi, Aghiad; Tawil, Ayman; Barada, Kassem A

2007-11-01

A 40-year-old previously healthy white man presented to the emergency department at American University of Beirut Medical Center, Beirut, Lebanon, with severe upper abdominal pain of 36-hour duration. The pain started a few hours after the intake of a single tablet of tiaprofenic acid and became more intense after the intake of another tablet 24 hours later. He had no other symptoms. He had no prior upper gastrointestinal (GI) symptoms, ulcer disease, steroidal or nonsteroidal anti-inflammatory drug use, or ethanol intake. Physical examination revealed mild upper abdominal tenderness. Complete blood count, amylase, lipase, and liver function tests were unremarkable. Computed tomography of the abdomen showed marked thickening of the duodenal wall with surrounding mesenteric streaking. Upper GI endoscopy revealed extensive ulceration involving the duodenal bulb, apex, and proximal D2, as well as a few gastric erosions. Histopathologic examination of duodenal biopsy samples showed extensive epithelial cell necrosis and infiltration of the lamina propria with neutrophils and eosinophils. The patient responded well to rabeprazole 20 mg BID and remains well 5 months later. We performed a literature search of PubMed for all English-language articles published between January 1970 and present (June 2007) using the key words tiaprofenic acid, nonsteroidal anti-inflammatory drugs, NSAID, duodenitis, duodenal erosion, duodenal ulcer, gastritis, gastric erosion, gastric ulcer, or peptic ulcer. We reviewed all randomized controlled trials involving NSAIDs found using PubMed, with a focus on their GI adverse effects. Based on the PubMed search, there were no published reports of acute transmural duodenitis and complicated duodenal ulcers associated with short-term exposure to tiaprofenic acid or other NSAIDs. The Naranjo adverse drug reaction (ADR) probability scale was used and a score of 6 was obtained, indicating a probable ADR from tiaprofenic acid use. We report a patient who developed symptomatic severe transmural duodenitis and periduodenal mesenteric streaking, consistent with a complicated ulcer, probably associated with very short-term exposure to tiaprofenic acid.

Management of overt upper gastrointestinal bleeding in a low resource setting: a real world report from Nigeria.

PubMed

Alatise, Olusegun I; Aderibigbe, Adeniyi S; Adisa, Adewale O; Adekanle, Olusegun; Agbakwuru, Augustine E; Arigbabu, Anthony O

2014-12-10

Upper gastrointestinal bleeding (UGIB) remains a common medical problem worldwide that has significant associated morbidity, mortality, and health care resource use. This study outlines the aetiology, clinical presentation, and treatment outcomes of patients with UGIB in a Nigerian low resource health facility. This was a descriptive study of consecutive patients who underwent upper gastrointestinal (GI) endoscopy for upper GI bleeding in the endoscopy unit of the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Osun State, Nigeria from January 2007 to December 2013. During the study period, 287 (12.4%) of 2,320 patients who underwent upper GI endoscopies had UGIB. Of these, 206 (72.0%) patients were males and their ages ranged from 3 to 100 years with a median age of 49 years. The main clinical presentation included passage of melaena stool in 268 (93.4%) of individuals, 173 (60.3%) had haematemesis, 110 (38.3%) had haematochezia, and 161 (56.1%) were dizzy at presentation. Observed in 88 (30.6%) of UGIB patients, duodenal ulcer was the most common cause, followed by varices [52 (18.1%)] and gastritis [51 (17.1%)]. For variceal bleeding, 15 (28.8%) and 21 (40.4%) of patients had injection sclerotherapy and variceal band ligation, respectively. The overall rebleeding rate for endoscopic therapy for varices was 16.7%. For patients with ulcers, only 42 of 55 who had Forrest grade Ia to IIb ulcers were offered endoscopic therapy. Endoscopic therapy was áin 90.5% of the cases. No rebleeding followed endoscopic therapy for the ulcers. The obtained Rockall scores ranged from 2 to 10 and the median was 5.0. Of all patients, 92.7% had medium or high risk scores. An increase in Rockall score was significantly associated with length of hospital stay and mortality (p < 0.001). The overall mortality rate was 5.9% (17 patients). Endoscopic therapy for UGIB in a resource-poor setting such as Nigeria is feasible, significantly reduces morbidity and mortality, and is cost effective. Efforts should be made to improve the accessibility of these therapeutic procedure for patients with UGIB in Nigeria.

Risks of Bleeding Recurrence and Cardiovascular Events With Continued Aspirin Use After Lower Gastrointestinal Hemorrhage.

PubMed

Chan, Francis K L; Leung Ki, En-Ling; Wong, Grace L H; Ching, Jessica Y L; Tse, Yee Kit; Au, Kim W L; Wu, Justin C Y; Ng, Siew C

2016-08-01

It is not clear whether use of low-dose aspirin should be resumed after an episode of lower gastrointestinal (GI) bleeding. We assessed the long-term risks of recurrent lower GI bleeding and serious cardiovascular outcomes after aspirin-associated lower GI bleeding. We performed a retrospective study of patients diagnosed with lower GI bleeding (documented melena or hematochezia and absence of upper GI bleeding) from January 1, 2000 through December 31, 2007 at the Prince of Wales Hospital in Hong Kong. Using the hospital registry, we analyzed data from 295 patients on aspirin and determined their outcomes during a 5-year period. Outcomes included recurrent lower GI bleeding, serious cardiovascular events, and death from other causes, as determined by an independent, blinded adjudication committee. Outcomes were compared between patients assigned to the following groups based on cumulative duration of aspirin use: <20% of the follow-up period (121 nonusers) vs ≥50% of the observation period (174 aspirin users). Within 5 years, lower GI bleeding recurred in 18.9% of aspirin users (95% confidence interval [CI], 13.3%-25.3%) vs 6.9% of nonusers (95% CI, 3.2%-12.5%; P = .007). However, serious cardiovascular events occurred in 22.8% of aspirin users (95% CI, 16.6%-29.6%) vs 36.5% of nonusers (95% CI, 27.4%-45.6%; P = .017), and 8.2% of aspirin users died from other causes (95% CI, 4.6%-13.2%) vs 26.7% of nonusers (95% CI, 18.7%-35.4%; P = .001). Multivariable analysis showed that aspirin use was an independent predictor of rebleeding, but protected against cardiovascular events and death. Among aspirin users with a history of lower GI bleeding, continuation of aspirin is associated with an increased risk of recurrent lower GI bleeding, but reduced risk of serious cardiovascular events and death. Copyright © 2016. Published by Elsevier Inc.

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients].

PubMed

Nantes, Óscar; Zozaya, José Manuel; Montes, Ramón; Hermida, José

2014-01-01

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Number and type of guideline implementation tools varies by guideline, clinical condition, country of origin, and type of developer organization: content analysis of guidelines.

PubMed

Liang, Laurel; Abi Safi, Jhoni; Gagliardi, Anna R

2017-11-15

Guideline implementation tools (GI tools) can improve clinician behavior and patient outcomes. Analyses of guidelines published before 2010 found that many did not offer GI tools. Since 2010 standards, frameworks and instructions for GI tools have emerged. This study analyzed the number and types of GI tools offered by guidelines published in 2010 or later. Content analysis and a published GI tool framework were used to categorize GI tools by condition, country, and type of organization. English-language guidelines on arthritis, asthma, colorectal cancer, depression, diabetes, heart failure, and stroke management were identified in the National Guideline Clearinghouse. Screening and data extraction were in triplicate. Findings were reported with summary statistics. Eighty-five (67.5%) of 126 eligible guidelines published between 2010 and 2017 offered one or more of a total of 464 GI tools. The mean number of GI tools per guideline was 5.5 (median 4.0, range 1 to 28) and increased over time. The majority of GI tools were for clinicians (239, 51.5%), few were for patients (113, 24.4%), and fewer still were to support implementation (66, 14.3%) or evaluation (46, 9.9%). Most clinician GI tools were guideline summaries (116, 48.5%), and most patient GI tools were condition-specific information (92, 81.4%). Government agencies (patient 23.5%, clinician 28.9%, implementation 24.1%, evaluation 23.5%) and developers in the UK (patient 18.5%, clinician 25.2%, implementation 27.2%, evaluation 29.1%) were more likely to generate guidelines that offered all four types of GI tools. Professional societies were more likely to generate guidelines that included clinician GI tools. Many guidelines do not include any GI tools, or a variety of GI tools for different stakeholders that may be more likely to prompt guideline uptake (point-of-care forms or checklists for clinicians, decision-making or self-management tools for patients, implementation and evaluation tools for managers and policy-makers). While this may vary by country and type of organization, and suggests that developers could improve the range of GI tools they develop, further research is needed to identify determinants and potential solutions. Research is also needed to examine the cost-effectiveness of various types of GI tools so that developers know where to direct their efforts and scarce resources.

Does emergency presentation of cancer represent poor performance in primary care? Insights from a novel analysis of linked primary and secondary care data.

PubMed

Murchie, Peter; Smith, Sarah M; Yule, Michael S; Adam, Rosalind; Turner, Melanie E; Lee, Amanda J; Fielding, Shona

2017-04-25

People diagnosed with cancer following emergency presentation have poorer short-term survival. To what extent this signifies a missed opportunity for earlier diagnosis in primary care remains unclear as little detailed data exist on the patient/general practitioner interaction beforehand. Analysis of primary care and regional data for 1802 cancer patients from Northeast Scotland. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) for patient and GP practice predictors of emergency presentation. Qualitative context coding of primary care interaction before emergency presentation. Emergency presentations equalled 20% (n=365). Twenty-eight per cent had no relevant prior GP contact. Of those with prior GP contact 30% were admitted while waiting to be seen in secondary care, and 19% were missed opportunities for earlier diagnosis. Associated predictors: no prior GP contact (OR=3.89; CI 95% 2.14-7.09); having lung (OR=23.24; 95% CI 7.92-68.21), colorectal (OR=18.49; CI 95% 6.60-51.82) and upper GI cancer (OR=18.97; CI 95% 6.08-59.23); ethnicity (OR=2.78; CI 95% 1.27-6.06). Our novel approach has revealed that emergency cancer presentation is more complex than previously thought. Patient delay, prolonged referral pathways and missed opportunities by GPs all contribute, but emergency presentation can also represent effective care. Resources should be used proportionately to raise public and GP awareness and improve post-referral pathways.

Electromagnetic-guided placement of nasoduodenal feeding tubes versus endoscopic placement: a randomized, multicenter trial.

PubMed

Kappelle, Wouter F W; Walter, Daisy; Stadhouders, Paul H; Jebbink, Hendrik J A; Vleggaar, Frank P; van der Schaar, Peter J; Kappelle, Jan Willem; van der Tweel, Ingeborg; Van den Broek, Medard F M; Wessels, Frank J; Siersema, Peter D; Monkelbaan, Jan F

2018-01-01

Electromagnetic-guided placement (EMP) of a nasoduodenal feeding tube by trained nurses is an attractive alternative to EGD-guided placement (EGDP). We aimed to compare EMP and EGDP in outpatients, ward patients, and critically ill patients with normal upper GI anatomy. In 3 centers with no prior experience in EMP, patients were randomized to placement of a single-lumen nasoduodenal feeding tube either with EGDP or EMP. The primary endpoint was post-pyloric position of the tube on abdominal radiography. Patients were followed for 10 days to assess patency and adverse events. The analyses were performed according to the intention-to-treat principle. In total, 160 patients were randomized to EGDP (N = 76) or EMP (N = 84). Three patients withdrew informed consent, and no abdominal radiography was performed in 2 patients. Thus, 155 patients (59 intensive care unit, 38%) were included in the analyses. Rates of post-pyloric tube position between EGDP and EMP were comparable (79% vs 82%, odds ratio 1.16; 90% confidence interval, 0.58-2.38; P = .72). Adverse events were observed in 4 patients after EMP (hypoxia, GI blood loss, atrial fibrillation, abdominal pain) and in 4 after EGDP (epistaxis N = 2, GI blood loss, hypoxia). Costs of tube placements were lower for EMP compared with EGDP: $519.09 versus $622.49, respectively (P = .04). Success rates and safety of EMP and EGDP in patients with normal upper GI anatomy were comparable. Lower costs and potential logistic advantages may drive centers to adopt EMP as their new standard of care. (Clinical trial registration number: NTR4286.). Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Brief Report: Risk of Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologic Treatments.

PubMed

Xie, Fenglong; Yun, Huifeng; Bernatsky, Sasha; Curtis, Jeffrey R

2016-11-01

To evaluate gastrointestinal (GI) perforation in rheumatoid arthritis (RA) patients receiving tofacitinib, tocilizumab, or other biologic agents. Using health plan data from 2006 through 2014, RA patients without prior GI perforation were identified. Those in whom treatment with tofacitinib or a biologic agent was being initiated were followed up for incident GI perforation with hospitalization. Crude incidence rates were calculated by exposure. Adjusted Cox proportional hazards models were used to evaluate the association between GI perforation and exposures. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. A cohort of 167,113 RA patients was analyzed. Among them, 4,755 began treatment with tofacitinib, 11,705 with tocilizumab, 115,047 with a tumor necrosis factor inhibitor (TNFi), 31,214 with abatacept, and 4,392 with rituximab. Compared to TNFi recipients, abatacept recipients were older, tofacitinib and rituximab recipients were younger, and tocilizumab recipients were similar in age. Patients beginning treatment with a non-TNFi agent were more likely to have previously received biologic agents than patients beginning treatment with a TNFi. The incidence of GI perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.55 (tocilizumab), 1.07 (abatacept), 0.73 (rituximab), and 0.83 (TNFi). Most perforations occurred in the lower GI tract: the incidence of lower GI tract perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.26 (tocilizumab), 0.76 (abatacept), 0.48 (rituximab), and 0.46 (TNFi). Lower GI tract perforation risk was significantly elevated with tocilizumab treatment, and numerically elevated with tofacitinib treatment, versus treatment with TNFi. Adjusted HRs were 2.51 (95% CI 1.31-4.80) for tocilizumab and 1.94 (95% CI 0.49-7.65) for tofacitinib. Older age (HR 1.16 per 5 years [95% CI 1.10-1.22]), diverticulitis/other GI conditions (HR 3.25 [95% CI 1.62-6.50]), and prednisone use at >7.5 mg/day (HR 2.29 [95% CI 1.39-3.78]) were associated with lower GI tract perforation. The incidence of upper GI tract perforation was similar among all drug exposures. The risk of lower GI tract perforation associated with tocilizumab treatment, and possibly tofacitinib treatment, is elevated compared to that associated with TNF blockade. © 2016, American College of Rheumatology.

[Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications].

PubMed

2017-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are a broad class of non glucocorticoid drugs which are extensively used in anti-inflammatory, analgesic, and antipyretic therapies. However, NSAIDs may cause many side effects, most commonly in gastrointestinal(GI) tract. Cardiovascular system, kidney, liver, central nervous system and hematopoietic system are also involved. NSAID-induced GI side effects not only endanger the patients' health, increase mortality, but also greatly increase the cost of medical care. Therefore, how to reduce GI side effects is of particular concern to clinicians. The Chinese Rheumatism Data Center(CRDC) and Chinese Systemic Lupus Erythematosus Treatment and Research Group(CSTAR) compose a "Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications" , as following: (1) GI lesions are the most common side effects of NSAIDs. (2) NSAID-induced GI side effects include gastritis, esophagitis, gastric and duodenal ulcers, bleeding, perforation and obstruction. (3) With the application of capsule endoscopy and small intestinal endoscopy, growing attention is being paid to the NASID-induced small intestine mucosa damage, which is mainly erosion and ulcer. (4) Risk factors related to NSAID-induced GI ulcers include: Helicobacter pylori (Hp) infection, age> 65 years, past history of GI ulcers, high doses of NSAIDs, multiple-drug combination therapy, and comorbidities, such as cardiovascular disease and nephropathy.(5) GI and cardiovascular function should be evaluated before using NSAIDs and gastric mucosal protective agents. (6) The risk of GI ulcers and complications caused by selective cyclooxygenase-2 (COX-2) inhibitors is less than that of non-selective COX-2 inhibitors. (7)Hp eradication therapy helps to cure GI ulcers and prevent recurrence when Hp infection is positive in NSAID-induced ulcers. (8) Proton pump inhibitor (PPI) is the first choice for the prevention and treatment of NSAID-induced GI injury. Gastric mucosal protective agents also suggested.(9) H 2 receptor antagonist (H 2 RA) can reduce the risk of NSAID-induced duodenal injury, however, the therapeutic effect of NSAID-induced gastric ulcer remains to be further confirmed. (10) Endoscopic treatment is the first recommendation for NSAID-induced peptic ulcers combined with upper GI bleeding, high-dose PPI effectively prevent rebleeding, reduce the possibility of surgery and mortality rate.

Motility of the oesophagus and small bowel in adults treated for Hirschsprung's disease during early childhood.

PubMed

Medhus, A W; Bjørnland, K; Emblem, R; Husebye, E

2010-02-01

Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung's disease (HD). In the present study, motility of the oesophagus and the small bowel was studied in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. [Correction added after online publication 15 Sep: The preceding sentence has been rephrased for better clarity.] Ambulatory small bowel manometry with recording sites in duodenum/jejunum was performed in 16 adult patients with surgically treated HD and 17 healthy controls. In addition, oesophageal manometry was performed with station pull-through technique. The essential patterns of small bowel motility were recognized in all patients and controls. During fasting, phase III of the migrating motor complex (MMC) was more prominent in patients with HD than in controls when accounting for duration and propagation velocity (P = 0.006). Phase I of the MMC was of shorter duration (P = 0.008), and phase II tended to be of longer duration (P = 0.05) in the patients. During daytime fasting, propagated clustered contractions (PCCs) were more frequent in the patients (P = 0.01). Postprandially, the patients demonstrated a higher contractile frequency (P = 0.02), a shorter duration of contractions (P = 0.008) and more frequent PCCs (P < 0.001). The patients had normal oesophageal motility. This study demonstrates that adult patients with HD have preserved essential patterns of oesophageal and small bowel motility. However, abnormalities mainly characterized by increased contractile activity of the small bowel during fasting and postprandially are evident. These findings indicate alterations in neuronal control of motility and persistent involvement of the upper GI tract in this disease.

Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

PubMed

Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

2016-10-15

In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Radiation induced genome instability: multiscale modelling and data analysis

NASA Astrophysics Data System (ADS)

Andreev, Sergey; Eidelman, Yuri

2012-07-01

Genome instability (GI) is thought to be an important step in cancer induction and progression. Radiation induced GI is usually defined as genome alterations in the progeny of irradiated cells. The aim of this report is to demonstrate an opportunity for integrative analysis of radiation induced GI on the basis of multiscale modelling. Integrative, systems level modelling is necessary to assess different pathways resulting in GI in which a variety of genetic and epigenetic processes are involved. The multilevel modelling includes the Monte Carlo based simulation of several key processes involved in GI: DNA double strand breaks (DSBs) generation in cells initially irradiated as well as in descendants of irradiated cells, damage transmission through mitosis. Taking the cell-cycle-dependent generation of DNA/chromosome breakage into account ensures an advantage in estimating the contribution of different DNA damage response pathways to GI, as to nonhomologous vs homologous recombination repair mechanisms, the role of DSBs at telomeres or interstitial chromosomal sites, etc. The preliminary estimates show that both telomeric and non-telomeric DSB interactions are involved in delayed effects of radiation although differentially for different cell types. The computational experiments provide the data on the wide spectrum of GI endpoints (dicentrics, micronuclei, nonclonal translocations, chromatid exchanges, chromosome fragments) similar to those obtained experimentally for various cell lines under various experimental conditions. The modelling based analysis of experimental data demonstrates that radiation induced GI may be viewed as processes of delayed DSB induction/interaction/transmission being a key for quantification of GI. On the other hand, this conclusion is not sufficient to understand GI as a whole because factors of DNA non-damaging origin can also induce GI. Additionally, new data on induced pluripotent stem cells reveal that GI is acquired in normal mature cells during genome reprogramming by the oncogene c-myc and three additional transcription factors. These and other data reveal the need for generalisation of current model of GI. One can expect that different early events of both DNA damaging and non-damaging origins merge in a single late pathway. To search for a deeper view we propose to redefine GI as genome destabilisation manifested in erosion of genome states and altered transitions between states. This changing view on GI may help to integrate the inducing factors of various origins in the single basic model of GI.

Gastrointestinal metastasis from primary lung cancer. Case series and systematic literature review.

PubMed

Balla, Andrea; Subiela, José D; Bollo, Jesús; Martínez, Carmen; Rodriguez Luppi, Carlos; Hernández, Pilar; Pascual-González, Yuliana; Quaresima, Silvia; Targarona, Eduard M

2018-04-01

Aim of the present study is to report clinical characteristics and outcomes of patients treated in authors' hospital for GI metastasis from primary lung cancer, and to report and analyse the same data concerning patients retrieved from a systematic literature review. We performed a retrospective analysis of prospectively collected data, and a systematic review using the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Ninety-one patients were included, 5 patients from the authors' hospital and 86 through PubMed database using the keywords "intestinal metastasis" AND "lung cancer". The median time between primary lung cancer diagnosis and GI metastasis diagnosis was 2 months and the median overall survival was 4 months. This group of patients present a poor prognosis and the gold standard treatment is not defined. None of the reported treatments had a significant impact on survival. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Dietary glycemic index and glycemic load and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Romieu, Isabelle; Ferrari, Pietro; Rinaldi, Sabina; Slimani, Nadia; Jenab, Mazda; Olsen, Anja; Tjonneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Lajous, Martin; Kaaks, Rudolf; Teucher, Birgit; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Vasilopoulo, Effie; Sacerdote, Carlotta; Tumino, Rosario; Masala, Giovanna; Sieri, Sabina; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Van-der-A, Daphne; van Gils, Carla H; Peeters, Petra H M; Lund, Eiliv; Skeie, Guri; Asli, Lene Angell; Rodriguez, Laudina; Navarro, Carmen; Amiano, Pilar; Sanchez, Maria-José; Barricarte, Aurelio; Buckland, Genevieve; Sonestedt, Emily; Wirfält, Elisabet; Hallmans, Göran; Johansson, Ingegerd; Key, Timothy J; Allen, Naomi E; Khaw, Kay-Tee; Wareham, Nicholas J; Norat, Teresa; Riboli, Elio; Clavel-Chapelon, Françoise

2012-08-01

The glycemic potential of a diet is associated with chronically elevated insulin concentrations, which may augment breast cancer (BC) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis. It is unclear whether this effect differs by BC phenotype. The objective was to investigate the relation between glycemic index (GI), glycemic load (GL), and total carbohydrate intake with BC by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34-66 y (5th to 95th percentiles) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary questionnaires. We used multivariable Cox proportional hazards models to quantify the association between GI, GL, and carbohydrate intake and BC risk. BC tumors were classified by receptor status. Overall GI, GL, and carbohydrates were not related to BC. Among postmenopausal women, GL and carbohydate intake were significantly associated with an increased risk of estrogen receptor-negative (ER(-)) BC when extreme quintiles (Q) were compared [multivariable HR(Q5-Q1) (95% CI) = 1.36 (1.02, 1.82; P-trend = 0.010) and HR(Q5-Q1) = 1.41 (1.05, 1.89; P-trend = 0.009), respectively]. Further stratification by progesterone receptor (PR) status showed slightly stronger associations with ER(-)/PR(-) BC [HR(Q5-Q1) (95% CI) = 1.48 (1.07, 2.05; P-trend = 0.010) for GL and HR(Q5-Q1) = 1.62 (1.15, 2.30; P-trend = 0.005) for carbohydrates]. No significant association with ER-positive BC was observed. Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(-) and ER(-)/PR(-) BC among postmenopausal women.

A Phase 1/2 Trial of Brief Androgen Suppression and Stereotactic Radiation Therapy (FASTR) for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauman, Glenn, E-mail: Glenn.bauman@lhsc.on.ca; Ferguson, Michelle; Lock, Michael

2015-07-15

Purpose: To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer. Methods and Materials: Men scoring ≥3 on the Vulnerable Elderly Scale (VES) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate. Androgen suppression was delivered for 12 months, and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks. The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity, with trial suspension specified if there were ≥6 of 15more » patients (40%) or ≥3 of 15 (20%) who experienced grade ≥2 or ≥3 gastrointestinal (GI) or genitourinary (GU) toxicity, respectively. Results: Sixteen men were enrolled, with 7 men meeting the criteria of VES ≥3 and 9 men having a VES <3 but choosing the condensed treatment. One man was not treated owing to discovery of a synchronous primary rectal cancer. Four patients (26%) experienced grade ≥2 toxicity at 6 weeks after treatment. There were 9 of 15 (60%) who experienced grade ≥2 GI or GU toxicity and 4 of 15 (26%) grade ≥3 GI or GU toxicity at 6 months, and 5 of 15 (30%) grade ≥2 GI and GU toxicity at 6 months. A review of the 15 cases did not identify any remedial changes, thus the phase 1 criteria were not met. Conclusion: This novel condensed treatment had higher than anticipated late toxicities and was terminated before phase 2 accrual. Treatment factors, such as inclusion of pelvic lymph node radiation therapy, planning constraints, and treatment margins, or patient factors related to the specific frail elderly population may be contributing.« less

USE OF A PHYSIOLOGICALLY BASED TOXICOKINETIC MODEL TO SIMULATE CHRONIC DIETARY EXPOSURE IN FISH

EPA Science Inventory

A physiologically based toxicokinetic (PBTK) model was developed to describe dietary uptake of hydrophobic organic chemicals by fish. The GI tract was modeled as four compartments corresponding to the stomach, pyloric ceca, upper intestine, and lower intestine. Partitioning coeff...

[Nonsteroidal Anti-inflammatory Drug and Aspirin-induced Peptic Ulcer Disease].

PubMed

Shim, Young Kwang; Kim, Nayoung

2016-06-25

Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.

Pantoprazole for the treatment of peptic ulcer bleeding and prevention of rebleeding.

PubMed

van Rensburg, Christo J; Cheer, Susan

2012-01-01

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.

Pantoprazole for the Treatment of Peptic Ulcer Bleeding and Prevention of Rebleeding

PubMed Central

van Rensburg, Christo J.; Cheer, Susan

2012-01-01

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers. PMID:24833934

Gastrointestinal and non-gastrointestinal presentation in patients with celiac disease.

PubMed

Ehsani-Ardakani, Mohammad Javad; Rostami Nejad, Mohammad; Villanacci, Vincenzo; Volta, Umberto; Manenti, Stefania; Caio, Giacomo; Giovenali, Paolo; Becheanu, Gabriel; Diculescu, Mircea; Pellegrino, Salvatore; Magazzù, Giuseppe; Casella, Giovanni; Di Bella, Camillo; Decarli, Nicola; Biancalani, Mauro; Bassotti, Gabrio; Hogg-Kollars, Sabine; Zali, Mohammad Reza; Rostami, Kamran

2013-02-01

Celiac disease (CD) may have a variety of different presentations. This study has aimed to explore the prevalence of gastrointestinal (GI) and non-GI symptoms in patients with CD according to data collected in Italy and Romania (Europe) and Iran (Middle East). This is a retrospective cross-sectional study conducted in Iran, Romania and Italy with data collection during the period from May 2009 - May 2011. For each center we included only patients with CD that was confirmed by endoscopy, small bowel biopsies and positive serology. GI symptoms such as abdominal pain, diarrhea, constipation, nausea and vomiting, weight loss and flatulence, as well as additional signs and symptoms of iron deficiency anemia (IDA), osteoporosis, hypertransaminasemia, and other related abnormalities were collected. Overall, 323 women and 127 men, whose mean age at diagnosis was 34.2 ± 16.47 years were included in this study. Of these, 157 subjects (34.9%) reported at least one GI symptom. The majority of cases had the following primary presenting GI symptoms: diarrhea (13.6%), dyspepsia and constipation (4.0%). Other disease symptoms were reported by 168 (37.3%) patients. The most presenting non-GI symptoms in the majority of cases were anemia (20.7%) and osteopenia (6%). There were statistically significant differences between the majority of symptoms when we compared the reported clinical symptoms from different countries. This study indicated that upper abdominal disorders such as abdominal pain and dyspepsia were the most common primary complaints among European patients, whereas Iranian patients had complaints of diarrhea and bloating as the classic presentations of CD. For non-GI symptoms, anemia was the most frequent complaint for both Iranian and Italian patients; however it was significantly higher in Iranians.

GUCY2C Signaling Opposes the Acute Radiation-Induced GI Syndrome.

PubMed

Li, Peng; Wuthrick, Evan; Rappaport, Jeff A; Kraft, Crystal; Lin, Jieru E; Marszalowicz, Glen; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Waldman, Scott A

2017-09-15

High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. Eliminating GUCY2C signaling exacerbated RIGS, amplifying radiation-induced mortality, weight loss, mucosal bleeding, debilitation, and intestinal dysfunction. Durable expression of GUCY2C, guanylin, and uroguanylin mRNA and protein by intestinal epithelial cells was preserved following lethal irradiation inducing RIGS. Oral delivery of the heat-stable enterotoxin (ST), an exogenous GUCY2C ligand, opposed RIGS, a process requiring p53 activation mediated by dissociation from MDM2. In turn, p53 activation prevented cell death by selectively limiting mitotic catastrophe, but not apoptosis. These studies reveal a role for the GUCY2C paracrine hormone axis as a novel compensatory mechanism opposing RIGS, and they highlight the potential of oral GUCY2C agonists (Linzess; Trulance) to prevent and treat RIGS in cancer therapy and nuclear disasters. Cancer Res; 77(18); 5095-106. ©2017 AACR . ©2017 American Association for Cancer Research.

Bioactivity-guided isolation of anticancer agents from Bauhinia kockiana Korth.

PubMed

Chew, Yik Ling; Lim, Yau Yan; Stanslas, Johnson; Ee, Gwendoline Cheng Lian; Goh, Joo Kheng

2014-01-01

Flowers of Bauhinia kockiana were investigated for their anticancer properties. Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was examined against the same cancer cell lines to deduce the bioactive functional group of the phenolic compounds. The results showed that the phenolic compounds could exhibit moderate to weak cytotoxicity towards certain cell lines (GI50 30 - 86 µM), but were inactive towards DU145 prostate cancer cell (GI50 > 100 µM). It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence microscopy showed that PC-3 cells were killed by apoptosis.

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

PubMed Central

Dolwani, Sunil; Graziano, J. Michael; Lanas, Angel; Longley, Marcus; Phillips, Ceri J.; Roberts, Stephen E.; Soon, Swee S.; Steward, Will

2016-01-01

Background Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. Methods In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. Results Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of ‘major’ incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). Conclusions The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer. PMID:27846246

Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice.

