Biallelic PMS2 mutations and a distinctive childhood cancer syndrome.

Biallelic mutations in PMS2, a gene usually associated in heterozygous form with hereditary nonpolyposis colorectal cancer (HNPCC), results in a recently described childhood cancer syndrome. The tumor spectrum encompasses atypical brain cancers, hematologic malignancies, and colonic polyposis and cancer. Cutaneous stigmata resembling café-au-lait macules with more diffuse margins are frequently seen. Onset is as young as 2 years. The risk of second malignancy is high. Evidence exists for surveillance for bowel cancer, but surveillance for the wider tumor spectrum is of uncertain benefit. We report a consanguineous Australian-Lebanese family with multiple affected individuals shown to be homozygous for a PMS2 exon 7 deletion. We also review published cases of biallelic mutations in HNPCC-related genes. Early recognition of this familial cancer syndrome is critical, and should prompt investigation for familial HNPCC mutations.

Autoaugmentation gastrocystoplasty: further studies of the sheep model.

OBJECTIVE: To report our experience with autoaugmentation gastrocystoplasty (AAGC, reported to result in an inconsistent augmentation effect in children) in a sheep model, specifically addressing issues of surgical techniques and postoperative bladder drainage that may affect the augmentation result, as many factors have been implicated in the poor outcome. MATERIALS AND METHODS: Ten 6-month-old male lambs had a suprapubic catheter placed by an open laparotomy. Intraoperative urodynamics were evaluated before and after detrusorotomy for autoaugmentation and after completing AAGC. The bladder was drained with no distension for 1 week after surgery and the urodynamic evaluation repeated on control and experimental animals 6 months after surgery. The animals were then killed and the bladders evaluated for gastric flap survival and histological changes in the native bladder and augmentation segments. The results were analysed using a one-sided Student's t-test. RESULTS: The median (range) native bladder volume at leak-point pressure was 110 (40-490) mL. Intraoperative bladder volumes after completing AAGC confirmed adequate augmentation segments in all animals. The urodynamic evaluation at 6 months after AAGC showed increases in bladder volumes in nine of 10 animals (0-1336 mL), significantly greater than the increase in volume in the control sheep (median 337.5 vs 115.3 mL; P < 0.05). The bladder compliance (volume/pressure at leak capacity) 6 months after AAGC was slightly better but not significantly higher than in controls (median 17.3 vs 10.8 mL/cmH(2)O; P > 0.05). The median (range) ratio of surviving gastric flap to native bladder circumferences was 34.5 (31-53)%. Histology showed scarring of the submucosal layer in one of 10 augmentation segments and normal urothelium in all bladders. CONCLUSION: AAGC produces reliable bladder augmentation and excellent bladder compliance in a sheep model of a non-neurogenic bladder. The gastric flap survived well and there was no bladder wall separation with simple postoperative catheter drainage.

Primary megaureter: results of surgical treatment.

BACKGROUND: The aim of this study was to assess the clinical and radiological outcome after surgical treatment for primary -megaureter. METHODS: A retrospective analysis of 16 patients who had reimplantation of 17 primary megaureters between January 1997 and April 2001 was performed. Patients who had additional urinary tract pathology were not included in this study. The intent of the study was to focus on the complex range of data points that were used to reach the decision to operate. RESULTS: Six of eight patients with febrile urinary tract infections prior to surgery have been without infections postoperatively. One patient who presented with daytime wetting has less wetting postoperatively, and one baby who presented with failure to thrive and postfeed vomiting, is feeding well postoperatively. On ultrasound investigation, the median diameter of the megaureter prior to operation was 11 mm (range 6-24 mm). One month after the operation, dilatation of the ureter could no longer be demonstrated in 10, was reduced in six, and increased in one of 17 ureters. Three months postoperatively, hydroureter was no longer detected in 14 and was reduced in three. In comparison, the hydronephrosis 1 month postoperatively was reduced in six, unchanged in seven and worse in four out of 17 kidneys, and 3 months after the operation, hydronephrosis was reduced in 13 and was unchanged in four compared with preoperative findings. Renograms at 3 months postoperatively showed free drainage in the 11 kidneys with impaired drainage preoperatively, and drainage continued to be normal in all six kidneys with normal drainage preoperatively. Median pre-operative renographic split function was 47% (range 39-54%), and was not significantly changed 3 months after the operation. CONCLUSIONS: When the decision to surgically intervene was made on a multifactorial basis, reimplantation of a primary mega-ureter resulted in improved clinical status, reduced dilation of the ureter and renal pelvis, and free drainage of the upper urinary tract.

Congenital posterior urethral obstruction: re-do fulguration.

In patients with congenital posterior urethral obstruction, transurethral fulguration (TUF) is usually the treatment of choice if the patient is in a stable condition. However, few papers have described the proportion of patients who need further fulguration. We reviewed 83 boys with a congenital obstructive posterior urethral membrane (COPUM) to assess the role of re-do fulguration, as judged by prospective video recordings. Between December 1990 and March 2000, 83 boys (aged from newborn to 15 years) underwent cystourethroscopy for investigation of a urethral anomaly and were found to have a COPUM. TUF was performed endoscopically with a hook diathermy electrode. Two to 3 months later boys who had cauterisation had a further urethroscopy and diathermy as required. Of the 83 membranous lesions in the posterior urethra, 38 were considered severe, 20 moderate, and 21 minor. Four patients had inadequate data to be properly classified. Eighteen (47.4%) of the 38 patients who had a severe obstructive membrane equired further endoscopic intervention to obliterate residual membrane elements. As over 45% of patients who had a severe obstructing membrane needed further fulguration, it is important to follow patients carefully and to repeat the cystourethroscopy.