Prolonged Recurrent Abdominal Pain is Associated With Ongoing Underlying Mucosal Inflammation in Patients who had an Episode of Acute Complicated Diverticulitis.

BACKGROUND: Recent data suggest continuous chronic inflammation in patients after an acute diverticulitis (AD) episode. GOALS: The aim of this article was to compare clinical parameters, inflammatory cytokine expression, and immune-cell infiltrates between patients after severe versus nonsevere AD, as defined by radiology examination during the acute episode. STUDY: Sixteen patients, after suffering an episode of AD, were included, and, of them, 8 had severe disease. Demographic data, disease characteristics, and inflammatory markers were collected. Tissue samples from diverticular and unaffected tissue were obtained during colonoscopy. Mucosal inflammation was assessed histologically and by measuring inflammatory cytokine mRNA expression. RESULTS: Clinically, continued nonspecific abdominal symptoms were significantly more prevalent among patients after severe AD compared with patients after nonsevere AD (P=0.0002). Patients after severe AD also had significantly higher C reactive protein levels (9.85±7.5 vs. 3±2.1 mg/dL; P=0.027) and tendency for higher calprotectin levels (115.7±85 vs. 35±8.7 mg/g; P=0.08). Reverse transcription polymerase chain reaction-determined cytokines levels were 5.4±4.4, 5.14±10, and 0.8±0.82 for tumor necrosis factor alpha, interleukin-6, and interleukin-1ß, respectively, in affected mucosa compared with 1.06±1.57, 1.56±2.1, and 0.35±0.5, respectively, in nonaffected mucosa (P=0.01, 0.05, 0.14, respectively). Cytokine expression in patients after nonsevere AD did not differ significantly between affected and nonaffected mucosa. Histologic scores for crypt distortion, lymphoid aggregates, and lymphocyte infiltration were all significantly higher in patients after severe AD compared with patients after nonsevere AD (P<0.05 for all comparisons). CONCLUSIONS: Patients after severe AD have more prolonged chronic symptoms, higher inflammatory markers, higher tissue inflammatory cytokine levels, and more inflammatory infiltrates in diverticular colonic tissue than patients after nonsevere AD. These results may contribute to patients' risk stratification and guide therapeutic decisions.

Pathophysiology of diverticular disease.

INTRODUCTION: Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

Role of visceral fat in colonic inflammation: from Crohn's disease to diverticulitis.

PURPOSE OF REVIEW: The composition of activated adipose tissue with adipocytes secreting a broad spectrum of immune-modulatory adipokines next to adipose tissue-derived stromal cells and professional immune effector cells in the visceral fat creates a complex network of inflammatory processes shaping local immune responses in the adjacent inflamed intestinal mucosa. RECENT FINDINGS: In Crohn's disease a particular phenomenon called 'creeping fat' can be observed. Here the hyperplastic mesenteric fat tissue not only grows around inflamed small intestinal segments but also furthermore affects the regulation of the mucosal immune system. Diverticular disease is highly prevalent in the western world but the knowledge about its immunopathology remains incomplete. Interestingly, adipose tissue also frequently covers the basolateral site of inflamed diverticula, hence locally reflecting the phenomenon seen in Crohn's disease. SUMMARY: This review aims to summarize the current knowledge in which measures this intraabdominal fat participates in the regulation of intestinal inflammation with a particular focus on differences and possible parallels in Crohn's disease and diverticulitis. The available data allow for suggesting that each inflamed diverticula mechanistically reflects Crohn's disease on a miniature scale.

Diverticulitis in immunosuppressed patients: A fatal outcome requiring a new approach?

