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Sample records for advanced gastrointestinal malignancies

  1. Gastrointestinal Malignancy and the Microbiome

    PubMed Central

    Abreu, Maria T.; Peek, Richard M.

    2014-01-01

    Microbial species participate in the genesis of a substantial number of malignancies—in conservative estimates, at least 15% of all cancer cases are attributable to infectious agents. Little is known about the contribution of the gastrointestinal (GI) microbiome to the development of malignancies. Resident microbes can promote carcinogenesis by inducing inflammation, increasing cell proliferation, altering stem cell dynamics, and producing metabolites such as butyrate, which affect DNA integrity and immune regulation. Studies in humans and rodent models of cancer have identified effector species and relationships among members of the microbial community in the stomach and colon that increase the risk for malignancy. Strategies to manipulate the microbiome, or the immune response to such bacteria, could be developed to prevent or treat certain GI cancers. PMID:24406471

  2. [Metachronous four primary malignancies in gastro-intestinal tract].

    PubMed

    Bae, Jung Min; Kim, Se Won; Kim, Sang Woon; Song, Sun Kyo

    2009-06-01

    Multiple primary malignancy was reported firstly by Billroth in 1889. Recently, multiple primary malignancies are considered to increase due to improved survival rate of cancer patients, advanced diagnostic tools, and increased use of chemotherapy and radiotherapy. In Korea, several cases of triple primary malignancies were reported. However, four primary malignancies in gastro-intestinal tract was rarely reported. Recently, we experienced a 70 year-old male who was diagnosed with metachronous four primary malignancies in rectum, ascending colon, stomach, and ampulla of Vater. We report this rare case of metachronous four primary malignancies with a review of literature.

  3. Role of stenting in gastrointestinal benign and malignant diseases

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Arena, Monica; Miraglia, Stefania; Consolo, Pierluigi; Iabichino, Giuseppe; Virgilio, Clara; Luigiano, Carmelo

    2015-01-01

    Advances in stents design have led to a substantial increase in the use of stents for a variety of digestive diseases. Initially developed as a non-surgical treatment for palliation of esophageal cancer, the stents now have an emerging role in the management of malignant and benign conditions as well as in all segments of the gastrointestinal tract. In this review, relevant literature search and expert opinions have been used to evaluate the key-role of stenting in gastrointestinal benign and malignant diseases. PMID:25992186

  4. Diet and Upper Gastrointestinal Malignancies

    PubMed Central

    Abnet, Christian C.; Corley, Douglas A.; Freedman, Neal D.; Kamangar, Farin

    2015-01-01

    Diet is believed to modulate cancer risk and this relationship has been widely studied in the gastrointestinal tract. Observational epidemiologic studies have provided most of the evidence for the effects of diet on cancer risk, because clinical trials to determine nutritional exposures are often impossible, impractical, or unaffordable. Although a few foods or nutrients are thought to protect against specific types of cancer, it seems clear that the strength and even direction of dietary associations (increasing or decreasing risk) is organ site- and even histology-specific, along the gastrointestinal tract. Although some hypotheses are supported by a substantial body of observational data (drinking hot maté contributes to esophageal cancer), there is not much data to support others. We discuss some highly touted hypotheses and draw interim conclusions about what is known, and what could be done to improve the level of evidence. The complex nature of diet and its associations can be productively investigated with disease-specific studies. However, public health recommendations for normal-risk individuals regarding diet and gastrointestinal cancer should probably emphasize the importance of eating for overall health, rather than eating specific foods to reduce risk for specific cancers. PMID:25680671

  5. Advances in gastrointestinal bleeding.

    PubMed

    Lanas, Ángel

    2016-09-01

    The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations.

  6. Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

    ClinicalTrials.gov

    2016-07-20

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

  7. Criteria for malignancy in gastrointestinal endocrine tumors.

    PubMed

    Bordi, Cesare; D'Adda, Tiziana; Azzoni, Cinzia; Pizzi, Silvia; Bottarelli, Lorena; Mormandi, Francesca; Antonetti, Tommaso; Luong, Tu Vinh; Rindi, Guido

    2006-01-01

    In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.

  8. Robotics in advanced gastrointestinal surgery: the bariatric experience.

    PubMed

    Kim, Keith; Hagen, Monika E; Buffington, Cynthia

    2013-01-01

    Robotic surgery for laparoscopic procedures such as advanced gastrointestinal surgery and abdominal malignancies is currently on the rise. The first robotic systems have been used since the 1990s with increasing number of clinical cases and broader clinical applications each year. Although high-evidence-level data are scarce, studies suggest that the technical advantages of robotic surgery result in a clinical value for procedures of advanced complexity such as Roux-en-Y gastric bypass and revisional bariatric surgery. Ultimately, the digital interface of the robotic system with the option to integrate augmented reality and real-time imaging will allow advanced applications particularly in the field of gastrointestinal surgery for malignancies.

  9. Gastrointestinal stromal tumors (GISTs) and second malignancies

    PubMed Central

    Rodriquenz, Maria Grazia; Rossi, Sabrina; Ricci, Riccardo; Martini, Maurizio; Larocca, Mario; Dipasquale, Angelo; Quirino, Michela; Schinzari, Giovanni; Basso, Michele; D’Argento, Ettore; Strippoli, Antonia; Barone, Carlo; Cassano, Alessandra

    2016-01-01

    Abstract Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-α genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-α mutation (n. 2) and exon 18 PDGFR-α mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. PMID:27661019

  10. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies.

    PubMed

    Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

    2015-03-21

    Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB's function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB's role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy.

  11. Lymphatic mapping for upper gastrointestinal malignancies.

    PubMed

    Kitagawa, Yuko; Kitajima, Masaki

    2004-06-01

    Recent studies on lymphatic mapping of upper gastrointestinal (GI) malignancies have provided new insights with regard to the sentinel node (SN) concept in solid tumors. At present, the SN concept seems to be valid not only for breast cancer, but also for esophageal and gastric cancers, which have multidirectional and complicated lymphatic flows. In addition to the staging merits, individualized surgical management has been proposed for upper GI cancer based on the SN concept. Gastric cancer is now a suitable target of SN-guided surgery after breast cancer because of its anatomical situation. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Because SNs in esophageal cancer are multiple and widespread, complete sampling of SNs is not a minimally invasive procedure, as it is in breast cancer. However, selective and modified lymphadenectomy targeting SNs for clinically N0 esophageal cancer instead of three-field lymph node dissection should become not only feasible but also clinically important. When performing chemoradiotherapy as curative treatment for cT1N0 esophageal cancer, lymphoscintigrams revealing the distribution of SNs in each individual case are useful to tailor the field of irradiation to control occult micrometastases. Although there are several issues to be resolved, this novel procedure has the potential to improve quality control in upper GI cancer.

  12. Advances in upper gastrointestinal endoscopy

    PubMed Central

    Graham, David G.; Banks, Matthew R.

    2015-01-01

    The rapidly moving technological advances in gastrointestinal endoscopy have enhanced an endoscopist’s ability to diagnose and treat lesions within the gastrointestinal tract. The improvement in image quality created by the advent of high-definition and magnification endoscopy, alongside image enhancement, produces images of superb quality and detail that empower the endoscopist to identify important lesions that have previously been undetectable. Additionally, we are now seeing technologies emerge, such as optical coherence tomography and confocal laser endomicroscopy, that allow the endoscopist to visualize individual cells on a microscopic level and provide a real time, in vivo histological assessment. Within this article we discuss these technologies, as well as some of the results from their early use in clinical studies. PMID:26918137

  13. Asbestos exposure and gastrointestinal malignancy review and meta-analysis

    SciTech Connect

    Frumkin, H.; Berlin, J.

    1988-01-01

    The epidemiologic literature linking asbestos exposure with gastrointestinal malignancy is reviewed. Problems in comparing studies are discussed, appropriate strategies for comparison are developed, and study results are pooled using a model which accounts for both intrastudy and interstudy variability. Stratification of cohorts by dose reveals that significant asbestos exposure, as indicated by a lung cancer standardized mortality ratio (SMR) of at least 200, is associated with an elevated gastrointestinal cancer SMR for five or six end points examined.

  14. Esophageal subepithelial lesion diagnosed as malignant gastrointestinal neuroectodermal tumor.

    PubMed

    Kim, Sung Bum; Lee, Si Hyung; Gu, Mi Jin

    2015-05-14

    A 21-year-old male visited our hospital with a complaint of aggravating dysphagia and odynophagia for a few days. Esophagogastroduodenoscopy showed huge bulging mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor teeth. Endoscopic ultrasonography showed an about 35 mm sized irregular margined in-homogenous hypoechoic lesion with an obscure layer of origin. Endoscopic ultrasonography fine needle aspiration revealed spindle cell proliferation without immunoreactivity for CD117, SMA, and cytokeratin. The patient underwent excision of the subepithelial lesion at the distal esophagus. On pathologic examination of the specimen, the tumor was composed of short fascicles of oval to spindle cells with eosinophilic and clear cytoplasm and vesicular nuclei. The tumor cells were positive for S-100 and SOX10 and negative for CD117, SMA, HMB-45, melan-A, cytokeratin, and CD99. The split-apart signal was detected in EWSR1 on FISH, suggesting a malignant gastrointestinal neuroectodermal tumor. At the time of writing, the patient is on radiation therapy at the operated site of esophagus and doing well, with no recurrence for three months. Malignant gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with features of clear cell sarcoma, without melanocytic differentiation, and shows a poor prognosis. This is the first reported case of malignant gastrointestinal neuroectodermal tumor arising as subepithelial lesion in the esophagus.

  15. Laparoscopic approach to gastrointestinal malignancies: toward the future with caution.

    PubMed

    Bencini, Lapo; Bernini, Marco; Farsi, Marco

    2014-02-21

    After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district.

  16. Upper Gastrointestinal Stent Insertion in Malignant and Benign Disorders

    PubMed Central

    Kang, Hyoun Woo

    2015-01-01

    Upper gastrointestinal (GI) stents are increasingly being used to manage upper GI obstructions. Initially developed for palliative treatment of esophageal cancer, upper GI stents now play an emerging role in benign strictures of the upper GI tract. Because recurrent obstruction and stent-related complications are common, new modifications of stents have been implemented. Self-expandable metal stents (SEMS) have replaced older plastic stents. In addition, newly designed SEMS have been developed to prevent complications. This review provides an overview of the various types, indications, methods, complications, and clinical outcomes of upper GI stents in a number of malignant and benign disorders dividing the esophagus and gastroduodenum. PMID:26064817

  17. Diabetes mellitus as a novel risk factor for gastrointestinal malignancies.

    PubMed

    Herrigel, Dana J; Moss, Rebecca A

    2014-10-01

    Evidence of an emerging etiologic link between diabetes mellitus and several gastrointestinal malignancies is presented. Although a correlation between pancreatic cancer and diabetes mellitus has long been suspected, the potential role diabetes mellitus plays in the pathogenicity of both hepatocellular carcinoma and colon cancer is becoming increasingly well defined. Further supporting the prospect of etiologic linkage, the association of diabetes mellitus with colon cancer is consistently demonstrated to be independent of obesity. An increasing incidence of diabetes and obesity in the United States has led to a recent surge in incidence of hepatocellular cancer on the background of nonalcoholic fatty liver disease, and this disease is expected to commensurately grow in incidence. Widespread recognition of this emerging risk factor may lead to a change in screening practices. Although the mechanisms underlying the correlation are still under investigation, the role of insulin, the insulin-like growth factor-I, and related binding and signaling pathways as regulators of cell growth and cell proliferation are implicated in carcinogenesis and tumor growth. The potential role of metformin and other medications for diabetes mellitus in the chemoprevention, carcinogenesis, and treatment of gastrointestinal malignancies is also presented.

  18. Association Between Coeliac Disease and Risk of Any Malignancy and Gastrointestinal Malignancy

    PubMed Central

    Han, Yuehua; Chen, Wuzhen; Li, Peiwei; Ye, Jun

    2015-01-01

    Abstract Coeliac disease (CD) is reported to be associated with risk of malignancy; however, this association remains unclear. We aimed to systematically evaluate the association between CD and risk of all malignancies as well as gastrointestinal (GI) malignancy specifically. The PUBMED and EMBASE databases were searched to identify eligible studies from 1960 to March 2015, without restriction. Two reviewers independently performed the study inclusion and data extraction methods. Odds ratios (ORs), risk ratios, or standardized incidence ratios were pooled using either a fixed- or a random-effects model. Sensitivity and subgroup analyses were used to explore sources of heterogeneity. A total of 17 studies were included in this meta-analysis. The pooled OR for risk of all malignancies was 1.25 (95% confidence interval [CI] 1.09–1.44), whereas the pooled OR for risk of GI malignancy was 1.60 (95% CI 1.39–1.84) and suggested an inverse association with CD. Moreover, patients with CD were at a higher risk of esophageal cancer (pooled OR = 3.72, 95% CI 1.90–7.28) and small intestinal carcinoma (pooled OR = 14.41, 95% CI 5.53–37.60), whereas no significant associations were observed for other GI cancers, including gastric, colorectal, liver, and pancreatic cancers. Subgroup analyses also indicated that the results were influenced by the CD diagnostic method, as well as the follow-up time after CD diagnosis. CD was associated with increased risk of all malignancies as well as GI malignancies, including esophageal cancer and small intestinal carcinoma. PMID:26402826

  19. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  20. Synchronous quintuple primary gastrointestinal tract malignancies: Case report

    PubMed Central

    Kim, Soo-Hong; Park, Byung-Soo; Kim, Hyun Sung; Kim, Jae Hun

    2017-01-01

    Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis. PMID:28104993

  1. [Advantages of endoscopic stenting for malignant gastrointestinal obstructions].

    PubMed

    Meier, P N; Manns, M P

    2006-03-01

    Self-expanding stents play a major role in the interdisciplinary treatment of gastrointestinal obstructions in patients with local nonresectable tumors, advanced metastasis, and pronounced comorbidity. Reinstenting the passage and sealing esophagotracheal fistulae is very effective as palliative treatment for esophageal tumor complications. In hepatobiliary occlusions, the success rate against cholestasis is also high. Enteral and colorectal stents are gaining favor. Required are an experienced endoscopy team and adequate equipment. The rate of procedural complications is generally low, but rare and severe complications such as perforation must be considered. Further improvements in the materials and construction of stents can be expected.

  2. Surgical palliation of gastric outlet obstruction in advanced malignancy

    PubMed Central

    Potz, Brittany A; Miner, Thomas J

    2016-01-01

    Gastric outlet obstruction (GOO) is a common problem associated with advanced malignancies of the upper gastrointestinal tract. Palliative treatment of patients’ symptoms who present with GOO is an important aspect of their care. Surgical palliation of malignancy is defined as a procedure performed with the intention of relieving symptoms caused by an advanced malignancy or improving quality of life. Palliative treatment for GOO includes operative (open and laparoscopic gastrojejunostomy) and non-operative (endoscopic stenting) options. The performance status and medical condition of the patient, the extent of the cancer, the patients prognosis, the availability of a curative procedure, the natural history of symptoms of the disease (primary and secondary), the durability of the procedure, and the quality of life and life expectancy of the patient should always be considered when choosing treatment for any patient with advanced malignancy. Gastrojejunostomy appears to be associated with better long term symptom relief while stenting appears to be associated with lower immediate procedure related morbidity. PMID:27648158

  3. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies.

    PubMed

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-21

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.

  4. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies

    PubMed Central

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-01

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve. PMID:26805818

  5. Advances in the management of malignant mesothelioma.

    PubMed

    Khalil, Mazen Y; Mapa, Marissa; Shin, Hyung Ju C; Shin, Dong M

    2003-07-01

    Malignant mesotheliomas are very aggressive tumors that originate from mesothelial cells, which form the serosal lining of the pleura, pericardial, and peritoneal cavities. Finding effective chemotherapeutic treatment for malignant mesothelioma is a challenge. There is no standard treatment because this tumor is relatively resistant to therapy. A resurgence of interest has been expressed in novel therapies and conventional treatments used in different ways. Several treatment modalities have been studied, including chemotherapy, radiotherapy, surgery, and immunotherapy. Chemotherapy can be administered systemically or directly into the pleura. This review presents the results of the most recent trials and highlights the most promising advances in the battle against this aggressive disease.

  6. Chemotherapy in advanced malignant diseases in Iraq

    PubMed Central

    Talib, Hussein

    1971-01-01

    This work discusses the experience of one surgical team in the Third Surgical Unit at the Republican Teaching Hospital, Baghdad, from 1967 to 1970. 112 patients with advanced malignant lesions in various parts of the body were dealt with. In 84, the intra-arterial route was adopted; in the remaining, systemic administration of cytotoxic agents either singly or in combination was employed. The results are reported in terms of subjective and objective response, and the various complications are discussed. ImagesFig. 1Fig. 2 PMID:5137574

  7. Oncocytic variant of malignant gastrointestinal neuroectodermal tumor: a potential diagnostic pitfall.

    PubMed

    Boland, Jennifer M; Folpe, Andrew L

    2016-11-01

    Malignant gastrointestinal neuroectodermal tumor (MGNET) is a very rare, aggressive malignant neoplasm that may occur in any location in the gastrointestinal tract. Malignant gastrointestinal neuroectodermal tumors typically consist of sheet-like to pseudopapillary proliferation of primitive-appearing epithelioid cells with a moderate amount of lightly eosinophilic cytoplasm, round nuclei and small nucleoli, often in association with osteoclast-like giant cells. By immunohistochemistry, these tumors show expression of S100 protein and SOX10, in the absence of expression of more specific melanocytic markers (eg, HMB45, Melan A). Genetically, malignant gastrointestinal neuroectodermal tumors are characterized by rearrangements of the EWSR1 or FUS genes with CREB1 or ATF1. We report a case of gastric malignant gastrointestinal neuroectodermal tumor occurring in a 46-year-old woman and showing striking oncocytic cytoplasmic change, a previously undescribed potential diagnostic pitfall. An initial needle biopsy showed large, eosinophilic cells with S100 protein and SOX10 expression and lacking expression of KIT, DOG1, Melan A, keratin, chromogranin, or smooth muscle actin, and was interpreted as representing a granular cell tumor. The subsequent excision specimen showed similar-appearing areas, but also contained small more primitive-appearing areas, lacking oncocytic change and having high nuclear grade and brisk mitotic activity. This resection specimen was initially diagnosed as a malignant granular cell tumor. However subsequent gene expression profiling studies showed an EWSR1-ATF1 fusion, confirmed with fluorescence in situ hybridization for EWSR1, and a final diagnosis of MGNET with oncocytic change was made. This case highlights a previously undescribed pitfall in the diagnosis of MGNET, oncocytic change, and suggests that MGNET should be included in the differential diagnosis for unusual oncocytic neoplasms of the gastrointestinal tract.

  8. Recent Advances in Human Protozoan Parasites of Gastrointestinal Tract

    DTIC Science & Technology

    1987-02-01

    frequency of oral-anal sexual contacts. No relation was seen between the presence or chance of gastrointestinal symptoms and infection with E...Lancet May 14: 1103. SPENCER MJ., CHAPIN M.R. & GARCIA L.S. 1962. Dientamoeba fragilis: A gastrointestinal protozoan infection in adults. American...ULIC EIL& p .( RECENT ADVANCES IN HUMAN PROTOZOAN PARASITES OF GASTROINTESTINAL TRACT J.H. Cross REPORT NO. CS -142 AD-A 182 878 ,ji.. ELECTE JULS j

  9. Endoscopic laser palliation for advanced malignant dysphagia.

    PubMed Central

    Bown, S G; Hawes, R; Matthewson, K; Swain, C P; Barr, H; Boulos, P B; Clark, C G

    1987-01-01

    Palliative treatment of malignant dysphagia aims to optimise swallowing for the maximum time possible with the minimum of general distress to these seriously ill patients. Thirty four patients considered unsuitable for surgery because of advanced malignancy, other major pathology or in whom previous surgery had been unsuccessful were treated endoscopically with the Nd YAG laser. Significant improvement was achieved in 29 (85%). On a scale of 0-4 (0 = normal swallowing; 4 = dysphagia for all fluids), mean improvement was 1.7, with 25 patients (74%) able to swallow most, or all solids after treatment. With increasing experience, the average number of treatment sessions required for each patient became less; initial time in hospital became comparable to that needed for intubation. Failures were caused by inappropriate patient selection (3), or laser related perforation (2). The mean survival in the whole group was 19 weeks (range 2-44). Eighteen patients needed further treatment for recurrent dysphagia, a mean of six weeks (range 2-15) after initial therapy. Ten of these responded, but eight eventually required insertion of a prosthetic tube. The duration of good palliation was very variable after initial laser therapy. Images Fig. 3 PMID:2443431

  10. Serological screening for a mucine-like carcinoma-associated antigen (MCA) in patients with gastrointestinal tract malignancies.

    PubMed

    Scheithauer, W; Mairinger, D

    1989-01-01

    Mouse monoclonal antibody b-12 identifies a high-molecular-mass glycoprotein antigen strongly expressed by breast carcinoma cells. Since immunohistochemical studies have also demonstrated some reactivity with other epithelial neoplasms, and since "mucine-like carcinoma-associated antigen" (MCA) has gained considerable interest as a tumor marker in breast cancer, we have investigated 34 patients with histologically proven advanced gastrointestinal malignancies for the presence of elevated MCA serum levels. Our data suggest that screening for and/or monitoring of MCA in these tumors is unlikely to have any practical clinical relevance. The possible role of MCA as a marker in tissue specimens for abortive adenomatous differentiation in gastrointestinal (and other) neoplasms, however, remains to be determined.

  11. [Ectopic pancreas mimicking advanced gastric malignancy--case report].

    PubMed

    Zawada, Iwona; Lewosiuk, Agnieszka; Hnatyszyn, Krzysztof; Patalan, Michał; Woyke, Stanisław; Kostyrka, Roman; Marlicz, Krzysztof; Starzyńska, Teresa

    2012-04-01

    Ectopic pancreas is the most common type of ectopic tissue in gastrointestinal tract. It is typically asymptomatic, presenting as a small submucosal lesion in prepyloric region of stomach. The diagnosis is usually incidental, during gastroscopy. The patient with symptomatic heterotropic pancreas, mimicking gastric malignancy was described.

  12. Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours

    PubMed Central

    Palazzo, L; Landi, B; Cellier, C; Cuillerier, E; Roseau, G; Barbier, J

    2000-01-01

    BACKGROUND/AIM—Some endoscopic ultrasonographic (EUS) features have been reported to be suggestive of malignancy in gastrointestinal stromal cell tumours (SCTs). The aim of this study was to assess the predictive value of these features for malignancy.
METHODS—A total of 56 histologically proven cases of SCT studied by EUS between 1989 and 1996 were reviewed. There were 42 gastric tumours, 12 oesophageal tumours, and two rectal tumours. The tumours were divided into two groups: (a) benign SCT, comprising benign leiomyoma (n = 34); (b) malignant or borderline SCT (n = 22), comprising leiomyosarcoma (n = 9), leiomyoblastoma (n = 9), and leiomyoma of uncertain malignant potential (n = 4). The main EUS features recorded were tumour size, ulceration, echo pattern, cystic spaces, extraluminal margins, and lymph nodes with a malignant pattern. The two groups were compared by univariate and multivariate analysis.
RESULTS—Irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern were most predictive of malignant or borderline SCT. Pairwise combinations of the three features had a specificity and positive predictive value of 100% for malignant or borderline SCT, but a sensitivity of only 23%. The presence of at least one of these three criteria had 91% sensitivity, 88% specificity, and 83% predictive positive value. In multivariate analysis, cystic spaces and irregular margins were the only two features independently predictive of malignant potential. The features most predictive of benign SCTs were regular margins, tumour size ⩽30 mm, and a homogeneous echo pattern. When the three features were combined, histology confirmed a benign SCT in all cases.
CONCLUSIONS—The combined presence of two out of three EUS features (irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern) had a positive predictive value of 100% for malignant or borderline gastrointestinal SCT. Tumours less than 30

  13. An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma.

    PubMed

    Insabato, Luigi; Guadagno, Elia; Natella, Valentina; Somma, Anna; Bihl, Michel; Pizzolorusso, Antonio; Mainenti, Pier Paolo; Apice, Gaetano; Tornillo, Luigi

    2015-09-01

    Very recently a new designation of "Malignant Neuroectodermal Gastrointestinal Tumor" has been proposed for an aggressive form of neuroectodermal tumor with features similar to that of Clear Cell Sarcoma of Soft Tissue, however without a melanocytic differentiation. Also known as "clear cell sarcoma-like tumors of the gastrointestinal tract", these tumors show some features strongly suggesting an origin from a gastrointestinal neuroectodermal precursor cell unable to differentiate along the melanocytic lineage. They occur mainly in young and middle-aged adults, and have a poor prognosis with a high rate of liver and lymphnode metastases. Histologically they are composed of epithelioid or oval-to spindle cells with a sheet-like or nested pattern of growth, strongly positive for neural markers (S-100, SOX10, and vimentin) and negative for the melanocytic ones. EWSR1 gene rearrangements including EWSR1-ATF1 or EWSR1-CREB1 GENE fusions are typically assessed in these tumors. Here we report a case of malignant neuroectodermal gastrointestinal tumor which immunophenotypically unusually expressed FLI-1, occurring in a 29-year-old man with a previous medical history of Ewing sarcoma. We finally suggest that this case might be a further evidence of a link between these two entities.

  14. Nutritional status and related factors of patients with advanced gastrointestinal cancer.

    PubMed

    Zhang, Liyan; Lu, Yuhan; Fang, Yu

    2014-04-14

    The scored Patient-Generated Subjective Global Assessment (PG-SGA) is considered to be the most appropriate tool for detecting malnutrition in cancer patients. In particular, malignant tumours derived from the gastrointestinal tract may impair nutrient intake and absorption and cause malnutrition. We carried out a cross-sectional study to assess the nutritional status and related factors of patients with gastrointestinal cancer. Nutritional status was determined using the scored PG-SGA in patients (n 498) with advanced gastrointestinal cancer admitted to the Gastrointestinal Medical Oncology Unit at Beijing Cancer Hospital between 1 August 2012 and 28 February 2013. The possible related factors including age, sex, hospitalisation frequency and pathology were explored. We found that 98% of the patients required nutrition intervention and 54% of the patients required improved nutrition-related symptom management and/or urgent nutritional support (PG-SGA score ≥9). Factors related to malnutrition were age (r 0.103, P<0.01), hospitalisation frequency (r -0.196, P<0.01) and sex (the prevalence of malnutrition was higher in men than in women (9.88 v. 8.54, P<0.01)). Patients with rectal cancer had a lower risk of malnutrition than patients with other types of gastrointestinal cancer (F=35.895, P<0.01). More attention should be paid to the nutritional status of gastrointestinal patients, especially those at a higher risk of malnutrition, such as elderly patients, those hospitalised for the first time, male patients and those with other types of gastrointestinal cancer except rectal cancer. The nutritional status of these patients should be evaluated and they should be given proper nutrition education and nutritional support in a timely manner.

  15. Can contrast-enhanced harmonic endosonography predict malignancy risk in gastrointestinal subepithelial tumors?

    PubMed Central

    Park, Hye Yoon; Jeon, Seong Woo; Lee, Hyun Seok; Cho, Chang Min; Bae, Han Ik; Seo, An Na; Kweon, Oh Kyung

    2016-01-01

    Background and Objectives: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) is a novel technology that can identify subepithelial tumors (SETs) by detecting the degree of enhancement, but whether CEH-EUS can predict the malignancy risk of gastrointestinal stromal tumors (GISTs) remains unclear. The aim of our study was to evaluate the diagnostic accuracy of CEH-EUS and its ability to discriminate among SETs and predict the malignancy risk of GISTs. Materials and Methods: We retrospectively included patients with suspected subepithelial lesions who underwent CEH-EUS preoperatively. Thirty-five patients with histologically proven GISTs and benign neoplasms were enrolled in the study. The images of CEH-EUS were categorized in accordance with microvasculature, parenchymal perfusion, and nonenhancing spots. The diagnostic performance of CEH-EUS was evaluated by comparing these findings with the histological diagnosis. Results: When we divided the enrolled patients into high- and low-grade malignancy and benign groups, nonenhancing spots on CEH-EUS were found more frequently in the high-grade malignancy group (63.6%), followed by the low-grade malignancy (46.7%) and benign groups (25.7%) (P = 0.022). However, based on the statistical validity of the CEH-EUS findings for the discrimination of SETs, the sensitivity was 53.8% for diagnostic performance and 63.6% for prediction of malignancy risk of GISTs. Conclusions: From our study results, it is unclear whether CEH-EUS alone has a diagnostic role in the discrimination of SETs and the prediction of malignancy risk of GISTs. Further studies with larger samples from multiple centers and use of other imaging analysis modalities are needed. PMID:28000630

  16. [The efficacy of SEMS for malignant upper gastrointestinal stenosis, evaluated by a "home index"].

    PubMed

    Yonechi, M; Sato, K; Saito, Y; Yamagiwa, T; Kikuchi, T; Kamiya, T; Saito, M; Nagase, K; Kashimura, J; Ikeya, S; Endo, T; Nakayama, H; Sugai, Y

    1999-12-01

    We used a self expandable metalic stent (SEMS) on 24 patients (average age 68.6 years, 20 males, 4 females) with malignant upper gastrointestinal stenosis from August, 1997 to March, 1999. The primary diseases of the 24 patients were gastric cancer (13 cases: 54%), esophageal cancer (10 cases: 42%) and paraesophageal lymph node metastasis of breast cancer (one case: 4%). In this study, we present a "Home Index" as an indicator to evaluate a patient's quality of life, and investigated the efficacy and problem of SEMS.

  17. Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies.

    PubMed

    Gheonea, Dan Ionuţ; Cârţână, Tatiana; Ciurea, Tudorel; Popescu, Carmen; Bădărău, Anca; Săftoiu, Adrian

    2011-01-07

    Gastrointestinal cancers represent a major cause of morbidity and mortality, with incomplete response to chemotherapy in the advanced stages and poor prognosis. Angiogenesis plays a crucial part in tumor growth and metastasis, with most gastrointestinal cancers depending strictly on the development of a new and devoted capillary network. Confocal laser endomicroscopy is a new technology which allows in vivo microscopic analysis of the gastrointestinal mucosa and its microvascularization during ongoing endoscopy by using topically or systemically administered contrast agents. Targeting markers of angiogenesis in association with confocal laser endomicroscopic examination (immunoendoscopy), as a future challenge, will add functional analysis to the morphological aspect of the neoplastic process. This review describes previous experience in endomicroscopic examination of the upper and lower digestive tract with emphasis on vascularization, resulting in a broad spectrum of potential clinical applications, and also preclinical research that could be translated to human studies.

  18. Octreotide acetate enables the administration of chemoradiotherapy, including the oral anticancer drug S-1, in gastric cancer patients with malignant gastrointestinal obstruction.

    PubMed

    Takahashi, Tsunehiro; Saikawa, Yoshiro; Igarashi, Takahiro; Tsuwano, Shinichi; Kumagai, Koshi; Nakamura, Rieko; Ooyama, Takashi; Wada, Norihito; Takeuchi, Hiroya; Takaishi, Hiromasa; Kitagawa, Yuko

    2010-07-01

    Advanced gastric cancer frequently results in the inability to ingest food or drink orally, a condition called malignant gastrointestinal obstruction (MGO). MGO is clinically defined as a gastrointestinal outlet obstruction caused by a large tumor, or malignant bowel obstruction with peritoneal dissemination. MGO impacts the quality of life by interfering with oral intake and by causing gastrointestinal symptoms, such as nausea, vomiting and abdominal pain. Octreotide acetate (OA) is an analogue of somatostatin which has been increasingly used to relieve gastrointestinal symptoms since it decreases the secretion of digestive juices and increases the absorption of water and electrolytes. In Japan, the oral anticancer drug S-1 was recently adopted as a key chemotherapeutic agent in advanced gastric cancer; however, its oral formulation precludes its utility in the MGO setting. This is a pilot study of chemoradiotherapy plus OA in gastric cancer with MGO. Patients were initially treated with OA to control gastrointestinal symptoms. Following resolution of their symptoms, the patients received chemotherapy with S-1 plus low-dose cisplatin and radiation. Irradiation was targeted at the primary tumor and surrounding lesions, including the lymph nodes. Grade 4 toxicity was observed in only 1 patient, and no treatment-related deaths were noted. After treatment, 3 patients achieved a partial response and 4 achieved stable disease. Of the 9 patients, 8 were able to tolerate solid food orally and were discharged. The outcomes of these cases suggest that OA is a useful adjunctive therapy that enables advanced gastric cancer patients with MGO to receive S-1-containing chemotherapy.

  19. Frequence, Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors1234

    PubMed Central

    Kramer, K.; Wolf, S.; Mayer, B.; Schmidt, S.A.; Agaimy, A.; Henne-Bruns, D.; Knippschild, U.; Schwab, M.; Schmieder, M.

    2015-01-01

    Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted. PMID:25622906

  20. Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions

    PubMed Central

    Bhatia, Nirav; Lalla, Yastira; Vu, An N.; Farah, Camile S.

    2013-01-01

    Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812

  1. [Advances in cellular immunotherapy for malignant melanoma].

    PubMed

    López, Mercedes; Escobar, Alejandro; Alfaro, Jorge; Fodor, Miguel; Larrondo, Milton; Ferrada, Carlos; Salazar-Onfray, Flavio

    2004-09-01

    An alternative strategy for cancer treatment is the manipulation of the immune system, denominated cancer immunotherapy. The immunotherapeutical use of cells of the immune system, like dendritic cells (DC), is being explored in different clinical protocols. Recently, we finalized a clinical phase I protocol, for the treatment of malignant melanoma, using DCs loaded with tumor lysates. Our results indicate that the subcutaneous application of DCs do not produce adverse effects. We also observed an increase of tumor specific T lymphocytes precursors in the blood, associated to hypersensitivity reactions (DTH) in 60% of the treated patients. In most cases, an stability in the disease was observed, although without a significant association between vaccination and survival. Additionally, therapies based on Interleukin-2 (IL-2) have been used with relative success in the treatment of some kind of tumors since 1985. However, problems associated to the toxicity of IL-2 still restrict its massive use. Our direct experience with the use of IL-2, indicates that low doses and its subcutaneous application, maintains the beneficial effects for patients, eliminating the adverse effects. Based on the accumulated evidence during last the five years, we decided to implement an optimized clinical protocol, which alternatively combines dendritic cells vaccines with the use of low doses of IL-2 for the reinforcement of the immunological system.

  2. Palliation of Postoperative Gastrointestinal Anastomotic Malignant Strictures with Flexible Covered Metallic Stents: Preliminary Results

    SciTech Connect

    Lee, Jeong-Min; Han, Young Min; Lee, Sang Yong; Kim, Chong Soo; Yang, Doo Hyun; Lee, Seung Ok

    2001-01-15

    Purpose: To evaluate the efficacy of the placement of covered metallic stents for palliation of gastrointestinal anastomotic strictures secondary to recurrent gastric cancer.Methods: Under fluoroscopic guidance, placement of one or two self-expandable covered metallic stents was attempted perorally in 11 patents (aged 48-76 years) with anastomotic stenoses due to recurrent gastric malignancies. The strictures involved both the afferent and efferent loops in three patients. All patients had poor peroral food intake with severe nausea and vomiting after ingestion. The technical and clinical success was evaluated.Results: Placement of the covered stent was technically successful in 13 of 15 (87%) attempts in ten patients. After the procedure, 9 of 11 (82%) patients overall were able to ingest at least a liquid diet and had markedly decreased incidence of vomiting. During the follow-up of 2-31 weeks (mean 8.5 weeks) there were no major complications.Conclusion: These preliminary results suggest that flexible, covered stents may provide effective palliation of malignant anastomotic stricture secondary to recurrent gastric cancer.

  3. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases

    PubMed Central

    Tontini, Gian Eugenio; Rath, Timo; Neumann, Helmut

    2016-01-01

    Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn’s disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID:26811662

  4. Oncolytic virotherapy for human malignant mesothelioma: recent advances.

    PubMed

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM.

  5. Oncolytic virotherapy for human malignant mesothelioma: recent advances

    PubMed Central

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM. PMID:27512676

  6. Supraclavicular lymph node metastases from malignant gastrointestinal stromal tumor of the jejunum: A case report with review of the literature

    PubMed Central

    Ma, Chi; Hao, Shao-Long; Liu, Xin-Cheng; Nin, Jin-Yao; Wu, Guo-Chang; Jiang, Li-Xin; Fancellu, Alessandro; Porcu, Alberto; Zheng, Hai-Tao

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumors of the alimentary tract. These tumors may have different clinical and biological behaviors. Malignant forms usually spread via a hematogenous route, and lymph node metastases rarely occur. Herein, we report a patient with a jejunal GIST who developed supraclavicular lymph node metastasis. We conclude that lymphatic diffusion via the mediastinal lymphatic station to the supraclavicular lymph nodes can be a potential metastatic route for GISTs. PMID:28348499

  7. Advances in the treatment of hematologic malignancies using immunoconjugates

    PubMed Central

    Palanca-Wessels, Maria Corinna

    2014-01-01

    Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotoxins (protein toxin), radioimmunoconjugates (radionuclide), and antibody drug conjugates (small-molecule drug). Optimization of each individual component of an IC (antibody, linker, and effector) is essential for therapeutic efficacy. Clinical trials have been conducted to investigate the effectiveness of ICs in hematologic malignancies both as monotherapy and in multiagent regimens in relapsed/refractory disease as well as frontline settings. These studies have yielded encouraging results particularly in lymphoma. ICs comprise an exciting group of therapeutics that promise to play an increasingly important role in the management of hematologic malignancies. PMID:24578502

  8. Advanced Cytologic Techniques for the Detection of Malignant Pancreatobiliary Strictures

    PubMed Central

    Moreno Luna, Laura E.; Kipp, Benjamin; Halling, Kevin C.; Sebo, Thomas J.; Kremers., Walter K.; Roberts, Lewis R.; Barr Fritcher, Emily G.; Levy, Michael J.; Gores, Gregory J.

    2006-01-01

    Background & Aims Two advanced cytologic techniques for detecting aneuploidy, digital image analysis (DIA) and fluorescence in situ hybridization (FISH) have recently been developed to help identify malignant pancreatobiliary strictures. The aim of this study was to assess the clinical utility of cytology, DIA, and FISH for the identification of malignant pancreatobiliary strictures. Methods Brush cytologic specimens from 233 consecutive patients undergoing ERCP for pancreatobiliary strictures were examined by all three techniques. Strictures were stratified as proximal (n=33) or distal (n=114) based on whether they occurred above or below the cystic duct, respectively. Strictures in patients with PSC (n=86) were analyzed separately. Results Despite the stratification, the performances of the tests were similar. Routine cytology has a low sensitivity (5–20%) but 100% specificity. Because of the high specificity for cytology, we assessed the performance of the other tests when routine cytology was negative. In this clinical context, FISH had an increased sensitivity (35–60%) when assessing for chromosomal gains (polysomy) while preserving the specificity of cytology. The sensitivity and specificity of DIA was intermediate as compared to routine cytology and FISH, but was additive to FISH values demonstrating only trisomy of chromosome 7 or chromosome 3. Conclusions These findings suggest that FISH and DIA increase the sensitivity for the diagnosis of malignant pancreatobiliary tract strictures over that obtained by conventional cytology while maintaining an acceptable specificity. PMID:17030177

  9. Recent advances in T-cell immunotherapy for haematological malignancies.

    PubMed

    Rouce, Rayne H; Sharma, Sandhya; Huynh, Mai; Heslop, Helen E

    2017-03-01

    In vitro discoveries have paved the way for bench-to-bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T-cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses. Honing manufacturing processes will increase the availability of T-cell products, while combining T-cell therapies has the ability to increase complete response rates. Lastly, innovative mechanisms to control these therapies may improve safety profiles while genome editing offers the prospect of modulating T-cell function. This review will focus on recent advances in T-cell immunotherapy, highlighting both clinical and pre-clinical advances, as well as exploring what the future holds.

  10. Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2017-01-03

    Adenocarcinoma of Unknown Primary; Adult Cholangiocarcinoma; Gallbladder Carcinoma; Gastric Adenocarcinoma; Malignant Gastrointestinal Neoplasm; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Stage III Ampulla of Vater Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IV Ampulla of Vater Cancer; Stage IV Gallbladder Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer

  11. The application of functional imaging techniques to personalise chemoradiotherapy in upper gastrointestinal malignancies.

    PubMed

    Wilson, J M; Partridge, M; Hawkins, M

    2014-09-01

    Functional imaging gives information about physiological heterogeneity in tumours. The utility of functional imaging tests in providing predictive and prognostic information after chemoradiotherapy for both oesophageal cancer and pancreatic cancer will be reviewed. The benefit of incorporating functional imaging into radiotherapy planning is also evaluated. In cancers of the upper gastrointestinal tract, the vast majority of functional imaging studies have used (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Few studies in locally advanced pancreatic cancer have investigated the utility of functional imaging in risk-stratifying patients or aiding target volume definition. Certain themes from the oesophageal data emerge, including the need for a multiparametric assessment of functional images and the added value of response assessment rather than relying on single time point measures. The sensitivity and specificity of FDG-PET to predict treatment response and survival are not currently high enough to inform treatment decisions. This suggests that a multimodal, multiparametric approach may be required. FDG-PET improves target volume definition in oesophageal cancer by improving the accuracy of tumour length definition and by improving the nodal staging of patients. The ideal functional imaging test would accurately identify patients who are unlikely to achieve a pathological complete response after chemoradiotherapy and would aid the delineation of a biological target volume that could be used for treatment intensification. The current limitations of published studies prevent integrating imaging-derived parameters into decision making on an individual patient basis. These limitations should inform future trial design in oesophageal and pancreatic cancers.

  12. Critical analysis of feeding jejunostomy following resection of upper gastrointestinal malignancies

    PubMed Central

    Blakely, Andrew M; Ajmal, Saad; Sargent, Rachel E; Ng, Thomas T; Miner, Thomas J

    2017-01-01

    AIM To assess nutritional recovery, particularly regarding feeding jejunostomy tube (FJT) utilization, following upper gastrointestinal resection for malignancy. METHODS A retrospective review was performed of a prospectively-maintained database of adult patients who underwent esophagectomy or gastrectomy (subtotal or total) for cancer with curative intent, from January 2001 to June 2014. Patient demographics, the approach to esophagectomy, the extent of gastrectomy, FJT placement and utilization at discharge, administration of parenteral nutrition (PN), and complications were evaluated. All patients were followed for at least ninety days or until death. RESULTS The 287 patients underwent upper GI resection, comprised of 182 esophagectomy (n = 107 transhiatal, 58.7%; n = 56 Ivor-Lewis, 30.7%) and 105 gastrectomy [n = 63 subtotal (SG), 60.0%; n = 42 total (TG), 40.0%]. 181 of 182 esophagectomy patients underwent FJT, compared with 47 of 105 gastrectomy patients (99.5% vs 44.8%, P < 0.0001), of whom most had undergone TG (n = 39, 92.9% vs n = 8 SG, 12.9%, P < 0.0001). Median length of stay was similar between esophagectomy and gastrectomy groups (14.7 d vs 17.1 d, P = 0.076). Upon discharge, 87 esophagectomy patients (48.1%) were taking enteral feeds, with 53 (29.3%) fully and 34 (18.8%) partially dependent. Meanwhile, 20 of 39 TG patients (51.3%) were either fully (n = 3, 7.7%) or partially (n = 17, 43.6%) dependent on tube feeds, compared with 5 of 8 SG patients (10.6%), all of whom were partially dependent. Gastrectomy patients were significantly less likely to be fully dependent on tube feeds at discharge compared to esophagectomy patients (6.4% vs 29.3%, P = 0.0006). PN was administered despite FJT placement more often following gastrectomy than esophagectomy (n = 11, 23.4% vs n = 7, 3.9%, P = 0.0001). FJT-specific complications requiring reoperation within 30 d of resection occurred more commonly in the gastrectomy group (n = 6), all after TG, compared to 1

  13. Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract.

    PubMed

    Stockman, David L; Miettinen, Markku; Suster, Saul; Spagnolo, Dominic; Dominguez-Malagon, Hugo; Hornick, Jason L; Adsay, Volkan; Chou, Pauline M; Amanuel, Benhur; Vantuinen, Peter; Zambrano, Eduardo V

    2012-06-01

    patients were alive with regional, lymph node, and liver metastases, and 2 patients were alive with no evidence of disease. The tumor described here is an aggressive form of neuroectodermal tumor that should be separated from other primitive epithelioid and spindle cell tumors of the gastrointestinal tract. The distinctive ultrastructural features and absence of melanocytic differentiation serve to separate them from soft tissue clear cell sarcomas involving the gastrointestinal tract. The designation "malignant gastrointestinal neuroectodermal tumor" is proposed for this tumor type.

  14. Advances in local ablation of malignant liver lesions

    PubMed Central

    Eisele, Robert M

    2016-01-01

    Local ablation of liver tumors matured during the recent years and is now proven to be an effective tool in the treatment of malignant liver lesions. Advances focus on the improvement of local tumor control by technical innovations, individual selection of imaging modalities, more accurate needle placement and the free choice of access to the liver. Considering data found in the current literature for conventional local ablative treatment strategies, virtually no single technology is able to demonstrate an unequivocal superiority. Hints at better performance of microwave compared to radiofrequency ablation regarding local tumor control, duration of the procedure and potentially achievable larger size of ablation areas favour the comparably more recent treatment modality; image fusion enables more patients to undergo ultrasound guided local ablation; magnetic resonance guidance may improve primary success rates in selected patients; navigation and robotics accelerate the needle placement and reduces deviation of needle positions; laparoscopic thermoablation results in larger ablation areas and therefore hypothetically better local tumor control under acceptable complication rates, but seems to be limited to patients with no, mild or moderate adhesions following earlier surgical procedures. Apart from that, most techniques appear technically feasible, albeit demanding. Which technology will in the long run become accepted, is subject to future work. PMID:27099433

  15. Uncommon gastrointestinal bleeding during targeted therapy for advanced renal cell carcinoma: A report of four cases

    PubMed Central

    FUJIHARA, SHINTARO; MORI, HIROHITO; KOBARA, HIDEKI; NISHIYAMA, NORIKO; AYAKI, MAKI; OHATA, RYO; UEDA, NOBUFUMI; SUGIMOTO, MIKIO; KAKEHI, YOSHIYUKI; MASAKI, TSUTOMU

    2015-01-01

    Clinically available targeted agents to treat advanced renal cell carcinoma (RCC) include sunitinib, sorafenib and temsirolimus. Sorafenib and sunitinib have been associated with bleeding in selected trials, but clinical and endoscopic characteristics of gastrointestinal bleeding are not well described. Herein, we report four cases of advanced RCC in which endoscopic hemostasis effectively resolved high-grade, life-threatening gastrointestinal bleeding that occurred during targeted therapy. Although stomatitis and mucositis have occurred during targeted therapies, life-threatening gastrointestinal bleeding is less common. In these four patients, the origins of gastrointestinal bleeding were identified, and complete endoscopic hemostasis was achieved. Endoscopies revealed variable characteristics including angiodysplasia, multiple gastric ulcers and oozing bleeding of the normal mucosa. Although the most effective diagnostic and treatment strategies are disputed, endoscopic examinations are best performed before starting targeted therapies. Additionally, these patients should be monitored even for rare life-threatening events. PMID:26722259

  16. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  17. Advanced MRI applications and findings of malignant phyllodes tumour: review of two cases.

    PubMed

    Alhabshi, Sharifah Majedah Idrus; Rahmat, Kartini; Abu Hassan, Hasyma; Westerhout, Caroline Judy; Chandran, Patricia Ann

    2013-05-01

    Phyllodes tumour or cystosarcoma phyllodes is a rare stromal breast tumour that is usually benign but on rare occasions can turn malignant. Non-specificity of the imaging features on sonography and mammography makes it difficult to distinguish malignant from benign counterparts solely based on imaging. The final diagnosis is still highly dependent on histopathological assessment. Herein, we describe two cases of malignant phyllodes tumour with emphasis on magnetic resonance (MR) imaging features using advanced MR applications.

