Histological inflammation in ulcerative colitis in deep remission under treatment with infliximab.

BACKGROUND AND OBJECTIVE: There are few data on how histological signs of inflammation develop under treatment with infliximab (IFX). We investigated the patterns of histological features of inflammation in patients with UC in sustained clinical and endoscopic remission under IFX. METHODS: We performed a retrospective study on 47 patients with UC in clinical and endoscopic remission and undergoing surveillance colonoscopy with biopsies while receiving maintenance therapy with IFX. Each colonic segment was evaluated based on the Mayo endoscopic subscore and the Geboes histology score (range 0-5.4). RESULTS: Globally, 6110 biopsy specimens were collected from 235 colonoscopies. At the beginning of the follow-up, histological features of inflammation were found in 48.9% of patients receiving maintenance IFX therapy; 25.9% of them had at least moderate inflammation based on histology scores. At the end of the follow-up, when patients were still under endoscopic and clinical remission, 40.4% of patients had at least one biopsy specimen with evidence of any histological inflammation during the follow-up, and 19.1% had biopsy specimens that met the Geboes criteria for histological inflammation and architectural alteration. In none of the different disease locations (pancolitis, left-sided colitis, distal colitis) histological inflammation improved significantly during the follow-up. CONCLUSIONS: Patients in clinical and endoscopic remission from UC under IFX still frequently have histological features of inflammation.

Lung ultrasonography may provide an indirect estimation of lung porosity and airspace geometry.

BACKGROUND: Echographic vertical artifacts (B-lines) in chest ultrasonography have often been associated with pathological patterns. A scientifically sound explanation of these artifacts has not yet been proposed. OBJECTIVES: The 'spongy' nature of the lung in its liquid and solid components and the changes that take place in peripheral airspace (PAS) geometry might be the key point to understanding these phenomena. METHODS: Six excised right rabbit lungs were obtained. Each lung underwent direct ultrasound evaluation in two different conditions: at complete tissue elastic recoil volume and at pulmonary expansion volume achieved by applying a constant positive pressure of 12 cm H2O. Lung volumes and densities were reported in both conditions. Histological examination was performed on three naturally collapsed lungs and on three lungs under positive pressure inflation after having been fixed in formalin solution. RESULTS: Mean volumes of naturally collapsed lungs and fixed expanded lungs were 11.2 ± 0.36 and 44.83 ± 3.03 ml, respectively. Mean densities were 0.622 ± 0.016 and 0.155 ± 0.007 g/ml, respectively. Ultrasound evaluation of collapsed lungs showed dense vertical artifacts and a 'white lung' pattern, while the evaluation of expanded lungs showed hyperechoic line and horizontal artifacts of reflection. Histological evaluation showed a different PAS geometry in collapsed lungs caused by alveolar size reduction and shape changes with unfolded and closed units modifying the peripheral porosity of the frothy nature of the lung. CONCLUSIONS: Airspace geometry, frothy nature and porosity are the determinants of the different behavior of ultrasound interacting with the subpleural lung parenchyma. Chest ultrasound may thus be interpreted as an indirect 'estimator' of lung porosity.

Mucosal expression of basic fibroblastic growth factor, syndecan 1 and tumour necrosis factor-α in Crohn's disease in deep remission under treatment with anti-TNFα antibodies.

BACKGROUND AND AIMS: Both inflammation and fibrosis may be detected in Crohn's disease (CD). The molecular pattern of Basic Fibroblastic Growth Factor (bFGF) and Syndecan-1 (SD1) expression is altered in stenosing CD, but we do not know what the behaviour of this teamwork factor is in CD in deep remission under treatment with anti-TNFα antibodies. Our aim was to compare the expression of bFGF, SD1 and TNF-α in patients with CD in deep remission under treatment with Infliximab (IFX) or Adalimumab (ADA) and a control group of patients with active CD. METHODS: We assessed the expression of bFGF, SD1 and TNF-α in 10 patients with active CD and in 28 patients with CD in sustained deep remission for at least 6 months. All patients underwent surveillance colonoscopy with biopsies, while receiving maintenance therapy with IFX or ADA. Analysis was conducted by real-time reverse transcriptase PCR (RT-PCR) in biopsy samples. RESULTS: We found that bFGF, SD1 and TNF-α were significantly reduced under treatment with anti-TNFα versus controls (p=0.000). bFGF and SD1 expression were similar between IFX and ADA patients (p=0.335 and p=0.289, respectively), while TNF-α was significantly under-expressed in ADA patients (p=0.008). CONCLUSIONS: bFGF, SD1 and TNF-α are significantly reduced in CD patients in deep remission under treatment with anti-TNFα, likely as an expression of optimal control of inflammation. The significance of the TNF-α under-expression in patients under treatment with ADA with respect to those under treatment with IFX should be elucidated in further studies.

