From diverticulosis to complicated diverticular disease: Progression of myogenic alterations and oxidative imbalance.

BACKGROUND: The natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex-vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease. METHODS: Colonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents. KEY RESULTS: Compared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction-relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF-1 was detected in both muscle and mucosa. CONCLUSION & INFERENCES: The different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD.

Computational analysis of mechanical stress in colonic diverticulosis.

Diverticulosis results from the development of pouch-like structures, called diverticula, over the colon. The etiology of the disease is poorly understood resulting in a lack of effective treatment approaches. It is well known that mechanical stress plays a major role in tissue remodeling, yet its role in diverticulosis has not been studied. Here, we used computational mechanics to investigate changes in stress distribution engendered over the colon tissue by the presence of a pouch-like structure. The objectives of the study were twofold: (1) observe how stress distribution changes around a single pouch and (2) evaluate how stress elevation correlates with the size of the pouch. Results showed that high stresses are concentrated around the neck of a pouch, and their values and propagation increase with the size of the pouch neck rather than the pouch surface area. These findings suggest that stress distribution may change in diverticulosis and a vicious cycle may occur where pouch size increases due to stress elevation, which in turn elevates stress further and so on. Significant luminal pressure reduction would be necessary to maintain stress at normal level according to our results and therapeutic approaches aimed directly at reducing stress should rather be sought after.

A curious case of colitis.

Segmental colitis associated with diverticulosis (SCAD) is a rare variant of chronic colitis that is limited to segments of the left colon that harbor diverticula. Histologically, SCAD is known to mimic chronic idiopathic inflammatory bowel disease. Patients usually present with hematochezia and cramping abdominal pain; SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy. Due to the histologic overlap with ulcerative colitis and occasional Crohn colitis, the implications of an inaccurate diagnosis are significant.

Association Between Colonic Diverticulosis and Colorectal Polyps, Advanced Neoplastic Lesions, and Colorectal Carcinomas: A Cross-Sectional, Retrospective Study.

PURPOSE: The aim of the present study was to evaluate the association of diverticulosis with colorectal polyps, advanced neoplastic lesions (ANLs), and colorectal cancers (CRCs). METHODS: The first-time colonoscopy records of 3496 patients were evaluated in this retrospective, cross-sectional cohort study. Data on clinical indications, presence of diverticulosis and diverticulitis, location of diverticula and polps, the size and number of polyps, and results of histopathologic examinations of polypectomies were noted. Categorical data were analyzed with χ test or the Fisher exact probability. P-values <0.05 (2 sided) were considered statistically significant. Statistical analyses were conducted with SPSS, version 18. RESULTS: Of the 3496 patients, 1691 were male individuals (48.4%) and 1805 (51.6%) were female individuals. Diverticulosis was present in 12.6% of patients. A total of 870 polyps were detected in 716 patients. A total of 170 polyps (19.5%) were classified as ANLs. CRC was diagnosed in 112 (3.2%) patients. A significant relationship between diverticulosis and colorectal polyps (odds ratio: 1.99; 95% confidence interval: 1.59-0.2.48, P<0.001) was found. Similarly, adenomas and ANLs were more frequent in diverticulosis (P<0.05). There was no significant relationship between diverticulosis and CRCs (P=0.243). CONCLUSIONS: Adenomatous polyps and ANLs were more frequently observed in patients with diverticulosis, but no significant relationship was found between CRC and diverticulosis. The results of this retrospective cross-sectional study need to be confirmed by longitudinal prospective cohort studies.

The "DICA" endoscopic classification for diverticular disease of the colon shows a significant interobserver agreement among community endoscopists.

