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Surgical treatment of inflammatory bowel disease: From the gastroenterologist's stand-point

WORLD JOURNAL OF GASTROINTESTINAL SURGERY 2024年第5期16卷 1235-1254页

作者： triantafillidis, john k. Metropolitan Gen Hosp Inflammatory Bowel Dis Unit 264 Mesogeion Ave Attica 15562 Greece Hellen Soc Gastrointestinal Oncol Athens 12461 Greece

Treatment of ulcerative colitis (UC) and Crohn's disease (CD) represents, in the majority of cases, a real challenge to the gastroenterologist's abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and experience. During the last two decades, our pharmaceutical arsenal was significantly strengthened, especially after the introduction of the so-called biological agents, drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the disease. However, colectomy is still necessary for some patients with severe UC although smaller compared to the past, precisely because of the improvements achieved in the available conservative treatment. Nevertheless, surgeries to treat colon dysplasia and cancer are increasing to some extent. At the same time, satisfactory improvements in surgical techniques, the pre-and post-operative care of patients, as well as the selection of the appropriate time for performing the surgery have been noticed. Regarding patients with CD, the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their disease. On the other hand, the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel in situ as possible. This article discusses the indications for surgical management of UC patients from the gastroenterologist's point of view, the results of the emerging new techniques such as transanal surgery and robotics, as well as alternative operations to the classic ileo-anal-pouch anastomosis. The author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant literature. The self-evident is emphasized, that is, to achieve an excellent therapeutic result in patients with severe inflammatory

关键词： Inflammatory bowel disease Ulcerative colitis Crohn's disease Surgery Treatment Ileo-anal-pouch anastomosis Indications Techniques LAPAROSCOPIC ILEOCECAL RESECTION CROHNS-DISEASE ULCERATIVE-COLITIS TERMINAL ILEITIS COLORECTAL-CANCER SURGERY COLECTOMY THERAPY RECURRENCE MECHANISMS

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Immunotherapy of gastric cancer:Present status and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 779-793页

作者： John K Triantafillidis Manousos M konstadoulakis Apostolos E Papalois Inflammatory Bowel Disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece Second Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528AtticaGreece Unit of Surgical Research and Training Second Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528AtticaGreece

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.

关键词： Gastric cancer Chemotherapy Immunotherapy Immune checkpoint inhibitors Bibliometrics Scientometrics

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Combination treatment of inflammatory bowel disease:Present status and future perspectives

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World Journal of Gastroenterology 2024年第15期30卷 2068-2080页

作者： John K Triantafillidis Constantinos G Zografos Manousos M konstadoulakis Apostolos E Papalois Inflammatory Bowel Disease Unit "Metropolitan General"HospitalHolargos 15562AtticaGreece Hellenic Society for Gastrointestinal Oncology 354 Iera OdosChaidari 12461AtticaGreece The 2^(nd)Department of Surgery University of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece Unit of Surgical Research and Training The 2^(nd)Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing d

关键词： Biologics for immune-mediated conditions Dual-targeted treatment Combination treatment Inflammatory bowel disease Crohn’s

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Early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 583-597页

作者： John K Triantafillidis konstantinos Georgiou Manousos M konstadoulakis Apostolos E Papalois Department of IBD and GI Endoscopy Metropolitan General HospitalHolargos 15562AthensGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece 2nd Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528Greece

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary tract.It should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather insufficient.The exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be available.The most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries.The existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from childhood.Changes that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of carcinogenesis.Even these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms.Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required.In this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis.Finally,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

关键词： Gastrointestinal cancer Endoscopy Epidemiology Early-onset Environment

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Chios mastic treatment of patients with active Crohn's disease

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World Journal of Gastroenterology 2007年第5期13卷 748-753页

作者： Andriana C kaliora Maria G Stathopoulou John K Triantafillidis George VZ Dedoussis Nikolaos k Andrikopoulos Department of Science of Dietetics-Nutrition Harokopio University Athens Greece Department of Gastroenterology Saint Panteleimon General State Hospital Nicea Athens Greece

AIM: To evaluate the effectiveness of mastic administra-tion on the clinical course and plasma inflammatory me-diators of patients with active Crohn’s disease (CD).METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attend-ing the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Ac-tivity Index (CDAI), Nutritional Risk Index (NRI), C-re-active protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values ± SE and P kind of side effects. CONCLUSION: The results suggest that mastic signifi-cantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately ac-tive CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.