  18. Deciphering molecular determinants of chemotherapy in gastrointestinal malignancy using systems biology approaches.

    PubMed

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2014-09-01

    Gastrointestinal cancers are asymptomatic in early tumor development, leading to high mortality rates. Peri- or postoperative chemotherapy is a common strategy used to prolong the life expectancy of patients with these diseases. Understanding the molecular mechanisms by which anticancer drugs exert their effect is crucial to the development of anticancer therapies, especially when drug resistance occurs and an alternative drug is needed. By integrating high-throughput techniques and computational modeling to explore biological systems at different levels, from gene expressions to networks, systems biology approaches have been successfully applied in various fields of cancer research. In this review, we highlight chemotherapy studies that reveal potential signatures using microarray analysis, next-generation sequencing (NGS), proteomic and metabolomic approaches for the treatment of gastrointestinal cancers.

  19. Advances in the systemic therapy of malignant pleural mesothelioma.

    PubMed

    Fennell, Dean A; Gaudino, Giovanni; O'Byrne, Kenneth J; Mutti, Luciano; van Meerbeeck, Jan

    2008-03-01

    Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

  20. Updates on surgical management of advanced gastric cancer: new evidence and trends. Insights from the First International Course on Upper Gastrointestinal Surgery--Varese (Italy), December 2, 2011.

    PubMed

    Rausei, Stefano; Dionigi, Gianlorenzo; Sano, Takeshi; Sasako, Mitsuru; Biondi, Alberto; Morgagni, Paolo; Garofalo, Alfredo; Boni, Luigi; Frattini, Francesco; D'Ugo, Domenico; Preston, Shaun; Marrelli, Daniele; Degiuli, Maurizio; Capella, Carlo; Sacco, Rosario; Ruspi, Laura; De Manzoni, Giovanni; Roviello, Franco; Pinotti, Graziella; Rovera, Francesca; Noh, Sung Hoon; Coit, Daniel; Dionigi, Renzo

    2013-11-01

    Between the Ninth International Gastric Cancer Congress (IGCC) in South-Korea (Seoul, 2011) and the Tenth IGCC in Italy (Verona, 2013), the Insubria University organized the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011), with the patronage of Italian Research Group for Gastric Cancer (IRGGC) and the International Gastric Cancer Association (IGCA). The Course was intended to be a comprehensive update and review on advanced gastric cancer (GC) staging and treatment from well-known international experts. Clinical, research, and educational aspects of the surgeon's role in the era of stage-adapted therapy were discussed. As highlighted in the meeting, in this final document we summarize and thoroughly analyze (with references only for well-acquired randomized control trials) the new and old open problems in surgical management of advanced GC. Between the Ninth (Seoul, 2011) and the Tenth (Verona,2013) International Gastric Cancer Congress, the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011) was organized by the University of Insubria. This congress received the patronage of the International Gastric Cancer Association and the Italian Research Group for Gastric Cancer. The aim was to discuss open issues in surgical management of advanced gastric malignancies. We considered the opinions of several recognized experts in the field from both the Eastern and Western world, focused on definition problems and oncological and technical issues to define the current principles of advanced gastric cancer (GC) surgery.

  1. Clinical applications of recent molecular advances in urologic malignancies: no longer chasing a "mirage"?

    PubMed

    Netto, George J

    2013-05-01

    As our understanding of the molecular events leading to the development and progression of genitourologic malignancies, new markers of detection, prognostication, and therapy prediction can be exploited in the management of these prevalent tumors. The current review discusses the recent advances in prostate, bladder, renal, and testicular neoplasms that are pertinent to the anatomic pathologist.

  2. Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review.

    PubMed

    East, James E; Vleugels, Jasper L; Roelandt, Philip; Bhandari, Pradeep; Bisschops, Raf; Dekker, Evelien; Hassan, Cesare; Horgan, Gareth; Kiesslich, Ralf; Longcroft-Wheaton, Gaius; Wilson, Ana; Dumonceau, Jean-Marc

    2016-11-01

    Background and aim: This technical review is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the utilization of advanced endoscopic imaging in gastrointestinal (GI) endoscopy. Methods: This technical review is based on a systematic literature search to evaluate the evidence supporting the use of advanced endoscopic imaging throughout the GI tract. Technologies considered include narrowed-spectrum endoscopy (narrow band imaging [NBI]; flexible spectral imaging color enhancement [FICE]; i-Scan digital contrast [I-SCAN]), autofluorescence imaging (AFI), and confocal laser endomicroscopy (CLE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. Main recommendations:1. We suggest advanced endoscopic imaging technologies improve mucosal visualization and enhance fine structural and microvascular detail. Expert endoscopic diagnosis may be improved by advanced imaging, but as yet in community-based practice no technology has been shown consistently to be diagnostically superior to current practice with high definition white light. (Low quality evidence.) 2. We recommend the use of validated classification systems to support the use of optical diagnosis with advanced endoscopic imaging in the upper and lower GI tracts (strong recommendation, moderate quality evidence). 3. We suggest that training improves performance in the use of advanced endoscopic imaging techniques and that it is a prerequisite for use in clinical practice. A learning curve exists and training alone does not guarantee sustained high performances in clinical practice. (Weak recommendation, low quality evidence.) Conclusion: Advanced endoscopic imaging can improve mucosal visualization and endoscopic diagnosis; however it requires training and the use of validated classification systems.

  3. Gastrointestinal Stent Update

    PubMed Central

    2010-01-01

    The use of self-expanding metallic stents in the upper gastrointestinal tract, placed under radiologic imaging or endoscopic guidance, is the current treatment of choice for the palliation of malignant gastrointestinal outlet obstructions. Advances in metallic stent design and delivery systems have progressed to the stage where this treatment is now considered a minimally invasive therapy. Metallic stent placement will broaden further into the field of nonsurgical therapy for the gastrointestinal tract. To date, metallic stents placed in the esophagus, gastric outlet, colorectum, and bile ducts are not intended to be curative, but rather to provide a palliative treatment for obstructions. The evolution of metallic stent technology will render such procedures not only palliative but also therapeutic, by enabling local drug delivery, and the use of biodegradable materials will reduce procedure-related complications. PMID:21103290

  4. Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma.

    PubMed

    Huse, Jason T; Holland, Eric C

    2010-05-01

    Malignant brain tumours continue to be the cause of a disproportionate level of morbidity and mortality across a wide range of individuals. The most common variants in the adult and paediatric populations - malignant glioma and medulloblastoma, respectively - have been the subject of increasingly intensive research over the past two decades that has led to considerable advances in the understanding of their basic biology and pathogenesis. This Review summarizes these developments in the context of the evolving notion of molecular pathology and discusses the implications that this work has on the design of new treatment regimens.

  5. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014

    PubMed Central

    Tsvetkova, E.; Sud, S.; Aucoin, N.; Biagi, J.; Burkes, R.; Samson, B.; Brule, S.; Cripps, C.; Colwell, B.; Falkson, C.; Dorreen, M.; Goel, R.; Halwani, F.; Maroun, J.; Michaud, N.; Tehfe, M.; Thirlwell, M.; Vickers, M.; Asmis, T.

    2015-01-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23–25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer. PMID:26300681

  6. The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology.

    PubMed

    Xue, Yue; Farris, Alton Brad; Quigley, Brian; Krasinskas, Alyssa

    2017-04-01

    The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.

  7. Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies.

    SciTech Connect

    Shen, Shang; Forero, Andres; LoBuglio, Albert F.; Breitz, H; Khazaeli, M B.; Fisher, Darrell R.; Wang, W Q.; Meredith, Ruby F.

    2005-04-01

    Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. Shen S, Forero A, Lobuglio AF, Breitz H, Khazaeli MB, Fisher DR, Wang W, Meredith RF. Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, and Radioisotopes Program at Pacific Northwest National Laboratory, Richland, Washington. Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)(4) and streptavidin, in conjunction with (90)Y/(111)In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted (90)Y/(111)In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. METHODS: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m(2) of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) (90)Y/(111)In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body (111)In images were acquired immediately and at 2-144 h after injection of (90)Y/(111)In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor (90)Y doses were calculated based on (111)In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. RESULTS: The (90)Y/(111)In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean (90)Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32-0.78) to whole body

  8. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors of the stomach: report of three cases.

    PubMed

    Oh, Ji Seon; Lee, Jae-Lyun; Kim, Mi-Jung; Ryu, Min-Hee; Chang, Heung Moon; Kim, Tae Won; Jang, Se Jin; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kang, Yoon-Koo

    2006-01-01

    Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

  9. Intercostal nerves block for mastectomy in two patients with advanced breast malignancy.

    PubMed

    Kolawole, Israel K; Adesina, Michael D; Olaoye, Iyiade O

    2006-03-01

    Regional anesthesia is recognized as an alternative to general anesthesia for modern breast cancer surgery. Various techniques of block have been described. Each has its unique problems. Regional anesthesia was chosen for simple mastectomy in two patients with advanced breast malignancy, due to compromised pulmonary status resulting from widespread malignant infiltration of both lungs. We used intercostal nerves block. The block was supplemented with an infraclavicular infiltration to interrupt the branches of the superficial cervical plexus that provide sensation to the upper chest wall and subcutaneous infiltration in the midline to block the nerve supply from the contralateral side. Anesthesia was generally effective and the operations were uneventful. Both patients and surgeons expressed satisfaction. We conclude that where patients have significant comorbidities that make general anesthesia undesirable, the use of intercostal nerves block remains a safe and reliable anesthetic option that allows the patient access to surgery for simple mastectomy.

  10. Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Carcinoma of the Appendix; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor; Liver Cancer; Pancreatic Cancer; Small Intestine Cancer

  11. Cholangiocarcinoma and malignant bile duct obstruction: A review of last decades advances in therapeutic endoscopy

    PubMed Central

    Bertani, Helga; Frazzoni, Marzio; Mangiafico, Santi; Caruso, Angelo; Manno, Mauro; Mirante, Vincenzo Giorgio; Pigò, Flavia; Barbera, Carmelo; Manta, Raffaele; Conigliaro, Rita

    2015-01-01

    In the last decades many advances have been achieved in endoscopy, in the diagnosis and therapy of cholangiocarcinoma, however blood test, magnetic resonance imaging, computed tomography scan may fail to detect neoplastic disease at early stage, thus the diagnosis of cholangiocarcinoma is achieved usually at unresectable stage. In the last decades the role of endoscopy has moved from a diagnostic role to an invaluable therapeutic tool for patients affected by malignant bile duct obstruction. One of the major issues for cholangiocarcinoma is bile ducts occlusion, leading to jaundice, cholangitis and hepatic failure. Currently, endoscopy has a key role in the work up of cholangiocarcinoma, both in patients amenable to surgical intervention as well as in those unfit for surgery or not amenable to immediate surgical curative resection owing to locally advanced or advanced disease, with palliative intention. Endoscopy allows successful biliary drainage and stenting in more than 90% of patients with malignant bile duct obstruction, and allows rapid reduction of jaundice decreasing the risk of biliary sepsis. When biliary drainage and stenting cannot be achieved with endoscopy alone, endoscopic ultrasound-guided biliary drainage represents an effective alternative method affording successful biliary drainage in more than 80% of cases. The purpose of this review is to focus on the currently available endoscopic management options in patients with cholangiocarcinoma. PMID:26078827

  12. What we learned from difficult hepatectomies in patients with advanced hepatic malignancy

    PubMed Central

    Jung, Bo Hyun; Lee, Jae Hoon; Lee, Sang Yeup; Song, Dae Keun; Hwang, Ji Woong; Hwang, Dae Wook; Lee, Young-Joo

    2011-01-01

    Backgrounds/Aims By reviewing difficult resections for advanced hepatic malignancies, we discuss the effectiveness and extended indications for hepatectomy in such patients. Methods We reviewed 7 patients who underwent extensive surgery between July 2008 and March 2011 for advanced hepatic malignancies. They had stage IV disease, except for in one case that was a stage IIIC (T4N0M0) hepatocellular carcinoma (HCC). Results Patient 1 with intrahepatic cholangiocarcinoma (IHCC) underwent right hemihepatectomy and resection of the bile duct and left portal vein. At 39 months after surgery, she had no recurrence or metastasis. Patient 2 with HCC underwent palliative right trisectionectomy. At 38 months after surgery, he is alive despite residual pulmonary metastases. Patient 3 with HCC invading the hepatic vein and diaphragm underwent right trisectionectomy and caval venoplasty. At 12 months after surgery, he had no recurrence or metastasis. Patient 4, who had 2 large HCCs and pulmonary thromboembolism, underwent a right trisectionectomy. At 7 months after surgery, he had no evidence of recurred HCC. Patient 5, who had IHCC invading her inferior vena cava and main portal vein, underwent preoperative radiotherapy, left hemihepatectomy, and caval resection. At 20 months after surgery, she is well despite a caval thrombus. Patient 6 and 7 underwent repeated surgery due to a recurred IHCC and metastatic colon cancer, respectively. In addition, they are alive during each 20 and 17 months after surgery. Conclusions Despite macroscopic extrahepatic metastases or major vessel involvement, extensive surgery for advanced hepatic malignancy may result in relatively favorable outcomes and be important modality for improving of survival in such patients. PMID:26421042

  13. Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update.

    PubMed

    Aprile, Giuseppe; Rihawi, Karim; De Carlo, Elisa; Sonis, Stephen T

    2015-11-07

    Gastrointestinal toxicities (GIT), including oral mucositis, nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.

  14. Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update

    PubMed Central

    Aprile, Giuseppe; Rihawi, Karim; De Carlo, Elisa; Sonis, Stephen T

    2015-01-01

    Gastrointestinal toxicities (GIT), including oral mucositis, nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient’s quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient’s outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient’s compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer. PMID:26557003

  15. Analysis of Clinical and Dosimetric Factors Associated With Change in Renal Function in Patients With Gastrointestinal Malignancies After Chemoradiation to the Abdomen

    SciTech Connect

    May, Kilian Salerno; Khushalani, Nikhil I.; Chandrasekhar, Rameela; Wilding, Gregory E.; Iyer, Renuka V.; Ma, Wen W.; Flaherty, Leayn; Russo, Richard C. C.; Fakih, Marwan; Kuvshinoff, Boris W.; Gibbs, John F.; Javle, Milind M.; Yang, Gary Y.

    2010-03-15

    Purpose: To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. Methods and Materials: A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose-volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema. Results: Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p < 0.0001). Mean decrease in CrCl was 21.37%. Pre-RT CrCl, percentage of bilateral renal volume receiving at least 10 Gy (V{sub 10}), and mean kidney dose were significantly associated with development of Grade >=2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively). Conclusions: We observed correlation between pre-RT CrCl, V{sub 10}, and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications.

  16. Molecular predictive markers in tumors of the gastrointestinal tract

    PubMed Central

    Papadopoulou, Eirini; Metaxa-Mariatou, Vasiliki; Tsaousis, Georgios; Tsoulos, Nikolaos; Tsirigoti, Angeliki; Efstathiadou, Chrisoula; Apessos, Angela; Agiannitopoulos, Konstantinos; Pepe, Georgia; Bourkoula, Eugenia; Nasioulas, George

    2016-01-01

    Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors’ genetic profiling using new breakthrough technologies such as next generation sequencing (NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection. During the last 10 years tremendous advances in the development of targeted therapies for patients with advanced cancer have been made, thus various targeted agents, associated with predictive biomarkers, have been developed or are in development for the treatment of patients with gastrointestinal cancer patients. This review summarizes the advances in the field of molecular biomarkers in tumors of the gastrointestinal tract, with focus on the available NGS platforms that enable comprehensive tumor molecular profile analysis. PMID:27895815

  17. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    SciTech Connect

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-10-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses.

  18. Evaluation of intrathecal drug delivery system for intractable pain in advanced malignancies

    PubMed Central

    Zheng, Shuyue; He, Liangliang; Yang, Xiaohui; Li, Xiuhua; Yang, Zhanmin

    2017-01-01

    Abstract Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients. A prospective cohort study was performed between July 2015 and October 2016. Fifty-three patients undergoing intractable cancer-related pain or intolerable drug-related adverse effects were recruited and received IDDS therapy with a patient-controlled intrathecal analgesia pump. The assessment was conducted during admission, in titration period, and followed up monthly to death by scheduled refill visits. Pain numeric rating scale scores, comprehensive toxicity scores, quality of life scores, systemic opioid use (basal and breakthrough dose), intrathecal morphine use (basal and patient-controlled intrathecal analgesia dose), and complications were recorded to evaluate the curative effect and safety. Between baseline and all subsequent follow-ups, statistically significant decreases in pain numeric rating scale scores and comprehensive toxicity scores were verified. A statistical improvement in quality of life scores was found after starting IDDS therapy. Both basal and breakthrough doses of systemic opioid showed a significant decrease during the follow-up period. And there was a modest escalation in the intrathecal morphine dose throughout the duration of study. No infective, device-related, and catheter-related complications were observed. The findings showed that IDDS therapy allowed for rapid and highly effective pain relief with less toxicity in comparison to conservative medications. Patients with

  19. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.

    PubMed

    Okano, Yudai; Satoh, Tetsurou; Horiguchi, Kazuhiko; Toyoda, Minoru; Osaki, Aya; Matsumoto, Shunichi; Tomaru, Takuya; Nakajima, Yasuyo; Ishii, Sumiyasu; Ozawa, Atsushi; Shibusawa, Nobuyuki; Shimada, Takehiro; Higuchi, Tetsuya; Chikamatsu, Kazuaki; Yamada, Masanobu

    2016-10-29

    The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6(th) administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7(th) administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7(th) administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.

  20. Advances in the diagnosis of key gastrointestinal nematode infections of livestock, with an emphasis on small ruminants.

    PubMed

    Roeber, Florian; Jex, Aaron R; Gasser, Robin B

    2013-12-01

    Parasitic nematodes (roundworms) of livestock have major economic impact globally. In spite of the diseases caused by these nematodes and some advances in the design of new therapeutic agents (anthelmintics) and attempts to develop vaccines against some of them, there has been limited progress in the establishment of practical diagnostic techniques. The specific and sensitive diagnosis of gastrointestinal nematode infections of livestock underpins effective disease control, which is highly relevant now that anthelmintic resistance (AR) is a major problem. Traditional diagnostic techniques have major constraints, in terms of sensitivity and specificity. The purpose of this article is to provide a brief background on gastrointestinal nematodes (Strongylida) of livestock and their control; to summarize conventional methods used for the diagnosis and discuss their constraints; to review key molecular-diagnostic methods and recent progress in the development of advanced amplification-based and sequencing technologies, and their implications for epidemiological investigations and the control of parasitic diseases.

  1. Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies

    PubMed Central

    Fisher, Kevin E.; Zhang, Linsheng; Wang, Jason; Smith, Geoffrey H.; Newman, Scott; Schneider, Thomas M.; Pillai, Rathi N.; Kudchadkar, Ragini R.; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Lawson, David H.; Delman, Keith A.; El-Rayes, Bassel F.; Wilson, Malania M.; Sullivan, H. Clifford; Morrison, Annie S.; Balci, Serdar; Adsay, N. Volkan; Gal, Anthony A.; Sica, Gabriel L.; Saxe, Debra F.; Mann, Karen P.; Hill, Charles E.; Khuri, Fadlo R.; Rossi, Michael R.

    2017-01-01

    We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. PMID:26801070

  2. Intensity-modulated radiotherapy reduces gastrointestinal toxicity in locally advanced pancreas cancer

    PubMed Central

    Prasad, Shreya; Cambridge, Lajhem; Huguet, Florence; Chou, Joanne F.; Zhang, Zhigang; Wu, Abraham J.; O'Reilly, Eileen M.; Allen, Peter; Goodman, Karyn A.

    2016-01-01

    Purpose We compared gastrointestinal (GI) and hematologic toxicity in patients with locally advanced pancreas cancer (LAPC) undergoing definitive chemoradiation using intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3D-CRT) planning. Methods and Materials We retrospectively studied 205 patients with LAPC undergoing IMRT (n=134) and 3D-CRT (n=71) between 05/03 and 03/12. Patient, tumor, and treatment characteristics and acute GI/hematology toxicity according to Common Terminology Criteria for Adverse Events v3.0 were recorded. Multivariable logistic regression models were used to test association between acute grade 2+ GI and hematologic toxicity outcomes and predictors. Propensity score analysis for grade 2+ GI toxicity was performed to reduce bias for confounding variables: age, gender, radiation dose, field size, and chemotherapy type. Results Median follow-up time for survivors was 22 months, similar between groups. Median RT dose was significantly higher for IMRT vs. 3D-CRT (5600 cGy vs 5040 cGy, P<.001); concurrent chemotherapy was mainly gemcitabine (56%) or 5-fluorouracil (5-FU, 38%). Grade 2+ GI toxicity occurred in 34% (n=24) of 3D-CRT compared with 16% (n=21) of IMRT patients. Using propensity-score analysis, 3D-CRT had significantly higher grade 2+ GI toxicity (odds ratio, 1.26 [95%CI, 1.08-1.45], P=.001). Grade 2+ hematologic toxicity was similar between IMRT and 3D-CRT groups but was significantly greater in recipients of concurrent gemcitabine over 5-FU (62% vs 29%, P<.0001). Conclusions IMRT is associated with significant lower grade 2+ GI toxicity versus 3D-CRT for patients undergoing definitive chemoradiotherapy for LAPC. Since IMRT is better tolerated at higher doses and may allow further dose escalation, potentially improving local control for this aggressive disease. Further prospective studies of dose-escalated chemoradiation using IMRT are warranted. PMID:26577010

  3. Applications and Advancements in the use of High-Resolution Microendoscopy for Detection of Gastrointestinal Neoplasia

    PubMed Central

    Louie, Justin S.; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

    2014-01-01

    The high-resolution microendoscope (HRME) is a novel imaging modality that allows real-time epithelial imaging at subcellular resolution. Used in concert with any standard endoscope, this portable, low cost, ‘optical biopsy’ technology has the ability to provide images of cellular morphology during a procedure. This technology has been the subject of a number of studies investigating its use in screening and surveillance of a range of gastrointestinal neoplasia, including esophageal adenocarcinoma(EAC), esophageal squamous cell cancer(ESCC), colorectal neoplasia(CRC) and anal neoplasia. These studies have shown that HRME is a modality that consistently provides high specificity, negative predictive value, and accuracy across different diseases. In addition, they have illustrated that HRME users can be relatively easily trained in a short period of time and that users have demonstrated solid inter-rater reliability. These features make HRME a potential complement to high definition white light imaging, narrow band imaging and other ‘red flag technologies’ in facilitating real-time clinical diagnosis, endoscopic therapy and margin determination. Further clinical validation is needed to determine whether this translates to reduced procedure times, pathology costs, and follow up procedures. Finally, the HRME has a relatively simple design compared to other similar technologies, making it portable, simple to maintain, and low cost. This may allow the HRME device to function in both advanced care settings as well as in places with less resources and specialized support systems. As a whole, the HRME device has shown good performance along with low-cost and portable construction, and its application in different conditions and settings has been promising. PMID:25108219

  4. Treatment approach in patients with hyperbilirubinemia secondary to liver metastases in gastrointestinal malignancies: a case series and review of literature

    PubMed Central

    Quidde, Julia; Azémar, Marc; Bokemeyer, Carsten; Arnold, Dirk; Stein, Alexander

    2016-01-01

    Background: Treatment of patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastases of gastrointestinal (GI) cancer is challenging. Regimen of oxaliplatin and fluoropyrimidine (FP)/folinic acid (FA) ± a monoclonal antibody (moAb), represents a feasible option considering the pharmacokinetics. Clinical data on the respective dosage and tolerability are limited and no recommendations are available. Methods: Consecutive patients with severe hyperbilirubinemia [>2 × upper limit of the normal range (ULN) and >2.4 mg/dl] due to liver metastases of GI cancer without options for drainage receiving oxaliplatin, FP/FA ± moAb were analyzed. To collect further data a review of the literature was performed. Results: A total of 12 patients were identified between 2011 and 2015. At treatment start, median bilirubin level was 6.1 mg/dl (>5 × ULN, range 2.7–13.6). The majority of patients (n = 11) received dose-reduced regimen with oxaliplatin (60–76%) and FP/FA (0–77%), rapidly escalating to full dose regimen. During treatment, bilirubin levels dropped more than 50% within 8 weeks or normalized within 12 weeks in 6 patients (responders). Median overall survival was 5.75 months (range 1.0–16.0 months) but was significantly prolonged in responders compared to nonresponders [9.7 and 3.0 months, p = 0.026 (two-sided test); 95% confidence interval (CI): 1.10–10.22]. In addition, case reports or series comprising a further 26 patients could be identified. Based on the obtained data a treatment algorithm was developed. Conclusion: Treatment with oxaliplatin, FP/FA ± moAb is feasible and may derive relevant benefits in patients with severe liver dysfunction caused by GI cancer liver metastases without further options of drainage. PMID:27239232

  5. Detection of malignant lesions in vivo in the upper gastrointestinal tract using image-guided Raman endoscopy

    NASA Astrophysics Data System (ADS)

    Bergholt, Mads Sylvest; Zheng, Wei; Lin, Kan; Ho, Khek Yu; Yeoh, Khay Guan; Teh, Ming; So, Jimmy Bok Yan; Huang, Zhiwei

    2012-01-01

    Raman spectroscopy is a vibrational analytic technique sensitive to the changes in biomolecular composition and conformations occurring in tissue. With our most recent development of near-infrared (NIR) Raman endoscopy integrated with diagnostic algorithms, in vivo real-time Raman diagnostics has been realized under multimodal wide-field imaging (i.e., white- light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 177 patients who previously underwent Raman endoscopy (n=2510 spectra) was used to render two robust models based on partial least squares - discriminant analysis (PLS-DA) for esophageal and gastric cancer diagnosis. The Raman endoscopy technique was validated prospectively on 4 new gastric and esophageal patients for in vivo tissue diagnosis. The Raman endoscopic technique could identify esophageal cancer in vivo with a sensitivity of 88.9% (8/9) and specificity of 100.0% (11/11) and gastric cancers with a sensitivity of 77.8% (14/18) and specificity of 100.0% (13/13). This study realizes for the first time the image-guided Raman endoscopy for real-time in vivo diagnosis of malignancies in the esophagus and gastric at the biomolecular level.

  6. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers

    PubMed Central

    Kim, Jung Hoon; Kim, Bum Jun; Kim, Hyeong Su; Kim, Jung Han

    2016-01-01

    Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers. However, the era of cancer immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we briefly review the current status and perspective of immunotherapeutic approaches in patients with gastrointestinal cancers. PMID:27698896

  7. Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation.

    PubMed

    Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Moulia, Violetta; Elka, Aspasia; Gaitanis, Georgios; Bassukas, Ioannis D

    2015-06-26

    Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real-time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i) assembling the technical specifications of portable systems and (ii) analyzing the spectral characteristics of in vivo measurements.

  8. Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation

    PubMed Central

    Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Moulia, Violetta; Elka, Aspasia; Gaitanis, Georgios; Bassukas, Ioannis D.

    2015-01-01

    Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real-time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i) assembling the technical specifications of portable systems and (ii) analyzing the spectral characteristics of in vivo measurements. PMID:26132563

  9. Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

    PubMed

    Yuji, Koichiro; Miyakoshi, Shigesaburo; Kato, Daisuke; Miura, Yuji; Myojo, Tomohiro; Murashige, Naoko; Kishi, Yukiko; Kobayashi, Kazuhiro; Kusumi, Eiji; Narimatsu, Hiroto; Hamaki, Tamae; Matsumura, Tomoko; Kami, Masahiro; Fukuda, Takahiro; Masuo, Shigeru; Masuoka, Kazuhiro; Wake, Atsushi; Ueyama, Junichi; Yoneyama, Akiko; Miyamoto, Ko; Nagoshi, Haruhisa; Matsuzaki, Michio; Morinaga, Shinichi; Muto, Yoshitomo; Takeue, Yoichi; Taniguchi, Shuichi

    2005-04-01

    We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.

  10. [Phase-II-study with vindesine (desacetyl-vinblastine-amide-sulfate) in advanced malignant diseases].

    PubMed

    Goldhirsch, A; Beer, M; Sonntag, R W; Tschopp, L; Cavalli, F; Ryssel, H J; Brunner, K W

    1980-07-08

    53 patients with advanced and measurable cancerr were treated with vindesine in doses of 3 mg/m2 (pretreated) and 4 mg/m2 (non pretreated) i.v. once weekly. 48 patients are evaluable for response: of 14 patients with squamous cell carcinoma of the lung, 1 partial remission (PR), 1 minor response (MR) and 1 no change (NC) were observed. In 5 patients with large cell carcinoma of the lung: 1 NC. In 3 with adenocarcinoma of the lung: 1 MR. One patient with nasopharyngeal carcinoma had progressive disease. Stable disease was observed in a patient with carcinoma of the tongue and in a patient with adenocarcinoma of the esophagus. Four patients with colorectal carcinoma had progressive disease. One MR was observed in a patient with breast cancer, while all of the other 3 patients had progressive disease. One carcinoma of the penis was stable. One MR was observed in a patient with Hodgkin's disease. One PR was observed in a case with no-Hodgkin's lymphoma. A patient with acute leukemia had progressive disease. Among 9 patients with malignant melanoma, 3 had an MR and 1 patient had stable disease. A patient with fibrosarcoma had progressive disease. Observed toxicity included leukopenia, thrombocytopenia, anemia, paresthesias, constipation, jaw pain, nausea, stomatitis, alopecia, loss of taste, pruritus and skin rash, weakness and fatigue.

  11. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review

    PubMed Central

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored “low to moderate” on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with

  12. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review.

    PubMed

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person's future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program's appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored "low to moderate" on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  13. Is surgery mandatory in locally advanced gastrointestinal stromal tumors after imatinib? A case report and literature review

    PubMed Central

    Congedo, Teresa; Ricci, Riccardo; Martini, Maurizio; Di Noia, Vincenzo; Di Dio, Carmela; Quirino, Michela; Barone, Carlo; Cassano, Alessandra

    2017-01-01

    Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment. PMID:28280629

  14. Pneumosinus Dilatans Helping Subcranial Resection in a Patient with Advanced Ethmoid Malignancy

    PubMed Central

    Joseph, Shawn T.; Thankappan, Krishnakumar; Buggaveeti, Rahul; Iyer, Subramania

    2014-01-01

    Subcranial approach is a useful procedure in the management of limited anterior skull base tumors. But the posterior and superior visualization may be limited, in ethmoid malignancies with a large intracranial extension. A 55-year-old male patient, a case of an ethmoid malignancy, with a large intracranial component was resected with adequate margins by a subcranial approach. The coincident pneumosinus dilatans helped the surgical resection. This case demonstrates that assessment of pneumatization of the frontal sinus is as important as the size and extent of the tumor, while deciding an anterior skull base surgical approach. Even large malignant lesions may be approached subcranially if the frontal sinus is proportionately large. Pneumosinus dilatans, though rare, can be used to the benefit of the patient in selecting a less invasive approach. PMID:26269730

  15. A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

    ClinicalTrials.gov

    2017-03-20

    Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3; Squamous Lung Cancer With FGFR1 Amplification; Bladder Cancer With FGFR3 Mutation or Fusion; Advanced Solid Tumors With FGFR1 Amplication; Advanced Solid Tumors With FGFR2 Amplication; Advanced Solid Tumors With FGFR3 Mutation

  16. Is early feeding after major gastrointestinal surgery a fashion or an advance? Evidence-based review of literature.

    PubMed

    Shrikhande, Shailesh V; Shetty, Guruprasad S; Singh, Kailash; Ingle, Sachin

    2009-01-01

    Early enteral nutrition (EN) after major digestive surgery has been receiving increasing attention. Supporting evidence has not been clear. This evidence-based review traces the development of early EN and analyses whether it is indeed an advance. We performed a PubMed search in October 2009 with the key words enteral nutrition, early feeding, and gastrointestinal surgery. Our emphasis was on earliest studies documenting the benefits or adverse effects of EN, comparative studies, documenting the benefits or adverse effects of EN, comparative studies, and randomized controlled trials. Thirty-one results were returned from which 17 were included for evaluation (1979-2009). Fifteen papers concluded that early EN was beneficial. In general, patients put on early EN and immunonutrition postoperatively seemed to have decreased hospital stay, decreased complication rates, decreased treatment and hospital costs, and even decreased morbidity and mortality; however, judicious use has been suggested. One study did not recommend early enteral feeding in well-nourished patients at low risk of nutrition-related complications and another suggested that immunonutrition is not beneficial and should not be used routinely. Early EN has been safely given after major digestive surgery since 1979. It benefits patients undergoing major gastrointestinal (GI) surgeries, with reduction in perioperative infection, better maintainance of nitrogen balance, and shorter hospital stay. Early EN may be superior to total parenteral nutrition (TPN). However, TPN is perhaps better tolerated in the immediate postoperative period. Early enteral immunonutrition should be used only in malnourished and in transfused patients. Early EN after major digestive surgery is an old advance that is now in fashion.

  17. 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

    SciTech Connect

    Nakamura, Akira; Shibuya, Keiko; Matsuo, Yukinori; Nakamura, Mitsuhiro; Shiinoki, Takehiro; Mizowaki, Takashi; Hiraoka, Masahiro

    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 of 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

  18. Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes

    PubMed Central

    Tseng, Yuan-Yun; Su, Chen-Hsing; Yang, Shun-Tai; Huang, Yin-Chen; Lee, Wei-Hwa; Wang, Yi-Chuan; Liu, Shou-Cheng; Liu, Shih-Jung

    2016-01-01

    Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic studies and onto C6 glioma-bearing rats for estimating the therapeutic efficacy. The chemotherapeutic agents were rapidly released from the 50:50 PLGA nanofibres after implantation, followed by the release of combretastatin (approximately 2 weeks later) from the 75:25 PLGA nanofibres. All drug concentrations remained higher in brain tissues than in the blood for more than 8 weeks. The experimental results, including attenuated malignancy, retarded tumour growth, and prolonged survival in tumour-bearing rats, demonstrated the efficacy of the BICC/PLGA nanofibrous membranes. Furthermore, the efficacy of BIC/PLGA and BICC/PLGA nanofibrous membranes was compared. The BICC/PLGA nanofibrous membranes more efficiently retarded the tumour growth and attenuated the malignancy of C6 glioma-bearing rats. Moreover, the addition of combretastatin did not significantly change the drug release behaviour of the BIC/PLGA nanofibrous membranes. The present advanced and novel interstitial chemotherapy and targeted treatment provide a potential strategy and regimen for treating GBM. PMID:27494894

  19. Improvement of Liver Function, Quality of Life and Survival after Insertion of Endoprosthesis in Advance Malignant Biliary Obstruction.

    PubMed

    Ullah, A A; Rahman, A; Chowdhury, L H; Bhuiya, A H

    2017-01-01

    Obstructive jaundice due to advance malignancy is a fatal problem. It most commonly occurs at the distal common bile duct or at the hilum of liver. Magnetic Resonance Cholangio Pancreatography (MRCP) and Computed Tomography (CT) are most useful in identifying the underlying cause as well as localize the position of the stricture. For those patients with unresectable disease, progressive jaundice constitutes an immediate threat to their survival, in addition to significant loss to their quality of life secondary to pruritus, malaise and cholangitis. Effective and lasting decompression of the biliary tree is a priority and consists of positioning of a biliary endoprosthesis (stent). To observe the improvement of liver function, quality of life and survival after successful insertion of endoprosthesis (stenting) in malignant biliary obstruction, a study was performed in the department of surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from September 2013 to August 2014, in 50 patients with clinically visible jaundice and unresectable disease. There were significant (p<0.001) reductions in the levels of serum bilirubin, serum alkaline phosphatase, serum SGPT and Prothrombin time from the time of admission to 2 weeks and 3 weeks after stenting. Physical and functional quality of life was greatly improved 2-4 weeks after stenting, where emotional quality remained the same throughout the study period. Successful palliation by stenting of malignant biliary obstruction is a priority to achieve improvements in liver function, quality of life and prolong survival. Endoscopic stent placement appears to be safe, well tolerated and can be offered without delay as a primary treatment option for all patients with unresectable malignant biliary lesion.

  20. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  1. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies.

    PubMed

    Choudary, Iqra; Barr, Paul M; Friedberg, Jonathan

    2015-12-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential.

  2. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies

    PubMed Central

    Choudary, Iqra; Barr, Paul M.; Friedberg, Jonathan

    2015-01-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential. PMID:26622997

  3. Sustained response of malignant pericardial effusion to intrapericardial bevacizumab in an advanced lung cancer patient: a case report and literature review

    PubMed Central

    Chen, Dawei; Zhang, Yan; Shi, Fang; Li, Minghuan; Zhu, Hui; Kong, Li; Yu, Jinming

    2015-01-01

    Malignant pericardial effusion (MPCE) is a common complication of advanced malignant tumors, and interferes severely with patient prognosis and quality of life. The standard treatment for this complication is intracavitary perfusion of chemotherapeutic drugs, which is limited by unsatisfactory therapeutic effects and serious adverse events. We report a patient with MPCE who was treated with bevacizumab by pericardial perfusion, resulting in a complete response. This case supports the use of intrapericardial bevacizumab as a potential treatment for MPCE. PMID:26491350

  4. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    PubMed Central

    2011-01-01

    Purpose To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Methods Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Results Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR). Conclusion Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted. PMID:21466696

  5. Stereotactic Ablative Radiosurgery for Locally Advanced or Recurrent Skull Base Malignancies with Prior External Beam Radiation Therapy

    PubMed Central

    Xu, Karen M.; Quan, Kimmen; Clump, David A.; Ferris, Robert L.; Heron, Dwight E.

    2015-01-01

    Purpose: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival, and toxicities in SABR for the treatment of previously irradiated malignant skull base tumors. Materials and methods: A total of 31 patients and 40 locally advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013, were retrospectively reviewed. The local control rate (LC), progression-free survival rate, overall survival (OS) rate, and toxicities were reported. Results: The median follow-up time of all patients was 11.4 months (range: 0.6–67.2 months). The median tumor volume was 27 cm3 (range: 2.4–205 cm3). All patients received prior external beam radiation therapy with a median radiation dose of 64 Gy (range: 24–75.6 Gy) delivered in 12–42 fractions. Twenty patients had surgeries prior to SABR. Nineteen patients received chemotherapy. Specifically, eight patients received concurrent cetuximab (Erbitux™) with SABR. The median time-to-progression (TTP) was 3.3 months (range: 0–16.9 months). For the 29 patients (93.5%) who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5–41.4 months). The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities. Conclusion: Stereotactic ablative radiotherapy has been shown to achieve low toxicities in locally advanced or recurrent, previously irradiated head and neck malignancies invading the skull base. PMID:25853093

  6. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

    PubMed

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-03-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

  7. The diagnostic value of CA 27-29, CA 15-3, mucin-like carcinoma antigen, carcinoembryonic antigen and CA 19-9 in breast and gastrointestinal malignancies.

    PubMed

    Frenette, P S; Thirlwell, M P; Trudeau, M; Thomson, D M; Joseph, L; Shuster, J S

    1994-01-01

    In the past decade, considerable interest has arisen for defining the role of various tumor markers in the diagnosis of cancer. This cross-sectional study evaluates four breast cancer markers (CA 27-29, CA 15-3, MCA and CEA) and two gastrointestinal (GI) markers (CA 19-9 and CEA) in 213 patients. Receiver operating curves (ROC) revealed a sensitivity for the 90% specificity cutoff for breast cancers compared to breast benign diseases of 70% for CA 27-29, 67.5% for CA 15-3, 52.5% for MCA and 40% for CEA. When GI tumors were compared to benign GI disease, the sensitivity for 90% specificity was 40.3% for CEA and 32.3% for CA 19-9. Comparison of breast cancer and GI malignancies with other malignancies leads to a marked shift of the ROC curve to the right and loss of specificity. Late stage for all breast and GI tumor markers was found to be a predictor of high serum antigen level (p < 0.001). The presence of liver metastases in breast cancer was associated with abnormal levels of CA 27-29 (p = 0.028). Pancreas adenocarcinomas had a higher CA 19-9 antigen level (p < 0.001) than other GI malignancies. CA 27-29 appears to be at least as sensitive and specific as CA 15-3 in patients with breast cancer. None of the above markers retain their specificity when compared with a control group consisting of other malignancies.

  8. Primary gastrointestinal lymphoma

    PubMed Central

    Ghimire, Prasanna; Wu, Guang-Yao; Zhu, Ling

    2011-01-01

    Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific, thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways. PMID:21390139

  9. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma.

    PubMed

    Van Meir, Erwin G; Hadjipanayis, Costas G; Norden, Andrew D; Shu, Hui-Kuo; Wen, Patrick Y; Olson, Jeffrey J

    2010-01-01

    Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development

  10. Alternative methods of interpreting quality of life data in advanced gastrointestinal cancer patients

    PubMed Central

    Nordin, K; Steel, J; Hoffman, K; Glimelius, B

    2001-01-01

    Understanding of how to analyse and interpret quality of life (QoL) data from clinical trials in patients with advanced cancer is limited. In order to increase the knowledge about the possibilities of drawing conclusions from QoL data of these patients, data from 2 trials were reanalysed. A total of 113 patients with pancreatic, biliary or gastric cancer were included in 2 randomised trials comparing chemotherapy and best supportive care (BSC) with BSC alone. Patient benefit was evaluated by the treating physician (subjective response) and by using selected scales and different summary measures of the EORTC QLQ-C30 questionnaire. An increasing number of drop-outs (mainly due to death) with time did not occur in a random fashion. Therefore, the mean scores in the different subscales of the QLQ-C30 obtained during the follow-up of interviewed patients did not reflect the outcome of the randomised population. The scores of the patient-provided summary measure, ‘Global health status/QoL’, were stable in a rather high proportion of the patients and could not discriminate between the 2 groups. 3 other summary measures revealed greater variability, and they all discriminated between the 2 groups. A high agreement was also seen between the changes in the summary measures and the subjective response. A categorisation of whether an individual patient had benefited or not from the intervention could overcome the problem with the selective attrition. © 2001 Cancer Research Campaign PMID:11720459

  11. Targeted ultra-deep sequencing unveils a lack of driver-gene mutations linking non-hereditary gastrointestinal stromal tumors and highly prevalent second primary malignancies: random or nonrandom, that is the question

    PubMed Central

    Kuo, Yung-Chia; Hsu, Hung-Chih; Chen, Jen-Shi; Chen, Tse-Ching; Wu, Ren-Chin; Chiu, Cheng-Tang; Yeh, Chun-Nan; Yeh, Ta-Sen

    2016-01-01

    The association of non-hereditary (sporadic) gastrointestinal stromal tumors (GISTs) and second primary malignancies is known to be nonrandom, although the underlying molecular mechanisms remain unknown. In this study, 136 of 749 (18.1%) patients with sporadic GISTs were found to have additional associated cancers, with gastrointestinal and genitourinary/gynecologic/breast cancers being the most prevalent. Gene mutations in GISTs and their associated colorectal cancers (CRCs) (n=9) were analyzed using a panel of 409 cancer-related genes, while a separate group of 40 sporadic CRCs not associated with GISTs served as controls. All 9 of the GISTs had either KIT (8 of 9) or PDGFRA (1 of 9) mutations that were not present in their associated CRCs. Conversely, all but one of the 9 GIST-associated CRCs exhibited an APC mutation, a TP53 mutation or both, while none of their corresponding GISTs harbored either APC or TP53 mutations. The genetic profile of CRCs with and without associated GISTs did not differ. Although population-based studies and case series worldwide, including ours, have unanimously indicated that the GIST-CRC association is nonrandom, our targeted ultra-deep sequencing unveiled a lack of driver-gene mutations linking sporadic GISTs to highly prevalent second primaries. Further studies are needed to elucidate other genetic alterations that may be responsible for this puzzling contradiction. PMID:27806309

  12. Asbestos-Induced Gastrointestinal Cancer: An Update

    PubMed Central

    Kim, Seok Jo; Williams, David; Cheresh, Paul; Kamp, David W

    2016-01-01

    Asbestos-related diseases, such as malignancies and asbestosis, remain a significant occupational and public health concern. Asbestos is still widely used in many developing countries despite being a recognized carcinogen that has been banned over 50 countries. The prevalence and mortality from asbestos-related diseases continue to pose challenges worldwide. Many countries are now experiencing an epidemic of asbestos-related disease that is the legacy of occupational exposure during the 20th century because of the long latency period (up to 40 years) between initial asbestos exposure and exhibition of disease. However, the gastrointestinal (GI) cancers resulting from asbestos exposure are not as clearly defined. In this review, we summarize some of the recent epidemiology of asbestos-related diseases and then focus on the evidence implicating asbestos in causing GI malignancies. We also briefly review the important new pathogenic information that has emerged over the past several years that may account for asbestos-related gastrointestinal cancers. All types of asbestos fibers have been implicated in the mortality and morbidity from GI malignancies but the collective evidence to date is mixed. Although the molecular basis of GI cancers arising from asbestos exposure is unclear, there have been significant advances in our understanding of mesothelioma and asbestosis that may contribute to the pathophysiology underlying asbestos-induced GI cancers. The emerging new evidence into the pathogenesis of asbestos toxicity is providing insights into the molecular basis for developing novel therapeutic strategies for asbestos-related diseases in future management. PMID:27158561

  13. An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2015-02-03

    Advanced Solid Tumors; Advanced Hodgkin's Lymphoma; Advanced Aggressive Non-Hodgkin's Lymphoma; Advanced Indolent Non-Hodgkin's Lymphoma; Advanced Pancreatic Adenocarcinoma; Advanced Triple-Negative Breast Cancer; Advanced Urothelial Carcinoma

  14. Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

    SciTech Connect

    Pugh, Thomas J.; Chen Changhu; Rabinovitch, Rachel; Eckhardt, S. Gail; Rusthoven, Kyle E.; Swing, Robyn; Raben, David

    2010-10-01

    Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, defined as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.

  15. Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease.

    PubMed

    Atkins, M B; Gould, J A; Allegretta, M; Li, J J; Dempsey, R A; Rudders, R A; Parkinson, D R; Reichlin, S; Mier, J W

    1986-09-01

    Seventeen patients with refractory malignant tumors were treated with recombinant human interleukin-2 (IL-2) administered by weekly bolus intravenous (IV) injection in a phase I dose escalation trial. Patients received 10,000 to 1,000,000 U/m2 per injection over a course of 3 to 33 weeks. Toxicity was dose related and consisted primarily of fever, chills, nausea, and vomiting. Hypotension was observed at doses of 500,000 U/m2 or higher and in one instance was sufficiently severe to require pressors. No tumor regression was seen and all patients eventually developed progressive disease. Blood levels of cortisol, ACTH, prolactin, and growth hormone as well as the acute phase reactant C-reactive protein (CRP) increased after the administration of IL-2 in most patients. Serum IL-2 levels in excess of 250 U/mL were detected five minutes after an IV injection of 1,000,000 U/m2, after which the levels declined with a half-life of approximately 25 minutes. No alteration in lymphocyte surface phenotype or enhancement in natural cell-mediated cytotoxicity against natural killer (NK)-sensitive and resistant tumor cell lines was observed when these parameters were measured weekly just before the IL-2 injections. However, a dramatic but transient decline in circulating lymphocytes and NK activity was noted within hours of receiving IL-2. This effect was independent of fever and was not abrogated by pretreatment with ibuprofen or metyrapone. The majority of patients developed serum IgG antibodies of IL-2 detectable with a sensitive enzyme-linked immunosorbent assay (ELISA) and a nitrocellulose dot blot assay. The development of anti-IL-2 antibodies was not associated with symptoms suggestive of serum sickness, reductions in serum complement levels, or deterioration in lymphocyte tumoricidal activity. This investigation provides insight into the in vivo actions of this potent biological response modifier and will assist in the design of future studies with IL-2 administered alone

  16. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    SciTech Connect

    Caravatta, Luciana; Padula, Gilbert D.A.; Macchia, Gabriella; Ferrandina, Gabriella; Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela; Mignogna, Samantha; Tambaro, Rosa; Rossi, Marco; Flocco, Mariano; Scapati, Andrea; and others

    2012-08-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  17. A phase I trial of chlorambucil administered in short pulses in patients with advanced malignancies.