BACKGROUND AND AIM: An endoscopic classification of Diverticular Disease (DD), called DICA (Diverticular Inflammation and Complication Assessment) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement levels for this classification among an endoscopist community setting. METHODS: A total of 66 endoscopists independently scored a set of DD endoscopic videos. The percentages of overall agreement on the DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of the inter-rater agreement. RESULTS: The overall agreement levels were: 70.2% for DICA 1, 70.5% for DICA 2, 81.3% for DICA 3. The free marginal κ was: 0.553 for DICA 1, 0.558 for DICA 2, 0.719 for DICA 3. The agreement levels among the expert group were: 78.8% for DICA 1, 80.2% for DICA 2, 88.5% for DICA 3. The free marginal κ among the expert group were: 0.682 for DICA 1, 0.712 for DICA 2, 0.828 for DICA 3. The agreement of expert raters on the single item of the DICA classification was superior to the agreement of the overall group. CONCLUSIONS: The overall inter-rater agreement for DICA score in this study ranges from moderate to good, with a significant improvement in the expert subgroup of raters. Diverticular Inflammation and Complication Assessment is a simple and reproducible endoscopic scoring system.

Efficacy of a New Nutraceutical Formulation in Patients with Symptomatic Uncomplicated Diverticular Disease (SUDD): a Prospective Observational Study.

BACKGROUND AND AIM: Symptomatic uncomplicated diverticular disease (SUDD) is characterized by abdominal pain, bloating and altered bowel habits (constipation or diarrhea) attributed to diverticula in the absence of macroscopic mucosal alterations. There is no consensus about management of these patients. DIVER-100®, an association of natural active ingredients may be effective in the treatment of patients with SUDD. The aim was to evaluate the efficacy and safety of DIVER-100® in patients with SUDD. METHODS: We conducted a prospective observational study to evaluate the efficacy of DIVER-100® in consecutive patients with SUDD, confirmed by radiology or endoscopy. All patients were treated with DIVER-100® 2 capsules/day 10 days per month, for 3 months. The primary endpoint was the clinical remission rate, defined as the reduction of abdominal pain and bloating, improvement of bowel habits and prevention of acute diverticulitis (AD). The secondary endpoint was the rate of adverse events. RESULTS: One hundred and one patients were consecutively enrolled at the Internal Medicine and Gastroenterology Unit, Sant'Orsola Hospital, Bologna, Italy. DIVER-100® was effective in inducing remission of symptoms in 12 patients (11.9%) at 3 months and in 10 patients (9.9%) at 6 months. DIVER-100® significantly reduced abdominal pain and bloating in 45.5% and 57.4% of patients respectively (p <0.001) after 3 months. No episodes of AD and no adverse events related to DIVER--100® were recorded at month 6 in the study population. CONCLUSIONS: DIVER-100® is a safe and effective nutraceutical compound in obtaining remission and symptom relief in SUDD patients. Further randomized, placebo-controlled clinical trials are needed to confirm these preliminary data.

Development and usefulness of the new endoscopic classification: DICA.

Colonic Diverticulosis is one of the most common anatomical findings during colonoscopy. This condition has 60% incidence in the population over 60 years old. About 20% of patients will develop Diverticular Disease, and 5% of them will evolve into Diverticulitis. Until the last years there weren't any approaches for the endoscopic classification of this pathology. In 2013, in Florence, the first endoscopic classification was developed: DICA (Diverticular Inflammation and Complication Assessment). The aim of this article is to focus on the process of the development and the validation of the classification by the pool of gastroenterology experts, and, as well, its usefulness during the clinical practice.

Animal Models of Diverticulosis: Review and Recommendations.

Diverticulosis is a structural alteration of the colon tissue characterized by the development of pouch-like structures called diverticula. It afflicts a significant portion of the population in Western countries, with a higher prevalence among the elderly. Diverticulosis is believed to be the result of a synergetic interaction between inherent tissue weakness, diet, colonic microstructure, motility, and genetic factors. A validated etiology has, however, not yet been established. Non-surgical treatment is currently lacking due to this poor understanding, and surgical colon resection is the only long-term solution following recurrent complications. With rising prevalence, the burden of diverticulosis on patients and hospital resources has increased over the past several years. More efficient and less invasive treatment approaches are, thus, urgently needed. Animal models of diverticulosis are crucial to enable a preclinical assessment and evaluation of such novel approaches. This review discusses the animal models of diverticulosis that have been proposed to date. The current models require either a significant amount of time to develop diverticulosis, present a relatively low success rate, or seriously deteriorate the animals' systemic health. Recommendations are thus provided to address these pitfalls through the selection of a suitable animal and the combination of multiple risk factors for diverticulosis.

