[History of surgical treatment of non-specific inflammatory bowel diseases]. / Historie chirurgické lécby nespecifických zánetu strevních.

Treatment of non-specific inflammatory bowel diseases was from the start accompanied by forced operations. In the 19th and early 20th century operations were burdened with high mortality, but most were more successful than the limited possibilities of conservative treatment. Gradually developed principles for the treatment of Crohns disease, a length of bowel sparing surgery are still valid today. Surgical treatment of ulcerative colitis passed the time of colonic irrigation, bypass surgery, limited resection to todays gold standard - proctocolectomy with ileo-pouch-anal anastomosis.

Evolving primary and secondary endpoints in randomized controlled trials leading to approval of biologics and small molecules in IBD: an historical perspective.

Introduction: Therapeutic goals in inflammatory bowel diseases (IBD) have evolved, over the last decades, from clinical response to complete remission (clinical and endoscopic remission).Areas covered: Development of biologics and small molecules has been associated with the development of new endpoints in IBD trials that could not have been achieved in the pre-biologics era. Herein, we focus on evolving endpoints for approved biologics and small molecules. We searched for relevant publications using Medline/PubMed, Embase and the Cochrane Library from their inception to 1 July 2019.Expert opinion: Endpoints differ between induction (clinical and endoscopic response) and maintenance trials (clinical and endoscopic remission) because the goal is to evaluate the anti-inflammatory effect of a given drug during induction, whereas full disease control is the ultimate goal during the maintenance phase in order to change patients' life and disease course. Histological healing has recently emerged as a new co-primary endpoint in ulcerative colitis, and is now part of the definition of mucosal healing in these trials. Whether new endpoints such as transmural and radiologic healing could become an endpoint and replace endoscopy in Crohn's disease trials in the near future requires further investigation.

Festschrift for Ronan O'Connell: pouchitis, ulcerative colitis and the microbiome.

The hypothesis of altered bacterial communities contributing to the development of pouchitis began a scientific quest to link host mucosal factors, microbial metabolism and spatial structure of the colonic microbiome in ulcerative colitis, reaching its apotheosis with the integration of advanced spatial sampling with laser capture microdissection, mucin array profiling, molecular microbiology and next-generation sequencing technologies. This article, part of a festschrift, summarises the contributions of the O'Connell lab to the field of host-microbial interactions in inflammatory bowel disease.

"The Leeds Idea": an historical account of the spondarthritis concept.

In the 1960s, Professor Verna Wright became increasingly interested in possible relationships between certain seronegative "variants of rheumatoid arthritis", as they were then generally known. At the Rheumatism Research Unit, a department within the division of medicine at Leeds University, he gathered around him a succession of research workers, whom he inspired to study aspects of these relationships. The focus was on family studies, as it was thought that genetic factors could be important. The striking association previously noted between sacroiliitis or full-blown ankylosing spondylitis and several of these disorders to be studied - e.g., psoriatic arthritis, ulcerative colitis, and the arthritis associated with Crohn's disease - was to be central for each of these studies. As a provisional collective name for these possibly related conditions, the term "Spondarthritides" was chosen. These were the days before HLA B27, and so the research tools were simply clinical, radiological (for sacroiliitis) and serological (for rheumatoid factor). The research programme confirmed not only links between the primary disorders with ankylosing spondylitis, but also links between the disorders themselves. Over subsequent years, the spondarthritis concept (dubbed by some "The Leeds Idea") has gained further strength from HLA studies internationally. And membership of the group of conditions fulfilling spondarthritis criteria has grown substantially. It is hoped that this now consolidated framework of spondylitis-related entities will pave the way for further research, with exciting prospects of gene-based prevention and/or cure through the increasing sophistication of molecular biology.

Clinical trials in ulcerative colitis: a historical perspective.

The clinical trial landscape in ulcerative colitis has evolved significantly in recent decades. Study endpoints have been shifting from mere clinical response to mucosal healing. It has become clear that the choice of combined clinical and endoscopic outcome criteria leads to a reduction in placebo responses, especially when central reading of the endoscopic images is performed. Accumulating evidence suggests that histological remission yields better long-term outcomes for ulcerative colitis patients than mucosal healing alone, and clinical trials with prolonged follow-up will have to address whether histological remission should be the ultimate treatment goal in ulcerative colitis. In recent years there has also been increasing interest in the implementation of patient-reported outcomes in clinical practice and research, and the regulatory authorities have set up guidelines for the development of such outcomes. This paper aims to provide a comprehensive review of historical aspects of clinical trials in ulcerative colitis and to discuss challenges and perspectives for clinical trials in the near future. A thorough analysis of all available landmark literature (both original papers and reviews) on clinical trials in ulcerative colitis was performed.

Clinical pharmacology in gastroenterology: development of new forms of treatment of inflammatory bowel disease.

