Prognostic value of various staging and grading systems in proximal colon cancer.

OBJECTIVE: To compare the ability of various methods of staging and grading to predict survival in proximal colon cancer. DESIGN: Retrospective study. SETTING: University hospital, Finland. SUBJECTS: 153 patients with primary proximal colon cancer. MAIN OUTCOME MEASURES: Staging by four classification systems, grading by two grading systems, and survival analysis based on Kaplan-Meier survival curves. RESULTS: In all staging systems the survival curves of different stages differed significantly from each other. The modified Dukes' classification was still the best predictor of survival. Grade of tumours had no significant effect on long term survival, but short term survival was affected adversely by the presence of anaplastic tissue. Tumours with no mucin had a worse prognosis than those that produced mucin. All staging methods were superior to either of the histological grading systems tested as prognosticators. Tumour depth correlated with the operator's clinical impression of radicality of operation, and also predicted survival. CONCLUSION: The clinicopathological modified Dukes' staging system was the most powerful prognosticator in proximal colonic cancer and its use in clinical practice should continue. Even a small amount of anaplastic tissue (> or = 5%) had an adverse effect on short term survival.     

Parental alcohol misuse is a powerful predictor for the risk of traumatic brain injury in childhood

Background: Although the positive relationship between parental alcohol use and children's injuries is well established, it is not known whether parental alcohol misuse is a risk factor for traumatic brain injuries (TBIs) of their children and whether subjects with childhood TBI have hazardous drinking habits in adolescence.

Methods: The authors conducted a longitudinal cohort study at Oulu University Hospital. The cohort consisted of 12 058 subjects born in 1966, of which 207 had sustained TBI before the age of 14 years. Data on parental alcohol problems were obtained from the Finnish Hospital Discharge Register and the adolescents' drinking habits were analysed based on a postal inquiry at the age of 14 years.

Results: Parental alcohol misuse (RR 1.99, CI 1.19-3.33) and male gender (RR 1.53, CI 1.12-2.08) significantly predicted the risk of childhood TBI. Drinking to intoxication at the age of 14 was significantly associated with parental alcohol misuse (RR 1.62, CI 1.34-1.96), belonging to a one-parent family (RR 1.80, CI 1.61-2.02) and mild TBI (RR 1.67, CI 1.20-2.33).

Conclusions: It was observed that parental alcohol misuse is a major risk factor for TBI in children and drinking to intoxication is a common drinking pattern of adolescents who have sustained TBI in childhood.     

Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis

Acute idiopathic tubulointerstitial nephritis (TIN) is considered a condition with a good long-term prognosis. However, there is evidence that some patients develop permanent renal impairment. The aim of this study was to evaluate the clinical characteristics of TIN at the time of diagnosis in children and determine whether the findings upon presentation predict renal outcome. The clinical data and biopsy findings from 26 children with idiopathic TIN admitted to four Finnish university hospitals were analyzed retrospectively. Twenty-five patients (96%) manifested renal insufficiency. After the mean follow-up time of 2.75 years (SD 2.5; 0.9–13.5), 4 patients (15%) had permanent renal insufficiency and 8 patients (31%) had persistent low-molecular weight proteinuria. Uveitis was found in 12 patients (46%). Four of these patients (33%) developed chronic uveitis. Our analysis showed that none of the laboratory or biopsy findings upon presentation prognosticated renal outcome. No correlation between renal disease and uveitis could be found either. The occurrence of uveitis among TIN patients was higher than previously reported. Uveitis may develop late and without recurrence of renal dysfunction. Therefore, follow-up by a pediatrician and by an ophthalmologist is warranted in children with acute TIN for at least 12 months from diagnosis.     

Diet does not explain the high prevalence of dyslipidaemia in paediatric renal transplant recipients

Dyslipidaemia exists frequently after renal transplantation (RTx) and promotes atherosclerosis. In this study, we examined the association between daily intake of nutrients and serum lipids after paediatric RTx. We studied 45 children with acceptably functioning kidney grafts and adequately completed food records at a median age of 10.6 years (range 4.3–17.2 years), a median 5.2 years (range 1.0–11.0) after RTx, and 178 healthy controls at a median age of 9.0 years (range 3.2–18.7 years). Serum total cholesterol (TC), triglyceride, and apolipoprotein B concentrations were higher in the RTx patients than in the controls (P < 0.001), despite similar dietary intakes of saturated and polyunsaturated fats, and cholesterol. Both the RTx patients and controls ingested a low amount of polyunsaturated fats [mean (SD) percent of total calories (E%) 4.8 (1.3) and 4.6 (1.5), respectively] and an excessive amount of saturated fats [mean (SD) E% 14.4 (2.4) and 14.1 (2.8), respectively]. In multiple regression analyses, dietary fibre was negatively associated with serum TC concentration. The standard deviation score for body mass index was negatively associated with serum concentration of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein diameter, and positively with serum triglyceride concentration. In addition, dietary total fat intake was positively associated with serum HDL-C. In conclusion, the higher prevalence of dyslipidaemia in our paediatric RTx patients than in the controls was not explained by the diet. However, the type of fat consumed implicates the counselling for a healthier dietary lifestyle, with an increase in the ingestion of polyunsaturated fats and a decrease in that of saturated fats.     

