Targeted Blood Brain Barrier Opening With Focused Ultrasound Induces Focal Macrophage/Microglial Activation in Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis (MS). EAE reflects important histopathological hallmarks, dissemination, and diversity of the disease, but has only moderate reproducibility of clinical and histopathological features. Focal lesions are less frequently observed in EAE than in MS, and can neither be constrained to specific locations nor timed to occur at a pre-specified moment. This renders difficult any experimental assessment of the pathogenesis of lesion evolution, including its inflammatory, degenerative (demyelination and axonal degeneration), and reparatory (remyelination, axonal sprouting, gliosis) component processes. We sought to develop a controlled model of inflammatory, focal brain lesions in EAE using focused ultrasound (FUS). We hypothesized that FUS induced focal blood brain barrier disruption (BBBD) will increase the likelihood of transmigration of effector cells and subsequent lesion occurrence at the sonicated location. Lesion development was monitored with conventional magnetic resonance imaging (MRI) as well as with magnetic resonance elastography (MRE) and further analyzed by histopathological means. EAE was induced in 12 6-8 weeks old female C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG) peptide. FUS-induced BBBD was performed 6, 7, and 9 days after immunization in subgroups of four animals and in an additional control group. MRI and MRE were performed on a 7T horizontal bore small animal MRI scanner. Imaging was conducted longitudinally 2 and 3 weeks after disease induction and 1 week after sonication in control animals, respectively. The scan protocol comprised contrast-enhanced T1-weighted and T2-weighted sequences as well as MRE with a vibration frequency of 1 kHz. Animals were sacrificed for histopathology after the last imaging time point. The overall clinical course of EAE was mild. A total of seven EAE animals presented with focal T2w hyperintense signal alterations in the sonicated hemisphere. These were most frequent in the group of animals sonicated 9 days after immunization. Histopathology revealed foci of activated microglia/macrophages in the sonicated right hemisphere of seven EAE animals. Larger cellular infiltrates or apparent demyelination were not seen. Control animals showed no abnormalities on MRI and did not have clusters of activated microglia/macrophages at the sites targeted with FUS. None of the animals had hemorrhages or gross tissue damage as potential side effects of FUS. EAE-animals tended to have lower values of viscoelasticity and elasticity in the sonicated compared to the contralateral parenchyma. This trend was significant when comparing the right sonicated to the left normal hemisphere and specifically the right sonicated compared to the left normal cortex in animals that underwent FUS-BBBD 9 days after immunization (right vs. left hemisphere: mean viscoelasticity 6.1 vs. 7.2 kPa; p = 0.003 and mean elasticity 4.9 vs. 5.7 kPa, p = 0.024; right vs. left cortex: mean viscoelasticity 5.8 vs. 7.5 kPa; p = 0.004 and mean elasticity 5 vs. 6.5 kPa; p = 0.008). A direct comparison of the biomechanical properties of focal T2w hyperintensities with normal appearing brain tissue did not yield significant results. Control animals showed no differences in viscoelasticity between sonicated and contralateral brain parenchyma. We here provide first evidence for a controlled lesion induction model in EAE using FUS-induced BBBD. The observed lesions in EAE are consistent with foci of activated microglia that may be interpreted as targeted initial inflammatory activity and which have been described as pre-active lesions in MS. Such foci can be identified and monitored with MRI. Moreover, the increased inflammatory activity in the sonicated brain parenchyma seems to have an effect on overall tissue matrix structure as reflected by changes of biomechanical parameters.

Prognostic value of CT integrated with clinical and laboratory data during the first peak of the COVID-19 pandemic in Northern Italy: A nomogram to predict unfavorable outcome.

PURPOSE: To evaluate the prognostic role of chest computed tomography (CT), alone or in combination with clinical and laboratory parameters, in COVID-19 patients during the first peak of the pandemic. METHODS: A retrospective single-center study of 301 COVID-19 patients referred to our Emergency Department (ED) from February 25 to March 29, 2020. At presentation, patients underwent chest CT and clinical and laboratory examinations. Outcomes included discharge from the ED after improvement/recovery (positive outcome), or admission to the intensive care unit or death (poor prognosis). A visual quantitative analysis was formed using two scores: the Pulmonary Involvement (PI) score based on the extension of lung involvement, and the Pulmonary Consolidation (PC) score based on lung consolidation. The prognostic value of CT alone or integrated with other parameters was studied by logistic regression and ROC analysis. RESULTS: The impact of the CT PI score [≥15 vs. ≤ 6] on predicting poor prognosis (OR 5.71 95 % CI 1.93-16.92, P = 0.002) was demonstrated; no significant association was found for the PC score. Chest CT had a prognostic role considering the PI score alone (AUC 0.722) and when evaluated with demographic characteristics, comorbidities, and laboratory data (AUC 0.841). We, therefore, developed a nomogram as an easy tool for immediate clinical application. CONCLUSIONS: Visual analysis of CT gives useful information to physicians for prognostic evaluations, even in conditions of COVID-19 emergency. The predictive value is increased by evaluating CT in combination with clinical and laboratory data.