    PubMed

    Blumenreich, M S; Woodcock, T M; Sherrill, E J; Richman, S P; Gentile, P S; Epremian, B E; Kubota, T T; Allegra, J C

    1988-01-01

    We carried out a phase I trial with chlorambucil. Thirty patients with advanced cancer were entered in six dose levels: 36, 48, 60, 84, 108, and 144 mg/m2. The drug was given in six divided oral doses every 6 hours and the regimen was repeated every 3 weeks. The median age was 62 years (31-84), median Karnofsky performance status (KPS) 60 (40-90). All patients but one had received prior radiation therapy, chemotherapy, or both. Central nervous system toxicity was dose limiting, occurring in 5 of 6 patients at 144 mg/m2. It was characterized by transient seizures, hallucinations, lethargy, stupor, and coma. Metoclopramide was successful in controlling nausea and vomiting, which was severe if the antiemetic was not used. Leukopenia (3 patients) and thrombocytopenia (2 patients) were mild. One patient with colorectal carcinoma had a minor response, and two patients with non-small cell lung cancer had stable disease. A safe dose for phase II trials is 108 mg/m2 in six 6-hourly oral doses.

  18. Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies

    PubMed Central

    Schenk, Erin; Wahner Hendrickson, Andrea E.; Northfelt, Donald; Toft, David O.; Ames, Matthew M.; Menefee, Michael; Satele, Daniel; Qin, Rui; Erlichman, Charles

    2014-01-01

    Summary Purpose To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib. Experimental design Phase I dose-escalating trial using a standard cohort “3+3” design performed in patients with advanced solid tumors. Patients were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle (days 1, 4, 8, 11 every 21 days). Results Seventeen patients were enrolled in this study, fifteen were evaluable for toxicity, and nine patients were evaluable for tumor response. The MTD was 250 mg/m2 of tanespimycin and 1.0 mg/m2 of bortezomib when used in combination. DLTs of abdominal pain (13%), complete atrioventricular block (7%), fatigue (7%), encephalopathy (7%), anorexia (7%), hyponatremia (7%), hypoxia (7%), and acidosis (7%) were observed. There were no objective responses. One patient had stable disease. Conclusions The recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m2 and 1.0 mg/m2respectively, on days 1, 4, 8 and 11 of a 21 day cycle. PMID:23543109

  19. Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed.

    PubMed

    Ando, Hidenori; Kobayashi, Sakiko; Abu Lila, Amr S; Eldin, Noha Essam; Kato, Chihiro; Shimizu, Taro; Ukawa, Masami; Kawazoe, Kazuyoshi; Ishida, Tatsuhiro

    2015-12-28

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the "fluid" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM.

  20. [Clinical evaluation of ureteral stenting for managing extrinsic ureteral obstruction due to gynecological and gastrointestinal cancer].

    PubMed

    Takehara, Kosuke; Onita, Toru; Mochizuki, Yasushi; Miyata, Yasuyoshi; Igawa, Tsukasa; Sakai, Hideki

    2014-01-01

    We retrospectively reviewed patients who were treated with an indwelling ureteral stent to manage extrinsic ureteral obstruction due to advanced gynecological and gastrointestinal cancers. A total of 34 patients, including 17 with gynecological cancer and 17 with gastrointestinal cancer, underwent a successful initial ureteral stent placement from January 2007 to December 2011. Functional ureteral stent failures, which required percutaneous nephrostomy within 3 months after initial ureteral stenting, occurred in 14 of the 34 patients (41%) during follow-up. The risk factors of functional ureteral stent failure were bilateral ureteral obstruction, elevated serum creatinine level, poor performance status, subsequent therapy for primary cancer after ureteral stent placement, presence of peritonitis carcinomatosa, and gastrointestinal cancer. Patients with gastrointestinal cancer had a higher rate of stent failure than did those with gynecological cancer (p = 0.01). Median survival from the diagnosis of hydronephrosis for patients with gastrointestinal and gynecological cancers was 9 and 23 months, respectively (p = 0. 02). Retrograde ureteral stenting is a useful treatment for malignant ureteral obstruction. However, patients with gastrointestinal cancer had a high stent failure rate and a short survival time from the diagnosis of hydronephrosis. Indications for retrograde ureteral stenting for malignant ureteral obstruction should be carefully considered while taking into account stent failure risk, patient prognosis and quality of life.

  1. Two novel cultured cell lines, A3/Kawakami and A4/Fukuda, derived from malignant lymphoma of B(non-T)-cell nature of the gastrointestinal tract.

    PubMed

    Hirose, M; Minato, K; Tobinai, K; Shimoyama, M; Watanabe, S; Abe, T; Deura, K

    1983-02-01

    A3/Kawakami was derived from ascitic lymphoma cells of a 68-year-old female patient with malignant lymphoma (non-Hodgkin's lymphoma, diffuse, large cell type) of the stomach and A4/Fukuda was derived from ascitic lymphoma cells of a 52-year-old female patient with double cancer of the colon (well-differentiated papillary adenocarcinoma and non-Hodgkin's lymphoma, diffuse, large cell type). The fresh ascitic lymphoma cells in the case of A3/Kawakami were surface immunoglobulin-positive, but the cultured A3/Kawakami cells no longer expressed any distinct markers. In the case of A4/Fukuda, the fresh ascitic lymphoma cells and cultured cells did not express any specific surface markers. Only 20% of A4/Fukuda cells were reactive with OKI1. However, a small amount of IgM could be detected in the cell extract and concentrated culture supernate of A4/Fukuda. In addition, A4/Fukuda cells heterotransplanted into anti-thymocyte sera-treated newborn hamster or athymic nude mice with a BALB/c genetic background were found to have weak surface immunoglobulin and distinct cytoplasmic immunoglobulin (gamma, mu). These data suggest that A4/Fukuda cells share the characteristics of the late differentiation stage of B-cell lineage (intermediate between mature B-cells and plasma cells). It was found that monoclonal antibodies, OKT4 and anti-Leu 3a, which are known to react specifically with inducer/helper T-cells, reacted to both A3/Kawakami and A4/Fukuda cells. The karyotypes of both A3/Kawakami and A4/Fukuda cells were very complicated but included some marker chromosomes such as 14q+.

  2. Association of high mobility group BOX-1 and receptor for advanced glycation endproducts with clinicopathological features of haematological malignancies: a systematic review

    PubMed Central

    Bhavsar, Sheila B.; Riley, Erinn M.; Caponetti, Gabriel C.; Agrawal, Devendra K.

    2017-01-01

    High-mobility group box 1 (HMGB1) is a versatile protein with nuclear and extracellular functions. In the extracellular milieu, HMGB1 binds to several receptors, notably the receptor for advanced glycation end-products (RAGE). The expressions of HMGB1 and RAGE have been described in a variety of cancers. However, the clinical values of HMGB1 and RAGE in haematological malignancies have yet to be evaluated. A systematic search through PubMed and the Web of Science for articles discussing the role of HMGB1 and RAGE in haematological malignancies produced 15 articles. Overexpression of HMGB1 was reported to be associated with malignancy and, in certain studies, poor prognosis and tumour aggressiveness. Only one included study investigated the clinical value of RAGE, in which no significant difference was found between expression of RAGE in CLL neoplastic cells and nonmalignant controls. The discussed associations of HMGB1 and RAGE with clinicopathological characteristics of patients with haematological malignancies warrants further investigation into the prognostic and diagnostic value of both of these molecules. PMID:28239277

  3. Gastrointestinal mucormycosis in immunocompromised hosts.

    PubMed

    Dioverti, M Veronica; Cawcutt, Kelly A; Abidi, Maheen; Sohail, M Rizwan; Walker, Randall C; Osmon, Douglas R

    2015-12-01

    Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non-specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.

  4. Lipomas of the gastrointestinal system.

    PubMed

    Dolai, Matilda; Andrejić, Bojana; Ivanov, Dejan

    2012-01-01

    Lipomas are rare benign tumors in the gastrointestinal system. Within the gastrointestinal system, 65% of the lipomas are located in the colon (sigmoid part of the colon or rectum) and rarely in the stomach and esophagus. The paper presents two gastrointestinal lipomas. First is the case of lipoma of the sigmoid colon and the other one is gastric lipoma. In both cases the material was sent for histopathological analysis due to suspicion of malignancy of the lesions. In both cases, the histopathologic analysis showed tumor made of mature adipocytes, localized in the submucosa both of the stomach and intestine. Hypercellularity and/or atypia of the cell was found in neither case. Lipomas are shown because of its atypical localization and clinically suspicious malignancy in the stomach and sigmoid colon. These cases show that the applied methods of preoperative diagnosis of tumors in the gastrointestinal system are not sufficient to determine the origin and biological behavior of tumors. Histopathological diagnosis provides a correct insight into the nature of tumors and determine the course of treatment. This paper presents a rare localization of lipomas in the gastrointestinal system. The preoperative diagnosis of lesions in the gastrointestinal system may not be sufficient to determine the origin and biological behavior of the lesions, hence the histopathological diagnosis gives an accurate insight into the nature of the change, preventing the possibility of further aggressive therapy.

  5. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective.

    PubMed

    Roeber, Florian; Jex, Aaron R; Gasser, Robin B

    2013-05-27

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases.

  6. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective

    PubMed Central

    2013-01-01

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases. PMID:23711194

  7. Is there a standard of care for the management of advanced pancreatic cancer?. Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 25-27, 2008.

    PubMed

    Saif, Muhammad Wasif

    2008-03-08

    Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, the outcome for this disease remains dismal. Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic and targeted agents have been pitted against or combined with gemcitabine in randomized phase III trials and no drug was shown to be superior to single-agent gemcitabine except two gemcitabine-containing combinations: capecitabine plus gemcitabine vs. gemcitabine and erlotinib. In this article, the author debates: "Is there a standard of care for the treatment of advanced pancreatic cancer?". In addition, he summarizes the key studies presented at the "Gastrointestinal Cancers Symposium" held in Orlando, FL, USA on January 25-27, 2008. The studies discussed here include the following: i) a phase I study of a chemotherapy doublet gemcitabine plus capecitabine, combined with a biologic doublet (bevacizumab plus erlotinib) in patients with advanced pancreatic adenocarcinoma (abstract #141); ii) a phase II study of gemcitabine, bevacizumab, and erlotinib in locally advanced and metastatic adenocarcinoma of the pancreas (abstract #151); iii) final results of the multicenter phase II study on gemcitabine, capecitabine, and bevacizumab in patients with advanced pancreatic cancer (abstract #198); iv) interim results from a phase II study of volociximab in combination with gemcitabine in patients with metastatic pancreatic cancer (abstract #142); v) a pilot study of combination chemotherapy with S-1 and irinotecan for advanced pancreatic cancer (abstract #155); vi) a multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer (abstract #212); vii) a phase I/II study of PHY906 plus capecitabine in patients with advanced pancreatic carcinoma (abstract #260); and viii) the final results of a phase II trial of

  8. Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review.

    PubMed

    Nguyen, Austin Huy; Detty, Shannon Q; Agrawal, Devendra K

    2017-01-01

    Inflammation and the immune system play a role in the development and progression of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). The pro-inflammatory and tumor-promoting effects of the high-mobility group box-1 (HMGB1) protein and the receptor for advanced glycation end products (RAGE) have been investigated in these cutaneous malignancies. The clinical implication of these molecules is not fully described. The National Library of Medicine database was searched for articles addressing the clinical relevance of HMGB1 and RAGE in melanoma, BCC, and SCC. This systematic review includes nine articles, with six summarizing RAGE in cutaneous malignancies and three involving HMGB1. RAGE has been found to be up-regulated in SCC lesions, as well as melanoma. Levels of RAGE were highest in stage IV melanomas. Lower levels of soluble RAGE have been associated with poor overall survival in melanoma. Sporadic extracellular expression of HMGB1 was evident in BCC and SCC lesions, which could be released by necrotic tumor cells. HMGB1 was found to be a prognostic marker in melanoma, and HMGB1 levels were elevated in patients who were non-responders to ipilimumab treatment. HMGB1 and RAGE could serve as potential prognostic markers or therapeutic targets in treating melanoma, BCC, and SCC, but further research regarding the clinical utility of the HMGB1-RAGE axis in cutaneous malignancies is warranted.

  9. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype

    PubMed Central

    SU, ZHONGWU; LI, GUO; LIU, CHAO; REN, SHULING; TIAN, YONGQUAN; LIU, YONG; QIU, YUANZHENG

    2016-01-01

    Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC. PMID:27108809

  10. Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model.

    PubMed

    Pantaleo, M A; Landuzzi, L; Nicoletti, G; Nanni, C; Boschi, S; Piazzi, G; Santini, D; Di Battista, M; Castellucci, P; Lodi, F; Fanti, S; Lollini, P-L; Biasco, G

    2009-09-01

    The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

  11. Gastrointestinal manifestations.

    PubMed

    Tanowitz, H B; Simon, D; Weiss, L M; Noyer, C; Coyle, C; Wittner, M

    1996-11-01

    Gastrointestinal disease is a common problem in the setting of HIV-1 infection. As patients live longer and other opportunistic pathogens are suppressed, these problems are becoming even more important in the quality of life.

  12. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    ClinicalTrials.gov

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  13. Immune targeting of cancer stem cells in gastrointestinal oncology

    PubMed Central

    Grossenbacher, Steven K.; Ames, Erik; Murphy, William J.

    2016-01-01

    The cancer stem cell (CSC) hypothesis postulates that a sub-population of quiescent cells exist within tumors which are resistant to conventional cytotoxic/anti-proliferative therapies. It is these CSCs which then seed tumor relapse, even in cases of apparent complete response to systemic therapy. Therefore, therapies, such as immunotherapy, which add a specific anti-CSC strategy to standard cytoreductive treatments may provide a promising new direction for future cancer therapies. CSCs are an attractive target for immune therapies since, unlike chemotherapy or radiotherapy, immune effector cells do not specifically require target cells to be proliferating in order to effectively kill them. Although recent advances have been made in the development of novel systemic and targeted therapies for advanced gastro-intestinal (GI) malignancies, there remains an unmet need for durable new therapies for these refractory malignancies. Novel immunotherapeutic strategies targeting CSCs are in pre-clinical and clinical development across the spectrum of the immune system, including strategies utilizing adaptive immune cell-based effectors, innate immune effectors, as well as vaccine approaches. Lastly, since important CSC functions are affected by the tumor microenvironment, targeting of both cellular (myeloid derived suppressor cells and tumor-associated macrophages) and sub-cellular (cytokines, chemokines, and PD1/PDL1) components of the tumor microenvironment is under investigation in the immune targeting of CSCs. These efforts are adding to the significant optimism about the potential utility of immunotherapy to overcome cancer resistance mechanisms and cure greater numbers of patients with advanced malignancy. PMID:27034806

  14. [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.

  15. Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review

    PubMed Central

    Fasano, Morena; Corte, Carminia Maria Della; Vicidomini, Giovanni; Scotti, Valerio; Rambaldi, Pier Francesco; Fiorelli, Alfonso; Accardo, Marina; De Vita, Ferdinando; Santini, Mario; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of ‘acute abdomen’, an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM. PMID:28105159

  16. Phase I trial of arginine deprivation therapy with ADI-PEG 20 plus docetaxel in patients with advanced malignant solid tumors

    PubMed Central

    Tomlinson, Benjamin K.; Thomson, James A.; Bomalaski, John S.; Diaz, Monica; Akande, Taiwo; Mahaffey, Nichole; Li, Tianhong; Dutia, Mrinal P.; Kelly, Karen; Gong, I-Yeh; Semrad, Thomas; Gandara, David R.; Pan, Chong-Xian; Lara, Primo N.

    2015-01-01

    Purpose This phase I study examined the toxicity and tolerability, of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies. Experimental Design Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, zubrod performance status 0–2 and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5–36 mg/m2, and up to ten doses of docetaxel 75 mg/m2 every three weeks. Primary endpoints were safety, toxicity and a recommended phase II dose. Circulating arginine levels were measured prior to each cycle. Tumor response was measured as a secondary endpoint every six weeks on study. Results Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1st dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3–4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with ten patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including two patients with PSA response) were documented and seven patients had stable disease. Conclusions ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted and expansion cohorts are now accruing for both castrate resistant prostate cancer and non-small cell lung cancer at a recommended phase II dose of 36 mg/m2. PMID:25739672

  17. A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies

    PubMed Central

    2013-01-01

    Background Dinaciclib, a small-molecule, cyclin-dependent kinase inhibitor, inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. We conducted an open-label, dose-escalation study to determine the safety, tolerability, and bioactivity of dinaciclib in adults with advanced malignancies. Methods Dinaciclib was administered starting at a dose of 0.33 mg/m2, as a 2-hour intravenous infusion once weekly for 3 weeks (on days 1, 8, and 15 of a 28-day cycle), to determine the maximum administered dose (MAD), dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and safety and tolerability. Pharmacodynamics of dinaciclib were assessed using an ex vivo phytohemagglutinin lymphocyte stimulation assay and immunohistochemistry staining for retinoblastoma protein phosphorylation in skin biopsies. Evidence of antitumor activity was assessed by sequential computed tomography imaging after every 2 treatment cycles. Results Forty-eight subjects with solid tumors were treated. The MAD was found to be 14 mg/m2 and the RP2D was determined to be 12 mg/m2; DLTs at the MAD included orthostatic hypotension and elevated uric acid. Forty-seven (98%) subjects reported adverse events (AEs) across all dose levels; the most common AEs were nausea, anemia, decreased appetite, and fatigue. Dinaciclib administered at the RP2D significantly inhibited lymphocyte proliferation, demonstrating a pharmacodynamic effect. Ten subjects treated at a variety of doses achieved prolonged stable disease for at least 4 treatment cycles. Conclusions Dinaciclib administered every week for 3 weeks (on days 1, 8, and 15 of a 28-day cycle) was generally safe and well tolerated. Initial bioactivity and observed disease stabilization support further evaluation of dinaciclib as a treatment option for patients with advanced solid malignancies. Trial registration ClinicalTrials.gov # NCT00871663 PMID:24131779

  18. Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only in non progressive patients

    PubMed Central

    2012-01-01

    Abstract Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib : an active agent only in non progressive patients. Background Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3–4 anaemia in 10% of patients. Whether EPO treatment is useful in the management of GIST patients receiving imatinib treatment is unknown. Methods A retrospective study of EPO treatment in GIST patients receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO treatment among the 319 GIST patients treated with imatinib in clinical trials or with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia of patients with GIST treated with imatinib was analyzed. Results There were 18 males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary tumour sites were mainly gastric (32%) and small bowel (29%). Sites of metastases were mainly liver (82%) and peritoneum (79%). The median delay between the initiation of imatinib treatment and EPO was 58 days (range 0–553). Median haemoglobin (Hb) level prior to EPO was 9 g/dL (range 6,9-11,8) and 11,7 g/dL (range 6,8-14,4) after 2 months. An increase of more than 2 g/dL was observed in 18 (53%) of patients. None of the 7 patients who progressed (PD) under imatinib treatment (400 mg/day) experienced HB response, as compared to 66% (18/27) of the remaining patients (PR + SD) (p = 0,002). Primary tumour site, liver metastases, peritoneal metastases, age, gender did not correlate with HB response to EPO. Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800 mg/day) vs 16/23 of others. Using logistic regression, only PD before EPO treatment was retained as a predictive factor for EPO response. Conclusion EPO enables to

  19. Ubiquitin proteasome system research in gastrointestinal cancer

    PubMed Central

    Zhong, Jia-Ling; Huang, Chang-Zhi

    2016-01-01

    The ubiquitin proteasome system (UPS) is important for the degradation of proteins in eukaryotic cells. It is involved in nearly every cellular process and plays an important role in maintaining body homeostasis. An increasing body of evidence has linked alterations in the UPS to gastrointestinal malignancies, including esophageal, gastric and colorectal cancers. Here, we summarize the current literature detailing the involvement of the UPS in gastrointestinal cancer, highlighting its role in tumor occurrence and development, providing information for therapeutic targets research and anti-gastrointestinal tumor drug design. PMID:26909134

  20. Ubiquitin proteasome system research in gastrointestinal cancer.

    PubMed

    Zhong, Jia-Ling; Huang, Chang-Zhi

    2016-02-15

    The ubiquitin proteasome system (UPS) is important for the degradation of proteins in eukaryotic cells. It is involved in nearly every cellular process and plays an important role in maintaining body homeostasis. An increasing body of evidence has linked alterations in the UPS to gastrointestinal malignancies, including esophageal, gastric and colorectal cancers. Here, we summarize the current literature detailing the involvement of the UPS in gastrointestinal cancer, highlighting its role in tumor occurrence and development, providing information for therapeutic targets research and anti-gastrointestinal tumor drug design.

  1. Phase I clinical and pharmacokinetic study of oral penclomedine (NSC 338720) in adults with advanced solid malignancy.

    PubMed

    Liu, Glenn; Berlin, Jordan; Tutsch, Kendra D; Van Ummersen, Lynn; Dresen, Amy; Marnocha, Rebecca; Arzomanian, Rhoda; Alberti, Dona; Feierabend, Chris; Binger, Kimberly; Wilding, George

    2002-03-01

    Penclomedine is a synthetic alpha-picoline derivative that has shown antitumor activity both in preclinical development and in Phase I work using an i.v. preparation. The main toxicities seen in those studies were dose dependent and mainly neurocerebellar, with hematological toxicity being far less severe. This Phase I trial of p.o. penclomedine was conducted to potentially alter the toxicity profile and to avoid the neurological side effects seen with i.v. penclomedine. Eligibility criteria included microscopic confirmation of a solid malignancy or lymphoma with a lack of effective anticancer therapy. Twenty patients were enrolled. The median age was 60.5 years, and the median performance status was one. All but one patient had received prior systemic therapy. The starting dose of penclomedine was 200 mg/m(2) p.o. for 5 days, and was escalated according to a traditional Fibonacci sequence until the maximum tolerated dose (MTD) was observed. No treatment-related deaths were observed during the study. The MTD was determined to be 800 mg/m(2) p.o. for 5 days. Dose-limiting toxicities included mainly neurocerebellar symptoms such as ataxia and dysmetria, but neurocortical symptoms, such as confusion, were seen as well. Myelosuppression was less common and resulted in the discontinuation of therapy in only two patients. Pharmacokinetics show that the observed MTD is consistent with the i.v. preparations, and that the bioavailability of p.o. penclomedine is 49 +/- 18%. This regimen can be considered for additional studies in patients with intracranial neoplasms, because good central nervous system penetration is evident. Further development of penclomedine metabolites, such as 4-O-demethylpenclomedine, should be considered to minimize dose-limiting neurotoxicity.

  2. First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

    PubMed Central

    Arrieta, Ó; Medina, L A; Estrada-Lobato, E; Hernández-Pedro, N; Villanueva-Rodríguez, G; Martínez-Barrera, L; Macedo, E O; López-Rodríguez, V; Motola-Kuba, D; Corona-Cruz, J F

    2012-01-01

    Background: Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as 99mTc-LD distribution in MPM lesions after chemotherapy administration. Methods: A total of 38 patients with non-resectable MPM received LD 40 mg m−2 and cisplatin 60 mg m−2 every 21 days. Gamma camera images of 99mTc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028). Results: In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4–5.9 months), and median overall survival (OS) was 19.6 months (15.2–37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001). Conclusion: The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. 99mTc-LD showed higher levels of tumour uptake as compared with surrounding tissues. PMID:22353806

  3. Cancer stem cells in human gastrointestinal cancer.

    PubMed

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh

    2016-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  4. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

    PubMed Central

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-01-01

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients. PMID:18506179

  5. State of the art in advanced endoscopic imaging for the detection and evaluation of dysplasia and early cancer of the gastrointestinal tract

    PubMed Central

    Coda, Sergio; Thillainayagam, Andrew V

    2014-01-01

    Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by

  6. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

    PubMed

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-06-03

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

  7. [Gastrointestinal bezoars].

    PubMed

    Espinoza González, Ricardo

    2016-08-01

    Gastrointestinal bezoars are a concretion of indigested material that can be found in the gastrointestinal tract of humans and some animals. This material forms an intraluminal mass, more commonly located in the stomach. During a large period of history animal bezoars were considered antidotes to poisons and diseases. We report a historical overview since bezoars stones were thought to have medicinal properties. This magic conception was introduced in South America by Spanish conquerors. In Chile, bezoars are commonly found in a camelid named guanaco (Lama guanicoe). People at Central Chile and the Patagonia believed that bezoar stones had magical properties and they were traded at very high prices. In Santiago, during the eighteenth century the Jesuit apothecary sold preparations of bezoar stones. The human bezoars may be formed by non-digestible material like cellulose (phytobezoar), hair (trichobezoar), conglomerations of medications or his vehicles (pharmacobezoar or medication bezoar), milk and mucus component (lactobezoar) or other varieties of substances. This condition may be asymptomatic or can produce abdominal pain, ulceration, gastrointestinal bleeding, gastric outlet obstruction, perforation and mechanical intestinal obstruction. We report their classification, diagnostic modalities and treatment.

  8. Pleural malignancies.

    PubMed

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent.

  9. Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: A phase I/II trial

    SciTech Connect

    Demirer, T.; Petersen, F.B.; Appelbaum, F.R.

    1995-07-15

    The purpose of this investigation was to define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual {sup 60}C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies. Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (Cy), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy. None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI. The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children. 36 refs., 1 fig., 3 tabs.

  10. Vemurafenib for the treatment of locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma: a NICE single technology appraisal.

    PubMed

    Beale, Sophie; Dickson, Rumona; Bagust, Adrian; Blundell, Michaela; Dundar, Yenal; Boland, Angela; Marshall, Ernie; Plummer, Ruth; Proudlove, Chris

    2013-12-01

    Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally advanced or metastatic BRAF V600-mutation positive malignant melanoma. The manufacturer of vemurafenib, Roche Products Limited, was invited by the National Institute for Health and Care Excellence (NICE) to submit evidence of the drug's clinical- and cost-effectiveness for its licenced indication, to inform the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. This article summarises the ERG's review of the evidence submitted by the manufacturer and also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG reviewed the clinical- and cost-effectiveness evidence in accordance with the decision problem defined by NICE. The ERG's analysis of the submitted economic model assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. It also included an assessment of the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results. The clinical evidence was derived from BRIM 3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national, phase III, randomised controlled trial (RCT). Clinical outcome results from the October 2011 data cut showed that median overall survival for patients treated with vemurafenib was 13.2 months compared with 9.6 months for those treated with dacarbazine. The ERG's main concern with the trial was the potential for confounding because of the early introduction of the crossover from the comparator drug to vemurafenib or another BRAF inhibitor. The submitted incremental cost-effectiveness ratio (ICER

  11. Trial of Dasatinib in Advanced Sarcomas

    ClinicalTrials.gov

    2017-03-20

    Rhabdomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Chondrosarcoma; Sarcoma, Ewing's; Sarcoma, Alveolar Soft Part; Chordoma; Epithelioid Sarcoma; Giant Cell Tumor of Bone; Hemangiopericytoma; Gastrointestinal Stromal Tumor (GIST)

  12. A phase II study of REOLYSIN(®) (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma.

    PubMed

    Mahalingam, Devalingam; Fountzilas, Christos; Moseley, Jennifer; Noronha, Nicole; Tran, Hue; Chakrabarty, Romit; Selvaggi, Giovanni; Coffey, Matthew; Thompson, Brad; Sarantopoulos, John

    2017-04-01

    REOLYSIN(®) (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN(®) on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN(®). Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN(®) in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN(®), including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN(®) combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN(®) with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.

  13. Management of gastrointestinal haemorrhage

    PubMed Central

    Ghosh, S; Watts, D; Kinnear, M

    2002-01-01

    A variety of endoscopic haemostatic techniques have enabled major advances in the management of not only bleeding peptic ulcers and bleeding varices, but also in a variety of bleeding lesions in the small intestine and in the colon. Indeed, the development and widespread implementation of endoscopic haemostasis has been one of the most important developments in clinical gastroenterology in the past two decades. An increasingly ageing cohort of patients with multiple co-morbidity are being treated and therefore improving the outcome of gastrointestinal bleeding continues to pose major challenges. PMID:11796865

  14. Dose-Volume Analysis of Predictors for Gastrointestinal Toxicity After Concurrent Full-Dose Gemcitabine and Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma

    SciTech Connect

    Huang Jiayi; Robertson, John M.; Ye Hong; Margolis, Jeffrey; Nadeau, Laura; Yan Di

    2012-07-15

    Purpose: To identify dosimetric predictors for the development of gastrointestinal (GI) toxicity in patients with locally advanced pancreatic adenocarcinoma (LAPC) treated with concurrent full-dose gemcitabine and radiotherapy (GemRT). Methods and Materials: From June 2002 to June 2009, 46 LAPC patients treated with definitive GemRT were retrospectively analyzed. The stomach and duodenum were retrospectively contoured separately to determine their dose-volume histogram (DVH) parameters. GI toxicity was defined as Grade 3 or higher GI toxicity. The follow-up time was calculated from the start of RT to the date of death or last contact. Univariate analysis (UVA) and multivariate analysis (MVA) using Kaplan-Meier and Cox regression models were performed to identify risk factors associated with GI toxicity. The receiver operating characteristic curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best DVH parameter to predict for GI toxicity. Results: Of the patients, 28 (61%) received concurrent gemcitabine alone, and 18 (39%) had concurrent gemcitabine with daily erlotinib. On UVA, only the V{sub 20Gy} to V{sub 35Gy} of duodenum were significantly associated with GI toxicity (all p {<=} 0.05). On MVA, the V{sub 25Gy} of duodenum and the use of erlotinib were independent risk factors for GI toxicity (p = 0.006 and 0.02, respectively). For the entire cohort, the V{sub 25Gy} of duodenum is the best predictor for GI toxicity (AUC = 0.717), and the 12-month GI toxicity rate was 8% vs. 48% for V{sub 25Gy} {<=} 45% and V{sub 25Gy} > 45%, respectively (p = 0.03). However, excluding the erlotinib group, the V{sub 35Gy} is the best predictor (AUC = 0.725), and the 12-month GI toxicity rate was 0% vs. 41% for V{sub 35Gy} {<=} 20% and V{sub 35Gy} > 20%, respectively (p = 0.04). Conclusions: DVH parameters of duodenum may predict Grade 3 GI toxicity after GemRT for LAPC. Concurrent use of erlotinib during GemRT may increase GI

  15. Malignant peritoneal mesothelioma

    PubMed Central

    Munkholm-Larsen, Stine; Cao, Christopher Q; Yan, Tristan D

    2009-01-01

    Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade. PMID:21160794

  16. Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells.

    PubMed

    Guan, Guofang; Li, Ranwei; Tang, Wenfang; Liu, Tiecheng; Su, Zhenzhong; Wang, Yan; Tan, Jingjin; Jiang, Shan; Wang, Ke

    2017-03-01

    This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif

  17. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

    SciTech Connect

    Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.; Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C.; Chang, Daniel T.

    2015-07-01

    Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  18. Malignant mesothelioma

    PubMed Central

    Moore, Alastair J; Parker, Robert J; Wiggins, John

    2008-01-01

    Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

  19. First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies

    PubMed Central

    Neidhart, Jeffrey D.; Ramanathan, Ramesh K.; Bassett, Dawn; Neidhart, James A.; Choi, Chung Hang J.; Chow, Warren; Chung, Vincent; Forman, Stephen J.; Garmey, Edward; Hwang, Jungyeon; Kalinoski, D. Lynn; Koczywas, Marianna; Longmate, Jeffrey; Melton, Roger J.; Morgan, Robert; Oliver, Jamie; Peterkin, Joanna J.; Ryan, John L.; Schluep, Thomas; Synold, Timothy W.; Twardowski, Przemyslaw; Davis, Mark E.; Yen, Yun

    2013-01-01

    Summary Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m2 and later bi-weekly at 12, 15, and 18 mg/m2. The maximum tolerated dose (MTD) was determined at 15 mg/m2 bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39-79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD (n=44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT Tmax values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing. PMID:23397498

  20. Novel phase I study combining G1 phase, S phase, and G2/M phase cell cycle inhibitors in patients with advanced malignancies

    PubMed Central

    Jain, Rajul K; Hong, David S; Naing, Aung; Wheler, Jennifer; Helgason, Thorunn; Shi, Nai-Yi; Gad, Yash; Kurzrock, Razelle

    2015-01-01

    PURPOSE: Cancer is a manifestation of aberrant cellular proliferation, and the cell cycle is one of the most successfully drugged targets in oncology. No prior study has been reported that simultaneously targets the 3 principal cell cycle phases populated by proliferating cells - G1, S, and G2/M. METHODS: Temsirolimus (G1 inhibitor), topotecan (S inhibitor), and bortezomib (G2/M inhibitor) were administered in combination to patients with advanced malignancies using a 3+3 dose escalation schedule to assess the safety and establish the maximum tolerated dose (primary endpoints) of this cell cycle targeting approach. An in silico pharmacodynamic model using established effects of each of these agents on the cell cycle was used to validate the regimen and to guide the dosing regimen. RESULTS: Sixty-two subjects were enrolled. The most common adverse events and dose-limiting toxicities were cytopenias, consistent with the cell cycle targeting approach employed. All cytopenias resolved to baseline values upon holding study drug administration. The maximum tolerated dose was temsirolimus 15 mg/kg IV D1, 8, 15; topotecan 2.8 mg/m2 IV D1, 8; and bortezomib 0.9 mg/m2 IV D1, 4, 8, 11 of a 21-day cycle. In silico modeling suggests the regimen induces cell population shifts from G2/M and S phases to G1 phase and the quiescent G0 phase. Eighteen percent of subjects (11/62) achieved partial response (n = 2, serous ovarian and papillary thyroid) or stable disease for > 6 months (n = 9). CONCLUSION: Combining drugs with inhibitory activity of G1 phase, S phase, and G2/M phase is safe and warrants further evaluation. PMID:26467427

  1. Rare gastrointestinal lymphomas: The endoscopic investigation

    PubMed Central

    Vetro, Calogero; Bonanno, Giacomo; Giulietti, Giorgio; Romano, Alessandra; Conticello, Concetta; Chiarenza, Annalisa; Spina, Paolo; Coppolino, Francesco; Cunsolo, Rosario; Raimondo, Francesco Di

    2015-01-01

    Gastrointestinal lymphomas represent up to 10% of gastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. However, the gastrointestinal tract can be the site of rarer lymphoma subtypes as a primary or secondary localization. Due to their rarity and the multifaceted histology, an endoscopic classification has not been validated yet. This review aims to analyze the endoscopic presentation of rare gastrointestinal lymphomas from disease diagnosis to follow-up, according to the involved site and lymphoma subtype. Existing, new and emerging endoscopic technologies have been examined. In particular, we investigated the diagnostic, prognostic and follow-up endoscopic features of T-cell and natural killer lymphomas, lymphomatous polyposis and mantle cell lymphoma, follicular lymphoma, plasma cell related disease, gastrointestinal lymphomas in immunodeficiency and Hodgkin’s lymphoma of the gastrointestinal tract. Contrarily to more frequent gastrointestinal lymphomas, data about rare lymphomas are mostly extracted from case series and case reports. Due to the data paucity, a synergism between gastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinical and prognostic features are different from nodal and extranodal or the bone marrow (in case of plasma cell disease) counterpart. Therefore, the approach should be based on the knowledge of the peculiar behavior and natural history of disease. PMID:26265987

  2. Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies.

    PubMed

    Larson, R A; Geller, R B; Janisch, L; Milton, J; Grochow, L B; Ratain, M J

    1995-01-01

    Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose

  3. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

    The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

  4. Oncological emergencies associated with gastrointestinal tumors

    PubMed Central

    Prenen, Klaas; Prenen, Hans

    2015-01-01

    Oncological emergencies are defined as acute life-threatening conditions in cancer patients either as a result of the malignancy or as a result of its treatment. In this review, we focus on oncological emergencies associated with gastrointestinal tumors. They can be categorized by their system of origin as hematologic, neurologic or metabolic. Furthermore, we discuss mechanical emergencies such as intestinal obstruction and vena cava superior syndrome as well as acute gastrointestinal bleeding and pulmonary embolism. The patients’ performance status as well as prognosis are essential during decision making for optimal treatment. PMID:26424367

  5. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016

    PubMed Central

    Bossé, D.; Ng, T.; Ahmad, C.; Alfakeeh, A.; Alruzug, I.; Biagi, J.; Brierley, J.; Chaudhury, P.; Cleary, S.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Ferland, E.; Galiatsatos, P.; Girard, S.; Gray, S.; Halwani, F.; Kopek, N.; Mahmud, A.; Martel, G.; Robillard, L.; Samson, B.; Seal, M.; Siddiqui, J.; Sideris, L.; Snow, S.; Thirwell, M.; Vickers, M.; Goodwin, R.; Goel, R.; Hsu, T.; Tsvetkova, E.; Ward, B.; Asmis, T.

    2016-01-01

    The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5–7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents PMID:28050151

  6. Giant Malignant Pheochromocytoma with Palpable Rib Metastases

    PubMed Central

    Gokce, Gokhan; Kilicli, Fatih; Elagoz, Sahande; Ayan, Semih; Gultekin, Emin Yener

    2014-01-01

    Pheochromocytoma is a rare and usually benign neuroendocrine neoplasm. Only 10% of all these tumors are malignant and there are no definitive histological or cytological criteria of malignancy. Single malignancy criteria are the presence of advanced locoregional disease or metastases. We report a case, with a giant retroperitoneal tumor having multiple metastases including palpable rib metastases, who was diagnosed as a malignant pheochromocytoma. The patient was treated with surgery. The literature was reviewed to evaluate tumor features and current diagnostic and therapeutic approaches for patients with metastatic or potentially malignant pheochromocytoma. PMID:25152826

  7. A Phase I and pharmacological study of the glutamine antagonist acivicin with the amino acid solution aminosyn in patients with advanced solid malignancies.

    PubMed

    Hidalgo, M; Rodriguez, G; Kuhn, J G; Brown, T; Weiss, G; MacGovren, J P; Von Hoff, D D; Rowinsky, E K

    1998-11-01

    Acivicin is a glutamine analogue antimetabolite that inhibits several glutamate-dependent synthetic enzymes. Previous studies of this agent administered on a 72-h continuous i.v. infusion schedule every 3 weeks demonstrated a high rate of severe, albeit reversible, central nervous system (CNS) toxicity at the 30 mg/m2/day dose level. Animal studies have shown that the CNS toxicity of acivicin can be prevented by a concomitant infusion of amino acids postulated to block drug uptake in the CNS by a saturable transport system that is common to endogenous amino acids. This study evaluated the feasibility of escalating acivicin doses in cancer patients by administering acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids (Aminosyn, 10%). Twenty-three patients with advanced malignancies were treated with acivicin on a 72-h continuous infusion schedule at doses ranging from 25 to 60 mg/m2/day every 3 weeks. Reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion, and decreased mental status, occurred in the two patients enrolled at the 60 mg/m2/day dose level, precluding further dose escalation. The maximum tolerated dose (MTD) and recommended dose for additional evaluation of acivicin on this schedule is 50 mg/m2/day. Other toxicities observed were dose-related neutropenia that was grade 4 in four patients (four courses), complicated with fever in three of those patients, and grade 3-4 thrombocytopenia in three patients (three courses). Pharmacokinetics studies performed in 15 patients revealed that the acivicin plasma Css increased from 0.44 microg/ml (range, 0.28-0.59 microg/ml) at the 25 mg/m2/day to 1.06 microg/ml (0.64-1.5 microg/ml) at the 50 mg/m2/dose level. Acivicin Css at the MTD was not significantly higher than previously reported values with single-agent acivicin on the same schedule of administration at the MTD of 25 mg/m2/day dose level (0.60 microg/ml; range, 0.43-0.81 microg/ml). Neurotoxicity did not

  8. Dysbiosis in gastrointestinal disorders.

    PubMed

    Chang, Christopher; Lin, Henry

    2016-02-01

    The recent development of advanced sequencing techniques has revealed the complexity and diverse functions of the gut microbiota. Furthermore, alterations in the composition or balance of the intestinal microbiota, or dysbiosis, are associated with many gastrointestinal diseases. The looming question is whether dysbiosis is a cause or effect of these diseases. In this review, we will evaluate the contribution of intestinal microbiota in obesity, fatty liver, inflammatory bowel disease, and irritable bowel syndrome. Promising results from microbiota or metabolite transfer experiments in animals suggest the microbiota may be sufficient to reproduce disease features in the appropriate host in certain disorders. Less compelling causal associations may reflect complex, multi-factorial disease pathogenesis, in which dysbiosis is a necessary condition. Understanding the contributions of the microbiota in GI diseases should offer novel insight into disease pathophysiology and deliver new treatment strategies such as therapeutic manipulation of the microbiota.

  9. Glycomic Approaches for the Discovery of Targets in Gastrointestinal Cancer

    PubMed Central

    Mereiter, Stefan; Balmaña, Meritxell; Gomes, Joana; Magalhães, Ana; Reis, Celso A.

    2016-01-01

    Gastrointestinal (GI) cancer is the most common group of malignancies and many of its types are among the most deadly. Various glycoconjugates have been used in clinical practice as serum biomarker for several GI tumors, however, with limited diagnose application. Despite the good accessibility by endoscopy of many GI organs, the lack of reliable serum biomarkers often leads to late diagnosis of malignancy and consequently low 5-year survival rates. Recent advances in analytical techniques have provided novel glycoproteomic and glycomic data and generated functional information and putative biomarker targets in oncology. Glycosylation alterations have been demonstrated in a series of glycoconjugates (glycoproteins, proteoglycans, and glycosphingolipids) that are involved in cancer cell adhesion, signaling, invasion, and metastasis formation. In this review, we present an overview on the major glycosylation alterations in GI cancer and the current serological biomarkers used in the clinical oncology setting. We further describe recent glycomic studies in GI cancer, namely gastric, colorectal, and pancreatic cancer. Moreover, we discuss the role of glycosylation as a modulator of the function of several key players in cancer cell biology. Finally, we address several state-of-the-art techniques currently applied in this field, such as glycomic and glycoproteomic analyses, the application of glycoengineered cell line models, microarray and proximity ligation assay, and imaging mass spectrometry, and provide an outlook to future perspectives and clinical applications. PMID:27014630

  10. World Association for the Advancement of Veterinary Parasitology (WAAVP): Guideline for the evaluation of drug efficacy against non-coccidial gastrointestinal protozoa in livestock and companion animals.

    PubMed

    Geurden, T; Olson, M E; O'Handley, R M; Schetters, T; Bowman, D; Vercruysse, J

    2014-08-29

    The current guideline was written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against non-coccidial gastrointestinal protozoan parasites, with Giardia spp. as the leading example. The information provided in this guideline deals with aspects of how to conduct controlled studies using experimental infection models (dose determination and dose confirmation) and efficacy studies in commercial facilities (field effectiveness studies). Furthermore, the selection of suitable animals, housing, infection procedure, choice of diagnostic technique and data analysis are discussed. This guideline is intended to assist investigators in conducting specific studies, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new drugs and to facilitate the worldwide adoption of uniform procedures. The primary parameter for drug efficacy is the reduction in either parasite excretion or parasite counts and a minimum efficacy of 90% is required against non-coccidial gastrointestinal protozoa. A supporting efficacy parameter is a significant difference in the proportion of infected animals between treated and non-treated groups. Persistent efficacy is considered as an additional claim to therapeutic efficacy.

  11. Malignant hyperthermia.

    PubMed

    Cantin, R Y; Poole, A; Ryan, J F

    1986-10-01

    The increasing use of intravenous and inhalation sedation in the dental office has the potential of increasing the incidence of malignant hyperthermia (MH) in susceptible subjects. The object of this article is to present two cases of MH and to discuss its pathophysiology, its clinical picture, and its management in the light of the current literature. Stringent screening procedures should be adopted and maintained in order to channel suspected cases to appropriate centers for expert consultation and management. It is further advocated that a program of education for patients and their families be instituted, as it is an essential prerequisite of effective prophylaxis.

  12. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  13. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  14. Meckel Diverticulum Harboring a Rare Gastrointestinal Stromal Tumor

    PubMed Central

    Berry, Andrew C.; Nakshabendi, Rahman; Kanar, Ozdemir; Hamer, Sean

    2017-01-01

    Background: Tumors within a Meckel diverticulum are a rare complication observed in only 0.5%-3.2% of symptomatic cases. The majority of tumors are benign, but some malignant tumors, such as gastrointestinal stromal tumors (GISTs) can occur. Case Report: We report the case of a 48-year-old female who presented with severe abdominal pain and nausea and was found to have a GIST arising from a Meckel diverticulum. Conclusion: The differential diagnosis of a pelvic mass in a middle-aged female presenting with gastrointestinal symptoms must remain broad. With an atypical presentation site, distinguishing benign tumors from malignant tumors such as GISTs is of paramount importance. PMID:28331460

  15. Stenting of the Upper Gastrointestinal Tract: Current Status

    SciTech Connect

    Katsanos, Konstantinos; Sabharwal, Tarun Adam, Andreas

    2010-08-15

    Minimally invasive image-guided insertion of self-expanding metal stents in the upper gastrointestinal tract is the current treatment of choice for palliation of malignant esophageal or gastroduodenal outlet obstructions. A concise review is presented of contemporary stenting practice of the upper gastrointestinal tract, and the procedures in terms of appropriate patient evaluation, indications, and contraindications for treatment are analyzed, along with available stent designs, procedural steps, clinical outcomes, inadvertent complications, and future technology. Latest developments include biodegradable polymeric stents for benign disease and radioactive or drug-eluting stents for malignant obstructions.

  16. Cholecystokinin and gastrin receptors targeting in gastrointestinal cancer.

    PubMed

    Rai, Rajani; Chandra, Vishal; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2012-12-01

    Cholecystokinin and Gastrin are amongst the first gastrointestinal hormone discovered. In addition to classical actions (contraction of gallbladder, growth and secretion in the stomach and pancreas), these also act as growth stimulants for gastrointestinal malignancies and cell lines. Growth of these tumours is inhibited by antagonists of the cholecystokinin and gastrin receptors. These receptors provides most promising approach in clinical oncology and several specific radiolabelled ligands have been synthesized for specific tumour targeting and therapy of tumours overexpressing these receptors. Therefore, definition of the molecular structure of the receptor involved in the autocrine/paracrine loop may contribute to novel therapies for gastrointestinal cancer. Hence, this review tries to focus on the role and distribution of these hormones and their receptors in gastrointestinal cancer with a brief talk about the clinical trial using available agonist and antagonist in gastrointestinal cancers.

  17. The impact of proton pump inhibitors on the human gastrointestinal microbiome

    PubMed Central

    Freedberg, Daniel E.; Lebwohl, Benjamin; Abrams, Julian A.