PubMed

Marczylo, Timothy H; Cooke, Darren; Brown, Karen; Steward, William P; Gescher, Andreas J

2009-11-01

Cyanidin-3-glucoside (C3G), an anthocyanin component of fruits and berries, possesses cancer chemopreventive properties in mouse models of carcinogenesis. Its pharmacokinetics and metabolism in mice have hitherto not been studied. C57BL6J mice received C3G by either gavage at 500 mg/kg or tail vein injection at 1 mg/kg. Blood, urine, bile and heart, lung, kidney, liver, prostate, brain and gastrointestinal (gi) mucosal tissues were obtained up to 2 h after administration. Levels of C3G and its anthocyanin metabolites were determined by HPLC with visible detection. Metabolites were identified by LC/MS/MS. After oral administration peak concentrations of anthocyanins occurred within 30 min after administration. Levels were highest in the urine and gi mucosa. In the gi mucosa and liver the predominant flavonoid species after oral administration was C3G, whilst after iv dosing the majority of anthocyanins was C3G metabolites. After oral or iv administration, C3G half-lives in the different biofluids and tissues ranged from 0.7 to 1.8 h and 0.3 to 0.7 h, respectively. Systemic bioavailabilities for parent C3G and total anthocyanins were 1.7 and 3.3%, respectively. The major metabolites of C3G were products of methylation and glucuronidation. Cyanidin was a minor metabolite in the gut. C3G and its metabolites were recovered from murine tissues which may be targets for cancer chemopreventive intervention. Anthocyanin levels achieved in the gi mucosa, prostate and the kidneys were of an order of magnitude consistent with pharmacological activity.

Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis

PubMed Central

Shohdy, Kyrillus S.; Lasheen, Shaimaa; Kassem, Loay; Abdel-Rahman, Omar

2017-01-01

Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Methods: Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Results: Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12–1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09–2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07–1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19–1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29–4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25–7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87–18.37, p = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44–3.21, p = 0.73). Conclusion: Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy. PMID:29090083

Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis.

PubMed

Shohdy, Kyrillus S; Lasheen, Shaimaa; Kassem, Loay; Abdel-Rahman, Omar

2017-11-01

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12-1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09-2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07-1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19-1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29-4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25-7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87-18.37, p = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44-3.21, p = 0.73). Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

Bi- and bisbibenzyls from the roots of Dichapetalum heudelotii and their antiproliferative activities.

PubMed

Osei-Safo, Dorcas; Dziwornu, Godwin Akpeko; Salgado, Antonio; Sunassee, Suthananda Naidu; Chama, Mary Anti

2017-10-01

Two new bisbibenzyls, heudelotol A (1) and B (2), along with the known bibenzyls, (E)-combretastatin A-1 (3) and combretastatin B-1 (4) have been isolated from the ethyl acetate extract of the roots of Dichapetalum heudelotii. Structure elucidation of all four isolated compounds was achieved using UV, IR, 1D and 2D NMR spectroscopy and HR-Mass Spectrometry. The compounds exhibited varying antiproliferative activity against six cancer cell lines using the CellTiter-Glo® Luminiscent Cell Viability Assay. Compound 3 was found to be the most active with sub-micromolar growth inhibition concentrations against all the cell lines (GI 50 0.03-0.72μM). However, it was about ten-fold less active than the positive control, taxol. The new bisbibenzyls heudelotol A and B exhibited good activity against human pancreatic adenocarcinoma (GI 50 9.04μM) and Burkitt's lymphoma (GI 50 4.67μM) respectively, and average activity against the other cancer cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel clinical staging for patients with end-stage gastrointestinal carcinoma.

PubMed

Yasuda, Naokuni; Nakashima, Osamu; Ohnaka, Toru; Kamisaka, Koji; Tsunoda, Akira; Kusano, Mitsuo

2006-01-01

We created a new clinical staging system for end-stage gastrointestinal (GI) carcinoma to clarify the therapeutic goals for these patients. Data were obtained from a retrospective review of medical charts. Based on daily clinical observation of 144 patients with end-stage GI carcinoma, we classified the terminal stages as A, B, C, and D. The mean durations of terminal stages A, B, C, and D were 19, 16.6, 6.6, and 1.8 days, respectively, in patients with end-stage gastric cancer and 28.5, 9.1, 5.4, and 1.9 days, respectively, in patients with colorectal cancer. Moreover, 88.0% of patients with gastric carcinoma and 82.6% of patients with colorectal carcinoma passed through terminal stages A, B, C, and D sequentially. The patients in terminal stage B experienced temporary relief of symptoms, but those in terminal stage C did not (P < 0.05). These terminal stages can easily be judged by clinical observation and may be an effective new tool with which to manage patients with end-stage GI carcinoma and their families.

Emergency transcatheter arterial embolization for massive gastrointestinal arterial hemorrhage.

PubMed

Shi, Zhong Xing; Yang, Jing; Liang, Hong Wei; Cai, Zhen Hua; Bai, Bin

2017-12-01

To evaluate the different arteriographic manifestations of acute arterial massive hemorrhage of the gastrointestinal (GI) tract and the efficacy of emergency transcatheter arterial embolization (ETAE).A total of 88 patients with acute massive GI bleeding who experienced failure of initial endoscopy and/or conservative treatment were referred to our interventional department for acute GI arteriography from January 2007 to June 2015. After locating the source of bleeding, appropriate embolic agents, such as spring coil, hydroxyl methyl acrylic acid gelatin microspheres, polyvinyl alcohol (PVA) particles, etc., were used to embolize the targeted vessels. The angiographic manifestations and the effects of embolization of acute arterial massive hemorrhage of the GI tract were retrospectively analyzed.Of the 88 patients, 54 were diagnosed with arterial hemorrhage of the upper GI tract and 34 with arterial hemorrhage of the lower GI tract. Eighty cases were associated with positive angiography, which showed the following: contrast extravasation (only); gastroduodenal artery stenosis; pseudoaneurysm (only); pseudoaneurysm rupture with contrast extravasation; pseudoaneurysms merged with intestinal artery stenosis; GI angiodysplasia; and tumor vascular bleeding. Eight cases were diagnosed with negative angiography. Seven-two patients underwent successful hemostasis, and a total of 81 arteries were embolized. The technical and clinical success rates (no rebleeding within 30 days) in performing transcatheter embolization on patients with active bleeding were 100% and 84.71%, respectively (72 of 85). Within 30 days, the postoperative rebleeding rate was 15.29% (13/85). Of these rebleeding cases, 2 patients were formerly treated with "blind embolization," 7 underwent interventional embolic retreatment, and 3 had surgical operations. All cases were followed-up for 1 month, and 3 patients died from multiple organ failure. No serious complications such as bowel ischemia necrosis were observed.ETAE is a safe, effective, and minimally invasive treatment; because of the diversified arteriographic manifestations of acute GI hemorrhage, the proper selection of embolic agents and the choice of reasonable embolization method are essential for successful hemostasis. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Feasibility of confocal endomicroscopy in the diagnosis of pediatric gastrointestinal disorders

PubMed Central

Venkatesh, Krishnappa; Cohen, Marta; Evans, Clair; Delaney, Peter; Thomas, Steven; Taylor, Christopher; Abou-Taleb, Ashraf; Kiesslich, Ralf; Thomson, Mike

2009-01-01

AIM: To evaluate the feasibility and utility of confocal laser endomicroscopy (CLE) in the description of normal gastrointestinal (GI) mucosa and in the diagnosis of GI disorders in children, in comparison to histology. METHODS: Forty-four patients (19 female) median age 10.9 years (range 0.7-16.6 years) with suspected or known GI pathology underwent esophago-gastro-duodenoscopy (OGD) (n = 36) and/or ileocolonoscopy (IC) (n = 31) with CLE using sodium fluorescein and acriflavine as contrast agents. Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists, respectively. RESULTS: Duodenum and ileum were intubated in all but one patient undergoing OGD and IC. The median procedure time was 16.4 min (range 7-25 min) for OGD and 27.9 min (range 15-45 min) for IC. A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures, and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures. Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis, Helicobacter pylori gastritis, celiac disease, inflammatory bowel disease, colonic heterotopia, and graft versus host disease. CONCLUSION: CLE offers the prospect of targeting biopsies to abnormal mucosa, thereby increasing diagnostic yield, reducing the number of biopsies, decreasing the burden on the histopathological services, and reducing costs. PMID:19437560

Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013)

USDA-ARS?s Scientific Manuscript database

High carbohydrate intake, glycemic index (GI), and glycemic load (GL) are hypothesized to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms, but epidemiologic evidence is inconsistent. This prospective cohort study investigates the impa...

Patient-Reported Outcome Results From the Open-Label Phase III AURELIA Trial Evaluating Bevacizumab-Containing Therapy for Platinum-Resistant Ovarian Cancer

PubMed Central

Stockler, Martin R.; Hilpert, Felix; Friedlander, Michael; King, Madeleine T.; Wenzel, Lari; Lee, Chee Khoon; Joly, Florence; de Gregorio, Nikolaus; Arranz, José Angel; Mirza, Mansoor Raza; Sorio, Roberto; Freudensprung, Ulrich; Sneller, Vesna; Hales, Gill; Pujade-Lauraine, Eric

2014-01-01

Purpose To determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial. Patients and Methods Patients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy–Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data. Results Baseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions. Conclusion Bevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer. PMID:24687829

Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer.

PubMed

Stockler, Martin R; Hilpert, Felix; Friedlander, Michael; King, Madeleine T; Wenzel, Lari; Lee, Chee Khoon; Joly, Florence; de Gregorio, Nikolaus; Arranz, José Angel; Mirza, Mansoor Raza; Sorio, Roberto; Freudensprung, Ulrich; Sneller, Vesna; Hales, Gill; Pujade-Lauraine, Eric

2014-05-01

To determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial. Patients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy-Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data. Baseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions. Bevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer.

Upregulation of bacterial-specific Th1 and Th17 responses that are enriched in CXCR5+CD4+ T cells in non-small cell lung cancer.

PubMed

Ma, Qin-Yun; Huang, Da-Yu; Zhang, Hui-Jun; Wang, Shaohua; Chen, Xiao-Feng

2017-11-01

The microbial community in the mucosal surfaces is involved in the development of human cancers, including gastric cancer and colorectal cancer. The respiratory tract in the lung also hosts a distinctive microbial community, but the correlation between this community and lung cancer is largely unknown. Here, we examined the Th1 and Th17 responses toward several bacterial antigens, in CD4 + T cells sourced from the peripheral blood (PB), the lung cancer (LC) tissue, and the gastrointestinal (GI) tract of non-small cell lung cancer (NSCLC) patients. Compared to healthy controls, the NSCLC patients presented significantly higher frequencies of Th1 and Th17 cells reacting to Streptococcus salivarius and S. agalactiae, in the PB, LC, and GI tract. Further investigation showed that the upregulation in anti-bacteria response was likely antigen-specific for two reasons. Firstly, the frequencies of Th1 and Th17 cells reacting to Escherichia coli, a typical GI bacterium, were not upregulated in the PB and the LC of NSCLC patients. Secondly, the S. salivarius and S. agalactiae responses could be partially blocked by Tü39, a MHC class II blocking antibody, suggesting that antigen-specific interaction between CD4 + T cells and antigen-presenting cells was required. We also found that S. salivarius and S. agalactiae could potently activate the monocytes to secrete higher levels of interleukin (IL)-6, IL-12, and tumor necrosis factor, which were Th1- and Th17-skewing cytokines. Interestingly, whereas CXCR5 + CD4 + T cells represented <20% of total CD4 + T cells, they represented 17%-82% of bacteria-specific Th1 or Th17 cells. Together, these data demonstrated that NSCLC patients presented a significant upregulation of bacterial-specific Th1 and Th17 responses that were enriched in CXCR5 + CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Microbial Biogeography and Core Microbiota of the Rat Digestive Tract

NASA Astrophysics Data System (ADS)

Li, Dongyao; Chen, Haiqin; Mao, Bingyong; Yang, Qin; Zhao, Jianxin; Gu, Zhennan; Zhang, Hao; Chen, Yong Q.; Chen, Wei

2017-04-01

As a long-standing biomedical model, rats have been frequently used in studies exploring the correlations between gastrointestinal (GI) bacterial biota and diseases. In the present study, luminal and mucosal samples taken along the longitudinal axis of the rat digestive tract were subjected to 16S rRNA gene sequencing-based analysis to determine the baseline microbial composition. Results showed that the community diversity increased from the upper to lower GI segments and that the stratification of microbial communities as well as shift of microbial metabolites were driven by biogeographic location. A greater proportion of lactate-producing bacteria (such as Lactobacillus, Turicibacter and Streptococcus) were found in the stomach and small intestine, while anaerobic Lachnospiraceae and Ruminococcaceae, fermenting carbohydrates and plant aromatic compounds, constituted the bulk of the large-intestinal core microbiota where topologically distinct co-occurrence networks were constructed for the adjacent luminal and mucosal compartments. When comparing the GI microbiota from different hosts, we found that the rat microbial biogeography might represent a new reference, distinct from other murine animals. Our study provides the first comprehensive characterization of the rat GI microbiota landscape for the research community, laying the foundation for better understanding and predicting the disease-related alterations in microbial communities.

Portal hypertension associated with sickle cell disease.

PubMed

Kumar, Sunil; Joshi, R; Jain, A P

2007-01-01

We report a 12-year-old girl with sickle cell disease who presented with pain in abdomen, fever, joint pain and hematemesis. On examination she had mild jaundice and splenomegaly. Upper GI endoscopy showed esophageal varices. She was treated with variceal band ligation and is well on folic acid supplements and propranolol.

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1

PubMed Central

Won, Sungho; Mattheisen, Manuel; Castaldi, Peter J.; Cho, Michael H.; Rutten, Erica; Hardin, Megan; Yip, Wai‐Ki; Rennard, Stephen I.; Lomas, David A.; Wouters, Emiel F.M.; Agusti, Alvar; Casaburi, Richard; Lange, Christoph P.; O'Connor, George; Hersh, Craig P.; Silverman, Edwin K.

2017-01-01

Abstract Background There have been a number of candidate gene association studies of cancer cachexia‐related traits, but no genome‐wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. Methods A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single‐nucleotide polymorphisms (SNPs). Results Two SNPs reached a level of genome‐wide significance (P < 5 × 10−8) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10−8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10−8). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (β meta‐analyis = 0.10, P meta‐analyis = 9.3 × 10−10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. Conclusions In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases. PMID:28044437

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

PubMed

McDonald, Merry-Lynn Noelle; Won, Sungho; Mattheisen, Manuel; Castaldi, Peter J; Cho, Michael H; Rutten, Erica; Hardin, Megan; Yip, Wai-Ki; Rennard, Stephen I; Lomas, David A; Wouters, Emiel F M; Agusti, Alvar; Casaburi, Richard; Lange, Christoph P; O'Connor, George; Hersh, Craig P; Silverman, Edwin K

2017-06-01

There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Two SNPs reached a level of genome-wide significance (P < 5 × 10 -8 ) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10 -8 ); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10 -8 ). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (β meta-analyis  = 0.10, P meta-analyis  = 9.3 × 10 -10 ). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Does emergency presentation of cancer represent poor performance in primary care? Insights from a novel analysis of linked primary and secondary care data

PubMed Central

Murchie, Peter; Smith, Sarah M; Yule, Michael S; Adam, Rosalind; Turner, Melanie E; Lee, Amanda J; Fielding, Shona

2017-01-01

Background: People diagnosed with cancer following emergency presentation have poorer short-term survival. To what extent this signifies a missed opportunity for earlier diagnosis in primary care remains unclear as little detailed data exist on the patient/general practitioner interaction beforehand. Methods: Analysis of primary care and regional data for 1802 cancer patients from Northeast Scotland. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) for patient and GP practice predictors of emergency presentation. Qualitative context coding of primary care interaction before emergency presentation. Results: Emergency presentations equalled 20% (n=365). Twenty-eight per cent had no relevant prior GP contact. Of those with prior GP contact 30% were admitted while waiting to be seen in secondary care, and 19% were missed opportunities for earlier diagnosis. Associated predictors: no prior GP contact (OR=3.89; CI 95% 2.14–7.09); having lung (OR=23.24; 95% CI 7.92–68.21), colorectal (OR=18.49; CI 95% 6.60–51.82) and upper GI cancer (OR=18.97; CI 95% 6.08–59.23); ethnicity (OR=2.78; CI 95% 1.27–6.06). Conclusions: Our novel approach has revealed that emergency cancer presentation is more complex than previously thought. Patient delay, prolonged referral pathways and missed opportunities by GPs all contribute, but emergency presentation can also represent effective care. Resources should be used proportionately to raise public and GP awareness and improve post-referral pathways. PMID:28334728

Endoscopic management of foreign bodies in the upper gastrointestinal tract: An analysis of 846 cases in China

PubMed Central

Yuan, Fangfang; Tang, Xiaowei; Gong, Wei; Su, Lei; Zhang, Yali

2018-01-01

Foreign body ingestion is a relatively common occurrence, which may lead to morbidity and mortality. The aim of the present study was to report the experience of management of upper gastrointestinal foreign bodies by endoscopy in a large center. All patients who presented at the Department of Gastroenterology at Nanfang Hospital (Guangzhou, China) with complaints regarding upper gastrointestinal (GI) foreign body ingestion from December 1987 to December 2013. Hospital medical charts and endoscopic records were examined to evaluate etiology, treatment, and outcomes for these patients. A total of 846 patients were enrolled in the present study, from which foreign bodies were detected in 737 (87.1%) patients via X-ray or endoscopy. The objects most frequently ingested were bones (n=395, 53.6%). The detected foreign bodies were predominantly located in the cervical esophagus (n=325, 44.1%). Endoscopic foreign body extraction was successful in 92.5% of cases, whereas surgery was required in 6 patients. The most frequently used endoscopic accessory devices were retrieval forceps (n=480, 65.1%). The complication rate was 6.9%, including mucosal laceration (n=10) and others, all of which were managed conservatively. Associated GI diseases were reported in 74 (10.0%) patients, including postesophagectomy (n=34) and others. In conclusion, the endoscopic procedure was safe and effective for the removal of foreign bodies from the upper gastrointestinal tract, with a high success rate and low complication rate. PMID:29434711

Investments in cancer research awarded to UK institutions and the global burden of cancer 2000–2013: a systematic analysis

PubMed Central

Maruthappu, Mahiben; Head, Michael G; Zhou, Charlie D; Gilbert, Barnabas J; El-Harasis, Majd A; Raine, Rosalind; Fitchett, Joseph R; Atun, Rifat

2017-01-01

Objectives To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000–2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). Design Systematic analysis of all open-access data. Setting and participants Public and philanthropic funding to all UK cancer research institutions, 2000–2013. Main outcome measures Number and financial value of cancer research investments reported in 2013 UK pounds (UK£). Mortality, DALYs and YLDs data were acquired from the Global Burden of Disease Study. A compound metric was adapted to estimate research investment relative to disease burden as measured by mortality, DALYs and YLDs. Results We identified 4299 funded studies with a total research investment of £2.4 billion. The highest fundings by anatomical sites were haematological, breast, prostate, colorectal and ovarian cancers. Relative to disease burden as determined by a compound metric combining mortality, DALYs and YLDs, gender-specific cancers were found to be highest funded—the five sites that received the most funding were prostate, ovarian, breast, mesothelioma and testicular cancer; the least well-funded sites were liver, thyroid, lung, upper gastrointestinal (GI) and bladder. Preclinical science accounted for 66.2% of award numbers and 62.2% of all funding. The top five areas of primary research focus by funding were pathogenesis, drug therapy, diagnostic, screening and monitoring, women's health and immunology. The largest individual funder was the Medical Research Council. In combination, the five lowest funded site-specific cancers relative to disease burden account for 47.9%, 44.3% and 20.4% of worldwide cancer mortality, DALYs and YLDs. Conclusions Research funding for cancer is not allocated according to relative disease burden. These findings are in line with earlier published studies. Funding agencies and industry should openly document their research investments to improve better targeting of research investment. PMID:28428185

Epigenetic Effects of Ethanol on the Liver and Gastrointestinal System

PubMed Central

Shukla, Shivendra D.; Lim, Robert W.

2013-01-01

The widening web of epigenetic regulatory mechanisms also encompasses ethanol-induced changes in the gastrointestinal (GI)–hepatic system. In the past few years, increasing evidence has firmly established that alcohol modifies several epigenetic parameters in the GI tract and liver. The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses. Furthermore, ethanol-induced fatty liver (i.e., steatohepatitis) and progression of liver cancer (i.e., hepatic carcinoma) may be consequences of the altered epigenetics. Modification of gene and/or protein expression via epigenetic changes also may contribute to the cross-talk among the GI tract and the liver as well as to systemic changes involving other organs. Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver–GI axis. PMID:24313164

Future Operations of HAARP with the UAF's Geophysical Institute

NASA Astrophysics Data System (ADS)

McCoy, R. P.

2015-12-01

The High frequency Active Aurora Research Program (HAARP) in Gakona Alaska is the world's premier facility for active experimentation in the ionosphere and upper atmosphere. The ionosphere affects communication, navigation, radar and a variety of other systems depending on, or affected by, radio propagation through this region. The primary component of HAARP, the Ionospheric Research Instrument (IRI), is a phased array of 180 HF antennas spread across 33 acres and capable of radiating 3.6 MW into the upper atmosphere and ionosphere. The array is fed by five 2500 kW generators, each driven by a 3600 hp diesel engine (4 + 1 spare). Transmit frequencies are selectable in the range 2.8 to 10 MHz and complex configurations of rapidly slewed single or multiple beams are possible. HAARP was owned by the Air Force Research Laboratory (AFRL/RV) in Albuquerque, NM but recently was transferred to the Geophysical Institute of the University of Alaska Fairbanks (UAF/GI). The transfer of ownership of the facility is being implemented in stages involving a Cooperative Research and Development Agreement (CRADA) and an Educational Partnership Agreement (EPA) which are complete, and future agreements to transfer ownership of the facility land. The UAF/GI plans to operate the facility for continued ionospheric and upper atmospheric experimentation in a pay-per-use model. In their 2013 "Decadal Survey in Solar and Space Physics" the National Research Council (NRC) made the recommendation to "Fully realize the potential of ionospheric modification…" and in their 2013 Workshop Report: "Opportunities for High-Power, High-Frequency Transmitters to Advance Ionospheric/Thermospheric Research" the NRC outlined the broad range of future ionospheric, thermospheric and magnetospheric experiments that could be performed with HAARP. HAARP is contains a variety of RF and optical ionospheric diagnostic instruments to measure the effects of the heater in real time. The UAF/GI encourages the scientific community to plan experiments at HAARP and bring their remote sensing instruments to HAARP for extended or permanent operation. The power and flexibility of HAARP and its unique location in the subarctic will help secure the future of this facility as the foremost laboratory for active experimentation in the ionosphere and upper atmosphere.

Rice Bran Extract Inhibits TMEM16A-Involved Activity in the Neonatal Rat Cochlea.

PubMed

Sharm, Kushal; Sung, Jiwon; Kim, Hyun-Jung; Oak, Min-Ho; Yi, Eunyoung

2017-04-01

TMEM16A is a Ca²⁺-activated Cl⁻ channel found in secretory glands, GI and respiratory tracts, and sensory organs, playing a major physiological role in fluid secretion, autonomous GI motility, and sensory transduction. In addition, overexpression of TMEM16A has been associated with cancer cell proliferation and invasion. Suppression of upregulated TMEM16A has been proposed as an effective anti-cancer strategy. While searching for a potential TMEM16A inhibitor, components of rice bran attracted our attention due to their anti-cancer potential in colon cancer cells, a type of cells known to overexpressing TMEM16A. Here, it was tested whether rice bran extract exhibits anti-TMEM16A activity. Rice bran extract was tested in the neonatal rat cochlear tissues where TMEM16A-involved spontaneous activity is generated as a part of normal development of the auditory pathway. Rice bran extract readily inhibited the TMEM16A-involved activity in the cochlear tissues and the effect was reversible upon washout. Taken together, rice bran extract appears to contain a putative TMEM16A inhibitor and the rice byproduct might serve as a source of a new anti-cancer agent.

The incidence of gastrointestinal pathology and subsequent anemia in young men presenting with iron deficiency without anemia.

PubMed

Carter, Dan; Bardan, Eytan; Derazne, Estela; Tzur, Dorit; Avidan, Benjamin

2016-10-01

The etiology of iron deficiency (ID) without anemia in young men is unclear, and there are no evidence-based recommendations for the required gastrointestinal (GI) evaluation. The aims of this study were to examine the incidence of significant GI pathology and the development of anemia during the follow-up of young men presenting with ID, but without anemia. All young men (18-30 years) who served in the Israel Defense Forces during the years 2005-2013 and had at least a single laboratory test indicative of ID without anemia were followed until the diagnosis of significant GI pathology or discharge from military service. The study population included 2061 young men (mean age 20.7±1.8). During follow-up of 3150 person years, significant GI pathologies were diagnosed in 39 patients: inflammatory bowel disease in 25 (1.2%), celiac disease in 8 (0.4%), and peptic disease in 4 (0.1%). No cases of GI-related cancer were diagnosed. ID anemia developed during follow-up in 203 (9.8%). Lower baseline hemoglobin levels, lower ferritin levels, and younger age at diagnosis were more common among those who developed anemia. The development of anemia was a predisposing factor for the diagnosis of GI pathology (risk ratio=3.60, 95% confidence interval 1.34-8.32, P=0.012). Significant GI pathology is very uncommon in young men presenting with ID. Overt anemia developed in close to 10% of the study cohort. Therefore, we advise simple GI evaluation (celiac serology, C-reactive protein or fecal calprotectin, and urease breath test) as well as follow-up in this population.

Novel Therapeutic Approaches Toward Treating Prostate Cancer

DTIC Science & Technology

2013-05-01

Kinases, Prostate Cancer, AKT inhibition, Mouse, Prostate Stem Cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...Bearss 0, Wierda WG, Gandhi V (2009) Pim kinase inhibitor, 5GI-1776, induces apoptosis in CLL lymphocytes. Blood 114:4150--4157. 27. Grey R, et aL...PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem eel! transplantation and rituximab: a Cancer and Leukemia

A randomized pilot trial of a videoconference couples communication intervention for advanced GI cancer.

PubMed

Porter, Laura S; Keefe, Francis J; Baucom, Donald H; Olsen, Maren; Zafar, S Yousuf; Uronis, Hope

2017-07-01

This study aims to test the feasibility and preliminary efficacy of a couple-based communication intervention for advanced GI cancer delivered via videoconference. Thirty-two couples were randomly assigned to either couples communication skills training (CCST) or an education comparison intervention, both delivered via videoconference. Participation was limited to couples who reported communication difficulties at screening. Patients and partners completed measures of relationship functioning and individual functioning at baseline and post-intervention. Eighty-eight percent of randomized dyads completed all six sessions and reported high levels of satisfaction with the intervention. Between-group effect sizes suggested that the CCST intervention led to improvements in relationship satisfaction for patients and partners and to improvements in intimacy and communication for patients. A couples-based communication intervention delivered via videoconference is feasible and acceptable in the context of advanced cancer. Preliminary findings suggest that the intervention shows promise in contributing to enhanced relationship functioning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A PHYSIOLOGICALLY BASED TOXICOKINETIC MODEL FOR DIETARY UPTAKE OF HYDROPHOBIC ORGANIC COMPOUNDS BY FISH: I. FEEDING STUDIES WITH 2,2',5,5'-TETRACHLOROBIPHENYL

EPA Science Inventory

A physiologically-based toxicokinetic (PBTK) model was developed to describe dietary uptake of hydrophobic organic compounds by fish. The gastrointestinal (GI) tract was modeled using four compartments corresponding to the stomach, pyloric ceca, upper intestine, and lower intesti...

The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

PubMed Central

Rubio, Carlos A.

2014-01-01

The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum) are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014) exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days), by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease), collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention. PMID:25437608

ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding.

PubMed

Gerson, Lauren B; Fidler, Jeff L; Cave, David R; Leighton, Jonathan A

2015-09-01

Bleeding from the small intestine remains a relatively uncommon event, accounting for ~5-10% of all patients presenting with gastrointestinal (GI) bleeding. Given advances in small bowel imaging with video capsule endoscopy (VCE), deep enteroscopy, and radiographic imaging, the cause of bleeding in the small bowel can now be identified in most patients. The term small bowel bleeding is therefore proposed as a replacement for the previous classification of obscure GI bleeding (OGIB). We recommend that the term OGIB should be reserved for patients in whom a source of bleeding cannot be identified anywhere in the GI tract. A source of small bowel bleeding should be considered in patients with GI bleeding after performance of a normal upper and lower endoscopic examination. Second-look examinations using upper endoscopy, push enteroscopy, and/or colonoscopy can be performed if indicated before small bowel evaluation. VCE should be considered a first-line procedure for small bowel investigation. Any method of deep enteroscopy can be used when endoscopic evaluation and therapy are required. VCE should be performed before deep enteroscopy if there is no contraindication. Computed tomographic enterography should be performed in patients with suspected obstruction before VCE or after negative VCE examinations. When there is acute overt hemorrhage in the unstable patient, angiography should be performed emergently. In patients with occult hemorrhage or stable patients with active overt bleeding, multiphasic computed tomography should be performed after VCE or CTE to identify the source of bleeding and to guide further management. If a source of bleeding is identified in the small bowel that is associated with significant ongoing anemia and/or active bleeding, the patient should be managed with endoscopic therapy. Conservative management is recommended for patients without a source found after small bowel investigation, whereas repeat diagnostic investigations are recommended for patients with initial negative small bowel evaluations and ongoing overt or occult bleeding.

Barriers to the implementation of practice guidelines in managing patients with nonvariceal upper gastrointestinal bleeding: A qualitative approach

PubMed Central

Hayes, Sean M; Murray, Suzanne; Dupuis, Martin; Dawes, Martin; Hawes, Ian A; Barkun, Alan N

2010-01-01

BACKGROUND/OBJECTIVE: Guidelines for the management of patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) are inconsistently applied by health care providers, potentially resulting in suboptimal care and patient outcomes. A needs assessment was performed to assess health care providers’ barriers to the implementation of these guidelines in Canada. METHODS: Semistructured telephone interviews were conducted by trained research personnel with 22 selectively sampled health care professionals actively treating and managing NVUGIB patients, including emergency room physicians (ER), intensivists (ICU), gastroenterologists (GI), gastroenterology nurses and hospital administrators. Participants were chosen from a representative sample of six Canadian community- and academic-based hospitals that participated in a national Canadian audit on the management of NVUGIB. RESULTS: Participants reported substantive gaps in the implementation of NVUGIB guidelines that included the following: lack of knowledge of the specifics of the NVUGIB guidelines (ER, ICU, nurses); limited belief in the value of guidelines, especially in areas where evidence is lacking (ER, ICU); limited belief in the value of available tools to support implementation of guidelines (GI); lack of knowledge of the roles and responsibilities of health care professions and disciplines, and lack of effective collaboration skills (ER, ICU and GI); variability of knowledge and skills of health care professionals within professions (eg, variability of nurses’ knowledge and skills in endoscopic procedures); and perceived overuse of intravenous proton pump inhibitor treatment, with limited concern regarding cost or side effect implications (all participants). CONCLUSIONS: In the present study population, ER, ICU and nurses did not adhere to NVUGIB guidelines because they were neither aware of nor familiar with them, whereas the GI lack of adherence to NVUGIB guidelines was influenced more by attitudinal and contextual barriers. These findings can guide the design of multifaceted educational and behavioural interventions when attempting to effectively disseminate existing guidelines, and for guideline implementation into practice. PMID:20485702

In vitro activity of almond skin polyphenols for scavenging free radicals and inducing quinone reductase.

