1
|
Papagrigoriadis S, Brandimarte G, Tursi A. Fistulating diverticulitis: a distinct clinical entity? Front Med (Lausanne) 2025; 12:1500053. [PMID: 40182848 PMCID: PMC11966039 DOI: 10.3389/fmed.2025.1500053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 02/14/2025] [Indexed: 04/05/2025] Open
Abstract
Introduction Diverticular disease (DD) of the colon has a number of phenotypes, including asymptomatic diverticulosis and complicated diverticulitis with bowel perforation or bleeding. The factor that affects the phenotype of this condition and leads to a wide range of clinical presentations is unknown. The formation of fistulas associated with diverticulitis has long been recognized, and they are treated according to ad hoc indications. We hypothesized that the formation of fistulas in diverticular disease exhibits such a wide range of variable anatomic features that it may be considered a distinct form of the condition, fistulating diverticulitis (FD). Methods We conducted a narrative review based on 50 years of publications covering a wide range of diverticulitis-associated fistulas, both common and uncommon. Results While there is abundant literature on common fistulas, such as colovesical and colovaginal fistulas, little is known about rarer fistulas, such as coloenteric fistulas, colocutaneous fistulas, and genitourinary tract fistulas. The majority of these fistulas are treated surgically, which is in contrast to the trend toward conservative management that is predominant in acute or chronic diverticulitis. Discussion Epidemiological and histological evidence support the hypothesis that FD may be a feature of chronic DD that requires individual management. Histopathology shows similarities with Crohn's disease. It remains unknown which underlying immune or genetic factors may be affecting the clinical presentation of these patients, leading to fistulation. We contend that there is adequate published evidence to characterize a distinct phenotype of FD that can involve the entire GI tract and other organs. Surgical guidelines may need to be modified to treat this small but important group, which predominantly requires surgical treatment.
Collapse
Affiliation(s)
- Savvas Papagrigoriadis
- IASO Hospital, Athens, Greece
- One Welbeck Digestive Health Centre, London, United Kingdom
| | - Giovanni Brandimarte
- Division of Internal Medicine and Gastroenterology, “Cristo Re” Hospital, Rome, Italy
| | - Antonio Tursi
- Territorial Gastroenterology Service, Barletta-Andria-Trani Local Health Agency, Andria, Italy
- Department of Medical and Surgical Sciences, School of Medicine, Catholic University, Rome, Italy
| |
Collapse
|
2
|
Jerala M, Remic T, Hauptman N, Homan P, Zajšek N, Petitjean M, Chen L, Zidar N. Thrombospondin 2, matrix Gla protein and digital analysis identified distinct fibroblast populations in fibrostenosing Crohn's disease. Sci Rep 2024; 14:13810. [PMID: 38877292 PMCID: PMC11178913 DOI: 10.1038/s41598-024-64672-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 06/11/2024] [Indexed: 06/16/2024] Open
Abstract
Fibrosis is an important complication in inflammatory bowel diseases. Previous studies suggest an important role of matrix Gla protein (MGP) and thrombospondin 2 (THBS2) in fibrosis in various organs. Our aim was to analyse their expression together with regulatory miRNAs in submucosal and subserosal fibroblasts in ulcerative colitis (UC) and Crohn's disease (CD) using immunohistochemistry and qPCR. Digital pathology was used to compare collagen fibre characteristics of submucosal and subserosal fibrosis. Immunohistochemistry showed expression of MGP, but not THBS2 in submucosa in UC and CD. In the subserosa, there was strong staining for both proteins in CD but not in UC. qPCR showed significant upregulation of THBS2 and MGP genes in CD subserosa compared to the submucosa. Digital pathology analysis revealed higher proportion of larger and thicker fibres that were more tortuous and reticulated in subserosal fibrosis compared to submucosal fibrosis. These results suggest distinct fibroblast populations in fibrostenosing CD, and are further supported by image analysis showing significant differences in the morphology and architecture of collagen fibres in submucosal fibrosis in comparison to subserosal fibrosis. Our study is the first to describe differences in submucosal and subserosal fibroblast populations, contributing to understanding of the pathogenesis of fibrostenosis in CD.
Collapse
Affiliation(s)
- Miha Jerala
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | - Tinkara Remic
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | - Nina Hauptman
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | - Pia Homan
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | - Neža Zajšek
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | | | - Li Chen
- PharmaNest Inc., Princeton, NJ, 08540, USA
| | - Nina Zidar
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia.
