Stoma reversal after intended restorative rectal cancer resection in Denmark: nationwide population-based study.

BACKGROUND: Data on stoma reversal following restorative rectal resection (RRR) with a diverting stoma are conflicting. This study investigated a Danish population-based cohort of patients undergoing RRR to evaluate factors predictive of stoma reversal during 3 years of follow-up. METHODS: Patients from national registries with rectal cancer undergoing RRR or Hartmann's procedure with curative intent between May 2001 and April 2012 were included. Patients with a diverting stoma were followed from the time of primary rectal cancer resection to date of stoma reversal, death, emigration, or end of 3-year follow-up. The cumulative incidence proportion (CIP) of stoma reversal at 1 and 3 years was calculated, treating death as a competing risk. Factors predictive of stoma reversal were explored using Cox regression analysis. RESULTS: Of 6859 patients included, 35·7, 41·9 and 22·4 per cent respectively had a RRR with a diverting stoma, RRR without a stoma, and Hartmann's procedure with an end-colostomy. In patients with a diverting stoma, the CIP of stoma reversal was 70·3 (95 per cent c.i. 68·4 to 72·1) per cent after 1 year, and 74·3 (72·5 to 76·0) per cent after 3 years. Neoadjuvant treatment (hazard ratio (HR) 0·75, 95 per cent c.i. 0·66 to 0·85), blood loss greater than 300 ml (HR 0·86, 0·76 to 0·97), anastomotic leak (HR 0·41, 0·33 to 0·50), T3 category (HR 0·63, 0·47 to 0·83), T4 category (HR 0·62, 0·42 to 0·90) and UICC stage IV (HR 0·57, 0·41 to 0·80) were possible predictors of delayed stoma reversal. CONCLUSION: In one-quarter of the patients the diverting stoma had not been reversed 3 years after the intended RRR procedure.

ANTECEDENTES: Los datos sobre el cierre del estoma (stoma reversal, SR) tras la exéresis el recto con intención reconstructiva (restorative rectal resection, RRR) y estoma derivativo (diverting stoma, DS) son contradictorios. Este estudio analizó los factores predictivos del SR en una cohorte danesa de base poblacional de pacientes sometidos a RRR con un seguimiento de 3 años. MÉTODOS: Los pacientes con cáncer de recto a los que se realizó una RRR o una operación de Hartmann (Hartmann's operation, HO) con intención curativa desde mayo de 2001 hasta abril de 2012, se seleccionaron a partir de registros nacionales. Los pacientes con SD fueron seguidos desde la resección primaria del cáncer rectal hasta la fecha del SR, del fallecimiento, de su cambio de residencia o hasta el final del seguimiento (3 años). Se calculó la tasa de incidencia acumulada (cumulative incidence proportion, CIP) de RS a 1 y 3 años utilizando la muerte como factor de riesgo competitivo. Se identificaron los factores predictivos de SR mediante regresión múltiple de Cox. RESULTADOS: De los 6.859 pacientes incluidos, el 35,7%, 41,9% y 22,4% tenían una RRR con DS, una RRR sin estoma y una HO con colostomía terminal, respectivamente. En pacientes con SD, el CIP de SR fue del 70,3% (i.c. del 95%: 68,4-72,1) al año y del 74,3% (i.c. del 95%: 72,5-76,0) a los 3 años. Se identificaron como posibles factores predictivos relacionados con el retraso del SR, el tratamiento neoadyuvante (cociente de riesgos instantáneos, hazard ratio, HR 0,75; i.c. del 95% 0,66-0,85), una pérdida de sangre > 300 mL (HR 0,86; i.c. del 95% 0,76-0,97), la fuga anastomótica (HR 0,41; i.c. del 95% 0,33-0,50), las categorías T3 (HR 0,63; i.c. del 95% 0,47-0,83) y T4 (HR 0,62; i.c. del 95% 0,42-0,90) y el estadio IV UICC (HR 0,57; i.c. del 95%: 0,41-0,80). CONCLUSIÓN: En una cuarta parte de los pacientes no se había cerrado el estoma derivativo tres años después de la resección de cáncer rectal con intención reconstructiva.

Pelvic insufficiency fractures frequently occur following preoperative chemo-radiotherapy for rectal cancer - a nationwide MRI study.