An Aberrant Microbiota is not Strongly Associated with Incidental Colonic Diverticulosis.

Colonic diverticula are protrusions of the mucosa through weak areas of the colonic musculature. The etiology of diverticulosis is poorly understood, but could be related to gut bacteria. Using mucosal biopsies from the sigmoid colon of 226 subjects with and 309 subjects without diverticula during first-time screening colonoscopy, we assessed whether individuals with incidental colonic diverticulosis have alternations in the adherent bacterial communities in the sigmoid colon. We found little evidence of substantial associations between the microbial community and diverticulosis among cases and controls. Comparisons of bacterial abundances across all taxonomic levels showed differences for phylum Proteobacteria (p = 0.038) and family Comamonadaceae (p = 0.035). The r-squared values measuring the strength of these associations were very weak, however, with values ~2%. There was a similarly small association between the abundance of each taxa and total diverticula counts. Cases with proximal only diverticula and distal only diverticula likewise showed little difference in overall microbiota profiles. This large study suggests little association between diverticula and the mucosal microbiota overall, or by diverticula number and location. We conclude that the mucosal adherent microbiota community composition is unlikely to play a substantial role in development of diverticulosis.

Sex differences in risk factors of uncomplicated colonic diverticulosis in a metropolitan area from Northern China.

As the world's most populated and rapidly aging country, there is limited information on sex-related differences in factors regarding uncomplicated colonic diverticulosis in China. We aimed to investigate sex differences in individual risk factor in a northern metropolis. Patients with colonic diverticulosis who underwent indicated colonoscopy were queried with respect to medical history and demographic features. Demographic information, life style factors and co-morbidities were retrieved from a prospective dataset. Multiple regression analyses were performed to determine precipitating factors of diverticula. Of 4,386 enrolled patients, colonic diverticulosis were detected in 218 cases (4.97%). Multiple logistic regression analysis implicated increasing age (OR = 1.05, 95%CI 1.03-1.06, P < 0.001), red meat ≥100 g/d (OR = 2.53, 95%CI 1.72-3.70, P < 0.001), smoking (OR = 2.14, 95%CI 1.05-4.33, P = 0.035), rheumatologic diseases (OR = 3.38, 95%CI 1.09-10.5, P = 0.035) and NSAIDs (OR = 2.11, 95%CI 1.12-3.97, P = 0.020) were significantly associated with diverticulosis in men, whilst advancing age (OR = 1.03, 95%CI 1.01-1.05, P = 0.013), BMI (OR = 1.12, 95%CI 1.04-1.19, P = 0.001), smoking (OR = 10.2, 95%CI 2.81-37.4, P < 0.001), rheumatologic diseases (OR = 8.04, 95%CI 3.05-21.2, P < 0.001), hypertension (OR = 1.76, 95%CI 1.01-3.06, P = 0.047), colonic polyps (OR = 3.12, 95%CI 1.82-5.36, P < 0.001) and antihypertensive medications (OR = 2.99, 95%CI 1.66-5.39, P < 0.001) in women. In conclusion, it is pivotal to take account of differentially sex-related factors in regard to the development of uncomplicated colonic diverticulosis.

Exogenous lipoid pneumonia induced by nasal decongestant.

INTRODUCTION: Lipoid pneumonia is a clinical condition that may be initially asymptomatic or confused with an infectious or malignant lung disease. OBJECTIVES: We report four cases of this pathological condition. METHODS: The first case concerned an 85-year old woman with bilateral confluent pulmonary opacities, ground-glass type. Diagnosis was based on the cytology of the bronchoalveolar lavage (BAL) fluid followed by its ultrastructural examination. The second case was a 47-year-old man with an isolated pulmonary nodule, which was surgically removed; the diagnosis of lipoid pneumonia was formulated on the basis of the histological and electron microscopy examination. The third case concerned a 73-year-old woman, with bilateral hypodense areas at the bases of the lungs where FDG PET/CT scan showed an increased uptake. Diagnosis was formulated by BAL cytology and electron microscopy examination. The fourth case was a 69-year-old man, who performed a virtual colonoscopy for diverticulosis putting in evidence a round mass (3 cm in diameter) with two small peripheral nodules, located in the pulmonary left lower lobe. The histopathological examination of transthoracic biopsy confirmed a lipoid pneumonia. RESULTS AND CONCLUSION: In all four cases, it was put in evidence a prolonged use of a nasal decongestant containing mineral oils. In literature, the most cases described are characterized by a subclinical evolution and were presented as ground glass opacities which evolve, in the later phases, in an interstitial involvement or in a peripheral mass, simulating a lung tumour.