Increased incidence of interstitial pneumonia detected on [18F]-FDG-PET/CT in asymptomatic cancer patients during COVID-19 pandemic in Lombardy: a casualty or COVID-19 infection?

PURPOSE: The study aimed to compare the incidence of interstitial pneumonia on [18F]-FDG PET/CT scans between two 6-month periods: (a) the COVID-19 pandemic peak and (b) control period. Secondly, we compared the incidence of interstitial pneumonia on [18F]-FDG PET/CT and epidemiological data from the regional registry of COVID-19 cases. Additionally, imaging findings and the intensity of [18F]-FDG PET/CT uptake in terms of maximum standardized uptake value (SUVmax) were compared. METHODS: We retrospectively analyzed [18F]-FDG PET/CT scans performed in cancer patients referred to nuclear medicine of Humanitas Gavazzeni in Bergamo from December 2019 to May 2020 and from December 2018 to May 2019. The per month incidence of interstitial pneumonia at imaging and the epidemiological data were assessed. To evaluate the differences between the two symmetric groups (period of COVID-19 pandemic and control), the stratified Cochran-Mantel-Haenszel test was used. Chi-square test or Fisher's exact test and t test or Wilcoxon test were performed to compare the distributions of categorical and continuous variables, respectively. RESULTS: Overall, 1298 patients were included in the study. The two cohorts-COVID-19 pandemic (n = 575) and control (n = 723)-did not statistically differ in terms of age, disease, or scan indication (p > 0.05). Signs of interstitial pneumonia were observed in 24 (4.2%) and 14 patients (1.9%) in the COVID-19 period and the control period, respectively, with a statistically significant difference (p = 0.013). The level of statistical significance improved further when the period from January to May was considered, with a peak in March (7/83 patients, 8.4% vs 3/134 patients, 2.2%, p = 0.001). The curve of interstitial pneumonia diagnosis overlapped with the COVID-19 incidence in the area of Lombardy (Spearman correlation index was equal to 1). Imaging data did not differ among the two cohorts. CONCLUSIONS: Significant increase of interstitial lung alterations at [18F]-FDG PET/CT has been demonstrated during the COVID-19 pandemic. Additionally, the incidence curve of imaging abnormalities resulted in resembling the epidemiological data of the general population. These data support the rationale to adopt [18F]-FDG PET/CT as sentinel modality to identify suspicious COVID-19 cases to be referred for additional confirmatory testing. Nuclear medicine physicians and staff should continue active surveillance of interstitial pneumonia findings, especially when new infection peak is expected.

Lanosterol Synthase Genetic Variants, Endogenous Ouabain, and Both Acute and Chronic Kidney Injury.

RATIONALE & OBJECTIVE: Studies of humans and animals have suggested that endogenous ouabain (EO) and related genes are mediators of acute (AKI) and chronic kidney injury. We sought to examine the relationship among EO levels, genetic variants in lanosterol synthase (LSS; an enzyme that catalyzes synthesis of cholesterol, a precursor of EO), and both AKI and chronic kidney injury. STUDY DESIGN: 2 prospective observational cohort studies and a cross-sectional study of kidney tissue. SETTING & PARTICIPANTS: (1) A prospective cohort study of patients undergoing cardiovascular surgery, (2) measurement of EO concentration in kidney tissue removed because of an adjacent tumor, and (3) a prospective cohort study of patients with newly diagnosed essential hypertension. EXPOSURE: Missense variant in LSS (A instead of C allele at rs2254524), which leads to a valine to leucine substitution at amino acid 642. OUTCOMES: Development of postoperative AKI in the cardiovascular surgery cohort, EO concentration in kidney tissue, and estimated glomerular filtration rate (eGFR) reductions in the essential hypertension cohort. ANALYTICAL APPROACH: Logistic regression for analysis of postoperative AKI, analysis of variance for EO concentration in kidney tissue, and generalized linear models for changes in eGFR over time. RESULTS: AKI incidence following cardiovascular surgery was greater among those with the LSS rs2254524 AA genotype (30.7%) than in those with the CC genotype (17.4%; P=0.001). LSS rs2254524 AA kidneys had higher EO concentrations than CC kidneys (2.14±0.29 vs 1.25±0.08ng/g; P<0.001). In the longitudinal study of patients with essential hypertension (median follow-up, 4 years; range, 1-15 years), eGFR decline was greater among the LSS rs2254524 AA genotype group (-4.39±1.18mL/min/1.73m2 per year) than in the AC or CC genotype groups (-1.07±0.55 and -2.00±0.45mL/min/1.73m2 per year respectively; P = 0.03). LIMITATIONS: These associations do not necessarily represent causal relationships; LSS rs2254524 variants may have effects on other steroid hormones. CONCLUSIONS: These findings support the potential value of LSS rs2254524 genotype-based risk stratification to identify patients at high risk for AKI before cardiovascular surgery, as well as predict accelerated eGFR in the setting of hypertension. These findings also suggest that LSS may in part drive EO-mediated kidney damage. EO may represent a new potential therapeutic target for the prevention of AKI and slowing of kidney damage in the setting of hypertension.