    2014-01-01

    Potent gastric acid suppression using proton pump inhibitors (PPIs) is common in clinical practice yet may have important effects on human health that are mediated through changes in the gastrointestinal microbiome. Acting through pH-dependent or pH-independent mechanisms, PPIs have the potential to alter the normal microbiota throughout the human gastrointestinal lumen. In the esophagus, PPIs change the normal bacterial milieu to decrease distal esophageal exposure to inflammatory Gram-negative bacteria which may lower the risk of Barrett's esophagus. In the stomach, PPIs alter the abundance and location of gastric Helicobacter pylori and other bacteria, which has implications for peptic ulcer disease and gastric malignancy. In the small bowel, PPIs cause polymicrobial small bowel bacterial overgrowth and have been associated with the diagnosis of celiac disease. In the colon, PPIs associate with incident but not recurrent Clostridium difficile infection, putatively through alterations in commensal colonic anaerobes. Our understanding of the effect of gastric acid suppression on the human gastrointestinal microbiome is incomplete but is rapidly advancing. PMID:25439276

  18. Incidence, risk factors and outcomes of de novo malignancies post liver transplantation

    PubMed Central

    Mukthinuthalapati, Pavan Kedar; Gotur, Raghavender; Ghabril, Marwan

    2016-01-01

    Liver transplantation (LT) is associated with a 2 to 7 fold higher, age and gender adjusted, risk of de novo malignancy. The overall incidence of de novo malignancy post LT ranges from 2.2% to 26%, and 5 and 10 years incidence rates are estimated at 10% to 14.6% and 20% to 32%, respectively. The main risk factors for de novo malignancy include immunosuppression with impaired immunosurveillance, and a number of patient factors which include; age, latent oncogenic viral infections, tobacco and alcohol use history, and underlying liver disease. The most common cancers after LT are non-melanoma skin cancers, accounting for approximately 37% of de novo malignancies, with a noted increase in the ratio of squamous to basal cell cancers. While these types of skin cancer do not impact patient survival, post-transplant lymphoproliferative disorders and solid organ cancer, accounting for 25% and 48% of malignancies, are associated with increased mortality. Patients developing these types of cancer are diagnosed at more advanced stages, and their cancers behave more aggressively compared with the general population. Patients undergoing LT for primary sclerosing cholangitis (particularly with inflammatory bowel disease) and alcoholic liver disease have high rates of malignancies compared with patients undergoing LT for other indications. These populations are at particular risk for gastrointestinal and aerodigestive cancers respectively. Counseling smoking cessation, skin protection from sun exposure and routine clinical follow-up are the current approach in practice. There are no standardized surveillance protocol, but available data suggests that regimented surveillance strategies are needed and capable of yielding cancer diagnosis at earlier stages with better resulting survival. Evidence-based strategies are needed to guide optimal surveillance and safe minimization of immunosuppression. PMID:27134701

  19. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

    PubMed

    Duffy, M J; Lamerz, R; Haglund, C; Nicolini, A; Kalousová, M; Holubec, L; Sturgeon, C

    2014-06-01

    Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

  20. Malignant hyperthermia

    PubMed Central

    Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene

  1. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

    PubMed Central

    Schaefer, Eric S; Baik, Christina

    2016-01-01

    Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%–7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

  2. Gastrointestinal radiation injury: Prevention and treatment

    PubMed Central

    Shadad, Abobakr K; Sullivan, Frank J; Martin, Joseph D; Egan, Laurence J

    2013-01-01

    With the recent advances in detection and treatment of cancer, there is an increasing emphasis on the efficacy and safety aspects of cancer therapy. Radiation therapy is a common treatment for a wide variety of cancers, either alone or in combination with other treatments. Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result. These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment. Radiation injury to the gastrointestinal tract can be minimised by either of two strategies: technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues, and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it. Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques, biological techniques may offer additional further promise. Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure, including biological, chemical and pharmacological agents. In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy, examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level. PMID:23345942

  3. Gastrointestinal endoscopy in the pregnant woman

    PubMed Central

    Friedel, David; Stavropoulos, Stavros; Iqbal, Shahzad; Cappell, Mitchell S

    2014-01-01

    About 20000 gastrointestinal endoscopies are performed annually in America in pregnant women. Gastrointestinal endoscopy during pregnancy raises the critical issue of fetal safety in addition to patient safety. Endoscopic medications may be potentially abortifacient or teratogenic. Generally, Food and Drug Administration category B or C drugs should be used for endoscopy. Esophagogastroduodenoscopy (EGD) seems to be relatively safe for both mother and fetus based on two retrospective studies of 83 and 60 pregnant patients. The diagnostic yield is about 95% when EGD is performed for gastrointestinal bleeding. EGD indications during pregnancy include acute gastrointestinal bleeding, dysphagia > 1 wk, or endoscopic therapy. Therapeutic EGD is experimental due to scant data, but should be strongly considered for urgent indications such as active bleeding. One study of 48 sigmoidoscopies performed during pregnancy showed relatively favorable fetal outcomes, rare bad fetal outcomes, and bad outcomes linked to very sick mothers. Sigmoidoscopy should be strongly considered for strong indications, including significant acute lower gastrointestinal bleeding, chronic diarrhea, distal colonic stricture, suspected inflammatory bowel disease flare, and potential colonic malignancy. Data on colonoscopy during pregnancy are limited. One study of 20 pregnant patients showed rare poor fetal outcomes. Colonoscopy is generally experimental during pregnancy, but can be considered for strong indications: known colonic mass/stricture, active lower gastrointestinal bleeding, or colonoscopic therapy. Endoscopic retrograde cholangiopancreatography (ERCP) entails fetal risks from fetal radiation exposure. ERCP risks to mother and fetus appear to be acceptable when performed for ERCP therapy, as demonstrated by analysis of nearly 350 cases during pregnancy. Justifiable indications include symptomatic or complicated choledocholithiasis, manifested by jaundice, cholangitis, gallstone

  4. Optimizing early upper gastrointestinal cancer detection at endoscopy.

    PubMed

    Veitch, Andrew M; Uedo, Noriya; Yao, Kenshi; East, James E

    2015-11-01

    Survival rates for upper gastrointestinal cancers are poor and oesophageal cancer incidence is increasing. Upper gastrointestinal cancer is also often missed during examinations; a predicament that has not yet been sufficiently addressed. Improvements in the detection of premalignant lesions, early oesophageal and gastric cancers will enable organ-preserving endoscopic therapy, potentially reducing the number of advanced upper gastrointestinal cancers and resulting in improved prognosis. Japan is a world leader in high-quality diagnostic upper gastrointestinal endoscopy and the clinical routine in this country differs substantially from Western practice. In this Perspectives article, we review lessons learnt from Japanese gastroscopy technique, training and screening for risk stratification. We suggest a key performance indicator for upper gastrointestinal endoscopy with a minimum total procedure time of 8 min, and examine how quality assurance concepts in bowel cancer screening in the UK could be applied to upper gastrointestinal endoscopy and improve clinical practice.

  5. Radiologic diagnosis of gastrointestinal perforation.

    PubMed

    Rubesin, Stephen E; Levine, Marc S

    2003-11-01

    Perforations of the gastrointestinal tract have many causes. Holes in the wall of gastrointestinal organs can be created by blunt or penetrating trauma, iatrogenic injury, inflammatory conditions that penetrate the serosa or adventitia, extrinsic neoplasms that invade the gastrointestinal tract, or primary neoplasms that penetrate outside the wall of gastrointestinal organs. This article provides a radiologic approach for investigating the wide variety of gastrointestinal perforations. General principles about contrast agents and studies are reviewed, and then perforations in specific gastrointestinal organs are discussed.

  6. A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

    PubMed Central

    Ganjoo, K. N.; Villalobos, V. M.; Kamaya, A.; Fisher, G. A.; Butrynski, J. E.; Morgan, J. A.; Wagner, A. J.; D'Adamo, D.; McMillan, A.; Demetri, G. D.; George, S.

    2014-01-01

    Background Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (−1, −2, and −3), and PDGFR (-α and-β) in patients with advanced GIST following failure of at least imatinib and sunitinib. Methods Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. Results Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2–7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5–37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6–5.2), and the median OS was 10.7 months (95% CI 3.9–NR). Conclusions Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in

  7. Current status of familial gastrointestinal polyposis syndromes

    PubMed Central

    Jung, Ioan; Gurzu, Simona; Turdean, Gligore Sabin

    2015-01-01

    Because of the rarity of familial gastrointestinal cancer-predisposing syndromes, their exploration in literature is not extensive. In this review, an update of the clinicopathological and molecular criteria of gastrointestinal familial polyposis syndromes with potential malignant transformation is performed. In addition, a guide for screening and surveillance was synthesized and a distribution of gene mutations according to the specific syndromes and geographic distribution was included. The following inherited polyposes syndromes were analyzed: familial adenomatous polyposis, the hamartomatous familial polyposes (Juvenile polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, hereditary mixed polyposis syndrome, Gorlin syndrome, Birt-Hogg-Dube syndrome, neurofibromatosis type I and multiple endocrine neoplasia syndrome 2B), Li-Fraumeni syndrome, and MUTYH-associated adenomatous polyposis. For proper medical care, subspecialization of gastroenterologists, pathologists, and genticists in the field of familial diseases should be introduced in the medical curriculum. PMID:26600934

  8. Increased incidence of second primary malignancy in patients with carcinoid tumors: case report and literature review.

    PubMed Central

    Rivadeneira, D. E.; Tuckson, W. B.; Naab, T.

    1996-01-01

    There is an increased incidence of second noncarcinoid neoplasms in patients with carcinoid tumors. This article reports a case of a synchronous malignant ileal carcinoid tumor in a patient with an adenocarcinoma of the sigmoid colon. This report illustrates the increased association of carcinoid tumors with other gastrointestinal malignancies. Images Figure 1 Figure 2 Figure 3 PMID:8667441

  9. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy—current perspectives

    PubMed Central

    Spiliotis, J.; Halkia, E.; de Bree, E.

    2016-01-01

    Peritoneal carcinomatosis (ptc) represents advanced malignant disease and has generally been associated with a grim prognosis. Peritoneal surface malignancy is often the major source of morbidity and mortality; it is of major concern in cancer management. Although ptc is categorized as metastatic disease, it represents a special disease pattern considered to be a locoregional disease limited to the abdominal cavity. The combination of cytoreductive surgery (crs) and intraoperative hyperthermic intraperitoneal chemotherapy (hipec) has successfully been used as locoregional treatment for selected patients with ptc from gastric, colorectal, and ovarian cancer; with mesothelioma; and with pseudomyxoma peritonei. In the prophylactic setting, hipec can also be used to prevent ptc in high-risk patients, and the first results of the “second-look” approach are promising. Patient selection—in which the risks of perioperative morbidity and mortality, which are analogous to those for any other major gastrointestinal surgery, are assessed—is of utmost importance. Those risks have to be weighed against the anticipated survival benefit, which depends mainly on tumour biology, extent of disease, and probability of achieving complete crs. The present review discusses the principles of crs and hipec, the most significant recent clinical data, and current perspectives concerning the application of this treatment modality in various malignancies. Ongoing trials and future directions are noted. It appears that the combination of crs and hipec is an indispensable tool in the oncologist’s armamentarium. PMID:27330364

  10. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    PubMed

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.

  11. Gastrointestinal toxicity associated to radiation therapy.

    PubMed

    Rodríguez, Mario López; Martín, Margarita Martín; Padellano, Laura Cerezo; Palomo, Alicia Marín; Puebla, Yamile Ibáñez

    2010-08-01

    Radiation therapy in combination with other treatments, such as surgery and chemotherapy, increases locoregional control and survival in patients with thoracic, abdominal and pelvic malignancies. Nevertheless, significant clinical toxicity with combined treatments may be seen in these patients. With the advent of tridimensional conformal radiotherapy (3D-CRT), dose-volume histograms (DVH) can be generated to assess the dose received by the organs at risk. The possible relationship between these parameters and clinical, anatomical and, more recently, genetic factors has to be considered. Treatment options include initial conservative medical therapies, endoscopic procedures, hyperbaric oxygen and surgery. Some pharmacological agents to prevent gastrointestinal toxicity are under investigation.

  12. Conventional radiological strategy of common gastrointestinal neoplasms

    PubMed Central

    Li, Yi-Zhuo; Wu, Pei-Hong

    2015-01-01

    This article summarizes the clinical characteristics and imaging features of common gastrointestinal (GI) neoplasms in terms of conventional radiological imaging methods. Barium studies are readily available for displaying primary malignancies and are minimally or not at all invasive. A neoplasm may be manifested as various imaging findings, including mucosal disruption, soft mass, ulcer, submucosal invasion and lumen stenosis on barium studies. Benign tumors typically appear as smoothly marginated intramural masses. Malignant neoplasms most often appear as irregular infiltrative lesions on barium examination. Tumor extension to adjacent GI segments may be indistinct on barium images. Cross-sectional images such as computed tomography and magnetic resonance imaging may provide more accurate details of the adjacent organ invasion, omental or peritoneal spread. PMID:25628800

  13. Malignant mesothelioma: Canadian perspective and research directions

    PubMed Central

    Lee, C.W.; Martin, J.; MacRae, R.; Tsao, M.S.; Nguyen, E.; Johnston, M.; Baas, P.; Laurie, S.; Feld, R.; Murray, N.; Shepherd, F.A.

    2008-01-01

    Since the 1960s, the incidence of malignant mesothelioma in Canada has increased dramatically because of work-related asbestos exposures. Treatment options are limited. Although chemotherapy is now an accepted standard in the management of advanced disease, uncertainty surrounds the roles of radical surgery and radiation. In March 2007, a symposium was held in Vancouver, B.C., to review the current approach to malignant mesothelioma in Canada and to discuss development of a national clinical research strategy.

  14. A Phase I Study of the First-in-Class Anti-Mitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Pardee, Timothy S.; Lee, King; Luddy, John; Maturo, Claudia; Rodriguez, Robert; Isom, Scott; Miller, Lance D.; Stadelman, Kristin M.; Levitan, Denise; Hurd, David; Ellis, Leslie R.; Harrelson, Robin; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2014-01-01

    Purpose The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the maximally tolerated dose (MTD), pharmacokinetics (PKs), and safety in patients with relapsed or refractory hematologic malignancies. Experimental Design Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. Results CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities (DLTs). At a dose of 2940 mg/m2 over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of ~1.34 hours. Of 21 evaluable, heavily pretreated, patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. Conclusion CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients. PMID:25165100

  15. TNF-α and Tumor Lysate Promote the Maturation of Dendritic Cells for Immunotherapy for Advanced Malignant Bone and Soft Tissue Tumors

    PubMed Central

    Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takata, Munetomo; Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Kimura, Hiroaki; Igarashi, Kentaro; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

    2012-01-01

    Background Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli. Methods Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-γ and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy. Results Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL-12 showed significant elevation at one and three months after DC-based immunotherapy. Conclusions Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors. PMID:23300824

  16. Osteoporosis and Gastrointestinal Disease

    PubMed Central

    Weinerman, Stuart

    2010-01-01

    Gastrointestinal disease is often overlooked or simply forgotten as a cause of osteoporosis. Yet, the consequences of osteoporotic fractures can be devastating. Although the bulk of the published experience regarding osteoporosis is derived from the postmenopausal population, this review will focus on gastrointestinal disorders implicated in osteoporosis, with an emphasis on inflammatory bowel disease and celiac disease. The unique aspects of gastrointestinal diseases associated with osteoporosis include early onset of disease (and, therefore, prolonged exposure to risk factors for developing osteoporosis, particularly with inflammatory bowel disease and celiac disease), malabsorption, and maldigestion of nutrients necessary for bone health and maintenance (eg, calcium, vitamin D), as well as the impact of glucocorticoids. These factors, when added to smoking, a sedentary lifestyle, hypogonadism, and a family history of osteoporosis, accumulate into an imposing package of predictors for osteoporotic fracture. This paper will review the identification and treatment strategies for patients with gastrointestinal disorders and osteoporosis. PMID:20978554

  17. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised. Canine olfactory detection of human malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate and skin cancers. Further research in this area may facilitate the development of a highly accurate aid to diagnosis for many malignancies, including melanoma. PMID:24127369

  18. Vasculitis and gastrointestinal involvement.

    PubMed

    Casella, G; Bronzino, B; Cutrino, L; Montani, N; Somma, A; Baldini, V

    2006-06-01

    The incidence of gastrointestinal involvement is relatively observed in patients with vasculitis processes. Vasculitis can be primary (necrotising or hypersensitivity) or secondary to another primary disease. Gastrointestinal involvement is present in up to 50% of the various forms of systemic vasculitis. Primary or secondary vasculitic process, according to the classification in necrotizing and hypersensitivity vasculitis, are described in this paper. A review of the literature on the the subject is also presented.

  19. Asbestos and Gastrointestinal Cancer

    PubMed Central

    Morgan, Robert W.; Foliart, Donna E.; Wong, Otto

    1985-01-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, we listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, we calculated summary SMRs for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMRs remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. Based on the results after reanalysis, the elevations in summary SMRs for stomach and total gastrointestinal tract cancer are of a magnitude that could result from diagnostic and investigator error. We conclude that more studies are required before stomach and colorectal cancers are documented as asbestos-related diseases. PMID:4036114

  20. Angiography and the gastrointestinal bleeder

    SciTech Connect

    Baum, S.

    1982-05-01

    The role of angiography in the diagnosis and treatment of gastrointestinal hemorrhage is discussed. Three categories of gastrointestinal bleeding are considered: upper gastrointestinal bleeding due to gastroesophageal varices, upper gastrointestinal bleeding of arterial or capillary origin, and lower gastrointestinal bleeding. The advantages and disadvantages of angiography are compared with those of radionuclide scanning and endoscopy or colonoscopy. It is anticipated that, as radionuclide scans are more widely employed, angiography will eventually be performed only in those patients with positive scans.

  1. Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function.

    PubMed

    Pan, Ping-Ying; Wang, George X; Yin, Bingjiao; Ozao, Junko; Ku, Teresa; Divino, Celia M; Chen, Shu-Hsia

    2008-01-01

    Tumor growth induced a significant increase of myeloid-derived suppressor cells (MDSCs) in the tumor-bearing host. In our previous study, we showed that MDSCs induced tumor-specific T-cell tolerance and the development of T regulatory cells (Tregs). Tumor-derived factors have been implicated in the accumulation of MDSCs. We hypothesize that reduction of MDSC accumulation in tumor-bearing hosts, through the blockade of tumor factors, can prevent T-cell anergy and Treg development and thereby improve immune therapy for the treatment of advanced tumors. Several tumor-derived factors were identified by gene array analysis. Among the candidate factors, stem- cell factor (SCF) is expressed by various human and murine carcinomas and was selected for further study. Mice bearing tumor cells with SCF siRNA knockdown exhibited significantly reduced MDSC expansion and restored proliferative responses of tumor-infiltrating T cells. More importantly, blockade of SCF receptor (ckit)-SCF interaction by anti-ckit prevented tumor-specific T-cell anergy, Treg development, and tumor angiogenesis. Furthermore, the prevention of MDSC accumulation in conjunction with immune activation therapy showed synergistic therapeutic effect when treating mice bearing large tumors. This information supports the notion that modulation of MDSC development may be required to achieve effective immune-enhancing therapy for the treatment of advanced tumors.

  2. Precursors to Lymphoproliferative Malignancies

    PubMed Central

    Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

    2013-01-01

    We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. PMID:23549397

  3. State of the Art in the Treatment of Gastrointestinal Stromal Tumors

    PubMed Central

    Garlipp, Benjamin; Bruns, Christiane J.

    2014-01-01

    Background Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal neoplasms of the gastrointestinal tract. Despite their biological and clinical heterogeneity, the majority of these tumors are positive for the receptor tyrosine kinase KIT and are driven by KIT- or platelet-derived growth factor receptor alpha (PDGFRA)-activating mutations. There are still uncertainties regarding their clinical and molecular characterization and the optimal treatment regimens, making it difficult to establish a universal treatment algorithm for these tumors. Summary From a clinical perspective, the main difference between GISTs and other gastrointestinal neoplasms is that the benign or malignant behavior of GISTs cannot be predicted from histopathology, but instead relies on empirically established scoring systems. Clinical data suggest that malignant potential may be an inherent quality of some GISTs rather than a feature acquired by the tumor during disease progression. Thus, some patients may require prolonged anti-tumor treatment even after complete surgical removal of the tumor. Key Message Although GISTs are the most frequently occurring mesenchymal neoplasms in the gastrointestinal tract, no universal treatment algorithms exist. This paper reviews the current evidence that guides the management of GISTs. Practical Implications The management of localized GISTs involves the use of surgical resection, with the inclusion of preoperative tyrosine kinase inhibitor treatment for locally advanced, primarily unresectable tumors and for resectable cases requiring extensive surgery. Imatinib is also indicated as adjuvant therapy after complete surgical removal of GISTs with a high estimated risk of recurrence unless specific mutations conferring imatinib resistance are present. The optimal duration of adjuvant treatment is still controversial. For patients with metastatic imatinib-sensitive GISTs, imatinib constitutes the first-line standard treatment

  4. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    SciTech Connect

    Partl, Richard; Richtig, Erika; Avian, Alexander; Berghold, Andrea; Kapp, Karin S.

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  5. A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies

    PubMed Central

    Mateo, Joaquin; Olmos, David; Dumez, Herlinde; Poondru, Srinivasu; Samberg, Nancy L; Barr, Sharon; Van Tornout, Jan M; Jie, Fei; Sandhu, Shahneen; Tan, Daniel S; Moreno, Victor; LoRusso, Patricia M; Kaye, Stan B; Schöffski, Patrick

    2016-01-01

    Background: The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK activation, which may be abrogated by mTORC2 inhibition. A first-in-human trial evaluating tolerability, pharmacokinetics and pharmacodynamics of the dual TORC1/TORC2 inhibitor OSI-027 was conducted. Methods: Dose escalation was pursued for three schedules of administration (three consecutive days per week (S1), once a week (S2) and daily dosing (S3)), until dose-limiting toxicities (DLT) were identified. Expansion cohorts with paired tumour biopsies were initiated based on tolerability and pharmacodynamics. Results: One hundred and twenty eight patients with advanced cancer were enrolled. DLT consisted predominantly of fatigue, renal function disturbances and cardiac events. OSI-027 exposure was dose proportional, with Tmax within 4 h and a half-life of ∼14 h. Expansion cohorts were initiated for S1 and S2, as MTD for S3 was overall considered suboptimal. Target modulation in peripheral blood mononuclear cells were observed from 30 mg, but in tumour biopsies 120 mg QD were needed, which was a non-tolerable dose due to renal toxicity. No RECIST responses were recorded, with stable disease >6 months in six (5%) patients. Conclusions: OSI-027 inhibits mTORC1/2 in patients with advanced tumour s in a dose-dependent manner but doses above the tolerable levels in S1 and S3 are required for a sustained biological effect in tumour biopsies. PMID:27002938

  6. Advanced malignancies treated with a combination of the VEGF inhibitor bevacizumab, anti-EGFR antibody cetuximab, and the mTOR inhibitor temsirolimus

    PubMed Central

    Liu, Xiaochun; Kambrick, Susan; Fu, Siqing; Naing, Aung; Subbiah, Vivek; Blumenschein, George R.; Glisson, Bonnie S.; Kies, Merrill S.; Tsimberidou, Apostolia M.; Wheler, Jennifer J.; Zinner, Ralph G.; Hong, David S.; Kurzrock, Razelle; Piha-Paul, Sarina A.

    2016-01-01

    BACKGROUND Bevacizumab and temsirolimus are active agents in advanced solid tumors. Temsirolimus inhibits mTOR in the PI3 kinase/AKT/mTOR pathway as well as CYP2A, which may be a resistance mechanism for cetuximab. In addition, temsirolimus attenuates upregulation of HIF-1α levels, which may be a resistance mechanism for bevacizumab. RESULTS The median age of patients was 60 years (range, 23-80 years). The median number of prior systemic therapies was 3 (range, 1-6). The maximum tolerated dose (MTD) was determined to be bevacizumab 10 mg/kg biweekly, temsirolimus 5 mg weekly and cetuximab 100/75 mg/m2 weekly. Grade 3 or 4 toxicities were seen in 52% of patients with the highest prevalence being hyperglycemia (14%) and hypophosphatemia (14%). Eighteen of the 21 patients were evaluable for response. Three patients were taken off the study before restaging for toxicities. Partial response (PR) was observed in 2/18 patients (11%) and stable disease (SD) lasting ≥ 6 months was observed in 4/18 patients (22%) (total = 6/18 (33%)). In 8 evaluable patients with squamous cell carcinoma of the head and neck (HNSCC) there were partial responses in 2/8 (25%) patients and SD ≥ 6 months in 1/8 (13%) patients (total = 3/8, (38%)). PATIENTS AND METHODS We analyzed safety and responses in 21 patients with advanced solid tumors treated with bevacizumab, cetuximab, and temsirolimus. CONCLUSION The combination of bevacizumab, cetuximab, and temsirolimus showed activity in HNSCC; however, there were numerous toxicities reported, which will require careful management for future clinical development. PMID:26933802

  7. Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin*

    PubMed Central

    Junqueira, Ana Lucia Ariano; Corbett, Ana Maria França; de Oliveira Filho, Jayme; Nasser, Kassila da Rosa; Haddad, Natalie Nejem; Tebet, Ana Carolina Franco

    2015-01-01

    Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy. PMID:26375228

  8. Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin.

    PubMed

    Junqueira, Ana Lucia Ariano; Corbett, Ana Maria França; Oliveira Filho, Jayme de; Nasser, Kassila da Rosa; Haddad, Natalie Nejem; Tebet, Ana Carolina Franco

    2015-01-01

    Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy.

  9. Circulating Carnosine Dipeptidase 1 Associates with Weight Loss and Poor Prognosis in Gastrointestinal Cancer

    PubMed Central

    Arner, Peter; Henjes, Frauke; Schwenk, Jochen M.; Darmanis, Spyros; Dahlman, Ingrid; Iresjö, Britt-Marie; Naredi, Peter; Agustsson, Thorhallur; Lundholm, Kent; Nilsson, Peter; Rydén, Mikael

    2015-01-01

    Background Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC. PMID:25898255

  10. Application of photodynamic therapy in gastrointestinal disorders: an outdated or re-emerging technique?

    PubMed Central

    Lee, Han Hee; Choi, Myung-Gyu; Hasan, Tayyaba

    2017-01-01

    Photodynamic therapy (PDT) is a promising therapeutic modality that involves the administration of a photosensitizer followed by local illumination with a specific wavelength of light in the presence of oxygen. PDT is minimally invasive, has high selectivity for cancer, and has good patient compliance due to the simplicity of the procedure; therefore, PDT is widely used as a palliative and salvage treatment in patients with various gastrointestinal malignancies. When used as a salvage treatment for locoregional failures after definitive chemoradiotherapy for esophageal cancer, favorable results have been reported. PDT in conjunction with biliary stenting is a promising palliative treatment for unresectable cholangiocarcinoma, and can be used as an advanced diagnostic and therapeutic strategy in peritoneal dissemination of gastric cancer. Recent clinical reports of PDT for treating non-resectable pancreatic cancer also show promising results. To widen the application of PDT, the integration of PDT with molecular imaging and nanotechnology is being extensively studied. Based on these new developments, PDT is likely to re-emerge as a valuable technique in the treatment of diverse gastrointestinal diseases. PMID:28049283

  11. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer

    PubMed Central

    Santhanam, Srikanth; Alvarado, David M.; Ciorba, Matthew A.

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant side effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapies are a promising new approach to harness the body’s own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway is a particularly promising target for immunotherapy. Indoleamine 2,3 dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and kynurenine pathway metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth and luminal microbiota. This pathway’s role in other gastrointestinal malignancies such as gastric, pancreatic, esophageal and gastrointestinal stromal tumors (GIST) is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal and colitis associated cancer. PMID:26297050

  12. Asbestos and gastrointestinal cancer

    SciTech Connect

    Morgan, R.W.; Foliart, D.E.; Wong, O.

    1985-07-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, the authors listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, summary SMRs were calculated for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMR remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. 59 references, 5 tables.

  13. A Prospective Study of an Alemtuzumab Containing Reduced-intensity Allogeneic Stem Cell Transplantation Program in Patients with Poor-Risk and Advanced Lymphoid Malignancies

    PubMed Central

    Sauter, Craig S.; Chou, Joanne F.; Papadopoulos, Esperanza B.; Perales, Miguel-Angel; Jakubowski, Ann A.; Young, James W.; Scordo, Michael; Giralt, Sergio; Castro-Malaspina, Hugo

    2015-01-01

    Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight advanced lymphoma patients underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporin-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years is 25% (95% CI: 13-40) and 44% (95% CI: 28-59%) respectively. Previous high-dose therapy and autologous stem cell transplantation (HDT-ASCT) and elevated LDH at the time of allo-SCT resulted in inferior OS. Within this cohort of high-risk lymphoma patients, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of POD, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT. PMID:24528216

  14. Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy

    PubMed Central

    Park, Haeseong; Garrido-Laguna, Ignacio; Naing, Aung; Fu, Siqing; Falchook, Gerald S.; Piha-Paul, Sarina A.; Wheler, Jennifer J.; Hong, David S.; Tsimberidou, Apostolia M.; Subbiah, Vivek; Zinner, Ralph G.; Kaseb, Ahmed O.; Patel, Shreyaskumar; Fanale, Michelle A.; Velez-Bravo, Vivianne M.; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2016-01-01

    Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (−78%) and perivascular epithelioid tumor (−54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma. PMID:27589687

  15. Gastrointestinal Stromal Tumor Arising From a Gastric Duplication Cyst

    PubMed Central

    Machicado, Jorge; Davogustto, Giovanni

    2016-01-01

    Gastric duplication cysts (GDC) are rarely diagnosed in adults, but previous cases have been associated with malignancy. We present a case of gastrointestinal stromal tumor (GIST) arising from a GDC in a 71-year-old woman who presented with 3 years of early satiety, anorexia, abdominal distention, and weight loss. Abdominal CT showed a 9.3 x 5.2 x 9.5-cm well-circumscribed cystic mass arising 3 cm above the gastroduodenal junction. The cyst was resected, and histopathology was consistent with GDC. Future studies are needed to clarify the malignant potential of GDC and the molecular pathways for its development. PMID:27144196

  16. Interventional Management of Gastrointestinal Fistulas

    PubMed Central

    Kwon, Se Hwan; Kim, Hyoung Jung; Park, Sun Jin; Park, Ho Chul

    2008-01-01

    Gastrointestinal (GI) fistulas are frequently very serious complications that are associated with high morbidity and mortality. GI fistulas can cause a wide array of pathophysiological effects by allowing abnormal diversion of the GI contents, including digestive fluid, water, electrolytes, and nutrients, from either one intestine to another or from the intestine to the skin. As an alternative to surgery, recent technical advances in interventional radiology and percutaneous techniques have been shown as advantageous to lower the morbidity and mortality rate, and allow for superior accessibility to the fistulous tracts via the use of fistulography. In addition, new interventional management techniques continue to emerge. We describe the clinical and imaging features of GI fistulas and outline the interventional management of GI fistulas. PMID:19039271

  17. Interventional management of gastrointestinal fistulas.

    PubMed

    Kwon, Se Hwan; Oh, Joo Hyeong; Kim, Hyoung Jung; Park, Sun Jin; Park, Ho Chul

    2008-01-01

    Gastrointestinal (GI) fistulas are frequently very serious complications that are associated with high morbidity and mortality. GI fistulas can cause a wide array of pathophysiological effects by allowing abnormal diversion of the GI contents, including digestive fluid, water, electrolytes, and nutrients, from either one intestine to another or from the intestine to the skin. As an alternative to surgery, recent technical advances in interventional radiology and percutaneous techniques have been shown as advantageous to lower the morbidity and mortality rate, and allow for superior accessibility to the fistulous tracts via the use of fistulography. In addition, new interventional management techniques continue to emerge. We describe the clinical and imaging features of GI fistulas and outline the interventional management of GI fistulas.

  18. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.

    PubMed

    Dumonceau, J-M; Tringali, A; Blero, D; Devière, J; Laugiers, R; Heresbach, D; Costamagna, G

    2012-03-01

    This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy about endoscopic biliary stenting. The present Clinical Guideline describes short-term and long-term results of biliary stenting depending on indications and stent models; it makes recommendations on when, how, and with which stent to perform biliary drainage in most common clinical settings, including in patients with a potentially resectable malignant biliary obstruction and in those who require palliative drainage of common bile duct or hilar strictures. Treatment of benign conditions (strictures related to chronic pancreatitis, liver transplantation, or cholecystectomy, and leaks and failed biliary stone extraction) and management of complications (including stent revision) are also discussed. A two-page executive summary of evidence statements and recommendations is provided. A separate Technology Review describes the models of biliary stents available and the stenting techniques, including advanced techniques such as insertion of multiple plastic stents, drainage of hilar strictures, retrieval of migrated stents and combined stenting in malignant biliary and duodenal obstructions.The target readership for the Clinical Guideline mostly includes digestive endoscopists, gastroenterologists, oncologists, radiologists, internists, and surgeons while the Technology Review should be most useful to endoscopists who perform biliary drainage.

  19. Vasculitis associated with malignancy.

    PubMed

    Mertz, L E; Conn, D L

    1992-02-01

    A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.

  20. Targeting immune checkpoints in malignant glioma

    PubMed Central

    Li, Tete; Liu, Yong-Jun; Chen, Wei; Chen, Jingtao

    2017-01-01

    Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the bodys anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered immune privileged and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma. In this review, we focus on immune checkpoint inhibitors, specifically, antagonizing monoclonal antibodies for programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO). We discuss advances in the working mechanisms of these immune checkpoint molecules, their status in malignant glioma, and current preclinical and clinical trials targeting these molecules in malignant glioma. PMID:27756892

  1. Hemostatic Powders in Gastrointestinal Bleeding: A Systematic Review.

    PubMed

    Chen, Yen-I; Barkun, Alan N

    2015-07-01

    Topical hemostatic agents and powders are an emerging modality in the endoscopic management of upper and lower gastrointestinal bleeding. This systematic review demonstrates the effectiveness and safety of these agents with special emphasis on TC-325 and Ankaferd Blood Stopper. The unique noncontact/nontraumatic application, ability to cover large areas of bleed, and ease of use make these hemostatic agents an attractive option in certain clinical situations, such as massive bleeding with poor visualization, salvage therapy, and diffuse bleeding from luminal malignancies.

  2. Gastrointestinal Bleeding from Metastatic Prostate Adenocarcinoma to the Stomach

    PubMed Central

    Koop, Andree; Brauhmbhatt, Bhaumik; Lewis, Jason

    2017-01-01

    We present a rare case of gastrointestinal (GI) bleeding associated with metastatic prostate adenocarcinoma to the stomach. Prostate cancer, which is the most common noncutaneous malignancy among men, rarely spreads to the stomach, with only 7 cases reported in the English literature. Symptoms may include abdominal pain, nausea, vomiting, and GI bleeding. Our patient was treated with epinephrine injection and bipolar cautery, but GI bleeding recurred 7 months later when he had worsening of his thrombocytopenia while using ibuprofen. PMID:28377935

  3. Giant rectal gastrointestinal stromal tumours: a diagnostic and therapeutic challenge

    PubMed Central

    Alder, L.S.; Elver, G.; Foo, F.J.; Dobson, M.

    2013-01-01

    Gastrointestinal stromal tumour (GIST are the most common mesenchymal tumours; however, rectal GISTs account for <5%. In the pelvis they represent a diagnostic challenge with giant GISTs likely to be malignant. They may present with urological, gynaecological or rectal symptoms. Sphincter-preserving surgery can be aided by neoadjuvant therapy. We present an uncommon case of giant rectal GIST masquerading as acute urinary retention. PMID:24968434

  4. Malignant Vagal Paraganglioma.

    PubMed

    Hamersley, Erin R S; Barrows, Amy; Perez, Angel; Schroeder, Ashley; Castle, James T

    2016-06-01

    Paragangliomas are rare, typically benign neuroendocrine tumors that represent a small portion of head and neck tumors. A small percentage of these are known to have malignant potential. They arise from the carotid body, jugular bulb or vagus nerves. There is limited literature discussing the management of malignant vagal paragangliomas. We present a case of a 25 year old female with a left malignant vagal paraganglioma. The following case presentation will describe the presentation, classic radiologic findings, and management of a malignant vagal paraganglioma along with a review of the literature.

  5. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

    ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881

  6. Biology and Treatment of Metastatic Gastrointestinal Neuroendocrine Tumors

    PubMed Central

    Strosberg, Jonathan R.; Nasir, Aejaz; Kvols, Larry

    2008-01-01

    Neuroendocrine malignancies of the gastroenteropancreatic axis include carcinoid and pancreatic endocrine tumors. These heterogeneous neoplasms arise from the enterochromaffin cells of the gastrointestinal tract and the islet cells of the pancreas. Histologically, most well-differentiated endocrine tumors consist of small, round, monomorphic cells, arranged in islands or trabeculae, with a distinct “salt-and-pepper” pattern of nuclear chromatin. Chromogranin and synaptophysin are useful as immunohistochemical markers of neuroendocrine differentiation. Other common features include the capacity to secrete peptide hormones and biogenic amines. A relatively indolent growth rate is characteristic of most gastrointestinal neuroendocrine tumors, with the exception of poorly differentiated tumors which are usually aggressive. Treatment strategies are designed to limit tumor progression and palliate hormonal syndromes. This article reviews the diverse biologic characteristics of gastrointestinal neuroendocrine tumors and current treatment options for metastatic disease. PMID:19259290

  7. Successful treatment of gastrointestinal mucormycosis in an adult with acute leukemia: case report and literature review

    PubMed Central

    Alghamdi, A.; Lutynski, A.; Minden, M.; Rotstein, C.

    2017-01-01

    Mucormycosis has emerged as an important cause of invasive fungal infection in patients with hematologic malignancies. Gastrointestinal mucormycosis is an unusual presentation of this invasive fungal infection, and it causes considerable morbidity and mortality. Such outcomes are due in part to a nonspecific presentation that results in delays in diagnosis and treatment. Successful treatment of gastrointestinal mucormycosis involves surgical debridement and appropriate antifungal therapy. PMID:28270734

  8. Treatment Option Overview (Gastrointestinal Carcinoid Tumors)

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  9. Treatment Options for Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  10. General Information about Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  11. Apollo gastrointestinal analysis

    NASA Technical Reports Server (NTRS)

    Nichols, B. L.; Huang, C. T. L.

    1975-01-01

    Fecal bile acid patterns for the Apollo 17 flight were studied to determine the cause of diarrhea on the mission. The fecal sterol analysis gave no indication of an infectious diarrhea, or specific, or nonspecific etiology occurring during the entire flight. It is assumed that the gastrointestinal problems encountered are the consequences of altered physiology, perhaps secondary to physical or emotional stress of flight.

  12. Pediatric functional gastrointestinal disorders

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional gastrointestinal disorders continue to be a prevalent set of conditions faced by the healthcare team and have a significant emotional and economic impact. In this review, the authors highlight some of the common functional disorders seen in pediatric patients (functional dyspepsia, irrita...

  13. Gastrointestinal endoscopy in pregnancy.

    PubMed

    Savas, Nurten

    2014-11-07

    Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most gastrointestinal disorders; however, limited information is available about clinical efficacy and safety in pregnant patients. The major risks of endoscopy during pregnancy include potential harm to the fetus because of hypoxia, premature labor, trauma and teratogenesis. In some cases, endoscopic procedures may be postponed until after delivery. When emergency or urgent indications are present, endoscopic procedures may be considered with some precautions. United States Food and Drug Administration category B drugs may be used in low doses. Endoscopic procedures during pregnancy may include upper gastrointestinal endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy, enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal endoscopic procedures in pregnant patients should be performed in hospitals by expert endoscopists and an obstetrician should be informed about all endoscopic procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus and pregnant patient, and may be performed during pregnancy when strong indications are present. Colonoscopy for pregnant patients may be considered for strong indications during the second trimester. Although therapeutic endoscopic retrograde cholangiopancreatography may be considered during pregnancy, this procedure should be performed only for strong indications and attempts should be made to minimize radiation exposure.

  14. Gastrointestinal endoscopy in pregnancy

    PubMed Central

    Savas, Nurten

    2014-01-01

    Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most gastrointestinal disorders; however, limited information is available about clinical efficacy and safety in pregnant patients. The major risks of endoscopy during pregnancy include potential harm to the fetus because of hypoxia, premature labor, trauma and teratogenesis. In some cases, endoscopic procedures may be postponed until after delivery. When emergency or urgent indications are present, endoscopic procedures may be considered with some precautions. United States Food and Drug Administration category B drugs may be used in low doses. Endoscopic procedures during pregnancy may include upper gastrointestinal endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy, enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal endoscopic procedures in pregnant patients should be performed in hospitals by expert endoscopists and an obstetrician should be informed about all endoscopic procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus and pregnant patient, and may be performed during pregnancy when strong indications are present. Colonoscopy for pregnant patients may be considered for strong indications during the second trimester. Although therapeutic endoscopic retrograde cholangiopancreatography may be considered during pregnancy, this procedure should be performed only for strong indications and attempts should be made to minimize radiation exposure. PMID:25386072

  15. Gastrointestinal Bleeding in Athletes.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1989-01-01

    Describes the scope and importance of gastrointestinal bleeding in runners and other athletes, discussing causes, sites, and implications of exercise-related bleeding. Practical tips to mitigate the problem, potentially more troublesome in women because of lower iron stores, are presented (e.g., gradual conditioning and avoidance of prerace…

  16. Updates in Tumor Profiling in Gastrointestinal Cancers.

    PubMed

    Perez, Kimberly; Safran, Howard P

    2015-10-01

    In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies. Work in colorectal cancer (CRC) has been in the forefront of these advances. With the continued development of NGS technology and the positive clinical experience in CRC, genome work has begun in esophagogastric, pancreatic, and hepatocellular carcinomas as well.

  17. Hydrogen Sulfide Signaling in the Gastrointestinal Tract

    PubMed Central

    2014-01-01

    Abstract Significance: The current literature regarding the effects of the gaseous signal molecule hydrogen sulfide (H2S) in the gastrointestinal system is reviewed. Bacterial, host and pharmaceutical-derived H2S are all considered and presented according to the physiological or pathophysiological effects of the gaseous signal molecule. These subjects include the toxicology of intestinal H2S with emphasis on bacterial-derived H2S, especially from sulfate-reducing bacteria, the role of endogenous and exogenous H2S in intestinal inflammation, and the roles of H2S in gastrointestinal motility, secretion and nociception. Recent Advances: While its pro- and anti-inflammatory, smooth muscle relaxant, prosecretory, and pro- and antinociceptive actions continue to remain the major effects of H2S in this system; recent findings have expanded the potential molecular targets for H2S in the gastrointestinal tract. Critical Issues: Numerous discrepancies remain in the literature, and definitive molecular targets in this system have not been supported by the use of competitive antagonism. Future Directions: Future work will hopefully resolve discrepancies in the literature and identify molecular targets and mechanisms of action for H2S. It is clear from the current literature that the long-appreciated relationship between H2S and the gastrointestinal tract continues to be strong as we endeavor to unravel its mysteries. Antioxid. Redox Signal. 20, 818–830. PMID:23582008

  18. Acute gastrointestinal complications after cardiac surgery.

    PubMed

    Halm, M A

    1996-03-01

    Gastrointestinal problems, with an incidence of about 1%, may complicate the postoperative period after cardiovascular surgery, increasing morbidity, length of stay, and mortality. Several risk factors for the development of these complications, including preexisting conditions; advancing age; surgical procedure, especially valve, combined bypass/valve, emergency, reoperative, and aortic dissection repair; iatrogenic conditions; stress; ischemia; and postpump complications, have been identified in multiple research studies. Ischemia is the most significant of these risk factors after cardiovascular surgery. Mechanisms that have been implicated include longer cardiopulmonary bypass and aortic cross-clamp times and hypoperfusion states, especially if inotropic or intra-aortic balloon pump support is required. These risk factors have been linked to upper and lower gastrointestinal bleeding, paralytic ileus, intestinal ischemia, acute diverticulitis, acute cholecystitis, hepatic dysfunction, hyperamylasemia, and acute pancreatitis. Gastrointestinal bleeding accounts for almost half of all complications, followed by hepatic dysfunction, intestinal ischemia, and acute cholecystitis. Identification of these gastrointestinal complications may be difficult because manifestations may be masked by postoperative analgesia or not reported by patients because they are sedated or require prolonged mechanical ventilation. Furthermore, clinical manifestations may be nonspecific and not follow the "classic" clinical picture. Therefore, astute assessment skills are needed to recognize these problems in high-risk patients early in their clinical course. Such early recognition will prompt aggressive medical and/or surgical management and therefore improve patient outcomes for the cardiovascular surgical population.

  19. Bronchial malignant melanoma.

    PubMed

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  20. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread.

    PubMed

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-03-16

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly.

  1. Gastrointestinal parasite infestation.

    PubMed

    Abd El Bagi, Mohamed E; Sammak, Bassam M; Mohamed, Abdulrahman E; Al Karawi, Mohamed A; Al Shahed, Mona; Al Thagafi, Mohamed A

    2004-03-01

    Twenty-five percent of the world's population could be suffering parasitic infestation. Highest prevalence is in underdeveloped agricultural and rural areas in the tropical and subtropical regions. In some areas incidence may reach 90% of the population. In contrast, some major economic projects intended to promote local development have, paradoxically, caused parasitic proliferation, e.g. bilharziasis in Egypt and Sudan and Chagas disease in Brazil. The commonest cosmopolitan gastrointestinal parasite is Entamoeba histolytica. Some intestinal parasite are endemic in temperate climates, e.g. Entrobius vermicularis. The AIDS epidemic has increased the prevalence and severity of parasitic disease, particularly Strongyloides stercolaris. Tropical parasites are seen in Western people who travel to tropical countries. Radiology has acquired a major role in diagnosis and management of gastrointestinal parasite infestations and their complications.

  2. [Microbiota and gastrointestinal diseases].

    PubMed

    Polanco Allué, I

    2015-12-01

    The bacterial colonisation is established immediately after birth, through direct contact with maternal microbiota, and may be influenced during lactation. There is emerging evidence indicating that quantitative and qualitative changes on gut microbiota contribute to alterations in the mucosal activation of the immune system, leading to intra- or extra-intestinal diseases. A balance between pathogenic and beneficial microbiota throughout childhood and adolescence is important to gastrointestinal health, including protection against pathogens, inhibition of pathogens, nutrient processing (synthesis of vitamin K), stimulation of angiogenesis, and regulation of host fat storage. Probiotics can promote an intentional modulation of intestinal microbiota favouring the health of the host. A review is presented on the modulation of intestinal microbiota on prevention, and adjuvant treatment of some paediatric gastrointestinal diseases.

  3. A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as a tumor-ablative regimen improved the survival of patients with advanced hematological malignancies

    PubMed Central

    Chen, Ping; Yuan, Xiaohong; Luo, Xiaofeng; Liu, Tingbo; Zheng, Jing; Zheng, Zhihong; Zheng, Xiaoyun; Chen, Xinji; Zhang, Langhui; Zheng, Hao; Chen, Zaisheng; Hua, Xueling; Le, Shaohua; Li, Jian; Chen, Zhizhe; Hu, Jianda

    2016-01-01

    Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not. Patients received FA5-BUCY, i.e., 5-day salvage chemotherapy (Fludarabine/Ara-C) and conditioning (Busulfan/Cyclophosphamide). GvHD prophylaxis included ATG, CsA, MMF and short-term MTX. All patients received stem cells from bone marrow and peripheral blood, and achieved successful engraftment, except two who died before. With a median follow-up of 269 days (120-1081), 42/63 patients are still alive and disease-free. Two-year OS and RFS were similar in patients not in remission and in those in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Non-relapse mortality and relapse incidence were 22.2% and 11.1%, respectively. Severe acute-GvHD occurred in 4/63 patients. Transplant-related mortality was low at day+100 (17.5%) and for the entire study period (20.6%). Unexpectedly, few patients experienced mild-to-moderate toxicity, and main causes of death were infection and GvHD. BM blast counts, age, and donor-recipient gender-pairs did not affect the outcome. Less chemotherapy cycles prior to HSCT might result in more favorable outcome. Thus, haplo-HSCT with FA5-BUCY appears promising for advanced disease, especially when TBI and amsacrine, used for FLAMSA, are not available and in pediatric patients for whom TBI is not recommended. PMID:27705929

  4. Noncoding RNAs in endocrine malignancy.

    PubMed

    Kentwell, Jessica; Gundara, Justin S; Sidhu, Stan B

    2014-05-01

    Only recently has it been uncovered that the mammalian transcriptome includes a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. Among numerous kinds of ncRNAs, short noncoding RNAs, such as microRNAs, have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. Long noncoding RNAs (lncRNAs) have only recently been implicated in playing a key regulatory role in cancer biology. The deregulation of ncRNAs has been demonstrated to have important roles in the regulation and progression of cancer development. In this review, we describe the roles of both short noncoding RNAs (including microRNAs, small nuclear RNAs, and piwi-interacting RNAs) and lncRNAs in carcinogenesis and outline the possible underlying genetic mechanisms, with particular emphasis on clinical applications. The focus of our review includes studies from the literature on ncRNAs in traditional endocrine-related cancers, including thyroid, parathyroid, adrenal gland, and gastrointestinal neuroendocrine malignancies. The current and potential future applications of ncRNAs in clinical cancer research is also discussed, with emphasis on diagnosis and future treatment.

  5. Gastrointestinal food allergies.

    PubMed

    Heine, Ralf G

    2015-01-01

    Gastrointestinal food allergies present during early childhood with a diverse range of symptoms. Cow's milk, soy and wheat are the three most common gastrointestinal food allergens. Several clinical syndromes have been described, including food protein-induced enteropathy, proctocolitis and enterocolitis. In contrast with immediate, IgE-mediated food allergies, the onset of gastrointestinal symptoms is delayed for at least 1-2 hours after ingestion in non-IgE-mediated allergic disorders. The pathophysiology of these non-IgE-mediated allergic disorders is poorly understood, and useful in vitro markers are lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative, although low-positive results may occur. Diagnosis therefore relies on the recognition of a particular clinical phenotype as well as the demonstration of clear clinical improvement after food allergen elimination and the re-emergence of symptoms upon challenge. There is a significant clinical overlap between non-IgE-mediated food allergy and several common paediatric gastroenterological conditions, which may lead to diagnostic confusion. The treatment of gastrointestinal food allergies requires the strict elimination of offending food allergens until tolerance has developed. In breast-fed infants, a maternal elimination diet is often sufficient to control symptoms. In formula-fed infants, treatment usually involves the use an extensively hydrolysed or amino acid-based formula. Apart from the use of hypoallergenic formulae, the solid diets of these children also need to be kept free of specific food allergens, as clinically indicated. The nutritional progress of infants and young children should be carefully monitored, and they should undergo ongoing, regular food protein elimination reassessments by cautious food challenges to monitor for possible tolerance development.