AIM: The aim of this prospective case-control study was to evaluate the rate of pelvic insufficiency fractures (PIFs) in Denmark using MRI at the 3-year follow-up. All patients had rectal cancer and had undergone surgery with or without preoperative chemo-radiotherapy (CRT). METHOD: Patients registered with primary rectal cancer in the Danish Colorectal Cancer Group database, who underwent rectal cancer resection from April 2011 through August 2012, were invited to participate in a national MRI study aiming to detect local recurrence and evaluate quality of the surgical treatment. Pelvic MRI including bone-specific sequences 3 years after treatment was obtained. The primary outcome was the rate of PIFs; secondary outcome was risk factors of PIFs evaluated in multivariate analysis. RESULTS: During the study period, 890 patients underwent rectal cancer surgery. Of these, 403 patients were included in the MRI study and had a 3-year follow-up MRI. PIFs were detected in 49 (12.2%; 95% CI 9.0-15.4) patients by MRI. PIFs were detected in 39 patients (33.6%; 95% CI 24.9-42.3) treated with preoperative CRT compared to 10 (3.5%; 95% CI 1.3-5.6) non-irradiated patients (P < 0.001). In a multivariate analysis female gender (OR = 3.52; 95% CI 1.7-7.5), age above 65 years (OR = 3.20; 95% CI 1.5-6.9) and preoperative CRT (OR = 14.20; 95% CI 6.1-33.1) were significant risk factors for PIFs. CONCLUSION: Preoperative CRT in the treatment of rectal cancer was associated with a 14-fold higher risk of PIFs after 3 years, whereas female gender and age above 65 years each tripled the risk of PIFs.

Persistent infections with infectious pancreatic necrosis virus (IPNV) of different virulence in Atlantic salmon, Salmo salar L.

Infectious pancreatic necrosis virus (IPNV) is a prevalent pathogen in fish worldwide. The virus causes substantial mortality in Atlantic salmon juveniles and smolts when transferred to sea water and persistent infection in surviving fish after disease outbreaks. Here, we have investigated the occurrence of the virus as well as the innate immune marker Mx in the head kidney (HK) of Atlantic salmon throughout an experimental challenge covering both a fresh and a seawater phase. The fish were challenged with a high (HV) and low virulence (LV) IPNV. Both isolates caused mortality due to reactivation of the virus after transfer to sea water. In the freshwater phase, higher levels of virus transcripts were detected in the HK of fish infected with LV IPNV compared to HV, suggesting that the HV isolate is able to limit its own replication to a level where the innate immune system is not alerted. Further, ex vivoHK leucocytes derived from fish infected with the two isolates were stimulated with CpG DNA. Significantly, higher IFN levels were found in the LV compared to the HV group in the freshwater phase. This suggests that the viruses attenuate the antiviral host immune response at different levels which may contribute to the observed differences in disease outcome.

CpG oligodeoxynucleotides and plasmid DNA stimulate Atlantic salmon (Salmo salar L.) leucocytes to produce supernatants with antiviral activity.

Unmethylated CpG dinucleotides are more frequent in the genomes of bacteria and viruses than of vertebrates. We report herein that plasmid DNA and synthetic oliogodeoxynucleotides (ODNs) containing unmethylated CpG induce production of antiviral cytokine activity in Atlantic salmon leucocytes, whereas ODNs with an inverted motif (GpC) or with methylated cytosines have nearly no stimulatory effect. The adherent cell population, representing mainly macrophages, is directly activated by CpG-ODN, while the effect on the non-adherent population is weak. Since the peak antiviral activity in ODN-stimulated leucocytes is seen after 48h, this might indicate that the unmethylated DNA stimulates the adherent cells to produce co-stimulatory molecules, which in turn stimulates production of antiviral cytokines in the non-adherent cell population. The potent immune activation by CpG ODNs points to possible new applications as adjuvant in fish vaccines.

Immunostimulatory CpG oligodeoxynucleotides stimulate expression of IL-1beta and interferon-like cytokines in rainbow trout macrophages via a chloroquine-sensitive mechanism.