Complicated diverticulitis in a de novo kidney transplanted patient.

Diverticular disease is frequent amongst the elderly and immunosuppressed patients. It mainly presents as sigmoid diverticulitis, but severe complications, like bleedings, infections and colon perforation may occur, frequently due to immunosuppressive therapy. Moreover, antibiotherapy and hemostatics may not efficiently control evolution in such cases. Early diagnose and adequate treatment of colonic diverticulosis complicated with lower gastrointestinal bleeding and diverticulitis in immunocompromised patients. We report a 55-year-old patient who underwent de novo renal transplantation one year ago and recently developed a severe diverticular bleeding complicated by hemorrhagic shock. Colonoscopic examination revealed diverticular disease with diverticulitis and severe, diffuse bleeding, mainly in the descending colon. Due to his immunocompromised status and unfavorable evolution under hemostatics, recombinant coagulation factor VIIa (rFVIIa) was given to avoid surgery. The bleeding stopped after two doses of rFVIIa. Unfortunately, after three weeks, lower quadrant pain, tenderness, abdominal distention, and fever occurred, in spite of immunosuppressive drug changing and adequate conservative therapy. Abdominal computed tomography (CT) scan revealed complicated diverticulitis, so patient underwent surgery, with partial colectomy, followed by total recovery. In conclusion, diverticulosis coli complicated with lower gastrointestinal bleeding and diverticulitis in immunocompromised patients was for us a challenging diagnosis, as well as a therapeutic issue. Treatment options, usually based on our local resources and expertise, considered conservatory therapy as the first choice, keeping surgical maneuvers just as a rescue solution.

Diagnóstico y tratamiento de la enfermedad diverticular del colon derecho: revisión de conjunto / Diagnosis and management of right colonic diverticular disease: A review

El objetivo de esta revisión es definir las características clínico-patológicas y aclarar el tratamiento de la enfermedad diverticular del colon derecho. Es poco frecuente en Europa, Estados Unidos y Australia, y más común en Asia. Durante los últimos años, su incidencia ha aumentado en Occidente, con diferentes distribuciones entre poblaciones. Muchos estudios han mostrado que es difícil diferenciar antes de la cirugía los síntomas de presentación de esta enfermedad de los de la apendicitis, ya que los síntomas y signos son similares, por lo que no es infrecuente encontrarse con un diagnóstico incorrecto. Con estudios de diagnóstico por la imagen exactos es posible establecer un diagnóstico preoperatorio preciso a fin de evaluar una estrategia de tratamiento adecuada. Actualmente, el tratamiento de esta enfermedad no está bien definido, no se han propuesto recomendaciones claras y no se sabe si también se pueden aplicar las recomendaciones para la enfermedad diverticular del colon izquierdo. Varios autores han señalado que el tratamiento conservador es el mejor enfoque, incluso en caso de reincidencia, y que la cirugía solo estaría indicada en determinados casos

The aim of this narrative review is to define the clinical-pathological characteristics and to clarify the management of right colonic diverticular disease. It is rare in Europe, USA and Australia and more common in Asia. In the recent years its incidence has increased in the West, with various distributions among populations. Many studies have reported that it is difficult to differentiate the presenting symptoms of this disease from those of appendicitis before surgery, because the signs and symptoms are similar, so misdiagnosis is not infrequent. With accurate imaging studies it is possible to reach a precise preoperative diagnosis, in order to assess an accurate treatment strategy. Currently the management of this disease is not well defined, no clear guidelines have been proposed and it is not known whether the guidelines for left colonic diverticular disease can also be applied for it. Several authors have stated that conservative management is the best approach, even in case of recurrence, and surgery should be indicated in selected cases

Segmental colitis associated diverticulosis syndrome.