BACKGROUND: Diagnosis and treatment of diverticulitis in immunosuppressed patients are more challenging than in immunocompetent patients, as maintenance immunosuppressive therapies may mask symptoms or impair the patient's ability to counteract the local and systemic infective sequelae of diverticulitis. The purpose of this study was to compare the in-hospital mortality and morbidity due to diverticulitis in immunosuppressed and immunocompetent patients and identify risk factors for lethal outcomes. METHODS: This retrospective study included consecutive in-patients who received treatment for colonic diverticulitis at our institution between April 2008 and April 2014. Patients were divided into immunocompetent and immunosuppressed groups. Primary end points were mortality and morbidity during treatment. Risk factors for death were evaluated. RESULTS: Of the 227 patients included, 15 (6.6%) were on immunosuppressive therapy for solid organ transplantation, autoimmune disease, or cerebral metastasis. Thirteen of them experienced colonic perforation and showed higher morbidity (p = 0.039). Immunosuppressed patients showed longer stays in hospital (27.6 v. 14.5 d, p = 0.016) and in the intensive care unit (9.8 v. 1.1 d, p < 0.001), a higher rate of emergency operations (66% v. 29.2%, p = 0.004), and higher in-hospital mortality (20% v. 4.7%, p = 0.045). Age, perforated diverticulitis with diffuse peritonitis, emergency operation, C-reactive protein > 20 mg/dL, and immunosuppressive therapy were significant predictors of death. Age (hazard ratio [HR] 2.57, p = 0.008) and emergency operation (HR 3.03, p = 0.003) remained significant after multivariate analysis. CONCLUSION: Morbidity and mortality due to sigmoid diverticulitis is significantly higher in immunosuppressed patients. Early diagnosis and treatment considering elective sigmoid resection for patients with former episodes of diverticulitis who are wait-listed for transplant is crucial to prevent death.

BACKGROUND: Le diagnostic et le traitement des diverticulites sont plus délicats chez les patients immunosupprimés que chez les patients immunocompétents, étant donné que les thérapies immunosuppressives d'entretien peuvent masquer les symptômes ou réduire la capacité du patient à lutter contre les infections locales ou systémiques pouvant découler de la diverticulite. La présente étude avait pour but de comparer les taux de mortalité et de morbidité en milieu hospitalier associés à la diverticulite chez des patients immunosupprimés et immunocompétents et de cerner les facteurs de risque de décès. METHODS: Cette étude rétrospective portait sur des patients traités consécutivement pour une diverticulite du côlon hospitalisés dans notre établissement entre avril 2008 et avril 2014. Les patients ont été divisés en 2 groupes : immunocompétents et immunosupprimés. Les résultats primaires à l'étude étaient la mortalité et la morbidité pendant le traitement, et nous avons évalué les facteurs de risque de décès. RESULTS: Parmi les 227 patients retenus, 15 (6,6 %) suivaient une thérapie immunosuppressive en raison d'une greffe d'organe plein, d'une maladie auto-immune ou de métastases cérébrales. Parmi eux, 13 ont subi une perforation du côlon et présentaient un taux de morbidité supérieur (p = 0,039). Les patients immunosupprimés sont restés plus longtemps à l'hôpital (27,6 j c. 14,5 j, p = 0,016) et à l'unité de soins intensifs (9,8 j c. 1,1 j, p < 0,001), et présentaient des taux supérieurs d'intervention d'urgence (66 % c. 29,2 %, p = 0,004) et de mortalité pendant l'hospitalisation (20 % c. 4,7 %, p = 0,045). L'âge, une diverticulite perforée avec péritonite diffuse, une opération d'urgence, un résultat de protéine C réactive > 20 mg/dL et une thérapie immunosuppressive étaient des prédicteurs de décès significatifs. L'âge (rapport de risque [RR] 2,57, p = 0,008) et une opération d'urgence (RR 3,03, p = 0,003) sont demeurés significatifs après l'exécution d'une analyse multivariée. CONCLUSION: Les taux de morbidité et de mortalité attribuables à une diverticulite du sigmoïde sont significativement plus élevés chez les patients immunosupprimés que chez les autres patients. Afin de prévenir les décès, il est essentiel de diagnostiquer et de traiter rapidement, possiblement par résection du sigmoïde, les patients ayant déjà souffert de diverticulite qui sont sur une liste d'attente pour une greffe.

Sigmoid Colectomy for Acute Diverticulitis in Immunosuppressed vs Immunocompetent Patients: Outcomes From the ACS-NSQIP Database.