PubMed

Chen, C-Y Oliver; Blumberg, Jeffrey B

2008-06-25

Observational studies and clinical trials suggest nut intake, including almonds, is associated with an enhancement in antioxidant defense and a reduction in the risk of cancer and cardiovascular disease. Almond skins are rich in polyphenols (ASP) that may contribute to these putative benefits. To assess their potential mechanisms of action, we tested the in vitro effect of ASP extracted with methanol (M) or a gastrointestinal juice mimic (GI) alone or in combination with vitamins C (VC) or E (VE) (1-10 micromol/L) on scavenging free radicals and inducing quinone reductase (QR). Flavonoid profiles from ASP-M and -GI extracts were different from one another. ASP-GI was more potent in scavenging HOCl and ONOO (-) radicals than ASP-M. In contrast, ASP-M increased and ASP-GI decreased QR activity in Hepa1c1c7 cells. Adding VC or VE to ASP produced a combination- and dose-dependent action on radical scavenging and QR induction. In comparison to their independent actions, ASP-M plus VC were less potent in scavenging DPPH, HOCl, ONOO (-), and O 2 (-) (*). However, the interaction between ASP-GI plus VC promoted their radical scavenging activity. Combining ASP-M plus VC resulted in a synergistic interaction, inducing QR activity, but ASP-GI plus VC had an antagonistic effect. On the basis of their total phenolic content, the measures of total antioxidant activity of ASP-M and -GI were comparable. Thus, in vitro, ASP act as antioxidants and induce QR activity, but these actions are dependent upon their dose, method of extraction, and interaction with antioxidant vitamins.

Clinical trial tests drug combination in mesothelioma of the lung or abdomen | Center for Cancer Research

Cancer.gov

Mesothelioma is an aggressive form of cancer caused by asbestos with no known cure and a very poor prognosis. Raffit Hassan, M.D., of the Thoracic and GI Malignancies Branch is leading a study to determine a safe dose of a combination drug therapy in patients with advanced mesothelioma. 

Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, T W; Ishwaran, H; Hofstetter, W L; Kelsen, D P; Apperson-Hansen, C; Blackstone, E H

2016-11-01

We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk-adjusted survival for each patient was developed using random survival forest analysis to identify data-driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1-3N0M0 squamous cell carcinoma (SCC) and pT1-2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre-treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer. © 2016 International Society for Diseases of the Esophagus.

A Randomized Controlled Trial for the Effectiveness of Progressive Muscle Relaxation and Guided Imagery as Anxiety Reducing Interventions in Breast and Prostate Cancer Patients Undergoing Chemotherapy

PubMed Central

Charalambous, Andreas; Giannakopoulou, Margarita; Bozas, Evangelos; Paikousis, Lefkios

2015-01-01

Objective. To test the effectiveness of guided imagery (GI) and progressive muscle relaxation (PMR) as stress reducing interventions in patients with prostate and breast cancer who undergo chemotherapy. Methods. Patients were randomly assigned to either the control group or the intervention group (PMR and GI). Patients were observed for a total duration of 3 weeks and assessed with the SAS and BECK-II questionnaires for anxiety and depression, respectively, in addiotion to two biological markers (saliva cortisol and saliva amylase) (trial registration number: NCT01275872). Results. 256 patients were registered and 236 were randomly assigned. In total 104 were randomised to the control group and 104 to the intervention group. Intervention's mean anxiety score and depression score changes were significantly different compared to the control's (b = −29.4, p < 0.001; b = −29.4, p < 0.001, resp.). Intervention group's cortisol levels before the intervention (0.30 ± 0.25) gradually decreased up to week 3 (0.16 ± 0.18), whilst the control group's cortisol levels before the intervention (0.21 ± 0.22) gradually increased up to week 3 (0.44 ± 0.35). The same interaction appears for the Amylase levels (p < 0.001). Conclusions. The findings showed that patients with prostate and breast cancer undergoing chemotherapy treatment can benefit from PMR and GI sessions to reduce their anxiety and depression. PMID:26347018

Reprogramming Intestinal Immunity by Novel L. Acidophilus Strains Results in Protective Immunity against Colon Cancer

DTIC Science & Technology

2015-11-01

particular, gastrointestinal (GI) inflammation and the predisposition to cancer. Probiotic lactobacilli have received much attention as examples of...responses, and would potentially lead to the development of novel probiotic platforms for cancer therapeutic application. We thus believe that such...Antigens Expressed by Probiotic Bacteria to Mucosal Dendritic Cells. Curr HIV Res, doi:ABS-73 [pii] (2010). 20 Tager, A. M. et al. Leukotriene B4

Anal metastasis from breast cancer: a case report and review of the literature.

PubMed

Bochicchio, Annamaria; Tartarone, Alfredo; Ignomirelli, Orazio; Latorre, Giuseppe; Cangiano, Rodolfo; Gallucci, Giuseppina; Coccaro, Mariarosa; Feudale, Elisa; Aieta, Michele

2012-03-01

Breast cancer usually metastasizes towards the lymph nodes, lung, bone, liver or brain; metastatic gastrointestinal involvement is rare and anal metastases are extremely rare. Necroscopic studies report a 6-18% incidence of extra-hepatic gastrointestinal metastases, and the most frequent sites of the GI tract involved are the stomach and the small intestine. We report a case with anal metastasis from breast cancer and a review of the associated literature.

Androgens and esophageal cancer: What do we know?

PubMed

Sukocheva, Olga A; Li, Bin; Due, Steven L; Hussey, Damian J; Watson, David I

2015-05-28

Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.

Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagar, Himanshu; Boothe, Dustin; Parikh, Amar

2013-11-15

Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, andmore » the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.« less

[Gastrointestinal bleeding].

PubMed

Lanas, Ángel

2015-09-01

In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Minimal differences in prevalence and spectrum of organic disease at upper gastrointestinal endoscopy between selected secondary care patients with symptoms of gastro-oesophageal reflux or dyspepsia.

PubMed

Irvine, Andrew J; Pinto-Sanchez, Maria Ines; Bercik, Premysl; Moayyedi, Paul; Ford, Alexander C

2017-04-01

Gastro-oesophageal reflux and dyspepsia are felt to be separate upper gastrointestinal (GI) conditions. We aimed to measure the degree of overlap between them, and assess whether endoscopic findings differed. Demographic, symptom, upper GI endoscopy and histology data were collected from consecutive adults in secondary care. Patients were categorised according to whether they reported gastro-oesophageal reflux alone, dyspepsia alone or both, and patient demographics and endoscopic findings were compared. Of 1167 patients, 97 (8.3%) had gastro-oesophageal reflux alone, 571 (48.9%) dyspepsia alone, and 499 (42.8%) overlap. Patients with overlap symptoms were more likely to smoke, compared with those with gastro-oesophageal reflux alone, or dyspepsia alone (p = .009), but there were no other differences. Patients with gastro-oesophageal reflux alone or overlap had a higher prevalence of erosive oesophagitis (18.6% and 15.4% respectively, p < .001), but this was still the commonest diagnosis among those with dyspepsia alone (7.2%). No significant differences were seen in prevalence of other endoscopic findings. Gastro-oesophageal reflux and dyspepsia symptoms commonly overlap. There were minimal differences in demographics or spectrum of underlying organic disease between various symptom groups, suggesting that restrictive classifications according to predominant symptom may not be clinically useful.

Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

PubMed

Garcia-Perez, Juan Carlos; Rodríguez-Perez, Rosa; Ballestero, Araceli; Zuloaga, Jaime; Fernandez-Puntero, Belen; Arias-Díaz, Javier; Caballero, María Luisa

2015-10-01

Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer.

Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

NASA Technical Reports Server (NTRS)

Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

2011-01-01

Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

Synergy between Prkdc and Trp53 regulates stem cell proliferation and GI-ARS after irradiation.

PubMed

Gurley, Kay E; Ashley, Amanda K; Moser, Russell D; Kemp, Christopher J

2017-11-01

Ionizing radiation (IR) is one of the most widely used treatments for cancer. However, acute damage to the gastrointestinal tract or gastrointestinal acute radiation syndrome (GI-ARS) is a major dose-limiting side effect, and the mechanisms that underlie this remain unclear. Here we use mouse models to explore the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation response. IR induces DNA double strand breaks and DNA-PK mutant Prkdc scid/scid mice are sensitive to GI-ARS due to an inability to repair these breaks. IR also activates the tumor suppressor p53 to trigger apoptotic cell death within intestinal crypt cells and p53 deficient mice are resistant to apoptosis. To determine if DNA-PK and p53 interact to govern radiosensitivity, we compared the response of single and compound mutant mice to 8 Gy IR. Compound mutant Prkdc scid/scid /Trp53 -/- mice died earliest due to severe GI-ARS. While both Prkdc scid/scid and Prkdc scid/scid /Trp53 -/- mutant mice had higher levels of IR-induced DNA damage, particularly within the stem cell compartment of the intestinal crypt, in Prkdc scid/scid /Trp53 -/- mice these damaged cells abnormally progressed through the cell cycle resulting in mitotic cell death. This led to a loss of Paneth cells and a failure to regenerate the differentiated epithelial cells required for intestinal function. IR-induced apoptosis did not correlate with radiosensitivity. Overall, these data reveal that DNA repair, mediated by DNA-PK, and cell cycle arrest, mediated by p53, cooperate to protect the stem cell niche after DNA damage, suggesting combination approaches to modulate both pathways may be beneficial to reduce GI-ARS. As many cancers harbor p53 mutations, this also suggests targeting DNA-PK may be effective to enhance sensitivity of p53 mutant tumors to radiation.

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deville, Curtiland, E-mail: deville@uphs.upenn.ed; Both, Stefan; Hwang, Wei-Ting

2010-11-01

Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinalmore » (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.« less

An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast.

PubMed

Balakrishnan, Bathmapriya; Shaik, Sufiya; Burman-Solovyeva, Irina

2016-01-01

Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT) of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis.

NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

PubMed Central

Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

2013-01-01

Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

Targeting Taxanes to Castration-Resistant Prostate Cancer Cells by Nanobubbles and Extracorporeal Shock Waves.

PubMed

Marano, Francesca; Rinella, Letizia; Argenziano, Monica; Cavalli, Roberta; Sassi, Francesca; D'Amelio, Patrizia; Battaglia, Antonino; Gontero, Paolo; Bosco, Ornella; Peluso, Rossella; Fortunati, Nicoletta; Frairia, Roberto; Catalano, Maria Graziella

2016-01-01

To target taxanes to castration-resistant prostate cancer cells, glycol-chitosan nanobubbles loaded with paclitaxel and docetaxel were constructed. The loaded nanobubbles were then combined with Extracorporeal Shock Waves, acoustic waves widely used in urology and orthopedics, with no side effects. Nanobubbles, with an average diameter of 353.3 ± 15.5 nm, entered two different castration-resistant prostate cancer cells (PC3 and DU145) as demonstrated by flow cytometry and immunofluorescence. The shock waves applied increased the amount of intracellular nanobubbles. Loading nanobubbles with paclitaxel and docetaxel and combining them with shock waves generated the highest cytotoxic effects, resulting in a paclitaxel GI50 reduction of about 55% and in a docetaxel GI50 reduction of about 45% respectively. Combined treatment also affected cell migration. Paclitaxel-loaded nanobubbles and shock waves reduced cell migration by more than 85% with respect to paclitaxel alone; whereas docetaxel-loaded nanobubbles and shock waves reduced cell migration by more than 82% with respect to docetaxel alone. The present data suggest that nanobubbles can act as a stable taxane reservoir in castration-resistant prostate cancer cells and shock waves can further increase drug release from nanobubbles leading to higher cytotoxic and anti-migration effect.

Invasive micropapillary carcinoma: a distinct type of adenocarcinomas in the gastrointestinal tract.

PubMed

Guzińska-Ustymowicz, Katarzyna; Niewiarowska, Katarzyna; Pryczynicz, Anna

2014-04-28

Invasive micropapillary carcinoma (IMPC) is a rare histological type of tumor, first described in invasive ductal breast cancer, than in malignancies in other organs such as lungs, urinary bladder, ovaries or salivary glands. Recent literature data shows that this histological lesion has also been found in cancers of the gastrointestinal system. The micropapillary components are clusters of neoplastic cells that closely adhere to each other and are located in distinct empty spaces. Moreover, clusters of neoplastic cells do not have a fibrous-vascular core. The IMPC cells show reverse polarity resulting in typical ''inside-out'' structures that determines secretary properties, disturbs adhesion and conditions grade of malignancy in gastrointestinal (GI) tract. Invasive micropapillary carcinoma in this location is associated with metastases to local lymph nodes and lymphovascular invasion. IMPC can be a prognostic factor for patients with cancers of the stomach, pancreas and with colorectal cancer since it is related with disease-free and overall survival. The purpose of this review is to present the characterization of invasive micropapillary carcinoma in colon, rectum, stomach and others site of GI tract, and to determine the immunohistological indentification of IMPC in those localization.

Remote clinical assessment of gastrointestinal endoscopy (tele-endoscopy): an initial experience.

PubMed Central

Kim, C. Y.; Etemad, B.; Glenn, T. F.; Mackey, H. A.; Viator, G. E.; Wallace, M. B.; Mokhashi, M. S.; Cotton, P. B.; Hawes, R. H.

2000-01-01

BACKGROUND: Gastrointestinal (GI) endoscopy is an effective tool to screen for cancers of the digestive tract. However, access to endoscopy is limited in many parts of South Carolina. This trial is a part of a prospective multi-part study for remote cancer screening in coastal South Carolina. This pilot study was to evaluate the quality of tele-endoscopy for cancer screening. METHODS: 10 patients scheduled for endoscopic procedures were observed simultaneously by the endoscopist and a remote observer connected over a 512 kbps ISDN line. Findings by both were compared for concordance on malignant or premalignant lesions. RESULTS: The image quality was adequate to support remote diagnosis of GI cancer and abnormal lesions by an experienced observer. However, assessment of the esophagogastric junction for Barrett's esophagus was equivocal. CONCLUSIONS: Overall, our tele-endoscopy setup shows great promise for remote supervision or observation of endoscopic procedures done by nurse endoscopists. Tele-endoscopy is both adequate and feasible for diagnosis of most gastrointestinal lesions. Subtle lesions still may be missed in our current setup. However, improvements are being made in our setup to address the problem with resolution prior to further evaluation. PMID:11079918

Genomic Instability and Radiation Risk in Molecular Pathways to Colon Cancer

PubMed Central

Kaiser, Jan Christian; Meckbach, Reinhard; Jacob, Peter

2014-01-01

Colon cancer is caused by multiple genomic alterations which lead to genomic instability (GI). GI appears in molecular pathways of microsatellite instability (MSI) and chromosomal instability (CIN) with clinically observed case shares of about 15–20% and 80–85%. Radiation enhances the colon cancer risk by inducing GI, but little is known about different outcomes for MSI and CIN. Computer-based modelling can facilitate the understanding of the phenomena named above. Comprehensive biological models, which combine the two main molecular pathways to colon cancer, are fitted to incidence data of Japanese a-bomb survivors. The preferred model is selected according to statistical criteria and biological plausibility. Imprints of cell-based processes in the succession from adenoma to carcinoma are identified by the model from age dependences and secular trends of the incidence data. Model parameters show remarkable compliance with mutation rates and growth rates for adenoma, which has been reported over the last fifteen years. Model results suggest that CIN begins during fission of intestinal crypts. Chromosomal aberrations are generated at a markedly elevated rate which favors the accelerated growth of premalignant adenoma. Possibly driven by a trend of Westernization in the Japanese diet, incidence rates for the CIN pathway increased notably in subsequent birth cohorts, whereas rates pertaining to MSI remained constant. An imbalance between number of CIN and MSI cases began to emerge in the 1980s, whereas in previous decades the number of cases was almost equal. The CIN pathway exhibits a strong radio-sensitivity, probably more intensive in men. Among young birth cohorts of both sexes the excess absolute radiation risk related to CIN is larger by an order of magnitude compared to the MSI-related risk. Observance of pathway-specific risks improves the determination of the probability of causation for radiation-induced colon cancer in individual patients, if their exposure histories are known. PMID:25356998

Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial.

PubMed

von Au, Alexandra; Milloth, Eva; Diel, Ingo; Stefanovic, Stefan; Hennigs, Andre; Wallwiener, Markus; Heil, Joerg; Golatta, Michael; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Schuetz, Florian; Domschke, Christoph

2016-01-01

Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness. In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter. Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts. We conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.

Hypofractionated Radiation Therapy (66 Gy in 22 Fractions at 3 Gy per Fraction) for Favorable-Risk Prostate Cancer: Long-term Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Nita; Faria, Sergio, E-mail: sergio.faria@muhc.mcgill.ca; Cury, Fabio

2013-07-01

Purpose: To report long-term outcomes of low- and intermediate-risk prostate cancer patients treated with high-dose hypofractionated radiation therapy (HypoRT). Methods and Materials: Patients with low- and intermediate-risk prostate cancer were treated using 3-dimensional conformal radiation therapy to a dose of 66 Gy in 22 daily fractions of 3 Gy without hormonal therapy. A uniform 7-mm margin was created around the prostate for the planning target volume, and treatment was prescribed to the isocenter. Treatment was delivered using daily ultrasound image-guided radiation therapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was definedmore » as the nadir prostate-specific antigen level plus 2 ng/mL. Results: A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rates were 97% and 92%, respectively. The 5- and 8-year actuarial overall survival rates were 92% and 88%, respectively. Only 1 patient died from prostate cancer at 92 months after treatment, giving an 8-year actuarial cancer-specific survival of 98%. Radiation therapy was well tolerated, with 57% of patients not experiencing any acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33%, respectively. There was no grade >3 toxicity. At last follow-up, the rate of grade ≥2 for both GI and GU toxicity was only 1.5%. Conclusions: Hypofractionation with 66 Gy in 22 fractions prescribed to the isocenter using 3-dimensional conformal radiation therapy produces excellent biochemical control rates, with moderate toxicity. However, this regimen cannot be extrapolated to the intensity modulated radiation therapy technique.« less

Prevalence of patient-reported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

PubMed

Tom, Ashlyn; Bennett, Antonia V; Rothenstein, Diana; Law, Ethel; Goodman, Karyn A

2018-01-01

Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45-56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS ≥ 3 and CTCAE ≥ 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen's kappa coefficient. Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of ≥3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score ≥3) improved during treatment (13.4% at week 5). "Poor" agreement was observed between patient- and clinician-reported proctitis (Cohen's k = 0.11; n = 58); however, there was "good" agreement for diarrhea (Cohen's k = 0.68; n = 58). Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4-5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments.

Abundance and phylogenetic identity of archaeoplankton in the permanent oxygen minimum zone of the eastern tropical South Pacific.

PubMed

Belmar, Lucy; Molina, Verónica; Ulloa, Osvaldo

2011-11-01

We assessed the abundance and molecular phylogeny of archaeoplankton in the oxygen minimum zone (OMZ) of the eastern tropical South Pacific, using specific-probe hybridization and phylogenetic analysis of the SSU-rRNA gene. Euryarchaea from Marine Group-II (MG-II) were most abundant in the surface oxic layer, representing 4.0±2.0% of the total picoplankton, while crenarchaea from Group I.1a (G-I.1a) peaked at the oxyclines, with a relative abundance of 8.1±4.3% (upper oxycline). In most of the stations, the abundance of both the groups decreased at the core of the OMZ, where a secondary maximum in cell density is commonly observed. The majority of the phylotypes affiliated with one of three groups: MG-II, euryarchaeal Marine Group-III (MG-III) and G-I.1a (75.9%, 12.8% and 10.3%, respectively). While MG-II phylotypes were found throughout the water column and G-I.1a ones were predominantly found within the oxyclines, MG-III phylotypes came almost exclusively from the OMZ core. Higher archaeal richness was found within the OMZ, with some of the exclusive lineages grouping with sequences from the deep ocean and hydrothermal vents. Moreover, G-I.1a sequences from the OMZ grouped into a different subcluster from the aerobic ammonium-oxidizer Nitrosopumilus maritimus. Thus, the community structure of archaeoplankton in OMZs is rich and distinct, with G-I.1a members particularly prominent at the oxyclines. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling

PubMed Central

Attar-Schneider, Oshrat; Pasmanik-Chor, Metsada; Tartakover-Matalon, Shelly

2015-01-01

Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis-multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex. PMID:25717031

International Digestive Endoscopy Network 2014: Turnpike to the Future

PubMed Central

Kim, Eun Young; Kwon, Kwang An; Choi, Il Ju; Ryu, Ji Kon

2014-01-01

Social networks are useful in the study of relationships between individuals or entire populations, and the ties through which any given social unit connects. Those represent the convergence of the various social contacts of that unit. Consequently, the term "social networking service" (SNS) became extremely familiar. Similar to familiar SNSs, International Digestive Endoscopy Network (IDEN) 2014 was based on an international network composed of an impressive 2-day scientific program dealing with a variety of topics for gastrointestinal (GI) diseases, which connects physicians and researchers from all over the world. The scientific programs included live endoscopic demonstrations and provided cutting-edge information and practice tips as well as the latest advances concerning upper GI, lower GI, and pancreatobiliary endoscopy. IDEN 2014 featured American Society for Gastrointestinal Endoscopy-Korean Society of Gastrointestinal Endoscopy (ASGE-KSGE)-joint sessions prepared through cooperation between ASGE and KSGE. Furthermore, IDEN 2014 provided a special program for young scientists called the 'Asian Young Endoscopist Award Forum' to foster networks, with many young endoscopists from Asian countries taking an active interest and participation. PMID:25324994

International digestive endoscopy network 2014: turnpike to the future.

PubMed

Kim, Eun Young; Kwon, Kwang An; Choi, Il Ju; Ryu, Ji Kon; Hahm, Ki Baik

2014-09-01

Social networks are useful in the study of relationships between individuals or entire populations, and the ties through which any given social unit connects. Those represent the convergence of the various social contacts of that unit. Consequently, the term "social networking service" (SNS) became extremely familiar. Similar to familiar SNSs, International Digestive Endoscopy Network (IDEN) 2014 was based on an international network composed of an impressive 2-day scientific program dealing with a variety of topics for gastrointestinal (GI) diseases, which connects physicians and researchers from all over the world. The scientific programs included live endoscopic demonstrations and provided cutting-edge information and practice tips as well as the latest advances concerning upper GI, lower GI, and pancreatobiliary endoscopy. IDEN 2014 featured American Society for Gastrointestinal Endoscopy-Korean Society of Gastrointestinal Endoscopy (ASGE-KSGE)-joint sessions prepared through cooperation between ASGE and KSGE. Furthermore, IDEN 2014 provided a special program for young scientists called the 'Asian Young Endoscopist Award Forum' to foster networks, with many young endoscopists from Asian countries taking an active interest and participation.

Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

NASA Technical Reports Server (NTRS)

Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

2016-01-01

An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

BROMODICHLOROMETHANE TOXICOKINETICS: LINKING METABOLISM TO EFFECT

EPA Science Inventory

Bromodichloromethane (BDCM), a trihalomethane (THM), is among the most prevalent disinfection byproducts found in chlorinated drinking water. Weak associations between THM exposure and cancers of the bladder and lower GI tract have been suggested by positive epidemiological s...

Criteria for Referring Patients With Outpatient Gastroenterological Disease for Specialist Consultation: A Review of the Literature

PubMed Central

De Coster, Carolyn; Cepoiu-Martin, Monica; Nash, Carla; Noseworthy, Tom W

2011-01-01

Background Demands on gastroenterology are growing, as a result of the high prevalence of digestive diseases, the impact of colon cancer screening programs and an aging population. Prioritizing referrals to gastroenterology would assist in managing wait times. Our objectives were (1) to assess whether there were consistent criteria to guide referrals from family physicians for gastroenterological outpatient consultation and (2) to determine if there were different levels of urgency or priority in referral criteria. Methods We conducted a scoping review, searching Medline, Embase and Cochrane databases from 1997 to 2009, using the terms referral, triage, consultation and at least one from a list of gastroenterology-specific search terms. Of 2978 initial results, 51 papers were retrieved, and 20 were retained after review by two reviewers. Additional publications were identified through hand searches of retained papers, website searches and nomination by a panel of specialists. Results Thirty-four papers, reports or websites were retained. No referral criteria covered the spectrum of disorders that might be referred by family physicians to gastroenterologists. Criteria for referral were most commonly listed for suspected colorectal cancer, followed by suspected upper GI cancer, hepatitis, and functional disorders. Conclusions A clinical panel comprised of gastroenterologists and primary care providers, informed by this literature review, are completing the work of formulating a Gastroenterology Priority Referral Score, and plan to test the reliability and validity of the tool for determining the relative urgency for referral from primary care to gastroenterology. PMID:27957014

Criteria for Referring Patients With Outpatient Gastroenterological Disease for Specialist Consultation: A Review of the Literature.

PubMed

De Coster, Carolyn; Cepoiu-Martin, Monica; Nash, Carla; Noseworthy, Tom W

2011-10-01

Demands on gastroenterology are growing, as a result of the high prevalence of digestive diseases, the impact of colon cancer screening programs and an aging population. Prioritizing referrals to gastroenterology would assist in managing wait times. Our objectives were (1) to assess whether there were consistent criteria to guide referrals from family physicians for gastroenterological outpatient consultation and (2) to determine if there were different levels of urgency or priority in referral criteria. We conducted a scoping review, searching Medline, Embase and Cochrane databases from 1997 to 2009, using the terms referral, triage, consultation and at least one from a list of gastroenterology-specific search terms. Of 2978 initial results, 51 papers were retrieved, and 20 were retained after review by two reviewers. Additional publications were identified through hand searches of retained papers, website searches and nomination by a panel of specialists. Thirty-four papers, reports or websites were retained. No referral criteria covered the spectrum of disorders that might be referred by family physicians to gastroenterologists. Criteria for referral were most commonly listed for suspected colorectal cancer, followed by suspected upper GI cancer, hepatitis, and functional disorders. A clinical panel comprised of gastroenterologists and primary care providers, informed by this literature review, are completing the work of formulating a Gastroenterology Priority Referral Score, and plan to test the reliability and validity of the tool for determining the relative urgency for referral from primary care to gastroenterology.

Rectal metastasis from lobular breast carcinoma 15 years after primary diagnosis.

PubMed

López Deogracias, Maite; Flores Jaime, Laura; Arias-Camisón, Iñaki; Zamacola, Ilde; Murillo Guibert, Jesús; Suescun García, Rosa; Querejeta Usabiaga, Juan; Martínez García, Francisco

2010-02-01

Lobular breast carcinoma represents 2-20% of infiltrative carcinomas of the breast. The incidence of extrahepatic gastrointestinal (GI) tract metastases observed in necropsy studies varies from 6% to 18% and the most commonly affected organ is the stomach, followed by colon and rectum [1-4]. Reported herein is the case of a 67-year-old woman who was primarily diagnosed and surgically treated for a lobular carcinoma of the breast 15 years ago and is now referred with back pain and right hydronephrosis caused by a metastasis in rectum. Frequently, the absence of specific symptoms of digestive metastases of breast cancer leads to a misdiagnosis of this pathology [5-7]. The treatment will be based on a detailed clinical history and histopathological findings. Metastases from breast cancer in GI tract tumours must be excluded in a patient with previous history of breast carcinoma, as in the case reported herein.

Effective Endovascular Stenting of Malignant Portal Vein Obstruction in Pancreatic Cancer

PubMed Central

Ellis, Christian M.; Shenoy, Sadashiv; Litwin, Alan; Soehnlein, Stephanie; Gibbs, John F.

2009-01-01

We report herein the case of a patient successfully treated by transhepatic portal venous stent placement for malignant portal vein obstruction with associated gastric and small bowel varices and repeated gastrointestinal bleeding. CT angiography and portography showed severe portal vein obstruction from recurrent pancreatic cancer 15 months following pancreaticoduodenectomy with tumor encasement and dilated collateral veins throughout the gastric and proximal small bowel wall as the suspected cause of the GI bleeding. Successful transhepatic endovascular stent placement of the splenic vein at the portal vein confluence followed by balloon dilation was performed with immediate decompression of the gastric and small bowel varices and relief of GI hemorrhage in this patient until his death four months later. The treatment for patients with this dilemma can prove to be difficult, but as we have shown endovascular stenting of the portal system is an effective treatment option. PMID:19826629

Effective endovascular stenting of malignant portal vein obstruction in pancreatic cancer.

PubMed

Ellis, Christian M; Shenoy, Sadashiv; Litwin, Alan; Soehnlein, Stephanie; Gibbs, John F

2009-01-01

We report herein the case of a patient successfully treated by transhepatic portal venous stent placement for malignant portal vein obstruction with associated gastric and small bowel varices and repeated gastrointestinal bleeding. CT angiography and portography showed severe portal vein obstruction from recurrent pancreatic cancer 15 months following pancreaticoduodenectomy with tumor encasement and dilated collateral veins throughout the gastric and proximal small bowel wall as the suspected cause of the GI bleeding. Successful transhepatic endovascular stent placement of the splenic vein at the portal vein confluence followed by balloon dilation was performed with immediate decompression of the gastric and small bowel varices and relief of GI hemorrhage in this patient until his death four months later. The treatment for patients with this dilemma can prove to be difficult, but as we have shown endovascular stenting of the portal system is an effective treatment option.

Partner-assisted emotional disclosure for patients with gastrointestinal cancer: results from a randomized controlled trial.

PubMed

Porter, Laura S; Keefe, Francis J; Baucom, Donald H; Hurwitz, Herbert; Moser, Barry; Patterson, Emily; Kim, Hong Jin

2009-09-15

For patients with cancer who are married or in an intimate relationship, their relationships with their partners play a critical role in their adaptation to illness. However, cancer patients and their partners often have difficulty in talking with each other about their cancer-related concerns. Difficulties in communication ultimately may compromise both the patient-partner relationship and the patient's psychological adjustment. The current study tested the efficacy of a novel partner-assisted emotional disclosure intervention in a sample of patients with gastrointestinal (GI) cancer. One hundred thirty patients with GI cancer and their partners were assigned randomly to receive 4 sessions of either partner-assisted emotional disclosure or a couples cancer education/support intervention. Patients and partners completed measures of relationship quality, intimacy with their partner, and psychological distress before randomization and at the end of the intervention sessions. Data were analyzed using multilevel modeling. Compared with an education/support condition, the partner-assisted emotional disclosure condition led to improvements in relationship quality and intimacy for couples in which the patient initially reported higher levels of holding back from discussing cancer-related concerns. Partner-assisted emotional disclosure is a novel intervention that builds on both the private emotional disclosure and the cognitive-behavioral marital literature. The results of this study suggested that this intervention may be beneficial for couples in which the patient tends to hold back from discussing concerns. The authors concluded that future research on methods of enhancing the effects of partner-assisted emotional disclosure is warranted. Copyright (c) 2009 American Cancer Society.

Transcatheter treatment of life-threatening lower gastrointestinal bleeding due to advanced pelvic malignancy.