  6. Management of gastrointestinal hemorrhage.

    PubMed Central

    Hilsden, R. J.; Shaffer, E. A.

    1995-01-01

    Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time. Images Figure 1 Figure 2 PMID:8563510

  7. The use of optical imaging techniques in the gastrointestinal tract

    PubMed Central

    Beg, Sabina; Wilson, Ana; Ragunath, Krish

    2016-01-01

    With significant advances in the management of gastrointestinal disease there has been a move from diagnosing advanced pathology, to detecting early lesions that are potentially amenable to curative endoscopic treatment. This has required an improvement in diagnostics, with a focus on identifying and characterising subtle mucosal changes. There is great interest in the use of optical technologies to predict histology and enable the formulation of a real-time in vivo diagnosis, a so-called ‘optical biopsy’. The aim of this review is to explore the evidence for the use of the current commercially available imaging techniques in the gastrointestinal tract. PMID:27429735

  8. Laparoscopic resection of duodenal gastrointestinal stromal tumour

    PubMed Central

    Zioni, Tammy; Dizengof, Vitaliy; Kirshtein, Boris

    2017-01-01

    Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results. PMID:28281485

  9. Human papillomavirus and gastrointestinal cancer: A review

    PubMed Central

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  10. Stages of Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  11. What Is Malignant Mesothelioma?

    MedlinePlus

    ... you learn about the treatment options and possible side effects, and point you to information and services to help you in your cancer journey. ... free PDFs of our malignant mesothelioma information ...

  12. Asbestos-related malignancy

    SciTech Connect

    Antmann, K.; Aisner, J.

    1986-01-01

    This book contains 20 chapters. Some of the chapter titles are: The Radiology of Asbestosis and Related Neoplasms; Computed Tomography and Malignant Mesothelioma; Radiation Therapy for Pleural Mesothelioma; and Radiation Therapy of Peritoneal Mesothelioma.

  13. Targeted therapy of gastrointestinal stromal tumours

    PubMed Central

    Jakhetiya, Ashish; Garg, Pankaj Kumar; Prakash, Gaurav; Sharma, Jyoti; Pandey, Rambha; Pandey, Durgatosh

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs. PMID:27231512

  14. Cytoreductive surgery for peritoneal malignancies--development of standards of care for the community.

    PubMed

    Esquivel, Jesus

    2007-07-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) continue to play an increasing role in the management of peritoneal surface malignancies of gastrointestinal origin. The prognosis of patients and the responses to cytoreductive surgery and HIPEC depend on the histology, the degree of malignant transformation, the adequacy of the cytoreductive surgery, and the response to systemic therapy. Continuous interaction between medical and surgical oncologists is needed to identify the most appropriate patients for and the most efficient sequence of the available therapeutic modalities.

  15. Management of non variceal upper gastrointestinal bleeding: position statement of the Catalan Society of Gastroenterology.

    PubMed

    García-Iglesias, Pilar; Botargues, Josep-Maria; Feu Caballé, Faust; Villanueva Sánchez, Càndid; Calvet Calvo, Xavier; Brullet Benedi, Enric; Cánovas Moreno, Gabriel; Fort Martorell, Esther; Gallach Montero, Marta; Gené Tous, Emili; Hidalgo Rosas, José-Manuel; Lago Macía, Amelia; Nieto Rodríguez, Ana; Papo Berger, Michel; Planella de Rubinat, Montserrat; Saló Rich, Joan; Campo Fernández de Los Ríos, Rafel

    2017-01-18

    In recent years there have been advances in the management of non-variceal upper gastrointestinal bleeding that have helped reduce rebleeding and mortality. This document positioning of the Catalan Society of Digestologia is an update of evidence-based recommendations on management of gastrointestinal bleeding peptic ulcer.

  16. Plague Masquerading as Gastrointestinal Illness

    PubMed Central

    Hull, Harry F.; Montes, Jean M.; Mann, Jonathan M.

    1986-01-01

    In clinical descriptions of human plague, fever and tender lymphadenitis are emphasized and gastrointestinal manifestations are rarely mentioned. A review of 71 human plague cases showed that gastrointestinal symptoms occurred commonly (57%). Vomiting (39%) was the most frequent symptom, with nausea (34%), diarrhea (28%) and abdominal pain (17%) occurring less often. Physicians treating patients who reside in or have recently visited plague-endemic areas should include plague in the differential diagnosis in the presence of gastrointestinal symptoms and fever. PMID:3788132

  17. Malignant colo-duodenal fistula; case report and review of the literature

    PubMed Central

    Soulsby, Ruth; Leung, Edmund; Williams, Nigel

    2006-01-01

    Background Colo-duodenal fistula is a rare complication of malignant and inflammatory bowel disease. Cases with malignant colo-duodenal fistulae can present with symptoms from the primary, from the fistula or from metastatic disease. The fistula often results in diarrhoea and vomiting with dramatic weight loss. Upper abdominal pain is usually present as is general malaise both from the presence of the disease and from the metabolic sequelae it causes. The diarrhoea relates to colonic bacterial contamination of the upper intestines rather than to a pure mechanical effect. Vomiting may be faeculant or truly faecal and eructation foul smelling but in the case reports this 'classic' symptomatology was often absent despite a fistula being present and patent enough to allow barium through it. Occasionally patients will present with a gastro-intestinal bleed. Case presentation We present an unusual case of colorectal carcinoma, where a 65 year old male patient presented with diarrhoea and vomiting secondary to a malignant colo-duodenal fistula near the hepatic flexure. Adenocarcinoma was confirmed on histology from a biopsy obtained during the patient's oesophageogastroduodenoscopy, and the fistula was demonstrated in his barium enema. Staging computed tomography showed a locally advanced carcinoma of the proximal transverse colon, with a fistula to the duodenum and regional lymphadenopathy. The patient was also found to have subcutaneous metastasis. Following discussions at the multidisciplinary meeting, this patient was referred for palliation, and died within 4 months after discharge from hospital. Conclusion We present the case, discuss the management and review the literature. Colo-duodenal fistulae from colonic primaries are rare but early diagnosis may allow curative surgery. This case emphasises the importance of accurate staging and repeated clinical examination. PMID:17147825

  18. Regorafenib: Antitumor Activity upon Mono and Combination Therapy in Preclinical Pediatric Malignancy Models

    PubMed Central

    Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Lanvers-Kaminsky, Claudia; Bawa, Olivia; Opolon, Paule; Vievard, Albane; Villa, Irène; Pagès, Mélanie; Bosq, Jacques; Vassal, Gilles; Zopf, Dieter; Geoerger, Birgit

    2015-01-01

    The multikinase inhibitor regorafenib (BAY 73–4506) exerts both anti-angiogenic and anti-tumorigenic activity in adult solid malignancies mainly advanced colorectal cancer and gastrointestinal stromal tumors. We intended to explore preclinically the potential of regorafenib against solid pediatric malignancies alone and in combination with anticancer agents to guide the pediatric development plan. In vitro effects on cell proliferation were screened against 33 solid tumor cell lines of the Innovative Therapies for Children with Cancer (ITCC) panel covering five pediatric solid malignancies. Regorafenib inhibited cell proliferation with a mean half maximal growth inhibition of 12.5 μmol/L (range 0.7 μmol/L to 28 μmol/L). In vivo, regorafenib was evaluated alone at 10 or 30 mg/kg/d or in combination with radiation, irinotecan or the mitogen-activated protein kinase kinase (MEK) inhibitor refametinib against various tumor types, including patient-derived brain tumor models with an amplified platelet-derived growth factor receptor A (PDGFRA) gene. Regorafenib alone significantly inhibited tumor growth in all xenografts derived from nervous system and connective tissue tumors. Enhanced effects were observed when regorafenib was combined with irradiation and irinotecan against PDGFRA amplified IGRG93 glioma and IGRM57 medulloblastoma respectively, resulting in 100% tumor regressions. Antitumor activity was associated with decreased tumor vascularization, inhibition of PDGFR signaling, and induction of apoptotic cell death. Our work demonstrates that regorafenib exhibits significant antitumor activity in a wide spectrum of preclinical pediatric models through inhibition of angiogenesis and induction of apoptosis. Furthermore, radio- and chemosensitizing effects were observed with DNA damaging agents in PDGFR amplified tumors. PMID:26599335

  19. The location of obstruction predicts stent occlusion in malignant gastric outlet obstruction

    PubMed Central

    Grunwald, Douglas; Cohen, Jonah; Bartley, Anthony; Sheridan, Jennifer; Chuttani, Ram; Sawhney, Mandeep S.; Pleskow, Douglas K.; Berzin, Tyler M.; Mizrahi, Meir

    2016-01-01

    Background: Gastric outlet obstruction (GOO) can occur with locally invasive or metastatic cancer involving the upper gastrointestinal tract at the pylorus or the duodenum. Endoscopic management with self-expanding metal stents (SEMSs) is often the preferred palliative approach. Stent occlusion is a common reason for failure and reintervention. We set out to determine whether the location of the malignant obstruction is associated with the angulation of the stent and can predict stent occlusion. Methods: We performed a retrospective review of consecutive patients who underwent successful duodenal stenting with SEMS for malignant GOO between 2006 and 2015 at a large advanced endoscopy referral center. We determined the location of obstruction, the stent angle, and the rate of technical and clinical success of stent placement. We then identified cases of subsequent stent occlusion confirmed by endoscopic evaluation. Results: A total of 100 consecutive patients were included in the study; 91 of these patients had enough data to evaluate SEMS occlusion. A total of 21 patients (23%) developed stent occlusion with a median time of 39 days. The risk of occlusion sequentially increased as the obstruction occurred more distally from the antrum to the third or fourth portion of the duodenum (p = 0.006). This relationship was maintained after controlling for stent angle (p = 0.05). Conclusions: A distal location of malignant GOO was strongly predictive of stent occlusion, independent of stent angle. This may be due to longer and more complex distal obstructions, along with foreshortening of the stent during placement and tumor infiltration. If replicated, these results will have implications for endoscopic practice and future device development. PMID:27803736

  20. Hereditary gastrointestinal cancer syndromes.

    PubMed

    Lynch, Henry T; Lynch, Jane F; Shaw, Trudy G

    2011-07-01

    The rapid growth of molecular genetics and its attendant germline mutation discoveries has enabled identification of persons who are at an inordinately high cancer risk and, therefore, ideal candidates for prevention. However, one must fully appreciate the extensive genotypic and phenotypic heterogeneity that exists in hereditary cancer. Once the causative germline mutation has been identified in a patient, high-risk members of the family can be similarly tested and identified and provided highly targeted surveillance and management opportunities. DNA testing can change the individual's presumed risk status and affect decision making by patients and their physicians regarding surveillance and management. Our purpose is to describe familial/hereditary cancers of the gastrointestinal tract, including familial Barrett's esophagus, hereditary diffuse gastric cancer, gastrointestinal stromal tumors, familial adenomatous polyposis and desmoid tumors, Lynch syndrome, small bowel cancer, and familial pancreatic cancer. We use our discussion of Lynch syndrome as a model for diagnostic and clinical translation strategies for all hereditary gastrointestinal tract cancers, which clearly can then be extended to cancer of all anatomic sites. Highly pertinent questions from the patient's perspective include the following: What kind of counseling will be provided to a patient with a Lynch syndrome mutation, and should that counseling be mandatory? Does the proband have the responsibility to inform relatives about the familial mutation, even if the relatives do not want to know whether they carry it? Is the patient is responsible for notifying family members that a parent or sibling has Lynch syndrome? Can notification be forced and, if so, under what circumstances? These questions point out the need for criteria regarding which family members to inform and how to inform them.

  1. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  2. Imatinib treatment for gastrointestinal stromal tumour (GIST).

    PubMed

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.

  3. Imatinib treatment for gastrointestinal stromal tumour (GIST)

    PubMed Central

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Abstract Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. PMID:19968734

  4. Molecular Testing for Gastrointestinal Cancer

    PubMed Central

    Lee, Hye Seung; Kim, Woo Ho; Kwak, Yoonjin; Koh, Jiwon; Bae, Jeong Mo; Kim, Kyoung-Mee; Chang, Mee Soo; Han, Hye Seung; Kim, Joon Mee; Kim, Hwal Woong; Chang, Hee Kyung; Choi, Young Hee; Park, Ji Y.; Gu, Mi Jin; Lhee, Min Jin; Kim, Jung Yeon; Kim, Hee Sung; Cho, Mee-Yon

    2017-01-01

    With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians. PMID:28219002

  5. Gastrointestinal Factors in Autistic Disorder: A Critical Review

    ERIC Educational Resources Information Center

    Erickson, Craig A.; Stigler, Kimberly A.; Corkins, Mark R.; Posey, David J.; Fitzgerald, Joseph F.; McDougle, Christopher J.

    2005-01-01

    Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it…

  6. Gastrointestinal Headache; a Narrative Review

    PubMed Central

    T Noghani, Majid; Rezaeizadeh, Hossein; Fazljoo, Sayed Mohammad Baqer; Keshavarz, Mansoor

    2016-01-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disorders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder. PMID:27800536

  7. Gastrointestinal Headache; a Narrative Review.

    PubMed

    T Noghani, Majid; Rezaeizadeh, Hossein; Fazljoo, Sayed Mohammad Baqer; Keshavarz, Mansoor

    2016-11-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disorders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder.

  8. Malignant Vestibular Schwannoma

    PubMed Central

    Gruber, B.; Petchenik, L.; Williams, M.; Thomas, C.; Luken, M.G.

    1994-01-01

    A 61-year-old woman underwent a translabyrinthine resection of a right intracanulicular acoustic neuroma, which had been detected in the work-up of sudden hearing loss. At the time of surgery, the tumor was roughly twice as large as indicated by the magnetic resonance scan taken only 2 months previously. The tumor eroded the vertical and transverse crests and extended well into the cerebellopontine angle. It was impossible to distinguish the facial nerve proximal to the geniculate ganglion. All visible tumor was resected, along with the facial nerve. Histological evaluation showed a highly cellular tumor, with many mitoses and areas of necrosis, meeting the criteria for malignant schwannoma. The patient has no stigmata of neurofibromatosis, and has no known relatives with that condition. This case is only the fourth reported of a malignant vestibular schwannoma. The relationships between vestibular schwannoma, neurofibromatosis, and malignancy are discussed. ImagesFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:17171176

  9. Sentinel nodes of malignancies originating in the alimentary tract.

    PubMed

    Fujii, Hirofumi; Kitagawa, Yuko; Kitajima, Masaki; Kubo, Atsushi

    2004-02-01

    The feasibility of the sentinel node concept for malignancies originating in the alimentary tract is attracting much interest among researchers in the field of gastrointestinal oncology. We have tested more than 350 such cases and obtained favorable and promising initial results. The detectability of sentinel nodes using endoscopically injected Tc-99m tin colloid for these tumors exceeded 90%. Although the false negative ratio was not so low (approximately 10%), most of these cases had an inaccurate preoperative evaluation of mural invasion and/or a technically unfavorable injection. When the indication is restricted to patients with early-stage disease, and when the radioactive colloid is properly administered, sentinel node navigation therapy would be applicable for gastrointestinal malignancies. To achieve successful sentinel node navigation surgery it is essential to accurately identify sentinel nodes, and lymphoscintigraphy is a very useful test to confirm the location of sentinel nodes preoperatively. However, image processing is required for lymphoscintigrams because the original image depicts only high activity at the injection site and faint radioactivity in the sentinel nodes. We have clearly imaged the silhouette of the body using Compton scattered photons, and have also proposed several methods to improve the contrast between the injection sites and sentinel nodes. Many sentinel nodes can be clearly visualized by subtraction of the background activity with heterogeneous distribution. The development of the portable gamma camera, enabling intraoperative imaging, also contributes to less invasive biopsy of sentinel nodes. We have obtained promising initial results using a portable imaging device with semiconductor detectors. These promising results suggest that sentinel node navigation therapy including radiotherapy will be a new therapy for early-stage gastrointestinal malignancies in the near future, with nuclear medicine contributing to the

  10. Giant malignant insulinoma

    PubMed Central

    Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis

    2015-01-01

    Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993

  11. Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

    PubMed

    Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

    2013-01-01

    Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

  12. Functional MR Imaging in Chest Malignancies.

    PubMed

    Broncano, Jordi; Luna, Antonio; Sánchez-González, Javier; Alvarez-Kindelan, Antonio; Bhalla, Sanjeev

    2016-02-01

    With recent advances in MR imaging, its application in the thorax has been feasible. The performance of both morphologic and functional techniques in the evaluation of thoracic malignances has improved not only differentiation from benign etiologies but also treatment monitoring based on a multiparametric approach. Several MR imaging-derived parameters have been described as potential biomarkers linked with prognosis and survival. Therefore, an integral approach with a nonradiating and noninvasive technique could be an optimal alternative for evaluating those patients.

  13. Hereditary gastrointestinal cancer.

    PubMed

    Hata, Keisuke; Yamamoto, Yoko; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kishikawa, Junko; Nagai, Yuzo; Anzai, Hiroyuki; Shinagawa, Takahide; Arakawa, Keiichi; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2016-10-01

    Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.

  14. [Gastrointestinal dysmotility in children].

    PubMed

    Fluge, G; Olafsdottir, E

    2001-03-20

    Motility disorders were previously impossible to penetrate, but new technics have made it possible to investigate these disorders. An overview of neurophysiological functions of the gastrointestinal tract is given, and various conditions representing primary and secondary motility disorders are discussed. Diagnostic procedures and treatment options are presented. The clinical picture of such disorders is demonstrated by two cases. A girl born in 1995, having megacystis microcolon hypoperistalsis syndrome was the first Norwegian individual to have an intestinal transplantation, which was performed in London, UK. A girl with hypoganglionosis is also reported. Since May 1998, manometry of the oesophagus was performed in 44 children, and pathological findings were demonstrated in 18 of these patients. The motoric activity of the stomach was investigated in 17 patients using two-dimensional ultrasound and electrogastrography pre- and post-prandially. Disturbed function was found in nine of these children. Anorectal manometry was performed in 147 individuals, and Hirschsprung's disease was diagnosed in four.

  15. Gastrointestinal infections in children.

    PubMed

    Mönkemüller, K E; Wilcox, C M

    2001-01-01

    Gastrointestinal infections in children are a major cause of morbidity and mortality worldwide. Children living in developing countries are particularly susceptible to infectious diarrhea because of poor standards of hygiene and sanitation. Although the magnitude of diarrheal illnesses in developed countries is less, costly hospital admissions are still frequent. The causal agent of infectious diarrhea is most frequently related to age, geographical location, lifestyle habits, use of antibiotics, associated medical conditions, social circumstances, and degree of immune competence. In this article we present some of the most important articles published in the field during the last year. The role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer disease has been shown in adults and children. Information about the natural history of H. pylori, symptomatology, and diagnostic therapeutic approaches for children are being generated constantly; we discuss some of the most relevant information in this review.

  16. Disorders of gastrointestinal hypomotility

    PubMed Central

    Bielefeldt, Klaus; Tuteja, Ashok; Nusrat, Salman

    2016-01-01

    Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases. PMID:27583135

  17. Molecular diagnostics in soft tissue sarcomas and gastrointestinal stromal tumors.

    PubMed

    Smith, Stephen M; Coleman, Joshua; Bridge, Julia A; Iwenofu, O Hans

    2015-04-01

    Soft tissue sarcomas are rare malignant heterogenous tumors of mesenchymal origin with over fifty subtypes. The use of hematoxylin and eosin stained sections (and immunohistochemistry) in the morphologic assessment of these tumors has been the bane of clinical diagnosis until recently. The last decade has witnessed considerable progress in the understanding and application of molecular techniques in refining the current understanding of soft tissue sarcomas and gastrointestinal stromal tumors beyond the limits of traditional approaches. Indeed, the identification of reciprocal chromosomal translocations and fusion genes in some subsets of sarcomas with potential implications in the pathogenesis, diagnosis and treatment has been revolutionary. The era of molecular targeted therapy presents a platform that continues to drive biomarker discovery and personalized medicine in soft tissue sarcomas and gastrointestinal stromal tumors. In this review, we highlight how the different molecular techniques have enhanced the diagnosis of these tumors with prognostic and therapeutic implications.

  18. Gastrointestinal leiomyosarcoma in a pygmy sperm whale (Kogia breviceps).

    PubMed

    Leone, Angelique; Dark, Michael; Kondo, Hirotaka; Rotstein, David S; Kiupel, Matti; Walsh, Michael T; Erlacher-Reid, Claire; Gordon, Nadia; Conway, Julia A

    2013-09-01

    An adult male pygmy sperm whale (Kogia breviceps) was stranded within a tidal pool on Fernandina Beach on the north Florida Atlantic coast (USA) and expired soon after discovery. Necropsy findings included a small intestinal mass markedly expanding the intestinal wall and partially obstructing the lumen. This finding likely led to the malnutrition and ultimately the stranding of this whale. The differential diagnoses for the mass based on gross evaluation included a duodenal adenocarcinoma, leiomyoma/sarcoma, gastrointestinal stroma tumor, and benign/malignant peripheral nerve sheath tumor, previously referred to as neurofibromas or schwannomas. The mass was presumptively diagnosed as a leiomyosarcoma via routine histopathology and confirmed by immunoreactivity for desmin and smooth actin (SMA). KIT, a gene name for CD 117, was negative, excluding a gastrointestinal stromal tumor (GIST). Leiomyosarcomas have been reported within numerous wild and domestic species, although this is the first reported case of any neoplasm in a pygmy sperm whale (K. breviceps).

  19. Malignant tumors of childhood

    SciTech Connect

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

  20. Early malignant syphilis*

    PubMed Central

    Ortigosa, Yara Martins; Bendazzoli, Paulo Salomão; Barbosa, Angela Marques; Ortigosa, Luciena Cegatto Martins

    2016-01-01

    Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment. PMID:28300925

  1. [Gastrointestinal stromal tumors: case reports and review of the literature].

    PubMed

    Bronzino, P; Colombini, M; Ferro, A; Gambetta, G; Gennaro, M; Ivaldi, L; Revetria, P

    2008-01-01

    The Authors describe four cases of gastrointestinal stromal tumours (GIST) two of them were localized in the stomach, the others in the ileum. GIST are neoplasms of mesenchymal origin which develop inside the wall of the digestive tract. The most frequent site is the stomach, followed by the small bowel; less commonly these tumors can affect the oesophagus, the colon and the rectum. GIST originate from precursors of the interstitial cells of Cajal, which are localized in the gastro-intestinal wall and are involved in the regulation of the peristalsis. The treatment is surgical resection. For advanced disease there is a new interesting treatment based on the imatinib, a tyrosine kinase inhibitor.

  2. Nutritional Aspects of Gastrointestinal Wound Healing

    PubMed Central

    Mukherjee, Kaushik; Kavalukas, Sandra L.; Barbul, Adrian

    2016-01-01

    Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with pro- and antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures. PMID:27867755

  3. Study of the fluorescence signal for gastrointestinal dysplasia detection

    NASA Astrophysics Data System (ADS)

    Pimenta, S.; Castanheira, E. M. S.; Minas, G.

    2014-08-01

    The detection of cancer at the dysplasia stage is one of the most important goals in biomedical research. Optical techniques, specifically diffuse reflectance and intrinsic fluorescence, may improve the ability to detect gastrointestinal (GI) cancers, since they have exquisite sensitivity to some intrinsic biomarkers present on the tissues. This work follows the research that has been done towards the implementation of a spectroscopy microsystem for the early detection of GI cancers. For that purpose, the behavior of the fluorescence signal, at different temperatures and considering the most important biomarkers in GI malignancy detection, was studied and presented.

  4. Photodynamic Therapy Using Endogenous Photosensitization for Gastrointestinal Tumors

    PubMed Central

    Webber, John; Kessel, David; Fromm, David

    1997-01-01

    Photodynamic therapy (PDT) is a novel approach in the treatment of carcinomas of the gastrointestinal tract. This review defines PDT, discusses means of photosensitization and considers the mechanisms by which PDT causes cell death of the target tissue while at the same time avoid damage to normal tissues. Additional considerations include the time of PDT application, activation of the photosensitizer, effectiveness and toxicity of PDT, potential need for additional modalities of treatment and concludes with application of PDT principals to the early detection of malignancy. Data regarding the long term effectiveness of PDT for digestive tract adenocarcinomas are lacking because this field is still in its infancy.

  5. Heterotopic Pancreatic Pseudocyst Radiologically Mimicking Gastrointestinal Stromal Tumor

    PubMed Central

    Sarsenov, Dauren; Tırnaksız, Mehmet Bülent; Doğrul, Ahmet Bülent; Tanas, Özlem; Gedikoglu, Gökhan; Abbasoğlu, Osman

    2015-01-01

    Heterotopic pancreas is a relatively common variant of foregut embryologic dystopia that can be described as pancreatic tissue found outside the normal anatomic location, being independent from vascular supply of normal pancreas. Having all features of pancreatic tissue except for the major duct structures, this ectopic tissue may be clinically recognized when pathologic changes take place. Inflammation, hemorrhagic or obstructive states, and eventually malignancy-related problems may become a diagnostic challenge for clinician and finally lead to consequences of misdiagnosis. In this article we will discuss a case of heterotopic pancreatic tissue located in gastric cardia, which was diagnosed preoperatively as gastrointestinal stromal tumor. PMID:25785332

  6. What Are the Key Statistics about Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... About Gastrointestinal Carcinoid Tumors What Are the Key Statistics About Gastrointestinal Carcinoid Tumors? Although the exact number ... a Gastrointestinal Carcinoid Tumor? What Are the Key Statistics About Gastrointestinal Carcinoid Tumors? What’s New in Gastrointestinal ...

  7. Autistic disorder and gastrointestinal disease.

    PubMed

    Horvath, Karoly; Perman, Jay A

    2002-10-01

    Autistic disorder is a pervasive developmental disorder manifested in the first 3 years of life by dysfunction in social interaction and communication. Many efforts have been made to explore the biologic basis of this disorder, but the etiology remains unknown. Recent publications describing upper gastrointestinal abnormalities and ileocolitis have focused attention on gastrointestinal function and morphology in these children. High prevalence of histologic abnormalities in the esophagus, stomach, small intestine and colon, and dysfunction of liver conjugation capacity and intestinal permeability were reported. Three surveys conducted in the United States described high prevalence of gastrointestinal symptoms in children with autistic disorder. Treatment of the digestive problems may have positive effects on their behavior.

  8. Gastrointestinal stromal tumor in an XYY/XY male.

    PubMed

    Limacher, Jean-Marc; Girard-Lemaire, Françoise; Jeandidier, Eric; Chenard-Neu, Marie-Pierre; Kassem, Maysoun; Flori, Elisabeth; Bergerat, Jean-Pierre

    2002-03-01

    A 32-year-old patient was diagnosed with a gastrointestinal stromal tumor of the small bowel. The pathologic diagnosis was confirmed by positive immunochemistry against CD34, and against CD117, the tyrosine-kinase c-kit. We performed a karyotypic analysis on the basis of the patient's tall stature and speech difficulties. One hundred thirty-two metaphases were obtained on PHA-stimulated peripheral blood; 123 of them presented an extra chromosome Y. Fluorescence in situ hybridization using a Y satellite III probe showed the presence of a sole copy of chromosome Y in the tumor cells precluding a direct relationship between the extra chromosome Y and the initiation of the tumor. This is, to our knowledge, the second occurrence of a nonhematologic malignancy reported in this genetic disorder. A review of the malignancies observed in men with the XYY constitution is presented.

  9. [Functional and motor gastrointestinal disorders].

    PubMed

    Mearin, Fermín; Perelló, Antonia; Balboa, Agustín

    2008-10-01

    Functional gastrointestinal (GI) and motility disorders generate a large volume of consultations in gastroenterology and primary care offices. The present article summarizes the most interesting studies presented in the annual meeting of the American Gastroenterological Association 2008. For all functional GI disorders, studies were presented that evaluated the applicability of diagnostic criteria in clinical practice and new data were presented on physiopathology (for example, mediation by neuromodulators such as serotonin, microinflammation, alterations in intestinal microbiota, and psychological factors). More specifically, the therapeutic results of new prokinetic agents in functional dyspepsia, such as acotiamide, were presented. This agent has been demonstrated to have good efficacy in symptom control, especially in patients with postprandial distress syndrome. In irritable bowel syndrome, data were presented on several drugs that act through diverse mechanisms of action and have been shown to be more effective than placebo in symptom control. These drugs include antiinflammatory agents such as mesalazine, antibiotics such as rifaximin, probiotics with distinct bacterial strains, and prokinetic agents such as lubiprostone. Highly promising results have been obtained in the treatment of constipation with prokinetics such as prucalopride and with novel laxatives such as linaclotide, as well as with techniques that continue to be shown to be effective such as anorectal biofeedback, which is also highly useful in patients with fecal incontinence. Another disorder that is less frequent but highly difficult to treat is gastroparesis. For several years, treatment in the most severe cases has consisted of implantation of a gastric pacemaker. Although the results are far from perfect, new data were presented that allow better patient selection to achieve greater symptom control. The list of new advances, both in knowledge of the physiopathology of these disorders and

  10. [Functional and motility gastrointestinal disorders].

    PubMed

    Mearin, Fermín; Rey, Enrique; Balboa, Agustín

    2011-10-01

    As in previous years, a huge number of studies were presented at the Congress of the American Gastroenterology Association (Digestive Diseases Week [DDW]), some of which were better than others. The present article attempts to extract and summarize the most interesting findings reported. In general terms, certain technological advances have been consolidated, with full incorporation into clinical practice, such as impedancemetry and high-resolution manometry. New physiopathological data are coming to light that increasingly indicate the inextricable link between organic and psychological factors (the biopsychosocial model) in functional gastrointestinal disorders (FGID). Despite the high hopes that the Rome III criteria would improve the diagnosis of FGID and especially that of functional dyspepsia, their practical application has been fairly discouraging. Moreover, at least two studies have demonstrated that these criteria cannot be used to differentiate subtypes of functional dyspepsia and that there is wide overlap with gastroesophageal reflux disease. New data were presented on the role of genetic, microinflammatory and psychological factors in the etiopathogenesis of the two main FGID: functional dyspepsia and irritable bowel syndrome (IBS). The results on the safety and efficacy of acotiamide in functional dyspepsia and of linaclotide and prucalopride in idiopathic and IBS-associated constipation were also presented. Several studies, and even meta-analyses, have demonstrated the utility of biofeedback in the treatment of constipation. Even so, the efficacy of this therapy has been questioned due to certain methodological deficiencies in some studies. In DDW 2011, studies confirming the utility of biofeedback, whether hospital- or home-based were presented, in dyssynergy constipation. The present article also mentions certain features of special interest in the diagnosis and treatment of rumination syndrome, thoracic pain of possible esophageal origin and

  11. Optical imaging of breast tumors and of gastrointestinal cancer by laser-induced fluorescence.

    PubMed

    Ebert, Bernd; Grosenick, Dirk

    2013-01-01

    Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.

  12. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer.

    PubMed

    Santhanam, Srikanth; Alvarado, David M; Ciorba, Matthew A

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant adverse effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapy is a promising new approach to harness the body's own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway (KP) is a particularly promising target for immunotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and KP metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth, and luminal microbiota. This pathway's role in other gastrointestinal (GI) malignancies such as gastric, pancreatic, esophageal, and GI stromal tumors is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal, and colitis-associated cancer.

  13. Beyond Standard Therapy: Drugs Under Investigation for The Treatment of Gastrointestinal Stromal Tumor

    PubMed Central

    Alturkmani, Hani J; Pessetto, Ziyan Y; Godwin, Andrew K

    2015-01-01

    Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival. PMID:26098203

  14. Hedgehog signaling and gastrointestinal cancer

    PubMed Central

    Saqui-Salces, Milena; Merchant, Juanita L.

    2017-01-01

    Hedgehog (Hh) signaling is critical for embryonic development and in differentiation, proliferation, and maintenance of multiple adult tissues. De-regulation of the Hh pathway is associated with birth defects and cancer. In the gastrointestinal tract, Hh ligands Sonic (Shh) and Indian (Ihh), as well as the receptor Patched (Ptch1), and transcription factors of Glioblastoma family (Gli) are all expressed during development. In the adult, Shh expression is restricted to the stomach and colon, while Ihh expression occurs throughout the luminal gastrointestinal tract, its expression being highest in the proximal duodenum. Several studies have demonstrated a requirement for Hh signaling during gastrointestinal tract development. However to date, the specific role of the Hh pathway in the adult stomach and intestine is not completely understood. The current review will place into context the implications of recent published data related to the biochemistry and cell biology of Hh signaling on the luminal gastrointestinal tract during development, normal physiology and subsequently carcinogenesis. PMID:20307590

  15. Epigenetic mechanisms and gastrointestinal development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review considers the hypothesis that nutrition during infancy affects developmental epigenetics in the gut, causing metabolic imprinting of gastrointestinal (GI) structure and function. Fundamentals of epigenetic gene regulation are reviewed, with an emphasis on the epigenetic mechanism of DNA ...

  16. The Gastrointestinal Microbiome

    PubMed Central

    Engen, Phillip A.; Green, Stefan J.; Voigt, Robin M.; Forsyth, Christopher B.; Keshavarzian, Ali

    2015-01-01

    The excessive use of alcohol is a global problem causing many adverse pathological health effects and a significant financial health care burden. This review addresses the effect of alcohol consumption on the microbiota in the gastrointestinal tract (GIT). Although data are limited in humans, studies highlight the importance of changes in the intestinal microbiota in alcohol-related disorders. Alcohol-induced changes in the GIT microbiota composition and metabolic function may contribute to the well-established link between alcohol-induced oxidative stress, intestinal hyperpermeability to luminal bacterial products, and the subsequent development of alcoholic liver disease (ALD), as well as other diseases. In addition, clinical and preclinical data suggest that alcohol-related disorders are associated with quantitative and qualitative dysbiotic changes in the intestinal microbiota and may be associated with increased GIT inflammation, intestinal hyperpermeability resulting in endotoxemia, systemic inflammation, and tissue damage/organ pathologies including ALD. Thus, gut-directed interventions, such as probiotic and synbiotic modulation of the intestinal microbiota, should be considered and evaluated for prevention and treatment of alcohol-associated pathologies. PMID:26695747

  17. Managing malignant pericardial effusion.

    PubMed Central

    Buzaid, A C; Garewal, H S; Greenberg, B R

    1989-01-01

    The involvement of the pericardium by metastatic tumors is not uncommon, particularly in patients with lung cancer, breast cancer, lymphomas, leukemias, and melanomas. There are five therapeutic modalities for the treatment of malignant pericardial effusion, including pericardiocentesis, pericardial sclerosis, systemic chemotherapy, radiotherapy, and surgical treatment. The optimal treatment selection is dependent principally on a patient's life expectancy; responsiveness of the tumor to chemotherapy, irradiation, or both; and whether or not cardiac tamponade is present at diagnosis. The overall prognosis of patients with malignant pericardial effusion is primarily influenced by the extent and histologic features of the underlying cancer. Although this condition is usually incurable, a reasonable period of useful palliation can be obtained in most patients. Images PMID:2471362

  18. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. )

    1992-01-01

    The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

  19. Managing Malignant Cerebral Infarction

    PubMed Central

    Sahuquillo, Juan; Sheth, Kevin N.; Kahle, Kristopher T.; Walcott, Brian P.

    2011-01-01

    Opinion statement Managing patients with malignant cerebral infarction remains one of the foremost challenges in medicine. These patients are at high risk for progressive neurologic deterioration and death due to malignant cerebral edema, and they are best cared for in the intensive care unit of a comprehensive stroke center. Careful initial assessment of neurologic function and of findings on MRI, coupled with frequent reassessment of clinical and radiologic findings using CT or MRI are mandatory to promote the prompt initiation of treatments that will ensure the best outcome in these patients. Significant deterioration in either neurologic function or radiologic findings or both demand timely treatment using the best medical management, which may include osmotherapy (mannitol or hypertonic saline), endotracheal intubation, and mechanical ventilation. Under appropriate circumstances, decompressive craniectomy may be warranted to improve outcome or to prevent death. PMID:21190097

  20. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  1. Asbestos-related malignancy

    SciTech Connect

    Talcott, J.A.; Antman, K.H.

    1988-05-01

    Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. 179 references.

  2. Malignant Catatonia Mimicking Pheochromocytoma

    PubMed Central

    Li, Dailin

    2013-01-01

    Malignant catatonia is an unusual and highly fatal neuropsychiatric condition which can present with clinical and biochemical manifestations similar to those of pheochromocytoma. Differentiating between the two diseases is essential as management options greatly diverge. We describe a case of malignant catatonia in a 20-year-old male who presented with concurrent psychotic symptoms and autonomic instability, with markedly increased 24-hour urinary levels of norepinephrine at 1752 nmol/day (normal, 89–470 nmol/day), epinephrine at 1045 nmol/day (normal, <160 nmol/day), and dopamine at 7.9 μmol/day (normal, 0.4–3.3 μmol/day). The patient was treated with multiple sessions of electroconvulsive therapy, which led to complete clinical resolution. Repeat urine collections within weeks of this presenting event revealed normalization or near normalization of his catecholamine and metanephrine levels. Malignant catatonia should be considered in the differential diagnosis of the hypercatecholamine state, particularly in a patient who also exhibits concurrent catatonic features. PMID:24251048

  3. Pembrolizumab in Treating Patients With Malignant Mesothelioma

    ClinicalTrials.gov

    2016-11-14

    Biphasic Mesothelioma; Epithelioid Mesothelioma; Peritoneal Malignant Mesothelioma; Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma; Pleural Sarcomatoid Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Sarcomatoid Mesothelioma

  4. Epigenetics in the hematologic malignancies

    PubMed Central

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. PMID:25472952

  5. The first 1000 cultured species of the human gastrointestinal microbiota

    PubMed Central

    Rajilić-Stojanović, Mirjana; de Vos, Willem M

    2014-01-01

    The microorganisms that inhabit the human gastrointestinal tract comprise a complex ecosystem with functions that significantly contribute to our systemic metabolism and have an impact on health and disease. In line with its importance, the human gastrointestinal microbiota has been extensively studied. Despite the fact that a significant part of the intestinal microorganisms has not yet been cultured, presently over 1000 different microbial species that can reside in the human gastrointestinal tract have been identified. This review provides a systematic overview and detailed references of the total of 1057 intestinal species of Eukarya (92), Archaea (8) and Bacteria (957), based on the phylogenetic framework of their small subunit ribosomal RNA gene sequences. Moreover, it unifies knowledge about the prevalence, abundance, stability, physiology, genetics and the association with human health of these gastrointestinal microorganisms, which is currently scattered over a vast amount of literature published in the last 150 years. This detailed physiological and genetic information is expected to be instrumental in advancing our knowledge of the gastrointestinal microbiota. Moreover, it opens avenues for future comparative and functional metagenomic and other high-throughput approaches that need a systematic and physiological basis to have an impact. PMID:24861948

  6. Primary gastrointestinal lymphoma

    PubMed Central

    Aledavood, Amir; Nasiri, Mohammad Reza Ghavam; Memar, Bahram; Shahidsales, Soodabeh; Raziee, Hamid Reza; Ghafarzadegan, Kamran; Mohtashami, Samira

    2012-01-01

    Background: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. Materials and Methods: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. Results: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. Conclusion: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma. PMID:23626617

  7. Gastrointestinal Physiology and Function.

    PubMed

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C; Grundy, David

    2017-02-08

    The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.

  8. Childhood functional gastrointestinal disorders

    PubMed Central

    Rasquin-Weber, A; Hyman, P; Cucchiara, S; Fleisher, D; Hyams, J; Milla, P; Staiano, A

    1999-01-01

    This is the first attempt at defining criteria for functional gastrointestinal disorders (FGIDs) in infancy, childhood, and adolescence. The decision-making process was as for adults and consisted of arriving at consensus, based on clinical experience. This paper is intended to be a quick reference. The classification system selected differs from the one used in the adult population in that it is organized according to main complaints instead of being organ-targeted. Because the child is still developing, some disorders such as toddler's diarrhea (or functional diarrhea) are linked to certain physiologic stages; others may result from behavioral responses to sphincter function acquisition such as fecal retention; others will only be recognizable after the child is cognitively mature enough to report the symptoms (e.g., dyspepsia). Infant regurgitation, rumination, and cyclic vomiting constitute the vomiting disorders. Abdominal pain disorders are classified as: functional dyspepsia, irritable bowel syndrome (IBS), functional abdominal pain, abdominal migraine, and aerophagia. Disorders of defecation include: infant dyschezia, functional constipation, functional fecal retention, and functional non-retentive fecal soiling. Some disorders, such as IBS and dyspepsia and functional abdominal pain, are exact replications of the adult criteria because there are enough data to confirm that they represent specific and similar disorders in pediatrics. Other disorders not included in the pediatric classification, such as functional biliary disorders, do occur in children; however, existing data are insufficient to warrant including them at the present time. For these disorders, it is suggested that, for the time being, clinicians refer to the criteria established for the adult population.


Keywords: infant vomiting; cyclic vomiting syndrome; functional dyspepsia in children; irritable bowel syndrome in children; functional abdominal pain in children; functional

  9. Developments in immunotherapy for gastrointestinal cancer.

    PubMed

    Diaz, J L; Wanta, S M; Fishbein, T M; Kroemer, A

    2015-08-01

    Gastrointestinal (GI) cancers are the most commonly occurring cancer worldwide. Colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. Despite the advent of screening and the declining incidence of CRC overall, most patients are not diagnosed at an early, localized stage. Due to resistance to chemotherapy, recurrence, and metastatic disease, those diagnosed with advanced disease have only a 12% 5-year survival rate. Given the overwhelming global impact of CRC, the need for advanced therapy is crucial. Targeted immunotherapy in addition to surgical resection, traditional chemotherapy, and radiation therapy is on the rise. For the purpose of this review, we focused on the advances of immunotherapy, particularly in CRC, with mention of research pertaining to particular advances in immunotherapy for other aspects of the GI system. We review basic immunology and the microenvironment surrounding colorectal tumors that lead to immune system evasion and poor responses to chemotherapy. We also examined the way these obstacles are proving to be the targets of tumor specific immunotherapy. We will present current FDA approved immunotherapies such as monoclonal antibodies (mAb) targeting tumor specific antigens, as well as vaccines, adoptive cell therapy, cytokines, and check-point inhibitors. A summation of prior research, current clinical trials, and prospective therapies in murine models help delineate our current status and future strategies on CRC immunotherapy.

  10. Gastrointestinal radiation injury: Symptoms, risk factors and mechanisms

    PubMed Central

    Shadad, Abobakr K; Sullivan, Frank J; Martin, Joseph D; Egan, Laurence J

    2013-01-01

    Ionising radiation therapy is a common treatment modality for different types of cancer and its use is expected to increase with advances in screening and early detection of cancer. Radiation injury to the gastrointestinal tract is important factor working against better utility of this important therapeutic modality. Cancer survivors can suffer a wide variety of acute and chronic symptoms following radiotherapy, which significantly reduces their quality of life as well as adding an extra burden to the cost of health care. The accurate diagnosis and treatment of intestinal radiation injury often represents a clinical challenge to practicing physicians in both gastroenterology and oncology. Despite the growing recognition of the problem and some advances in understanding the cellular and molecular mechanisms of radiation injury, relatively little is known about the pathophysiology of gastrointestinal radiation injury or any possible susceptibility factors that could aggravate its severity. The aims of this review are to examine the various clinical manifestations of post-radiation gastrointestinal symptoms, to discuss possible patient and treatment factors implicated in normal gastrointestinal tissue radiosensitivity and to outline different mechanisms of intestinal tissue injury. PMID:23345941

  11. Malignant Pleural Effusion: Medical Approaches for Diagnosis and Management

    PubMed Central

    2014-01-01

    Malignant pleural effusions (MPEs) are the second leading cause of exudative pleural effusions after parapneumonic effusions. In the vast majority of cases, a MPE signifies incurable disease associated with high morbidity and mortality. Considerable advances have been made for the diagnosis of MPEs, through the development of improved methods in the specialized cytological and imaging studies. The cytological or histological confirmation of malignant cells is currently important in establishing a diagnosis. Furthermore, despite major advancements in cancer treatment for the past two decades, management of MPE remains palliative. This article presents a comprehensive review of the medical approaches for diagnosis and management of MPE. PMID:24920947

  12. Malignant pleural effusion: medical approaches for diagnosis and management.

    PubMed

    Nam, Hae-Seong

    2014-05-01

    Malignant pleural effusions (MPEs) are the second leading cause of exudative pleural effusions after parapneumonic effusions. In the vast majority of cases, a MPE signifies incurable disease associated with high morbidity and mortality. Considerable advances have been made for the diagnosis of MPEs, through the development of improved methods in the specialized cytological and imaging studies. The cytological or histological confirmation of malignant cells is currently important in establishing a diagnosis. Furthermore, despite major advancements in cancer treatment for the past two decades, management of MPE remains palliative. This article presents a comprehensive review of the medical approaches for diagnosis and management of MPE.

  13. Hypercalcemia of malignancy and new treatment options

    PubMed Central

    Sternlicht, Hillel; Glezerman, Ilya G

    2015-01-01

    Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP). Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25-dihydroxyvitamin D (calcitriol) and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient’s symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor κB ligand, and the calcimimetic cinacalcet. Finally, anti-PTHrP antibodies have been successfully deployed in animal models of disease. Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory

  14. Report from the 13th annual Western canadian gastrointestinal cancer consensus conference; calgary, alberta; september 8-10, 2011.

    PubMed

    Vickers, M M; Pasieka, J; Dixon, E; McEwan, S; McKay, A; Renouf, D; Schellenberg, D; Ruether, D

    2012-12-01

    The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8-10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer.