BACKGROUND: The management of acute diverticulitis in immunosuppressed patients is increasingly debated. The appropriate timing and type of operation remains controversial. OBJECTIVE: This study examines the impact of immunosuppression on mortality and morbidity following colectomies for diverticulitis in the emergency and elective settings. DESIGN SETTINGS: With the use of the American College of Surgeons National Surgical Quality Improvement Program database, the outcomes of immunosuppressed compared with immunocompetent patients who underwent colectomy for acute diverticulitis were compared. PATIENTS: The multi-institutional database was queried for patients who underwent colectomy for acute diverticulitis from 2005 to 2012. MAIN OUTCOMES MEASURES: The impact of immunosuppression on mortality, major morbidity, organ space infection, infectious complications, and wound dehiscence was assessed. RESULTS: Of 26,987 patients, 1332 were immunosuppressed and 25,655 were immunocompetent; 4271 patients had emergency (596 immunosuppressed and 3675 immunocompetent) and 22,716 patients had elective (736 immunosuppressed and 21,980 immunocompetent) colectomies for diverticulitis. In both groups, mortality and major morbidity were significantly higher in the emergency (immunosuppressed 16% and 45%, immunocompetent 4% and 28%) compared with the elective setting (immunosuppressed 2% and 25%, immunocompetent 0.4% and 12%), p < 0.001. On multivariate regression for the emergency setting, immunosuppression significantly increased mortality (OR, 1.79; 95% CI, 1.17-2.75) and did not significantly increase morbidity. On multivariate regression for the elective setting, mortality was similar in immunosuppressed and immunocompetent groups; however, major morbidity (OR, 1.46; 95% CI, 1.17-1.83) and wound dehiscence (OR, 2.69; 95% CI, 1.63-4.42) were significantly increased in immunosuppressed compared with immunocompetent patients. LIMITATIONS: The retrospective design and standardized outcomes are based on heterogeneous data. CONCLUSIONS: Emergency colectomy for diverticulitis is associated with higher mortality in immunosuppressed than in immunocompetent patients, whereas elective colectomy is associated with comparable mortality. In the elective setting, immunosuppressed compared with immunocompetent patients are at increased risk of major morbidity and wound dehiscence.

Emergency surgery for perforated diverticulitis in the immunosuppressed patient.

AIM: Immunosuppression is believed to worsen outcomes for patients who require surgery for perforated diverticulitis. The aim of this study was to compare surgical outcomes between immunocompromised and immunocompetent patients undergoing surgery for complicated diverticulitis. METHOD: All patients who underwent emergency surgery for complicated diverticulitis between 2004 and 2012 in a single unit were studied. Patients were classified as immunosuppressed (group I) or immunocompetent (group II). Operation type and postoperative morbidity and mortality were compared between groups. The impact of operating surgeons' specialization and the Peritonitis Severity Score (PSS) were also evaluated to determine their impact on the restoration of gastrointestinal (GI) continuity. RESULTS: One-hundred and sixteen patients (mean age: 63.7 years), 41.4% women, were included. Fifty-three (45.7%) patients were immunosuppressed (group I): 42 underwent Hartmann's procedure (HP) (79.2%), nine (17.0%) underwent resection and primary anastomosis (RPA) with ileostomy (IL) and two (3.8%) underwent RPA without IL. In group II, 15 HP (23.8%), nine RPA with IL (14.3%) and 39 RPA without IL (61.9%) were performed. Postoperative morbidity and mortality were 79.2% and 26.4%, respectively, in group I and 63.5% and 6.3%, respectively, in group II. The overall mean PSS was 9.5, with a mean PSS of 11.1 in group I and of 8.1 in group II. The decision to perform a primary anastomosis differed significantly between colorectal surgeons and general surgeons in the patients with a PSS of 9-10-11. CONCLUSION: In immunocompromised patients, RPA with IL can be a safe surgical option, whereas HP should be reserved for patients with a PSS of > 11. Colorectal surgical specialization is associated with higher rates of restoration of GI continuity in patients with perforated diverticulitis, especially in patients with an intermediate PSS score. Evaluation of each patient's PSS facilitates decision making in surgery for perforated diverticulitis.