PubMed

Spinosa, D J; Angle, J F; McGraw, J K; Maurer, E J; Hagspiel, K D; Matsumoto, A H

1998-01-01

We present two patients with life-threatening, massive, lower gastrointestinal (GI) bleeding and locally advanced cervical carcinoma. Selective pelvic arteriography demonstrated that the site of bleeding originated from a pseudoaneurysm of the right internal iliac artery with fistulous communication to the sigmoid colon in one patient and from the left internal iliac artery into the rectum in the second patient. Transcatheter embolotherapy was then performed using balloon occlusion in one patient and coil embolization in the second patient. The iliac arteries should also be evaluated in patients with pelvic cancer who present with lower GI bleeding.

Distinctive aspects of peptic ulcer disease, Dieulafoy's lesion, and Mallory-Weiss syndrome in patients with advanced alcoholic liver disease or cirrhosis

PubMed Central

Nojkov, Borko; Cappell, Mitchell S

2016-01-01

AIM: To systematically review the data on distinctive aspects of peptic ulcer disease (PUD), Dieulafoy’s lesion (DL), and Mallory-Weiss syndrome (MWS) in patients with advanced alcoholic liver disease (aALD), including alcoholic hepatitis or alcoholic cirrhosis. METHODS: Computerized literature search performed via PubMed using the following medical subject heading terms and keywords: “alcoholic liver disease”, “alcoholic hepatitis”,“ alcoholic cirrhosis”, “cirrhosis”, “liver disease”, “upper gastrointestinal bleeding”, “non-variceal upper gastrointestinal bleeding”, “PUD”, ‘‘DL’’, ‘‘Mallory-Weiss tear”, and “MWS’’. RESULTS: While the majority of acute gastrointestinal (GI) bleeding with aALD is related to portal hypertension, about 30%-40% of acute GI bleeding in patients with aALD is unrelated to portal hypertension. Such bleeding constitutes an important complication of aALD because of its frequency, severity, and associated mortality. Patients with cirrhosis have a markedly increased risk of PUD, which further increases with the progression of cirrhosis. Patients with cirrhosis or aALD and peptic ulcer bleeding (PUB) have worse clinical outcomes than other patients with PUB, including uncontrolled bleeding, rebleeding, and mortality. Alcohol consumption, nonsteroidal anti-inflammatory drug use, and portal hypertension may have a pathogenic role in the development of PUD in patients with aALD. Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients. The frequency of bleeding from DL appears to be increased in patients with aALD. DL may be associated with an especially high mortality in these patients. MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism, and is associated with aALD. Patients with aALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics. Pre-endoscopic management of acute GI bleeding in patients with aALD unrelated to portal hypertension is similar to the management of aALD patients with GI bleeding from portal hypertension, because clinical distinction before endoscopy is difficult. Most patients require intensive care unit admission and attention to avoid over-transfusion, to correct electrolyte abnormalities and coagulopathies, and to administer antibiotic prophylaxis. Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal. Prompt endoscopy, after initial resuscitation, is essential to diagnose and appropriately treat these patients. Generally, the same endoscopic hemostatic techniques are used in patients bleeding from PUD, DL, or MWS in patients with aALD as in the general population. CONCLUSION: Nonvariceal upper GI bleeding in patients with aALD has clinically important differences from that in the general population without aALD, including: more frequent and more severe bleeding from PUD, DL, or MWS. PMID:26755890

Outcome of non-variceal acute upper gastrointestinal bleeding in relation to the time of endoscopy and the experience of the endoscopist: A two-year survey

PubMed Central

Parente, Fabrizio; Anderloni, Andrea; Bargiggia, Stefano; Imbesi, Venerina; Trabucchi, Emilio; Baratti, Cinzia; Gallus, Silvano; Porro, Gabriele Bianchi

2005-01-01

AIM: To prospectively assess the impact of time of endoscopy and endoscopist’s experience on the outcome of non-variceal acute upper gastrointestinal (GI) bleeding patients in a large teaching hospital. METHODS: All patients admitted for non-variceal acute upper GI bleeding for over a 2-year period were potentially eligible for this study. They were managed by a team of seven endoscopists on 24-h call whose experience was categorized into two levels (high and low) according to the number of endoscopic hemostatic procedures undertaken before the study. Endoscopic treatment was standardized according to Forrest classification of lesions as well as the subsequent medical therapy. Time of endoscopy was subdivided into two time periods: routine (8 a.m.-5 p.m.) and on-call (5 p.m.-8 a.m.). For each category of experience and time periods rebleeding rate, transfusion requirement, need for surgery, length of hospital stay and mortality we compared. Multivariate analysis was used to discriminate the impact of different variables on the outcomes that were considered. RESULTS: Study population consisted of 272 patients (mean age 67.3 years) with endoscopic stigmata of hemorrhage. The patients were equally distributed among the endoscopists, whereas only 19% of procedures were done out of working hours. Rockall score and Forrest classification at admission did not differ between time periods and degree of experience. Univariate analysis showed that higher endoscopist’s experience was associated with significant reduction in rebleeding rate (14% vs 37%), transfusion requirements (1.8±0.6 vs 3.0±1.7 units) as well as surgery (4% vs 10%), but not associated with the length of hospital stay nor mortality. By contrast, outcomes did not significantly differ between the two time periods of endoscopy. On multivariate analysis, endoscopist’s experience was independently associated with rebleeding rate and transfusion requirements. Odds ratios for low experienced endoscopist were 4.47 for rebleeding and 6.90 for need of transfusion after the endoscopy. CONCLUSION: Endoscopist’s experience is an important independent prognostic factor for non-variceal acute upper GI bleeding. Urgent endoscopy should be undertaken preferentially by a skilled endoscopist as less expert staff tends to underestimate some risk lesions with a negative influence on hemostasis. PMID:16437658

Permeability and toxicity characteristics of L-cysteine and 2-methyl-thiazolidine-4-carboxylic acid in Caco-2 cells.

PubMed

Kartal-Hodzic, Alma; Marvola, Tuuli; Schmitt, Mechthild; Harju, Kirsi; Peltoniemi, Marikki; Sivén, Mia

2013-01-01

Acetaldehyde is a known mutagenic substance and has been classified as a group-one carcinogen by the WHO. It is possible to bind acetaldehyde locally in the gastrointestinal (GI) tract with the semi-essential amino acid l-cysteine, which reacts covalently with acetaldehyde and forms compound 2-methyl-thiozolidine-4-carboxylic acid (MTCA). The Caco-2 cell line was used to determine the permeation of l-cysteine and MTCA, as well as the possible cell toxicity of both substances. Neither of the substances permeated through the Caco-2 cells at the concentrations used in this study, and only the highest concentration of MTCA affected the viability of the cells in the MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) test. These results showed that when l-cysteine is administered in formulations releasing it locally in the lower parts of GI tract, it is not absorbed but can react with acetaldehyde, and that neither l-cysteine nor MTCA is harmful to the cells when present locally in the upper parts of GI tract. This study also shows that MTCA is sensitive at a lower pH of 5.5. Since stable MTCA is desired in different parts of the GI tract, this observation raises concern over the influence of lower pH on l-cysteine-containing product ability to bind and eliminate carcinogenic acetaldehyde.

Gastrodoudenal Embolization: Indications, Technical Pearls, and Outcomes

PubMed Central

Kuyumcu, Gokhan; Latich, Igor; Hardman, Rulon L.; Fine, Gabriel C.

2018-01-01

The gastroduodenal artery (GDA) is frequently embolized in cases of upper GI bleed that has failed endoscopic therapy. Additionally, it may be done for GDA pseudoaneurysms or as an adjunctive procedure prior to Yttrim-90 (Y90) treatment of hepatic tumors. This clinical review will summarize anatomy and embryology of the GDA, indications, outcomes and complications of GDA embolization. PMID:29724061

Five-year follow-up using a prostate stent as fiducial in image-guided radiotherapy of prostate cancer.

PubMed

Carl, Jesper; Sander, Lotte

2015-06-01

To report results from the five-year follow-up on a previously reported study using image-guided radiotherapy (IGRT) of localized or locally advanced prostate cancer (PC) and a removable prostate stent as fiducial. Patients with local or locally advanced PC were treated using five-field 3D conformal radiotherapy (3DRT). The clinical target volumes (CTV) were treated to 78 Gy in 39 fractions using daily on-line image guidance (IG). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were scored using the radiotherapy oncology group (RTOG) score and the common toxicity score of adverse events (CTC) score. Urinary symptoms were also scored using the international prostate symptom score (IPSS). Median observation time was 5.4 year. Sixty-two of the 90 patients from the original study cohort were eligible for toxicity assessment. Overall survival, cancer-specific survival and biochemical freedom from failure were 85%, 96% and 80%, respectively at five years after radiotherapy. Late toxicity GU and GI RTOG scores≥2 were 5% and 0%. Comparing pre- and post-radiotherapy IPSS scores indicate that development in urinary symptoms after radiotherapy may be complex. Prostate image-guided radiotherapy using a prostate stent demonstrated survival data comparable with recently published data. GU and GI toxicities at five-year follow-up were low and comparable to the lowest toxicity rates reported. These findings support that the precision of the prostate stent technique is at least as good as other techniques. IPSS revealed a complex development in urinary symptoms after radiotherapy.

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peeters, Stephanie T.H.; Lebesque, Joos V.; Heemsbergen, Wilma D.

2006-03-15

Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}).more » The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.« less

Stomach arteriovenous malformation resected by laparoscopy-assisted surgery: A case report.

PubMed

Hotta, Masahiro; Yamamoto, Kazuhito; Cho, Kazumitsu; Takao, Yoshimune; Fukuoka, Takeshi; Uchida, Eiji

2016-05-01

Arteriovenous malformations of the stomach are an uncommon cause of upper GI bleeding. We report a case of stomach arteriovenous malformation in an 85-year-old Asian man who presented with massive hematemesis. Initial esophagogastroduodenoscopy did not detect this lesion, but contrast multi-detector CT confirmed GI bleeding. Multi-detector CT revealed a mass of blood vessels underlying the submucosa that arose from the right gastroepiploic artery. Repeat esophagogastroduodenoscopy showed that the lesion was a submucosal tumor with erosion and without active bleeding in the lower body of the stomach on the greater curvature. We performed partial gastrectomy via laparoscopy-assisted surgery. The histopathological diagnosis was arteriovenous malformation. © 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.

2012-08-01

Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADTmore » and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.« less

Analysis of Gastric Adenocarcinoma Data in a Pan-GI Context to Reveal Genes, Pathways, and Interactions that Yield Novel Therapeutic Advantages

DTIC Science & Technology

2017-09-01

that Yield Novel Therapeutic Advantages PRINCIPAL INVESTIGATOR: Rehan Akbani CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer ...mdanderson.org, jajani@mdanderson.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) The University of Texas MD Anderson Cancer Center...is the study of gastric cancer , where the purpose is to reveal new insights into the biology of the disease that could potentially have therapeutic

Impact of esophagogastroduodenoscopy and ileocolonoscopy on diagnosis and therapy in patients with rheumatic diseases-a retrospective cohort study.

PubMed

Schäfer, Valentin Sebastian; Fleck, Martin; Ehrenstein, Boris; Peters, Ann-Kathrin; Hartung, Wolfgang

2016-07-01

Many rheumatic diseases as well as their medications may cause gastrointestinal (GI) pathologies; in addition, some primary GI diseases may contribute or lead to rheumatic disease manifestations. The aim of this study is to analyze the clinical relevance of esophagogastroduodenoscopy (EGD) and ileocolonoscopy (IC) in patients suffering from inflammatory rheumatic diseases. A retrospective chart review was performed for all rheumatological inpatients who underwent EGD and/or IC within 2 years. Within 2 years, 456 patients (261 female, 195 male) underwent 752 endoscopic investigations of the GI tract (419 EGDs and 333 ICs). Of all patients, 152 (33.3%) did not report any GI complaints. However, 28 of these asymptomatic patients (18.4%) suffered from esophagitis, a gastric ulcer could be identified in 20 patients (13%), whereas unspecific colitis was diagnosed in 19 patients (12.5%). In addition, 14 patients (9.2%) suffered from clinically unapparent Crohn's disease and two patients from Whipple's disease. In one patient with polymyalgia rheumatica, colon cancer was diagnosed. Altogether 304 patients reported GI complaints. Of these, 292 (39%) endoscopic investigations had impact on the final diagnosis or therapeutic strategy. The antirheumatic medication or the concomitant medication was changed in 18% of the patients due to the endoscopic findings; in 29 patients (6.5%) the initially clinically presumed diagnosis had to be corrected. In 70 patients (15%) with an undefined rheumatic diagnosis prior to endoscopy, endoscopic findings were decisive to establish the final diagnosis. EGD and IC have a high diagnostic impact on patients with rheumatic diseases presenting with or without concomitant GI symptoms.

Preclinical development of a non-toxic oral formulation of monoethanolamine, a lipid precursor, for prostate cancer treatment

PubMed Central

Saxena, Roopali; Yang, Chunhua; Rao, Mukkavilli; Turaga, Ravi Chakra; Garlapati, Chakravarthy; Gundala, Sushma Reddy; Myers, Kimberly; Ghareeb, Ahmed; Bhattarai, Shristi; Kamilinia, Golnaz; Bristi, Sangina; Su, Dan; Gadda, Giovanni; Rida, Padmashree C. G.; Cantuaria, Guilherme H.; Aneja, Ritu

2018-01-01

Purpose Most currently-available chemotherapeutic agents target rampant cell division in cancer cells, thereby affecting rapidly-dividing normal cells resulting in toxic side-effects. This non-specificity necessitates identification of novel cellular pathways that are reprogrammed selectively in cancer cells and can be exploited to develop pharmacologically superior and less-toxic therapeutics. Despite growing awareness on dysregulation of lipid metabolism in cancer cells, targeting lipid biosynthesis is still largely uncharted territory. Herein, we report development of a novel non-toxic orally-deliverable anticancer formulation of monoethanolamine (Etn), for prostate cancer by targeting the Kennedy pathway of phosphatidylethanolamine (PE) lipid biosynthesis. Experimental Design We first evaluated GI-tract stability, drug-drug interaction liability, pharmacokinetic and toxicokinetic properties of Etn to evaluate its suitability as a non-toxic orally-deliverable agent. We next performed in vitro and in vivo experiments to investigate efficacy and mechanism of action. Results Our data demonstrate that Etn exhibits excellent bioavailability, GI-tract stability, and no drug-drug interaction liability. Remarkably, orally-fed Etn inhibited tumor growth in four weeks by ~67% in mice bearing human prostate cancer PC-3 xenografts without any apparent toxicity. Mechanistically, Etn exploits selective overexpression of choline kinase in cancer cells, resulting in accumulation of phosphoethanolamine (PhosE), accompanied by downregulation of HIF-1α that induces metabolic stress culminating into cell death. Conclusions Our study provides first evidence for the superior anticancer activity of Etn, a simple lipid precursor formulation, whose non-toxicity conforms to FDA-approved standards, compelling its clinical development for prostate cancer management. PMID:28167510

[Gas gangrene of the abdominal wall due to underlying GI pathology: seven cases].

PubMed

Monneuse, O; Gruner, L; Barth, X; Malick, P; Timsit, M; Gignoux, B; Tissot, E

2007-01-01

Gas gangrene of the abdominal wall is a rare clinical occurrence with high rates of morbidity and mortality. The primary source of the infection is often unknown. To analyze the primary underlying intestinal etiologies and diagnostic approaches of gas gangrene of the abdominal wall, and to highlight specific treatment problems, particularly that of constructing a colostomy exteriorized through a massively infected abdominal wall. Seven cases of abdominal wall gas gangrene due to a gastrointestinal etiology were identified. (Cases arising from proctologic sources or related to recent abdominal surgery were excluded.) During the same period, 39 other patients presenting with abdominal wall gangrene from non-intestinal sources were treated. The etiologies were: perforated sigmoid diverticulitis (n=2), perforated appendicitis (n=1), acute pancreatitis with associated cecal perforation (n=1), and perforated colorectal cancer (n=3). Four of the seven patients died despite treatment (mortality of 57%). The clinical presentations of these seven cases demonstrate that a GI source must be suspected whenever a patient presents with abdominal wall gas gangrene, even when there are no specific GI symptoms. Imaging, particularly with CT scan, is essential both to visualize the extent of tissue necrosis and to reveal underlying primary GI pathology. This optimizes the surgical approach both by allowing for complete debridement and drainage of infected tissue, and by focussing the intervention on correction of the underlying primary GI source of infection.

GOAL: multicenter, open-label, post-marketing study of flavocoxid, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin.

PubMed

Pillai, Lakshmi; Burnett, Bruce P; Levy, Robert M

2010-05-01

GOAL (Gauging Osteoarthritis [OA] with Limbrel*), an open-label, post-marketing study was performed to determine the overall efficacy and gastrointestinal (GI) tolerability of flavocoxid, a novel, plant-based, anti-inflammatory medication, in a 'real world' clinical practice setting. To this end, the study enrolled several unique patient types including nonsteroidal anti-inflammatory drug (NSAID) naïve patients, those who had used NSAIDs in the past, regardless of outcome (positive or negative), and those who had previously taken a gastroprotective medication to improve GI tolerability or continued to take it as a precautionary measure to prevent NSAID-associated GI damage. A total of 1067 individuals at 41 rheumatology practices were enrolled and prescribed flavocoxid, 500 mg b.i.d., for 60 days. The Physician Global Assessment of Disease (PGAD) visual analog scale (VAS) was used as a global measure to assess the signs and symptoms of OA, including joint discomfort, functional stiffness, functional mobility and quality of life. In addition, overall tolerability and upper GI tolerability were assessed by individual questions scored on a 5-part Likert scale. The physicians also monitored any interruption in, or cessation of use of flavocoxid due to a GI issue as well as changes in the use of gastroprotective medications. Adverse event (AE) monitoring was also conducted. Of the 1005 patients who completed all follow-up visits, physicians recorded an average improvement in VAS scores from 60.1 +/- 18.8 at baseline to 42.5 +/- 21.9 at 8 weeks (p < 0.001) in 65.8% of patients. The PGAD VAS noted the most significant improvement in those patients with moderate to severe OA (baseline VAS [0 = least severe, 100 = most severe]: 0-25 mm, -3.5 +/- 6.9; 26-50 mm, -10.1 +/- 17.0; 51-75 mm, -19.3 +/- 19.5; 76-100 mm, -29.6 +/- 23.6; p < 0.001) and in those patients who were historically non-responders to NSAIDs (40.3 +/- 21.1 vs. 66.3 +/- 17.7 at baseline; p < 0.001). Patients who had previously responded well to NSAIDs had VAS scores of 42.6 +/- 19.8 vs. 58.0 +/- 18.0 (p < 0.001) and NSAID naïve subjects showed improvement in VAS scores from 60.5 +/- 18.0 at baseline to 46.3 +/- 23.7 (p < 0.001). The study recorded a low incidence ( approximately 10%) of AEs reported to physicians and good overall tolerability to flavocoxid. Flavocoxid showed improved upper GI tolerability in almost 50% of previous NSAID users (p < 0.001) and reduced therapy interruption in approximately 90% of previous NSAID users with a history of GI-related therapy interruptions (p < 0.0001). Finally, the use of flavocoxid resulted in a >30% reduction in or cessation of the use of gastroprotective medications such as proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2s) in subjects (p < 0.001). Within a 'real world' clinical rheumatology practice setting, flavocoxid demonstrated significant efficacy in the management of OA in multiple patient types and displayed significant potential for reducing the possibility of adverse GI side-effects and use of gastroprotective agents associated with more traditional OA medications. A limitation of this study was that it was open-label and not rigorously controlled. The large population may compensate for this lack of control.

Asian consensus on the relationship between obesity and gastrointestinal and liver diseases.

PubMed

Koh, Jianyi Calvin; Loo, Wai Mun; Goh, Khean Lee; Sugano, Kentaro; Chan, Wah Kheong; Chiu, Wai Yan Philip; Choi, Myung-Gyu; Gonlachanvit, Sutep; Lee, Wei-Jei; Lee, Wei Jie Jonathan; Lee, Yeong Yeh; Lesmana, Laurentius A; Li, You-Ming; Liu, Chun Jen; Matsuura, Bunzo; Nakajima, Atsushi; Ng, Enders Kwok Wai; Sollano, Jose D; Wong, Simon Kin Hung; Wong, Vincent W S; Yang, Yunsheng; Ho, Khek Yu; Dan, Yock Young

2016-08-01

The incidence of obesity is increasing in Asia, with implications on gastrointestinal (GI) and liver diseases. The Gut and Obesity in Asia Workgroup comprises regional experts with the aim of studying relationship between obesity and the GI and liver diseases in Asia. Through literature review and the modified Delphi process, consensus statements examining the impact of obesity on esophageal, gastric, pancreatic, colorectal, and liver diseases, exploring relationship between gut microbiome and obesity, and assessing obesity therapies have been produced by the Gut and Obesity in Asia Workgroup. Sixteen experts participated with 9/15 statements having strong consensus (>80% agreement). The prevalence of obesity in Asia is increasing (100% percentage agreement in brackets), and this increased prevalence of obesity will result in a greater burden of obesity-related GI and liver diseases (93.8%). There was consensus that obesity increases the risk of gastric cancer (75%) and colorectal neoplasia (87.5%). Obesity was also associated with Barrett's esophagus and esophageal adenocarcinoma (66.7%) and pancreatic cancer (66.7%) in Asia. The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asia is on the rise (100%), and the risk of NAFLD in Asia (100%) is increased by obesity. Obesity is a risk factor for the development of hepatocellular carcinoma (93.8%). Regarding therapy, it was agreed that bariatric surgery was an effective treatment modality for obesity (93.8%) but there was less agreement on its benefit for NAFLD (62.5%). These experts' consensus on obesity and GI diseases in Asia forms the basis for further research, and its translation into addressing this emerging issue. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

PubMed Central

Wang, Jingya; Wei, Caimiao; Tucker, Susan L.; Myles, Bevan; Palmer, Matthew; Hofstetter, Wayne L.; Swisher, Stephen G.; Ajani, Jaffer A.; Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing; Lin, Steven H.

2013-01-01

Purpose While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ2 or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis. Results The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104–3.688; OR, 1.704; 95% CI, 1.03–2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365–7.289; OR, 1.55; 95% CI, 0.78–3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation. PMID:23845841

Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jingya; Wei, Caimiao; Tucker, Susan L.

2013-08-01

Purpose: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials: From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ{sup 2} or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factorsmore » that were significant on univariate analysis. Results: The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions: The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.« less

Investments in cancer research awarded to UK institutions and the global burden of cancer 2000-2013: a systematic analysis.

PubMed

Maruthappu, Mahiben; Head, Michael G; Zhou, Charlie D; Gilbert, Barnabas J; El-Harasis, Majd A; Raine, Rosalind; Fitchett, Joseph R; Atun, Rifat

2017-04-20

To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). Systematic analysis of all open-access data. Public and philanthropic funding to all UK cancer research institutions, 2000-2013. Number and financial value of cancer research investments reported in 2013 UK pounds (UK£). Mortality, DALYs and YLDs data were acquired from the Global Burden of Disease Study. A compound metric was adapted to estimate research investment relative to disease burden as measured by mortality, DALYs and YLDs. We identified 4299 funded studies with a total research investment of £2.4 billion. The highest fundings by anatomical sites were haematological, breast, prostate, colorectal and ovarian cancers. Relative to disease burden as determined by a compound metric combining mortality, DALYs and YLDs, gender-specific cancers were found to be highest funded-the five sites that received the most funding were prostate, ovarian, breast, mesothelioma and testicular cancer; the least well-funded sites were liver, thyroid, lung, upper gastrointestinal (GI) and bladder. Preclinical science accounted for 66.2% of award numbers and 62.2% of all funding. The top five areas of primary research focus by funding were pathogenesis, drug therapy, diagnostic, screening and monitoring, women's health and immunology. The largest individual funder was the Medical Research Council. In combination, the five lowest funded site-specific cancers relative to disease burden account for 47.9%, 44.3% and 20.4% of worldwide cancer mortality, DALYs and YLDs. Research funding for cancer is not allocated according to relative disease burden. These findings are in line with earlier published studies. Funding agencies and industry should openly document their research investments to improve better targeting of research investment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Lung and Upper Aerodigestive Cancer | Division of Cancer Prevention

Cancer.gov

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B-glucans from Grifola frondosa and Ganoderma lucidum in breast cancer: an example of complementary and integrative medicine

PubMed Central

Rossi, Paola; Difrancia, Raffaele; Quagliariello, Vincenzo; Savino, Elena; Tralongo, Paolo; Randazzo, Cinzia Lucia; Berretta, Massimiliano

2018-01-01

Culinary and medicinal mushrooms are widely used in Asian countries, both as dietary supplements and as nutraceutical foods. They have recently become popular in Europe, as well, for their nutritional and health benefits. In particular, epidemiological studies conducted in Asia suggest that mushroom intake, together with other phytotherapy substances, protects against cancer, specifically gastrointestinal (GI) and breast cancers. Most of the data come from in vitro studies and in vivo experimental animal models. Therefore, in order to translate the updated knowledge to clinical research (i.e., from bench to bedside) a systematic translational research program should be initiated. Future randomized controlled trials comparing the effects of G. frondosa and G. lucidum on conventional treatment outcomes are warranted. The purpose of this review was to describe the emerging mechanisms of action of the mushrooms’ anticancer functions which makes their use in clinical practice so promising. Clinical effects of mycotherapy (specifically, the use of Ganoderma lucidum and Grifola frondosa) on long-term survival, tumor response, host immune functions, inflammation, and QoL in cancer patients were also addressed. Adverse events associated with mycotherapy were also investigated. Emerging data point to a potential role of G. lucidum for modulating the carcinogenic potential of GI microbiota, which suggests a new complementary and integrated approach to breast cancer treatment. PMID:29872510

Exsanguinating upper GI bleeds due to Unusual Arteriovenous Malformation (AVM) of stomach and spleen: a case report.

PubMed

Khan, Mohammad Iqbal; Baqai, Muhammad Tariq; Baqai, Mohammad Fahd; Mufti, Naveed

2009-05-01

In this paper we are reporting one case of exsanguinating upper gastrointestinal tract (GIT) bleed requiring massive blood transfusion and immediate life saving surgery. A 30 years old female, 12 weeks pregnant was referred to our hospital from the earth-quake affected area of Kashmir with history of upper abdominal pain, haematemesis and melaena for one week. After stabilizing the patient, upper gastro-intestinal endoscopy was performed. It revealed gastric ulcer just distal to the gastro-esophageal junction on the lesser curvature. Biopsy from the ulcer edge led to profuse spurting of the blood and patient went into state of shock. Immediate resuscitation led to rebleeding and recurrence of post haemorrahagic shock. The patient was immediately explored and total gastrectectomy with splenectomy concluded as life saving procedure. A review of literature was conducted to make this report possible.

Reducing Toxicity of Radiation Treatment of Advanced Prostate Cancer

DTIC Science & Technology

2015-10-01

steady state hematopoiesis with normalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cells from RTA...ongoing. 7 KEY RESEARCH ACCOMPLISHMENTS: • Identified radiation protection of different organ systems (GI tract, skin and hematopoiesis ) by RTA

Necrotizing Soft-Tissue Infections: Clinical Guidelines

DTIC Science & Technology

2009-10-01

viscus, liposuction , infected arteriovenous grafts, and invasive cancer. As many as half of these patients may not be able to identify a previous lesion...Fractures Liposuction Seawater, seafood Surgery Spider bite Childbirth, C section Burns NSTI, necrotizing soft-tissue infection; GI, gastrointestinal; HIV

A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

PubMed

Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

2018-05-30

The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.

PubMed

Formagio, Anelise S Nazari; Tonin, Lilian T Düsman; Foglio, Mary Ann; Madjarof, Christiana; de Carvalho, João Ernesto; da Costa, Willian Ferreira; Cardoso, Flávia P; Sarragiotto, Maria Helena

2008-11-15

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.

Targeting Taxanes to Castration-Resistant Prostate Cancer Cells by Nanobubbles and Extracorporeal Shock Waves

PubMed Central

Argenziano, Monica; Cavalli, Roberta; Sassi, Francesca; D’Amelio, Patrizia; Battaglia, Antonino; Gontero, Paolo; Bosco, Ornella; Peluso, Rossella; Fortunati, Nicoletta; Frairia, Roberto; Catalano, Maria Graziella

2016-01-01

To target taxanes to castration-resistant prostate cancer cells, glycol-chitosan nanobubbles loaded with paclitaxel and docetaxel were constructed. The loaded nanobubbles were then combined with Extracorporeal Shock Waves, acoustic waves widely used in urology and orthopedics, with no side effects. Nanobubbles, with an average diameter of 353.3 ± 15.5 nm, entered two different castration-resistant prostate cancer cells (PC3 and DU145) as demonstrated by flow cytometry and immunofluorescence. The shock waves applied increased the amount of intracellular nanobubbles. Loading nanobubbles with paclitaxel and docetaxel and combining them with shock waves generated the highest cytotoxic effects, resulting in a paclitaxel GI50 reduction of about 55% and in a docetaxel GI50 reduction of about 45% respectively. Combined treatment also affected cell migration. Paclitaxel-loaded nanobubbles and shock waves reduced cell migration by more than 85% with respect to paclitaxel alone; whereas docetaxel-loaded nanobubbles and shock waves reduced cell migration by more than 82% with respect to docetaxel alone. The present data suggest that nanobubbles can act as a stable taxane reservoir in castration-resistant prostate cancer cells and shock waves can further increase drug release from nanobubbles leading to higher cytotoxic and anti-migration effect. PMID:28002459

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype.

PubMed

Lal, Shruti; Cheung, Edwin C; Zarei, Mahsa; Preet, Ranjan; Chand, Saswati N; Mambelli-Lisboa, Nicole C; Romeo, Carmella; Stout, Matthew C; Londin, Eric; Goetz, Austin; Lowder, Cinthya Y; Nevler, Avinoam; Yeo, Charles J; Campbell, Paul M; Winter, Jordan M; Dixon, Dan A; Brody, Jonathan R

2017-06-01

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro , as HuR-deficient MIA PaCa-2 (MIA.HuR-KO (-/-) ) cells had increased apoptosis when compared with isogenic wild-type (MIA.HuR-WT (+/+) ) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a two-dimensional culture into three dimensional (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared with control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. Although not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO (-/-) ) showed significantly reduced in vivo tumor growth compared with controls (HCT.HuR-WT (+/+) ). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications: The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. Mol Cancer Res; 15(6); 696-707. ©2017 AACR . ©2017 American Association for Cancer Research.

The Association between Oral Hygiene and Gastric Pathology in Patients with Dyspepsia: a Cross-Sectional Study in Southeast Iran.

