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      The significance of a nineteenth century definition in the era of genomics: linitis plastica

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          Abstract

          Background

          Linitis plastica due to gastric adenocarcinoma is a condition with a long history, but still lacks a standardized definition and is commonly confused with Borrmann type IV, Lauren diffuse, and signet-cell type gastric cancer. The absence of a clear definition is a problem when investigating its biological characteristics and role as a possible independent factor for prognosis. Nevertheless, the biological behavior for linitis plastica, which is unique, may be valuable in risk stratification and have implications for treatment. A definition of linitis plastica based on molecular or genomic criteria could represent a useful starting point for investigating new targeted therapies.

          Main body

          This literature review of linitis plastica will focus on the current classifications for gastric cancer, illustrating how the concept of linitis plastica relates to them in most cases and identifying a clear and reproducible definition. Moreover, the review will highlight the diagnostic challenges associated with linitis plastica, its prognostic implications, and the therapeutic options available. Future perspectives for its management are also addressed.

          Conclusion

          Linitis plastica is a carcinoma with a scirrhous stroma, involving the submucosal and muscular layers of the stomach even in the absence of mucosal alteration. In most cases, the primary cancer cells are signet-ring cells or scattered cells in the context of a poorly differentiated carcinoma. Diagnosis is challenging. Staging should be thorough, including diagnostic laparoscopy in all cases due to the high incidence of peritoneal involvement. The prognostic significance of linitis plastica is still controversial. Curative-intent surgery, when feasible, should be performed, with a multimodality treatment approach. Cancer-stroma interactions are important features of this disease, and represent attaining potential target for future therapies. Future pathologic assessments of gastric cancer should report the stromal reaction in order to allow better characterization of the tumor.

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          Most cited references69

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          Tumors: wounds that do not heal-redux.

          H F Dvorak (2015)
          Similarities between tumors and the inflammatory response associated with wound healing have been recognized for more than 150 years and continue to intrigue. Some years ago, based on our then recent discovery of vascular permeability factor (VPF)/VEGF, I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound-healing response to induce the stroma they required for maintenance and growth. Work over the past few decades has supported this hypothesis and has put it on a firmer molecular basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and wounds that includes the following: increased vascular permeability; extravasation of plasma, fibrinogen and other plasma proteins; activation of the clotting system outside the vascular system; deposition of an extravascular fibrin gel that serves as a provisional stroma and a favorable matrix for cell migration; induction of angiogenesis and arterio-venogenesis; subsequent degradation of fibrin and its replacement by "granulation tissue" (highly vascular connective tissue); and, finally, vascular resorption and collagen synthesis, resulting in the formation of dense fibrous connective tissue (called "scar tissue" in wounds and "desmoplasia" in cancer). A similar sequence of events also takes place in a variety of important inflammatory diseases that involve cellular immunity. ©2015 American Association for Cancer Research.
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            Clinicopathological Variation of Lauren Classification in Gastric Cancer.

            The investigation of prognostic factor for gastric cancer is still desirable because of dismal prognosis in gastric cancer. Lauren's classification is currently a useful histological classification. There are few large series evaluating the prognostic significance of Lauren's classification in gastric cancer. From January 1987 to December 2013, a total of 3071 patients received gastrectomy for gastric cancer. According Lauren's classification, 1423(46.3%) patients were intestinal type, 1000 patients (32.6%) were diffuse type, and 648 patients (21.1%) were mixed type. The clinicopathological characteristics and prognosis in Lauren's classification were analyzed in these patients. Our results showed that patients with intestinal type gastric cancer (57.7%) had a better 5-year overall survival than diffuse type (45.6%) and mixed type (43.4%, P < 0.001). The clinicopathological characteristics showed that gastric cancer patients with intestinal type were older (P < 0.001), male predominant (P < 0.001), smaller tumor size (P < 0.001), distal stomach predominant (P < 0.001), relative well differentiated (P < 0.001), less advanced Borrmann type (P < 0.001), less scirrhous type stromal reaction(P < 0.001), less infiltrating type of Ming's histology type(P < 0.001), less tumor invasion depth and less lymphovascular invasion (P < 0.001). Multivariate analysis with overall survival as an endpoint showed that age (P = 0.005), Borrmann classification (P < 0.001), pathological T category (P = 0.023), pathological N category (P < 0.001) and Lauren's classification (P = 0.003) were significant correlated in gastric cancer. Lauren's classification is an independent prognostic factor in gastric cancer patient undergoing gastrectomy. Lauren's classification can serve as a prognostic marker for gastric cancer patient receiving gastrectomy. The clinicopathological appearance and prognosis of mixed type gastric cancer is similar to diffuse type gastric cancer.
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              Tranilast: a review of its therapeutic applications.

              Tranilast (N-[3',4'-dimethoxycinnamoyl]-anthranilic acid) is an analog of a tryptophan metabolite. Initially, tranilast was identified as an anti-allergic agent, and used in the treatment of inflammatory diseases, such as bronchial asthma, atypical dermatitis, allergic conjunctivitis, keloids and hypertrophic scars. Subsequently, the results showed that it could be also effective in the management of a wide range of conditions. The beneficial effects of tranilast have also been seen in a variety of disease states, such as fibrosis, proliferative disorders, cancer, cardiovascular problems, autoimmune disorders, ocular diseases, diabetes and renal diseases. Moreover, several trials have shown that it has very low adverse effects and it is generally well tolerated by patients. In this review, we have attempted to accurately summarize previously published studies relating to the use of tranilast for a range of disorders and discuss the drug's possible mode of action. The major mode of the drug's efficacy appears to be the suppression of the expression and/or action of the TGF-β pathway, but the drug affects other factors as well. The findings presented in this review demonstrate the potential of tranilast for the control of a vast array of pathological situations, furthermore, it is a prescribed drug without severe side effects.
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                Author and article information

                Contributors
                (713) 563-0766 , bbadgwell@mdanderson.org
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                5 July 2017
                5 July 2017
                2017
                : 15
                : 123
                Affiliations
                [1 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Surgical Oncology, , The University of Texas MD Anderson Cancer Center, ; Unit 1484, 1515 Holcombe Blvd., Houston, TX 77030 USA
                [2 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Pathology, , The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                Article
                1187
                10.1186/s12957-017-1187-3
                5498981
                28679451
                5ea08985-437e-4f2a-a5d6-63c182b8f927
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 December 2016
                : 22 June 2017
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Surgery
                gastric cancer,linitis plastica,borrmann type iv,scirrhous carcinoma,diffuse,signet ring
                Surgery
                gastric cancer, linitis plastica, borrmann type iv, scirrhous carcinoma, diffuse, signet ring

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