Different strategies for mechanical VENTilation during CardioPulmonary Bypass (CPBVENT 2014): study protocol for a randomized controlled trial.

BACKGROUND: There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. METHODS/DESIGN: The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2 ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization. DISCUSSION: The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02090205 . Registered on 8 March 2014.

Feasibility of Anesthesia Maintenance With Sevoflurane During Cardiopulmonary Bypass: A Pilot Pharmacokinetics Study.

OBJECTIVE: Adequate maintenance of hypnosis during anesthesia throughout surgery using sevoflurane alone was investigated. In addition, sevoflurane pharmacokinetics during cardiopulmonary bypass were analyzed. DESIGN: This was a pilot pharmacokinetic study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 10 patients aged between 18 and 75 years who underwent elective mitral valve surgery. INTERVENTIONS: The end-tidal and sevoflurane plasma concentrations were measured throughout cardiac surgery procedures involving cardiopulmonary bypass. The sevoflurane plasma concentration was measured using gas chromatography. In addition, the ratio between sevoflurane alveolar concentration and inspired concentration over time (FA/FI) was analyzed to describe wash-in and wash-out curves. MEASUREMENTS AND MAIN RESULTS: Hypnosis was maintained adequately throughout surgery using sevoflurane alone. The bispectral index was maintained between 40 and 60 during cardiopulmonary bypass. The end-tidal sevoflurane was significantly different before and during cardiopulmonary bypass (1.86%±0.54% v 1.30%±0.58%, respectively; p<0.001). However, the sevoflurane plasma concentration was not significantly different before and after cardiopulmonary bypass start-up (40.55 µg/mL [76.62-125.33] before cardiopulmonary bypass and 36.24 µg/mL [56.49-81-42] during cardiopulmonary bypass). This mismatch possibly can be explained by changes that occured after cardiopulmonary bypass start-up, such as reductions of body temperature (36.33°C±0.46°C v 32.98°C±2.38°C, respectively; p<0.001) and hematocrit (35.62%±3.98% v 25.5%±3.08%, respectively; p<0.001). The sevoflurane alveolar concentration varied according to sevoflurane plasma concentration and bispectral index values. No adverse events regarding sevoflurane administration during cardiopulmonary bypass were observed. CONCLUSIONS: Sevoflurane end-tidal values were reliable indicators of adequate anesthesia during all cardiac surgery procedures involving cardiopulmonary bypass.

Mortality in Multicenter Critical Care Trials: An Analysis of Interventions With a Significant Effect.

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

Urinary neutrophil gelatinase-associated lipocalin time course during cardiac surgery.

BACKGROUND: NGAL is one of the most promising AKI biomarkers in cardiac surgery. However, the best timing to dose it and the reference values are still matter of discussion. AIM OF THE STUDY: We performed a uNGAL perioperative time course, to better understand its perioperative kinetics and its role in AKI diagnosis. SETTING OF THE STUDY: San Raffaele University Hospital, cardiac surgery department. MATERIAL AND METHODS: We enrolled in this prospective observational study 19 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Based on preoperative characteristics, they were divided in low-risk and high-risk patients. uNGAL measurements were collected at pre-defined times before, during, and up to 24 hours after surgery. STATISTICAL ANALYSIS: Data were analysed by use of SAS 1999-2001 program or IBM SPSS Statistics. RESULTS: In low-risk patients, uNGAL had the highest value immediately after general anesthesia induction (basal dosage: uNGAL: 12.20ng×ml -1 , IQR 14.00). It later decreased significantly (3.40 ng×ml -1 , IQR 4.80; P = 0.006) during CPB, and finally return to its original value 24 hours after surgery. In high-risk patients, uNGAL increased immediately after surgery; it had the highest value on ICU arrival (38,20 ng×ml -1 ; IQR 133,10) and remained high for several hours. A difference in uNGAL levels between the two groups was already observed at the end of surgery, but it became statistically significant on ICU arrival (P = 0.002). CONCLUSION: This study helps to better understand the different kinetics of this new biomarker in low-risk and high-risk cardiac patients.