| |
Collapse
|
3
|
Cameron R, Walker MM, Thuresson M, Roelstraete B, Sköldberg F, Olén O, Talley NJ, Ludvigsson JF. Mortality risk increased in colonic diverticular disease: a nationwide cohort study. Ann Epidemiol 2022; 76:39-49. [DOI: 10.1016/j.annepidem.2022.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 10/04/2022] [Accepted: 10/11/2022] [Indexed: 11/01/2022]
|
4
|
Sabo CM, Dumitrascu DL, Bjarnason I. Symptomatic Uncomplicated Diverticular Disease. COLONIC DIVERTICULAR DISEASE 2022:87-97. [DOI: 10.1007/978-3-030-93761-4_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
5
|
Hanna MH, Kaiser AM. Update on the management of sigmoid diverticulitis. World J Gastroenterol 2021; 27:760-781. [PMID: 33727769 PMCID: PMC7941864 DOI: 10.3748/wjg.v27.i9.760] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/11/2021] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
Diverticular disease and diverticulitis are the most common non-cancerous pathology of the colon. It has traditionally been considered a disease of the elderly and associated with cultural and dietary habits. There has been a growing evolution in our understanding and the treatment guidelines for this disease. To provide an updated review of the epidemiology, pathogenesis, classification and highlight changes in the medical and surgical management of diverticulitis. Diverticulitis is increasingly being seen in young patients (< 50 years). Genetic contributions to diverticulitis may be larger than previously thought. Potential similarities and overlap with inflammatory bowel disease and irritable bowel syndrome exist. Computed tomography imaging represents the standard to classify the severity of diverticulitis. Modifications to the traditional Hinchey classification might serve to better delineate mild and intermediate forms as well as better classify chronic presentations of diverticulitis. Non-operative management is primarily based on antibiotics and supportive measures, but antibiotics may be omitted in mild cases. Interval colonoscopy remains advisable after an acute attack, particularly after a complicated form. Acute surgery is needed for the most severe as well as refractory cases, whereas elective resections are individualized and should be considered for chronic, smoldering, or recurrent forms and respective complications (stricture, fistula, etc.) and for patients with factors highly predictive of recurrent attacks. Diverticulitis is no longer a disease of the elderly. Our evolving understanding of diverticulitis as a clinical entity has led into a more nuanced approach in both the medical and surgical management of this common disease. Non-surgical management remains the appropriate treatment for greater than 70% of patients. In individuals with non-relenting, persistent, or recurrent symptoms and those with complicated disease and sequelae, a segmental colectomy remains the most effective surgical treatment in the acute, chronic, or elective-prophylactic setting.
Collapse
Affiliation(s)
- Mark H Hanna
- Division of Colorectal Surgery, Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010-3000, United States
| | - Andreas M Kaiser
- Division of Colorectal Surgery, Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010-3000, United States
| |
Collapse
|
6
|
Zidar N. Histopathology of Fibrosis in Crohn's Disease: The Importance of Understanding Its Pathogenesis. Gastroenterology 2020; 158:2313-2314. [PMID: 32201180 DOI: 10.1053/j.gastro.2020.02.060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 02/06/2020] [Indexed: 01/18/2023]
Affiliation(s)
- Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
7
|
Zidar N, Langner C, Jerala M, Boštjančič E, Drobne D, Tomažič A. Pathology of Fibrosis in Crohn's Disease-Contribution to Understanding Its Pathogenesis. Front Med (Lausanne) 2020; 7:167. [PMID: 32432120 PMCID: PMC7215240 DOI: 10.3389/fmed.2020.00167] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 04/14/2020] [Indexed: 12/22/2022] Open
Abstract
Background: Despite significant progress in the research of fibrosis in various organs, fibrosis remains a poorly understood complication of Crohn's disease (CD). We analyzed pathologic features of fibrosis and inflammation in CD and compared them with the normal bowel, aiming to clarify whether fibrosis in CD pathogenetically resembles fibrosis in other organs. Methods: Resection specimens from 30 patients with CD were included. Normal bowel from resection specimens of colorectal carcinoma was used for comparison. Trichrome Masson staining, immunohistochemistry for α-smooth muscle actin, fibroblast activation protein, CD34 and erg, in situ hybridization for TGF-β1 and analysis of selected fibrosis-related microRNAs were performed. Results: In normal bowel, CD34-positive fibroblasts/pericytes were detected in the submucosa and subserosa, particularly around blood vessels. In CD, fibrosis prevailed in the submucosa and subserosa, together with proliferation of myofibroblasts and disappearance of CD34-positive fibroblasts/pericytes. TGF-β1 was present in the lamina propria in normal bowel and CD, and in deeper parts of the bowel wall in CD. MicroRNAs miR-29c, miR-155 miR-150, and miR-155, which have been demonstrated to contribute to fibrosis in various organs, showed significant deregulation in CD. Conclusions: Distribution of fibroblasts/pericytes in the submucosa and subserosa of normal bowel, their disappearance in fibrosis in CD, together with the appearance of myofibroblasts, suggest that fibroblasts/pericytes are the most likely source of myofibroblasts in CD. Furthemore, fibrosis-related microRNAs showed deregulation in fibrotic areas. Pathogenesis of fibrosis in CD is thus comparable to fibrosis in other organs, in which myofibroblasts are the key effector cells, and pericytes have emerged as the main origin of myofibroblasts. Fibrosis in CD should be regarded as a result of (over)response of the bowel wall to the presence of inflammation in deep structures of the bowel wall, presenting another example of a common pathogenetic pathway of fibrosis development.
Collapse
Affiliation(s)
- Nina Zidar
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia
| | - Cord Langner
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Miha Jerala
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia
| | - Emanuela Boštjančič
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia
| | - David Drobne
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Aleš Tomažič
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia
- Department of Abdominal Surgery, University Medical Center, Ljubljana, Slovenia
| |
Collapse
|