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs are known to stimulate immune responses and are potent adjuvants in higher vertebrates, but so far the effects in fish are poorly described. We here report that CpG ODNs induce IL-1beta expression and production of interferon-like cytokines in rainbow trout head-kidney macrophages, whereas ODNs with an inverted motif (GpC) have a much less stimulatory effect. We further demonstrate that endosomal maturation is essential for CpG signalling, as chloroquine, a compound known to block endosomal acidification, inhibits cytokine expression in the macrophages.

Serum amyloid A transcription in Atlantic salmon (Salmo salar L.) hepatocytes is enhanced by stimulation with macrophage factors, recombinant human IL-1 beta, IL-6 and TNF alpha or bacterial lipopolysaccharide.

Serum amyloid A (A-SAA) has previously been reported to be an acute-phase protein in salmonids. Hepatocytes represent a major source of A-SAA in salmonids, but nothing is known about hepatocyte SAA synthesis in fish. In the present work, the expression of A-SAA transcripts in primary cultures of Atlantic salmon hepatocytes in response to macrophage derived cytokines, human recombinant cytokines and bacterial lipopolysaccharide (LPS) was studied by Northern blot analysis. The macrophage supernatants were prepared by stimulating Atlantic salmon head kidney macrophages with LPS, yeast glucan or a leukocyte derived macrophage activating factor (MAF). The supernatants from glucan- or MAF-stimulated macrophages had no effect on A-SAA expression of the hepatocytes, while supernatants from LPS-stimulated macrophages gave about a 2-fold increase in expression. The combination of either glucan and MAF, or LPS and MAF were more effective and these supernatants gave a 3.4- and 5.2-fold increase in A-SAA expression, respectively. The hepatocytes were also treated with the human recombinant cytokines TNFalpha, IL-1beta and IL-6, alone or in combination. The A-SAA response to each of them alone was modest, but TNFalpha and IL-6 or IL-1beta and IL-6 in combination gave a higher response than each cytokine alone. These data suggest that the expression of A-SAA by hepatocytes from Atlantic salmon is induced by cytokine-like molecules. Interestingly, hepatocytes treated directly with LPS gave a more than 10-fold increase in SAA mRNA expression, but it is not known if this is a direct effect of LPS on the hepatocytes or if it is mediated by other contaminating cell types.

Is bladder outlet obstruction normal in elderly men without lower urinary tract symptoms?

The aim of the present study was to correlate basic voiding parameters, including uroflowmetry, symptom score, and residual urine volume with the results of pressure-flow studies applying the Abrams/Griffith nomogram, in a series of urologically asymptomatic elderly men. Twenty-nine consecutive male volunteers (median age, 66 years) without past or present urological complaints participated. Fifteen (52%) of the 29 subjectively normal men proved to have bladder outlet obstruction (BOO). Qmax <10 mL/s had a positive predictive value of 100% in diagnosing obstruction, whereas the predictive information of higher flow rates proved very modest. No significant difference existed between obstructed and unobstructed persons at any cutoff value concerning symptom score. The sensitivity as well as the positive predictive value of a residual urine volume >50 mL was zero. It is concluded that a surprisingly high prevalence of BOO in asymptomatic elderly men was demonstrated and that the correlation between pressure flow investigations and alternative diagnostic tests, i.e., flow rate, symptom score, and residual volume was weak in this group of men. It is suggested that a possible explanation for the high frequency of BOO observed in the evaluated asymptomatic men could be that the values defining obstruction have been set too low. Neurourol. Urodynam. 18:545-552, 1999.

Uroflow in women: an overview and suggestions for the future.

The literature on uroflowmetry in women is presented and evaluated. Uroflowmeters are described and found generally sufficiently accurate, although the errors arising from electronic evaluation may invalidate the test. Six flow curve patterns are proposed in accordance with described pathological conditions. From the literature it is summarized that the normal Qmax is 20-36 ml/s. Qmax is linearly correlated to the voided volume, increasing by 5.6 ml/s/100 ml. Pregnancy, age and menstrual cycle do not influence Qmax. Several pathological conditions have been associated with specific flow curve patterns. These conditions are described and associations with the proposed flow definitions made.

Home uroflowmetry by means of the Da Capo home uroflowmeter.