Detection of endoscopic and histological inflammation after an attack of colonic diverticulitis is associated with higher diverticulitis recurrence.

BACKGROUND & AIMS: Colonic diverticulitis shows a high recurrence rate, but the factors associated with such recurrence are still unknown. The aim of our study was to investigate the role of endoscopic and histological inflammation as predictors for the recurrence of diverticulitis. METHODS: One hundred and thirty patients suffering from Acute Uncomplicated Diverticulitis (AUD) (81 males, 49 females, mean age 64.71 years, range 40-85) were prospectively assessed. All patients had AUD confirmed by computerized tomography (CT) and endoscopy. Clinical, endoscopic and histological follow-up was performed after 6, 12 and thereafter 24 months after diagnosis of AUD. RESULTS: Sixteen patients were lost to follow-up. Diverticulitis recurred in 18 patients (13.84%): 15 (13.15%) patients showed recurrence of AUD, whilst 3 (2.63%) showed recurrence of complicated diverticulitis. At the end of the follow-up period, endoscopic inflammation was still detected in 31 (27.67%) patients, and active histological inflammation in 41 patients (36.6 %). Only detection of endoscopic and of histological inflammation during the follow-up was a predictor of diverticulitis recurrence (Log rank test, p = 0.0004). CONCLUSIONS: Detection of endoscopic and histological inflammation after attack of AUD was identified as a predictor of diverticulitis recurrence.

Ex vivo lung sonography: morphologic-ultrasound relationship.

Ultrasound (US) interstitial syndrome is a sonographic lung pattern characterized by the presence of acoustic artifacts (B-lines and white lung). The purpose of this study was to demonstrate how interstitial syndrome is determined by acoustic interactions in lungs of variable density and in healthy organs deflated to a nonphysiologic level of density. Normal rabbit lungs were studied ex vivo by US at varying known degrees of inflation, and their histologic appearances were described. In this experimental setting, US interstitial syndrome recognizes a mechanism related to tissue density or porosity. Artifacts (B-lines and white lung) appear in the normal rabbit lung through air-dependent increases in density. As in pathologic conditions, US interstitial syndrome can be reproduced in histologically normal lungs that are deflated to a critical level (>0.45 g/mL) of density, which is not achievable under physiologic conditions.

Segmental colitis associated with diverticulosis: a 5-year follow-up.

BACKGROUND AND AIMS: Literature data about the outcome of segmental colitis associated with diverticulosis (SCAD) are scarce. Our aim was to assess the clinical outcome of SCAD according to the type of disease. PATIENTS/METHODS: Twenty-seven SCAD patients underwent a 5-year follow-up (13 males, 14 females; mean age, 63.71 years; range, 50-85 years). Eleven patients were affected by type A, eight by type B, four by type C and four by type D SCAD. During the follow-up, all type B, C, and D patients were under continuous medical treatment. Five type A patients refused any maintaining treatment, but accepted to undergo the clinical, endoscopic, and histological follow-up. RESULTS/FINDINGS: Five type A patients taking therapy (83.33%), two type A not taking therapy (50%), all type C patients (100%), five type B patients (62.5%) and none of type D (0%) were under continuous remission at the end of the follow-up. All type D patients required further steroid course to obtain remission, and two patients required azathioprine to maintain remission. INTERPRETATIONS/CONCLUSIONS: SCAD B and D patients fail to maintain long-term remission, often requiring immunosuppressive treatment. SCAD A and C patients show a more benign course; however, long-term treatment guarantees longer remission also in those patients.

Tumour necrosis factor-alpha expression in segmental colitis associated with diverticulosis down-regulates after treatment.