A new clinical multivariable model that predicts postoperative acute kidney injury: impact of endogenous ouabain.

BACKGROUND: Acute kidney injury (AKI) is an important complication of cardiac surgery. Recently, elevated levels of endogenous ouabain (EO), an adrenal stress hormone with haemodynamic and renal effects, have been associated with worse renal outcome after cardiac surgery. Our aim was to develop and evaluate a new risk model of AKI using simple preoperative clinical parameters and to investigate the utility of EO. METHODS: The primary outcome was AKI according to Acute Kidney Injury Network stage II or III. We selected the Northern New England Cardiovascular Disease Study Group (NNECDSG) as a reference model. We built a new internal predictive risk model considering common clinical variables (CLIN-RISK), compared this model with the NNECDSG model and determined whether the addition of preoperative plasma EO improved prediction of AKI. RESULTS: All models were tested on >800 patients admitted for elective cardiac surgery in our hospital. Seventy-nine patients developed AKI (9.9%). Preoperative EO levels were strongly associated with the incidence of AKI and clinical complication (total ICU stay and in-hospital mortality). The NNECDSG model was confirmed as a good predictor of AKI (AUC 0.74, comparable to the NNECDSG reference population). Our CLIN-RISK model had improved predictive power for AKI (AUC 0.79, CI 95% 0.73-0.84). Furthermore, addition of preoperative EO levels to both clinical models improved AUC to 0.79 and to 0.83, respectively (ΔAUC +0.05 and +0.04, respectively, P < 0.01). CONCLUSION: In a population where the predictive power of the NNECDSG model was confirmed, CLIN-RISK was more powerful. Both clinical models were further improved by the addition of preoperative plasma EO levels. These new models provide improved predictability of the relative risk for the development of AKI following cardiac surgery and suggest that EO is a marker for renal vascular injury.

Extracorporeal venovenous membrane oxygenation in the treatment of respiratory insufficiency following cardiac surgery.

Following cardiac surgery, patients can develop acute respiratory failure. We present the case of a 66-year-old male successfully treated with extracorporeal venovenous membrane oxygenation (vvECMO) for acute respiratory failure postsurgery and review the literature on vvECMO in this specific setting.

Preoperative urinary neutrophil gelatinase-associated lipocalin and outcome in high-risk heart failure patients undergoing cardiac surgery.

OBJECTIVE: To investigate the ability of early urinary neutrophil gelatinase-associated lipocalin to predict postoperative complications in adult patients with ventricular dysfunction undergoing cardiac surgery. DESIGN: Prospective observational study. SETTING: Single-center study, university hospital. PARTICIPANTS: Fifty-six adult high-risk cardiac surgical patients with preoperative cardiac failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics were obtained, and neutrophil gelatinase-associated lipocalin was measured at baseline and at several time points after surgery. Patient characteristics and neutrophil gelatinase-associated lipocalin levels were related to renal and patient outcome. On multivariate analyses, preoperative urinary neutrophil gelatinase-associated lipocalin was an independent predictor of length of intensive care stay (p = 0.004) and in-hospital stay (p = 0.04), but not of acute kidney injury or renal replacement therapy and was not associated with baseline renal function. CONCLUSIONS: In a cohort of high-risk cardiac surgery patients, preoperative urinary neutrophil gelatinase-associated lipocalin value provided prognostic information that was independent of the onset of acute kidney injury or of preoperative renal function.

A survey on the use of intra-aortic balloon pump in cardiac surgery.

Intra-aortic balloon pump (IABP) is an established tool in the management of cardiac dysfunction in cardiac surgery. The best timing for IABP weaning is unknown and varies greatly among cardiac centers. The authors investigated the differences in IABP management among 66 cardiac surgery centers performing 40,675 cardiac surgery procedures in the 12-month study period. The centers were contacted through email, telephone, or in person interview. IABP management was very heterogeneous in this survey: In 43% centers it was routinely removed on the first postoperative day, and in 34% on the second postoperative day. In 50% centers, it was routinely removed after extubation of the patients whereas in 15% centers it was removed while the patients were sedated and mechanically ventilated. In 66% centers, patients were routinely receiving pharmacological inotropic support at the time of removal of IABP. The practice of decreasing IABP support was also heterogeneous: 57% centers weaned by reducing the ratio of beat assistance whereas 34% centers weaned by reducing balloon volume. We conclude that the management of IABP is heterogeneous and there is a need for large prospective studies on the management of IABP in cardiac surgery.