Kinetic-dynamic aspects of the development of slow-release mesalazine, Pentasa (now an established treatment of inflammatory bowel disease (IBD)), and cyclosporin, a T cell selective immunosuppressant (still in the investigative phase), are reviewed as examples of Danish contributions at an early stage to international, clinical drug research. Apart from increasing the therapeutic options for patients with IBD, current and future studies with these (and other) drugs may add important clues to a more precise understanding of the basic pathogenetic mechanisms (e.g. cytokines, adhesion molecules) involved in these diseases. The future development and clinical implementation of novel drug designs in IBD and other gastrointestinal diseases may be expected to benefit from a continued or even closer collaboration between clinical gastroenterologists and basic research institutions, including the pharmaceutical industry at an early stage.

A tale of two diseases: the history of inflammatory bowel disease.

'Inflammatory bowel disease' (IBD) sounds like a straightforward term - a disease of inflammation in the bowel. However, the history of IBD reveals a story of a nefariously complex set of idiopathic conditions. IBD defies definition, in part because its pathophysiology is not completely understood. For the same reason and despite substantial advances in research, IBD also defies cure. At best, IBD can be defined as a disease of disruption - disrupted physiology, microbiology, immunology and genetics. The term 'IBD' is most often used to describe two separate conditions: ulcerative colitis (UC) and Crohn's disease (CD). This paper reviews the history of IBD, considering the ever-evolving understanding of both UC and CD. Beyond its intrinsic interest, the history of IBD exemplifies a pattern that is becoming increasingly familiar in the 21st century - the story of a chronic, incurable disease that defies the best efforts to treat it.

The death of Albert Prince Consort: the case against typhoid fever.

The case against typhoid fever as the cause of the Prince's death rests partly on some uncharacteristic clinical features during the terminal 22 days of his illness, and partly on other aspects of his temperament and emotionally threatening life events, which tend to favour ulcerative colitis or Crohn's disease. That he had been intermittently unwell with abdominal symptoms for several months before the terminal stage of his illness, only 9 days after this sensitive and vulnerable man was confronted by an intensely personal insult, lends further support to a diagnosis of inflammatory bowel disease. His many admirable qualities unfortunately did not include those needed to surmount deeply injured feelings at his son's behaviour, notably flexibility, sufficient sense of humour and tolerance of human frailty. Had he been able to swear or laugh at his son's foolishness, it might have saved him, and so might adequate psychological management. Some patients with fulminating inflammatory bowel disease, if that is what the Prince had, decline such help, preferring to brood rather than speak, and take their bottled-up feelings of resentment to the grave.

Lester R. Dragstedt 1893-1975. Chronic ulcerative colitis. A summary of evidence implicating Bacterium necrophorum as an etiologic agent.

Lester Dragstedt was born in Anaconda, Montana, the son of Swedish immigrant parents. His entire college and professional education took place at the University of Chicago, where he received a B.S. degree in 1915, a master's degree in physiology in 1916, a Ph.D. in physiology in 1920, and the M.D. degree (from Rush) in 1921. His first academic appointment was as a physiologist at the State University of Iowa. In 1925 Dragstedt was recruited by Dallas B. Phemister to help design the new University Hospital research facilities on the campus of the University of Chicago. Following completion of this responsibility Phemister appointed Dragstedt as Associate Professor of Surgery, stating, "I can teach surgery to a physiologist; I am interested in teaching physiology to surgeons." In 1947 Dragstedt succeeded Phemister as chairman, a post he occupied until his retirement in 1959. Dragstedt was regarded as a skilled clinician as well as a dexterous and artistic surgeon. But he was particularly recognized for his contributions as physiologist-surgeon in the treatment of diseases of the pancreas, parathyroids, and especially diseases of the stomach. In 1943, he performed a transthoracic vagotomy on a patient with a duodenal ulcer who refused to accept the standard operation, subtotal gastrectomy. A lesser known but classical work of Dragstedt and his coworkers is reproduced here for this series. Dragstedt was the originator of the skin-grafted ileostomy in the treatment of ulcerative colitis. The author describes a complete "take" of the split-thickness graft in four patients, although he observed that the "resulting ileostomy looked somewhat like a penis." One can only surmise about the psychologic disability that would be produced. The stoma could, however, be fitted with an appliance that would minimize the risk of abdominal wall digestion. When reading the article and understanding the experimental studies proposing the possible causative organism of ulcerative colitis, one is impressed by Dragstedt's creative thinking. Dragstedt's renown as a basic scientist was illustrated by his election to the National Academy of Sciences. Following his Chicago retirement he became again a full-time physiologist with appointments as research professor in both the department of surgery and the department of physiology at the University of Florida College of Medicine. Active until the end, he died at his summer home on Elk Lake, Michigan on July 16, 1975.