BACKGROUND AND AIMS: Tumour necrosis factor-α (TNF-α) expression may be increased in segmental colitis associated with diverticulosis (SCAD). Our aim was to assess TNF-α expression in SCAD in relationship to the treatment. METHODS: 10 patients affected by severe (type B and D) SCAD were studied (6 males, 4 females, mean age 60.54 years, range 43-85 years). All patients were treated with beclomethasone dipropionate 10 mg/day plus a probiotic preparation VSL#3 for 8 weeks. At that time, clinical, endoscopic and histological reassessment was performed. Controls were 5 patients with active ulcerative colitis (UC). RESULTS: After treatment, all SCAD B and no SCAD D patients were in remission. The TNF-α expression dropped from 42.7% (+/-7.58) to 15.7% (+/-2.6) in SCAD B patients (p=0.001), and from 40% (+/-5.9) to 28.6% (+/-5.3) in SCAD D patients (p=0.005). In UC patients, the TNF-α expression dropped from 45.5% (+/-5.09) to 22.5% (+/-2.5) (p=0.001). Neither SCAD B nor SCAD D patients showed a significant difference in TNF-α expression compared to UC after treatment. Finally, TNF-α was significantly overexpressed in SCAD D than in SCAD B at the end of treatment (p=0.048). CONCLUSIONS: TNF-α expression in SCAD down regulates after treatment, and seems to be related to the clinical response to therapy. This behaviour, similar to that of Inflammatory Bowel Diseases (IBD), confirms that this disease should be considered as a subtype of IBD.

Tumour necrosis factor-alpha expression in segmental colitis associated with diverticulosis is related to the severity of the endoscopic damage.

BACKGROUND: Tumour necrosis factor-α expression may be increased in segmental colitis associated with diverticulosis. AIMS: To assess tumour necrosis factor-α expression in segmental colitis associated with diverticulosis in relation with the severity of the endoscopic damage. METHODS: 21 patients affected by segmental colitis associated with diverticulosis were studied (15 M, 6 F, mean age 58.87 years, range 43-85 years). Segmental colitis associated with diverticulosis was graduated as mild-moderate (patterns A and C) and severe (patterns B and D). Ten patients with moderate-to-severe ulcerative colitis, 10 patients with moderate-to-severe Crohn's disease, and 10 patients with irritable bowel syndrome served as control groups. RESULTS: Tumour necrosis factor-α expression was significantly higher in segmental colitis associated with diverticulosis B (42.7%) and segmental colitis associated with diverticulosis D (40%) than in segmental colitis associated with diverticulosis A (19.1%) and segmental colitis associated with diverticulosis C (21.1%).Tumour necrosis factor-α expression was lower in segmental colitis associated with diverticulosis A and C than in ulcerative colitis and Crohn's disease, whilst no different tumour necrosis factor-α expression was found between segmental colitis associated with diverticulosis B and D and both ulcerative colitis and Crohn's disease.Finally, tumour necrosis factor-α expression was significantly lower in irritable bowel syndrome (8%±4) than in every type of segmental colitis associated with diverticulosis. CONCLUSIONS: Tumour necrosis factor-α expression in segmental colitis associated with diverticulosis seems to be related to the severity of the endoscopic damage. This behaviour, similar to that of the inflammatory bowel diseases (IBD), confirms that this disease should be considered as a subtype of IBD.

Hydrocele with surprise. Case report and review of literature.

INTRODUCTION: Hydrocele is a fluid collection between tunica vaginalis and testis. Approximately 10% of testicular cancers occurs with a reactive hydrocele. CASE REPORT: A 64 year old male presented with a 30 year history of left hydrocele, progressively increasing. Physical examination demonstrated a left large hydrocele, transilluminable, not under pressure. Ultrasonography showed a "corpusculated hydrocele with vaginal hypertrophy jutting out near the head of the epididymis, perhaps caused by an inflammatory reaction [...]" As the patient showed only a minimal discomfort due to the groin swelling, without pain, surgical excision was planned without priority (Class C < 180 days). RESULTS: The surgical exploration showed a paratesticular papillary neoplasm of 3 cm. Intraoperative pathologic examination of a frozen sample demonstrated a "borderline papillary cystadenoma". The Left orchifunicolectomy was performed. The definitive histological examination showed a "left paratesticular Papillary Serous Tumor of Low Malignant Potential (PSTLMP) with morfoimmunoistochemical features of Mullerian origin of neoplasm". Computed tomography (CT) was negative for lymph nodes and metastasis. In agreement with the oncologist we decide for atchful waiting. DISCUSSION: Despite of rich personal experience of resections and eversions of the vaginal tunic, an urologist rarely observes a case of paratesticular cancer. A PubMed search found 28 citations between 1985 and 2010 with 42 reported cases of paratesticolar neoplasm, including 27 with malignancy features. Rhabdomyosarcoma is the most common, followed by mesothelioma, adenocarcinoma and neuroblastoma. This case report consists of a "borderline" neoplasm for which in the literature, after orchiectomy, it is reported no case of recurrence or metastasis (with a follow up of up to 18 years). CONCLUSION: The banality of the disease never must underestimate the possibility of an undetected cancer.