Use of an endoscopic ultrasound probe for the evaluation of the Müllerian rudiments in patients with Rokitansky syndrome.

OBJECTIVE: To assess the use of an endoscopic ultrasound probe in the evaluation of the uterine horns in a series of patients who were undergoing laparoscopy for the creation of a neovagina. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology in a tertiary care and referral center for Rokitansky syndrome. PATIENT(S): Thirty patients with Rokitansky syndrome who were undergoing laparoscopically assisted creation of a neovagina. INTERVENTION(S): Preoperative assessment with a pelvic transabdominal ultrasound scan and pelvic magnetic resonance imaging (MRI). An endoscopic ultrasound probe was used to study the uterine horns during laparoscopy. MAIN OUTCOME MEASURE(S): Presence or absence of the uterine rudiments, presence or absence of the endometrial cavity, and Doppler ultrasound vascularization of the rudiments. RESULT(S): Of the 24 uterine horns sized >or=2 cm that were identified at endoscopic ultrasound, 22 and 19, respectively, had been recognized at MRI and transabdominal ultrasound scan. The endoscopic ultrasound probe diagnosed 12 cavitated horns, of which 9 and 7 were seen at MRI and transabdominal ultrasound scan, respectively. CONCLUSION(S): Our experience shows the feasibility and accuracy of the endoscopic ultrasound probe in evaluating the structure of the rudimentary uterine horns in Rokitansky syndrome.

The role of interventional radiology in biliary complications after orthotopic liver transplantation: a single-center experience.

This study evaluated interventional radiological experience in the management of biliary complications of OLT at the National Cancer Institute of Milan. Seventeen patients who had undergone orthotopic liver transplantation in various hospital were referred to our unit with biliary complications. Group I consisted of 8 patients with anastomotic biliary fistula who came to our attention a short time after transplantation. Group II consisted of 9 patients with anastomotic strictures who came to our attention in a longer period. Two different interventional radiological approaches were used: (a) percutaneous transhepatic biliary drainage (PTBD) in the presence of fistulas in patients of group I; and (b) percutaneous transhepatic biliary drainage combined with dilatation of the strictures with a balloon catheter in patients of group II. On the whole resolution of the biliary complications was achieved in 13 of the 17 cases treated (76.5%), 5 of 8 in group I and 8 of 9 in group II. No secondary stenosis after PTBD were observed in group I, whereas two patients of group II needed a second dilatation. Percutaneous biliary drainage is indicated as a valid treatment in the management of biliary complications, either to allow closure of the fistula either to perform balloon dilatation of stenosis.

Correlation between radiotherapy and suture fistulas following colo-anal anastomosis for carcinoma of the rectum evaluation of 152 consecutive patients.

INTRODUCTION: The aim of this study was to evaluate the prevalence of suture fistulas and their possible correlation with adjuvant therapy in patients who underwent colo-anal anastomosis and J pouch reconstruction with a protective colostomy. The reliability of the radiological screening and monitoring program was also verified. METHODS: One hundred and fifty-two consecutive patients were evaluated radiologically with water-soluble radio-opaque contrast enema before surgery for closure of the protective colostomy. Fifty-seven patients were treated with surgery alone (group A) and 95 patients received adjuvant treatment (group B). RESULTS: A total of 54 fistulas were seen: 17 in group A (28.9% of patients in group A) and 37 in group B (38.9% of patients in group B). Six fistulas involved the rectovaginal septum. All fistulas were managed medically. The time to resolution was 30 days in 76.4% of patients in group A and about 50 days in 82% of patients in group B. Rectovaginal fistulas always took much longer to heal in both groups and failed to heal in two of the four cases in group B. CONCLUSIONS: Two factors appear to contribute to the high prevalence of fistulas in this series: extension of radiological screening to all operated patients and adjuvant radiotherapy. However, the postoperative course was not compromised by radiotherapy in that these fistulas resolved with medical treatment alone, although healing took longer. The incidence of rectovaginal fistulas was substantially the same in the two groups, but two of the four occurring in group B did not heal. Postoperative monitoring with water-soluble contrast enema appears to be the diagnostic procedure of choice because it is well tolerated, non-invasive and a reliable aid in planning surgical bowel recanalization since no false negative cases were detected clinically after closure of the colostomy.