PubMed

Zahedi, Leili; Jafari, Elham; Torabi Parizi, Molook; Shafieipour, Sara; Hayat Bakhsh Abbasi, Mehdi; Darvish Moghadam, Sodaif; Zahedi, Mohammad Javad

2017-01-01

BACKGROUND Many studies have reported an association between periodontal infections and some systemic diseases such as respiratory and cardiovascular diseases. Some studies found a direct association between chronic gastritis caused by Helicobacter pylori (HP) infection and poor periodontal health. METHODS In a cross-sectional study from November 2014 to December 2015 in Kerman, the largest province in southeast Iran, patients with dyspepsia who were candidate for diagnostic upper gastrointestinal (GI) endoscopy were included in our study. Decayed, Missing, and Filled Teeth (DMFT) index and Loe plaque index that are two popular indexes in dental epidemiology were used to assess the oral health by a dentist before the upper GI endoscopy. According to the Loe plaque index, score: 0= no plaque, score: 1= a film of plaque attaching to the free gingival border and near area of the tooth, score: 2= moderate reposition of deposits within the gingival pocket, score :3= plenty of soft matter within the gingival pocket±on the tooth and gingival border. Scores ≤1, 2 and 3 equal to good, moderate, and poor oral hygiene, respectively. During upper GI endoscopy a total of six biopsy samples were taken from fundus, body, and antrum. A pathologist reported these samples according to Sidney's classification into superficial gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia. RESULTS According to Sidney's classification 77 (89.5%) patients had superficial gastritis, 3 (3.5%) had atrophic gastritis, and 6 (7%) had intestinal metaplasia. HP was found in 80.2% of the gastric mucosal biopsy samples. There were not statistically significant relationship between Sidney's classification, presence of HP in gastric mucosal biopsies, and hygiene indicators ( p >0.05). No relation was found between the DMFT index and superficial gastritis, atrophic gastritis, and intestinal metaplasia ( p >0.05). Gastric infection with HP was found in 70%, 75%, and 100% of patients with mild, moderate, and sever DMFT index, respectively. CONCLUSION Our study showed that there might be a relation between poor oral hygiene and gastric precancerous lesions. In addition, HP infection in gastric histopathology might be associated with periodontal disease.

The Association between Oral Hygiene and Gastric Pathology in Patients with Dyspepsia: a Cross-Sectional Study in Southeast Iran

PubMed Central

Zahedi, Leili; Jafari, Elham; Torabi Parizi, Molook; Shafieipour, Sara; Hayat Bakhsh Abbasi, Mehdi; Darvish Moghadam, Sodaif; Zahedi, Mohammad Javad

2017-01-01

BACKGROUND Many studies have reported an association between periodontal infections and some systemic diseases such as respiratory and cardiovascular diseases. Some studies found a direct association between chronic gastritis caused by Helicobacter pylori (HP) infection and poor periodontal health. METHODS In a cross-sectional study from November 2014 to December 2015 in Kerman, the largest province in southeast Iran, patients with dyspepsia who were candidate for diagnostic upper gastrointestinal (GI) endoscopy were included in our study. Decayed, Missing, and Filled Teeth (DMFT) index and Loe plaque index that are two popular indexes in dental epidemiology were used to assess the oral health by a dentist before the upper GI endoscopy. According to the Loe plaque index, score: 0= no plaque, score: 1= a film of plaque attaching to the free gingival border and near area of the tooth, score: 2= moderate reposition of deposits within the gingival pocket, score :3= plenty of soft matter within the gingival pocket±on the tooth and gingival border. Scores ≤1, 2 and 3 equal to good, moderate, and poor oral hygiene, respectively. During upper GI endoscopy a total of six biopsy samples were taken from fundus, body, and antrum. A pathologist reported these samples according to Sidney’s classification into superficial gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia. RESULTS According to Sidney’s classification 77 (89.5%) patients had superficial gastritis, 3 (3.5%) had atrophic gastritis, and 6 (7%) had intestinal metaplasia. HP was found in 80.2% of the gastric mucosal biopsy samples. There were not statistically significant relationship between Sidney’s classification, presence of HP in gastric mucosal biopsies, and hygiene indicators (p>0.05). No relation was found between the DMFT index and superficial gastritis, atrophic gastritis, and intestinal metaplasia (p>0.05). Gastric infection with HP was found in 70%, 75%, and 100% of patients with mild, moderate, and sever DMFT index, respectively. CONCLUSION Our study showed that there might be a relation between poor oral hygiene and gastric precancerous lesions. In addition, HP infection in gastric histopathology might be associated with periodontal disease. PMID:28316764

Compliance with preoperative oral nutritional supplements in patients at nutritional risk--only a question of will?

PubMed

Grass, F; Bertrand, P C; Schäfer, M; Ballabeni, P; Cerantola, Y; Demartines, N; Hübner, M

2015-04-01

Preoperative nutrition has been shown to reduce morbidity after major gastrointestinal (GI) surgery in selected patients at risk. In a randomized trial performed recently (NCT00512213), almost half of the patients, however, did not consume the recommended dose of nutritional intervention. The present study aimed to identify the risk factors for noncompliance. Demographic (n = 5) and nutritional (n = 21) parameters for this retrospective analysis were obtained from a prospectively maintained database. The outcome of interest was compliance with the allocated intervention (ingestion of ⩾ 11/15 preoperative oral nutritional supplement units). Uni- and multivariate analyses of potential risk factors for noncompliance were performed. The final analysis included 141 patients with complete data sets for the purpose of the study. Fifty-nine patients (42%) were considered noncompliant. Univariate analysis identified low C-reactive protein levels (P = 0.015), decreased recent food intake (P = 0.032) and, as a trend, low hemoglobin (P = 0.065) and low pre-albumin (P = 0.056) levels as risk factors for decreased compliance. However, none of them was retained as an independent risk factor after multivariate analysis. Interestingly, 17 potential explanatory parameters, such as upper GI cancer, weight loss, reduced appetite or co-morbidities, did not show any significant correlation with reduced intake of nutritional supplements. Reduced compliance with preoperative nutritional interventions remains a major issue because the expected benefit depends on the actual intake. Seemingly, obvious reasons could not be retained as valid explanations. Compliance seems thus to be primarily a question of will and information; the importance of nutritional supplementation needs to be emphasized by specific patients' education.

Endoscopy services in KwaZulu-Natal Province, South Africa, are insufficient for the burden of disease: Is patient care compromised?

PubMed

Loots, E; Clarke, D L; Newton, K; Mulder, C J

2017-10-31

Endoscopy services are central to the diagnosis and management of many gastrointestinal (GI) diseases. To evaluate the adequacy of endoscopy services in the public sector hospitals of KwaZulu-Natal (KZN) Province, South Africa, in 2016. A cross-sectional study was performed using a questionnaire completed by the clinical heads of endoscopy units in the public hospitals in KZN. The heads of 11 of the 12 endoscopy units responded. Two units were in tertiary-level hospitals and nine in regional hospitals. A total of 22 353 endoscopic procedures were performed annually, averaging 2 032 cases per annum per centre; they were performed by 89 endoscopists, of whom 72 (80.1%) were general surgeons. There were 0.06 registered gastroenterologists (GEs) per 100 000 population. Each endoscopist performed an average of 263 endoscopies per annum. There were 1.18 endoscopy rooms available per unit, and two units had on-site fluoroscopy available. The average waiting period for an upper endoscopy was 27 (range 7 - 60) days, for colonoscopy 29 (range 7 - 90) days and for duodenoscopy/endoscopic retrograde cholangiopancreatography 13 (range 4 - 20) days. This included patients with alarm symptoms for GI cancers. Equipment breakages interrupted most services, except for one hospital that had a service contract. Unit heads cited lack of equipment, trained staff and maintenance contracts as major shortcomings. Endoscopy units in KZN are not adequately equipped to deal with the endoscopy workload and services are plagued by frequent disruptions, which impact negatively on service delivery. There is a need to train more GEs. Patient care is compromised in these public hospitals.

Step-up training for colorectal and gastric ESD and the challenge of ESD training in the proximal colon: results from a German Center.

PubMed

Ebigbo, Alanna; Probst, Andreas; Römmele, Christoph; Messmann, Helmut

2018-05-01

The endoscopic submucosal dissection (ESD) of cancerous and precancerous lesions in the gastrointestinal (GI) tract is an effective but difficult-to-learn procedure, especially for Western endoscopists. We developed a step-up training protocol and evaluated its outcome on a single endoscopist using specific performance measures. The training protocol included a 12-month period of 50 observational and supervised ESD cases as well as 24 animal procedures. After completion of the protocol, ESD competency was evaluated in the first 30 independent ESD cases. Majority of lesions were located in the stomach and rectum. Performance measures included R0-resection rate, complication rate and resection speed. R0 resection rate was 93 %, complication rate was 7 % and median resection speed was 6,77 cm 2 /h. 1 case of delayed perforation with subsequent hemicolectomy occurred in the descending colon. The ESD step-up training protocol used in this study on a single endoscopist showed excellent outcomes for lesions in the rectum and stomach. However, ESD training in the upper colon remains a challenge.

Potent anti-proliferative effects against oral and cervical cancers of Thai medicinal plants selected from the Thai/Lanna medicinal plant recipe database "MANOSROI III".

PubMed

Manosroi, Aranya; Akazawa, Hiroyuki; Pattamapun, Kassara; Kitdamrongtham, Worapong; Akihisa, Toshihiro; Manosroi, Worapaka; Manosroi, Jiradej

2015-07-01

Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including oral and cervical cancers. To investigate anti-proliferative activity on human cervical (HeLa) and oral (KB) cancer cell lines of medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III". Twenty-three methanolic plant crude extracts were tested for phytochemicals and anti-proliferative activity on HeLa and KB cell lines for 24 h by the sulforhodamine B (SRB) assay at the doses of 1 × 10(1)-1 × 10(-6 )mg/ml. The nine extracts with the concentrations giving 50% growth inhibition (GI50) lower than 100 µg/ml were further semi-purified by liquid/liquid partition in order to evaluate and enhance the anti-proliferative potency. All extracts contained steroids/triterpenoids, but not xanthones. The methanolic extracts of Gloriosa superba L. (Colchinaceae) root and Albizia chinensis (Osbeck) Merr. (Leguminosae-Mimosoideae) wood gave the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.91 (6.0- and 0.31-fold of cisplatin and doxorubicin) and 0.16 µg/ml (28.78- and 82.29-fold of cisplatin and doxorubicin), respectively. Hexane and methanol-water fractions of G. superba exhibited the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.15 (37- and 1.9-fold of cisplatin and doxorubicin) and 0.058 µg/ml (77.45- and 221.46-fold of cisplatin and doxorubicin), respectively. This study has demonstrated the potential of plants selected from MANOSROI III database especially G. superba and A. chinensis for further development as anti-oral and cervical cancer agents.

The GI Project: a prototype electronic textbook for high school biology.

PubMed

Calhoun, P S; Fishman, E K

1997-01-01

A prototype electronic science textbook for secondary education was developed to help bridge the gap between state-of-the-art medical technology and the basic science classroom. The prototype combines the latest in radiologic imaging techniques with a user-friendly multimedia computer program to teach the anatomy, physiology, and diseases of the gastrointestinal (GI) tract. The program includes original text, illustrations, photographs, animations, images from upper GI studies, plain radiographs, computed tomographic images, and three-dimensional reconstructions. These features are intended to create a stimulus-rich environment in which the high school science student can enjoy a variety of interactive experiences that will facilitate the learning process. The computer-based book is a new educational tool that promises to play a prominent role in the coming years. Current research suggests that computer-based books are valuable as an alternative educational medium. Although it is not yet clear what form textbooks will take in the future, computer-based books are already proving valuable as an alternative educational medium. For beginning students, they reinforce the material found in traditional textbooks and class presentations; for advanced students, they provide motivation to learn outside the traditional classroom.

Review on sedation for gastrointestinal tract endoscopy in children by non-anesthesiologists

PubMed Central

Orel, Rok; Brecelj, Jernej; Dias, Jorge Amil; Romano, Claudio; Barros, Fernanda; Thomson, Mike; Vandenplas, Yvan

2015-01-01

AIM: To present evidence and formulate recommendations for sedation in pediatric gastrointestinal (GI) endoscopy by non-anesthesiologists. METHODS: The databases MEDLINE, Cochrane and EMBASE were searched for the following keywords “endoscopy, GI”, “endoscopy, digestive system” AND “sedation”, “conscious sedation”, “moderate sedation”, “deep sedation” and “hypnotics and sedatives” for publications in English restricted to the pediatric age. We searched additional information published between January 2011 and January 2014. Searches for (upper) GI endoscopy sedation in pediatrics and sedation guidelines by non-anesthesiologists for the adult population were performed. RESULTS: From the available studies three sedation protocols are highlighted. Propofol, which seems to offer the best balance between efficacy and safety is rarely used by non-anesthesiologists mainly because of legal restrictions. Ketamine and a combination of a benzodiazepine and an opioid are more frequently used. Data regarding other sedatives, anesthetics and adjuvant medications used for pediatric GI endoscopy are also presented. CONCLUSION: General anesthesia by a multidisciplinary team led by an anesthesiologist is preferred. The creation of sedation teams led by non-anesthesiologists and a careful selection of anesthetic drugs may offer an alternative, but should be in line with national legislation and institutional regulations. PMID:26240691

Combinatorial protein engineering of proteolytically resistant mesotrypsin inhibitors as candidates for cancer therapy.

PubMed

Cohen, Itay; Kayode, Olumide; Hockla, Alexandra; Sankaran, Banumathi; Radisky, Derek C; Radisky, Evette S; Papo, Niv

2016-05-15

Engineered protein therapeutics offer advantages, including strong target affinity, selectivity and low toxicity, but like natural proteins can be susceptible to proteolytic degradation, thereby limiting their effectiveness. A compelling therapeutic target is mesotrypsin, a protease up-regulated with tumour progression, associated with poor prognosis, and implicated in tumour growth and progression of many cancers. However, with its unique capability for cleavage and inactivation of proteinaceous inhibitors, mesotrypsin presents a formidable challenge to the development of biological inhibitors. We used a powerful yeast display platform for directed evolution, employing a novel multi-modal library screening strategy, to engineer the human amyloid precursor protein Kunitz protease inhibitor domain (APPI) simultaneously for increased proteolytic stability, stronger binding affinity and improved selectivity for mesotrypsin inhibition. We identified a triple mutant APPIM17G/I18F/F34V, with a mesotrypsin inhibition constant (Ki) of 89 pM, as the strongest mesotrypsin inhibitor yet reported; this variant displays 1459-fold improved affinity, up to 350 000-fold greater specificity and 83-fold improved proteolytic stability compared with wild-type APPI. We demonstrated that APPIM17G/I18F/F34V acts as a functional inhibitor in cell-based models of mesotrypsin-dependent prostate cancer cellular invasiveness. Additionally, by solving the crystal structure of the APPIM17G/I18F/F34V-mesotrypsin complex, we obtained new insights into the structural and mechanistic basis for improved binding and proteolytic resistance. Our study identifies a promising mesotrypsin inhibitor as a starting point for development of anticancer protein therapeutics and establishes proof-of-principle for a novel library screening approach that will be widely applicable for simultaneously evolving proteolytic stability in tandem with desired functionality for diverse protein scaffolds. © 2016 Authors; published by Portland Press Limited.

Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib.

PubMed

Hickinson, D Mark; Marshall, Gayle B; Beran, Garry J; Varella-Garcia, Marileila; Mills, Elizabeth A; South, Marie C; Cassidy, Andrew M; Acheson, Kerry L; McWalter, Gael; McCormack, Rose M; Bunn, Paul A; French, Tim; Graham, Alex; Holloway, Brian R; Hirsch, Fred R; Speake, Georgina

2009-06-01

Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an exploratory principal component analysis revealed a separation between the genomic profiles of sensitive and resistant cell lines. Subsequently, a hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A hypothesis-free analysis identified 46 gene transcripts that were strongly differentiated, seven of which had a known association with EGFR and head and neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed Affymetrix data, and EGFR gene mutation, amplification, and genomic gain correlated strongly with gefitinib sensitivity. We identified biomarkers that predict for in vitro responsiveness to gefitinib, seven of which have known association with EGFR and head and neck cancer. These in vitro predictive biomarkers may have potential utility in the clinic and warrant further investigation.

Transcatheter Arterial Embolization for Gastrointestinal Bleeding Associated with Gastric Carcinoma: Prognostic Factors Predicting Successful Hemostasis and Survival.

PubMed

Park, Sangik; Shin, Ji Hoon; Gwon, Dong-Il; Kim, Hyoung Jung; Sung, Kyu-Bo; Yoon, Hyun-Ki; Ko, Gi-Young; Ko, Heung Kyu

2017-07-01

To evaluate outcomes of transcatheter arterial embolization (TAE) for gastric cancer-related gastrointestinal (GI) bleeding and factors associated with successful TAE and improved survival after TAE. This retrospective study included 43 patients (34 men; age 60.6 y ± 13.6) with gastric cancer-related GI bleeding undergoing angiography between January 2000 and December 2015. Clinical course, laboratory findings, and TAE characteristics were reviewed. Technical success of TAE was defined as target area devascularization, and clinical success was defined as bleeding cessation with hemodynamic stability during 72 hours after TAE. Student t test was used for comparison of continuous variables, and Fisher exact test was used for categorical variables. Univariate and multivariate analysis were performed to identify predictors of successful TAE and 30-day survival after TAE. TAE was performed in 40 patients. Technical and clinical success rates of TAE were 85.0% and 65.0%, respectively. Splenic infarction occurred in 2 patients as a minor complication. Rebleeding after TAE occurred in 7 patients. Death related to bleeding occurred in 5 patients. Active bleeding (P = .044) and higher transfusion requirement (3.3 U ± 2.6 vs 1.8 U ± 1.7; P = .039) were associated with TAE failure. Successful TAE predicted improved 30-day survival after TAE on univariate and multivariate analysis (P = .018 and P = .022; odds ratio, 0.132). TAE for gastric cancer-associated GI bleeding may be a lifesaving procedure. Severe bleeding with a higher transfusion requirement and active bleeding on angiography predicted TAE failure. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?

PubMed

Krabbe, Laura-Maria; Lotan, Yair; Bagrodia, Aditya; Gayed, Bishoy A; Darwish, Oussama M; Youssef, Ramy F; Bolenz, Christian; Sagalowsky, Arthur I; Raj, Ganesh V; Shariat, Shahrokh F; Kapur, Payal; Margulis, Vitaly

2014-04-01

Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel. Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status. During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score. Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bowel perforation in type IV vascular Ehlers-Danlos syndrome. A systematic review.

PubMed

El Masri, H; Loong, T-H; Meurette, G; Podevin, J; Zinzindohoue, F; Lehur, P-A

2018-05-01

Spontaneous gastrointestinal (GI) perforation is a well-known complication occurring in patients suffering from Type IV vascular Ehlers-Danlos syndrome (EDS IV). The aim of the present study was to review the current literature on spontaneous GI perforation in EDS IV and illustrate the surgical management and outcome when possible. A systematic review of all the published data on EDS IV patients with spontaneous GI perforation between January 2000 and December 2015 was conducted using three major databases PUBMED, EMBASE, and Cochrane Central Register of Controlled Trails. References of the selected articles were screened to avoid missing main articles. Twenty-seven published case reports and four retrospective studies, including 31 and 527 cases, respectively, matched the search criteria. A case from our institution was added. Mean age was 26 years (range 6-64 years). The most frequent site of perforation was the colon, particularly the sigmoid, followed by small bowel, upper rectum, and finally stomach. The majority of cases were initially managed with Hartmann's procedure. In recurrent perforations, total colectomy was performed. The reperforation rate was considerably higher in the "partial colectomy with anastomosis" group than in the Hartmann group. Colonic perforation is the most common spontaneous GI perforation in EDS IV patients. An unexpected fragility of the tissues should raise the possibility of a connective tissue disorder and prompt further investigation with eventual management of these high-risk patients with a multidisciplinary team approach in dedicated centres. In the emergency setting, a Hartmann procedure should be performed.

The Role of MMP-1 in Breast Cancer Growth and Metastasis to the Brain in a Xenograft Model

DTIC Science & Technology

2012-12-07

growing metastases [32]. Fitzgerald et al. [33] reported high proliferation rates of brain metastases of this cell line, as we also found for metastases of...EP: Brain metastases: the HER2 paradigm. Clin Cancer Res 2007, 13:1648–1655. 3. Palmieri D, Fitzgerald D, Shreeve SM, et al: Analyses of resected...2005, 87:273–286. 9. Murray GI, Duncan ME, O’Neil P, et al: Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat

The outcomes of esophageal and gastric cancer treatments in a retrospective study, single center experience.

PubMed

Alimoghaddam, Kamran; Jalali, Arash; Aliabadi, Leyla Sharifi; Ghaffari, Fatemeh; Maheri, Roghieh; Eini, Ezzat; Mashhadireza, Maryam; Mousavi, Seied Asadollah; Bahar, Babak; Jahani, Mohammad; Ghavamzadeh, Ardeshir

2014-01-01

Esophageal and gastric cancers are among the most common cancers in Iran. Usually survival of these cases is poor despite of treatment. Here we studied outcome of these cases in our center to have an estimation of general prognosis of patients. In this retrospective study, we reviewed the data of patient's files before treatment, including cancer stage at diagnosis, types of treatments and outcomes. We studied 368 patients treated between 1995 and 2011. The study included 368 patients (248 [67.4%] males and 120 [32.6%] females) with a median age of 58 (range: 23 - 94). Sixty nine patients (18.8%) had esophageal cancer with a median age of 58.5 years (range: 33 - 84), and 47.8% (33/69) of whom were male. Sixty five (17.7%) were reported to have gastro-esophageal junction (GEJ) with a median age of 62.0 (range: 32 - 94), among them 72.3% (47/65) of whom were male and finally Two hundred thirty four (63.6%) had gastric cancer with a median age of 57.0 (range: 23 - 82), which 71.8% (168/234) of whom were male. The Median follow-up was 10 months. The majority of patients were diagnosed at an advanced stage of disease. Stage III or IV was observed in 65.0% (39/60) of patients with esophageal cancer, 75.0% (33/44) with GEJ cancer and 65.4% (121/185) with gastric cancer. In this study, 58% of patients with esophageal cancer, 50.8% with GEJ and gastric cancers had unresectable disease or metastases at presentation. One-year EFS was 51.8% (95% CI: 39.8 - 67.3%), 32.8% (95% CI: 22.1 - 48.7%), and 56.7% (95% CI: 50.1 - 64.3%) in patients with esophageal, GEJ and gastric cancers, respectively (p = 0.002). The 1-year OS was 54.5% (95% CI: 42.6 - 69.8%), 39.5% (95 CI: 28.1 - 55.5%), and 68.2% (95% CI: 61.8 - 75.3%), respectively (p < 0.001). Cancers of the upper gastrointestinal (GI) tract contribute to the high mortality and morbidity rates because they are more likely to be diagnosed at late or advanced stages of disease. Cancer of the GEJ has a poor prognosis compared to esophageal and gastric cancers. Moreover, treatment protocols may need improvement to achieve better results.

Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer.

PubMed

Koontz, Bridget F; Chino, Junzo; Lee, W Robert; Hahn, Carol A; Buckley, Niall; Huang, Samuel; Kim, Jay; Reagan, Robert; Joyner, Raymond; Anscher, Mitchell S

2009-01-01

Dose escalation has been shown beneficial in prostate cancer. Brachytherapy (BT) provides an opportunity for dose escalation beyond what can be safely delivered using only teletherapy methods. The purpose of this study was to determine cancer control and morbidity of external beam radiation therapy (EBRT) plus low-dose-rate (LDR) BT boost in patients with prostate cancer treated at Duke University Health System. Between June 1997 and August 2007, 199 patients were consecutively treated at our facility with 46Gy EBRT followed by 100Gy palladium-103 ((103)Pd) or 120Gy iodine-125 ((125)I) LDR prostate implant. Treatment characteristics and followup data were retrospectively analyzed. Intermediate risk was defined as T2b-c, Gleason score 7 (GS 7), or prostate-specific antigen (PSA) of 10.1-19.9ng/mL. High risk was defined as GS 8-10, PSA>20, T3+, or two intermediate risk factors. The Radiation Therapy Oncology Group toxicity scale was used to report morbidity for gastrointestinal (GI) and genitourinary (GU) effects. PSA recurrence was defined as nadir+2ng/mL. Median followup was 4.2 years for all patients, 4.8 years for high-risk patients. Risk categories were as follows: 20% low risk, 47% intermediate risk, and 33% high risk. Forty five percent of patients received adjuvant androgen deprivation therapy (ADT). The median length of time since end of ADT to last followup was 2.7 years in all patients, 2.0 years for high-risk patients. Five-year biochemical relapse-free survival was 87% for all, 81% for high-risk patients. PSA control was similar at 92% for all and 86% for high-risk patients. Five-year actuarial risk of any and Grade 3 late GI morbidity was 38% and 7% respectively, and any and Grade 3 late GU morbidity was 21% and 3%, respectively. There were no significant differences in risk of Grade 2+GI or GU morbidity with choice of isotope. EBRT plus LDR BT has acceptable morbidity and, with 5-year followup, provides excellent cancer control even in high-risk patients.

Detection of gastritis by /sup 99m/Tc-labeled red-blood-cell scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilton, G.P.; Wahl, R.L.; Juni, J.E.

1984-10-01

Gastritis is a common condition, with a variety of causes, that is diagnosed most often by barium upper gastrointestinal tract series or endoscopy. The authors report a case in which gastritis without active bleeding was apparent in scintiscans obtained during the evaluation of GI bleeding using /sup 99m/Tc-labeled red blood cells (TcRBC). The scintigraphic findings that suggest gastritis are described.

Water-soluble upper GI based on clinical findings is reliable to detect anastomotic leaks after laparoscopic gastric bypass.

PubMed

Katasani, V G; Leeth, R R; Tishler, D S; Leath, T D; Roy, B P; Canon, C L; Vickers, S M; Clements, R H

2005-11-01

Anastomotic leak after laparoscopic Roux-en-Y gastric bypass (LGB) is a major complication that must be recognized and treated early for best results. There is controversy in the literature regarding the reliability of upper GI series (UGI) in diagnosing leaks. LGB was performed in patients meeting NIH criteria for the surgical treatment of morbid obesity. All leaks identified at the time of surgery were repaired with suture and retested. Drains were placed at the surgeon's discretion. Postoperatively, UGI was performed by an experienced radiologist if there was a clinical suspicion of leak. From September 2001 until October 2004, a total of 553 patients (age 40.4 +/- 9.2 years, BMI 48.6 +/- 7.2) underwent LGB at UAB. Seventy-eight per cent (431 of 553) of patients had no clinical evidence suggesting anastomotic leak and were managed expectantly. Twenty-two per cent (122 of 553) of patients met at least one inclusion criteria for leak and underwent UGI. Four of 122 patients (3.2%) had a leak, two from anastomosis and two from the perforation of the stapled end of the Roux limb. No patient returned to the operating room without a positive UGI. High clinical suspicion and selectively performed UGI based on clinical evidence is reliable in detecting leaks.

Endoscopic Ultrasound of the Upper Gastrointestinal Tract and Mediastinum: Diagnosis and Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prasad, Priyajit; Wittmann, Johannes; Pereira, Stephen P.

2006-12-15

Endoscopic ultrasound (EUS) has developed significantly over the last two decades and has had a considerable impact on the imaging and staging of mass lesions within or in close proximity to the gastrointestinal (GI) tract. In conjunction with conventional imaging such as helical computed tomography and magnetic resonance imaging, the indications for EUS include (1) differentiating between benign and malignant lesions of the mediastinum and upper GI tract, (2) staging malignant tumors of the lung, esophagus, stomach, and pancreas prior to surgery or oncological treatment, (3) excluding common bile duct stones before laparoscopic cholecystectomy, thereby avoiding the need for endoscopicmore » retrograde cholangiopancreatography (ERCP) in some patients, and (4) assessing suspected lesions that are either equivocal or not seen on conventional imaging. In recent years, EUS has charted a course similar to that taken by ERCP, evolving from a purely diagnostic modality to one that is interventional and therapeutic. These indications include (5) obtaining a tissue diagnosis by EUS-guided fine-needle aspiration or trucut-type needle biopsy and (6) providing therapy such as coeliac plexus neurolysis and pancreatic pseudocyst drainage-in many cases, more accurately and safely than conventional techniques. Emerging investigational techniques include EUS-guided enteric anastomosis formation and fine-needle injection therapy for malignant disease.« less

A Preliminary Observation of Weight Loss Following Left Gastric Artery Embolization in Humans

PubMed Central

Gunn, Andrew J.; Oklu, Rahmi

2014-01-01

Background/Objectives. Embolization of the left gastric artery (LGA), which preferentially supplies the gastric fundus, has been shown to produce weight loss in animal models. However, weight loss after LGA embolization in humans has not been previously established. The aim of this study was to evaluate postprocedural weight loss in patients following LGA embolization. Subjects/Methods. A retrospective analysis of the medical records of patients who underwent LGA embolization for upper gastrointestinal (GI) bleeding was performed. Postprocedural weight loss in this group was compared to a control group of patients who had undergone embolization of other arteries for upper GI bleeding. Results. The experimental group (N = 19) lost an average of 7.3% of their initial body weight within three months of LGA embolization, which was significantly greater than the 2% weight loss observed in the control group (N = 28) (P = 0.006). No significant differences were seen between the groups in preprocedural body mass index (BMI), age, postprocedural care in the intensive care unit, history of malignancy, serum creatinine, or left ventricular ejection fraction. Conclusions. The current data suggest that body weight in humans may be modulated via LGA embolization. Continued research is warranted with prospective studies to further investigate this phenomenon. PMID:25349724

[Laparoscopic Proximal Gastrectomy as a Surgical Treatment for Upper Third Early Gastric Cancer].

PubMed

Park, Do Joong; Park, Young Suk; Ahn, Sang Hoon; Kim, Hyung Ho

2017-09-25

Recently, the incidence of upper third gastric cancer has increased, and with it the number of endoscopic submucosal dissection (ESD) procedures performed has been increasing. However, if ESD is not indicated or non-curable, surgical treatment may be necessary. In the case of lower third gastric cancer, it is possible to preserve the upper part of the stomach; however, in the case of upper third gastric cancer, total gastrectomy is still the standard treatment option, regardless of the stage. This is due to the complications associated with upper third gastric cancer, such as gastroesophageal reflux after proximal gastrectomy rather than oncologic problems. Recently, the introduction of the double tract reconstruction method after proximal gastrectomy has become one of the surgical treatment methods for upper third early gastric cancer. However, since there has not been a prospective comparative study evaluating its efficacy, the ongoing multicenter prospective randomized controlled trial (KLASS-05) comparing laparoscopic proximal gastrectomy with double tract reconstruction and laparoscopic total gastrectomy is expected to be important for determining the future of treatment of upper third early gastric cancer.

Upper gastrointestinal series after Roux-en-Y gastric bypass for morbid obesity: effectiveness in leakage detection. a systematic review of the literature.