Faecal calprotectin in colonic diverticular disease: a case-control study.

BACKGROUND AND AIMS: Information about faecal calprotectin (FC) in colonic diverticular disease (DD) are lacking. We assessed FC in colonic DD, comparing it with irritable bowel syndrome (IBS) patients and healthy controls. Moreover, we compared FC levels in different degrees of DD and assessed FC in symptomatic DD before and after treatment. MATERIALS AND METHODS: Forty-eight consecutive patients with a new endoscopic diagnosis of DD (16 with asymptomatic diverticulosis, 16 with symptomatic uncomplicated DD, 16 with acute uncomplicated diverticulitis), 16 healthy controls, and 16 IBS patients were studied. FC was assessed by semi-quantitative method and compared with histological inflammation. Moreover, FC was reassessed in symptomatic DD after 8 weeks of treatment. RESULTS/FINDINGS: FC was not increased in healthy controls and IBS patients. No difference was found between asymptomatic diverticulosis, healthy controls, and IBS patients (p = n.s.). We found higher FC values in acute uncomplicated diverticulitis (p < 0.0005) and in symptomatic uncomplicated DD (p < 0.005) than in healthy controls and in IBS patients. FC values correlated with inflammatory infiltrate (p < 0.0005). FC decreased after treatment to normal values both in acute uncomplicated diverticulitis (p < 0.0005) and in symptomatic uncomplicated DD (p < 0.005) after treatment. INTERPRETATIONS/CONCLUSIONS: FC may be useful to detect colonic inflammation in DD and in distinguishing symptomatic DD from IBS, as well as in assessing response to therapy in DD.

Assessment and grading of mucosal inflammation in colonic diverticular disease.

GOAL: The aim of this study was to assess and grade the mucosal inflammatory infiltrate in different degrees of diverticular disease (DD) and to compare them with healthy matched controls. BACKGROUND: Mucosal inflammation in colonic DD has never been investigated. In particular, it is unknown whether inflammation may be found in every degree of DD. MATERIALS AND METHODS: Thirty consecutive patients with a new endoscopic diagnosis of DD (10 with asymptomatic diverticulosis, 10 with symptomatic uncomplicated DD, and 10 with acute uncomplicated diverticulitis) and 10 healthy controls were studied. RESULTS: A neutrophilic inflammatory infiltrate was found only in acute uncomplicated diverticulitis (overall score, 26). The mean lymphocytic cell density was significantly higher in symptomatic DD (median lymphocytic density, 7) and acute uncomplicated diverticulitis (median lymphocytic density, 11). Subdividing the patients according to different degrees of DD, we found higher lymphocytic cell density even in asymptomatic diverticulosis (median lymphocytic density, 6.5) than healthy controls (median lymphocytic density, 4; P<0.02). CONCLUSIONS: We found an increased inflammatory infiltrate in DD according to the degree of the disease and higher than healthy controls. Moreover, also asymptomatic diverticulosis shows higher inflammatory cell density than controls.

Epithelial cell proliferation of the colonic mucosa in different degrees of colonic diverticular disease.

GOAL: This study assesses the epithelial cell proliferation in different degrees of diverticular disease and compares this with two different control groups. BACKGROUND: Hyperproliferation of the colonic mucosa has been recently described in diverticular disease (DD), but it is unknown whether this finding is present in every degree of DD. PATIENTS AND METHODS: Thirty consecutive patients with a new endoscopic diagnosis of DD (10 with asymptomatic diverticulosis, 10 with symptomatic uncomplicated DD, and 10 with acute uncomplicated diverticulitis) were enrolled. Ten matched healthy people and 10 patients with ulcerative colitis (UC) (5 with UC in remission and 5 with active UC) were enrolled as control groups. The Ki-67 antigen index of the whole crypt and the upper third was separately evaluated. RESULTS: Ki-67 index of the whole crypt and the upper third of the crypt was significantly higher in all degrees of DD compared with the healthy control group. In particular, asymptomatic diverticulosis showed a threefold higher Ki-67 index compared with that of the healthy control group (5.4% and 5.6% vs. 1.6% and 1.8%, respectively, P = 0.005), and similar to that of UC in remission (5.4% and 5.6% vs. 5.9% and 5.8%, respectively, P = not significant). CONCLUSIONS: We found an upward shifting of cellular proliferation of the colonic mucosa in patients with different degrees of DD. In particular, asymptomatic diverticulosis seems to show the same risk for colonic carcinoma as that of UC.