Influence of CD68+ macrophages and neutrophils on anastomotic healing following laparoscopic sigmoid resection due to diverticulitis.

BACKGROUND: The aim of this prospective study was to evaluate the predictive value of a potential preexisting low-grade inflammation regarding the incidence of anastomotic leakage in elective laparoscopic sigmoid resection due to diverticulitis. METHODS: Patients with either chronically recurrent diverticulitis or sigmoid stenosis caused by chronic diverticulitis were included in this study. All patients with acute local or systemic inflammation were excluded. Detailed patient information (e.g. American Society of Anesthesiologists (ASA) grade, comorbidities, duration of hospital stay, and anastomotic leakage) was prospectively recorded. CD68(+) macrophages, neutrophils, CD3(+) T-lymphocytes, CD11c(+) dendritic cells, MHCII, TNFR1, and NF-κB were evaluated by immunohistochemistry within the acquired sample of colonic bowel wall tissue. Clinical and immunohistochemical data was compared between groups (leakage vs. no leakage). Additionally, a matched-pair analysis was performed due to the widely heterogeneous groups concerning the number of patients and to minimize the effect of extraneous variables. RESULTS: A total of 83 patients were included in the study, of which 7 patients suffered an anastomotic leakage. Neither the clinical nor the immunohistochemical parameters were significantly different between the groups. The matched-pair analysis revealed a nonsignificant increase in mean duration of hospital stay for the group with anastomotic leakage and a significantly higher percentage of CD68(+) macrophages and neutrophils in the colonic wall obtained at the index operation in both the mucosal and submucosal layers for the leakage group. CONCLUSIONS: A preexisting low-grade inflammation represented by infiltrates of macrophages and neutrophils is a predictor for increased risk of developing colon anastomotic leakage.

[Inflammatory nature of colon diverticula].

On the basis of morphological and immunological study of biopsies of the colon in patients with diverticulosis was revealed that microscopic inflammation of the mouth of the diverticulum is characterized by several features that include excessive proliferation of the epithelium, the predominance of macrophage reaction in the development of the immune response, increased cell adhesion and unusual ratio between the expression of cytokines and other regulatory molecules. Changes in the structure of the formed diverticula tissue are associated with dysregulation of many processes of tissue metabolism and morphogenesis. These include the dysregulation of cell renewal of the epithelium (increased level of proliferation of epithelial cells and inhibition of apoptosis), degradation of extracellular matrix components, moderate vascular reaction. All these processes take place on the background a particular form of immune protection and adaptation mechanisms.

Association of steroid use with complicated sigmoid diverticulitis: potential role of activated CD68+/CD163+ macrophages.

BACKGROUND: Immunosupression and, especially, intake of steroids have previously been identified as risk factors for complicated types of sigmoid diverticulitis. However, little is known about the underlying molecular and cellular mechanisms. We aimed to elucidate the potential role of activated macrophages in this respect. METHODS: A consecutive series of n = 101 patients having undergone surgical resection for sigmoid diverticulitis at our institution was analyzed regarding the inflammatory infiltrate and prevalence of comorbid diseases as well as risk factors, including steroid use. Fifty-seven patients had complicated types of diverticulitis with severe inflammation (group A). Forty-four patients had moderate inflammation, most of whom had been operated for chronically recurrent diverticulitis (group B). Randomly selected 50 patients (n = 20/group A/n = 30 group B) underwent immunolabelling against CD68 and CD163. RESULTS: Using immunofluorescence double labeling experiments we found a strong positive correlation of CD68 expression with CD163 expression (т = 0.934). High CD68 expression (x ≥ 23%) and high CD163 expression (x ≥ 22%) within stromal cells of the lamina propria was significantly associated with steroid use (CD68, p = 0.012 and CD163, p = 0.004, respectively) and complicated sigmoid diverticulitis with severe inflammation (CD68, p = 0.0001 and CD163, p = 0.001, respectively). CONCLUSIONS: Inflammation, especially mediated by activated (CD68+/CD163+) macrophages in histopathological specimen might resemble the cellular link between steroid use and complicated types of sigmoid diverticulitis. Macrophages might be a suitable target for future supportive/preventive therapies. However, as long as we are lacking such strategies, we must bear in mind that steroid intake is a risk factor for complicated diverticulitis, especially when indicating surgical resection.