关键词： Crohn氏病希腊乳香玛蒂脂 C反应蛋白保守治疗抗氧化剂

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Sedation in gastrointestinal endoscopy: Current issues

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World Journal of Gastroenterology 2013年第4期19卷 463-481页

作者： John K Triantafillidis Emmanuel Merikas Dimitrios Nikolakis Apostolos E Papalois Department of Gastroenterology and Center for Inflammatory Bowel Disease "Saint Panteleimon" General HospitalNikaia12461 HaidariGreece Experimental Research Center ELPEN Pharmaceuticals19009 AthensGreece

Diagnostic and therapeutic endoscopy can successfully be performed by applying moderate(conscious) sedation.Moderate sedation,using midazolam and an opioid,is the standard method of sedation,although propofol is increasingly being used in many countries because the satisfaction of endoscopists with propofol sedation is greater compared with their satisfaction with conventional sedation.Moreover,the use of propofol is currently preferred for the endoscopic sedation of patients with advanced liver disease due to its short biologic half-life and,consequently,its low risk of inducing hepatic encephalopathy.In the future,propofol could become the preferred sedation agent,especially for routine colonoscopy.Midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam.Among opioids,pethidine and fentanyl are the most popular.A number of other substances have been tested in several clinical trials with promising results.Among them,newer opioids,such as remifentanil,enable a faster recovery.The controversy regarding the administration of sedation by an endoscopist or an experienced nurse,as well as the optimal staffing of en-doscopy units,continues to be a matter of discussion.Safe sedation in special clinical circumstances,such as in the cases of obese,pregnant,and elderly individuals,as well as patients with chronic lung,renal or liver disease,requires modification of the dose of the drugs used for sedation.In the great majority of patients,sedation under the supervision of a properly trained endoscopist remains the standard practice worldwide.In this review,an overview of the current knowledge concerning sedation during digestive endoscopy will be provided based on the data in the current literature.

关键词： Gastrointestinal endoscopy Endoscopy Sedation Analgesia Digestive system

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Favorable response to subcutaneous administration of infliximab in rats with experimental colitis

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World Journal of Gastroenterology 2005年第43期11卷 6843-6847页

作者： John K Triantafillidis Apostolos E Papalois Aikaterini Parasi Emmanuel Anagnostakis Stavros Burnazos Aristofanis Gikas Emmanuel G Merikas Emmanuel Douzinas Maria karagianni Helen Sotiriou Department of Gastroenterology Experimental Research Unit Department of Pathology

AIM: To investigate the influence of infliximab (Remicade)on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats.METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1:colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7th d, all animals were killed. The colon was fixed in 10%buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured.RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared withthe untreated ones was found (0.47±0.44, 1.09±0.86,0.43±0.31 vs 18.73±10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4.CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats.Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW.Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 1

关键词：大肠炎肿瘤坏死因子病理机制临床表现

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A comprehensive review on bitter gourd (Momordica charantia L.) as a gold mine of functional bioactive components for therapeutic foods

Food Production, Processing and Nutrition

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Food Production, Processing and Nutrition 2022年第1期4卷 107-120页

作者： k.S.Gayathry Jenny Ann john Faculty of Ocean Science and Technology Kerala(Department of Food Science and Technology)Kerala University of Fisheries and Ocean Studies(KUFOS)Panangad P.O.KochiKerala682506India

Bitter gourd is a tropical wine grown mainly in India, China and South East Asia. The plant is cultivated mainly for its fruit part which is edible. Bitter gourd is unaccepted widely due to its bitter taste. Nevertheless, the fruit is a source of several key nutrients. The plant, as a whole contains, more than 60 phyto-medicines that are active against more than 30 diseases, including cancer and diabetes. Currently, the incorporation of the bioactive compounds isolated from bitter gourd into functional foods and beverages finds a new horizon. Nanoencapsulation and novel green extraction methods can be employed to improve the yield and quality of extracted compounds and their stability while incorporation into food products. The present review is an attempt to throw light to nutritional aspects, various bioactive compounds present and important nutraceutical properties of the bitter gourd plant in detail.