The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men

INTRODUCTION: Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population. Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established. METHODS: We studied the association of LRP5 polymorphisms with peak bone mass in young men. The study included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture history were recorded. Bone mineral content (BMC), density (BMD) and scan area were measured for the lumbar spine and proximal femur by dual energy X-ray absorptiometry (DXA). Blood and urine were collected for determination of bone turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5 were analyzed and correlated with bone parameters. RESULTS: Only the A1330V polymorphism of LRP5 significantly associated with bone parameters. In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture history was similar for the genotypes. CONCLUSION: The polymorphic valine variant at position 1330 of LRP5 was significantly associated with reduced BMC and BMD values in healthy young Finnish men. The results provide evidence for the crucial role of LRP5 in peak bone mass acquisition.     

Laparoscopic sigmoid and rectal resection using an electrothermal bipolar vessel sealing device

BACKGROUND: Laparoscopic colonic resection has gained popularity as a method to treat colonic diseases. The electrothermal bipolar vessel sealer (EBVS; LigaSure Atlas) is a modern device that allows the secure sealing of vessels with a diameter of up to 7 mm. The aim of the present study was to evaluate the suitability of the device for laparoscopic colonic surgery. METHODS: The immediate outcome of 114 consecutive patients who underwent a sigmoid or rectal resection was prospectively analyzed. The intention was to perform all operations with the EBVS for dissection and ligation of the mesenterial vessels. Details on patient characteristics, peroperative and postoperative complications, and postoperative recovery were recorded prospectively and analyzed. RESULTS: One hundred and fourteen patients were scheduled for elective left-sided colonic or rectal resection. Massive intra-abdominal adhesions in 1 patient required a conversion of the laparoscopic procedure to an open one; In total, 113 laparoscopic operations were thus performed. The mean operative time was 87.7 +/- 2.8 minutes, and the mean time for patients to tolerate solid food was 3.4 +/- 0.1 days and the time to discharge from hospital was 4.6 +/- 0.2 days. There were nine (8.0%) general complications, and additionally, 10.6% of patients suffered from surgical complications. CONCLUSIONS: The electrothermal bipolar vessel sealer is suitable and safe for laparoscopic sigmoid and rectal resections. The use of the device probably reduces the operative time.     

Cyclosporin A for the treatment of severe Henoch-Schönlein glomerulonephritis

We evaluated the efficacy of cyclosporin A (CyA) for treating pediatric patients with severe Henoch-Schönlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria. Seven pediatric HSP-GN patients (5 boys, 2 girls) were treated with CyA, with a mean age of 10.6 years at diagnosis (range 7.2–15.2 years) and mean follow-up times of 6.0 years (range 4.4–8.9 years) from diagnosis and 5.2 years (range 3.4–7.7 years) from the beginning of the CyA treatment. All had developed nephrotic-range proteinuria within 1–3 months of the HSP diagnosis. A renal biopsy was performed on all the patients, and two showed rapidly progressive glomerulonephritis. They all received additional angiotensin converting enzyme inhibitor medication and one to three types of immunosuppressive treatment had been tried in five of the seven patients before CyA was initiated at a mean interval of 0.7 years after diagnosis (range 0.1–2.0 years). All the patients responded to the CyA treatment within a mean of 1.4 months (range 1 week to 4 months). Four patients achieved a stable remission and had been without CyA treatment for a mean of 3.7 years (range 2.9–5.3 years) by the end of the follow-up. Three patients seemed to become CyA dependent, since they developed proteinuria when the treatment was stopped. CyA treatment had been started significantly earlier (P=0.045) in the former group (mean 0.2 years, range 0.1–0.3 years) than in the latter (mean 1.5 years, range 1.2–2.0 years). Renal function was preserved in all patients, the glomerular filtration rate, plasma cystatin C, serum albumin, and serum creatinine being within normal limits at the end of the follow-up. We conclude that CyA treatment for severe treatment-resistant HSP-GN is promising, since four of the seven patients enjoy stable remission and all have retained their renal function after a mean follow-up of 6.0 years. However, some patients seem to develop CyA-dependent nephritis.The results were presented as a poster at the 36th meeting of the European Society for Pediatric Nephrology in Bilbao     

Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/PI3K pathway

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.