  15. Virtual reality simulators for gastrointestinal endoscopy training

    PubMed Central

    Triantafyllou, Konstantinos; Lazaridis, Lazaros Dimitrios; Dimitriadis, George D

    2014-01-01

    The use of simulators as educational tools for medical procedures is spreading rapidly and many efforts have been made for their implementation in gastrointestinal endoscopy training. Endoscopy simulation training has been suggested for ascertaining patient safety while positively influencing the trainees’ learning curve. Virtual simulators are the most promising tool among all available types of simulators. These integrated modalities offer a human-like endoscopy experience by combining virtual images of the gastrointestinal tract and haptic realism with using a customized endoscope. From their first steps in the 1980s until today, research involving virtual endoscopic simulators can be divided in two categories: investigation of the impact of virtual simulator training in acquiring endoscopy skills and measuring competence. Emphasis should also be given to the financial impact of their implementation in endoscopy, including the cost of these state-of-the-art simulators and the potential economic benefits from their usage. Advances in technology will contribute to the upgrade of existing models and the development of new ones; while further research should be carried out to discover new fields of application. PMID:24527175

  16. Gastroesophageal reflux and congenital gastrointestinal malformations

    PubMed Central

    Marseglia, Lucia; Manti, Sara; D’Angelo, Gabriella; Gitto, Eloisa; Salpietro, Carmelo; Centorrino, Antonio; Scalfari, Gianfranco; Santoro, Giuseppe; Impellizzeri, Pietro; Romeo, Carmelo

    2015-01-01

    Although the outcome of newborns with surgical congenital diseases (e.g., diaphragmatic hernia; esophageal atresia; omphalocele; gastroschisis) has improved rapidly with recent advances in perinatal intensive care and surgery, infant survivors often require intensive treatment after birth, have prolonged hospitalizations, and, after discharge, may have long-term sequelae including gastro-intestinal comorbidities, above all, gastroesophageal reflux (GER). This condition involves the involuntary retrograde passage of gastric contents into the esophagus, with or without regurgitation or vomiting. It is a well-recognized condition, typical of infants, with an incidence of 85%, which usually resolves after physiological maturation of the lower esophageal sphincter and lengthening of the intra-abdominal esophagus, in the first few months after birth. Although the exact cause of abnormal esophageal function in congenital defects is not clearly understood, it has been hypothesized that common (increased intra-abdominal pressure after closure of the abdominal defect) and/or specific (e.g., motility disturbance of the upper gastrointestinal tract, damage of esophageal peristaltic pump) pathological mechanisms may play a role in the etiology of GER in patients with birth defects. Improvement of knowledge could positively impact the long-term prognosis of patients with surgical congenital diseases. The present manuscript provides a literature review focused on pathological and clinical characteristics of GER in patients who have undergone surgical treatment for congenital abdominal malformations. PMID:26229394

  17. Dual Roles for Immunity in Gastrointestinal Cancers

    PubMed Central

    Ferrone, Cristina; Dranoff, Glenn

    2010-01-01

    Histopathologic examination reveals that most human tumors are associated with diverse immune cell infiltrates, but the roles of host reactions in disease pathogenesis and prognosis remain to be fully clarified. Recent investigations in genetically engineered murine tumor models have uncovered dual functions for immune responses during cancer development and progression. Alterations in tumor cell gene expression profiles and coding sequences may trigger the activation of cytotoxic lymphocytes, which act to restrain tumor growth. In contrast, persistent inflammatory reactions, which may be driven by infection, environmental toxins, or impaired immune regulation, create a microenvironment that fosters tumor cell growth, survival, invasion, and dissemination. The dynamic interplay of these competing responses appears to be a critical event in cancer pathogenesis, with tumor promotion and immune evasion proving dominant in clinically evident disease. Nonetheless, longitudinal studies of patient cohorts have demonstrated that particular histopathologic and genetic signatures of cytotoxic lymphocyte reactions provide important prognostic information. Here, we discuss the dual roles of immunity in cancer development, focusing on gastrointestinal malignancies, given the depth of recent insights into the mechanisms underlying these tumors. PMID:20644090

  18. Role of vitamins in gastrointestinal diseases

    PubMed Central

    Masri, Omar A; Chalhoub, Jean M; Sharara, Ala I

    2015-01-01

    A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available. PMID:25954093

  19. Giant gastrointestinal stromal tumor of the stomach.

    PubMed

    Ionescu, Sever; Barbu, Emil; Ionescu, Călin; Costache, Adrian; Bălăşoiu, Maria

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the digestive tract. Gastric localization is the most frequent. The aim of this study is to evaluate the importance of immunohistochemical factors (CD117, CD34, α-SMA, vimentin, p53, Ki67) in diagnostic and size tumor and mitotic activity as prognostic factors for these tumors. We present the case of a 66-year-old male patient with a giant gastric GIST. Like in the vast majority, the symptomatology in this patient has long been faint, despite the large tumor size, and when it became manifest, it was nonspecific. Imagery wise, the computer tomography (CT) scan was the most efficient, showing the origin of the tumor from the greater curvature of the stomach, its dimensions, as well as the relations with the other abdominal viscera. Surgery in this patient was en-bloc, according to the principles of GIST. The histological aspect is characterized by a proliferation of spindle cells positive for CD117 and CD34. Despite complete microscopic resection, the size of the tumor (25×20×27 cm) and the mitotic activity (21÷5 mm2) remains important relapse factor.

  20. Role of vitamins in gastrointestinal diseases.

    PubMed

    Masri, Omar A; Chalhoub, Jean M; Sharara, Ala I

    2015-05-07

    A tremendous amount of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to the standard therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the positive outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychologically accepted by patients as a natural compound with relative safety and low cost, their use should be encouraged in the fields where positive data are available.

  1. Cytohistological discordance on gastrointestinal brushings: Facts unfolded

    PubMed Central

    Tyagi, Ruchita; Kaur, Jagpal; Kaur, Gursheen; Selhi, Pavneet Kaur; Puri, Harpreet Kaur; Sood, Neena

    2016-01-01

    Introduction: Brush cytology is a rapid, cost-effective, and reliable tool to diagnose gastrointestinal tract (GIT) lesions in low-resource settings. Most of the studies on GIT brushings have focused on upper GI lesions. We have studied the diagnostic accuracy of brush cytology in the entire length of GIT and correlated the cytological diagnosis with histopathology. The aim of this study is to study diagnostic utility of brush cytology of GIT lesions in the context of correlation with biopsy and study the factors responsible for cytohistological discordance. Materials and Methods: A retrospective analysis of 101 cases of prebiopsy brush cytology samples of GIT lesions was done over a period of 1 year (June 2014 to May 2015). The cytological diagnosis was compared with histopathological diagnosis and percentage of correlation was calculated. The reasons for discordance were noted and studied. Results: The cytological diagnosis of 79 (78.2%) correlated with histopathological diagnosis. There was discordance in cytological and histological diagnosis in 22 cases (21.8%). Inadequacy of cytological sample and overlap of nuclear atypia caused by regenerative changes and malignancy were significant factors for cytohistological discordance. Conclusion: The diagnostic accuracy of brush cytology can be improved by taking appropriate measures to eliminate factors responsible for fallacies in cytological diagnosis. PMID:27833250

  2. Primary anorectal malignant melanoma: an uncommon anorectal pathology.

    PubMed

    Juanmartiñena Fernández, José Francisco; Fernández-Urien, Ignacio; Córdoba, Alicia

    2016-09-01

    Anorectal malignant melanoma (AMM) is most common primary melanoma of gastrointestinal tract, accounting for 0.05% and 1% of all colorectal and anal cancers. We reported an 85 year-old woman with no significant past medical history who presented two-month period of rectal bleeding, abdominal pain, tenesmus and 2kg weight-loss. Laboratory markers were unremarkable, although rectal examination revealed two small haemorrhoids and a firm, non-obstructing mass in the lower rectum. Colonoscopy confirmed presence of an ulcerated pigmented neoplasm arising at dental line [A,B]. No distant metastases were found on computed tomography [C] although presented metastatic regional lymph nodes on pelvic MRI [D]. Therefore, abdominoperineal resection was performed, confirming loco-regional disease. Histopathology showed malignant melanoma with positive stains in immunohistochemistry for protein S100, HMB-45 and Melan-A [E,F,G,H] and stained negative for c-Kit.

  3. Gastrointestinal Amyloidosis Presenting with Multiple Episodes of Gastrointestinal Bleeding

    SciTech Connect

    Kim, Sang Hyeon Kang, Eun Ju; Park, Jee Won; Jo, Jung Hyun; Kim, Soo Jin; Cho, Jin Han; Kang, Myong Jin; Park, Byeong Ho

    2009-05-15

    Amyloidosis is characterized by the extracellular deposition of amyloid protein in various organs. Gastrointestinal involvement in amyloidosis is common, but a diagnosis of amyloidosis is often delayed. Severe gastrointestinal hemorrhage in amyloidosis is rare but can be fatal in some cases. We experienced a case of a 49-year-old man who presented with recurrent massive hematochezia. Although embolization was performed eight times for bleeding from different sites of the small intestine, hematochezia did not cease. We report the case, with a review of the literature.

  4. Synchronous gastric gastrointestinal stromal tumor (GIST) and other primary neoplasms of gastrointestinal tract: report of two cases.

    PubMed

    Kaur, Ramneet; Bhalla, Sunita; Nundy, Samiran; Jain, Sunila

    2013-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract with a malignant potential. However, uncommonly they can be associated with synchronous tumors of different histogenesis. We herein report two cases of gastric GIST with synchronous tumors. The first case is of a 50-year-old male patient who was suspected with GIST of stomach and was incidentally found to have an associated duodenal neuroendo-crine neoplasm. The second case is of a 62-year-old male who, while undergoing surgery for a primary colon adenocarcinoma, was incidentally detected to have a coexistent gastric GIST initially suspected to be a metastatic nodule. Coexistence of gastric GIST with neuroendocrine tumor is extremely rare. To the best of our knowledge this is the second case of gastric GIST coexisting with duodenal neuroendocrine tumor to be reported in the literature. Similarly, association of GIST with adenocarcinoma is uncommon. We herein analyze the pathological findings of two such cases, and we review the malignant potential of these synchronous tumors.

  5. Trends in Gastrointestinal Cancer Mortality Rate in Hungary.

    PubMed

    Farkas, Klaudia; Szűcs, Mónika; Nyári, Tibor András

    2016-10-01

    The aim of this study was to investigate the annual death trends for gastrointestinal cancer in Hungary between 1963 and 2012. Data on the numbers of cancer deaths were obtained from the published nationwide population register. Numbers of deaths from esophageal, gastric and colorectal cancer were available during the study period. However, the mortality data for hepatic, pancreatic and gallbladder cancer have been published only since 1979. Joinpoint regression was applied to investigate the annual trends in the rates of cancer mortality. The annual mortality rates of gastric and gallbladder cancer decreased throughout the study period. Furthermore, declines in mortality from esophageal and hepatic cancers have been observed since 1998 and 1995, respectively. However, the rates of colorectal and pancreatic cancer mortality have been increasing in the past few years. Nevertheless, the mortality rates of colorectal and pancreatic cancers have increased in males aged 40-59 years during the study period. Moreover, significantly higher risks of gastrointestinal cancer-related deaths have been observed in males as compared with females except for death related to cancer of the gallbladder. The presented data suggest that the Hungarian mortality rates are particularly high. The detection of gastrointestinal cancers at an early stage would significantly improves the outcome of these malignancies.

  6. Ectopic Pancreas Imitating Gastrointestinal Stromal Tumor (GIST) In The Stomach.

    PubMed

    Zińczuk, Justyna; Bandurski, Roman; Pryczynicz, Anna; Konarzewska-Duchnowska, Emilia; Kemona, Andrzej; Kędra, Bogusław

    2015-05-01

    Ectopic pancreas is a rare congenital disorder defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. Most cases of ectopic pancreas are asymptomatic, but it may become clinically evident depending on the size, location and the pathological changes similar to those observed in case of the normal pancreas. It is often an incidental finding and can be located at different sites in the gastrointestinal tract. The most common locations are: the stomach, duodenum or the proximal part of small intestine. The risk of malignancy, bleeding and occlusion are the most serious complications. Despite the development in diagnostics, it still remains a challenge for the clinician to differentiate it from neoplasm. In this report, we described a case of 28-years old woman who presented recurrent epigastric pain. The upper gastrointestinal endoscopy revealed gastrointestinal stromal tumor on the border of the body and antrum of the back wall of great curvature of the stomach. The histopathological examination after surgery showed heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of gastric mass lesions.

  7. Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

    PubMed Central

    Onsongo, Getiria; Stone, Matthew D.; Chen, Xiao-Bing; Kooren, Joel A.; Refsland, Eric W.; Griffin, Robert J.; Ondrey, Frank G.; Wu, Baolin; Le, Chap T.; Rhodus, Nelson L.; Carlis, John V.; Griffin, Timothy J.

    2010-01-01

    Background Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need. Methodology/Principal Findings To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells. Conclusions/Significance Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early. PMID:20567502

  8. Therapeutic uses of gastrointestinal peptides.

    PubMed

    Redfern, J S; O'Dorisio, T M

    1993-12-01

    The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are

  9. Correlation between cellular phone use and epithelial parotid gland malignancies.

    PubMed

    Duan, Y; Zhang, H Z; Bu, R F

    2011-09-01

    The authors investigated the association between cellular phone use and epithelial parotid gland malignancy. The subjects were 136 cases who were treated for this condition at the authors' hospital from January 1993 to March 2010, and 2051 controls who did not have salivary gland tumours and were admitted to the oral and maxillofacial surgery department during the same period. Logistic analysis was used to examine the relationship between cellular phone use and risk of epithelial parotid gland malignancy and mucoepidermoid carcinoma. Overall, the frequency of cellular phone use was not significantly associated with epithelial parotid gland malignancy. Female gender, advanced age, married status, high income, and smoking were associated with an elevated risk of epithelial parotid gland malignancy, especially mucoepidermoid carcinoma. Residence in a rural area was associated with reduced risk of epithelial parotid gland malignancy. The results suggest a possible dose-response relationship of cellular phone use with epithelial parotid gland malignancy. The authors suggest that the association of cellular phone use and epithelial parotid gland malignancy and mucoepidermoid carcinoma requires further investigation with large prospective studies.

  10. Novel immunotherapies in lymphoid malignancies

    PubMed Central

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J.; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted ‘breakthrough’ designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  11. Sense of taste in the gastrointestinal tract.

    PubMed

    Iwatsuki, Ken; Uneyama, Hisayuki

    2012-01-01

    Recent advances in molecular biology have led to the investigation of the molecular mechanism by which chemicals such as odors and tastants are perceived by specific chemosensory organs. For example, G protein-coupled receptors expressed within the nasal epithelium and taste receptors in the oral cavity have been identified as odorant and taste receptors, respectively. However, there is much evidence to indicate that these chemosensory receptors are not restricted to primary chemosensory cells; they are also expressed and have function in other cells such as those in the airways and gastrointestinal (GI) tract. This short review describes the possible mechanisms by which taste signal transduction occurs in the oral cavity and tastants/nutrients are sensed in the GI tract by taste-like cells, mainly enteroendocrine and brush cells. Furthermore, it discusses the future perspectives of chemosensory studies.

  12. Gastrointestinal Symptoms of Marathon Runners

    PubMed Central

    Keeffe, Emmet B.; Lowe, Daniel K.; Goss, J. Richard; Wayne, Robert

    1984-01-01

    A survey of 707 participants in the 13th Annual Trail's End Marathon in Seaside, Oregon, showed a high incidence of gastrointestinal disturbances, predominantly of the lower tract, associated with long-distance running. The urge to defecate, both during and immediately after running, occurred in over a third of runners. Bowel movements (35%) and diarrhea (19%) were relatively common after running, and runners occasionally interrupted hard runs or races for bowel movements (18%) or diarrhea (10%). Lower gastrointestinal disturbances were more frequent in women than in men and in younger than in older runners. Awareness of the frequency and nature of gastrointestinal symptoms documented by this survey will assist physicians in evaluating abdominal complaints in runners. PMID:6506684

  13. Gastrointestinal symptoms of marathon runners.

    PubMed

    Keeffe, E B; Lowe, D K; Goss, J R; Wayne, R

    1984-10-01

    A survey of 707 participants in the 13th Annual Trail's End Marathon in Seaside, Oregon, showed a high incidence of gastrointestinal disturbances, predominantly of the lower tract, associated with long-distance running. The urge to defecate, both during and immediately after running, occurred in over a third of runners. Bowel movements (35%) and diarrhea (19%) were relatively common after running, and runners occasionally interrupted hard runs or races for bowel movements (18%) or diarrhea (10%). Lower gastrointestinal disturbances were more frequent in women than in men and in younger than in older runners. Awareness of the frequency and nature of gastrointestinal symptoms documented by this survey will assist physicians in evaluating abdominal complaints in runners.

  14. Prevention of malignant melanoma

    PubMed Central

    Chaidemenos, G; Stratigos, A; Papakonstantinou, M; Tsatsou, F

    2008-01-01

    The results of Primary Prevention programs, aiming at the decrease of melanoma incidence, were less encouraging than those of Secondary prevention which aims at an early diagnosis of malignant melanoma. Australia was the country with the best results obtained in both Prevention strategies, especially in avoiding intense, though intermittent, UV exposure. The success of these programs encouraged health authorities to initiate their application to other disorders. New sunscreens containing substances correcting the UV-damaged DNA may offer a promising result in the decades to come. However, so far no one epidemiological study has proved the prevention of malignant melanoma with the use of sun protecting agents. A meta-analysis verified the connection between melanoma and solarium use. The protective role of vitamin D in the development of prostate, breast and colon cancer was shown in a meta-analysis. The authors, however, suggest that fair-skinned persons should take oral supplementation of vitamin D, instead of exposing themselves to the sun. The Hellenic Society of Dermatology and Venereology published the results of 5-year-prevention programs in Greece. Their favorable results in the early diagnosis of melanoma justify an intense continuation of these efforts. PMID:18923759

  15. Spontaneous Perforation as a First Presentation of Ileal Gastrointestinal Stromal Tumour (GIST) with Synchronous Breast Sarcoma.

    PubMed

    Sharma M, Bir Kumar; Barad, Arun Kumar; Padu, Kemba; Singh K, Sridartha; Singh Th, Sudhir Chandra

    2014-05-01

    Gastrointestinal Stromal Tumours (GIST's) are the most common mesenchymal neoplasms of the gastrointestinal tract. Majority of the GISTs are asymptomatic and often diagnosis is incidental. Synchronous second malignancies have been reported in patients with GIST. We report a case of 50-year-old female presenting with features of hollow viscous perforation, found to have ileal GIST with perforations along with a synchronous breast sarcoma. GIST with spontaneous perforation as its first clinical manifestation is rare. Synchronous occurrence of an ileal GIST with a breast sarcoma is unique and deserves reporting. This case report highlights the varied nature of clinical presentation of the GIST and also stresses on the importance of extensive search for the synchronous second malignancies in the extra abdominal sites as well.

  16. Blood thinners and gastrointestinal endoscopy

    PubMed Central

    Ahmed, Monjur

    2016-01-01

    As the number of diagnostic and therapeutic gastrointestinal endoscopies is increasing, and there is an increase in number of patients taking blood thinners, we are seeing more and more patients on blood thinners prior to endoscopic procedures. Gastrointestinal bleeding or thromboembolism can occur in this category of patients in the periendoscopic period. To better manage these patients, endoscopists should have a clear concept about the various blood thinners in the market. Patients’ risk of thromboembolism off anticoagulation, and the risk of bleeding from endoscopic procedures should be assessed prior to endoscopy. The endoscopic procedure should be done when it is safe to do it. PMID:27668068

  17. [Full attention to several key issues in surgical treatment for the elderly patients with gastrointestinal cancer].

    PubMed

    Zhu, Zhenggang

    2016-05-01

    With the development of population aging in our country, the incidence of gastrointestinal cancer is increasing. The risk of developing gastrointestinal cancer in elderly over 75 years was 5-6 times and the risk of death of gastrointestinal cancer was 7-8 times of the general population. As compared to non-elderly, the incidence of gastric cancer was not decreased obviously but the total incidence of colorectal cancer was increased more quickly. Therefore, screening of gastrointestinal cancer should be performed in the elderly for early discovery, diagnosis and treatment. Because of the insidious onset of the illness in elderly patients, gastrointestinal cancers are mostly diagnosed at advanced or late stage (stage III or IV). Well differentiated cancer is more common, such as papillary or tubular adenocarcinoma. Lauren type, Borrmann II or III are more common in gastric cancer, which are relatively favorable. Compared with non-elderly patients, many elderly patients also suffer from comorbid diseases with higher operation risk and postoperative complication rates. Therefore, we must pay great attention to the perioperative management and the surgical operation for the elderly patients. In this paper, several key issues involved the development trend of incidence and mortality of gastrointestinal cancer, the clinicopathological characteristics, the comorbidity and surgical treatment in the elderly patients with gastrointestinal cancer will be elaborated, aiming at promoting further attention to the clinical therapeutic strategies, management measures and prognostic factors for the elderly patients with gastrointestinal cancer.

  18. Progress in oncolytic virotherapy for the treatment of thyroid malignant neoplasm.

    PubMed

    Guan, Mingxu; Romano, Gaetano; Coroniti, Roberta; Henderson, Earl E

    2014-11-01

    Thyroid malignant neoplasm develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Oncolytic virotherapy has significantly progressed as therapeutics in recent years. The advance is that oncolytic viruses can be designed with biological specificity to infect, replicate and lyse tumor cells. Significant advances in virotherapy have being achieved to improve the accessibility, safety and efficacy of the treatment. Therefore, it is necessary to summarize and bring together the main areas covered by these investigations for the virotherapy of thyroid malignant neoplasm. We provide an overview of the progress in virotherapy research and clinical trials, which employ virotherapy for thyroid malignant neoplasm as well as the future prospect for virotherapy of thyroid malignant neoplasms.

  19. Whole Pelvic Intensity-modulated Radiotherapy for Gynecological Malignancies: A Review of the Literature

    PubMed Central

    Hymel, Rockne; Jones, Guy C.; Simone, Charles B.

    2015-01-01

    Radiation therapy has long played a major role in the treatment of gynecological malignancies. There is increasing interest in the utility of intensity-modulated radiotherapy (IMRT) and its application to treat gynecological malignancies. Herein, we review the state-of-the-art use of IMRT for gynecological malignancies and report how it is being used alone as well as in combination with chemotherapy in both the adjuvant and definitive settings. Based on dosimetric and clinical evidence, IMRT can reduce gastrointestinal, genitourinary, and hematological toxicities compared with 3D conformal radiotherapy for gynecologic malignancies. We discuss how these attributes of IMRT may lead to improvements in disease outcomes by allowing for dose escalation of radiation therapy, intensification of chemotherapy, and limiting toxicity-related treatment breaks. Currently accruing trials investigating pelvic IMRT for cervical and endometrial cancers are discussed. PMID:25600840

  20. Oral potentially malignant disorders: Is malignant transformation predictable and preventable?

    PubMed Central

    van der Waal, Isaäc

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed. Key words:Oral potentially malignant disorders, oral leukoplakia, oral lichen planus. PMID:24905952

  1. Malignant lymphoma of bone.

    PubMed

    Dürr, Hans Roland; Müller, Peter Ernst; Hiller, Erhard; Maier, Markus; Baur, Andrea; Jansson, Volkmar; Refior, Hans Jürgen

    2002-02-01

    Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed because of unspecific clinical signs and equivocal radiographs. Therapy in general is multimodal, including surgery and radio- and chemotherapy. Our objective was to demonstrate the clinical and radiological aspects of the lesion to optimize diagnostic approaches and to evaluate treatment and prognostic factors. Thirty-six patients with malignant lymphoma of bone who were surgically treated over a 15-year-period were retrospectively reviewed. Seventeen of them showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease with multiple bone or visceral involvement was apparent (dNHL). Six patients suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment was indicated for diagnostic reasons or complications due to the disease. Radiation and chemotherapy were part of the oncological treatment. The patients' mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients was pain, with an average duration of 8 months. In the secondary cases, bone involvement appeared on average 57 months after the initial diagnosis. An osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic sign associated with this disease. The 5-year survival rate was 61% (PLB 88%, dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant factor in the prognosis. Extraskeletal involvement significantly decreased survival. No correlation was found between gender, age, location, or histological subtypes and survival. Bone involvement in NHL appears late in the extraskeletal disease. The clinical appearance is nonspecific, and the delay between the onset of symptoms and diagnosis is often long. One of the major radiologic signs is the existence of a soft-tissue tumor

  2. Computed tomography of the gastrointestinal tract

    SciTech Connect

    Meyers, M.A.

    1986-01-01

    This volume presents computed tomography of the major disease states involving the gastrointestinal tract, mesentery, and peritoneal cavity. Computed Tomography of the Gastrointestinal Tract combined experience of l5 authorities includes illustrations (most of these radiographs).

  3. Microwave ablation of liver malignancies: comparison of effects and early outcomes of percutaneous and intraoperative approaches with different liver conditions : New advances in interventional oncology: state of the art.

    PubMed

    De Cobelli, Francesco; Marra, Paolo; Ratti, Francesca; Ambrosi, Alessandro; Colombo, Michele; Damascelli, Anna; Sallemi, Claudio; Gusmini, Simone; Salvioni, Marco; Diana, Pietro; Cipriani, Federica; Venturini, Massimo; Aldrighetti, Luca; Del Maschio, Alessandro

    2017-04-01

    Liver thermal ablation is an alternative treatment for hepatocellular carcinoma (HCC) and secondary liver malignancies. Microwave ablation (MWA) produces large ablation zones (AZ) in short time; however, AZ prediction is based on preclinical ex vivo models, rising concerns about reproducibility and safety in humans. We aimed to investigate the effects produced by a new-generation MWA system on human liver in vivo with different approaches (percutaneous or intraoperative) and liver conditions (cirrhosis or previous chemotherapy treatment), in comparison with manufacturer-provided predictions based on ex vivo animal models. Complete tumor ablation (CA) and early clinical outcomes were also assessed. From October 2014, 60 consecutive patients (cirrhotic = 31; non-cirrhotic = 10; chemotherapy-treated = 19) with 81 liver nodules (HCC = 31; mets = 50) underwent MWA procedures (percutaneous = 30; laparotomic = 18; laparoscopic = 12), with a 2450 MHz/100 W generator with Thermosphere™ Technology (Emprint™, Medtronic). A contrast-enhanced CT or MR was performed after one month to assess CA and measure AZ. A linear correlation between AZ volumes and ablation times was observed in vivo, without differences from manufacturer-provided ex vivo predictions in all operative approaches and liver conditions. Other independent variables (sex, age, nodule location) showed no relationship when added to the model. Median (IQR) longitudinal and transverse roundness-indexes of the AZs were, respectively, 0.77(0.13) and 0.93(0.11). CA at 1 month was 93% for percutaneous and 100% for intraoperative procedures (p = 0.175). Thirty-day morbidity and mortality were 3% and 0%. MWA with Thermosphere™ Technology produces predictable AZs on human liver in vivo, according to manufacturer-provided ex vivo predictions. In our experience, this new-generation MWA system is effective and safe to treat liver malignancies in different operative and clinical settings.

  4. Nox enzymes and oxidative stress in the immunopathology of the gastrointestinal tract.

    PubMed

    Rokutan, Kazuhito; Kawahara, Tsukasa; Kuwano, Yuki; Tominaga, Kumiko; Nishida, Keisei; Teshima-Kondo, Shigetada

    2008-07-01

    Chronic inflammation caused by Helicobacter pylori infection or inflammatory bowel disease (IBD) is closely linked to cancer development. Innate immune abnormalities and enhanced production of reactive oxygen species through a phagocyte NADPH oxidase (Nox2) are key issues in understanding the pathogenesis of inflammation-dependent carcinogenesis. Besides Nox2, functionally distinct homologues (Nox1, Nox3, Nox4, Nox5, Duox1, and Duox2) have been identified. Nox1 and Duox2 are highly expressed in the gastrointestinal tract. Although the functional roles of Nox/Duox in the gastrointestinal tract are still unclear, we will review their potential roles in the gastrointestinal immunopathology, particularly in H. pylori-induced inflammation, IBD, and malignancy.

  5. Primary malignant tumors of the small bowel.

    PubMed

    Mittal, V K; Bodzin, J H

    1980-09-01

    Primary malignant tumors of the small bowel are uncommon and are often diagnosed at an advanced stage. A 10 year survey (1967 to 1977) of the clinical records at one hospital revealed 39 cases of primary malignant tumors of the small bowel. The most common symptoms were abdominal pain (89.7 percent) and weight loss (77 percent). Six patients presented with complications of enterovesical fistula, bleeding and perforation. Preoperative diagnosis was suspected in 27 cases (69.2 percent). Adenocarcinoma was the most common tumor, followed by carcinoid tumor, lymphoma, leiomyosarcoma and melanoma. The treatment of choice was surgical resection whenever possible. Curative resection was attempted in 25 cases. Adjuvant radiotherapy and chemotherapy was used in four patients with lymphoma. Twenty-seven patients (69.2 percent) are alive from 1 to 6 years after diagnosis and treatment. The 5 year survival rate is 35 percent. Earlier diagnosis is essential if the prognosis for patients with small bowel malignancy is to be improved.

  6. Fertility issues in patients with hematologic malignancies.

    PubMed

    Loren, Alison W

    2015-01-01

    An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients.

  7. What's New in Gastrointestinal Stromal Tumor Research and Treatment?

    MedlinePlus

    ... Stromal Tumor (GIST) About Gastrointestinal Stromal Tumor What’s New in Gastrointestinal Stromal Tumor Research and Treatment? There ... the Key Statistics About Gastrointestinal Stromal Tumors? What’s New in Gastrointestinal Stromal Tumor Research and Treatment? More ...

  8. Malignant Pleural Mesothelioma

    PubMed Central

    Tsao, Anne S.; Wistuba, Ignacio; Roth, Jack A.; Kindler, Hedy Lee

    2009-01-01

    Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript. PMID:19255316

  9. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  10. Mucoadhesion and the gastrointestinal tract.

    PubMed

    Varum, Felipe J O; McConnell, Emma L; Sousa, Joao J S; Veiga, Francisco; Basit, Abdul W

    2008-01-01

    The concept of mucoadhesion is one that has the potential to improve the highly variable residence times experienced by drugs and dosage forms at various sites in the gastrointestinal tract, and consequently, to reduce variability and improve efficacy. Intimate contact with the mucosa should enhance absorption or improve topical therapy. A variety of approaches have been investigated for mucoadhesion in the gastrointestinal tract, particularly for the stomach and small intestine. Despite interesting results in these sites, mucoadhesive approaches have not yet shown success in humans. The potential of the lower gut for these applications has been largely neglected, although the large intestine in particular may benefit, and the colon has several factors that suggest mucoadhesion could be successful there, including lower motility and the possibility of a lower mucus turnover and thicker mucus layer. In vitro studies on colonic mucoadhesion show promise, and rectal administration has shown some positive results in vivo. This review considers the background to mucoadhesion with respect to the physiological conditions of the gastrointestinal tract as well as the principles that underlie this concept. Mucoadhesive approaches to gastrointestinal drug delivery will be examined, with particular attention given to the lower gut.

  11. [Motility and functional gastrointestinal disorders].

    PubMed

    Mearin, Fermín; Rey, Enrique; Balboa, Agustín

    2014-09-01

    This article discusses the studies on functional and motor gastrointestinal disorders presented at the 2014 Digestive Diseases Week conference that are of greatest interest to us. New data have been provided on the clinical importance of functional gastrointestinal disorders, with recent prevalence data for irritable bowel syndrome and fecal incontinence. We know more about the pathophysiological mechanisms of the various functional disorders, especially irritable bowel syndrome, which has had the largest number of studies. Thus, we have gained new data on microinflammation, genetics, microbiota, psychological aspects, etc. Symptoms such as abdominal distension have gained interest in the scientific community, both in terms of patients with irritable bowel syndrome and those with constipation. From the diagnostic point of view, the search continues for a biomarker for functional gastrointestinal disorders, especially for irritable bowel syndrome. In the therapeutic area, the importance of diet for these patients (FODMAP, fructans, etc.) is once again confirmed, and data is provided that backs the efficacy of already marketed drugs such as linaclotide, which rule out the use of other drugs such as mesalazine for patients with irritable bowel syndrome. This year, new forms of drug administration have been presented, including metoclopramide nasal sprays and granisetron transdermal patches for patients with gastroparesis. Lastly, a curiosity that caught our attention was the use of a vibrating capsule to stimulate gastrointestinal transit in patients with constipation.

  12. Challenges and prospects for pharmacotherapy in functional gastrointestinal disorders

    PubMed Central

    Sanger, Gareth J.; Chang, Lin; Bountra, Chas; Houghton, Lesley A.

    2010-01-01

    Functional gastrointestinal disorders, such as irritable bowel syndrome and functional dyspepsia, are complex conditions with multiple factors contributing to their pathophysiology. As a consequence they are difficult to treat and have posed significant challenges to the pharmaceutical industry when trying to develop new and effective treatments. This review provides an overview of these difficulties and how the industry is reshaping its drug developmental strategies. It describes some of the more significant and encouraging advances that have occurred, and discusses how future research might embrace the opportunities provided by advances in genetic and in particular, epigenetic research. PMID:21180610

  13. Primary malignant melanoma of prostate.

    PubMed

    Doublali, M; Chouaib, A; Khallouk, A; Tazi, M F; El Fassi, M J; Farih, My H; Elfatmi, H; Bendahou, M; Benlemlih, A; Lamarti, O

    2010-05-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate.

  14. Genetics Home Reference: malignant hyperthermia

    MedlinePlus

    ... 26(5):413-25. Citation on PubMed Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat. 2006 Oct;27(10):977-89. Review. Citation on PubMed Rosenberg H, Davis M, James D, Pollock N, Stowell K. Malignant ...

  15. A gist of gastrointestinal stromal tumors: A review

    PubMed Central

    Rammohan, Ashwin; Sathyanesan, Jeswanth; Rajendran, Kamalakannan; Pitchaimuthu, Anbalagan; Perumal, Senthil-Kumar; Srinivasan, UP; Ramasamy, Ravi; Palaniappan, Ravichandran; Govindan, Manoharan

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mesenchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularly-targeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors. PMID:23847717

  16. Gastrointestinal tract access for urological natural orifice transluminal endoscopic surgery

    PubMed Central

    Miakicheva, Olga; Hamilton, Zachary; Beksac, Alp T; Berquist, Sean W; Hassan, Abd-elrahman; Holden, Marc; Derweesh, Ithaar H

    2016-01-01

    We conducted a literature review of natural orifice transluminal endoscopic surgery (NOTES), focusing on urologic procedures with gastrointestinal tract access, to update on the development of this novel surgical approach. As part of the methods, a comprehensive electronic literature search for NOTES was conducted using PubMed and Cochrane Library from March 2002 to February 2016 for papers reporting urologic procedures performed utilizing gastrointestinal tract access. A total of 11 peer-reviewed studies examining utility of gastrointestinal access for NOTES urologic procedures were noted, with the first report in 2007. The procedures reported in the studies were total/radical nephrectomy, partial nephrectomy, adrenalectomy, and prostatectomy. The transgastric approach was identified in five studies examining total/radical nephrectomy (n = 2), partial nephrectomy (n = 1), partial cystectomy (n = 1), and adrenalectomy (n = 1). Six studies evaluated transrectal approach for NOTES, describing total/radical nephrectomy (n = 3), partial nephrectomy (n = 1), robotic nephrectomy with adrenalectomy (n = 1) and prostatectomy (n = 1). Feasibility was reported in all studies. Most studies were preclinical and acute, and limited by concerns regarding restricted instrumentation and infection risk. We concluded that gastrointestinal access for urologic NOTES demonstrates promise as described by outlined feasibility studies in preclinical models. Nonetheless, clinical application awaits further advancements in surgical technology and concerns regarding infectious potential. PMID:27909547

  17. Inflammatory Fibroid Polyp of the Stomach Mimics Malignancy on 18F FDG PET/CT Imaging.

    PubMed

    Bilgin, Sabriye Sennur; Bilgin, Mehmet; Savas, Recep; Erdogan, Ezgi Basak

    2016-09-01

    Inflammatory fibroid polyps (IFPs) are rare non-neoplastic and proliferating submucosal lesions of the gastrointestinal tract. The classic IFP, which was first described by Vanek, consists of prominent blood vessels and is characterized by a heavy inflammatory infiltrate, which is rich in eosinophilic granulocytes. The clinical presentation depends on the size and location. Inflammatory fibroid polyps cannot be differentiated from malignancy without histological examination. We report a case of IFP in the stomach that mimicked a primary gastric malignancy showing an increased F-FDG uptake.

  18. The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM)

    Cancer.gov

    The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM) was formed to promote international, multidisciplinary collaborations to advance our understanding of the etiology and outcomes of kidney cancer.

  19. Malignant eroticized countertransference.

    PubMed

    Chessick, R D

    1997-01-01

    Gabbard (1994) divided the pathology of therapists, both male and female, who commit sexual boundary violations into those who are psychotic, those who are predatory psychopaths, those engaging in masochistic surrender, and those called "the lovesick therapist." Lovesick therapists are the most common type and manifest crucial narcissistic themes of "a desperate need for validation by their patients, a hunger to be loved and idealized, and a tendency to use patients to regulate their own self-esteem" (p. 127). Among the psychodynamic aspects of this curiously circumscribed area of loss of reality testing that makes it difficult for the therapist to see how self-destructive and harmful such enactment is, are an unconscious reenactment of incestuous longings, a misperception of the patient's wish for maternal nurturance as a sexual overture, enactments of rescue fantasies, a projected idealization of the self of the therapist, a confusion of the therapist's needs with the patient's needs, a fantasy that love is curative, acting out disavowed rage at the patient, or rage at an organization, an institute, or one's training analyst, a manic defense against mourning, a narcissistic fantasy that their sexual affair is an exception, insecurity regarding masculine identity, and assorted primitive preoedipal themes. Gabbard's (1991) erotized countertransference is one variety of what I have termed malignant eroticized countertransference. His variety is a development that occurs under the pressure of the patient's preemptive and compelling expressions of lust and love, the patient's erotic transference. But malignant eroticized countertransference can also occur without the patient having offered any such expressions; it can even occur on first meeting the patient when he or she walks into the office! This is akin to the romantic "love-at-first-sight" theme so favored in the movies and by novelists, but it is always pathological when it occurs in the therapeutic situation

  20. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

    PubMed Central

    Mirrakhimov, Aibek E.

    2015-01-01

    Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. PMID:26713296

  1. Gynaecological Malignancies from Palliative Care Perspective

    PubMed Central

    Mishra, Kamlesh

    2011-01-01

    Of the approximately 80,000 new cases of all cancers detected every year in India, 10–15% are gynecological malignancies. As per population-based registries under the National Cancer Registry Program, the leading sites of cancer among women are the cervix uteri, breast, and oral cavity. About 50–60% of all cancers among women in India are mainly of the following four organs: cervix uteri, breast, corpus uteri, and ovaries. Over 70% of these women report for diagnostic and treatment services at an advanced stage of disease, resulting in poor survival and high mortality rates. Among all gynecological cancers, ovarian cancer is the deadliest one and, in 2/3rd of the cases, is detected in an advanced stage. But, in India and in other developing countries, due to inadequate screening facilities for the preventable cancer cervix, this kills more women than any other cancer in females. Gynecology Oncologist as a sub-specialist has an immensely important role in curtailing the menace of gynecological malignancies by providing comprehensive preventive, curative, palliative and follow-up services, with the aim of assuring a good quality of life to women as a cornerstone of cancer management. PMID:21811372

  2. Nanotechnology applications in hematological malignancies (Review)

    PubMed Central

    SAMIR, AHMED; ELGAMAL, BASMA M; GABR, HALA; SABAAWY, HATEM E

    2015-01-01

    A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

  3. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies

    PubMed Central

    Smith, Jill P.; Fonkoua, Lionel K.; Moody, Terry W.

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin - responsive tumors. PMID:26929735

  4. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies.

    PubMed

    Smith, Jill P; Fonkoua, Lionel K; Moody, Terry W

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin--responsive tumors.

  5. Malignant giant pheochromocytoma: a case report and review of the literature

    PubMed Central

    Arcos, Cristina Torres; Luque, Virgilio Ruiz; Luque, José Aguilar; García, Pablo Martínez; Jiménez, Antonia Brox; Muñoz, Macarena Márquez

    2009-01-01

    Malignant pheochromocytoma is a rare disease and surgical resection is the only curative treatment. There are no definitive histological or cytological criteria of malignancy, as it is impossible to determine this condition in the absence of advanced locoregional disease or metastases. We report a case of a patient with a giant retroperitoneal tumour, the second largest to be published, which was diagnosed as a malignant pheochromocytoma; it was treated with surgery. The literature is reviewed to evaluate tumour features and criteria to distinguish between benign and malignant pheochromocytomas. PMID:20019963

  6. Defining vascular signatures of malignant hepatic masses: role of MDCT with 3D rendering.

    PubMed

    Ahmed, Sameer; Johnson, Pamela T; Fishman, Elliot K

    2013-08-01

    Malignant hepatic masses, both primary and metastatic lesions, have characteristic CT appearances and enhancement patterns. Owing to advances in CT resolution, high-quality vascular maps can be generated with 3D rendering tools to aid hepatic mass evaluation. These renderings enable identification of neovascularity, which is critical for distinguishing malignant from benign lesions, and facilitate identification of small hyperenhancing malignant hepatic tumors. In this review, CT features of malignant hepatic masses are discussed in conjunction with a demonstration of the role for 3D vascular mapping.

  7. European Society of Gastrointestinal Endoscopy - Establishing the key unanswered research questions within gastrointestinal endoscopy.

    PubMed

    Rees, Colin J; Ngu, Wee Sing; Regula, Jaroslaw; Bisschops, Raf; Saftoiu, Adrian; Dekker, Evelien; Gralnek, Ian; Ciocirlan, Mihai; Dinis-Ribeiro, Mario; Jover, Rodrigo; Meisner, Søren; Spada, Cristiano; Hassan, Cesare; Valori, Roland; Hucl, Tomas; Le Moine, Olivier; Domagk, Dirk; Kaminski, Michal F; Bretthauer, Michael; Rutter, Matthew D; Aabakken, Lars; Ponchon, Thierry; Fockens, Paul; Siersema, Peter D

    2016-10-01

    Background and study aim: Gastrointestinal endoscopy is a rapidly evolving research field. The European Society of Gastrointestinal Endoscopy (ESGE) plays a key role in shaping opinion and endoscopy activity throughout Europe and further afield. Establishing key unanswered questions within the field of endoscopy and prioritizing those that are important enables researchers and funders to appropriately allocate resources. Methods: Over 2 years, the ESGE Research Committee gathered information on research priorities and refined them through a modified Delphi approach. Consultations were held with the ESGE Governing Board and Quality Improvement Committee to identify important unanswered questions. Research workshops were held at the 21st United European Gastroenterology Week. Research questions were refined by the ESGE Research Committee and Governing Board, compiled into an online survey, and distributed to all ESGE members, who were invited to rank each question by priority. Results: The final questionnaire yielded 291 responses from over 60 countries. The three countries with the highest response rates were Spain, Italy, and United Kingdom. Most responders were from teaching hospitals (62 %) and were specialist endoscopists (51 %). Responses were analyzed with weighted rankings, resulting in prioritization of 26 key unanswered questions. The top ranked generic questions were: 1) How do we define the correct surveillance interval following endoscopic diagnosis? 2) How do we correctly utilize advanced endoscopic imaging? 3) What are the best markers of endoscopy quality? Conclusion: Following this comprehensive process, the ESGE has identified and ranked the key unanswered questions within the field of gastrointestinal endoscopy. Researchers, funders, and journals should prioritize studies that seek to answer these important questions.

  8. [Pelvic actinomycosis simulating adnexal malignant tumor].

    PubMed

    Benkiran, L; Gamra, L; Lamalmi, N; Essouyeh, M; Regragui, A; Amrani, M; Souadka, A; Melabbas, M A

    2002-01-01

    The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists.

  9. Malignancy and chronic renal failure.

    PubMed

    Peces, Ramon

    2003-01-01

    Increased incidence of cancer at various sites is observed in patients with end-stage renal disease (ESRD). Certain malignant diseases, such as lymphomas and carcinomas of the kidney, prostate, liver and uterus, show an enhanced prevalence compared with the general population. In particular, renal cell carcinoma (RCC) shows an excess incidence in ESRD patients. A multitude of factors, directly or indirectly associated with the renal disease and the treatment regimens, may contribute to the increased tumor formation in these patients. Patients undergoing renal replacement therapy (RRT) are prone to develop acquired cystic kidney disease (ACKD), which may subsequently lead to the development of RCC. In pre-dialysis patients with coexistent renal disease, as in dialysis and transplant patients, the presence of ACKD may predispose to RCC. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse, are additional risk factors for malignancy. Malignancy following renal transplantation is an important medical problem during the follow-up. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. The type of malignancy is different in various countries and dependent on genetic and environmental factors. Finally, previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and post-malignancy screening.

  10. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  11. Updates in Gastrointestinal Oncology – insights from the 2008 44th annual meeting of the American Society of Clinical Oncology

    PubMed Central

    Javle, Milind; Hsueh, Chung-Tsen

    2009-01-01

    We have reviewed the pivotal presentations rcelated to colorectal cancer (CRC) and other gastrointestinal malignancies from 2008 annual meeting of the American Society of Clinical Oncology (ASCO). We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. The report on KRAS status in patients with metastatic CRC receiving epidermal growth factor receptor (EGFR) targeted antibody treatment has led to a change in National Comprehensive Cancer Network guideline that recommends only patients with wild-type KRAS tumor should receive this treatment. The results of double biologics (bevacizumab and anti-EGFR antibody) plus chemotherapy as first-line treatment in patients with metastatic CRC has shown a worse outcome than bevacizumab-based regimen. Microsatellite Instability has again been confirmed to be an important predictor in patients with stage II colon cancer receiving adjuvant treatment. Adjuvant gemcitabine therapy for pancreatic cancer was investigated by the CONKO-001 study; this resulted in superior survival as compared with observation and can be regarded as an acceptable option, without the addition of radiotherapy. The addition of bevacizumab to gemcitabine and erlotinib was not supior to gemcitabine and erlotinib for advanced disease. Second-line therapy for advanced pancreatic cancer with 5-fluorouracil and oxaliplatin resulted in a survival benefit. Irinotecan plus cisplatin and paclitaxel plus cisplatin result in similar survival when combined with radiotherapy for esophageal cancer. The novel fluoropyrimidine S1 appears to be active in gastric cancer, as a single agent or as combination therapy. Adjuvant intraperitoneal mitomycin-C may decrease the incidence of peritoneal recurrence of gastric cancer. Sorafenib is an effective agent in Asian patients with hepatocellular carcinoma secondary to hepatitis B; its utility in child's B cirrhosis remains to be proven. Sunitinib is also an active agent in

  12. Microcoil Embolization for Acute Lower Gastrointestinal Bleeding

    SciTech Connect

    D'Othee, Bertrand Janne Surapaneni, Padmaja; Rabkin, Dmitry; Nasser, Imad; Clouse, Melvin

    2006-02-15

    Purpose. To assess outcomes after microcoil embolization for active lower gastrointestinal (GI) bleeding. Methods. We retrospectively studied all consecutive patients in whom microcoil embolization was attempted to treat acute lower GI bleeding over 88 months. Baseline, procedural, and outcome parameters were recorded following current Society of Interventional Radiology guidelines. Outcomes included technical success, clinical success (rebleeding within 30 days), delayed rebleeding (>30 days), and major and minor complication rates. Follow-up consisted of clinical, endoscopic, and pathologic data. Results. Nineteen patients (13 men, 6 women; mean age {+-} 95% confidence interval = 70 {+-} 6 years) requiring blood transfusion (10 {+-} 3 units) had angiography-proven bleeding distal to the marginal artery. Main comorbidities were malignancy (42%), coagulopathy (28%), and renal failure (26%). Bleeding was located in the small bowel (n = 5), colon (n 13) or rectum (n = 1). Technical success was obtained in 17 patients (89%); 2 patients could not be embolized due to vessel tortuosity and stenoses. Clinical follow-up length was 145 {+-} 75 days. Clinical success was complete in 13 (68%), partial in 3 (16%), and failed in 2 patients (11%). Delayed rebleeding (3 patients, 27%) was always due to a different lesion in another bowel segment (0 late rebleeding in embolized area). Two patients experienced colonic ischemia (11%) and underwent uneventful colectomy. Two minor complications were noted. Conclusion. Microcoil embolization for active lower GI bleeding is safe and effective in most patients, with high technical and clinical success rates, no procedure-related mortality, and a low risk of bowel ischemia and late rebleeding.

  13. Gastrointestinal lesions associated with spondyloarthropathies

    PubMed Central

    Orlando, Ambrogio; Renna, Sara; Perricone, Giovanni; Cottone, Mario

    2009-01-01

    Subclinical gut inflammation has been described in up to two-thirds of patients with spondyloarthropathies (SpA). Arthritis represents an extra-intestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease (IBD), Whipple’s disease, Behcet’s disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis. Moreover about two-thirds of nonsteroidal anti-inflammatory drug users demonstrate intestinal inflammation. Arthritis may manifest as a peripheral or axial arthritis. The spondyloarthropathy family consists of the following entities: ankylosing spondylitis, undifferentiated spondyloarthritis, reactive arthritis, psoriatic arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis. This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal anti-inflammatory drugs users. PMID:19468992

  14. Quality control in gastrointestinal surgery.

    PubMed

    Ramírez-Barba, Ector Jaime; Arenas-Moya, Diego; Vázquez-Guerrero, Arturo

    2011-01-01

    We analyzed the Mexican legal framework, identifying the vectors that characterize quality and control in gastrointestinal surgery. Quality is contemplated in the health protection rights determined according to the Mexican Constitution, established in the general health law and included as a specific goal in the actual National Development Plan and Health Sector Plan. Quality control implies planning, verification and application of corrective measures. Mexico has implemented several quality strategies such as certification of hospitals and regulatory agreements by the General Salubrity Council, creation of the National Health Quality Committee, generation of Clinical Practice Guidelines and the Certification of Medical Specialties, among others. Quality control in gastrointestinal surgery must begin at the time of medical education and continue during professional activities of surgeons, encouraging multidisciplinary teamwork, knowledge, abilities, attitudes, values and skills that promote homogeneous, safe and quality health services for the Mexican population.