PubMed

Quartararo, Giovanni; Facchiano, Enrico; Scaringi, Stefano; Liscia, Gadiel; Lucchese, Marcello

2014-07-01

The aim of this study is to evaluate the results of routine and selective postoperative upper gastrointestinal series (UGIS) after Roux-en-Y gastric bypass (RYGB) for morbid obesity in different published series to assessing its utility and cost-effectiveness. A search in PubMed's MEDLINE was performed for English-spoken articles published from January 2002 to December 2012. Keywords used were upper GI series, RYGB, and obesity. Only cases of anastomotic leaks were considered. A total of 22 studies have been evaluated, 15 recommended a selective use of postoperative UGIS. No differences in leakage detection or in clinical benefit between routine and selective approaches were found. Tachycardia and respiratory distress represent the best criteria to perform UGIS for early diagnosis of anastomotic leak after a RYGB.

Mediterranean Diet Pyramid: A Proposal for Italian People

PubMed Central

D’Alessandro, Annunziata; De Pergola, Giovanni

2014-01-01

Bread was a staple in the traditional Mediterranean diet of the early 1960s, as well as nowadays; however, it was a stone ground sourdough bread in Nicotera and probably in the Greek cohorts of the Seven Countries Study. In the present review, the nutritional characteristics of this food are analyzed in relation to its protective effects on coronary heart disease, metabolic diseases and cancer. According to our traditions, cultural heritage and scientific evidence, we propose that only cereal foods with low glycemic index (GI) and rich in fiber have to be placed at the base of the Mediterranean diet pyramid, whereas refined grains and high GI starchy foods have to be sited at the top. PMID:25325250

GI Stromal Tumors: 15 Years of Lessons From a Rare Cancer.

PubMed

Cioffi, Angela; Maki, Robert G

2015-06-01

A confluence of factors, most prominently the recognition of GI stromal tumor (GIST) as a specific sarcoma subtype and the availability of imatinib, led to the "Big Bang" of GIST therapy (ie, the successful treatment of the first patient with GIST with imatinib in 2000). The trail blazed by imatinib for chronic myelogenous leukemia and GIST has become a desired route to regulatory approval of an increasing number of oral kinase inhibitors and other novel therapeutics. In this review, the status of GIST management before and after GIST's "Big Bang" and new steps being taken to further improve on therapy are reviewed. © 2015 by American Society of Clinical Oncology.

Mediterranean diet pyramid: a proposal for Italian people.

PubMed

D'Alessandro, Annunziata; De Pergola, Giovanni

2014-10-16

Bread was a staple in the traditional Mediterranean diet of the early 1960s, as well as nowadays; however, it was a stone ground sourdough bread in Nicotera and probably in the Greek cohorts of the Seven Countries Study. In the present review, the nutritional characteristics of this food are analyzed in relation to its protective effects on coronary heart disease, metabolic diseases and cancer. According to our traditions, cultural heritage and scientific evidence, we propose that only cereal foods with low glycemic index (GI) and rich in fiber have to be placed at the base of the Mediterranean diet pyramid, whereas refined grains and high GI starchy foods have to be sited at the top.

Molecular Characteristics of Multicorn, a New Large Proteolytic Assembly and Potential Anti-Cancer Drug Target, in Human Breast Cancer Cells

DTIC Science & Technology

2005-05-01

modifications: peptide N-terminal glutamine to pyroglutamic transformation, oxidation of methionine, acetylation of protein N-terminus, and...or identical with human tripeptidyl peptidase II (TPPII) with a sequence of 1249 amino acids , accession number CAH72179, GI:55661755, derived from the...34In- Gel" Digestion Procedure for the Micropreparation of Internal Protein Fragments for Amino Acid Sequencing. Anal. Biochem., 224, 451-455. Osmulski

Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

PubMed Central

Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

2011-01-01

Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

Extraskeletal osteosarcoma, telangiectatic variant arising from the small bowel mesentery.

PubMed

Hussain, Muhammad I; Al-Akeely, Mohammed H; Alam, Mohammed K; Jasser, Nayel A

2011-09-01

Extraskeletal osteosarcoma (EOS) is a highly aggressive and rare malignant soft tissue tumor, characterized by the production of neoplastic osseous tissue without attachment to the bone or periosteum. It rarely involves the visceral organs. Only 3 cases of mesenteric EOS have been reported in English literature. Here, we describe a male patient of 40 years, who was diagnosed to have EOS arising from small bowel mesentery. This patient presented with lower gastrointestinal (GI) bleeding. Upper GI endoscopy and colonoscopy were normal. Computed tomography scan demonstrated a well defined multi-loculated mixed density mass lesion measuring about 13x7x7 cm in lower abdomen adjacent to small bowel loops with liver metastasis. Palliative en bloc resection of tumor with adjacent small bowel was performed. The histopathology revealed a telangiectatic type osteosarcoma of mesentery. Diagnosis of EOS, its management and the outcome in context of the current literature are discussed.

A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm.

PubMed

Khemissa, Faïza; Mineur, Laurent; Amsellem, Caroline; Assenat, Eric; Ramdani, Mohamed; Bachmann, Patrick; Janiszewski, Chloé; Cristiani, Isabelle; Collin, Fideline; Courraud, Julie; de Forges, Hélène; Dechelotte, Pierre; Senesse, Pierre

2016-03-01

Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect(®) (CP) or a control isocaloric diet (without TGF-β2 or glutamine). Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3-4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3-4 hematological toxicities or reasons for treatment interruption. This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Introducing sexual orientation and gender identity into the electronic health record: one academic health center's experience.

PubMed

Callahan, Edward J; Sitkin, Nicole; Ton, Hendry; Eidson-Ton, W Suzanne; Weckstein, Julie; Latimore, Darin

2015-02-01

Many U.S. populations experience significant health disparities. Increasing health care providers' awareness of and education about sexual orientation (SO) and gender identity (GI) diversity could help reduce health disparities among lesbian, gay, bisexual, and transgender (LGBT) patients. The authors share the University of California, Davis, Health System's (UCDHS's) experience as it became the first U.S. academic health center to formally introduce patient SO/GI demographic data into its electronic health record (EHR) as a step toward reducing LGBT health disparities. Adding these data to the EHR initially met with resistance. The authors, members of the UCDHS Task Force for Inclusion of SO/GI in the EHR, viewed this resistance as an invitation to educate leaders, providers, and staff about LGBT health disparities and to expose providers to techniques for discussing SO/GI with patients. They describe the strategies they employed to effect institutional culture change, including involvement of senior leadership, key informant interviews, educational outreach via grand rounds and resident workshops, and creation of a patient safety net through inviting providers to self-identify as welcoming LGBT patients. The ongoing cultural change process has inspired spin-off projects contributing to an improved climate for LGBT individuals at UCDHS, including an employee organization supporting SO/GI diversity, support for and among LGBT medical learners through events and listservs, development and implementation of an LGBT health curriculum, and creation of peer navigator programs for LGBT patients with cancer. The authors reflect on lessons learned and on institutional pride in and commitment to providing quality care for LGBT patients.

Indomethacin-5-fluorouracil-methyl ester dry emulsion: a potential oral delivery system for 5-fluorouracil.

PubMed

Wang, Jing; Hu, Yanchen; Li, Ling; Jiang, Tongying; Wang, Siling; Mo, Fengkui

2010-06-01

To produce a combined effect of indomethacin (IDM) and 5-fluorouracil (5FU) for cancer therapy, the side effects of IDM on the gastrointestinal (GI) tract were reduced and the oral adsorption of 5FU was improved. Indomethacin-5-fluorouracil-methyl ester (IFM) dry emulsion was prepared and evaluated as a potential oral delivery system for 5FU. IFM was synthesized by formation of an ester between IDM and 5FU intermediate and then characterized by structure, melting point, solubility, apparent partition coefficient, and incubation with GI tract contents and plasma. Gum acacia and sodium carboxymethyl cellulose (CMC-Na) were applied as the adsorbent and solid carrier to prepare IFM dry emulsion. IFM dry emulsion was then characterized by reconstitution in water and in situ intestinal perfusion experiment. Physicochemical properties of the new synthesized compound confirmed the formation of IFM. Incubation of IFM in the contents of the GI tract and plasma revealed that IFM was not relatively stable in GI contents during the time period of transit through the GI tract, whereas it was very unstable in plasma and released 5FU rapidly. The IFM dry emulsion could be easily reconstituted in water, and the mean particle size was 2.416 microm. The absorption rate constant (K) for IFM with concentration of 2, 5, and 10 microg/mL in the in situ perfusion experiment were 0.473, 0.423, and 0.433/h, respectively, demonstrating passive diffusion of IFM across the biological membranes. This study indicates that the IFM dry emulsion may represent a potentially useful oral delivery system for 5FU.

Towards a Population Synthesis Model of Objects formed by Self-Gravitating Disc Fragmentation and Tidal Downsizing

NASA Astrophysics Data System (ADS)

Forgan, Duncan; Rice, Ken

2013-07-01

Recently, the gravitational instability (GI) model of giant planet and brown dwarf formation has been revisited and recast into what is often referred to as the "tidal downsizing" hypothesis. The fragmentation of self-gravitating protostellar discs into gravitationally bound embryos - with masses of a few to tens of Jupiter masses, at semi major axes above 30 - 40 AU - is followed by a combination of grain sedimentation inside the embryo, radial migration towards the central star and tidal disruption of the embryo's upper layers. The properties of the resultant object depends sensitively on the timescales upon which each process occurs. Therefore, GI followed by tidal downsizing can theoretically produce objects spanning a large mass range, from terrestrial planets to giant planets and brown dwarfs. Whether such objects can be formed in practice, and what proportions of the observed population they would represent, requires a more involved statistical analysis. We present a simple population synthesis model of star and planet formation via GI and tidal downsizing. We couple a semi-analytic model of protostellar disc evolution to analytic calculations of fragmentation, initial embryo mass, grain growth and sedimentation, embryo migration and tidal disruption. While there are key pieces of physics yet to be incorporated, it represents a first step towards a mature statistical model of GI and tidal downsizing as a mode of star and planet formation. We show results from four runs of the population synthesis model, varying the opacity law and the strength of migration, as well as investigating the effect of disc truncation during the fragmentation process.

Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis

PubMed Central

Geusens, Piet; Lems, Willem

2008-01-01

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver. PMID:18728796

No increase in prevalence of somatization in functional vs organic dyspepsia: a cross-sectional survey.

PubMed

Gracie, D J; Bercik, P; Morgan, D G; Bolino, C; Pintos-Sanchez, M I; Moayyedi, P; Ford, A C

2015-07-01

Psychological factors are associated with functional gastrointestinal (GI) disorders. Literature suggests that somatization is associated with functional dyspepsia (FD). However, the relationship between organic dyspepsia (OD), FD, and FD subtypes and somatization is poorly described. We aimed to examine this issue in a cross-sectional study of secondary care patients. Demographic and GI symptom data were collected from 4224 adult patients via the Rome III questionnaire. Somatization data were collected using the patient health questionnaire-12. Mean somatization score and number of somatic symptoms were compared between patients with organic and FD, and between FD subtypes using analysis of variance. The same comparison was undertaken for the proportion of patients reporting individual somatic symptoms. Exactly, 783 patients met criteria for dyspepsia, of whom 231 (29.5%) had organic disease following upper GI endoscopy. Mean somatization scores and number of somatic symptoms were no higher in functional vs OD (p = 0.23; p = 0.19). In addition, while the prevalence of somatization in FD was relatively high, there was no difference in severity of somatization in FD subgroups. Somatization is associated with functional and OD to the same degree. Overall severity of somatization did not appear to vary according to FD subtype. © 2015 John Wiley & Sons Ltd.

Gastrointestinal Bleeding Following LVAD Placement from Top to Bottom.

PubMed

Cushing, Kelly; Kushnir, Vladimir

2016-06-01

Left ventricular assist devices (LVADs) are an increasingly prevalent form of mechanical support for patients with end-stage heart failure. These devices can be implanted both as a bridge to transplant and as definitive/destination therapy. Gastrointestinal (GI) bleeding is one of the most common and recalcitrant long-term complications following LVAD implantation, with an incidence approaching 30 %. This review will discuss what is known about the pathophysiology of GI bleeding in LVADs and the currently available options for medical and/or endoscopic management. The pathophysiology of bleeding is multifactorial, with hemodynamic alterations, acquired von Willebrand factor deficiency, and coagulopathy being most often implicated. The majority of bleeding events in this population result from angioectasias and gastroduodenal erosive disease. While these bleeding events are significant and often require transfusion therapy, they are rarely life threatening. Endoscopy remains the standard of care with upper endoscopy offering the highest diagnostic yield in these patients. However, the effectiveness of endoscopic hemostasis in this population is not well established. A small number of studies have evaluated medical therapy and alterations in LVAD settings as a means of preventing or treating bleeding with variable results. In summary, GI bleeding with LVADs is a common occurrence and will continue to be as more LVADs are being performed for destination therapy.

Upper functional gastrointestinal disorders in young adults.

PubMed

Adibi, Peyman; Behzad, Ebrahim; Shafieeyan, Mohammad; Toghiani, Ali

2012-01-01

Functional Gastrointestinal disorders (FGID) are common disorders in gastroenterology which are common in young adults. The aim of this study is evaluating the prevalence of upper FGID in iranian young adults. This was a cross-sectional study which was on 995 persons who were going to marry. A ROME III based questionnaire was used to determine the frequency of upper GI Syndromes among the sample population. Our results determined 74 subjects had functional dyspepsia (36 subjects diagnosed as postprandial distress syndrome patient and Epigastric pain syndrome was seen in 38 subjects). Functional heartburn was diagnosed in 52 participants. Globus was seen in 35 subjects and 41 had unspecified excessive belching. Many epidemiologic studies were done all around the world but there are different reports about prevalence and incidence of FGIDs. Our results were agreed with reported prevalence of FGIDs in Iran in adults. And our findings were agreed with some other Asian studies.

Effect of the glycemic index of the diet on weight loss, modulation of satiety, inflammation, and other metabolic risk factors: a randomized controlled trial.

PubMed

Juanola-Falgarona, Martí; Salas-Salvadó, Jordi; Ibarrola-Jurado, Núria; Rabassa-Soler, Antoni; Díaz-López, Andrés; Guasch-Ferré, Marta; Hernández-Alonso, Pablo; Balanza, Rafael; Bulló, Mònica

2014-07-01

Low-glycemic index (GI) diets have been proven to have beneficial effects in such chronic conditions as type 2 diabetes, ischemic heart disease, and some types of cancer, but the effect of low-GI diets on weight loss, satiety, and inflammation is still controversial. We assessed the efficacy of 2 moderate-carbohydrate diets and a low-fat diet with different GIs on weight loss and the modulation of satiety, inflammation, and other metabolic risk markers. The GLYNDIET study is a 6-mo randomized, parallel, controlled clinical trial conducted in 122 overweight and obese adults. Participants were randomly assigned to one of the following 3 isocaloric energy-restricted diets for 6 mo: 1) a moderate-carbohydrate and high-GI diet (HGI), 2) a moderate-carbohydrate and low-GI diet (LGI), and 3) a low-fat and high-GI diet (LF). At weeks 16 and 20 and the end of the intervention, changes in body mass index (BMI; in kg/m(2)) differed significantly between intervention groups. Reductions in BMI were greater in the LGI group than in the LF group, whereas in the HGI group, reductions in BMI did not differ significantly from those in the other 2 groups (LGI: -2.45 ± 0.27; HGI: -2.30 ± 0.27; LF: -1.43 ± 0.27; F = 4.616, P = 0.012; pairwise comparisons: LGI compared with HGI, P = 1.000; LGI compared with LF, P = 0.016; HGI compared with LF, P = 0.061). The decrease in fasting insulin, homeostatic model assessment of insulin resistance, and homeostatic model assessment of β cell function was also significantly greater in the LGI group than in the LF group (P < 0.05). Despite this tendency for a greater improvement with a low-GI diet, the 3 intervention groups were not observed to have different effects on hunger, satiety, lipid profiles, or other inflammatory and metabolic risk markers. A low-GI and energy-restricted diet containing moderate amounts of carbohydrates may be more effective than a high-GI and low-fat diet at reducing body weight and controlling glucose and insulin metabolism. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN54971867. © 2014 American Society for Nutrition.

Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota

PubMed Central

Xiao, Hui-wen; Li, Yuan; Luo, Dan; Dong, Jia-li; Zhou, Li-xin; Zhao, Shu-yi; Zheng, Qi-sheng; Wang, Hai-chao; Cui, Ming; Fan, Sai-jun

2018-01-01

Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings. PMID:29371696

Cancer Cachexia: Cause, Diagnosis, and Treatment.

PubMed

Mattox, Todd W

2017-10-01

Patients with cancer frequently experience unintended weight loss due to gastrointestinal (GI) dysfunction caused by the malignancy or treatment of the malignancy. However, others may present with weight loss related to other symptoms not clearly associated with identifiable GI dysfunction such as anorexia and early satiety. Cancer cachexia (CC) is a multifactorial syndrome that is generally characterized by ongoing loss of skeletal muscle mass with or without fat loss, often accompanied by anorexia, weakness, and fatigue. CC is associated with poor tolerance of antitumor treatments, reduced quality of life (QOL), and negative impact on survival. Symptoms associated with CC are thought to be caused in part by tumor-induced changes in host metabolism that result in systemic inflammation and abnormal neurohormonal responses. Unfortunately, there is no single standard treatment for CC. Nutrition consequences of oncologic treatments should be identified early with nutrition screening and assessment. Pharmacologic agents directed at improving appetite and countering metabolic abnormalities that cause inefficient nutrient utilization are currently the foundation for treating CC. Multiple agents have been investigated for their effects on weight, muscle wasting, and QOL. However, few are commercially available for use. Considerations for choosing the most appropriate treatment include effect on appetite, weight, QOL, risk of adverse effects, and cost and availability of the agent.

Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening.

PubMed

Urakami, Shinji; Inoshita, Naoko; Oka, Suguru; Miyama, Yu; Nomura, Sachio; Arai, Masami; Sakaguchi, Kazushige; Kurosawa, Kazuhiro; Okaneya, Toshikazu

2018-02-01

To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers. © 2017 The Japanese Urological Association.

Accuracy of the water-siphon test associated to barium study in a high prevalence gastro-oesophageal reflux disease population: a novel statistical approach.

PubMed

Fiorentino, Eugenio; Matranga, Domenica; Pantuso, Gianni; Cabibi, Daniela; Bonventre, Sebastiano; Barbiera, Filippo

2010-06-01

Gastro-oesophageal reflux disease (GORD) is 'a condition which develops when the reflux of gastric content causes troublesome symptoms or complications'. Instrumental diagnostic tests generally used for GORD are 24-hour pH-metry and upper gastrointestinal (GI) endoscopy but barium study associated with provocative manoeuvres such as the water-siphon test (WST), has also been used for GORD. The aim of this paper was to estimate the accuracy of several tests in patients with GORD in a tertiary care setting, focusing on WST, which is rapid and non-invasive, simple to perform and well-tolerated by patients. A total of 172 consecutive patients, symptomatic for reflux referred to a tertiary medical centre, were considered and data regarding the WST, 24-hour pH-metry, upper GI endoscopy with histology were analysed using latent class analysis, a multivariable statistical method for estimating the accuracy of tests when a gold standard is not available. The overall proportion of GORD in the sample was estimated at 0.664 [95% confidence interval (CI) = (0.589; 0.731)]. WST proved to be the most sensitive [Se = 0.886; 95% CI = (0.688; 1.000)] compared with pH-metry [Se = 0.620; 95% CI = (0.493; 0.745)] and endoscopy with histology [Se = 0.534; 95% CI = (0.273; 0.789)]. It was less specific [Sp = 0.537; 95% CI = (0.003; 1.000)] than pH-metry [Sp = 0.547; 95% CI = (0.281; 0.813)], and even less than endoscopy with histology [Sp = 0.862; 95% CI = (0.495; 1.00)]. Positive predictive values were estimated at 0.792 [95% CI = (0.721; 0.862)] for WST, 0.731 [95% CI = (0.643; 0.819)] for pH-metry and 0.886 [95% CI = (0.811; 0.961)] for endoscopy with histology. Negative predictive values were estimated at 0.707 [95% CI = (0.573; 0.841)] for WST, 0.422 [95% CI = (0.310; 0.534)] for pH-metry and 0.484 [95% CI = (0.387; 0.581)] for endoscopy with histology. Water-siphon test might possibly be useful in patients with suspected GORD because it is highly sensitive and predictive. A positive outcome of the WST associated with a barium study can certainly justify upper GI endoscopy and support any pharmacological treatment of GORD.

NK and NK-like T-cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status.

PubMed

Ko, Y H; Cho, E-Y; Kim, J-E; Lee, S-S; Huh, J-R; Chang, H-K; Yang, W-I; Kim, C-W; Kim, S-W; Ree, H J

2004-05-01

To analyse the clinicopathological findings of extranasal CD56+ cytotoxic T- or NK-cell lymphomas in different organs and to compare Epstein-Barr virus (EBV)+ and EBV- lymphoma of non-blastoid cytomorphology. Fifty-one cases of cCD3+ T-cell intracellular antigen (TIA-1)+ CD56+ lymphomas of extranodal/extranasal origin were included in the study. The primary sites of the CD56+ tumours were soft tissue (n = 10), the gastrointestinal (GI) tract (n = 13), the skin (n = 15), upper aerodigestive tract excluding nasal and nasopharyngeal regions (n = 11), the testis (n = 1), and parotid gland (n = 1). TCR gene rearrangement was detected in seven of 47 cases examined (16%). EBV was positive in 39 of 51 cases (76%). The positive rate of EBV was higher in tumours of soft tissue (80%), GI tract (92%), and skin (80%), and lowest in the upper aerodigestive tract excluding the nasal and nasopharyngeal region (50%). Tumours of the soft tissue and the upper aerodigestive tract tended to present with localized disease (P = 0.002). The 2-year survival rate was lowest for tumours of the GI tract (P = 0.0256). EBV- TCR- lymphoma showed less necrosis (P = 0.0133) and a better 2-year survival rate (P = 0.0066) than EBV+ TCR- lymphoma. Patients with EBV+ TCR+ lymphomas tended to present with localized disease, more often than EBV+ TCR- lymphoma (P = 0.0186). Significant prognostic factors in all CD56+ lymphomas were the site (P = 0.0256), EBV status (P = 0.0026), necrosis with or without perforation (P = 0.0338) and the presence of pleomorphic large tumour cells (P = 0.0428). Cox's regression analysis adjusting for other pathological parameters showed EBV status to be the only independent prognostic factor (P = 0.018). Extranodal CD56+ EBV- lymphoma at extranasal sites is a clinically less aggressive malignancy and displays less necrosis than CD56+ EBV+ lymphoma. Because CD56+ EBV+ TCR+ lymphomas show similar pathological and clinical findings to CD56+ EBV+ TCR- lymphomas, nasal-type NK/T-cell lymphomas at extranasal sites should be diagnosed as such on the basis of EBV+, cytotoxic T or NK phenotype irrespective of the genotype determined by molecular study.

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodda, Sree; Tyldesley, Scott; Department of Surgery, University of British Columbia, Vancouver, British Columbia

Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. Methods and Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GUmore » and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. Results: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). Conclusions: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of erectile dysfunction were observed.« less

ACG Clinical Guideline: Management of Patients With Acute Lower Gastrointestinal Bleeding.

PubMed

Strate, Lisa L; Gralnek, Ian M

2016-04-01

This guideline provides recommendations for the management of patients with acute overt lower gastrointestinal bleeding. Hemodynamic status should be initially assessed with intravascular volume resuscitation started as needed. Risk stratification based on clinical parameters should be performed to help distinguish patients at high- and low-risk of adverse outcomes. Hematochezia associated with hemodynamic instability may be indicative of an upper gastrointestinal (GI) bleeding source and thus warrants an upper endoscopy. In the majority of patients, colonoscopy should be the initial diagnostic procedure and should be performed within 24 h of patient presentation after adequate colon preparation. Endoscopic hemostasis therapy should be provided to patients with high-risk endoscopic stigmata of bleeding including active bleeding, non-bleeding visible vessel, or adherent clot. The endoscopic hemostasis modality used (mechanical, thermal, injection, or combination) is most often guided by the etiology of bleeding, access to the bleeding site, and endoscopist experience with the various hemostasis modalities. Repeat colonoscopy, with endoscopic hemostasis performed if indicated, should be considered for patients with evidence of recurrent bleeding. Radiographic interventions (tagged red blood cell scintigraphy, computed tomographic angiography, and angiography) should be considered in high-risk patients with ongoing bleeding who do not respond adequately to resuscitation and who are unlikely to tolerate bowel preparation and colonoscopy. Strategies to prevent recurrent bleeding should be considered. Nonsteroidal anti-inflammatory drug use should be avoided in patients with a history of acute lower GI bleeding, particularly if secondary to diverticulosis or angioectasia. Patients with established high-risk cardiovascular disease should not stop aspirin therapy (secondary prophylaxis) in the setting of lower GI bleeding. [corrected]. The exact timing depends on the severity of bleeding, perceived adequacy of hemostasis, and the risk of a thromboembolic event. Surgery for the prevention of recurrent lower gastrointestinal bleeding should be individualized, and the source of bleeding should be carefully localized before resection.

Practice and Impact of Multidisciplinary Tumor Boards on Patient Management: A Prospective Study

PubMed Central

Charara, Raghid N.; Kreidieh, Firas Y.; Farhat, Rania A.; Al-Feghali, Karine A.; Khoury, Katia E.; Haydar, Ali; Nassar, Lara; Berjawi, Ghina; Shamseddine, Ali

2017-01-01

Purpose Multidisciplinary tumor boards (MTBs) have become commonplace. The use, attendance, and function of MTBs need continued assessment and improvement. Methods We prospectively recorded and assessed all cases presented at MTBs between October 2013 and December 2014. Data were collected before and during each MTB. Data were analyzed using SPSS for Windows version 23 (SPSS, Chicago, IL). Results Five hundred three cases were presented: 234 cases (46%) at GI cancer MTBs, 149 cases (29.6%) at breast cancer MTBs, 69 cases (13.7%) at thoracic/head and neck cancer MTBs, and 51 cases (10.7%) at neuro-oncology MTBs. A total of 86.7% of MTB cases were presented to make plans for management. Plans for upfront management were made in 67% of the breast cancer cases, 63% of GI cases, 59% of thoracic/head and neck cases, and 49% of neuro-oncology cases. Three hundred ninety-four cases (78.3%) were presented by medical oncologists, whereas only 74 cases (14.7%) were presented by surgeons, and 10 cases (2%) were presented by radiation oncologists. The majority of MTBs, with the exception of the neurosurgery MTBs, were led by medical oncologists. Surgeons presented the least number of cases but attended the most, and their contributions to discussions and decision making were essential. Conclusion MTBs enhance the multidisciplinary management of patients with cancer. Upfront multidisciplinary decision making should be considered as an indicator of benefit from MTBs, in addition to changes in management plans made at MTBs. Increasing the contributions of surgeons to MTBs should include bringing more of their own cases for discussion. PMID:28717766

Real-time fluorescence target/background (T/B) ratio calculation in multimodal endoscopy for detecting GI tract cancer

NASA Astrophysics Data System (ADS)

Jiang, Yang; Gong, Yuanzheng; Wang, Thomas D.; Seibel, Eric J.

2017-02-01

Multimodal endoscopy, with fluorescence-labeled probes binding to overexpressed molecular targets, is a promising technology to visualize early-stage cancer. T/B ratio is the quantitative analysis used to correlate fluorescence regions to cancer. Currently, T/B ratio calculation is post-processing and does not provide real-time feedback to the endoscopist. To achieve real-time computer assisted diagnosis (CAD), we establish image processing protocols for calculating T/B ratio and locating high-risk fluorescence regions for guiding biopsy and therapy in Barrett's esophagus (BE) patients. Methods: Chan-Vese algorithm, an active contour model, is used to segment high-risk regions in fluorescence videos. A semi-implicit gradient descent method was applied to minimize the energy function of this algorithm and evolve the segmentation. The surrounding background was then identified using morphology operation. The average T/B ratio was computed and regions of interest were highlighted based on user-selected thresholding. Evaluation was conducted on 50 fluorescence videos acquired from clinical video recordings using a custom multimodal endoscope. Results: With a processing speed of 2 fps on a laptop computer, we obtained accurate segmentation of high-risk regions examined by experts. For each case, the clinical user could optimize target boundary by changing the penalty on area inside the contour. Conclusion: Automatic and real-time procedure of calculating T/B ratio and identifying high-risk regions of early esophageal cancer was developed. Future work will increase processing speed to <5 fps, refine the clinical interface, and apply to additional GI cancers and fluorescence peptides.

Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer

ClinicalTrials.gov

2017-09-04

Cancer of Head; Cancer of Head and Neck; Cancer of Neck; Cancer of the Head; Cancer of the Head and Neck; Cancer of the Neck; Head and Neck Cancer; Head Cancer; Head Neoplasms; Head, Neck Neoplasms; Neck Cancer; Neck Neoplasms; Neoplasms, Head; Neoplasms, Head and Neck; Neoplasms, Neck; Neoplasms, Upper Aerodigestive Tract; UADT Neoplasms; Upper Aerodigestive Tract Neoplasms

[Anorexia-cachexia frequency and its gastrointestinal symptoms association in paliative patients at the Instituto Nacional de Cancerología, México].

PubMed

Pérez Camargo, Dana Aline; Allende Pérez, Silvia R; Meneses García, Abelardo; De Nicola Delfin, Luigina; Copca Mendoza, Erika Thalía; Sánchez López, Miriam S; Flores García, Martha Karen; Verástegui Avilés, Emma

2014-10-01

Anorexia-cachexia is a frequent syndrome among cancer patients, specially in late stages: the global prevalence of para-neoplastic anorexia-cachexia ranges between 20-40% in the diagnostic stage and between 70-80% in the late stage of the disease. The co-existence of functional or structural digestive abnormalities is frequently observed among cancer patients; this is a consequence of the tumor growth and of those systemic phenomena related to metabolism, which are affected by the relationship tumor-host specific to anorexia- cachexia. This study aimed at establishing the frequency of anorexia-cachexia, as well as its relationship to GI symptoms in the context of palliative care patients at the Instituto Nacional de Cancerología, México City. Analytic cross-sectional study including 100 patients diagnosed with late-stage cancer, age range 18-80, and a Karnofsky score > 50, as well as an ECOG <2; patients with a bad general health status were not allowed in the study. After reviewing inclusion and exclusion criteria, participants fulfilled the FAACT questionnaire, as well as the EGS. Patients recruitment was carried out by the Instituto Nacional de Cancerología. Results and discussion: Results show that 61% (n=61)of the patients had anorexia-cachexia, and 39% (n=39)did not. 56% of the sample participants (n=34) were women, and 44% (n=27) were men. GI symptoms associated with anorexia-cachexia were: nausea (p= 0.0001), vomiting (p=0.004), early satiety (p=0.0005), dysgeusia(p=0.0005) and dysphagia (p=0.001). Anorexia and cachexia are among the most devastating and frequent symptoms in late-stage cancer patients and they are also associated with GI symptoms affecting the physical, psychosocial and existential aspects of the patient's life. Data from this research validate the importance of an early nutrition support in palliative patients so that they can achieve a better quality of life. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Navesh K.; Li Tianyu; Chen, David Y.

Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dosemore » was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.« less

Synthesis of Gold Nanoparticles Using Garcinia Indica Fruit Rind Extract

NASA Astrophysics Data System (ADS)

Krishnaprabha, M.; Pattabi, Manjunatha

2016-10-01

This report presents the easily reproducible biosynthesis of gold nanoparticles (AuNPs) at room temperature with extract prepared using three year old dried Garcinia Indica (GI) fruit rind. Due to the presence of two major bioactive compounds garcinol and hydroxy citric acid, rinds of GI fruit exhibit anti-cancer and anti-obesity properties. The quantity of fruit rind extract directed the morphology of the as synthesized particles. The nucleation and growth of AuNPs and catalytic activity are studied using UV-Vis spectroscopy. The crystalline nature of biosynthesized AuNPs is corroborated by X-ray Diffraction techniques. The morphology is studied using field emission scanning electron microscopy (FESEM). Fourier transform infra-red (FTIR) spectroscopy analysis revealed that biomolecules were involved in the synthesis and capping of AuNPs. As the Fermi potential of noble metal NPs becomes more negative, they are used in various electron transfer processes. The AuNPs produced using GI extract showed excellent catalytic activity when used as a catalyst in the reduction of well-known toxic pollutant 4-Nitrophenol (4-NP) to 4-Aminophenol (4-AP) in the presence of excess sodium borohydride.

Tethered capsule OCT endomicroscopy for upper gastrointestinal tract imaging by using ball lens probe (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dong, Jing; Gora, Michalina J.; Reddy, Rohith; Trasischker, Wolfgang; Poupart, Oriane; Lu, Weina; Carruth, Robert W.; Grant, Catriona N.; Soomro, Amna R.; Tiernan, Aubrey R.; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.

2016-03-01

While endoscopy is the most commonly used modality for diagnosing upper GI tract disease, this procedure usually requires patient sedation that increases cost and mandates its operation in specialized settings. In addition, endoscopy only visualizes tissue superfically at the macroscopic scale, which is problematic for many diseases that manifest below the surface at a microscopic scale. Our lab has previously developed technology termed tethered capsule OCT endomicroscopy (TCE) to overcome these diagnostic limitations of endoscopy. The TCE device is a swallowable capsule that contains optomechanical components that circumferentially scan the OCT beam inside the body as the pill traverses the organ via peristalsis. While we have successfully imaged ~100 patients with the TCE device, the optics of our current device have many elements and are complex, comprising a glass ferrule, optical fiber, glass spacer, GRIN lens and prism. As we scale up manufacturing of this device for clinical translation, we must decrease the cost and improve the manufacturability of the capsule's optical configuration. In this abstract, we report on the design and development of simplificed TCE optics that replace the GRIN lens-based configuration with an angle-polished ball lens design. The new optics include a single mode optical fiber, a glass spacer and an angle polished ball lens, that are all fusion spliced together. The ball lens capsule has resolutions that are comparable with those of our previous GRIN lens configuration (30µm (lateral) × 7 µm (axial)). Results in human subjects show that OCT-based TCE using the ball lens not only provides rapid, high quality microstructural images of upper GI tract, but also makes it possible to implement this technology inexpensively and on a larger scale.

Endogenous peptide YY and neuropeptide Y inhibit colonic ion transport, contractility and transit differentially via Y1 and Y2 receptors

PubMed Central

Tough, IR; Forbes, S; Tolhurst, R; Ellis, M; Herzog, H; Bornstein, JC; Cox, HM

2011-01-01

BACKGROUND AND PURPOSE Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit using wild-type, single and double peptide knockout mice, comparing mucosal responses with those from human colon. EXPERIMENTAL APPROACH Mucosae were pretreated with a Y1 (BIBO3304) or Y2 (BIIE0246) receptor antagonist and changes in short-circuit current recorded. Colonic transit and colonic migrating motor complexes (CMMCs) were assessed in vitro and upper gastrointestinal and colonic transit measured in vivo. KEY RESULTS Y receptor antagonists revealed tonic Y1 and Y2 receptor-mediated antisecretory effects in human and wild-type mouse colon mucosae. In both, Y1 tone was epithelial while Y2 tone was neuronal. Y1 tone was reduced 90% in PYY−/− mucosa but unchanged in NPY−/− tissue. Y2 tone was partially reduced in NPY−/− or PYY−/− mucosae and abolished in tetrodotoxin-pretreated PYY−/− tissue. Y1 and Y2 tone were absent in NPYPYY−/− tissue. Colonic transit was inhibited by Y1 blockade and increased by Y2 antagonism indicating tonic Y1 excitation and Y2 inhibition respectively. Upper GI transit was increased in PYY−/− mice only. Y2 blockade reduced CMMC frequency in isolated mouse colon. CONCLUSIONS AND IMPLICATIONS Endogenous PYY and NPY induced significant mucosal antisecretory tone mediated by Y1 and Y2 receptors, via similar mechanisms in human and mouse colon mucosa. Both peptides contributed to tonic Y2-receptor-mediated inhibition of colonic transit in vitro but only PYY attenuated upper GI transit. PMID:21457230

Effect of listening to Vedic chants and Indian classical instrumental music on patients undergoing upper gastrointestinal endoscopy: A randomized control trial.

PubMed

Padam, Anita; Sharma, Neetu; Sastri, O S K S; Mahajan, Shivani; Sharma, Rajesh; Sharma, Deepak

2017-01-01

A high level of preoperative anxiety is common among patients undergoing medical and surgical procedures. Anxiety impacts of gastroenterological procedures on psychological and physiological responses are worth consideration. To analyze the effect of listening to Vedic chants and Indian classical instrumental music on anxiety levels and on blood pressure (BP), heart rate (HR), and oxygen saturation in patients undergoing upper gastrointestinal (GI) endoscopy. A prospective, randomized controlled trial was done on 199 patients undergoing upper GI endoscopy. On arrival, their anxiety levels were assessed using state and trait scores and various physiological parameters such as HR, BP, and SpO 2 . Patients were randomly divided into three groups: Group I of 67 patients who were made to listen prerecorded Vedic chants for 10 min, Group II consisting of 66 patients who listened to Indian classical instrumental music for 10 min, and Group III of 66 controls who remained seated for same period in the same environment. Thereafter, their anxiety state scores and physiological parameters were reassessed. A significant reduction in anxiety state scores was observed in the patients in Group I (from 40.4 ± 8.9 to 38.5 ± 10.7; P < 0.05) and Group II (from 41.8 ± 9.9 to 38.0 ± 8.6; P < 0.001) while Group III controls showed no significant change in the anxiety scores. A significant decrease in systolic BP ( P < 0.001), diastolic BP ( P < 0.05), and SpO 2 ( P < 0.05 was also observed in Group II. Listening to Vedic chants and Indian classical instrumental music has beneficial effects on alleviating anxiety levels induced by apprehension of invasive procedures and can be of therapeutic use.

Anticancer activity of synthetic bis(indolyl)methane-ortho-biaryls against human cervical cancer (HeLa) cells.

PubMed

Jamsheena, Vellekkatt; Shilpa, Ganesan; Saranya, Jayaram; Harry, Nissy Ann; Lankalapalli, Ravi Shankar; Priya, Sulochana

2016-03-05

Bis(indolyl)methane appended biaryls were designed, synthesized and evaluated in human cervical cancer cell lines (HeLa) for their anticancer activities and compared against normal rat cardiac myoblasts (H9C2) cells. Compounds 1-12 were synthesized, with variations in one of the phenyl unit, in a single step by condensation of biaryl-2-carbaldehydes with indole in the presence of para-toluenesulfonic acid. Compound 1 exhibited a GI50 value of 11.00 ± 0.707 μM and the derivatives, compounds 4 and 11 showed a GI50 value of 8.33 ± 0.416 μM and 9.13 ± 0.177 μM respectively in HeLa cells and was found to be non-toxic to H9C2 cells up to 20 μM. Furthermore, compounds 1, 4 and 11 induced caspase dependent cellular apoptosis in a concentration-dependent manner, reduced mitochondrial membrane potential, inhibited the cell migration and downregulated the production of MMP-2 and MMP-9 in HeLa cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

PubMed Central

Scarpignato, C

2013-01-01

Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro-duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called “inclusion complexes” that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition to our therapeutic armamentarium. PMID:23394552

Pelvic radiation disease: Updates on treatment options

PubMed Central

Frazzoni, Leonardo; La Marca, Marina; Guido, Alessandra; Morganti, Alessio Giuseppe; Bazzoli, Franco; Fuccio, Lorenzo

2015-01-01

Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments. PMID:26677440

Duodenal endoscopic findings and histopathologic confirmation of intestinal lymphangiectasia in dogs.

PubMed

Larson, R N; Ginn, J A; Bell, C M; Davis, M J; Foy, D S

2012-01-01

The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported. To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity. 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies. Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated. Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%. Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Clinical outcomes of image guided radiation therapy (IGRT) with gold fiducial vaginal cuff markers for high-risk endometrial cancer.

PubMed

Monroe, Alan T; Pikaart, Dirk; Peddada, Anuj V

2013-06-01

To report two year clinical outcomes of image guided radiation therapy (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk endometrial cancer patients. Twenty-six consecutive high-risk endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and regional lymph nodes were treated with vaginal cuff fiducial-based IGRT. Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich technique. Brachytherapy followed external radiation in 11 patients to a median dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy in 25 fractions. All 656 fractions were successfully imaged and treated. The median overall translational shift required for correction was 9.1 mm (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos. Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in eight patients (30%) and grade 3 toxicity occurred in one. At two years, there have been no local or regional failures and actuarial overall survival is 95%. Daily image guidance for high-risk endometrial cancer results in a low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor control at two years. Vaginal cuff translations can be substantial and may possibly result in underdosing if not properly considered.

Meal context and food preferences in cancer patients: results from a French self-report survey.

PubMed

Guerdoux-Ninot, Estelle; Kilgour, Robert D; Janiszewski, Chloé; Jarlier, Marta; Meuric, Jocelyne; Poirée, Brigitte; Buzzo, Solange; Ninot, Grégory; Courraud, Julie; Wismer, Wendy; Thezenas, Simon; Senesse, Pierre

2016-01-01

The present study examined patient self-reports of descriptions, experiences and consequences of meal disturbances and food preferences within a cultural context (i.e., French meal traditions) in various treated cancer patients along their disease trajectory. Over 800 questionnaires were sent to 20 cancer treatment centres in France. During a 9-month period, 255 questionnaires were received from five centres. Inclusion criteria included those French patients over 18 years of age, could read and understand French, had an Eastern Cooperative Oncology Group score between 0 and 2, experienced treatment-induced nutrition changes and/or had decreased oral intake. Dietetic staff assessed clinical characteristics while patients completed a 17-item questionnaire. The majority of patients were diagnosed with breast, gastro-intestinal (GI) tract and head and neck cancers (62 %). Half of the patients (49 %) experienced weight loss >5 %. The main treatment-induced side effects were fatigue, nausea, dry mouth, hypersensitivity to odors and GI tract transit disorders. These discomforts affected eating and drinking in 83 % of patients, inducing appetite loss and selected food aversion. Food preference appeared heterogeneous. Food taste, odor and finally appearance stimulated appetite. Finally, dietary behaviors and satisfaction were driven by the extent to which food was enjoyed. During oncologic treatments, eating and drinking were affected in more than three-quarters of patients. As recommended by practice guidelines, nutritional assessment and follow-up are required. Personalized nutritional counseling should include the role of the family, patient's meal traditions, and food habits.

Salvage HDR Brachytherapy for Recurrent Prostate Cancer After Previous Definitive Radiation Therapy: 5-Year Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chien Peter; Weinberg, Vivian; Shinohara, Katsuto

Purpose: Evaluate efficacy and toxicity of salvage high-dose-rate brachytherapy (HDRB) for locally recurrent prostate cancer after definitive radiation therapy (RT). Methods and Materials: We retrospectively analyzed 52 consecutively accrued patients undergoing salvage HDRB between 1998 and 2009 for locally recurrent prostate cancer after previous definitive RT. After pathologic confirmation of locally recurrent disease, patients received 36 Gy in 6 fractions. Twenty-four patients received neoadjuvant hormonal therapy before salvage, and no patients received adjuvant hormonal therapy. Determination of biochemical failure after salvage HDRB was based on the Phoenix definition. Overall survival (OS) and bF distributions were calculated using the Kaplan-Meier method.more » Univariate analyses were performed to identify predictors of biochemical control. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities, based on Common Terminology Criteria for Adverse Events (version 4), were documented. Results: Median follow-up after salvage HDRB was 59.6 months. The 5-year OS estimate was 92% (95% confidence interval [CI]: 80%-97%) with median survival not yet reached. Five-year biochemical control after salvage was 51% (95% CI: 34%-66%). Median PSA nadir postsalvage was 0.1 (range: 0-7.2) reached at a median of 10.2 months after completing HDRB. As for complications, acute and late grade 3 GU toxicities were observed in only 2% and 2%, respectively. No grade 2 or higher acute GI events and 4% grade 2 GI late events were observed. On univariate analysis, disease-free interval after initial definitive RT (P=.07), percent of positive cores at the time of diagnosis (P=.08), interval from first recurrence to salvage HDRB (P=.09), and pre-HDRB prostate-specific antigen (P=.07) were each of borderline significance in predicting biochemical control after salvage HDRB. Conclusions: Prostate HDRB is an effective salvage modality with relatively few long-term toxicities. We provide potential predictors of biochemical control for prostate salvage HDRB.« less

Haemoglobin responses to transfusion in severe iron deficiency anaemia: potential impact of gastrointestinal disorders.

PubMed

Bosch, X; Montori, E; Guerra-García, M; Costa-Rodríguez, J; Quintanilla, M H; Tolosa-Chapasian, P E; Moreno, P; Guasch, N; López-Soto, A

2017-04-01

Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes. © 2017 International Society of Blood Transfusion.

Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jawad, Maha Saada; Dilworth, Joshua T.; Gustafson, Gary S.

Purpose: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. Methods and Materials: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0.more » The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ{sup 2} test. P values <.05 were considered significant. Results: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years. Conclusions: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.« less

Dual drug delivery using "smart" liposomes for triggered release of anticancer agents

NASA Astrophysics Data System (ADS)

Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

2013-07-01

Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG2000-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG2000-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI50 = 6.5 μg/ml) than positive control (Adriamycin, GI50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called "smart liposomes" which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia.

About the Lung and Upper Aerodigestive Cancer Research Group | Division of Cancer Prevention

Cancer.gov

The Lung and Upper Aerodigestive Cancer Research Group conducts and supports research on the prevention and early detection of lung and head and neck cancers, as well as new approaches to clinical prevention studies including cancer immunoprevention.Phase 0/I/II Cancer Prevention Clinical Trials ProgramThe group jointly administers the Phase 0/I/II Cancer Prevention Clinical

A role for neuropeptide Y in the gender-specific gastrointestinal, corticosterone and feeding responses to stress.

PubMed

Forbes, S; Herzog, H; Cox, H M

2012-08-01

Exposure to an acute stress inhibits gastric emptying and stimulates colonic transit via central neuropeptide Y (NPY) pathways; however, peripheral involvement is uncertain. The anxiogenic phenotype of NPY(-/-) mice is gender-dependent, raising the possibility that stress-induced gastrointestinal (GI) responses are female-dominant through NPY. The aim of this study was to determine GI transit rates, corticosterone levels and food intake after acute restraint (AR) or novel environment (NE) stress in male and female NPY(-/-) and WT mice. Upper gastrointestinal transit (UGIT) (established 30 min after oral gavage) and corticosterone levels were determined under basal or restrained conditions (30 min) and after treatment i.p. with Y(1) antagonist BIBO3304 or Y(2) antagonist BIIE0246. Faecal pellet output (FPO) was established after AR and treatment i.p. with NPY in the NE, as were colonic bead expulsion rates. UGIT and FPO were similar in unrestrained male and female mice. NPY(-/-) females displayed significantly slower UGIT than NPY(-/-) males after AR, but both genders displayed significantly higher FPO and reduced food intake relative to WT counterparts. Peripheral NPY treatment increased bead expulsion time in WT mice. AR male NPY(-/-) mice had higher levels of corticosterone than male WT mice; whilst in AR WT mice, after peripheral Y(1) and Y(2) receptor antagonism in males, and Y(2) antagonism in females, corticosterone was significantly elevated. NPY possesses a role in the gender-dependent susceptibility to stress-induced GI responses. Furthermore, NPY inhibits GI motility through Y(2) receptors and corticosterone release via peripheral Y(1) and Y(2) receptors. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Molecular cloning of motilin and mechanism of motilin-induced gastrointestinal motility in Japanese quail.

PubMed

Apu, Auvijit Saha; Mondal, Anupom; Kitazawa, Takio; Takemi, Shota; Sakai, Takafumi; Sakata, Ichiro

2016-07-01

Motilin, a peptide hormone produced in the upper intestinal mucosa, plays an important role in the regulation of gastrointestinal (GI) motility. In the present study, we first determined the cDNA and amino acid sequences of motilin in the Japanese quail and studied the distribution of motilin-producing cells in the gastrointestinal tract. We also examined the motilin-induced contractile properties of quail GI tracts using an in vitro organ bath, and then elucidated the mechanisms of motilin-induced contraction in the proventriculus and duodenum of the quail. Mature quail motilin was composed of 22 amino acid residues, which showed high homology with chicken (95.4%), human (72.7%), and dog (72.7%) motilin. Immunohistochemical analysis showed that motilin-immunopositive cells were present in the mucosal layer of the duodenum (23.4±4.6cells/mm(2)), jejunum (15.2±0.8cells/mm(2)), and ileum (2.5±0.7cells/mm(2)), but were not observed in the crop, proventriculus, and colon. In the organ bath study, chicken motilin induced dose-dependent contraction in the proventriculus and small intestine. On the other hand, chicken ghrelin had no effect on contraction in the GI tract. Motilin-induced contraction in the duodenum was not inhibited by atropine, hexamethonium, ritanserin, ondansetron, or tetrodotoxin. However, motilin-induced contractions in the proventriculus were significantly inhibited by atropine and tetrodotoxin. These results suggest that motilin is the major stimulant of GI contraction in quail, as it is in mammals and the site of action of motilin is different between small intestine and proventriculus. Copyright © 2016 Elsevier Inc. All rights reserved.

Lumiracoxib: the evidence of its clinical impact on the treatment of osteoarthritis

PubMed Central

Profit, Louise; Chrisp, Paul

2007-01-01

Introduction: The symptoms of osteoarthritis (OA) include joint pain, stiffness, and a reduced ability to perform normal daily activities, which result in decreased quality of life. There is currently no known cure or means of preventing the progression of joint damage due to OA. Therefore, treatment focuses on the control of symptoms, including the use of various agents [including nonselective and selective nonsteroidal antiinflammatory drugs (NSAIDs)] to provide pain relief and reduce inflammation. Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of OA. Aims: To review the evidence for the treatment of OA with lumiracoxib. Evidence review: There is evidence that lumiracoxib reduces the pain and stiffness associated with OA, and is as effective as nonselective NSAIDs, and the COX-2 inhibitor celecoxib. There is some evidence that lumiracoxib treatment results in a lower incidence of upper gastrointestinal (GI) ulcer complications compared with nonselective NSAIDs. However, evidence suggests that there is no GI benefit in patients receiving concomitant aspirin medication. With the exception of GI ulcers, the evidence indicates that lumiracoxib has a tolerability profile similar to nonselective NSAIDs: low risk of cardiovascular (CV) events and a low incidence of edema. Changes in liver function occur in some patients, largely at doses >100 mg. The cost effectiveness of lumiracoxib compared with nonselective NSAIDs remains to be determined. Clinical value: Lumiracoxib is an alternative treatment option for OA which provides effective pain relief without the GI complications associated with nonselective NSAIDs, and with a low risk of CV events. Lumiracoxib is contraindicated in patients with current, previous, or at risk of, hepatic impairment. PMID:21221181

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

2016-11-01

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

2017-01-01

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

Research Training Program in Breast Cancer

DTIC Science & Technology

2001-07-01

more anaplastic, and have higher levels histopathology , lower proliferation levels, and less of chromosomal instability than their Wnt-I transgenic...mediated the more differentiated histopathology observed in the GI arrest checkpoint (el-Deiry et al., 1993; Harper et p53+/+ tumors. Several...mammary tumor virus promoter identical histopathological type, intertumoral variation (Tsukamoto et al., 1988). The female Wnt-] transgenic may be

Invasive lobular breast carcinoma metastasising to the rectum.

PubMed

Cherian, Nishant; Qureshi, Nafees Ahmad; Cairncross, Callum; Solkar, Mamoon

2017-08-03

Gastrointestinal (GI) metastasis from a primary breast carcinoma is uncommon, with the rectum being one of the least reported sites in the literature. We report a case of a 79-year-old woman who underwent treatment for an infiltrative lobular carcinoma of the right breast with nodal involvement, and 10 years later developed recurrence in the form of rectal metastasis. Spread to the GI tract is most commonly seen with lobular breast carcinomas. Any patient with a history of breast cancer presenting typically or atypically with abdominal symptoms or altered bowel habit should raise a high index of suspicion for recurrent or metastatic disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Infected colonic mass revealing a lung adenocarcinoma.

PubMed

Doussot, Alexandre; Chalumeau, Claire; Combier, Christophe; Cheynel, Nicolas; Facy, Olivier

2013-12-01

We report the case of lung adenocarcinoma revealed by infected colonic tumor in a 62-year-old man. An en bloc surgical resection was performed with uneventful recovery. The pathologic report concluded in a right mesocolic lymph node metastases from a mildly differentiated adenocarcinoma from pulmonary origin. GI metastases of lung cancer are described in the literature and are frequently asymptomatic in patient with a known primary cancer. In this patient, the complication of the metastases revealed the primary and immunochemistry permitted to adapt the systemic chemotherapy. Copyright © 2012. Published by Elsevier Masson SAS.

Gastric myeloid sarcoma without acute myeloblastic leukemia

PubMed Central

Huang, Xiao-Li; Tao, Jin; Li, Jian-Zhong; Chen, Xiao-Liang; Chen, Jian-Ning; Shao, Chun-Kui; Wu, Bin

2015-01-01

Myeloid sarcomas (MS) involve extramedullary blast proliferation from one or more myeloid lineages that replace the original tissue architecture, and these neoplasias are called granulocytic sarcomas, chloromas or extramedullary myeloid tumors. Such tumors develop in lymphoid organs, bones (e.g., skulls and orbits), skin, soft tissue, various mucosae, organs, and the central nervous system. Gastrointestinal (GI) involvement is rare, while the occurrence of myeloid sarcomas in patients without leukemia is even rare. Here, we report a case of a 38-year-old man who presented with epigastric pain and progressive jaundice. An upper GI endoscopy had shown extensive multifocal hyperemic fold thickening and the spread of nodular lesions in the body of the stomach. Biopsies from the gastric lesions indicated myeloid sarcoma of the stomach. However, concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia. For diagnosis, the immunohistochemical markers must be checked when evaluating a suspected myeloid sarcoma case. Accurate MS diagnosis determines the appropriate therapy and prognosis. PMID:25717265

Primary care physician perceptions of non-steroidal anti-inflammatory drug and aspirin-associated toxicity: results of a national survey.

PubMed

Chey, W D; Eswaren, S; Howden, C W; Inadomi, J M; Fendrick, A M; Scheiman, J M

2006-03-01

To assess primary care physician perceptions of non-steroidal anti-inflammatory drug (NSAID) and aspirin-associated toxicity. A group of gastroenterologists and internal medicine physicians created a survey, which was administered via the Internet to a large number of primary care physicians from across the US. One thousand primary care physicians participated. Almost one-third of primary care physicians recommended 325 mg rather than 81 mg of aspirin/day for cardioprotection. Fifty-nine percent thought enteric-coated or buffered aspirin reduced the risk of upper gastrointestinal (GI) bleeding. Seventy-six percent believed that Helicobacter pylori infection increased the risk of NSAID ulcers but fewer than 25% tested NSAID users for this infection. More than two-thirds were aware that aspirin co-therapy decreased the GI safety benefits of the cyclo-oxygenase 2 selective NSAIDs. However, 84% felt that aspirin with a cyclo-oxygenase 2 selective NSAID was safer than aspirin with a non-selective NSAID. When presented a patient at high risk for NSAID-related GI toxicity, almost 50% of primary care physicians recommended a proton pump inhibitor and cyclo-oxygenase 2 selective NSAID. This survey has identified areas of misinformation regarding the risk-benefit of NSAIDs and aspirin and the utilization of gastroprotective strategies. Further education on NSAIDs for primary care physicians is warranted.

Management protocol for acute gastrointestinal bleeding.

PubMed

Singhal, Dinesh; Kakodkar, Rahul; Nundy, Samiran

2006-05-01

Gastro-intestinal haemorrhage is not uncommon and is manifested as haematemesis, melaena or haematochezia. The first step is to resuscitate the patient if necessary and then proceed to make a diagnosis as well as divide patients into high and low-risk groups after taking a good history and performing a physical examination especially to detect the presence of an enlarged spleen. Then one should proceed with an endoscopy and other investigations chosen carefully for their usefulness. Control of bleeding is then tailored to the diagnosis and is usually with drugs, endoscopy, angio-embolisation and surgery in that order. The mortality rate for upper GI bleeding varies from 10 to 30% depending on the proportion of patients with variceal haemorrhage included. For lower GI bleeding mortality is in the region of 20% and for obscure GI bleeding outpatient mortality is 12%. The main points to remember are that the management of these patients in India should be different from those described in Western textbooks and suited to their specific needs and the facilities available locally. However, in spite of the widespread lack of complex diagnostic techniques and a shortage of blood for transfusion we believe that by adopting an aggressive step-by-step approach tailored to our own environment we will be able to save most of our patients who are usually young and have few comorbid conditions.

Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models

PubMed Central

Suarez-Arroyo, Ivette J.; Rosario-Acevedo, Raysa; Aguilar-Perez, Alexandra; Clemente, Pedro L.; Cubano, Luis A.; Serrano, Juan; Schneider, Robert J.; Martínez-Montemayor, Michelle M.

2013-01-01

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers. PMID:23468988

Anti-tumor effects of Ganoderma lucidum (reishi) in inflammatory breast cancer in in vivo and in vitro models.

PubMed

Suarez-Arroyo, Ivette J; Rosario-Acevedo, Raysa; Aguilar-Perez, Alexandra; Clemente, Pedro L; Cubano, Luis A; Serrano, Juan; Schneider, Robert J; Martínez-Montemayor, Michelle M

2013-01-01

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: a meta-analysis.

PubMed

Gatto, Nicole M; Kelsh, Michael A; Mai, Diem Ha; Suh, Mina; Proctor, Deborah M

2010-08-01

We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI=0.77-1.34)]; esophagus [1.17 (95% CI=0.90-1.51)]; stomach [1.09 (95% CI=0.93-1.28)]; colon [0.89 (95% CI=0.70-1.12)]; and rectum [1.17 (95% CI=0.98-1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR=1.49 (95% CI=1.06-2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype

PubMed Central

Lal, Shruti; Cheung, Edwin C.; Zarei, Mahsa; Preet, Ranjan; Chand, Saswati N.; Mambelli-Lisboa, Nicole C.; Romeo, Carmella; Stout, Matthew C.; Londin, Eric; Goetz, Austin; Lowder, Cinthya Y.; Nevler, Avinoam; Yeo, Charles J.; Campbell, Paul M.; Winter, Jordan M.; Dixon, Dan A.; Brody, Jonathan R.

2017-01-01

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer related deaths in the U.S., while colorectal cancer (CRC) is the third most common cancer. The RNA binding protein HuR (ELAVL1), supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and CRC tumor cohorts as compared to normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and CRC (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro, as HuR-deficient MIA PaCa-2 (MIA.HuR-KO(−/−)) cells had increased apoptosis when compared to isogenic wild-type (MIA.HuR-WT(+/+)) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a 2D culture into 3D (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared to control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. While not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO(−/−)) showed significantly reduced in vivo tumor growth compared to controls (HCT.HuR-WT(+/+)). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. PMID:28242812

Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer.

PubMed

Kim, Hun Jung; Phak, Jeong Hoon; Kim, Woo Chul

2017-10-01

We report our experience with Cyberknife to deliver hypofractionated stereotactic body radiotherapy (SBRT) boost combined with whole pelvis radiotherapy (WPRT) to patients with intermediate- to high-risk prostate cancer. From March 2008 to July 2014, 39 patients with newly diagnosed, intermediate- and high-risk (National Comprehensive Cancer Network definition) localized prostate cancer were treated with WPRT and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy) and the SBRT boost dose was 21 Gy (3 fractions of 7 Gy). No one received androgen deprivation therapy before biochemical relapse. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. Thirty-nine patients with a median 53.6 months (range 14-74 months) follow-up were analyzed. The median pretreatment PSA was 15.97 ng/mL. The estimated 5-year biochemical failure (BCF)-free survival was 94.7%. Two BCFs were observed in only high-risk group. The median PSA nadir was 0.30 ng/mL at median 36 months and PSA bounce occurred in 15.4% (n = 6) of patients at median 12 months. No grade 3 acute toxicity was noted. A total of 23% of the patients had grade 2 acute genitourinary (GU) toxicities and 21% had grade 2 acute gastrointestinal (GI) toxicities. At 2 months, most complications had returned to baseline. GU and GI toxicities were observed. WPRT followed by SBRT boost using Cyberknife in intermediate- and high-risk prostate cancer is feasible with minimal toxicity and encouraging BCF-free survival. © 2016 John Wiley & Sons Australia, Ltd.

Distribution, function and physiological role of melatonin in the lower gut

PubMed Central

Chen, Chun-Qiu; Fichna, Jakub; Bashashati, Mohammad; Li, Yong-Yu; Storr, Martin

2011-01-01

Melatonin is a hormone with endocrine, paracrine and autocrine actions. It is involved in the regulation of multiple functions, including the control of the gastrointestinal (GI) system under physiological and pathophysiological conditions. Since the gut contains at least 400 times more melatonin than the pineal gland, a review of the functional importance of melatonin in the gut seems useful, especially in the context of recent clinical trials. Melatonin exerts its physiological effects through specific membrane receptors, named melatonin-1 receptor (MT1), MT2 and MT3. These receptors can be found in the gut and their involvement in the regulation of GI motility, inflammation and pain has been reported in numerous basic and clinical studies. Stable levels of melatonin in the lower gut that are unchanged following a pinealectomy suggest local synthesis and, furthermore, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut. PMID:22025877

Milk diets influence doxorubicin-induced intestinal toxicity in piglets.

