Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis

AIM: To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC).METHODS: In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS: Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression.CONCLUSION: The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.     

Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer.METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as “front-positive” and in 41% as “front-negative”. The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the “front-positive” tumors.CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.     

Laminarthrectomy as a surgical approach for decompressing the spinal canal: assessment of preoperative versus postoperative dural sac cross-sectional areal (DSCSA)

Introduction

Surgery for lumbar spinal stenosis (LSS) is today the most frequently performed procedure in the adult lumbar spine. Long-term benefit of surgery for LSS is well documented both in randomized and in non-randomized trials. In this paper, we present the results from laminarthrectomy as an alternative surgical approach, which have theoretical advantages over other approaches. In this study, we wanted to study the clinical and radiological results of laminarthrectomy. Dural sac cross-sectional areal (DSCSA) is an objective method to quantify the degree of central stenosis in the spinal canal, and was used to measure whether we were able to achieve an adequate decompression of the spinal canal with laminarthrectomy as a surgical approach.

Materials and methods

All patients operated on with this approach consecutively in the period 1 January 2008 to 31 March 2009 were included in the study. All perioperative complications were noted. Clinical results were measured by means of a questionnaire. The patients that agreed to attend the study had an MRI taken of the operated level. DSCSA before and after surgery of the actual level were measured by three observers. We then performed a correlation test between increase of area and clinical results. We also tested for inter- and intra-observer reability.

Results

Fifty-six laminarthrectomy were performed. There were 17 % complications, none of them were life-threatening or disabling. 46 patients attended the study and answered the questionnaire. Thirty-four patients (83 %) reported clinical improvement, whereas six (13 %) patients reported no improvement, and two (4 %) patients reported that they were worse. Mean ODI was 23.0. Mean EQ-5D was 0.77. Mean VAS-score for back-pain was 3.1 and mean VAS-score for leg-pain was 2.8. Mean DSCSA were measured to 80 mm² before surgery and 161 mm² after surgery. That gave an increase of DSCSA of 81 mm² (101 %). We found a significant positive correlation between increase of area and clinical results. We also found consistent inter- and intra-observer reability.

Discussion

In this study, the clinical results of laminarthrectomy were good, and comparable with other reports for LSS. The rates of complications are also comparable with other reports in spinal surgery. A significant increase in the spinal canal diameter was achieved. Within the limitations a retrospective study gives, we conclude that laminarthrectomy seems to be a safe and effective surgical approach for significant decompressing the adult central spinal canal, and measurement of DSCSA, before and after surgery seems to be a good way to quantify the degree of decompression.     

Too tight to give birth? Assessment of pelvic floor muscle function in 277 nulliparous pregnant women

Introduction and hypothesis

Theoretically, tight or strong pelvic floor muscles may impair the progress of labor and lead to instrumental deliveries. We aimed to investigate whether vaginal resting pressure, pelvic floor muscle strength, or endurance at midpregnancy affect delivery outcome.

Methods

This was a prospective cohort study of women giving birth at a university hospital. Vaginal resting pressure, pelvic floor muscle strength, and endurance in 300 nulliparous pregnant women were assessed at mean gestational week 20.8 (±1.4) using a high precision pressure transducer connected to a vaginal balloon. Delivery outcome measures [acute cesarean section, prolonged second stage of labor (> 2 h), instrumental vaginal delivery (vacuum and forceps), episiotomy, and third- and fourth-degree perineal tear) were retrieved from the hospital’s electronic birth records.

Results

Twenty-three women were lost to follow-up, mostly because they gave birth at another hospital. Women with prolonged second stage had significantly higher resting pressure than women with second stage less than 2 h; the mean difference was 4.4 cmH₂O [95 % confidence interval (CI) 1.2–7.6], p?<?0.01, adjusted odds ratio 1.049 (95 % CI 1.011–1.089, p?=?0.012). Vaginal resting pressure did not affect other delivery outcomes. Pelvic floor muscle strength and endurance similarly were not associated with any delivery outcomes.

Conclusions

While midpregnancy vaginal resting pressure is associated with prolonged second stage of labor, neither vaginal resting pressure nor pelvic floor muscle strength or endurance are associated with operative delivery or perineal tears. Strong pelvic floor muscles are not disadvantageous for vaginal delivery.     

Renal impairment in children with posterior urethral valves

Background

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

Methods

We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

Results

The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p?=?0.024), nadir serum creatinine (p?<?0.001), and last known serum creatinine level (p?=?0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p?=?0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

Conclusions

Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.     

HRQoL after coronary artery bypass grafting and percutaneous coronary intervention for stable angina

Objectives. To assess the health related quality of life (HRQoL) and the change in the NYHA class after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the management of stable coronary artery disease (CAD). The study was non-randomized. CABG group consisted of 240 patients and 229 patients were treated with PCI. HRQoL was measured prospectively by the 15D instrument. Results. Three-year survival was 95.0 and 95.6% (NS). The HRQoL improved statistically in both groups until 6 months after treatment but deteriorated towards the end of the follow-up of 36 months. Clinically evident improvement of the HRQoL and decrease of the NYHA class took place more frequently among CABG patients. Conclusions. Despite initially more serious preoperative state and more demanding procedure CABG patients achieve equal level of HRQoL when compared with PCI patients. CABG patients may also obtain better relief from symptoms in mid-term follow-up. HRQoL cannot be the only factor to determine outcome after invasive treatment of CAD but it has to be placed in the context of the overall situation.