Are liver contour and bone fusion comparable to fiducials for IGRT in liver SBRT?

Introduction: Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration. Material and methods: Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. µ, Æ©, and σ values and margins were obtained. Results: Lateral displacements of less than 3 mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors µ, σ and Æ© of the fusions with hepatic contour and bone reference in SI were 0.26 mm, 4 mm and 3 mm, and 0.8 mm, 5 mm and 3 mm respectively. Conclusion: Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.

Influence in the outcome of neuropathic pediatric patients after early treatment.

BACKGROUND: Clean intermittent catheterization (CIC) and anticholinergic drugs are the mainstay treatment for neuropathic bladder (NB). However, there is not consensus about the time therapy should be started in pediatric patients. AIM: To analyze the impact of early start (first year of life) of CIC and anticholinergic treatment on long-term renal and bladder function. Our hypothesis is that those children who start conservative treatment in the first year of life have better outcome in terms of bladder and renal function and less need of surgical procedures, compared to those who started treatment later in life. PATIENTS AND METHOD: Retrospective study of pediatric patients with NB treated in our hospital (1995-2005) dividing them for comparison in two groups: group 1 started treatment in the first year of life and group 2 between 1 and 5 years old. Collected data included: date of CIC and anticholinergic initiation, presence of VUR or UHN, renal function, UTIs, renal scars, bladder behavior, surgery and urinary continence. RESULTS: Sixty-one patients were included, 25 in group 1 and 36 in group 2. Initially vesico-ureteral reflux (VUR) and overactive bladders were more frequent in group 2. In group 1 one overactive bladder changed to low compliant and in group 2, one normal bladder and 4 overactive bladders changed. At the end of follow-up there were 11 low compliant bladders in group 1 and 17 in group 2. However, in group 1, only 2 patients required bladder augmentation (BA) while in group 2, 12 patients needed it. At the end of the study only 2 patients in group 2 had slight renal insufficiency. CONCLUSIONS: Patients who started conservative treatment in the first year of life have better long-term outcome in terms of UTI, renal scars and surgical procedures. Even if they initially had low compliant bladders, these patients require less BA.

Influence in the outcome of neuropathic pediatric patients after early treatment. / Influencia del inicio precoz del tratamiento conservador en la evolución del paciente pediátrico con vejiga neuropática.

BACKGROUND: Clean intermittent catheterization (CIC) and anticholinergic drugs are the mainstay treatment for neuropathic bladder (NB). However, there is not consensus about the time therapy should be started in pediatric patients. AIM: To analyze the impact of early start (first year of life) of CIC and anticholinergic treatment on long-term renal and bladder function. Our hypothesis is that those children who start conservative treatment in the first year of life have better outcome in terms of bladder and renal function and less need of surgical procedures, compared to those who started treatment later in life. PATIENTS AND METHOD: Retrospective study of pediatric patients with NB treated in our hospital (1995-2005) dividing them for comparison in two groups: group 1 started treatment in the first year of life and group 2 between 1 and 5 years old. Collected data included: date of CIC and anticholinergic initiation, presence of VUR or UHN, renal function, UTIs, renal scars, bladder behavior, surgery and urinary continence. RESULTS: Sixty-one patients were included, 25 in group 1 and 36 in group 2. Initially vesico-ureteral reflux (VUR) and overactive bladders were more frequent in group 2. In group 1 one overactive bladder changed to low compliant and in group 2, one normal bladder and 4 overactive bladders changed. At the end of follow-up there were 11 low compliant bladders in group 1 and 17 in group 2. However, in group 1, only 2 patients required bladder augmentation (BA) while in group 2, 12 patients needed it. At the end of the study only 2 patients in group 2 had slight renal insufficiency. CONCLUSIONS: Patients who started conservative treatment in the first year of life have better long-term outcome in terms of UTI, renal scars and surgical procedures. Even if they initially had low compliant bladders, these patients require less BA.