Predictive value of serologic markers of degree of histologic damage in acute uncomplicated colonic diverticulitis.

BACKGROUND: Acute uncomplicated diverticulitis (AUD) may show histologic and serologic signs of inflammation. GOALS: To assess whether serologic markers of inflammation may be predictive of abnormal histology in AUD. STUDY: Twenty-one consecutive patients affected by AUD were studied (15 Males, 6 Females, mean age 66.19 y, range 43 to 85 y). Diagnosis of AUD was based on specific endoscopic and CT scan patterns. Several serologic markers were assessed [White blood cells (WBC), Erytro-sedimentation Rate, C-reactive protein (CRP), fibrinogen, α1-acid glycoprotein]. Neutrophilic and lymphocytic inflammatory infiltrate was also scored. RESULTS: WBC was increased in 4/21 pts (19.4%), Erytro-sedimentation Rate in 12/21 pts (57.14%), CRP in 13/21 pts (61.9%), fibrinogen in 5/21 pts (23.8%), and α1-acid glycoprotein in 6/21 pts (28.57%). All serologic markers were related with the degree of histologic damage. In patients scoring 3 in neutrophilic infiltrate (severe active inflammation), all markers showed a statistical significant relation (ranging from P=0.004 for WBC to P=0.00001 for fibrinogen). CRP was the most sensitive marker of mild-moderate histologic damage, as it was increased in 4/10 (40%) patients scoring 0 or 1 in neutrophilic infiltrate (absence of mild active inflammation) (P=0.005). CONCLUSIONS: Serologic markers showed a strict relation with the degree of histologic damage in AUD. Moreover, CRP is the most sensitive marker of mild-moderate histologic damage.

[Clinical value of serum cytokines in diverticular disease of the colon in elderly patients].

This article demonstrated changes in the level of pro-and anti-inflammatory cytokines in serum of patients of older age groups with small symptom diverticular disease of the colon. Was considered one of the links of the possible pathogenesis of this nosology, touched upon the contribution of involutive changes in the formation of the features of nonspecific immunity and the development of autoimmune reactions in elderly patients.

Involvement of central immunity in uncomplicated diverticular disease.

OBJECTIVE: The pathogenesis of symptoms of uncomplicated diverticular disease (UDD) is unclear, but changes in gut microflora and physiologic inflammation may be implicated. The objective of the study was to investigate the distribution of gut homing lymphocytes in peripheral blood and intestinal mucosa of UDD patients, and the effects of luminal antibiotic treatment. MATERIAL AND METHODS: Ten UDD patients and 10 age- and gender-matched healthy subjects underwent peripheral blood sampling, and colonoscopy with biopsies taken from the transverse and sigmoid colon. Treatment consisted of a 2-month course of rifaximin 1.2 g/day for 15 days/month. Blood sample and mucosal biopsies were repeated in UDD patients at the end of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4, CD8, CD25, CD19, CD45, CD62L, CD103). RESULTS: In peripheral blood, both CD4+ and CD8+/CD103+ were significantly higher in patients at baseline than in controls (0.95% versus 0.36%, and 0.5% versus 0.09%, respectively). After treatment, peripheral CD4+/CD103+ decreased (0.27%), while CD8+/CD103+ did not change (0.35%); on the contrary, peripheral CD25+ increased, the CD4+ subpopulation showing significantly higher levels than those in controls. No difference was found between lymphocytes in the diverticular sigmoid mucosa of patients at baseline and those in controls, but there was a significant decrease in CD8+/CD62L+ after treatment. In the normal transverse colon, CD4+/CD62L+ of patient at baseline were significantly lower than in controls. After treatment, CD4+/CD103+ levels significantly increased, while CD8+/CD62L+ levels significantly decreased. CONCLUSIONS: Both central and mucosal immunity may be modified in UDD patients, with an increased recruitment of CD103+ lymphocytes. A 2-month course of rifaximin appears to reduce CD103+ levels, suggesting a decrease in mobilization of mucosal homing.