  15. Glutamine and the gastrointestinal tract.

    PubMed

    Ziegler, T R; Bazargan, N; Leader, L M; Martindale, R G

    2000-09-01

    The amino acid glutamine has become one of the most intensively studied nutrients in the field of nutrition and metabolic support. A variety of studies in cell culture systems, animal models of gut mucosal atrophy, injury/repair and adaptation and a limited number of clinical trials demonstrate trophic and cytoprotective effects of glutamine in small bowel and colonic mucosal cells. Although the routine clinical use of glutamine-enriched parenteral and enteral nutrient solutions remains controversial, available data demonstrate both the safety and metabolic and clinical efficacy of glutamine treatment in selected patient groups. Basic investigations are elucidating underlying mechanisms of glutamine action in intestinal cells. These will inform preclinical and clinical investigations designed to determine glutamine efficacy in selected gastrointestinal disorders. Emerging clinical trials will further define the utility of adjunctive glutamine supplementation as a component of specialized nutrition support in gastrointestinal disease.

  16. Paraneoplastic thrombocytosis in gastrointestinal cancer.

    PubMed

    Baranyai, Zsolt; Jósa, Valéria; Tóth, Ambrus; Szilasi, Zsuzsanna; Tihanyi, Balazs; Zaránd, Attila; Harsanyi, Laszlo; Szállási, Zoltán

    2016-06-01

    It has been demonstrated recently in several solid tumors that thrombocytosis at diagnosis may correlate with tumor invasion, metastatic progression and worse outcome. Several details of the pathomechanism of the relationship of thrombocytosis and cancer have been elucidated; however, the complete process is not clearly understood. Several hypotheses have been proposed. Recently, it was suggested that in ovarian cancer elevated IL-6 production by the tumor may induce increased megakaryopoiesis via hepatic thrombopoietin production leading to thrombocytosis. The importance of the prognostic power of elevated platelet count is still debated in gastrointestinal cancer. The aims of this review were to evaluate the prognostic significance of thrombocytosis in gastrointestinal tumors, to see whether clinical practice confirmed the hypotheses and to reveal the causes of the inconsistent findings.

  17. Gastrointestinal complications postthoracotomy and postvagotomy.

    PubMed

    Kokoska, E R; Naunheim, K S

    1998-08-01

    Postthoracotomy gastrointestinal complications, although relatively uncommon, can be associated with significant morbidity and mortality. It is necessary to identify patients who are at high risk for gastrointestinal complications during the preoperative evaluation. Appropriate stress ulcer prophylaxis should be provided to high-risk patients, and enteral feeds should be initiated as early in the postoperative course as possible. Postoperative hypotension and massive blood transfusions can be avoided with early reexploration in the case of postoperative hemorrhage. Finally, unexplained abdominal pain must not be ignored; a high index of suspicion should be maintained, with early and liberal use of diagnostic tools such as standard radiography, CT, endoscopy, and angiography. Consultation should be requested from a surgeon experienced in abdominal catastrophes. Early laparotomy with aggressive operative management can be lifesaving therapy but must be not applied in a cavalier fashion, as many of these disorders can and should be managed conservatively.

  18. Malignant renal tumors in children

    PubMed Central

    Sanchez, Thomas Ray; Wootton-Gorges, Sandra

    2015-01-01

    Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. PMID:28326263

  19. Gastrointestinal endoscopy: infection and disinfection.

    PubMed Central

    O'Connor, H J; Axon, A T

    1983-01-01

    The past decade has seen the development of an array of complex flexible fibreoptic instruments for gastrointestinal (GI) endoscopy, and an increasing use of these for diagnostic and therapeutic purposes. It has been recognised more recently that the use of contaminated endoscopic equipment can lead to serious and occasionally fatal infections. Infection with a wide variety of micro-organisms has been reported following oesophago-gastroduodenoscopy (OGD) and endoscopic retrograde cholangio-pancreatography (ERCP). PMID:6414894

  20. The role of surgery in the palliation of malignancy.

    PubMed

    Sallnow, L; Feuer, D

    2010-11-01

    Surgery has always had an important role to play in the palliation of advanced malignancy and the advent of new techniques and procedures means that this role will continue to evolve. The field is not built on a strong evidence base, however, and the lack of consensus regarding definitions of palliative surgery and few validated outcome measures mean good prospective trials are difficult to carry out. In this review we propose a definition of palliative surgery from the literature and review the current role of surgical palliation in advanced malignancy. We discuss the central role of good decision-making and the influence of multidisciplinary working on this process. The barriers to carrying out research, both in surgery and in advanced cancer patient populations, are examined and the economic impacts considered.

  1. Malignant glioma: lessons from genomics, mouse models, and stem cells.

    PubMed

    Chen, Jian; McKay, Renée M; Parada, Luis F

    2012-03-30

    Eighty percent of malignant tumors that develop in the central nervous system are malignant gliomas, which are essentially incurable. Here, we discuss how recent sequencing studies are identifying unexpected drivers of gliomagenesis, including mutations in isocitrate dehydrogenase 1 and the NF-κB pathway, and how genome-wide analyses are reshaping the classification schemes for tumors and enhancing prognostic value of molecular markers. We discuss the controversies surrounding glioma stem cells and explore how the integration of new molecular data allows for the generation of more informative animal models to advance our knowledge of glioma's origin, progression, and treatment.

  2. Seminars: controversies in the management of pediatric thyroid malignancy.

    PubMed

    Gingalewski, Cynthia A; Newman, Kurt D

    2006-12-15

    Thyroid cancer in children is a rare malignancy with unusual biological behavior. It often presents at advanced stages, yet behaves in a benign manner, when compared to its adult counterpart. Surgeons have debated the risks and benefits of aggressive surgical procedures for over a decade. A consensus treatment plan for childhood thyroid cancer has not been achieved, however radical surgical procedures have, in general, fallen out of favor. The best operative and adjuvant strategy for these children can only be determined when a better understanding of the tumor cell biology and genetics of this cancer is known. This review discusses the current controversies in the management of differentiated childhood thyroid malignancy.

  3. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency.

    PubMed

    Agarwal, Shradha; Mayer, Lloyd

    2013-09-01

    Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency.

  4. [Collagen diseases with gastrointestinal manifestations].

    PubMed

    Takahashi, Hiroki; Ohara, Mikiko; Imai, Kohzoh

    2004-06-01

    Collagen vascular diseases are known to present with a diverse array of gastrointestinal manifestations. These can be classified as: 1) gastrointestinal damage due to the collagen vascular disease itself; 2) adverse events caused by pharmacotherapies; or 3) gastrointestinal infections following immunosuppression due to corticosteroid (CS) administration. The first group includes lupus enteritis and protein-losing gastroenteropathy in systemic lupus erythematosus (SLE), reflux esophagitis, chronic intestinal pseudo-obstruction, and pneumatosis cystoids intestinalis in systemic sclerosis, amyloidosis in rheumatoid arthritis, bowel ulcer and bleeding in rheumatoid vasculitis and microscopic polyangiitis, and ileocecal ulcer in Behcet disease. In particular, colonic ulcers associated with SLE represent refractory lesions resistant to CS. Analysis of reported cases showing colonic lesions with SLE (22 cases in Japan) revealed that mean duration of SLE was 9.9 years and 77% of colonic lesions were observed in the rectum and sigmoid colon. Half of the patients developed intestinal perforation or penetration, and 6 of the 11 patients with perforation died. The second group includes lesions in the small and large intestine due to nonsteroidal anti-inflammatory drugs (NSAIDs) and CSs, in addition to peptic ulcers. As perforation in CS-treated patients displays relatively high incidence with poor prognosis, careful attention to such complications is needed. The third group includes candidal esophagitis and cytomegalovirus (CMV) enteritis. Prompt diagnosis is required to prevent colonic bleeding and perforation due to CMV.

  5. Combined Arterial Infusion and Stent Implantation Compared with Metal Stent Alone in Treatment of Malignant Gastroduodenal Obstruction

    SciTech Connect

    Wang Zhongmin; Chen Kemin; Gong Ju; Zheng Yunfeng; Wang Tianxiang

    2009-09-15

    Many patients with malignant gastroduodenal obstruction have an unresectable primary lesion and distant metastases, which may prompt palliative management to allow the patient to eat and to improve the quality of life. Intraluminal metallic stent implantation (MSI) under fluoroscopic guidance has been reported to be an effective option for symptomatic relief in these patients, with a good safety record. An alternative, dual interventional therapy (DIT), has been used during the last decade, in which prosthesis insertion is followed by intra-arterial chemotherapy via the tumor-feeding arteries. The aim of this study was to compare success rates, complication rates, and survival time between MSI and DIT in patients who presented with gastroduodenal obstruction from advanced upper gastrointestinal tract cancer. All consecutive patients with malignant gastroduodenal obstruction seen at our center between October 2002 and August 2007 were retrospectively studied. Patients were treated palliatively by either MSI or DIT by the patient's or the next of kin's decision. Outcomes included technical and clinical success, complication rates, and survival. Of the 164 patients with malignant gastric and duodenal outlet obstructions, 80 (49%) underwent stent insertion as the primary therapy, while the remaining 84 (51%) received DIT. Clinical characteristics were similar between the two groups. In the MSI cohort initial stent implantation was successful in 73 patients (91%), two stents were used in 5 patients, and delayed additional stent insertion for stent obstruction related to tumor overgrowth was required in 3 patients during follow-up. In the DIT cohort the technical success rate was 94%, 3 patients required two stents, and stent obstruction occurred in 2 patients after initial stent placement. Early postprocedural clinical success, indicated by average dysphagia score, improved significantly in both groups: MSI group, from 4.56 to 1.51 (P < 0.01); and DIT group, from 4

  6. Upper gastrointestinal barium evaluation of duodenal pathology: A pictorial review

    PubMed Central

    Gupta, Pankaj; Debi, Uma; Sinha, Saroj Kant; Prasad, Kaushal Kishor

    2014-01-01

    Like other parts of the gastrointestinal tract (GIT), duodenum is subject to a variety of lesions both congenital and acquired. However, unlike other parts of the GIT viz. esophagus, rest of the small intestine and large intestine, barium evaluation of duodenal lesions is technically more challenging and hence not frequently reported. With significant advances in computed tomography technology, a thorough evaluation including intraluminal, mural and extramural is feasible in a single non-invasive examination. Notwithstanding, barium evaluation still remains the initial and sometimes the only imaging study in several parts of the world. Hence, a thorough acquaintance with the morphology of various duodenal lesions on upper gastrointestinal barium examination is essential in guiding further evaluation. We reviewed our experience with various common and uncommon barium findings in duodenal abnormalities. PMID:25170399

  7. Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases.

    PubMed

    Konturek, P C; Haziri, D; Brzozowski, T; Hess, T; Heyman, S; Kwiecien, S; Konturek, S J; Koziel, J

    2015-08-01

    In the recent decade our understanding of the role of the human gut microbiome has been revolutionized by advances in development of molecular methods. Approximately, up to 100 trillion (10(14)) microorganisms per human body colonize the intestinal tract making an additional acquired organ that provides many vital functions to the host. A healthy gut microbiome can be defined by the presence of the various classes of microbes that enhance metabolism, resistance to infection and inflammation, prevention against cancer and autoimmunity and that positively influence so called braingut axis. Diet represents one of the most important driving forces that besides environmental and genetic factors, can define and influence the microbial composition of the gut. Aging process due to different changes in gut physiology (i.e. gastric hypochlorhydria, motility disorders, use of drugs, degenerative changes in enteric nervous system) has a profound effect on the composition, diversity and functional features of gut microbiota. A perturbed aged gut microbiome has been associated with the increasing number of gastrointestinal (e.g. Clostridium difficile infection - CDI) and non-gastrointestinal diseases (metabolic syndrome, diabetes mellitus, fatty liver disease, atherosclerosis etc.). Fecal microbiota transplantation (FMT) is a highly effective method in the treatment of refractory CDI. FMT is the term used when stool is taken from a healthy individual and instilled during endoscopy (colonoscopy or enteroscopy) into a gut of the sick person to cure certain disease. FMT represents an effective therapy in patient with recurrent CDI and the effectiveness of FMT in the prevention of CDI recurrence had reached approx. 90%. There is also an increasing evidence that the manipulation of gut microbiota by FMT represents a promising therapeutic method in patients with inflammatory bowel disease and irritable bowel syndrome. There is also an increased interest in the role of FMT for the

  8. Stenting of the Lower Gastrointestinal Tract: Current Status

    SciTech Connect

    Katsanos, Konstantinos; Sabharwal, Tarun Adam, Andreas

    2011-06-15

    Colon obstruction due to colorectal cancer is a major surgical emergency. Patients with acute bowel obstruction are usually poor surgical candidates with 10-20% operative mortality and 40-50% operative morbidity rates. Colorectal stenting is an image-guided, minimally invasive procedure, and typical indications include either palliation of inoperable malignant disease or temporary bowel decompression as a bridge to surgery. Colorectal stenting allows the patient to recover before definite elective surgical resection, reducing perioperative morbidity and mortality, overall hospital stay, and associated health care costs. Palliative stenting improves quality of life compared to surgery. A concise review is provided of contemporary stenting practice of the lower gastrointestinal tract, the colon in particular, and both palliative and preoperative adjuvant procedures are evaluated in terms of relevant patient oncology, insertion technique, available stent designs, technical and clinical outcomes, associated complications, and cost-benefit analysis.

  9. Clinical applications of liquid biopsies in gastrointestinal oncology

    PubMed Central

    Zhu, Jason

    2016-01-01

    “Liquid biopsies” are blood based assays used to detect and analyze circulating tumor products, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating messenger RNA (mRNA), circulating microRNA (miRNA), circulating exosomes, and tumor educated platelets (TEP). For patients with gastrointestinal (GI) malignancies, blood based biopsies may offer several advantages. First, tumor tissue samples are often challenging to procure, and when obtainable, are often insufficient for genomic profiling. Second, blood based assays offer a real-time overview of the entire tumor burden, and allow anatomically unbiased genomic profiling. Third, given the convenience and relative safety of liquid biopsies, this technology may facilitate identification of genomic alterations that confer sensitivity and resistance to targeted therapeutics. This review will assess the clinical applications of circulating tumor products for patients with GI tumors. PMID:27747082

  10. Gastrointestinal stem cells in health and disease: from flies to humans.

    PubMed

    Li, Hongjie; Jasper, Heinrich

    2016-05-01

    The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific populations of stem cells. To maintain tissue homeostasis, the proliferative activity of stem and/or progenitor cells has to be carefully controlled and coordinated with regionally distinct programs of differentiation. Metaplasias and dysplasias, precancerous lesions that commonly occur in the human gastrointestinal tract, are often associated with the aberrant proliferation and differentiation of stem and/or progenitor cells. The increasingly sophisticated characterization of stem cells in the gastrointestinal tract of mammals and of the fruit fly Drosophila has provided important new insights into these processes and into the mechanisms that drive epithelial dysfunction. In this Review, we discuss recent advances in our understanding of the establishment, maintenance and regulation of diverse intestinal stem cell lineages in the gastrointestinal tract of Drosophila and mice. We also discuss the field's current understanding of the pathogenesis of epithelial dysfunctions.

  11. Cannabinoids and the gastrointestinal tract

    PubMed Central

    PERTWEE, R

    2001-01-01

    The enteric nervous system of several species, including the mouse, rat, guinea pig and humans, contains cannabinoid CB1 receptors that depress gastrointestinal motility, mainly by inhibiting ongoing contractile transmitter release. Signs of this depressant effect are, in the whole organism, delayed gastric emptying and inhibition of the transit of non-absorbable markers through the small intestine and, in isolated strips of ileal tissue, inhibition of evoked acetylcholine release, peristalsis, and cholinergic and non-adrenergic non-cholinergic (NANC) contractions of longitudinal or circular smooth muscle. These are contractions evoked electrically or by agents that are thought to stimulate contractile transmitter release either in tissue taken from morphine pretreated animals (naloxone) or in unpretreated tissue (γ-aminobutyric acid and 5-hydroxytryptamine). The inhibitory effects of cannabinoid receptor agonists on gastric emptying and intestinal transit are mediated to some extent by CB1 receptors in the brain as well as by enteric CB1 receptors. Gastric acid secretion is also inhibited in response to CB1 receptor activation, although the detailed underlying mechanism has yet to be elucidated. Cannabinoid receptor agonists delay gastric emptying in humans as well as in rodents and probably also inhibit human gastric acid secretion. Cannabinoid pretreatment induces tolerance to the inhibitory effects of cannabinoid receptor agonists on gastrointestinal motility. Findings that the CB1 selective antagonist/inverse agonist SR141716A produces in vivo and in vitro signs of increased motility of rodent small intestine probably reflect the presence in the enteric nervous system of a population of CB1 receptors that are precoupled to their effector mechanisms. SR141716A has been reported not to behave in this manner in the myenteric plexus-longitudinal muscle preparation (MPLM) of human ileum unless this has first been rendered cannabinoid tolerant. Nor has it been

  12. General Information about Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  13. Treatment Option Overview (Malignant Mesothelioma)

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  14. Treatment Options for Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  15. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  16. Malignant external otitis: CT evaluation

    SciTech Connect

    Curtin, H.D.; Wolfe, P.; May, M.

    1982-11-01

    Malignant external otitis is an aggressive infection caused by Pseudomonas aeruginosa that most often occurs in elderly diabetics. Malignant external otitis often spreads inferiorly from the external canal to involve the subtemporal area and progresses medially towards the petrous apex leading to multiple cranial nerve palsies. The computed tomographic (CT) findings in malignant external otitis include obliteration of the normal fat planes in the subtemporal area as well as patchy destruction of the bony cortex of the mastoid. The point of exit of the various cranial nerves can be identified on CT scans, and the extent of the inflammatory mass correlates well with the clinical findings. Four cases of malignant external otitis are presented. In each case CT provided a good demonstration of involvement of the soft tissues at the base of the skull.

  17. Telomerase Activation in Hematological Malignancies

    PubMed Central

    Ropio, Joana; Merlio, Jean-Philippe; Soares, Paula; Chevret, Edith

    2016-01-01

    Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies. PMID:27618103

  18. Primary malignant melanoma of prostate

    PubMed Central

    Doublali, M.; Chouaib, A.; Khallouk, A.; Tazi, M. F.; El Fassi, M. J.; Farih, My. H.; Elfatmi, H.; Bendahou, M.; Benlemlih, A.; Lamarti, O.

    2010-01-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate. PMID:20882159

  19. Molecular Diagnosis for Breast Malignancy

    DTIC Science & Technology

    1997-07-01

    AD GRANT NUMBER DAMD17-94-J-4033 TITLE: Molecular Diagnosis for Breast Malignancy PRINCIPAL INVESTIGATOR: Wen-Tien Chen, Ph.D. CONTRACTING...Biomedical Laboratories. - Signature -^yjgf Wen-Tien Chen, Ph.D. Page 4 Molecular diagnosis for breast malignancy (1) FRONT COVER: (2) SF 298...June 8-9, 1995 (abstract). Chen, W.-T, Goldstein LA, Pineiro-Sänchez M, Howard L, Ghersi G, Salamone M, Flessate D, Yeh Y. 1977. " Molecular Diagnosis for

  20. Malignant tumours after renal transplantation.

    PubMed

    Fahlenkamp, D; Reinke, P; Kirchner, S; Schnorr, D; Lindeke, A; Loening, S A

    1996-10-01

    In 1243 patients after renal transplantation, 39 malignant tumours were detected in 37 patients. The average latency period between transplantation and tumour disease was 72 months. Tumours included 8 malignant lymphomas, 7 dermatomas and 24 visceral tumours. The patients who developed a tumour had received fewer blood transfusions before transplantation than a tumour-free control group of 60 patients with renal transplants. Rejection crises occurred in a significantly smaller number of tumour patients compared with the control group.

  1. Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.

    PubMed

    Tas, Faruk; Yildiz, Ibrahim; Kilic, Leyla; Ciftci, Rumeysa; Keskin, Serkan; Sen, Fatma

    2016-01-01

    Carboplatin-paclitaxel chemotherapy combination is the standard first-line treatment of advanced ovarian cancer and is the most commonly used treatment combination shown to be effective in advanced non-small-cell lung cancer (NSCLC). The most important dose-limiting side effect is hematologic toxicity. In this study, the severity of treatment-related myelotoxicity is compared in patients with advanced ovarian and lung cancers who received same schedule of carboplatin-paclitaxel. The study was prospectively performed from February 2009 to July 2011 and involved 103 patients with stages Ic-IV ovarian (n = 51) and advanced NSCLC (n = 52) who were administered a maximum of 6 cycles of carboplatin-paclitaxel as a first-line treatment. Full blood counts were measured before treatment, before each chemotherapy cycle during therapy, and at the first and sixth month after therapy. The median ages were 59 years (range, 35-77 years) for patients with NSCLC and 56 years (range, 38-75 years) for patients with ovarian cancer. The frequencies of anemia were 17% and 28.6% before the initiation of chemotherapy, 39.2% and 68.0% at the third cycle of treatment, and 44.2% and 45.2% at the sixth cycle of treatment in patients with NSCLC and ovarian cancer, respectively. Initial leukopenia rates were 3.4% and 0%; at the third cycle 46.0% and 41.2%; and at the sixth cycle 41.9% and 48.8% in patients with NSCLC and ovarian cancer, respectively. At the third cycle, 2.5% of the patients with NSCLC and 10.4% of the patients with ovarian cancer had thrombocytopenia, and at the sixth cycle, 23.3% of the patients with NSCLC and 25% of the patients with ovarian cancer had thrombocytopenia. Hemoglobin, leukocyte, and platelet values at the third cycle were significantly lower than those at admission in both cancer groups. Declines in hemoglobin levels in patients with NSCLC and in platelets in patients with ovarian cancer at the sixth cycle were statistically significant compared with the third

  2. Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor.

    PubMed

    Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Delle Fave, Gianfranco; Jensen, Robert T

    2013-03-01

    Foregut neuroendocrine tumors [NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor (EGFR) by growth factors, gastrointestinal (GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGFα and various GI hormones to stimulate growth of the human foregut carcinoid,BON, the somatostatinoma QGP-1 and the rat islet tumor,Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGFα and the other growth-stimulating GI hormones increased Tyr(1068) EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs.

  3. Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor

    PubMed Central

    Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Fave, Gianfranco Delle; Jensen, Robert T.

    2012-01-01

    Foregut Neuroendocrine Tumors[NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor(EGFR) by growth factors, gastrointestinal(GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGFα and various GI hormones to stimulate growth of the human foregut carcinoid, BON, the somatostatinoma QGP-1 and the rat islet tumor, Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGFα and the other growth-stimulating GI hormones increased Tyr1068 EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs. PMID:23220008

  4. Interpretability of the PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventor (PedsQL) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls....

  5. Immune Modulation in Hematologic Malignancies

    PubMed Central

    Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2015-01-01

    The therapeutic potential of the immune system in the context of hematologic malignancies has long been appreciated particularly due to the curative impact of allogeneic hematopoietic stem cell transplantation. The role of immune system in shaping the biology and evolution of these tumors is now well recognized. While the contribution of the immune system in anti-tumor effects of certain therapies such as immune-modulatory drugs and monoclonal antibodies active in hematologic malignancies is quite evident, the immune system has also been implicated in anti-tumor effects of other targeted therapies. The horizon of immune-based therapies in hematologic malignancies is rapidly expanding with promising results from immune-modulatory drugs, immune-checkpoint blockade and adoptive cellular therapies, including genetically-modified T cells. Hematologic malignancies present distinct issues (relative to solid tumors) for the application of immune therapies due to differences in cell of origin/developmental niche of tumor cells, and patterns of involvement such as common systemic involvement of secondary lymphoid tissues. This article discusses the rapidly changing landscape of immune modulation in hematologic malignancies and emphasizes areas wherein hematologic malignancies present distinct opportunities for immunologic approaches to prevent or treat cancer. PMID:26320065

  6. Review article: anorexia and cachexia in gastrointestinal cancer.

    PubMed

    Ockenga, J; Valentini, L

    2005-10-01

    In patients with gastrointestinal malignancies, i.e. cancers of the stomach, colon, liver, biliary tract or pancreas, progressive undernutrition can be regularly observed during the course of illness. Undernutrition significantly affects the patients' quality of life, morbidity and survival. Pathogenetically, two different causes are relevant in the development of undernutrition in patients with gastrointestinal cancer. One cause is reduced nutritional intake. This condition is referred to as anorexia and can be worsened by the side effects of cancer therapy. The other cause is the release of endogenous transmitters and/or other products of the tumour leading to the cachexia syndrome, which is characterized by loss of body weight, negative nitrogen balance and fatigue. Cancer anorexia and cancer cachexia may have synergistic negative effects in affecting the patients' status. In this review, current nutritional support strategies with respect to different clinically relevant situations are described. An algorithm of the treatment strategies, including dietetic counselling, oral supplements, enteral and parenteral nutritional support is given. One focus is the approach of nutrition-focused patient care, which shows promising results. In addition, the possibilities of pharmacological intervention are discussed.

  7. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

    PubMed Central

    Verma, Sugreev; Kesh, Kousik; Ganguly, Nilanjan; Jana, Sayantan; Swarnakar, Snehasikta

    2014-01-01

    The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is

  8. Malignancies in a renal transplant population: The St. Michael's Hospital experience

    PubMed Central

    Saleeb, R.; Faragalla, H.; Yousef, G. M.; Stewart, R.; Streutker, C. J.

    2016-01-01

    Introduction: Previous publications have shown an increased incidence of various malignancies amongst renal transplant populations. The objective of this study was to analyze the rate and types of malignancies occurring in the St. Michael's Hospital renal transplant population and to determine whether our results were comparable to those previously published. Methods: After approval by the hospital's research ethic board, review of the records and pathology of the 1584 patients in the renal transplant clinic database patients was performed. The reports dated back to the year 1970. Results: Amongst the 1584 renal transplant patients, 106 patients with 132 dysplastic and malignant posttransplant lesions were identified. The highest incidence amid the malignancies was in nonmelanoma skin malignancies squamous cell carcinoma (SCC), basal cell carcinoma, and Kaposi sarcoma, with a total of 32 patients having 54 separate tumors (2.02% of all patients, 43.2% of tumors). Following skin tumors in incidence were genitourinary (28 tumors), gastrointestinal tract (GIT) lesions (8 adenocarcinomas, 14 dysplastic lesions, 1 low grade neuroendocrine tumor/carcinoid), posttransplant lymphoproliferative disorders (PTLDs) (10 cases), gynecologic (6 carcinomas), cervical/anal/vulvar dysplasia and invasive (SCCs) (4), and thyroid (3 papillary tumors). Nine patients had tumors of multiple sites/types. With respect to outcome, 14 patients died of malignancy, with the highest mortality being in the GIT malignancies (six patients). Second in mortality were the PTLD and skin tumor groups. Discussion: Information on the incidence and outcome of various malignancies in renal transplant patients is important in designing guidelines for the follow-up of these patients regarding tumor screening and prevention. The rate of malignancies in our group is comparable to that reported in other centers. PMID:27141185

  9. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  10. Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases

    PubMed Central

    Berna, Marc J.; Jensen, Robert T.

    2009-01-01

    In this paper, the estabished and possible roles of CCK1 and CCK2 receptors in gastrointestinal (GI) and metabolic diseases are reviewed and available results from human agonist/antagonist studies are discussed. While there is evidence for the involvement of CCK1R in numerous diseases including pancreatic disorders, motility disorders, tumor growth, regulation of satiety and a number of CCK-deficient states, the role of CCK1R in these conditions is not clearly defined. There are encouraging data from several clinical studies of CCK1R antagonists in some of these conditions, but their role as therapeutic agents remains unclear. The role of CCK2R in physiological (atrophic gastritis, pernicious anemia) and pathological (Zollinger-Ellison syndrome) hypergastrinemic states, its effects on the gastric mucosa (ECL cell hyperplasia, carcinoids, parietal cell mass) and its role in acid-peptic disorders are clearly defined. Furthermore, recent studies point to a possible role for CCK2R in a number of GI malignancies. Current data from human studies of CCK2R antagonists are presented and their potential role in the treatment of these conditions reviewed. Furthermore, the role of CCK2 receptors as targets for medical imaging is discussed. Even though cholecystokinin (CCK) and gastrin were among the first gastrointestinal hormones discovered [1,2], both their physiological roles as well as their roles in clinically relevant gastrointestinal diseases remain unclear and even controversial in many cases [3–6]. The structural characterization of CCK and gastrin [7,8], pharmacological identification [9–13] and cloning [14,15] of CCK and gastrin receptors (CCK1R, CCK2R), characterization of receptor location, peptide and receptor genes, development of receptor antagonists and receptor/agonist knockout animals [16–21] have led to important advancements in our understanding of the physiological and pathophysiological role of CCK and gastrin signaling [3]. Most of these topics

  11. Adoptive cell transfer therapy for malignant gliomas.

    PubMed

    Ishikawa, Eiichi; Takano, Shingo; Ohno, Tadao; Tsuboi, Koji

    2012-01-01

    To date, various adoptive immunotherapies have been attempted for treatment of malignant gliomas using nonspecific and/or specific effector cells. Since the late 1980s, with the development of rIL-2, the efficacy of lymphokine-activated killer (LAK) cell therapy with or without rIL-2 for malignant gliomas had been tested with some modifications in therapeutic protocols. With advancements in technology, ex vivo expanded tumor specific cytotoxic T-lymphocytes (CTL) or those lineages were used in clinical trials with higher tumor response rates. In addition, combinations of those adoptive cell transfer using LAK cells, CTLs or natural killer (NK) cells with autologous tumor vaccine (ATV) therapy were attempted. Also, a strategy of high-dose (or lymphodepleting) chemotherapy followed by adoptive cell transfer has been drawing attentions recently. The most important role of these clinical studies using cell therapy was to prove that these ex vivo expanded effector cells could kill tumor cells in vivo. Although recent clinical results could demonstrate radiologic tumor shrinkage in a number of cases, cell transfer therapy alone has been utilized less frequently, because of the high cost of ex vivo cell expansion, the short duration of antitumor activity in vivo, and the recent shift of interest to vaccine immunotherapy. Nevertheless, NK cell therapy using specific feeder cells or allergenic NK cell lines have potentials to be a good choice of treatment because of easy ex vivo expansion and their efficacy especially when combined with vaccine therapy as they are complementary to each other. Also, further studies are expected to clarify the efficacy of the high-dose chemotherapy followed by a large scale cell transfer therapy as a new therapeutic strategy for malignant gliomas.

  12. Cutaneous manifestation of gastrointestinal disease

    PubMed Central

    Kerstetter, Justin

    2016-01-01

    The gastrointestinal (GI) and cutaneous systems are closely linked in origin. Skin manifestations are frequently seen as a part of different GI syndromes. Gastroenterologists play an important role in recognizing the symptoms, patient workup and arriving at appropriate diagnoses, often in consultation with dermatologists. This review discusses the diseases with both cutaneous and intestinal involvement. Hereditary polyposis GI cancers, hereditary nonpolyposis colorectal cancers (CRCs), hamartomatous disorders, and inflammatory bowel disease (IBD) are reviewed with emphasis on the genetic basis, diagnostic, histologic findings, screening modalities, and therapeutic options. PMID:27034812

  13. Gastrointestinal Complications After Bariatric Surgery

    PubMed Central

    Ma, Irene T.

    2015-01-01

    Bariatric surgery is increasingly being performed in the medically complicated obese population as convincing data continue to mount, documenting the success of surgery not only in achieving meaningful weight loss but also in correcting obesity-related illnesses. Several surgical procedures with varying degrees of success and complications are currently being performed. This article discusses the short- and long-term gastrointestinal complications for the 4 most common bariatric surgical procedures: laparoscopic adjustable gastric banding, vertical sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion with duodenal switch. PMID:27118949

  14. Immunobiology of the gastrointestinal tract.

    PubMed

    Galant, S P

    1976-06-01

    The interplay between the gut and immune abnormality appears to be a logical extension of the thesis that secretory IgA is the major immunologic line of defense between the outside environment and the host. Thus immunologic deficiency, particularly of IgA and combined T- and B-lymphocyte abnormalites, profoundly influences gut integrity. Conversely, gut pathology is bound to interfere with immunologic function, so that both humoral and cellular immunity may be impaired. Finally, hypersensitivity phenomena in the gut, resulting in immune injury, may cause gastrointestinal disturbances. As better diagnostic tools have become available, more direct evidence of hypersensitivity immune injury has been described.

  15. PET/MR Imaging in Cancers of the Gastrointestinal Tract.

    PubMed

    Paspulati, Raj Mohan; Gupta, Amit

    2016-10-01

    PET/computed tomography (PET/CT) is an established hybrid imaging technique for staging and follow-up of gastrointestinal (GI) tract malignancies, especially for colorectal carcinoma. Dedicated hybrid PET/MR imaging scanners are currently available for clinical use. Although they will not replace regular use of PET/CT, they may have utility in selected cases of GI tract malignancies. The superior soft tissue contrast resolution and depiction of anatomy and the functional information obtained from diffusion-weighted imaging (DWI) provided by MR imaging in PET/MR imaging are advantages over CT of PET/CT for T staging and follow-up of rectal carcinoma and for better characterization of liver lesions. Functional information from DWI and use of liver-specific MR imaging contrast agents are an added advantage in follow-up of liver metastases after systemic and locoregional treatment. New radiotracers will improve the utility of PET/MR imaging in staging and follow-up of tumors, which may not be [18F]-2-fluoro-2-deoxy-d-glucose avid, such as hepatocellular carcinoma and neuroendocrine tumors. PET/MR imaging also has application in selected cases of cholangiocarcinoma, gallbladder cancer, and pancreatic carcinoma for initial staging and follow-up assessment.

  16. Regulators of Actin Dynamics in Gastrointestinal Tract Tumors

    PubMed Central

    Steinestel, Konrad; Wardelmann, Eva; Hartmann, Wolfgang; Grünewald, Inga

    2015-01-01

    Reorganization of the actin cytoskeleton underlies cell migration in a wide variety of physiological and pathological processes, such as embryonic development, wound healing, and tumor cell invasion. It has been shown that actin assembly and disassembly are precisely regulated by intracellular signaling cascades that respond to changes in the cell microenvironment, ligand binding to surface receptors, or oncogenic transformation of the cell. Actin-nucleating and actin-depolymerizing (ANFs/ADFs) and nucleation-promoting factors (NPFs) regulate cytoskeletal dynamics at the leading edge of migrating cells, thereby modulating cell shape; these proteins facilitate cellular movement and mediate degradation of the surrounding extracellular matrix by secretion of lytic proteases, thus eliminating barriers for tumor cell invasion. Accordingly, expression and activity of these actin-binding proteins have been linked to enhanced metastasis and poor prognosis in a variety of malignancies. In this review, we will summarize what is known about expression patterns and the functional role of actin regulators in gastrointestinal tumors and evaluate first pharmacological approaches to prevent invasion and metastatic dissemination of malignant cells. PMID:26345720

  17. Nonalcoholic Lipid Accumulation and Hepatocyte Malignant Transformation

    PubMed Central

    Gu, Juanjuan; Yao, Min; Yao, Dengbing; Wang, Li; Yang, Xuli; Yao, Dengfu

    2016-01-01

    Abstract Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing, highlighting its status as a public health concern, particularly due to its significant association with other comorbidities, such as diabetes. However, nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor, with its own prevalence increasing in recent years, and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus, exposure to aflatoxin, or alcohol liver disease. The deeply worrisome aspects of all of these high risk factors, however, are their remarkable presence within populations. Systemic and genetic mechanisms involved in the malignant transformation of liver cells, as well as useful biomarkers of early stage HCC are being investigated. However, the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely unknown. In this review, some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation. PMID:27350942

  18. Massive lower gastrointestinal bleeding associated with solitary rectal ulcer in a patient with Behçet's disease.

    PubMed

    Bes, C; Dağlı, Ü; Yılmaz, F; Soy, M

    2015-09-16

    Solitary rectal ulcer syndrome is a rare benign disorder that has a wide range of clinical presentations and variable endoscopic findings which makes it difficult to diagnose and treat. The clinical and endoscopic picture in this condition can also mimic malign ulceration, malignancy or Crohn's disease. Behçet's disease can affect the gastrointestinal tract. However to the best of our knowledge, no case with solitary rectal ulceration has been reported so far in literature. We herein present a patient diagnosed with Behçet's disease admitted to our clinic with rectal bleeding due to solitary rectal ulceration.

  19. Evidence-Based Recommendations on Upper Gastrointestinal Tract Stenting: A Report from the Stent Study Group of the Korean Society of Gastrointestinal Endoscopy

    PubMed Central

    Jee, Sam Ryong; Kim, Kyung Ho; Kim, Sang Gyun; Cho, Jun-Hyung

    2013-01-01

    Endoscopic stents have evolved dramatically over the past 20 years. With the introduction of uncovered self-expanding metal stents in the early 1990s, they are primarily used to palliate symptoms of malignant obstruction in patients with inoperable gastrointestinal (GI) cancer. At present, stents have emerged as an effective, safe, and less invasive alternative for the treatment of malignant GI obstruction. Clinical decisions about stent placement should be made based on the exact understanding of the patient's condition. These recommendations based on a critical review of the available data and expert consensus are made for the purpose of providing endoscopists with information about stent placement. These can be helpful for management of patients with inoperable cancer or various nonmalignant conditions in the upper GI tract. PMID:23964331

  20. Pharmacokinetics and safety of DTS-108, a human oligopeptide bound to SN-38 with an esterase-sensitive cross-linker in patients with advanced malignancies: a Phase I study

    PubMed Central

    Coriat, Romain; Faivre, Sandrine J; Mir, Olivier; Dreyer, Chantal; Ropert, Stanislas; Bouattour, Mohammed; Desjardins, Robert; Goldwasser, François; Raymond, Eric

    2016-01-01

    Background DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing 7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage. Methods The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1–2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design. SN-38 and SN-38 glucuronide (SN-38G) levels were evaluated with fluorescence high-performance liquid chromatography (HPLC) test, then liquid chromatography–tandem mass spectrometry (LC/MS/MS) methods. Results Forty-two patients received DTS-108 across 14 dosing cohorts (range 3–416 mg/m2). At 416 mg/m2, three out of six patients had grade 4 neutropenia thereby defining the MTD and the RP2D at 313 mg/m2. Fluorescence HPLC was inaccurate to quantify DTS-108 and its metabolites (SN-38 and SN-38G). New processes and analytical LC/MS/MS methods for testing SN-38 were implemented. At a dose of 313 mg/m2, mean DTS-108, SN-38, and SN-38G area under the plasma concentration–time curve to infinity (coefficients of variation %) were 439,293 (24%), 1,992 (34%), and 4,538 (46%) h·ng/mL. Stable disease (according to Response Evaluation Criteria in Solid Tumors) was observed in nine patients. Conclusion Assessing SN-38 concentration using fluorescence HPLC is questionable since this method failed to monitor dose escalation of DTS-108, a new topoisomerase I inhibitor, due to ex vivo degradation. LC/MS/MS methods were consistent in evaluating SN-38 exposures allowing drug monitoring. The maximum tolerated dose of DTS-108 was 416 mg/m2. The RP2D for intravenous DTS-108 was 313 mg/m2 every 2 weeks in patients with advanced/metastatic solid

  1. The cytologic criteria of malignancy.

    PubMed

    Fischer, Andrew H; Zhao, Chengquan; Li, Qing Kay; Gustafson, Karen S; Eltoum, Isam-Eldin; Tambouret, Rosemary; Benstein, Barbara; Savaloja, Lynnette C; Kulesza, Peter

    2010-07-01

    Cytology and cell biology are two separate fields that share a focus on cancer. Cancer is still diagnosed based on morphology, and surprisingly little is known about the molecular basis of the defining structural features. Cytology uses the smallest possible biopsy for diagnosis by reducing morphologic "criteria of malignancy" to the smallest scale. To begin to develop common ground, members of the American Society of Cytopathology Cell Biology Liaison Working Group classify some of the "criteria of malignancy" and review their relation to current cell biology concepts. The criteria of malignancy are extremely varied, apparently reflecting many different pathophysiologies in specific microenvironments. Criteria in Group 1 comprise tissue-level alterations that appear to relate to resistance to anoikis, alterations in cell adhesion molecules, and loss of apical-basal polarity. Criteria in Group 2 reflect genetic instability, including chromosomal and possibly epigenetic instability. Criteria in Groups 3 are subcellular structural changes involving cytoplasmic components, nuclear lamina, chromatin and nucleoli that cannot be accounted for by genetic instability. Some distinct criteria in Group 3 are known to be induced by cancer genes, but their precise structural basis remains obscure. The criteria of malignancy are not closely related to the histogenetic classification of cancers, and they appear to provide an alternative, biologically relevant framework for establishing common ground between cytologists and cell biologists. To understand the criteria of malignancy at a molecular level would improve diagnosis, and likely point to novel cell physiologies that are not encompassed by current cell biology concepts.

  2. Microbes in Gastrointestinal Health and Disease

    PubMed Central

    NEISH, ANDREW S.

    2010-01-01

    Most, if not all, animals coexist with a complement of prokaryotic symbionts that confer a variety of physiologic benefits. In humans, the interaction between animal and bacterial cells is especially important in the gastrointestinal tract. Technical and conceptual advances have enabled rapid progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of the human gut microbiota, allowing us to establish its role in human health and disease. The human host coevolved with a normal microbiota over millennia and developed, deployed, and optimized complex immune mechanisms that monitor and control this microbial ecosystem. These cellular mechanisms have homeostatic roles beyond the traditional concept of defense against potential pathogens, suggesting these pathways contribute directly to the well-being of the gut. During their coevolution, the bacterial microbiota has established multiple mechanisms to influence the eukaryotic host, generally in a beneficial fashion, and maintain their stable niche. The prokaryotic genomes of the human microbiota encode a spectrum of metabolic capabilities beyond that of the host genome, making the microbiota an integral component of human physiology. Gaining a fuller understanding of both partners in the normal gut-microbiota interaction may shed light on how the relationship can go awry and contribute to a spectrum of immune, inflammatory, and metabolic disorders and may reveal mechanisms by which this relationship could be manipulated toward therapeutic ends. PMID:19026645

  3. Digestive Enzyme Supplementation in Gastrointestinal Diseases

    PubMed Central

    Ianiro, Gianluca; Pecere, Silvia; Giorgio, Valentina; Gasbarrini, Antonio; Cammarota, Giovanni

    2016-01-01

    Background: Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. Methods: This review, performed through a non-systematic search of the available literature, will provide an overview of the current knowledge of digestive enzyme supplementation in gastrointestinal disorders, discussion of the use of pancreatic enzymes, lactase (β-galactosidase) and conjugated bile acids, and also exploring the future perspective of digestive enzyme supplementation. Results: Currently, the animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy. Conclusion: New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency, whereas the combination of different enzymes might constitute an intriguing therapeutic option in the future. PMID:26806042

  4. Advances in alimentary tract imaging.

    PubMed

    Maglinte, Dean-Dt; Sandrasegaran, Kumaresan; Tann, Mark

    2006-05-28

    Advances in imaging techniques are changing the way radiologists undertake imaging of the gastrointestinal tract and their ability to answer questions posed by surgeons. In this paper we discuss the technological improvements of imaging studies that have occurred in the last few years and how these help to better diagnosing alimentary tract disease.

  5. Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies

    PubMed Central

    Hamberg, P; Steeghs, N; Loos, W J; van de Biessen, D; den Hollander, M; Tascilar, M; Verweij, J; Gelderblom, H; Sleijfer, S

    2010-01-01

    Background: This study aimed to define the maximally tolerated dose (MTD) of sunitinib combined with two different infusion schedules of ifosfamide. Methods: Patients with advanced solid tumours, good performance score, good organ function, and no standard therapy available were eligible. Continuous once daily sunitinib, in escalating doses per cohort, was combined with ifosfamide, 9 g m−2 for 3 days or 6 g m−2 for 5 days, administered every 3 weeks. Pharmacokinetic (PK) and pharmacodynamic (PD) assessments were performed. Results: With growth-factor support, the MTD of sunitinib combined with either ifosfamide schedule was 12.5 mg in 32 patients enrolled. Neutropenia-related adverse events were dose-limiting toxicities. Sunitinib did not affect ifosfamide PK. Ifosfamide significantly decreased exposure to sunitinib and increased exposure to its metabolite, SU12662. No consistent changes in PD parameters were observed. Conclusion: With growth-factor support, the MTD of sunitinib with both ifosfamide schedules was 12.5 mg. Ifosfamide produced decreased sunitinib blood levels because of CYP3A induction. As PK interactions cannot explain the relatively low sunitinib doses that can be combined with ifosfamide, synergy in toxicity is likely. Whether this also holds true for anti-tumour activity needs to be further explored. PMID:20485286

  6. Vasculitides of the gastrointestinal tract.

    PubMed

    Ahn, Eric; Luk, Adriana; Chetty, Runjan; Butany, Jagdish

    2009-05-01

    Systemic vasculitis is often not considered as a possible diagnosis by clinicians because of its low prevalence compared with other more common diseases. Vasculitis can affect any end organ, and it is therefore often missed early on in disease progression. Gastrointestinal (GI) manifestations of vasculitis are considered rare and the presentation is often nonspecific. However, if there is significant involvement of the major vessels of the gastrointestinal system, life-threatening sequelae, including perforation and bowel ischemia, may occur. This makes early and immediate management crucial to improve long-term morbidity and mortality. Diagnosis of various GI vasculitides often relies on correlation of clinical manifestations with pathology and additional investigations. This paper reviews the various vasculitides that affect the GI tract, including systemic lupus erythematosus, mixed connective tissue disease, Henoch Schönlein purpura, polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, microscopic polyangiitis, enterocolic lymphocytic phlebitis, and Behcet's disease. Segmental arterial mediolysis, mistakenly believed to be a vasculitis, is also discussed.

  7. Feline gastrointestinal eosinophilic sclerosing fibroplasia.

    PubMed

    Craig, L E; Hardam, E E; Hertzke, D M; Flatland, B; Rohrbach, B W; Moore, R R

    2009-01-01

    A retrospective study of cases of a unique intramural inflammatory mass within the feline gastrointestinal tract was performed in order to describe and characterize the lesion. Twenty-five cases were identified from archival surgical and postmortem tissues. The lesion most often occurred as an ulcerated intramural mass at the pyloric sphincter (n = 12) or the ileocecocolic junction or colon (n = 9); the remaining cases were in the small intestine. Seven cases also had lymph node involvement. The lesions were characterized by eosinophilic inflammation, large reactive fibroblasts, and trabeculae of dense collagen. Intralesional bacteria were identified in 56% of the cases overall and all of the ileocecocolic junction and colon lesions. Fifty-eight percent of cats tested had peripheral eosinophilia. Cats treated with prednisone had a significantly longer survival time than those receiving other treatments. We propose that this is a unique fibroblastic response of the feline gastrointestinal tract to eosinophilic inflammation that in some cases is associated with bacteria. The lesion is often grossly and sometimes histologically mistaken for neoplasia.

  8. Gastrointestinal citrate absorption in nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Fegan, J.; Khan, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

  9. Ghrelin and gastrointestinal stromal tumors

    PubMed Central

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-01-01

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs. PMID:28348480

  10. Functional and motor gastrointestinal disorders.

    PubMed

    Mearin, Fermín; Rey, Enrique; Balboa, Agustín

    2016-09-01

    This article discusses the most interesting presentations at Digestive Disease Week, held in San Diego, in the field of functional and motor gastrointestinal disorders. One of the most important contributions was undoubtedly the presentation of the new Rome IV diagnostic criteria for functional gastrointestinal disorders. We therefore devote some space in this article to explaining these new criteria in the most common functional disorders. In fact, there has already been discussion of data comparing Rome IV and Rome III criteria in the diagnosis of irritable bowel syndrome, confirming that the new criteria are somewhat more restrictive. From the physiopathological point of view, several studies have shown that the aggregation of physiopathological alterations increases symptom severity in distinct functional disorders. From the therapeutic point of view, more data were presented on the efficacy of acotiamide and its mechanisms of action in functional dyspepsia, the safety and efficacy of domperidone in patients with gastroparesis, and the efficacy of linaclotide both in irritable bowel syndrome and constipation. In irritable bowel syndrome, more data have come to light on the favourable results of a low FODMAP diet, with emphasis on its role in modifying the microbiota. Finally, long-term efficacy data were presented on the distinct treatment options in achalasia.