[Growing up with a bladder augmentation]. / Creciendo con una ampliación vesical.

INTRODUCTION: This study assesses long-term outcome of patients with neuropatic bladders who underwent a bladder augmentation before puberty. PATIENTS AND METHODS: A total of 21 patients with low compliant neuropathic bladders who did not respond satisfactory to clean intermittent catheterization and/or anticholinergic therapy underwent bladder augmentation (mean age 8.3 yr, range; 2.5-12). Eighteen patients (86%) had VUR and/or ureterohydronephrosis and 17 (81%) had DMSA renal scars. Renal function was normal in all cases except one. All patients were followed at regular intervals with serum electrolyte and creatinine determination, urinary tract imaging, urodynamic evaluation and 24-hour urine collection. In the 18 cases augmented with intestine, urine cytology, cystoscopy and biopsy were also performed. RESULTS: Mean follow-up was 11 yr (8-14.5) and mean age at the end of follow-up was 19 yr (13.3-26.8). Urodynamic studies showed a significant improvement in bladder compliance. Upper urinary tract dilatation disappeared in all patients, VUR in 13/15p (86%) and no new renal scarring occurred. Renal function was normal at the end of follow-up in 20. Only 1 patient had UTI and another had a bladder stone. All patients are dry and 2 of them do not need clean intermittent catheterization. Urine cytology and cystoscopy were normal and no malignat lessions have been found in the biopsy specimens. CONCLUSIONS: Bladder augmentation done pre-puberty preserves renal function and resolves VUR and/or hydronephrosis in most cases without reimplanting the ureters. Close lifelong follow-up, including a cystoscopy, improves the results and prevents complications.

Annual, daily and diurnal variations in pollen from Olea europaea L. in the atmosphere of Granada (Spain).

The allergenic capacity of Olea europaea L. pollen is very important in several cities of the southern Iberian Peninsula, producing most pollinoses diagnosed in these cities. We have carried out a study on the annual, daily and diurnal variations in pollen from O. europaea in the atmosphere of Granada (Spain) during 4 consecutive years. Samplings were carried out with the aid of a Burkard spore trap. Very low levels of Olea pollen grains were first detected in the atmosphere from the end of April. Pollen levels peaked in May and June, and started to decrease from the last days of June and in July. Pollen in the atmosphere is related to meteorological parameters: temperature has a positive influence on pollinization and rainfall produces a negative effect. The diurnal variation pattern of pollen grain concentrations was quite homogeneous throughout the study, featuring an important increase around midday and a moderate decrease in the first hours of the morning and in the late evening.

[Results of kidney transplantation in children weighing less than 11 kilograms]. / Resultados del trasplante renal en niños con un peso inferior a 11 kilogramos.

Weigh and age are risk factors of graft failure. The aim of the study is to review the characteristics and the outcome of cadaver renal transplant in children weighing less than 11 Kg. From 1985 to 1999 10 cadaver renal transplant were performed in 10 children (7 boys and 3 girls). Primary renal disease were renal dysplasia(3), posterior urethral valves(5) and congenital nephrotic syndrome(2). All except two suffered end stage disease from birth. The cadaver donor age ranged from 4 to 45 years (mean 12.3). Cold ischaemia time was 14 to 30 hours (median 22.8 h). Grafts were placed extraperitoneally in the iliac fossa in all patients and special care was taken in aggressive intravascular volume expansion. In the first 5 children initial immunosuppression consisted of CyA, Pd and Aza. After 1991, the other five received sequential induction therapy with polyclonal antibodies and triple therapy (CyA, Pd, Aza). Renal function was evaluated as GFR yearly by Swartz formula and the actuarial and graft survival rates were obtained by Kaplan-Meier analysis. Patient survival was 90% at 1 and 10 years. Graft survival was 80% at 1 and 5 years; it decreased to 64% at 7 years. Seven continue with their first graft and the mean follow-up time is 6.6 years. Their renal function measured by the mean of GFR yearly decreased lightly from 102 ml/min/1.73 m2 at 1 year to 87.6 ml/min/1.73 m2 at 5 years. A successful patient and graft survival can be achieved in young receiving kidneys and small reciepients can improve their physical and mental development after transplantation.