[Response of immunocompetent cells and structural changes of colon mucosa in patients with diverticulum disease].

It was established the activisation of macrophages and plasma cells with raise their adhesion in diverticular disease. The express of immune response depends on unit or plural diverticuls. Epithelial cells proliferation is on the increase in the cript and mouth region of diverticul. The small undifferential epithelial cells migrated from depth to top of cripts. These cells formed some fields of cells connected by means of branches. Therefore the chronic inflammation and local disturbance of epithelium regeneration were established in diverticular disease.

How inflammation changes neuromuscular function and its relevance to symptoms in diverticular disease.

Diverticulosis is largely asymptomatic but recent evidence suggests that episodes of acute diverticulitis double the risk of subsequently suffering from recurrent noninflammatory pain. Numerous animal models demonstrate how inflammation is followed by circular muscle hypertrophy, abnormalities of innervation, and increased sensitivity to cholinergic agents. There is also an impairment of norepinephrine and acetylcholine release and damage to nitrergic neurons. These changes are also associated with visceral hypersensitivity. Many of the features, including visceral hypersensitivity are also seen in symptomatic patients with diverticulosis. The trinitrobenzene sulfonic acid colitis model demonstrates that inflammation is followed by long lasting increases in tachykinin and other neuropeptide immunoreactivity. These changes occur both in the mucosa and myenteric plexus and parallel changes seen in resections and mucosal biopsies in diverticular patients. These neural abnormalities may be responsible for the visceral hypersensitivity, which explains why symptoms correlate poorly with objective abnormalities such as intraluminal pressure or motor patterns. Treatment of visceral hypersensitivity might be more effective than current therapies that often leave pain unaltered.

A hypothesis: is diverticulitis a type of inflammatory bowel disease?

It is accepted by epidemiologists that diverticula formation in the colon is related to a deficiency in dietary fiber intake, but the cause of acute diverticulitis remains unknown. A hypothesis is presented that acknowledges from the literature that fiber deficiency is also related to an altered intestinal microecology with a change in the bacterial flora. It is hypothesized that the change in the flora with a decrease in their influence on the immune process permits a low-grade chronic inflammation in the mucosa, which is the first step in developing an acute infection of diverticula or diverticulitis. There is some evidence that the low-grade chronic inflammation is present in subjects with diverticula, which is the forerunner of acute diverticulitis. This hypothesis is strengthened by early reports that anti-inflammatory mucosal agents such as mesalamine and immune process regulators such as probiotics may improve diverticulitis.

Diagnosis and treatment of chronic and recurrent diverticulitis.

In Western countries the prevalence of diverticular disease has increased over the past century. Although, most patients remain asymptomatic, among those who experience an attack of diverticulitis, one-third will have recurrent symptoms, and a further third will have a subsequent episode. The indications for surgery after treatment of acute diverticulitis is still under debate. Uncomplicated disease less commonly as thought, progresses to a life threatening situation such as free perforation. Among those who develop complicated diverticulitis, it is often their first presentation. Fistula to the urinary tract often require surgery; however, complicated disease such as an abscess or phlegmon can be managed conservatively and subsequent surgery is selective depending on the recovery from the initial episode. Patients with chronic diverticular disease (persistent pain in the absence of inflammation) have greatly improved quality of life with surgery. The question of greater virulence of disease among young patients may no longer be true and recommendations for surgery may parallel that of older patients. Immunocompromised patients should have definitive surgical therapy early on in the course of the disease. Right-sided disease remains uncommon in the Western world and a conservative approach in the absence of free perforation is recommended. In right-sided disease and in young patients, misdiagnosis is common. In the elective setting, a laparoscopic approach is rapidly becoming preferred because of less morbidity and shorter hospital stay. The treatment of diverticular disease is rapidly undergoing reevaluation, and novel therapies and increased conservative approaches are evolving. Prospective randomized trials are needed, but remain difficult owing to the uncertain natural history of the disease.