OBJECTIVE: The Da Capo home flowmeter was tested versus the Urodyn 1000 flowmeter. The two flowmeters are based on different principles. The Da Capo is a portable, battery powered flowmeter designed to record all voidings during a period of time (e.g. 24 h) for a single patient. METHODS: The flowmeters were tested with regard to accuracy of measurement of the voided volume and maximum flow (Qmax). Further, the Da Capo was tested by 10 healthy male volunteers, median age 47 years, range 21-57. RESULTS: Both flowmeters were very accurate measuring Qmax and voided volume. A few artifacts arose, i.e. extremely high Qmax values were recorded. All test persons found the flowmeter easy to handle. CONCLUSION: The weight transducer based Da Capo home flowmeter proved as accurate as the stationary flowmeters. It is easy to handle and it provides all-day monitoring of uroflow and voided volume.

[Waiting lists for men with benign urinary disorders]. / Ventelisteprojekt for maend med benigne vandladningsforstyrrelser.

This paper reflects the problems in having a large non-specific waiting-list. One hundred and twenty-eight patients were on a waiting-list under the main diagnosis of prostatism. This diagnosis revealed seven patients with cancer in the urinary tract system. Only two-thirds of the patients on the waiting-list were interested in further examination and treatment. This paper emphasizes the need for a more specific referral, when dealing with symptoms from the lower urinary tract system.

Uroflowmetry.

Uroflowmetry is a widely used noninvasive screening modality for patients who present with symptoms of lower urinary dysfunction. However, it should be recognized that uroflowmetry represents the compound effect of bladder and urethral function because it may easily be misinterpreted. In elderly men with "prostatism", uroflowmetry is often sufficient to indicate treatment, while the value in women is less prominent. In pediatrics, more sophisticated urodynamic testing is crucial.

Yeast beta-glucan stimulates respiratory burst activity of Atlantic salmon (Salmo salar L.) macrophages.

Previous studies have shown that head kidney macrophages isolated from glucan injected rainbow trout (Oncorhychus mykiss) and Atlantic salmon (Salmo salar L.) have increased ability to kill Aeromonas salmonicida. The present work was aimed at investigating the in vitro effects of glucan on the respiratory burst and bactericidal potential of Atlantic salmon head kidney macrophages. Salmon macrophages were incubated for 1-7 days with various concentrations of yeast beta-glucan (MacroGard) and tested for respiratory burst activity by the reduction of nitroblue-tetrazolium (NBT) after exposure to phorbol myristate acetate (PMA) or opsonized zymosan. The macrophages showed a marked increase in respiratory burst activity 4 to 7 days after addition of glucan. Macrophages treated with 0.1-1 microgram mL-1 gave a maximum respiratory burst response, whereas 10 micrograms mL-1 had no effect and 50 micrograms mL-1 was inhibitory. The glucan also triggered respiratory burst activity directly, but this occurred only at relative high concentrations with a maximal effect at > or = 200 micrograms mL-1. The validity of using the NBT-assay as a measure of respiratory burst activity was confirmed by using inhibitors of O2- production (superoxide dismutase, trifluoperazine and diphenylene iodonium). Despite the stimulatory effect of glucan on the respiratory burst activity of salmon macrophages, these cells did not show increased bactericidal activity against the avirulent and virulent strain of A. salmonicida. Upregulation of burst activity alone is thus apparently not sufficient to enhance bactericidal activity against this pathogen by Atlantic salmon macrophages.

Long-term probability of prostatism vs general morbidity and mortality. Prospectively obtained data in a randomly selected cohort aged > 50 years.

In a 7-year study of 178 randomly selected healthy men older than 50, data were respectively obtained concerning treatment for benign prostatic hypertrophy (BPH) and overall morbidity and mortality. Plain symptom scores were calculated in all cases and urinary voiding was recorded in 112. The maximum flow rate was read and the pattern of flow curve determined. Log rank test and survival curves were used in evaluation of results. The general risk of death or disease overshadowing BPH greatly exceeded the probability of surgery for prostatism. The only factor predicting need for prostatectomy was a symptom score higher than 6 points. If the symptom score is low and indications for treatment are otherwise, relative, an expectant attitude to surgery for BPH is advocated.

Longitudinal observations on normal and abnormal voiding in men over the age of 50 years.