[Pediatric renal transplantation from related living donor]. / Trasplante renal pediátrico de donante vivo relacionado.

Living related donor (LRD) provides significant advantages when compared with cadaveric donor (CAD) in term of improved patient and graft survival and shorten waiting time. From 1985, 176 kidney transplants were performed at our Center. Of these, 156 (89%) were from CAD and 20 (11%) were from LRD, first degree. The purpose of this paper is to show our experience at 5 years with use of LRD. All donors underwent standardized metabolic workup, angiography assessed and renal function test. Twelve children received their first transplant and 8 were retransplant (6-second, 1-third and 1-fourth). Immunosuppressive therapy consisted of globulin antithymocyte, azathioprine, cyclosporine and prednisolone, using FK506 and mycophenolate mofetil in some of them. Four kidneys with multiple renal arteries were reconstructed ex vivo with microsurgical technique before transplantation. The most significant morbidity was due to FK506-associated thrombotic microangiopathy (TMA) with graft lost. All patients (donor and recipient) survived. Five years graft survival rate is 95% and mean glomerular filtration rate is 81.33 ml/min/1.73 m2.

Are urodynamic studies really needed during bladder augmentation follow-up?

OBJECTIVE: We assessed clinical and urodynamic outcomes, over a minimum 10-year follow-up period, of neuropathic bladder patients treated with a bladder augmentation (BA) to determine if periodic urodynamic studies are needed. MATERIAL AND METHODS: Thirty-two patients with poorly compliant bladders underwent BA at a mean age of 11 years (2.5-18). Mean follow-up was 12 years (10-14.5) and mean patient age at the end of the study was 22 years (12.2-33). During follow-up all patients were controlled at regular intervals with urinary tract imaging, serum electrolyte and creatinine levels, cystoscopy and urodynamic studies. Preoperative, 1-year post-BA and latest urodynamic studies results were compared. RESULTS: Urodynamic studies at 1-year post-BA showed a significant increase in bladder capacity and a decrease in end-filling detrusor pressure compared with preoperative values (396 vs 106 ml; 10 vs 50 cm H(2)O, P<0.0001). The increase in bladder capacity was more significant at the end of the study than after 1 year (507.8 vs 396 ml, P<0.002). Thirteen patients had phasic contractions after 1 year and 11 at the end (not significant, NS), and these contractions were more frequent with colon than with ileum (NS). At the end of follow-up, phasic contraction pressure had decreased while trigger volume had increased (35 vs 28 cm H(2)O; 247 vs 353 ml, NS). All patients are dry and have normal renal function, except one who had mild renal insufficiency before BA. CONCLUSION: BA improves bladder capacity and pressure, and these changes are maintained over time (although phasic contractions do not disappear). Repeated urodynamic studies are only necessary when upper urinary tract dilatation or incontinence does not improve.

Enterocystoplasty in children with neuropathic bladders: long-term follow-up.