Segmental colitis associated diverticulosis (SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn's disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa (i.e., "rectal sparing") is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required.

How to Differentiate Segmental Colitis Associated With Diverticulosis and Inflammatory Bowel Diseases.

The segmental colitis associated with diverticulosis," better known by its acronym "SCAD," is a chronic inflammatory process localized in the colonic area presenting diverticulosis, and therefore mainly in the sigmoid colon. By definition, both the rectum and the right colon are spared from any inflammation both endoscopically and from a histologic point of view. Recent data have hypothesized that SCAD may be an independent clinical entity within the inflammatory bowel disease set of diseases. Compared with inflammatory bowel disease, SCAD seems to have a more benign outcome, with low rate of complications.

Do Appendicitis and Diverticulitis Share a Common Pathological Link?

OBJECTIVE: The aim of this study was to determine whether there is an association between appendicitis and diverticulitis. DESIGN: This study is a retrospective cohort analysis. SETTING: This study was conducted in a subspecialty practice at a tertiary care facility. PATIENTS: We examined the rate of appendectomy among 4 cohorts of patients: 1) patients with incidentally identified diverticulosis on screening colonoscopy, 2) inpatients with medically treated diverticulitis, 3) patients who underwent left-sided colectomy for diverticulitis, and 4) patients who underwent colectomy for left-sided colorectal cancer. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The primary outcome measured was the appendectomy rate. RESULTS: We studied a total of 928 patients in this study. There were no differences in the patient characteristics of smoking status, nonsteroidal use, or history of irritable bowel syndrome across the 4 study groups. Patients with surgically treated diverticulitis had significantly more episodes of diverticulitis (2.8 ± 1.9) than the medically treated group (1.4 ± 0.8) (p < 0.0001). The rate of appendectomy was 8.2% for the diverticulosis control group, 13.5% in the cancer group, 23.5% in the medically treated diverticulitis group, and 24.5% in the surgically treated diverticulitis group (p < 0.0001). After adjusting for demographics and other clinical risk factors, patients with diverticulitis had 2.8 times higher odds of previous appendectomy (p < 0.001) than the control groups. LIMITATIONS: The retrospective study design is associated with selection, documentation, and recall bias. CONCLUSIONS: Our data reveal significantly higher appendectomy rates in patients with a diagnosis of diverticulitis, medically or surgically managed, in comparison with patients with incidentally identified diverticulosis. Therefore, we propose that appendicitis and diverticulitis share similar risk factors and potentially a common pathological link.

Risk factors associated with colonic diverticulosis among patients from a defined geographic area.

BACKGROUND: Only a few data regarding colonic diverticulosis are available in Italy. We examined the frequency of colonic diverticulosis and its associations with risk factors in a homogeneous Northern Sardinian population undergoing colonoscopy for any reason in the last decades. METHODS: This was a retrospective single-center study. Medical records of patients undergoing colonoscopy for any indication between 1995 and 2013 were reviewed. Demographic information including age, gender, geographic area (urban, rural), marital status, smoking habit, occupation, body mass index, and comorbidities were collected. Presence, number, and extension of diverticula were assessed by colonoscopy. The diagnosis of diverticulosis was defined by the presence of more than five diverticula. RESULTS: A total of 4458 records were collected (39.8 % males). Analysis by birth cohorts showed a significant progressive age-related increase in the prevalence of diverticulosis. The average prevalence was 18.9 % without significant variation across the 19-year observation period. In 101 (12.1 %) subjects diverticula were single or few. Seventy-one percent of diverticula were located predominantly in the left side, 2 % in the right side, and 14.3 % were spread throughout the colon. There was a significant association with obesity but not with smoking habits, marital status, or urban versus rural environment. A strong association was observed between the presence of diverticulosis and cardiovascular and other gastrointestinal and lung disease (p < 0.0001). These associations were also confirmed by the logistic regression analysis. CONCLUSIONS: In this endoscopic study, colonic diverticulosis in Northern Sardinia showed prevalence similar to other series in Western countries, and it was predominantly left sided and age related.