Gastro Education

Ricardo Escalante studied medicine at the Universidad de Los Andes 1979. Postgraduate in General Surgery at the Military Hospital “Dr. Arlos Arvelo “UCV1984. Postgraduate of Coloproctologist Surgeon of the Federal University of São Paulo, Brazil. Marketing Specialist UCV. Master’s Degree in Health Management IESA. He entered the MCP in 1987 and graduated in 1994. He started as an intern in the Military Hospital “Dr. Carlos Arvelo” until becoming Deputy Surgery Service and Emergency Head of Adults, doing teaching activity in the Postgraduate Surgery attached to the UCV. He is the President of the Venezuelan Society of Coloproctology. Currently, he is Director of the International Advisory Committee of the International Society of University Colon & Rectal Surgeons. Enter as Lieutenant and arrive to Colonel of the Army Force of Venezuela,

retired in 2005.

Diverticulosis of the colon is the most frequent structural alteration of the colon diagnosed at colonoscopy. It describes the presence of diverticula without any endoscopic sign of inflammation or clinical symptom and it becomes ‘diverticular disease’ (DD) if symptoms develop. DD of the colon is not only a growing clinical problem for national health systems since its prevalence is high in developed countries, but also it is increasing in countries where it was thought to be lower. To date, there is no consensus about the proper classification of DD. Some classifications are based on imaging, i.e. appearance of the disease at abdominal computerized tomography (CT) (e.g. Buckey, Ambrosetti or Hinchey’s modified classification). Other classifications focus on clinical features of DD (e.g. the classification of the Scientific Committee of the European Association for Endoscopic Surgery, Sheth classification and, in particular, the Hansen-Stock classification which is widely used in northern Europe). An endoscopic classification of diverticulosis and DD has only been developed recently. This is surprising if we consider the high number of colonoscopies performed worldwide, that diverticulosis is the most frequently recognized alteration at colonoscopy and that endoscopic signs of diverticular inflammation are found in 0.48–1.7% of patients undergoing colonoscopy. Furthermore, some characteristics of the colon harboring diverticula have already been identified as predictive of the outcome of the disease. For example, radiology has shown diverticulosis extension as one of the strongest predictors of recurrence of diverticulitis. However, little is known whether specific endoscopic findings are able to influence the outcome of DD, and patients may differ from each other. For example, having scattered sigmoid diverticula may be different from having diffuse diverticulosis and rigidity of the colon at inflation, but whether this difference has a prognostic significance is little known. We recently implemented and validated a more specific endoscopic classification of DD of the colon: Diverticular Inflammation and Complication Assessment (DICA).  DICA classification takes into account few endoscopic findings of the colon with diverticula and hopefully, DICA will better predict the course of the disease. In a first retrospective analysis examining the outcome of DD according to DICA classification, DICA 2 score was associated with a higher risk of diverticulitis and DD recurrence than DICA 1 score. The study, however, was limited by the scant number of patients enrolled and by the absence of cases with the DICA 3 score, the most severe score. Thus, we sought to perform a larger retrospective study on the predictive role of all DICA scores.

Dr. Antoni worked in Thrombosis Research Center, Temple University Medical School, Philadelphia, USA, having faculty position, investigated a role of plasma and intestinal tissue kallikrein kinin system in experimental IBD, in collaboration with Prof. Dr. RB Sartor, NC, and Chapel Hill, US. Currently working as Professor, Silesian Medical University doing research, medical practice, and teaching students. He has supervised two large research projects founded by Polish Ministry of Sciences related to pathogenesis and treatment of human IBD. He also continued IBD coagulation study to evaluate the link of coagulation-inflammation in joints and gut diseases, and antiplatelets agents (Clopidogrel) interactions with proton pump inhibitors.His recent projects were also related to the tissue kallikrein-kinin system, and kinin receptors in colorectal polyps, and colorectal cancer as well as the significance of angiogenesis-related to kinins agrowthrow factors in ulcerative colitis.