OBJECTIVE: This study assesses clinical outcome, after at least 8 years, of augmentation done before or at puberty in neuropathic bladders. PATIENTS AND METHODS: A total of 29 children with neuropathic bladders who did not respond satisfactorily to clean intermittent catheterisation and anti-cholinergic therapy underwent enterocystoplasty at a mean age of 11.8 years (range 3-18). Twenty-one children (72.4%) had vesicoureteral reflux (VUR) and/or ureterohydronephrosis and 22 (75.8%) had dimercapto-succinic acid scars, but all had normal renal function. All patients were followed at regular intervals with urinary tract imaging, serum electrolytes, creatinine, urodynamic evaluation and 24-h urine collection. Urine cytology, cystoscopy and biopsy were performed at the end of follow-up. RESULTS: Mean follow-up was 11 years (range 8-14.5) and mean age at the end of follow-up was 22.2 years (range 13.2-31). Urodynamic studies showed a significant improvement in bladder compliance in all patients. Upper urinary tract dilatation disappeared in all, VUR in 13/17 (76.4%), and no new renal scarring occurred in any patient. At the end of follow-up, renal function was normal in all according to serum creatinine, but cystatin C levels were normal in 27 and elevated in two. Significant proteinuria and low concentrations of renin and aldosterone were present in 80% and 82%, respectively. Only one patient had urinary tract infection, three had bladder stones, and in another a catheterisable channel was made. All patients were dry with normal urine cytology and cystoscopy, and no malignant lesions have been found in the biopsy specimens. CONCLUSION: Enterocystoplasty has preserved renal function and resolved VUR and/or hydronephrosis in most patients. The future implications of proteinuria and the low serum levels of renin and aldosterone, as well as the best indicator for measuring renal function, have yet to be determined. Close, life-long follow-up, including cystoscopy, is necessary to prevent complications.

Bilateral laparoscopic nephrectomy with simultaneous peritoneal dialysis catheter implantation.

Bilateral nephrectomy prior to transplantation is indicated in some patients with end-stage renal disease. The indications for bilateral nephrectomy include persistent heavy proteinuria, refractory hypertension, and urinary tract infections. We report an eight-month-old baby with male pseudohermaphroditism and renal failure secondary to diffuse mesangial sclerosis. While awaiting renal transplantation, dialysis became necessary and the child presented standard drug therapy-resistant hypertension. A bilateral nephrectomy was performed simultaneously to peritoneal dialysis catheter implantation by using laparoscopy. At the present time, the patient is doing well with ambulatory dialysis and all antihypertensive medication has been discontinued. We recommend this technique in children who require bilateral nephrectomy and peritoneal dialyisis. Not only is it somewhat less aggressive than traditional open surgery, but it also reduces post-operative pain, allows earlier initiation of peritoneal dialysis, and improves cosmetic appearance.

Double renal transplantation--a strategy with donors under 3 years old.

OBJECTIVE: To evaluate the transplantation of both kidneys from donors under 3 years old to older pediatric recipients, in order to provide adequate renal mass and improve graft survival. PATIENTS AND METHODS: Seven patients received a double kidney transplant from a donor under 3 years old (mean age 2.7 years). The primary renal disease was obstructive uropathy in two patients, and hemolytic uraemic syndrome, tuberous sclerosis, nephronoptisis, reflux nephropathy and nephrotic syndrome (one patient each). Recipients were 14-18 years old and had a mean height of 165.2 cm. Five were in dialysis and it was the second transplantation for two. Both kidneys were sequentially placed in the same iliac fossa; the first was placed the most cranially with the second placed caudal to the first. The surgical technique was similar to that used to place a single graft. Immunosuppression induction employed monoclonal antibodies followed by a triple therapeutic regime (mofetyl micofenolate/steroids/tacrolimus). RESULTS: Diuresis was started immediately with all the grafts and there was no thrombosis in any patient. One patient lost both grafts due to recurrence of her primary disease. Another patient developed lymphocele 1 year post transplant and required laparoscopic drainage. The grafts in six patients are doing well after a follow up of 1 to 7 years. CONCLUSION: Double transplant of both kidneys from a donor under 3 years old can provide sufficient renal mass for adequate renal function and does not present a higher risk of complications.

Pharmacological study of the new mucolytic drug N-guanyl-cysteine.