A cohort of 200 men over the age of 50 years was selected at random. Initially 112 men participated. After 5 years 61 were participating, and 2 years later 34 men still had no voiding problems, while 19 had had treatment for prostatism. A history was obtained and all 112 had symptom analysis and uroflow examination. The uroflow variables Qmax, Qave, Qmax-time, Q "corrected", volume and the ratio Qmax/Qmax-time were recorded together with the symptom score and subjective evaluation. After 5 and 7 years all primary data were reviewed in the 61 and 34 men respectively, while a full history was obtained in the rest. The 3 sets of data were evaluated separately as 3 cross-sectional investigations and as paired data sets by means of non-parametrical statistical analysis. Comparing the 3 sets of data longitudinally, significant differences were found in Qmax, Qave, Qcor and Acc. A correlation analysis showed that Qmax, Qave, Q "corrected" and volume decreases significantly with advancing age in asymptomatic men, while no correlation with age was found in the 19 treated men. On the basis of the 93 men, untreated for 7 years, nomograms of Qmax, Volume and Acc were constructed using 2.5, 25, 50, 75 and 97.5% percentiles in 5-year groups. Likewise, a nomogram on symptom score was constructed on the basis of the 82 men, asymptomatic and untreated for 7 years. In conclusion, uroflow in subjectively normal men over the age of 50 years shows increasing abnormality with advancing age. At the same time elderly men tolerate a considerable amount of symptoms of infravesical obstruction. The severity of symptoms increased with advancing age, but differently in persons likely and not likely to need operation.

Use of a dot enzyme-linked immunosorbent assay on absorbed sera for the diagnosis of bovine paratuberculosis.

This study describes the response of cattle to a dot enzyme-linked immunosorbent assay (ELISA) using sera absorbed with Mycobacterium phlei. Results obtained by visual observation are compared with those obtained using a densitometer. Infection status of cattle was determined by faecal culture. Cattle of different levels of exposure and disease manifestation were examined. A significantly higher dot ELISA response was observed (using both absorbed and non-absorbed sera) in animals with heavy shedding of M. paratuberculosis than in animals which tested negative by faecal culture or shed M. paratuberculosis at lower levels (P < 0.05). Paratuberculosis was diagnosed by visual determination of dot ELISA results using non-absorbed sera in 29 of 44 (65.9%) clinically-suspect animals giving positive results by faecal culture, and 85 of 93 (91.4%) cattle testing negative by faecal culture. With absorbed sera, the sensitivity of visual determination decreased to 15 of 44 (34.1%), while specificity increased to 91 of 93 (97.8%). Approximately 75% of cattle yielding positive results by dot ELISA were heavy bacterial shedders (> 1,500 colonies/g of faeces) at the time of serological testing. Comparison of the dot ELISA results determined visually with results obtained by objective densitometric measurement showed compatible specificity. Sensitivity of the dot ELISA was 65.9% for non-absorbed sera using visual evaluation and 87.5% using densitometric evaluation at a cut-off optical density value of 0.2. For absorbed sera, the values were 34.1% and 82.5%, respectively.

Mechanical versus visual evaluation of urinary flow curves and patterns.

Flow curves from 100 consecutive patients were obtained using the Urodyn 1000 mictiograph. Four observers evaluated the flow curves blindly, i.e. without access to the mechanically estimated values. Further, the flow curve pattern was decided upon in each case. The 4 observers agreed very meticulously in the evaluation while they disagreed with the mechanically obtained results. The visually read values were significantly lower than the mechanically determined ones. At the same time the difference in Qmax was most pronounced in abnormal curves. In conclusion the mechanical evaluation of uroflow curves may be misleading and should not replace the visual evaluation.

Comparison of subjective and objective test evaluations for use of Mycobacterium phlei-adsorbed serum in a dot-enzyme-linked immunosorbent assay for diagnosis of paratuberculosis in cattle.