Introduction & Aim: Kallikreins cleave kininogens to release kinins. Kinins exert their biological effect by activating constitutive bradykinin receptor -2 (BR2), which are rapidly desensitized, and inducible by inflammatory cytokines bradykinin receptor-1 (BR1), resistant to desensitization. Intestinal tissue kallikrein (ITK) may hydrolyze growth factors and peptides whereas kinins increase capillary permeability, evoke pain, stimulate synthesis of nitric oxide and cytokines and promote adhesion molecule – neutrophil cascade. Thus activation of the intestinal kallikrein-kinin system may have relevance to idiopathic inflammatory bowel

disease (IBD).

Materials & Methods: The distribution and significance of the ITK – kinin components has been investigated in experimental and human IBD.

Results: Our and other results have demonstrated that ITK is localized in intestinal goblet cells, and it is released into interstitial space during inflammation. Kallistatin, an inhibitor of tissue kallikrein, has been shown in epithelial and goblet cells and was decreased in the inflamed intestine as well as in plasma compared with noninflammatory controls. Alterations in both the distribution and levels of kinin receptors in intestinal tissue of IBD patients were demonstrated. B1R was upregulated in inflamed intestine,and has been found to be expressed in a basal part of normal intestine but in the apical portion of enterocytes in the inflamed tissue. In addition ITK and B1R (but not B2R) were visualized in macrophages forming granuloma in Crohn’s disease. In animal studies B2R blockade decreased intestinal contraction, however, had limited effect on inflammatory lesions. Recent results documented B1R upregulation, in part dependent of TNF-α, in experimental enterocolitis, and demonstrated that selective, nonpeptide B1R receptor antagonist decreased morphological and biochemical features of intestinal inflammation. In addition, both B1R and B2R have been indicated to mediate epithelial ion transport that leads to secretory diarrhea.

Conclusions: Taken together it seems that upregulation of B1R in human and animal intestinal inflammation provides a structural basis for the kinins function and selective B1R antagonist may have potential in the therapeutic trial of IBD patients.

Chau Ting Yeh obtained his MD Degree at National Taiwan University (Taiwan) and Ph.D. in the Department of Molecular Microbiology and Immunology, University of Southern California (USA). He is the Director of Liver Research Center at the Chang Gung Memorial Hospital, Taiwan, since 2007. His research interests focus on (i) HBV antiviral drug-related mutants and their oncogenic potential, and (ii) new strategies to apply genomic markers for precision medicine to treat hepatocellular carcinoma. He has published more than 200 papers in SCI-indexed journals.

The optimal therapeutic strategy to treat advanced hepatocellular carcinoma (HCC) (Barcelona-Clinic Liver Cancer [BCLC] stage C) is still under debate. Despite that clinical use of the approved targeted drug, sorafenib, could significantly improve overall survival for ~2 months in unresectable HCCs, patients benefit the most from sorafenib are mostly in BCLC stage B but not stage C. Furthermore, only 0-3% of sorafenibtreated patients achieved the complete response. Systemic or intra-hepatic arterial infusion chemotherapy thus remains a viable option in some treatment guidelines. Recently, we have discovered an SNP marker, GALNT14-rs9679162, which was associated with outcomes of multiple gastrointestinal cancers.

Additionally, it was found that three genomic markers, GALNT14 rs9679162, WWOX-rs13338697, and rs6025211, were tightly associated with chemotherapy responses in BCLC stage C HCC patients. By retrospectively analyzing outcomes of 171 real world BCLC stage C HCC patients, receiving 5-FU, mitoxantrone, and cisplatin combination chemotherapy as the first line, followed by other therapeutic modalities, we have developed a genomic-marker guided therapeutic roadmap. In 17/171 (9.9%) patients who had a complete match of the aforementioned favorable triple-SNP signature, 6/17 (35.3%) achieved complete response with no detectable viable HCC tissues remained after chemotherapy. Subsequently, the non-complete responders had received various different regimens, including sorafenib, thalidomide, tamoxifen, TS-1, radiotherapy, and FOLFOX. Of them, only sorafenib (P=0.001) and thalidomide (P=0.015) could significantly prolong overall survival. As such, we recommended the use of triple-SNP-signature as a pre-therapeutic test to identify patients who could benefit the most from chemotherapy, while others should be provided with sorafenib or thalidomide.