Severe diverticulitis after heart, lung, and heart-lung transplantation.

BACKGROUND: In this study, we reviewed our experience with severe diverticulitis in patients who have undergone heart and/or lung transplantation to assess whether transplant recipients are at increased risk of having severe diverticulitis compared with the general population. METHODS: We reviewed the records of patients who underwent heart and/or lung transplantation from 1984 to 2000, inclusive, and identified patients with severe diverticulitis that required surgery or that resulted in death. We compared this incidence with the incidence of such complications in the general population, served by the same institution during a 2-year period, 1999 to 2000. RESULTS: A total of 953 patients underwent transplantation in the study period. The mean follow-up was 57 months, a total follow-up of 4528 patient-years. Nine patients (mean age, 54 years) had severe diverticulitis that required surgical intervention (8 patients) or that resulted in death (1 patient died without surgical intervention). During 1999 to 2000, 16 patients (mean age, 66 years) from the general population were treated for severe diverticulitis that required surgical intervention, 3 of whom died. From census and area health data, we found that the study institution serves approximately 90000 people older than 40 years, with a total follow-up of 180000 patient-years. The incidence rate ratio for severe diverticulitis when comparing the transplant with the non-transplant groups was 22.2 (95% confidence interval; 9.9-50.0; p < 0.001). CONCLUSIONS: Patients with severe diverticulitis who have undergone heart and/or lung transplantation can be treated surgically with a small mortality rate. Transplant recipients probably are at substantially increased risk of experiencing severe diverticulitis.

Acute recurrent diverticulitis is prevented by oral administration of a polybacterial lysate suspension.

AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal bacteria within the diverticular lumen, leading to a balancing between normal probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae, mainly Escherichia coli and Proteus spp, are the genders that usually cause the disease-related symptoms, due to their ability to adhere to intestinal mucosa. The intestine is well known as the largest human lymphoepithelial organ and daily produces more antibodies, mainly secretory IgAs, than do all other lymphoid tissues. IgAs have different immune and anti-inflammatory properties. The aim of this study was to verify the efficacy of an oral immunostimulant highly-purified, polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and in the improvement of symptoms. METHODS: The study was carried out on 83 consecutive patients suffering from recurrent symptomatic acute diverticulitis and with at least 2 attacks in the previous year; patients were randomly assigned to receive (group A) an oral polybacterial lysate suspension or to a no-treatment clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in group A and 35 in group B) terminated the study period. the sums of the scores for symptoms, reported on day schedules, were calculated and examined by means of ANOVA statistical analysis. Statistical differences between group A vs group B were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the administration of an oral enterovaccine for the prophylaxis of recurrent diverticulitis is effective and well tolerated, probably due to a direct stimulation of IgA-mediated mucosal defences.

T cell receptor delta repertoire in inflamed and noninflamed colon of patients with IBD analyzed by CDR3 spectratyping.

Gamma/delta T cells might play an important role in autoimmune conditions like inflammatory bowel disease (IBD). In the present study, we characterized the T cell receptor (TCR)-delta repertoire by complementarity determining region 3 (CDR3) spectratyping in the inflamed and noninflamed mucosa and in the peripheral blood of subjects with Crohn's disease and ulcerative colitis. In contrast to previously published data about alpha/beta T cells, we rarely found oligoclonal expansions of gamma/delta T cells specific only for the inflamed mucosa. The same dominant gamma/delta T cell expansions were also present in the noninflamed colon. Furthermore, the peripheral gamma/delta TCR repertoire was oligoclonal but clearly distinct from that in the inflamed intestine. Thus our results do not support a role for antigen-specific gamma/delta T cells in IBD, and dominant gamma/delta T cells of the peripheral blood are not likely to be derived from the inflamed gut. However, in several patients, the TCR-delta-repertoire was highly diversified, whereas in others we observed a loss of dominant gamma/delta T cell clones when inflamed and noninflamed mucosa were compared. In conclusion, those changes indicate that gamma/delta T cells might play an important role in a subset of patients with IBD.