PubMed

Shen, Rene L; Pontoppidan, Peter E L; Rathe, Mathias; Jiang, Pingping; Hansen, Carl Frederik; Buddington, Randal K; Heegaard, Peter M H; Müller, Klaus; Sangild, Per T

2016-08-01

Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated with doxorubicin (DOX) treatment. Five-day-old pigs were administered DOX (1 × 100 mg/m(2)) or an equivalent volume of saline (SAL) and either fed formula (DOX-Form, n = 9, or SAL-Form, n = 7) or bovine colostrum (DOX-Colos, n = 9, or SAL-Colos, n = 7). Pigs were euthanized 5 days after initiation of chemotherapy to assess markers of small intestinal function and inflammation. All DOX-treated animals developed diarrhea, growth deficits, and leukopenia. However, the intestines of DOX-Colos pigs had lower intestinal permeability, longer intestinal villi with higher activities of brush border enzymes, and lower tissue IL-8 levels compared with DOX-Form (all P < 0.05). DOX-Form pigs, but not DOX-Colos pigs, had significantly higher plasma C-reactive protein, compared with SAL-Form. Plasma citrulline was not affected by DOX treatment or diet. Thus a single dose of DOX induces intestinal toxicity in preweaned pigs and may lead to a systemic inflammatory response. The toxicity is affected by type of enteral nutrition with more pronounced GI toxicity when formula is fed compared with bovine colostrum. The results indicate that bovine colostrum may be a beneficial supplementary diet for children subjected to chemotherapy and subsequent intestinal toxicity. Copyright © 2016 the American Physiological Society.

Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1 whereas isoliquiritigenin stimulates

PubMed Central

Dunlap, Tareisha L.; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

2015-01-01

Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by up-regulating P450 1B1. The present study tested the three authenticated medicinal species of licorice, [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)], used by women as dietary supplements, for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI > GG > GU and LigC ≅ LicA > LigF. The Michael acceptor chalcone LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the non-tumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1 μM, 10 μM) decreased cytokine- and TCDD-induced, P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50=12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women’s health. Additionally, the differential effects of the Glycyrrhiza species on estrogen metabolism emphasize the importance of standardization of botanical supplements to species-specific bioactive compounds. PMID:26134484

Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force.

PubMed

Dehmer, Steven P; Maciosek, Michael V; Flottemesch, Thomas J; LaFrance, Amy B; Whitlock, Evelyn P

2016-06-21

Evidence indicates that aspirin is effective for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) but also increases the risk for gastrointestinal (GI) and cerebral hemorrhages. To assess the net balance of benefits and harms from routine aspirin use across clinically relevant age, sex, and CVD risk groups. Decision analysis using a microsimulation model. 3 systematic evidence reviews. Men and women aged 40 to 79 years with a 10-year CVD risk of 20% or less, and no history of CVD and without elevated risk for GI or cerebral hemorrhages that would contraindicate aspirin use. Lifetime, 20 years, and 10 years. Clinical. Low-dose aspirin (≤100 mg/d). Primary outcomes are length and quality of life measured in net life-years and quality-adjusted life-years. Benefits include reduced nonfatal myocardial infarction, nonfatal ischemic stroke, fatal CVD, CRC incidence, and CRC mortality. Harms include increased fatal and nonfatal GI bleeding and hemorrhagic stroke. Lifetime net quality-adjusted life-years are positive for most adults initiating aspirin at ages 40 to 69 years, and life expectancy gains are expected for most men and women initiating aspirin at ages 40 to 59 years and 60 to 69 years with higher CVD risk. Harms may exceed benefits for persons starting aspirin in their 70s and for many during the first 10 to 20 years of use. Results are most sensitive to the relative risk for hemorrhagic stroke and CVD mortality but are affected by all relative risk estimates, baseline GI bleeding incidence and case-fatality rates, and disutilities associated with aspirin use. Aspirin effects by age are uncertain. Stroke benefits are conservatively estimated. Gastrointestinal bleeding incidence and case-fatality rates account only for age and sex. Lifetime aspirin use for primary prevention initiated at younger ages (40 to 69 years) and in persons with higher CVD risk shows the greatest potential for positive net benefit. Agency for Healthcare Research and Quality.

ASCEND-8: A Randomized Phase 1 Study of Ceritinib, 450 mg or 600 mg, Taken with a Low-Fat Meal versus 750 mg in Fasted State in Patients with Anaplastic Lymphoma Kinase (ALK)-Rearranged Metastatic Non-Small Cell Lung Cancer (NSCLC).

PubMed

Cho, Byoung Chul; Kim, Dong-Wan; Bearz, Alessandra; Laurie, Scott A; McKeage, Mark; Borra, Gloria; Park, Keunchil; Kim, Sang-We; Ghosn, Marwan; Ardizzoni, Andrea; Maiello, Evaristo; Greystoke, Alastair; Yu, Richard; Osborne, Karen; Gu, Wen; Scott, Jeffrey W; Passos, Vanessa Q; Lau, Yvonne Y; Wrona, Anna

2017-09-01

Ceritinib, 750 mg fasted, is approved for treatment of patients with ALK receptor tyrosine kinase gene (ALK)-rearranged (ALK-positive) NSCLC previously treated with crizotinib. Part 1 of the ASCEND-8 study determined whether administering ceritinib, 450 mg or 600 mg, with a low-fat meal may enhance gastrointestinal (GI) tolerability versus 750 mg fasted in patients with ALK-positive NSCLC while maintaining similar exposure. ASCEND-8 is a multicenter, randomized, open-label, phase 1 study. Part 1 investigated the steady-state pharmacokinetics (PK) and safety of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg fasted in patients with advanced ALK-positive NSCLC who were either treatment naive or pretreated with chemotherapy and/or crizotinib. Part 2 will assess efficacy and safety of ceritinib in treatment-naive patients. As of June 16, 2016, 137 patients were randomized (450 mg fed [n = 44], 600 mg fed [n = 47], and 750 mg fasted [n = 46]); 135 patients received ceritinib. Median follow-up duration was 4.14 months. At steady state, relative to 750 mg fasted, 450 mg with food demonstrated comparable PK as assessed by maximum (peak) concentration of drug in plasma and area under the plasma concentration-time curve from time zero to 24 hours, whereas 600 mg with food demonstrated approximately 25% higher PK. Relative to 750 mg fasted, 450 mg with food was associated with a lower proportion of patients with GI toxicities, mostly grade 1 (diarrhea [43.2%], nausea [29.5%], and vomiting [18.2%]); there were no grade 3 or 4 events, study drug discontinuations, or serious AEs due to GI toxicities. Ceritinib, 450 mg with food, had similar exposure and a more favorable GI safety profile than ceritinib, 750 mg in fasted patients with ALK-positive NSCLC. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Colorectal breast carcinoma metastasis diagnosed as an obstructive colonic primary tumor. A case report and review of the literature.

PubMed

Théraux, J; Bretagnol, F; Guedj, N; Cazals-Hatem, D; Panis, Y

2009-12-01

Common sites of colorectal breast carcinoma metastasis are bones, lungs, the central nervous system and the liver. Metastases in the gastrointestinal (GI) tract are rare and especially involve the stomach rather than the colon. Clinical or radiological features usually cannot differentiate them from a primary colorectal tumor, resulting in inappropriate treatment. In some cases, this lesion suggests multifocal spread of breast cancer with peritoneal carcinomatosis. Colorectal breast cancer metastasis is a rare finding and there is no consensus on the management of these lesions. The present case report describes a 69-year-old female with metastatic breast cancer presenting as an obstructive tumor of the transverse colon.

Physical exercises for breast cancer survivors: effects of 10 weeks of training on upper limb circumferences

PubMed Central

Di Blasio, Andrea; Morano, Teresa; Bucci, Ines; Di Santo, Serena; D’Arielli, Alberto; Castro, Cristina Gonzalez; Cugusi, Lucia; Cianchetti, Ettore; Napolitano, Giorgio

2016-01-01

[Purpose] The aims of this study were to verify the effects on upper limb circumferences and total body extracellular water of 10 weeks of Nordic Walking (NW) and Walking (W), both alone and combined with a series of exercises created for breast cancer survivors, the ISA method. [Subjects and Methods] Twenty breast cancer survivors were randomly assigned to 4 different training groups and evaluated for upper limb circumferences, total body and extracellular water. [Results] The breast cancer survivors who performed NW, alone and combined with the ISA method, and Walking combined with the ISA method (but not alone) showed significantly reduced arm and forearm circumferences homolateral to the surgical intervention. [Conclusion] For breast cancer survivors, NW, alone and combined with the ISA method, and Walking combined with the ISA method should be prescribed to prevent the onset and to treat light forms of upper limb lymphedema because Walking training practiced alone had no significant effect on upper limb circumference reduction. PMID:27821934

Predictors for in-hospital mortality and need for clinical intervention in upper GI bleeding: a 5-year observational study.

PubMed

Balaban, D V; Strâmbu, V; Florea, B G; Cazan, A R; Brătucu, M; Jinga, M

2014-01-01

Upper GI bleeding (UGIB) is a potentially life threatening gastrointestinal emergency whose effective management depends on early risk stratification. We retrospectively studied 151 patients admitted to our unit with UGIB between 1st January 2007 and 31st December 2011 and in whom we calculated the clinical and complete Rockall, the Glasgow-Blatchford and modified Glasgow-Blatchford risk scores. We performed an analysis of the predictive value of these scores for in-hospital mortality and need for clinical intervention. Of the 151 patients enrolled, 68.87% were male, and the mean age was 59.48 years. One in three patients had a history of chronic liver disease and one in eight had a previous episode of UGIB. Clinically, 58.3% of the patients presented with melena, 18.5% with hematemesis and 23.1% with both hematemesis and melena. 22% of cases were variceal hemorrhages and the other non-variceal. 16 patients died during hospitalization. The prognostic accuracy of all four scores for in-hospital death and need for clinical intervention was good, the complete Rockall score having the best performance (AUROC 0.849 and 0.653 respectively). The Rockall and Blatchford scores were good predictors of mortality and need for clinical intervention in our study. The good predictive performance of these scores highlight the need for their use in day-to-day practice to select patients with likelihood of poor clinical outcome. Celsius.

In vivo deep tissue fluorescence imaging of the murine small intestine and colon

NASA Astrophysics Data System (ADS)

Crosignani, Viera; Dvornikov, Alexander; Aguilar, Jose S.; Stringari, Chiara; Edwards, Roberts; Mantulin, Williams; Gratton, Enrico

2012-03-01

Recently we described a novel technical approach with enhanced fluorescence detection capabilities in two-photon microscopy that achieves deep tissue imaging, while maintaining micron resolution. This technique was applied to in vivo imaging of murine small intestine and colon. Individuals with Inflammatory Bowel Disease (IBD), commonly presenting as Crohn's disease or Ulcerative Colitis, are at increased risk for developing colorectal cancer. We have developed a Giα2 gene knock out mouse IBD model that develops colitis and colon cancer. The challenge is to study the disease in the whole animal, while maintaining high resolution imaging at millimeter depth. In the Giα2-/- mice, we have been successful in imaging Lgr5-GFP positive stem cell reporters that are found in crypts of niche structures, as well as deeper structures, in the small intestine and colon at depths greater than 1mm. In parallel with these in vivo deep tissue imaging experiments, we have also pursued autofluorescence FLIM imaging of the colon and small intestine-at more shallow depths (roughly 160μm)- on commercial two photon microscopes with excellent structural correlation (in overlapping tissue regions) between the different technologies.

Tumor margin detection using optical biopsy techniques

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Li, Jiyou; Li, Zhongwu; Zhou, Lixin; Chen, Ke; Pu, Yang; He, Yong; Zhu, Ke; Li, Qingbo; Alfano, Robert R.

2014-03-01

The aim of this study is to use the Resonance Raman (RR) and fluorescence spectroscopic technique for tumor margin detection with high accuracy based on native molecular fingerprints of breast and gastrointestinal (GI) tissues. This tumor margins detection method utilizes advantages of RR spectroscopic technique in situ and in real-time to diagnose tumor changes providing powerful tools for clinical guiding intraoperative margin assessments and postoperative treatments. The tumor margin detection procedures by RR spectroscopy were taken by scanning lesion from center or around tumor region in ex-vivo to find the changes in cancerous tissues with the rim of normal tissues using the native molecular fingerprints. The specimens used to analyze tumor margins include breast and GI carcinoma and normal tissues. The sharp margin of the tumor was found by the changes of RR spectral peaks within 2 mm distance. The result was verified using fluorescence spectra with 300 nm, 320 nm and 340 nm excitation, in a typical specimen of gastric cancerous tissue within a positive margin in comparison with normal gastric tissues. This study demonstrates the potential of RR and fluorescence spectroscopy as new approaches with labeling free to determine the intraoperative margin assessment.

Prospective, randomized comparison of 3 different hemoclips for the treatment of acute upper GI hemorrhage in an established experimental setting.

PubMed

Kato, Masayuki; Jung, Yunho; Gromski, Mark A; Chuttani, Ram; Matthes, Kai

2012-01-01

Recently, endoscopic clip application devices have undergone redesign and improvements to optimize their clinical use and effectiveness. Initially designed for the treatment of bleeding nonvariceal lesions, these devices are also increasingly used for the closure of perforations, fistulas, and anastomotic leaks. Several clinical studies, both randomized and nonrandomized, have used endoscopic hemoclips for hemostasis. However, no comparative studies have yet been reported in the literature comparing the latest endoscopic clip devices for usability and effectiveness for hemostasis of acute upper GI hemorrhage. We aimed to compare the usability and efficacy of 3 different types of endoscopic clip application devices in an established experimental setting by using a porcine ex-vivo simulator of upper GI hemorrhage. Randomized, controlled, ex-vivo study. Academic medical center. Spurting vessels were created within ex-vivo porcine stomachs as published in prior studies. The vessels were attached to a pressure transducer to record the pressure of the circulating blood replacement. Before the initiation of bleeding, each vessel was randomized to 1 of 3 endoscopic clipping devices: 2 different commonly used hemoclips deployed through the working channel and 1 novel clip deployed via an over-the-scope applications device. Two investigators treated 45 bleeding sites (15 bleeding sites for each device at various randomized locations in the stomach: fundus, body, and antrum). Usability was measured via the endpoints of procedure time and quantity of clips required to achieve hemostasis. Efficacy was measured via the endpoint of pressure increase (Δp) from baseline to after treatment. All of the 45 hemostasis treatments were carried out successfully. The mean procedure times were significantly different among the hemoclips, with the clip deployed in an over-the-scope fashion requiring significantly less time to attain hemostasis compared with the other 2 clips. For number of clips needed to attain hemostasis, the clip deployed in an over-the-scope fashion was significantly superior to the others. There were also significant differences among the changes in pressure (Δp ± SD) among the different hemoclips tested. Ex-vivo study. In this prospective, randomized ex-vivo study, we observed significant differences in the usability (time to achieve hemostasis and number of clips required) and the efficacy (change in pressure achieved by the hemoclips) among the 3 clips. The clip applied in the over-the-scope fashion was superior to the other 2 tested clips with regard to time to achieve hemostasis and number of clips required. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.

PubMed

Shin, Andrea; Camilleri, Michael; Busciglio, Irene; Burton, Duane; Smith, Steven A; Vella, Adrian; Ryks, Michael; Rhoten, Deborah; Zinsmeister, Alan R

2013-11-01

RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Gut Microbiota and Inflammation

PubMed Central

Hakansson, Asa; Molin, Goran

2011-01-01

Systemic and local inflammation in relation to the resident microbiota of the human gastro-intestinal (GI) tract and administration of probiotics are the main themes of the present review. The dominating taxa of the human GI tract and their potential for aggravating or suppressing inflammation are described. The review focuses on human trials with probiotics and does not include in vitro studies and animal experimental models. The applications of probiotics considered are systemic immune-modulation, the metabolic syndrome, liver injury, inflammatory bowel disease, colorectal cancer and radiation-induced enteritis. When the major genomic differences between different types of probiotics are taken into account, it is to be expected that the human body can respond differently to the different species and strains of probiotics. This fact is often neglected in discussions of the outcome of clinical trials with probiotics. PMID:22254115

Reducing radiation-induced gastrointestinal toxicity — the role of the PHD/HIF axis

PubMed Central

Olcina, Monica M.; Giaccia, Amato J.

2016-01-01

Radiotherapy is an effective treatment strategy for cancer, but a significant proportion of patients experience radiation-induced toxicity due to damage to normal tissue in the irradiation field. The use of chemical or biological approaches aimed at reducing or preventing normal tissue toxicity induced by radiotherapy is a long-held goal. Hypoxia-inducible factors (HIFs) regulate the production of factors that may protect several cellular compartments affected by radiation-induced toxicity. Pharmacological inhibitors of prolyl hydroxylase domain–containing enzymes (PHDs), which result in stabilization of HIFs, have recently been proposed as a new class of radioprotectors. In this review, radiation-induced toxicity in the gastrointestinal (GI) tract and the main cellular compartments studied in this context will be discussed. The effects of PHD inhibition on GI radioprotection will be described in detail. PMID:27548524

Synthesis and antiproliferative activity of imidazo[1,2-a]pyrimidine Mannich bases.

PubMed

Aeluri, Raghunath; Alla, Manjula; Polepalli, Sowjanya; Jain, Nishant

2015-07-15

A series of imidazo[1,2-a]pyrimidine Mannich bases were designed, synthesized in two phases. Mannich bases were obtained by one pot three component condensation of imidazo[1,2-a]pyrimidine with secondary amine or piperazine and excess of formaldehyde solution in methanol. The synthesized Mannich bases were screened for in vitro growth inhibition against a panel of 3 different human cancer cell lines. Most of the synthesized compounds exhibited antiproliferative activity with GI50 values ranging from 0.01 to 79.4 μM. Compounds 5e, 6b and 7k were found to be effective inhibitors of growth of all cell lines, with GI50 values similar to that of standard drug. The structure and activity relationship has been disclosed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence. The incorporation of additional symptoms makes the scoring more detailed.

Low glycemic index diet, exercise and vitamin D to reduce breast cancer recurrence (DEDiCa): design of a clinical trial.

PubMed

Augustin, Livia S A; Libra, Massimo; Crispo, Anna; Grimaldi, Maria; De Laurentiis, Michele; Rinaldo, Massimo; D'Aiuto, Massimiliano; Catalano, Francesca; Banna, Giuseppe; Ferrau', Francesco; Rossello, Rosalba; Serraino, Diego; Bidoli, Ettore; Massarut, Samuele; Thomas, Guglielmo; Gatti, Davide; Cavalcanti, Ernesta; Pinto, Monica; Riccardi, Gabriele; Vidgen, Edward; Kendall, Cyril W C; Jenkins, David J A; Ciliberto, Gennaro; Montella, Maurizio

2017-01-23

Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. May 11, 2016; NCT02786875 . 2015-005147-14.

Anthropometrics Identify Wasting in Patients Undergoing Surgery for Encapsulating Peritoneal Sclerosis

PubMed Central

Campbell, Rosalind; Augustine, Titus; Hurst, Helen; Pararajasingam, Ravi; van Dellen, David; Armstrong, Sheilagh; Bartley, Carol; Birtles, Linda; Summers, Angela

2015-01-01

♦ Introduction: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis in which gastrointestinal (GI) symptoms reduce appetite and dietary intake. Adequate nutrition is important, especially if surgery is required. Although the incidence of EPS is low, the present report is able to detail preoperative nutrition status and treatment in a large cohort of patients from a national EPS referral center. ♦ Methods: Of 51 patients admitted to this EPS specialist center hospital for their first peritonectomy in the study period, 50 had a preoperative dietetic assessment, and 49 underwent upper-arm anthropometry. ♦ Results: Mean body mass index (BMI) was 20.6 kg/m2. Mean weight loss was 14% of body weight in the preceding 6 months, with 35 of 50 patients losing more than 10%. On anthropometry, 25 of 49 patients were below the 5th percentile for mid-arm circumference (MAC), 17 of 49 were below for triceps skinfold thickness (TSF), and 21 of 49 were below for mid-arm muscle circumference (MAMC). Mean handgrip strength (HGS) was 60% of normal, with 43 of 49 patients being below 85% of normal. Appetite was poor in 21 of 50 patients, and 37 of 50 had upper and 40 of 50 had lower GI symptoms. By subjective global assessment, 27 of 51 patients were graded as severely malnourished, and 5 of 51, as well-nourished. Mean serum albumin was 28 g/L and did not correlate with BMI, MAC, TSF, MAMC, or HGS. In most patients, C-reactive protein was elevated (mean: 111 mg/L). Preoperative parenteral nutrition was given to 46 of 51 patients for a mean of 21 days. ♦ Discussion: Our findings demonstrate the poor nutrition status of patients admitted for EPS surgical intervention. Anthropometrics reveal depleted fat and lean body mass in EPS patients, which might be a result of anorexia and inflammation, and the reason that albumin was not an accurate marker of nutrition. Poor nutrition status is likely to negatively affect outcome in this patient group. ♦ Conclusions: Early recognition of GI symptoms may herald a diagnosis of EPS. Optimization of preoperative nutrition status with intensive nutrition support is needed. PMID:24584612

Anthropometrics Identify Wasting in Patients Undergoing Surgery for Encapsulating Peritoneal Sclerosis.

PubMed

Campbell, Rosalind; Augustine, Titus; Hurst, Helen; Pararajasingam, Ravi; van Dellen, David; Armstrong, Sheilagh; Bartley, Carol; Birtles, Linda; Summers, Angela

2015-01-01

♦ Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis in which gastrointestinal (GI) symptoms reduce appetite and dietary intake. Adequate nutrition is important, especially if surgery is required. Although the incidence of EPS is low, the present report is able to detail preoperative nutrition status and treatment in a large cohort of patients from a national EPS referral center. ♦ Of 51 patients admitted to this EPS specialist center hospital for their first peritonectomy in the study period, 50 had a preoperative dietetic assessment, and 49 underwent upper-arm anthropometry. ♦ Mean body mass index (BMI) was 20.6 kg/m(2). Mean weight loss was 14% of body weight in the preceding 6 months, with 35 of 50 patients losing more than 10%. On anthropometry, 25 of 49 patients were below the 5th percentile for mid-arm circumference (MAC), 17 of 49 were below for triceps skinfold thickness (TSF), and 21 of 49 were below for mid-arm muscle circumference (MAMC). Mean handgrip strength (HGS) was 60% of normal, with 43 of 49 patients being below 85% of normal. Appetite was poor in 21 of 50 patients, and 37 of 50 had upper and 40 of 50 had lower GI symptoms. By subjective global assessment, 27 of 51 patients were graded as severely malnourished, and 5 of 51, as well-nourished. Mean serum albumin was 28 g/L and did not correlate with BMI, MAC, TSF, MAMC, or HGS. In most patients, C-reactive protein was elevated (mean: 111 mg/L). Preoperative parenteral nutrition was given to 46 of 51 patients for a mean of 21 days. ♦ Our findings demonstrate the poor nutrition status of patients admitted for EPS surgical intervention. Anthropometrics reveal depleted fat and lean body mass in EPS patients, which might be a result of anorexia and inflammation, and the reason that albumin was not an accurate marker of nutrition. Poor nutrition status is likely to negatively affect outcome in this patient group. ♦ Early recognition of GI symptoms may herald a diagnosis of EPS. Optimization of preoperative nutrition status with intensive nutrition support is needed. Copyright © 2015 International Society for Peritoneal Dialysis.

Black breast cancer survivors experience greater upper extremity disability.

PubMed

Dean, Lorraine T; DeMichele, Angela; LeBlanc, Mously; Stephens-Shields, Alisa; Li, Susan Q; Colameco, Chris; Coursey, Morgan; Mao, Jun J

2015-11-01

Over one-third of breast cancer survivors experience upper extremity disability. Black women present with factors associated with greater upper extremity disability, including: increased body mass index (BMI), more advanced disease stage at diagnosis, and varying treatment type compared with Whites. No prior research has evaluated the relationship between race and upper extremity disability using validated tools and controlling for these factors. Data were drawn from a survey study among 610 women with stage I-III hormone receptor positive breast cancer. The disabilities of the arm, shoulder and hand (QuickDASH) is an 11-item self-administered questionnaire that has been validated for breast cancer survivors to assess global upper extremity function over the past 7 days. Linear regression and mediation analysis estimated the relationships between race, BMI and QuickDASH score, adjusting for demographics and treatment types. Black women (n = 98) had 7.3 points higher average QuickDASH scores than White (n = 512) women (p < 0.001). After adjusting for BMI, age, education, cancer treatment, months since diagnosis, and aromatase inhibitor status, Black women had an average 4-point (95 % confidence interval 0.18-8.01) higher QuickDASH score (p = 0.04) than White women. Mediation analysis suggested that BMI attenuated the association between race and disability by 40 %. Even several years post-treatment, Black breast cancer survivors had greater upper extremity disability, which was partially mediated by higher BMIs. Close monitoring of high BMI Black women may be an important step in reducing disparities in cancer survivorship. More research is needed on the relationship between race, BMI, and upper extremity disability.

Exposure to biomass smoke as a risk factor for oesophageal and gastric cancer in low-income populations: A systematic review.

PubMed

Kayamba, Violet; Heimburger, Douglas C; Morgan, Douglas R; Atadzhanov, Masharip; Kelly, Paul

2017-06-01

Upper gastrointestinal cancers contribute significantly to cancer-related morbidity and mortality in sub-Saharan Africa, but they continue to receive limited attention. The high incidence in young adults remains unexplained, and the risk factors have not been fully described. A literature search was conducted using the electronic database PubMed. Beginning from January 1980 to February 2016, all articles evaluating biomass smoke exposure with oesophageal and gastric cancer were reviewed. Over 70% of the African population relies on biomass fuel, meaning most Africans are exposed to biomass smoke throughout their lives. Cigarette smoke is an established risk factor for upper gastrointestinal cancers, and some of its carcinogenic constituents are also present in biomass smoke. We found eight case-control studies reporting associations between exposure to biomass smoke and oesophageal cancer, and two linking biomass smoke to gastric cancer. All of these papers reported significant positive associations between exposure and cancer risk. Further research is needed in order to fully define the constituents of biomass smoke, which could each have varying specific and synergistic or independent contributions to the development of upper gastrointestinal cancers. Exposure to biomass smoke is an environmental factor influencing the development of upper gastrointestinal cancers, especially in low-resource settings.

Validation of the FACT-B+4-UL questionnaire and exploration of its predictive value in women submitted to surgery for breast cancer.

PubMed

Andrade Ortega, Juan Alfonso; Millán Gómez, Ana Pilar; Ribeiro González, Marisa; Martínez Piró, Pilar; Jiménez Anula, Juan; Sánchez Andújar, María Belén

2017-06-21

The early detection of upper limb complications is important in women operated on for breast cancer. The "FACT-B+4-UL" questionnaire, a specific variant of the Functional Assessment of Cancer Therapy-Breast (FACT-B) is available among others to measure the upper limb function. The Spanish version of the upper limb subscale of the FACT-B+4 was validated in a prospective cohort of 201 women operated on for breast cancer (factor analysis, internal consistency, test-retest reliability, construct validity and sensitivity to change were determined). Its predictive capacity of subsequent lymphoedema and other complications in the upper limb was explored using logistic regression. This subscale is unifactorial and has a great internal consistency (Cronbach's alpha: 0.87), its test-retest reliability and construct validity are strong (intraclass correlation coefficient: 0.986; Pearson's R with "Quick DASH": 0.81) as is its sensitivity to change. It didn't predict the onset of lymphedema. Its predictive capacity for other upper limb complications is low. FACT-B+4-UL is useful in measuring upper limb disability in women surgically treated for breast cancer; but it does not predict the onset of lymphoedema and its predictive capacity for others complications in the upper limb is low. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Roux-en-Y or Billroth II Reconstruction After Radical Distal Gastrectomy for Gastric Cancer: A Multicenter Randomized Controlled Trial.

PubMed

So, Jimmy Bok-Yan; Rao, Jaideepraj; Wong, Andrew Siang-Yih; Chan, Yiong-Huak; Pang, Ning Qi; Tay, Amy Yuh Ling; Yung, Man Yee; Su, Zheng; Phua, Janelle Niam Sin; Shabbir, Asim; Ng, Enders Kwok Wai

2018-02-01

The aim of the study was to compare the clinical symptoms between Billroth II (B-II) and Roux-en-Y (R-Y) reconstruction after distal subtotal gastrectomy (DG) for gastric cancer. Surgery is the mainstay of curative treatment for gastric cancer. The technique for reconstruction after DG remains controversial. Both B-II and R-Y are popular methods. This is a prospective multicenter randomized controlled trial. From October 2008 to October 2014, 162 patients who underwent DG were randomly allocated to B-II (n = 81) and R-Y (n = 81) groups. The primary endpoint is Gastrointestinal (GI) Symptoms Score 1 year after surgery. We also compared the nutritional status, extent of gastritis on endoscopy, and quality of life after surgery between the 2 procedures at 1 year. Operative time was significantly shorter for B-II than for R-Y [mean difference 21.5 minutes, 95% confidence interval (95% CI) 3.8-39.3, P = 0.019]. The B-II and R-Y groups had a peri-operative morbidity of 28.4% and 33.8%, respectively (P = 0.500) and a 30-day mortality of 2.5% and 1.2%, respectively (P = 0.500). GI symptoms score did not differ between R-Y versus B-II reconstruction (mean difference -0.45, 95% CI -1.21 to 0.31, P = 0.232). R-Y resulted in a lower median endoscopic grade for gastritis versus B-II (mean difference -1.32, 95% CI -1.67 to -0.98, P < 0.001). We noted no difference in nutritional status (R-Y versus B-II mean difference -0.31, 95% CI -3.27 to 2.65, P = 0.837) and quality of life at 1 year between the 2 groups too. Although BII is associated with a higher incidence of heartburn symptom and higher median endoscopic grade for gastritis, BII and RY are similar in terms of overall GI symptom score and nutritional status at 1 year after distal gastrectomy.

Glycemic index, glycemic load, and risk of type 2 diabetes: results from 3 large US cohorts and an updated meta-analysis123

PubMed Central

Bhupathiraju, Shilpa N; Tobias, Deirdre K; Malik, Vasanti S; Pan, An; Hruby, Adela; Manson, JoAnn E; Willett, Walter C; Hu, Frank B

2014-01-01

Background: Epidemiologic evidence for the relation between carbohydrate quality and risk of type 2 diabetes (T2D) has been mixed. Objective: We prospectively examined the association of dietary glycemic index (GI) and glycemic load (GL) with T2D risk. Design: We prospectively followed 74,248 women from the Nurses’ Health Study (1984–2008), 90,411 women from the Nurses’ Health Study II (1991–2009), and 40,498 men from the Health Professionals Follow-Up Study (1986–2008) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by using a validated questionnaire and updated every 4 y. We also conducted an updated meta-analysis, including results from our 3 cohorts and other studies. Results: During 3,800,618 person-years of follow-up, we documented 15,027 cases of incident T2D. In pooled multivariable analyses, those in the highest quintile of energy-adjusted GI had a 33% higher risk (95% CI: 26%, 41%) of T2D than those in the lowest quintile. Participants in the highest quintile of energy-adjusted GL had a 10% higher risk (95% CI: 2%, 18%) of T2D. Participants who consumed a combination diet that was high in GI or GL and low in cereal fiber had an ∼50% higher risk of T2D. In the updated meta-analysis, the summary RRs (95% CIs) comparing the highest with the lowest categories of GI and GL were 1.19 (1.14, 1.24) and 1.13 (1.08, 1.17), respectively. Conclusion: The updated analyses from our 3 cohorts and meta-analyses provide further evidence that higher dietary GI and GL are associated with increased risk of T2D. PMID:24787496