The pharmacological evaluation of N-guanyl-cysteine (IQB-782) is reported. This new cysteine derivative shows a potent mucolytic-expectorant activity in different test systems. Thus, IQB-782 protects rats against tobacco-smoke-induced respiratory airway obstruction, increases the tracheo-bronchial mucus secretion in rabbits and increases the pulmonary excretion of fluorescein in mice, an index of broncho-secretagogue activity. Like other mucolytics, IQB-782 is also effective in vitro in reducing the viscosity of a suspension of gastric mucin. This new drug is apparently devoid of any cardiovascular or autonomic activity and shows a moderate CNS depressant effect. IQB-782 is consequently a new thiol derivative which may offer some advantages in the treatment of different types of obstructive pulmonary disease.

Should we treat vesicoureteral reflux in patients who simultaneously undergo bladder augmentation for neuropathic bladder?

PURPOSE: If high pressure is responsible for vesicoureteral reflux in neurogenic bladders, eliminating the high pressure should resolve reflux in noncompliant bladders. Nevertheless, the need for simultaneous ureteral reimplantation and bladder augmentation remains controversial in patients with a noncompliant bladder and vesicoureteral reflux. MATERIALS AND METHODS: Bladder augmentation was performed in 8 boys and 8 girls with a noncompliant bladder and vesicoureteral reflux at a mean age of 10 years (range 2 to 17) because they had not responded satisfactorily to clean intermittent catheterization and anticholinergic therapy alone. No effort had been made to correct reflux surgically in these patients. Before bladder augmentation reflux was grade II to III in 4 ureters (3 patients) and IV to V in 18 (13). The bladder was augmented with intestine in 14 patients and with ureter in 2. Mean followup was 5.2 years (range 2.8 to 7.5). RESULTS: After bladder augmentation bladder compliance improved in all patients. Of the 18 ureters with high grade reflux 2 were used for bladder augmentation, and reflux resolved in 13, was downgraded in 1 and persisted in 2. Of the 4 ureters with low grade reflux, reflux disappeared in 2 and was down graded in 2. The rate of high and low grade vesicoureteral reflux resolution or improvement was 87.5% and 100%, respectively. At the end of the study only 3 patients had persistent reflux, which was downgraded in 2. No urinary tract infections developed in any patient and none was receiving chemoprophylaxis 6 months postoperatively. CONCLUSIONS: Our experience indicates that antireflux procedures are not routinely needed in patients with a noncompliant bladder and associated vesicoureteral reflux who undergo bladder augmentation.

[Neutropenic enterocolitis in children with cancer]. / La enterocolitis neutropénica en el niño con cáncer.

OBJECTIVES: Neuropenic enterocolitis (NEC) is a destructive lesion of the ileocecal region occurring in cancer patients treated with chemotherapy. Its clinical picture is one of febrile acute abdominal extension with bloody diarrhea and low neutrophil counts. Our aim was to determine the incidence of NEC in children with cancer and to review the indications of surgery in these cases. MATERIAL AND METHODS: The records of children with cancer treated with chemotherapy in the last 6 years at Hospital Infantile La Paz were reviewed. We selected those patients who had abdominal pain and neutropenia and whose physical examination and radiological findings were consistent with NEC. RESULTS: Twelve cases of NEC were diagnosed during this period among 432 malignancies. The symptoms most frequently seen were abdominal pain and distension, nausea and vomiting. The neutrophil count was consistently below 500/ml. All patients were receiving chemotherapy before the onset of the clinical picture. Five children were operated upon. In three of these we found various ileocecal perforations, in one a gastric perforation and in the remaining one a diffuse inflammation of the ileocecal area. Two non-operated patients died from NEC. The remaining children recovered without problems with medical therapy. CONCLUSION: Pediatric surgeons treating neutropenic cancer patients should be familiar with this condition, that must be suspected early in granulocytopenic patients with acute abdominal extension. Aggressive surgical management is indicated in cases with severe peritonitis, bowel perforation or massive lower gastrointestinal bleeding, irrespective of the degree of neutropenia. Medical support should aim at reestablishing normal neutrophil counts.