Use of a dot-ELISA with serum adsorbed with Mycobacterium phlei or with nonadsorbed serum was compared. In addition, results attained using visual observation were compared with those obtained using a densitometer. Infection status of cattle was determined by results of culture of feces from a number of cattle with various degrees of exposure (low prevalence and test-negative) and disease manifestation (clinical suspect vs subclinical infection). Two paratuberculosis-negative herds, fecal culture-confirmed clinically suspect cases of paratuberculosis, and cows from 2 paratuberculosis-infected herds with diagnosis confirmed on the farm (low infection rate) were tested. Significant (P less than 0.05) increase in the dot-ELISA response was found in cattle with heavy M paratuberculosis shedding when nonadsorbed and adsorbed sera were used, compared with the response in cattle that were fecal culture-negative or were shedding M paratuberculosis at lower amounts. Paratuberculosis was diagnosed by visual determination in 29 of 44 (65.9%) of fecal culture-positive, clinically suspect cattle when nonadsorbed serum was used. Results of the visual test were negative in 85 of 93 (91.4%) of the fecal culture-negative cattle when nonadsorbed serum was used. However, when using M phlei-adsorbed serum, the sensitivity of the visual determination decreased to 34.1% (15/44), and the specificity increased to 97.8% (91/93).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic accuracy of a Mycobacterium phlei-absorbed serum enzyme-linked immunosorbent assay for diagnosis of bovine paratuberculosis in dairy cows.

The purpose of this study was to describe the responses of sera from five groups of cattle to an enzyme-linked immunosorbent assay (ELISA) for paratuberculosis by using serum absorbed with Mycobacterium phlei at a single working dilution. The infection status of the cattle was determined by fecal culture. Cattle with different levels of exposure (high versus low prevalence and test negative) and disease manifestation (clinically suspect infection versus subclinical infection) were examined, as follows: (i) two paratuberculosis-negative herds; (ii) a fecal culture-confirmed, clinically suspect cases of paratuberculosis; (iii) cows from a paratuberculosis-infected herd with a high infection rate, as determined by fecal culture, but with no clinical cases at the time of sampling; (iv) cows from three paratuberculosis-infected herds known to have paratuberculosis diagnosed on the farm (low infection rate determined by fecal culture); and (v) one fecal culture-negative herd with known serologically positive cattle. Results generally showed a decreased ELISA response when absorbed rather than nonabsorbed serum from each animal was used. The results of the fecal culture confirmed clinically suspect cases, which were analyzed in relation to the amount of colonies isolated from the animals on fecal culture (0, +, ++,+++ , ++++, and above). There was a significant increase in the ELISA response for animals with heavy Mycobacterium paratuberculosis shedding ( ++++ or above), when both unabsorbed and absorbed sera were used, compared with the response in animals that were fecal culture negative or that shed M. paratuberculosis at lower levels (less than +) (P less than 0.05). The effects on sensitivity and specificity by using different cutoff points for the five groups of cattle with different levels of exposure is described, since sera were not discretely segregated into distinct groups of positive and negative samples. The specificity of the ELISA in the two fecal culture-negative herds was 100% at an ELISA cutoff of an optical density (OD) of 0.1 and above for absorbed serum. For unabsorbed serum the specificity was 62.9% at a similar cutoff value. Similarly, the specificity of the fecal culture-negative, serologically positive herd increased from 37.5 to 72.2 at an ELISA cutoff value of 0.1 to 0.2 (OD) by using absorbed versus unabsorbed serum from 75.0 to 94.4 at an ELISA cutoff value of 0.2 to 0.3 (OD).

Age-related variation in urinary flow variables and flow curve patterns in elderly males.

A group of randomly selected males, over 50 years of age, was examined with regard to history and urinary flow rate. Originally, the group had comprised 93 men without voiding problems, 15 who, although suffering from voiding problems, had not yet contacted their doctor, and 4 who had contacted their doctor because of voiding problems. Five years later the data were re-examined and 61 men were fully investigated again; in the remaining 51 patients only the history was updated. The 2 sets of data were evaluated separately as 2 cross-sectional investigations and as paired data sets by means of non-parametric statistical analysis. All uroflow variables were considered, i.e. Qmax, Qave, Qmax-time, Q "corrected", volume and the ratio Qmax/Qmax-time. In addition, the flow curve configuration was classified as normal or abnormal. When compared as 2 cross-sectional investigations, the latter confirmed the results of the first. Qmax, Qave, Q "corrected" and volume decreased with advancing age, but no correlation could be demonstrated between Qmax-time and age. The flow curve pattern altered, so that a normal flow curve was seldom seem at an advanced age. Uroflow variables tended towards the abnormal with advancing years and symptoms increased concurrently. These changes were largely accepted by the elderly males. Thus the decision to operate for benign prostatic hyperplasia should be based on both history and urinary flow.