  11. Ghrelin and gastrointestinal stromal tumors.

    PubMed

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-03-14

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

  12. Role of laparoscopy in hepatobiliary malignancies

    PubMed Central

    Arumugam, Prabhu; Balarajah, Vickna; Watt, Jennifer; Abraham, Ajit T.; Bhattacharya, Satyajit; Kocher, Hemant M.

    2016-01-01

    The many benefits of laparoscopy, including smaller incision, reduced length of hospital stay and more rapid return to normal function, have seen its popularity grow in recent years. With concurrent improvements in non-surgical cancer management the importance of accurate staging is becoming increasingly important. There are two main applications of laparoscopic surgery in managing hepato-pancreatico-biliary (HPB) malignancy: accurate staging of disease and resection. We aim to summarize the use of laparoscopy in these contexts. The role of staging laparoscopy has become routine in certain cancers, in particular T2 staged, locally advanced gastric cancer, hilar cholangiocarcinoma and non-Hodgkin's lymphoma. For other cancers, in particular colorectal, laparoscopy has now become the gold standard management for resection such that there is no role for stand-alone staging laparoscopy. In HPB cancers, although staging laparoscopy may play a role, with ever improving radiology, its role remains controversial. PMID:27377496

  13. Diagnostic procedures for submucosal tumors in the gastrointestinal tract

    PubMed Central

    Ponsaing, Laura Graves; Kiss, Katalin; Loft, Annika; Jensen, Lise Ingemann; Hansen, Mark Berner

    2007-01-01

    This review is part one of three, which will present an update on diagnostic procedures for gastrointestinal (GI) submucosal tumors (SMTs). Part two identifies the classification and part three the therapeutic methods regarding GI SMTs. Submucosal tumors are typically asymptomatic and therefore encountered incidentally. Advances in diagnostic tools for gastrointestinal submucosal tumors have emerged over the past decade. The aim of this paper is to provide the readers with guidelines for the use of diagnostic procedures, when a submucosal tumor is suspected. Literature searches were performed to find information on diagnostics for gastrointestinal submucosal tumors. Based on the searches, the optimal diagnostic procedures and specific features of the submucosal tumors could be outlined. Standard endoscppy, capsule endoscopy and push-and-pull enteroscopy (PPE) together with barium contrast X-ray do not alone provide sufficient information, when examining submucosal tumors. Endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI) and fluorodeoxyglucose-labeled positron emission tomography (FDG-PET) are recommended as supplementary tools. PMID:17659668

  14. Barbed suture for gastrointestinal closure: a randomized control trial.

    PubMed

    Demyttenaere, Sebastian V; Nau, Peter; Henn, Matthew; Beck, Catherine; Zaruby, Jeffrey; Primavera, Michael; Kirsch, David; Miller, Jeffrey; Liu, James J; Bellizzi, Andrew; Melvin, W Scott

    2009-09-01

    In an effort to make laparoscopic suturing more efficient, the V-Loc advanced wound closure device (Covidien, Mansfield, MA) has been produced. This device is a self-anchoring barbed suture that obviates the need for knot tying. The goal of this initial feasibility study was to investigate the use of the barbed suture in gastrointestinal enterotomy closure. A randomized study of 12 pigs comparing enterotomy closure with barbed versus a nonbarbed suture of similar tensile strength was performed. To this end, 25 mm enterotomies were made in the stomach (1 control, 1 treatment), jejunum (2 controls, 2 treatments), and descending colon (1 control, 1 treatment). Animals were killed at 3, 7, and 14 days postoperatively (4 each group) and their gastrointestinal tracts harvested; 6 of the 8 enterotomies from each pig underwent burst strength testing. The remaining 2 were fixed in formalin and sent for histological examination. All 12 pigs survived until they were killed without any major complications. Enterotomy closure with barbed suture revealed adhesion scores, burst strength pressures, and histology scores that were similar to those for the control. Jejunal closures resulted in 6 failures at 7 days (3 control, 3 barbed) and 4 failures at 14 days (2 control, 2 barbed). The barbed suture significantly reduced suturing time in the stomach, jejunum, and colon. The V-Loc wound closure device appears to offer comparable gastrointestinal closure to 3-0 Maxon while being significantly faster. Further studies with V-Loc are required to assess its use in laparoscopic surgery.

  15. Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps

    PubMed Central

    Bergin, Ingrid L.; Witzmann, Frank A.

    2013-01-01

    The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures. PMID:24228068

  16. Gastrointestinal Parasites and the Neural Control of Gut Functions

    PubMed Central

    Halliez, Marie C. M.; Buret, André G.

    2015-01-01

    Gastrointestinal motility and transport of water and electrolytes play key roles in the pathophysiology of diarrhea upon exposure to enteric parasites. These processes are actively modulated by the enteric nervous system (ENS), which includes efferent, and afferent neurons, as well as interneurons. ENS integrity is essential to the maintenance of homeostatic gut responses. A number of gastrointestinal parasites are known to cause disease by altering the ENS. The mechanisms remain incompletely understood. Cryptosporidium parvum, Giardia duodenalis (syn. Giardia intestinalis, Giardia lamblia), Trypanosoma cruzi, Schistosoma species and others alter gastrointestinal motility, absorption, or secretion at least in part via effects on the ENS. Recent findings also implicate enteric parasites such as C. parvum and G. duodenalis in the development of post-infectious complications such as irritable bowel syndrome, which further underscores their effects on the gut-brain axis. This article critically reviews recent advances and the current state of knowledge on the impact of enteric parasitism on the neural control of gut functions, and provides insights into mechanisms underlying these abnormalities. PMID:26635531

  17. Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps.

    PubMed

    Bergin, Ingrid L; Witzmann, Frank A

    2013-01-01

    The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures.

  18. Gastrointestinal metastases from prostate cancer: a review of the literature.

    PubMed

    Maines, Francesca; Caffo, Orazio; Veccia, Antonello; Galligioni, Enzo

    2015-01-01

    The availability of active new drugs for the treatment of advanced castration-resistant prostate cancer has significantly prolonged overall survival, thus changing the natural history of the disease and raising the likelihood of observing metastases in atypical sites. This review of the literature describes the frequency, clinical-pathological features and presenting symptoms of non-liver gastrointestinal metastases (GIm) from prostate cancer. Its purpose is to increase clinical awareness of the increasing incidence of such GIm, contributing to the early detection, accurate diagnosis and, when feasible, appropriate management.

  19. Gastrointestinal factors in autistic disorder: a critical review.

    PubMed

    Erickson, Craig A; Stigler, Kimberly A; Corkins, Mark R; Posey, David J; Fitzgerald, Joseph F; McDougle, Christopher J

    2005-12-01

    Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

  20. Thyroid Gland Malignancies.

    PubMed

    Cabanillas, Maria E; Dadu, Ramona; Hu, Mimi I; Lu, Charles; Gunn, Gary Brandon; Grubbs, Elizabeth G; Lai, Stephen Y; Williams, Michelle D

    2015-12-01

    Surgery remains the most important effective treatment for differentiated (DTC) and medullary thyroid cancer (MTC). Radioactive iodine (RAI) is another important treatment but is reserved only for DTC whose disease captures RAI. Once patients fail primary therapy, observation is often recommended, as most DTC and MTC patients will have indolent disease. However, in a fraction of patients, systemic therapy must be considered. In recent decades 4 systemic therapies have been approved by the United States FDA for DTC and MTC. Sorafenib and lenvatinib are approved for DTC and vandetanib and cabozantinib for MTC. Anaplastic thyroid cancer (ATC) is a rare and rapidly progressive form of thyroid cancer with a very high mortality rate. Treatment of ATC remains a challenge. Most patients are not surgical candidates at diagnosis due to advanced disease. External beam radiation and radiosensitizing radiation are the mainstay of therapy at this time. However, exciting new drugs and approaches to therapy are on the horizon but it will take a concerted, worldwide effort to complete clinical trials in order to find effective therapies that will improve the overall survival for this devastating disease.

  1. XYY male and hematologic malignancy.

    PubMed

    Oguma, N; Shigeta, C; Kamada, N

    1996-09-01

    Two cases of XYY male with refractory anemia with excess of blasts are reported, and previous reported XYY males with hematologic malignancy are reviewed. Altogether 26 cases were collected for analysis: acute myeloid leukemia (10), acute lymphocytic leukemia (seven), acute leukemia (two), chronic myelocytic leukemia (three), myelodysplastic syndrome (three), and essential thrombocythemia (one). The age at the time of diagnosis ranged in age from 7.5 to 81 years. In three of six XYY/XY mosaicism cases, XYY clone was associated with malignancy. However, in two cases XYY clone was not involved. The evidence presented here suggests that the event of an XYY male with hematologic malignancy is incidental rather than a genetic etiology.

  2. Cyclosporin-A associated malignancy

    PubMed Central

    Durnian, Jonathan M; Stewart, Rosalind MK; Tatham, Richard; Batterbury, Mark; Kaye, Stephen B

    2007-01-01

    The use of cyclosporin is well established within the ophthalmology community, especially against sight threatening intraocular inflammation. It is well known however, that immunosuppression in general is a risk factor for the development of malignancy and numerous studies point to the risk imposed by cyclosporin. This article analyses and reviews all relevant studies with regard to the development of malignancy associated with the use of cyclosporin and extrapolates this into the ophthalmic setting. This is to enable clinicians to assess the risks in individual patients and to present a monitoring regime which can be used in patients undergoing cyclosporin treatment. The review is solely concerned with the risk of the development of malignancy following cyclosporin immunosuppression and not with any other adverse effect. PMID:19668519

  3. Eosinophilic Dermatosis of Hematologic Malignancy.

    PubMed

    Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

    2017-03-22

    Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients.

  4. Performance and Clinical Role of Endoscopic Ultrasound Fine Needle Aspiration for Diagnosing Gastrointestinal Intramural Lesions

    PubMed Central

    Sung, Hea Jung; Park, Eun Young; Moon, Sung Jin; Lim, Chul Hyun; Kim, Jin Su; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gyu; Choi, Kyu Yong

    2013-01-01

    Background/Aims We evaluated the performance, clinical role, and diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in gastrointestinal intramural lesions. Methods Procedural and pathologic data were reviewed from consecutive patients undergoing EUS-FNA for intramural lesions. Final diagnoses were determined by surgical histopathologic conformation and the diagnosis of malignancy, including clinical follow-up with repeat imaging. Results Forty-six patients (mean age, 47 years; 24 males) underwent EUS-FNA. Lesions were located in the stomach (n=31), esophagus (n=5), and duodenum (n=10). The median lesion size was 2 cm (range, 1 to 20.6). Final diagnoses were obtained in 22 patients (48%). EUS-FNA was diagnostic in 40 patients (87%). The diagnostic accuracy of cytology for differentiating between benign and malignant lesions was 82%; diagnostic error occurred in three patients (6%). The cytologic results influenced clinical judgment in 78% cases. The primary reasons for negative or no clinical impact were false-negative results, misdirected patient management, and inconclusive cytology. Conclusions EUS-FNA exhibited an 87% diagnostic yield for gastrointestinal intramural lesions; the accuracy of cytology for differentiating malignancy was 82%. The limitations of EUS-FNA were primarily because of nondiagnostic sampling (9%) and probable diagnostic error (6%); these factors may influence the clinical role of EUS-FNA. PMID:24340255

  5. Report from the 13th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; September 8–10, 2011

    PubMed Central

    Vickers, M.M.; Pasieka, J.; Dixon, E.; McEwan, S.; McKay, A.; Renouf, D.; Schellenberg, D.; Ruether, D.

    2012-01-01

    The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8–10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer. PMID:23300370

  6. Second Malignant Neoplasms Following Radiotherapy

    PubMed Central

    Kumar, Sanath

    2012-01-01

    More than half of all cancer patients receive radiotherapy as a part of their treatment. With the increasing number of long-term cancer survivors, there is a growing concern about the risk of radiation induced second malignant neoplasm [SMN]. This risk appears to be highest for survivors of childhood cancers. The exact mechanism and dose-response relationship for radiation induced malignancy is not well understood, however, there have been growing efforts to develop strategies for the prevention and mitigation of radiation induced cancers. This review article focuses on the incidence, etiology, and risk factors for SMN in various organs after radiotherapy. PMID:23249860

  7. [Kinase inhibitors against hematological malignancies].

    PubMed

    Tojo, Arinobu

    2014-06-01

    Dysregulation of protein phosphorylation, especially on tyrosine residues, plays a crucial role in development and progression of hematological malignancies. Since remarkable success in imatinib therapy of CML and Ph+ALL, extensive efforts have made to explore candidate molecular targets and next breakthrough drugs. Now that next generation ABL kinase inhibitors are available for CML, the therapeutic algorithm has been revolutionized. As for AML and lymphoid malignancies, many kinase inhibitors targeting FLT3, BTK and aurora-A are on early and late clinical trials, and a number of promising drugs including ibrutinib are picked up for further evaluation.

  8. What Are the Risk Factors for Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... Gastrointestinal Stromal Tumors Be Prevented? Gastrointestinal Stromal Tumor (GIST) Causes, Risk Factors, and Prevention What Are the ... few known risk factors for gastrointestinal stromal tumors (GISTs). Being older These tumors can occur in people ...

  9. What Happens After Treatment for Gastrointestinal Stromal Tumor?

    MedlinePlus

    ... Tumor Is No Longer Working Gastrointestinal Stromal Tumor (GIST) After Treatment What Happens After Treatment for Gastrointestinal ... For some people with a gastrointestinal stromal tumor (GIST), treatment may remove or destroy the cancer. Completing ...

  10. What Are the Key Statistics about Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... About Gastrointestinal Stromal Tumor What Are the Key Statistics About Gastrointestinal Stromal Tumors? Gastrointestinal stromal tumors (GISTs) ... They are slightly more common in men. Survival statistics for GIST are discussed in “ Survival rates for ...

  11. Upper gastrointestinal hemorrhage caused by superwarfarin poisoning

    PubMed Central

    Zhao, Shu-Lei; Li, Peng; Ji, Ming; Zong, Ye; Zhang, Shu-Tian

    2010-01-01

    Superwarfarins are a class of rodenticides. Gastrointestinal hemorrhage is a fatal complication of superwarfarin poisoning, requiring immediate treatment. Here, we report a 55-year-old woman with tardive upper gastrointestinal hemorrhage caused by superwarfarin poisoning after endoscopic cold mucosal biopsy. PMID:20355251

  12. Upper gastrointestinal fiberoptic endoscopy in pediatric patients.

    PubMed

    Prolla, J C; Diehl, A S; Bemvenuti, G A; Loguercio, S V; Magalhães, D S; Silveira, T R

    1983-11-01

    Upper gastrointestinal fiberendoscopy in pediatric patients is done safely and under local anesthesia in most instances. This study of 47 children confirmed the value of fiberendoscopy in establishing the etiology of upper gastrointestinal hemorrhage and the presence of esophageal varices. It also contributed significantly to the management of patients with disphagia, pyrosis, epigastric pain, and ingestion of foreign bodies. No significant morbidity was caused.

  13. The Nervous System and Gastrointestinal Function

    ERIC Educational Resources Information Center

    Altaf, Muhammad A.; Sood, Manu R.

    2008-01-01

    The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

  14. Skull metastasis from rectal gastrointestinal stromal tumours.

    PubMed

    Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica

    2009-09-01

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach.

  15. Gastric gastrointestinal stromal tumor with incomplete duplication cyst - a case with possibility of neoplasia in fetal-period malformed tissues.

    PubMed

    Lewitowicz, Piotr; Matykiewicz, Jaroslaw; Koziel, Dorota; Gluszek, Stanislaw Z; Sosnowski, Zbigniew; Horecka-Lewitowicz, Agata; Nasierowska-Guttmejer, Anna

    2015-03-01

    The coincidence of GIST and other gastric malignancies are documented well but arising GIST from congenital anomalies is still rarity in literature. To date, only a few papers have been concerned on the possibility of arising neoplasms from duplication cyst of gastrointestinal tract. There, are dominating usual cancers, neuroendocrine cancers or lymphomas but GIST has been noted only once. Here, we report a case of 73 years old female-patient with typical gastric stromal tumor comprised centrally locked an incomplete duplication cyst.

  16. Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency.

    PubMed

    Laszewski, M J; Kemp, J D; Goeken, J A; Mitros, F A; Platz, C E; Dick, F R

    1990-09-01

    The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.

  17. A case of a pseudo colonic mass causing gastrointestinal bleeding in a patient with a left ventricular assist device

    PubMed Central

    Huntington, Justin T.; Plews, Robert L.; Mansfield, Sara A.; Drosdeck, Joseph M.; Evans, David C.

    2016-01-01

    There are many complications associated with the left ventricular assist devices (LVADs), including gastrointestinal bleeding (GIB). We present a case of a pseudo colonic mass visualized on colonoscopy during workup for GIB in an LVAD patient necessitating a right colectomy with final pathology negative for malignancy. A review of the literature in regards to the pathology, diagnosis, and treatment of this interesting condition is included. PMID:27722118

  18. Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2017-03-28

    Adenocarcinoma of the Gastroesophageal Junction; Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Cholangiocarcinoma; Recurrent Colorectal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Intestinal Carcinoma; Small Intestinal Adenocarcinoma; Stage III Colorectal Cancer; Stage III Gastric Cancer; Stage III Hepatocellular Carcinoma; Stage III Pancreatic Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Small Intestinal Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Small Intestinal Cancer; Stage IIIC Gastric Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Hepatocellular Carcinoma; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colorectal Cancer; Stage IVA Hepatocellular Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Hepatocellular Carcinoma; Stage IVB Pancreatic Cancer; Unresectable Pancreatic Carcinoma; Unresectable Small Intestinal Carcinoma

  19. Therapeutic Advances in Functional Gastrointestinal Disease: Irritable Bowel Syndrome

    PubMed Central

    Gaman, Alexandru; Bucur, Maria Cristina

    2009-01-01

    Reported prevalence rates of irritable bowel syndrome (IBS) are between 8% to 20% in the US general population with an average medical expenditure of US$1.35 billion direct and US$205 million indirect costs. Current pathophysiologic theories are based on abnormalities of both the brain and gut, thus setting a new stage for current and future therapeutic approaches. There are numerous treatment options in IBS acting centrally and peripherally by influencing motility and visceral sensitivity. Clinical evidence is variable; however, newer emerging treatments are being evaluated using better-designed clinical trials. Accurate assessment of IBS drug efficacy is still hampered by heterogeneity of the IBS population. Novel methods such as pharmacogenomics or brain imaging may be helpful in the future to better understand and characterize IBS patient subtypes, and this in turn will lead to more specific and efficient therapeutic options. Patient subpopulation measurement of side effects is also a clinical challenge and further understanding could improve treatment efficacy by enhancing the patient compliance. PMID:19936327

  20. Gastrointestinal Manifestations in Systemic Autoimmune Diseases

    PubMed Central

    COJOCARU, M.; COJOCARU, Inimioara Mihaela; SILOSI, Isabela; VRABIE, Camelia Doina

    2011-01-01

    ABSTRACT In an autoimmune disease, the immune system attacks and harms the body's own tissues. The systemic autoimmune diseases include collagen vascular diseases, the systemic vasculitides, Wegener granulomatosis, and Churg-Strauss syndrome. These disorders can involve any part of the gastrointestinal tract, hepatobiliary system and pancreas. They can cause a variety of gastrointestinal manifestations that are influenced by the pathophysiologic characteristics of the underlying disease process. There is a wide variation of gastrointestinal manifestations from these autoimmune disorders including, but not limited to: oral ulcers, dysphagia, gastroesophageal reflux disease, abdominal pain, constipation, diarrhea, fecal incontinence, pseudo-obstruction, perforation and gastrointestinal bleeding. Clinical workup should be initiated by the patient's subjective complaints. In this review, we analyze the effects of autoimmune diseases on the gastrointestinal tract. PMID:21977190

  1. What Happens after Treatment for Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... for Gastrointestinal Carcinoid Tumors? For some people with gastrointestinal (GI) carcinoid tumor, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. ...

  2. Gastrointestinal regulation of food intake

    PubMed Central

    Cummings, David E.; Overduin, Joost

    2007-01-01

    Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes. PMID:17200702

  3. Mast cells in gastrointestinal disorders.

    PubMed

    Bischoff, Stephan C

    2016-05-05

    Mast cells are constitutively found in the gastrointestinal (GI) tract. The three major physiological functions of GI mast cells comprise of - as far as we know - regulation of GI functions, namely epithelial and endothelial functions, crosstalk with the enteric nervous system, and contribution to the host defense against bacterial, viral and parasitic agents. A number of chronic GI diseases, including inflammatory bowel disease (Crohn's disease, ulcerative colitis), celiac disease, irritable bowel syndrome, and food allergies, are thought to be associated with mast cell hyperplasia and humoral activity. Clinical conditions characterized by a decrease in mast cell functionality are not known so far. In the present review, we summarize current evidence which show that human mast cells play a central role at the GI barrier, both in health and disease.

  4. Radiological Features of Gastrointestinal Lymphoma

    PubMed Central

    Lo Re, Giuseppe; Federica, Vernuccio; Midiri, Federico; Picone, Dario; La Tona, Giuseppe; Galia, Massimo; Lo Casto, Antonio; Lagalla, Roberto; Midiri, Massimo

    2016-01-01

    Gastrointestinal lymphomas represent 5–20% of extranodal lymphomas and mainly occur in the stomach and small intestine. Clinical findings are not specific, thus often determining a delay in the diagnosis. Imaging features at conventional and cross-sectional imaging must be known by the radiologist since he/she plays a pivotal role in the diagnosis and disease assessment, thus assisting in the choice of the optimal treatment to patients. This review focuses on the wide variety of imaging presentation of esophageal, gastric, and small and large bowel lymphoma presenting their main imaging appearances at conventional and cross-sectional imaging, mainly focusing on computed tomography and magnetic resonance, helping in the choice of the best imaging technique for the disease characterization and assessment and the recognition of potential complications. PMID:26819598

  5. Visceral Pain and Gastrointestinal Microbiome

    PubMed Central

    Chichlowski, Maciej; Rudolph, Colin

    2015-01-01

    A complex set of interactions between the microbiome, gut and brain modulate responses to visceral pain. These interactions occur at the level of the gastrointestinal mucosa, and via local neural, endocrine or immune activity; as well as by the production of factors transported through the circulatory system, like bacterial metabolites or hormones. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. There are critical sensitive periods that can impact visceral pain responses in adulthood. In this review we provide a brief background of the intestinal microbiome and emerging concepts of the bidirectional interactions between the microbiome, gut and brain. We also discuss recent work in animal models, and human clinical trials using prebiotics and probiotics that alter the microbiome with resultant alterations in visceral pain responses. PMID:25829337

  6. [Functional and motor gastrointestinal disorders].

    PubMed

    Mearin, Fermín; Rey, Enrique; Balboa, Agustín

    2015-09-01

    This article discusses the most interesting studies on functional and motor gastrointestinal disorders presented at Digestive Diseases Week (DDW), 2015. Researchers are still seeking biomarkers for irritable bowel syndrome and have presented new data. One study confirmed that the use of low-dose antidepressants has an antinociceptive effect without altering the psychological features of patients with functional dyspepsia. A contribution that could have immediate application is the use of transcutaneous electroacupuncture, which has demonstrated effectiveness in controlling nausea in patients with gastroparesis. New data have come to light on the importance of diet in irritable bowel syndrome, although the effectiveness of a low-FODMAP diet seems to be losing momentum with time. Multiple data were presented on the long-term efficacy of rifaximin therapy in patients with irritable bowel syndrome and diarrhoea. In addition, among other contributions, and more as a curiosity, a study evaluated the effect of histamine in the diet of patients with irritable bowel syndrome.

  7. Cutavirus in Cutaneous Malignant Melanoma

    PubMed Central

    Fridholm, Helena; Vinner, Lasse; Kjartansdóttir, Kristín Rós; Friis-Nielsen, Jens; Asplund, Maria; Herrera, Jose A.R.; Steiniche, Torben; Mourier, Tobias; Brunak, Søren; Willerslev, Eske; Izarzugaza, Jose M.G.; Hansen, Anders J.; Nielsen, Lars P.

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be investigated. PMID:28098541

  8. Malignant haemangioendothelioma involving the liver

    PubMed Central

    Pollard, Stella M.; Millward-Sadler, G. H.

    1974-01-01

    The features of four cases of malignant haemangioendothelioma involving the liver and other organs are described. Two cases were associated with a microangiopathic haemolytic anaemia. The nature of the tumours and possible pathogenesis for the anaemias are discussed. Images PMID:4832301

  9. The Origin of Malignant Malaria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

  10. Gastrointestinal manifestations in cystic fibrosis.

    PubMed

    Eggermont, E

    1996-08-01

    CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product that is defective in cystic fibrosis, is present in the apical membrane of the epithelial cells from the stomach to the colon. In the foregut, the clinical manifestations are not directly related to the primary defect of the CFTR chloride channel. The most troublesome complaints and symptoms originate from the oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal wall, the clinical expression of CF depends largely on the decreased secretion of fluid and chloride ions, the increased permeability of the paracellular space between adjacent enterocytes and the sticky mucous cover over the enterocytes. As a rule, the brush border enzyme activities are normal and there is some enhanced active transport as shown for glucose and alanine. The results of continuous enteral feeding of CF patients clearly show that the small intestinal mucosa, in the daily situation, is not functioning at maximal capacity. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, meconium ileus equivalent, intussusception, volvulus and silent appendicitis. In recent years colonic strictures, after the use of high-dose pancreatic enzymes, are being increasingly reported; the condition has recently been called CF fibrosing colonopathy. The CF gastrointestinal content itself differs mainly from the normal condition by the lower acidity in the foregut and the accretion of mucins and proteins, eventually resulting in intestinal obstruction, in the ileum and colon. Better understanding of the CF gastrointestinal phenotype may contribute to improvement of the overall wellbeing of these patients.

  11. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  12. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

    PubMed

    Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-02-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.

  13. [Gastrointestinal stromal tumors: report of a clinical case and review of the literature].

    PubMed

    Bronzino, P; Cassinelli, G; Arena, E; Rassu, P C; Partipilo, F; Rusca, I; Cuneo, A E; Casaccia, M

    2002-01-01

    In this case report, the Authors describe a case of stromal gastric tumour, in a male 65 years old, who presented gastrointestinal bleeding. Gastro-Intestinal Stromal Tumors (GISTs) are neoplasm with an incidence of 1-3 per cent of the digestive tract malignant neoplasms. The rarity of this disease, its visceral wall localization, the histopathological characteristics make the diagnosis difficult. Moreover there is no correlation between the behaviour of these neoplasms and the histologic features. Surgery represents the main treatment for GISTs based on complete resection, followed by a long-term follow-up. Chemotherapy and radiotherapy don't seem to play a crucial role in the treatment of these neoplasms. A new treatment with inhibitors of the tyrosinekinase is under discussion. Follow-up represents the only way to evaluate the effective behaviour of the disease, due to the lack of classic prognostic factors impact.

  14. The Influence of the Gut Microbiome on Obesity, Metabolic Syndrome and Gastrointestinal Disease

    PubMed Central

    Parekh, Parth J; Balart, Luis A; Johnson, David A

    2015-01-01

    There is a fine balance in the mutual relationship between the intestinal microbiota and its mammalian host. It is thought that disruptions in this fine balance contribute/account for the pathogenesis of many diseases. Recently, the significance of the relationship between gut microbiota and its mammalian host in the pathogenesis of obesity and the metabolic syndrome has been demonstrated. Emerging data has linked intestinal dysbiosis to several gastrointestinal diseases including inflammatory bowel disease, irritable bowel syndrome, nonalcoholic fatty liver disease, and gastrointestinal malignancy. This article is intended to review the role of gut microbiota maintenance/alterations of gut microbiota as a significant factor as a significant factor discriminating between health and common diseases. Based on current available data, the role of microbial manipulation in disease management remains to be further defined and a focus for further clinical investigation. PMID:26087059

  15. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  16. Long-term experience with (laterally) extended endopelvic resection (LEER) in relapsed pelvic malignancies.

    PubMed

    Höckel, Michael

    2015-03-01

    Gynecologic cancers recurring in the pelvis are generally advanced in malignant progression limiting curative treatment approaches. The cancer field theory links cancer progression to reversed morphogenesis and allows the exact anatomical delineation of the cancer field, i.e., the tissue compartment of potential tumor infiltration related to the tumor's ontogenetic stage. Cancer surgery is redefined with the resection of ontogenetic stage-related cancer fields instead of the mere removal of the malignant tumor with an uninvolved tissue margin. Most gynecologic pelvic malignancies recurring in the pelvis represent ontogenetic stages 3 and 4. (Laterally) extended endopelvic resection ((L)EER) has been designed to resect the cancer fields of gynecologic tumors in these advanced ontogenetic stages. This paper reports long-term experience with (L)EER for relapsed pelvic malignancies strongly supporting the cancer field theory and the principle and practice of cancer field resection.

  17. Development of the technique of terahertz pulse spectroscopy for diagnostic malignant tumors during gastrointestinal surgeries

    NASA Astrophysics Data System (ADS)

    Goryachuk, A. A.; Khodzitsky, M. K.; Borovkova, M. A.; Khamid, A. K.; Dutkinskii, P. S.; Shishlo, D. A.

    2016-08-01

    Samples of fresh excised tissues obtained from patients who had undergone gastric cancer have been investigated. Samples were consisted of cancer zone, normal zone and zone mixed of normal and cancer tissues. Their optical properties and spectral features were investigated by terahertz time-domain spectroscopy (TDS) in reflection mode. It was found that waveforms of reflected signals from normal and cancer tissues were well distinguished so it can be concluded that it is easy to discriminate gastric cancer tissue from normal by using THz TDS.

  18. Ion channels in gastrointestinal smooth muscle and interstitial cells of Cajal.

    PubMed

    Lyford, Gregory L; Farrugia, Gianrico

    2003-12-01

    A requirement for normal gastrointestinal motility is the tight regulation of ion channels expressed in interstitial cells of Cajal and smooth muscle. Interstitial cells of Cajal generate the slow wave and amplify neuronal signals; smooth muscle functions as the final effector organ. Recent advances in our understanding of the expression and mechano-regulation of these different subtypes of ion channels have allowed the development of hypotheses on how ion channels transduce a variety of inputs into electrical signals that directly or indirectly regulate gastrointestinal motor activity.

  19. Biologic response modifiers in gynecologic malignancies.

    PubMed Central

    Dutcher, J. P.; Wadler, S.; Wiernik, P. H.

    1988-01-01

    Biological therapy is currently being investigated in the treatment of a number of malignancies. The hypothesis for the use of this therapeutic modality involves an attempt to stimulate an already existent but perhaps suboptimal immune response to foreign protein, including tumor. Immunologic therapy appears to work best against small-volume disease, as indicated from animal studies. This condition is potentially achievable in advanced ovarian cancer, where surgery is capable of producing multi-log reduction in tumor mass, and thus immunotherapy may be an option in this disease. The attraction of biologic therapy in patients with ovarian cancer is the potential to treat relatively localized but often chemotherapy-resistant disease. In cervical cancer, the rationale for the use of interferon is somewhat different in that this disease may be a manifestation of a virally induced proliferative lesion. Thus, the antiviral properties of interferon are being investigated in both limited and advanced cervical cancer. Both of these hypothesis have pre-clinical data to support them. This paper presents the pre-clinical and clinical work currently available for consideration of future use. PMID:2461003

  20. Skin: A mirror of internal malignancy

    PubMed Central

    Vora, Rita V.; Kota, RahulKrishna S.; Diwan, Nilofar G.; Jivani, Nidhi B.; Gandhi, Shailee S.

    2016-01-01

    Skin manifestations are a reflection of many of the internal diseases. Sometimes, skin disease may be the only manifestation of the internal disease. Internal malignancies may give rise to a number of cutaneous manifestations through their immunological, metabolic, and metastatic consequences. Curth proposed criteria to establish a causal relationship between a dermatosis and a malignant internal disease. Malignancy can present with a plethora of cutaneous manifestations. Here, we describe in brief about various skin manifestations of internal malignancies. PMID:28144085

  1. Detection of gastrointestinal bleeding by radionuclide scintigraphy

    SciTech Connect

    Gupta, S.; Luna, E.; Kingsley, S.; Prince, M.; Herrera, N.

    1984-01-01

    Scanning with Technetium /sup 99m/ labeled autologous red blood cells was performed in 59 patients with clinical suspicion of acute and/or intermittent, chronic gastrointestinal bleeding. In 36 patients (61%), a definite site of bleeding could be demonstrated. A strong correlation with other modalities such as upper and lower gastrointestinal endoscopy, contrast angiography, and surgical exploration was found. Overall sensitivity of the procedure was 91%; specificity 100% and accuracy 93.3%. It is suggested that radionuclide scintigraphy provides a completely noninvasive, simple, and sensitive procedure which may be routinely used for the detection and localization of gastrointestinal bleeding.

  2. A Giant Brunneroma Causing Gastrointestinal Bleeding and Severe Anemia Requiring Transfusion and Surgery

    PubMed Central

    Laclé, Miangela M.; Borel Rinkes, Inne H. M.

    2017-01-01

    Brunner's gland hamartoma, also called hyperplasia, adenoma, and Brunneroma, is an extremely rare benign proliferative lesion of Brunner's glands in the duodenum. While being mostly small and asymptomatic, they can result in gastrointestinal bleeding and obstruction. We report the case of a 54-year-old man presenting with melena and severe anemia requiring blood transfusion. CT scans showed a large mass of 8 cm in diameter, presumably arising in the duodenum. Endoscopic biopsies were not conclusive. As we were unable to determine the nature of the mass preoperatively and due to the severe symptoms, its size, and the uncertain malignant potential, a classic Whipple procedure was performed. The resected specimen showed extensive proliferation of Brunner's glands without signs of malignancy. PMID:28299229

  3. A Giant Brunneroma Causing Gastrointestinal Bleeding and Severe Anemia Requiring Transfusion and Surgery.

    PubMed

    Frenkel, Nicola C; Laclé, Miangela M; Borel Rinkes, Inne H M; Molenaar, Izaak Q; Hagendoorn, Jeroen

    2017-01-01

    Brunner's gland hamartoma, also called hyperplasia, adenoma, and Brunneroma, is an extremely rare benign proliferative lesion of Brunner's glands in the duodenum. While being mostly small and asymptomatic, they can result in gastrointestinal bleeding and obstruction. We report the case of a 54-year-old man presenting with melena and severe anemia requiring blood transfusion. CT scans showed a large mass of 8 cm in diameter, presumably arising in the duodenum. Endoscopic biopsies were not conclusive. As we were unable to determine the nature of the mass preoperatively and due to the severe symptoms, its size, and the uncertain malignant potential, a classic Whipple procedure was performed. The resected specimen showed extensive proliferation of Brunner's glands without signs of malignancy.

  4. Malignant melanoma of the foot and ankle.

    PubMed

    John, K J; Hayes, D W; Green, D R; Dickerson, J

    2000-04-01

    Malignant melanoma is a serious and devastating skin disease that podiatrists may be called upon to treat. It is pertinent that delays in diagnosis and treatment of malignant melanoma be avoided. Some of the topics discussed in this article are causes, clinical features, classification, and treatment of malignant melanoma, focusing on the foot and ankle.

  5. Abnormal activated partial thromboplastin time and malignancy.

    PubMed

    Delicata, M; Hambley, H

    2011-08-01

    Malignancy often results in clotting abnormalities. The aetiology of haemostasis problems in cancer is complex, and is still not completely understood. We describe a case of a patient with malignant mesothelioma, who was found to have elevated activated partial thromboplastin time, due to lupus anticoagulant. We suggest that patients with malignancy should have their coagulation checked prior to any invasive procedures.

  6. Malignant Transformation of Pulmonary Benign Metastasizing Leiomyoma

    PubMed Central

    Song, Kyung Sub; Keum, Dong Yoon; Hwang, Il Seon

    2017-01-01

    Pulmonary benign metastasizing leiomyoma (PBML) is defined as metastasis of a leiomyoma to lung tissue. It was first reported in 1937. P BML is known as a benign disease, but can undergo malignant transformation. Only 1 case of the malignant transformation of PBML to leiomyosarcoma has been reported previously. In this report, we present a case of malignant transformation of PBML. PMID:28180107

  7. Recent advances in dermoscopy

    PubMed Central

    Russo, Teresa; Piccolo, Vincenzo; Lallas, Aimilios; Argenziano, Giuseppe

    2016-01-01

    The use of dermoscopy has offered a new morphological dimension of skin lesions and has provided an effective diagnostic tool to differentiate melanoma from other benign or malignant skin tumors but also to support the clinical diagnosis in general dermatology. The aim of this article is to provide an overview of the most recent and important advances in the rising world of dermoscopy. PMID:26949523

  8. Pharmacology and physiology of gastrointestinal enteroendocrine cells

    PubMed Central

    Mace, O J; Tehan, B; Marshall, F

    2015-01-01

    Gastrointestinal (GI) polypeptides are secreted from enteroendocrine cells (EECs). Recent technical advances and the identification of endogenous and synthetic ligands have enabled exploration of the pharmacology and physiology of EECs. Enteroendocrine signaling pathways stimulating hormone secretion involve multiple nutrient transporters and G protein-coupled receptors (GPCRs), which are activated simultaneously under prevailing nutrient conditions in the intestine following a meal. The majority of studies investigate hormone secretion from EECs in response to single ligands and although the mechanisms behind how individual signaling pathways generate a hormonal output have been well characterized, our understanding of how these signaling pathways converge to generate a single hormone secretory response is still in its infancy. However, a picture is beginning to emerge of how nutrients and full, partial, or allosteric GPCR ligands differentially regulate the enteroendocrine system and its interaction with the enteric and central nervous system. So far, activation of multiple pathways underlies drug discovery efforts to harness the therapeutic potential of the enteroendocrine system to mimic the phenotypic changes observed in patients who have undergone Roux-en-Y gastric surgery. Typically obese patients exhibit ∼30% weight loss and greater than 80% of obese diabetics show remission of diabetes. Targeting combinations of enteroendocrine signaling pathways that work synergistically may manifest with significant, differentiated EEC secretory efficacy. Furthermore, allosteric modulators with their increased selectivity, self-limiting activity, and structural novelty may translate into more promising enteroendocrine drugs. Together with the potential to bias enteroendocrine GPCR signaling and/or to activate multiple divergent signaling pathways highlights the considerable range of therapeutic possibilities available. Here, we review the pharmacology and physiology of

  9. Imaging of malignancies of the biliary tract- an update

    PubMed Central

    2014-01-01

    Malignancies of the biliary tract include cholangiocarcinoma, gallbladder cancers and carcinoma of the ampulla of Vater. Biliary tract adenocarcinomas are the second most common primary hepatobiliary cancer. Due to their slow growing nature, non-specific and late symptomatology, these malignancies are often diagnosed in advanced stages with poor prognosis. Apart from incidental discovery of gall bladder carcinoma upon cholecystectomy, early stage biliary tract cancers are now detected with computed tomography (CT) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP). Accurate characterization and staging of these indolent cancers will determine outcome as majority of the patients’ are inoperable at the time of presentation. Ultrasound is useful for initial evaluation of the biliary tract and gallbladder masses and in determining the next suitable modality for further evaluation. Multimodality imaging plays an integral role in the management of the biliary tract malignancies. The imaging techniques most useful are MRI with MRCP, endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and positron emission tomography (PET). In this review we will discuss epidemiology and the role of imaging in detection, characterization and management of the biliary tract malignancies under the three broad categories of cholangiocarcinomas (intra- and extrahepatic), gallbladder cancers and ampullary carcinomas. PMID:25608662

  10. Intercellular communication in malignant pleural mesothelioma: properties of tunneling nanotubes

    PubMed Central

    Ady, Justin W.; Desir, Snider; Thayanithy, Venugopal; Vogel, Rachel I.; Moreira, André L.; Downey, Robert J.; Fong, Yuman; Manova-Todorova, Katia; Moore, Malcolm A. S.; Lou, Emil

    2014-01-01

    Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs). TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined changes in TnT length over time in comparison to cell proliferation. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo. PMID:25400582

  11. Idiopathic Inflammatory Myopathies and Malignancy: a Comprehensive Review.

    PubMed

    Tiniakou, Eleni; Mammen, Andrew L

    2017-02-01

    The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases (collectively known as myositis) affecting the skeletal muscles as well as other organ systems such as skin, lungs, and joints. The primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and immune-mediated necrotizing myopathy (IMNM). Patients with these diseases experience progressive proximal muscle weakness, have characteristic muscle biopsy findings, and produce autoantibodies that are associated with unique clinical features. One distinguishing feature of these patients is that they are also known to have an increased risk of cancer. Since the first description of the association in 1916, it has been extensively reported in the medical literature. However, there have been significant variations between the different studies with regard to the degree of cancer risk in patients with IIM. These discrepancies can, in part, be attributed to differences in the definition of malignancy-associated myositis used in different studies. In recent years, significant advances have been made in defining specific features of IIM that are associated with the development of malignancy. One of these has been myositis-specific antibodies (MSAs), which are linked to distinct clinical phenotypes and categorize patients into groups with more homogeneous features. Indeed, patients with certain MSAs seem to be at particularly increased risk of malignancy. This review attempts a systematic evaluation of research regarding the association between malignancy and myositis.

  12. Epidemiological Survey of Sinonasal Malignancy in North-East Iran

    PubMed Central

    Poursadegh, Mehdi; Poursadegh, Farid; Esmaeili, Majid; Bakhshaee, Mehdi

    2015-01-01

    Introduction: Sinonasal malignancies are uncommon neoplasms with several histological subtypes. These malignancies have a poor prognosis and, because of the nonspecific nature of the symptoms, most patients are diagnosed late when the disease is already at an advanced stage. Therefore, most sinonasal malignancies tend to be treated with surgery and postoperative radiotherapy. Understanding the incidence and prevalence of clinical symptoms, pathology, diagnosis, and subsequent prognosis of the disease is important for early diagnosis. Materials and Methods: Medical records of patients with a confirmed diagnosis of sinonasal malignancy in a tertiary referral center from 1998 to 2009 were retrospectively investigated by chronological examination. Information relating to symptoms, pathology, and treatment of patients were collected from the checklists and used to generate tables and graphs, while descriptive statistical tests were used to compare data. Results: The records of 69 patients were examined, including 45 (65.2%) male and 24 (34.8%) female patients with a combined mean age of 54.07±16.04 years. Twenty-one patients (30.4%) were aged less than 45 years and 48 (69.6%) were more than 45 years of age. The most common symptom was facial swelling in 46 (66.6%) patients and the most common kind of tumor was squamous cell carcinoma in 28 (40.6%) patients. The primary location of the tumor in most patients was the maxillary sinus (54 patients; 78.3%). A majority of patients present in advanced stage (stage III or more) with intraorbital (39.1%) or intracranial (4.3%) involvement, or regional lymphatic (28.99%) or distance metastasis (7.2%). The most common treatment was surgery (17 patients; 24.6%). Conclusion: Due to their nonspecific symptoms, most sinonasal malignancies are diagnosed at an advanced stage of the disease. Therefore, all patients with nonspecific symptoms, especially older males, should be evaluated for sinonasal malignancies in order to

  13. Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

    SciTech Connect

    Yadav, Budhi S. Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

    2009-04-01

    Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

  14. Isocitrate dehydrogenase mutations in myeloid malignancies

    PubMed Central

    Medeiros, B C; Fathi, A T; DiNardo, C D; Pollyea, D A; Chan, S M; Swords, R

    2017-01-01

    Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (also called the ‘citric acid' or Krebs) cycle. Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Mutant IDH enzymes have neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. The prognostic significance of mutant IDH (mIDH) is controversial but appears to be influenced by co-mutational status and the specific location of the mutation (IDH1-R132, IDH2-R140, IDH2-R172). Treatments specifically or indirectly targeted to mIDH are currently under clinical investigation; these therapies have been generally well tolerated and, when used as single agents, have shown promise for inducing responses in some mIDH patients when used as first-line treatment or in relapsed or refractory AML or MDS. Use of mIDH inhibitors in combination with drugs with non-overlapping mechanisms of action is especially promising, as such regimens may address the clonal heterogeneity and the multifactorial pathogenic processes involved in mIDH myeloid malignancies. Advances in mutational analysis have made testing more rapid and convenient, and less expensive; such testing should become part of routine diagnostic workup and repeated at

  15. Malignant change in dermatitis artefacta.

    PubMed Central

    Alcolado, J. C.; Ray, K.; Baxter, M.; Edwards, C. W.; Dodson, P. M.

    1993-01-01

    Dermatitis artefacta is a chronic skin lesion produced by self-trauma. Avoidance of further trauma, topical steroids and psychological therapy all play a part in the treatment of such lesions. Unresolved lesions may become large and disfiguring and subject to infection. We report a case of one such lesion in an elderly woman who persistently excoriated a cholecystectomy scar over 40 years. Malignant transformation occurred in a manner analogous to the neoplastic change observed in other types of chronic ulcer (Marjolin's ulcer). The squamous cell carcinoma presented with widespread metastases from which the patient eventually died. Recent literature concerning Marjolin's ulcers is reviewed and it is noted that this is the first reported case of death caused by malignant change in dermatitis artefacta. Images Figure 1 PMID:8234114

  16. The diagnostic value of endoscopic ultrasonography and contrast-enhanced harmonic endoscopic ultrasonography in gastrointestinal stromal tumors

    PubMed Central

    Zhao, Yanchao; Qian, Linxue; Li, Peng; Zhang, Shutian

    2016-01-01

    Objective: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) and contrast-enhanced harmonic (CEH) EUS in patients with gastrointestinal stromal tumors (GISTs). Patients and Methods: About 19 patients with suspected GISTs underwent EUS and CEH-EUS before tumor resection. The malignant potential was assessed according to the modified Fletcher classification system. Patients were divided into lower (Group I) and higher (Group II) malignant potential group. The clinical characteristics and EUS/CEH-EUS features were compared between two groups. Results: The tumor size in Group II was significantly larger than that in Group I (14.6 ± 5.8 mm vs. 32.1 ± 8.4 mm, P < 0.05). Heterogeneous echogenicity was observed in 4 (4/8) cases in Group II and none in Group I (P < 0.05). Irregular intratumoral vessels were detected in 6 cases in Group II and none in Group I (P < 0.05). The sensitivity and specificity of irregular vessel detection for discriminating higher from lower malignant potential GISTs were 75% and 100%, respectively. The positive predictive value and negative predictive value of detection of irregular vessels to high malignant potential GISTs were 33% and 100%, respectively. Conclusion: Detection of irregular intratumoral vessels can predict higher malignant potential before tumor resection. The tumor size and echogenicity are assistant factors for malignant potential assessment. Endoscopic resection is an efficacious treatment with good security for appropriate patients. PMID:27080610

  17. [Malignant fibrous histiocytoma. Case report].

    PubMed

    Morlino, A; Rossi, M T; Fabrizio, T; Scutari, F

    2010-03-01

    Malignant fibroous histiocytoma (MFH) is an aggressive soft tissue sarcoma, that most frequently occurs in the muscles of the extremities and in abdominal or in retroperitoneal space of young adults. It is seldom confined to the skin and subcutaneous tissue. It is rarely diagnosed before excision and pathological exam, and has an unfavorable prognostic in some cases. This work reports the case of a 94 years old patient with originally cutaneous MFH stressing the importance of the early diagnosis.

  18. Endobronchial metastases from extrathoracic malignancies.

    PubMed

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, Oğuz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient.

  19. 21 CFR 876.1725 - Gastrointestinal motility monitoring system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gastrointestinal motility monitoring system. 876... Gastrointestinal motility monitoring system. (a) Identification. A gastrointestinal motility monitoring system is a... esophageal motility monitor and tube, the gastrointestinal motility (electrical) system, and...

  20. 21 CFR 876.1725 - Gastrointestinal motility monitoring system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastrointestinal motility monitoring system. 876... Gastrointestinal motility monitoring system. (a) Identification. A gastrointestinal motility monitoring system is a... esophageal motility monitor and tube, the gastrointestinal motility (electrical) system, and...