关键词： Bitter gourd Bioactive Nutraceutical Extraction Encapsulation

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Obesity:an evolutionary context

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Life Metabolism 2022年第1期1卷 10-24页

作者： john R.Speakman Joel k.Elmquist Shenzhen key Laboratory of Metabolic Health Center for Energy Metabolism and ReproductionShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina School of Biological Sciences University of AberdeenAberdeenUK State key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental biologyChinese Academy of SciencesBeijingChina CAS Center of Excellence in Animal Evolution and Genetics KunmingChina Departments of Internal Medicine and Pharmacology Center for Hypothalamic ResearchUniversity of Texas SouthwesternDallasTXUSA

People completely lacking body fat(lipodystrophy/lipoatrophy)and those with severe obesity both show profound metabolic and other health issues.Regulating levels of body fat somewhere between these limits would,therefore,appear to be adaptive.Two different models might be contemplated.More traditional is a set point(SP)where the levels are regulated around a fixed level.Alternatively,dual-intervention point(DIP)is a system that tolerates fairly wide variation but is activated when critically high or low levels are breached.The DIP system seems to fit our experience much better than an SP,and models suggest that it is more likely to have evolved.A DIP system may have evolved because of two contrasting selection pressures.At the lower end,we may have been selected to avoid low levels of fat as a buffer against starvation,to avoid disease-induced anorexia,and to support reproduction.At the upper end,we may have been selected to avoid excess storage because of the elevated risks of predation.This upper limit of control seems to have malfunctioned because some of us deposit large fat stores,with important negative health effects.Why has evolution not protected us against this problem?One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary history.By chance,it fell apart more in some people than others,and these people are now unable to effectively manage their weight in the face of the modern food glut.To understand the evolutionary context of obesity,it is important to separate the adaptive reason for storing some fat(i.***.the lower intervention point),from the nonadaptive reason for storing lots of fat(a broken upper intervention point).The DIP model has several consequences,showing how we understand the obesity problem and what happens when we attempt to treat it.

关键词： obesity BMI body fat adiposity evolution selection adaptive leptin resistance metabolic programming dual-intervention point model set-point model

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Structural characterization and mass spectrometry fragmentation signatures of macrocyclic alkanes isolated from a Sydney Basin torbanite,Australia

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Acta Geochimica 2023年第3期42卷 488-494页

作者： Xianxin Meng Hong Lu Zhirong Zhang Ping’an Peng john k.Volkman State key Laboratory of Organic Geochemistry Guangzhou Institute of Geochemistry and Institutions of Earth ScienceChinese Academy of SciencesGuangzhou 510640China CAS Center for Excellence in Deep Earth Science Guangzhou 510640China University of the Chinese Academy of Sciences Beijing 100049China Wuxi Institute of Petroleum Geology PEPRISSINOPEC2060 Lihu Rd.Wuxi 214126JiangsuChina key Laboratory of Oil and Gas Resources and Exploration Technology Ministry of EducationCollege of Resources and EnvironmentYangtze UniversityWuhan 430100China

Individual hydrocarbons identified to be macrocyclic alkanes in a torbanite from the Sydney Basin(Australia)were successfully isolated from its extracts using preparative gas chromatography and analyzed by NMR.Saturated cyclic structures were confirmed by single peaks in the NMR~1H and~(13)C spectra indicating single forms of H and C atoms exist in these biomarker molecules.This is consistent with the methylene unit in a ring system assignment of the macrocyclic alkanes and accounts for a formula of(CH2)n.The unusual molecular structures of these compounds are consistent with those that were identified from previous GC retention index data and co-injection with a standard supports the previous research.The mass spectral fragmentation behaviors of representative cyclic alkanes were further investigated by comparing them with the mass spectra of isolated individual macrocyclic alkanes.The characteristic fragment ions in the macrocyclic alkanes of(M–28)+and base peaks of m/z 97,111,125,etc.,can be assigned as being generated by simple a-/i-cleavage and hydrogen rearrangement.These fragmentation pathways combined with retention indices should assist in differentiating these compounds from monounsaturated alkenes and alkylated monocyclics having similar mass spectral characteristics in other geological samples.

关键词： Macrocyclic alkanes Torbanite NMR Preparative GC MS fragmentation

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