Organ-confined clear cell renal cell carcinoma: the prognostic impact of microvascular invasion, nuclear grade and tumour size.

The frequency of diagnosed and treated organ-confined renal cell carcinoma is increasing. The prognosis of this group of tumours is difficult to predict. The main purpose of this study was to examine the prognostic significance of microvascular invasion, tumour size and nuclear grade in a complete cohort of 76 consecutive patients with organ-confined clear cell renal cell carcinoma treated with radical nephrectomy. Patient ages ranged from 39 to 88 years (mean 66 years). Median follow-up was 10.2 years (range 0.1-19.4 years). The tumours were graded according to Fuhrman. Representative histological sections were stained for CD31, which decorates endothelial cells, in order to assess microvascular invasion (MVI). In univariate analysis, microvascular invasion (p<0.01), tumour size (TS) (p=0.01), TNM stage (p=0.01) and Fuhrman nuclear grade (p=0.02) were significant predictors of cancer-specific survival. Multivariate analysis, adjusted for age, revealed that microvascular invasion, tumour size and nuclear grade were independent covariates. According to our findings microvascular invasion is a strong independent prognostic predictor, and including this in the histopathology report should be considered together with nuclear grade and tumour size.

Bladder rupture due to accidental oxygen insufflation via an indwelling urethral catheter--a report of two cases.

Two cases of bladder rupture caused by accidental insufflation of oxygen through an indwelling urethral catheter are described. Both patients were ill with multiple diseases. Conservative treatment, including an open indwelling urethral catheter, and surveillance of abdominal status seem appropriate when managing this complication.

Brain-derived neurotrophic factor promotes survival and chemoprotection of human neuroblastoma cells.

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and protection against neuronal damage. We addressed whether BDNF might promote survival and chemoprotection in neuroblastoma (NB) using a drug-sensitive human NB cell line. All-trans-retinoic acid (ATRA) induces a striking phenotypic differentiation of NB1643 cells, and exogenous BDNF treatment promotes survival of these differentiated cells. ATRA induces TRKB expression, and exogenous BDNF stimulates both autophosphorylation of TRKB and induction of the immediate early gene, FOS, in these cells. BDNF mRNA is expressed in NB1643 cells. Because the time course of TRKB induction closely parallels phenotypic differentiation of these cells, it seems probable that ATRA induces differentiation of NB1643 cells by establishing an autocrine loop involving BDNF and TRKB. Exogenous BDNF treatment resulted in a further increase in neurite outgrowth, which again suggests that an autocrine loop is involved in differentiation of NB1643 cells in response to ATRA. We then tested whether BDNF might afford drug resistance in NB and found that BDNF does indeed protect in this NB model against cisplatin, a DNA-damaging agent actually used in the treatment of NB.

Brain derived neurotrophic factor protects human neuroblastoma cells from DNA damaging agents.

Neurotrophins are required for survival of neurons during development and may act as survival factors to cells undergoing stress. We tested whether brain derived neurotrophic factor (BDNF) protects neuroblastoma (NB) cells from cytotoxic agents using a model NB cell line, NB 1643, which expresses functional tropomyosin related kinase B (TRKB) following treatment with all-trans-retinoic acid. TRKB is the receptor for BDNF. BDNF increases the EC50 values in survival assays for cisplatin, doxorubicin, and topotecan by two to three fold. Thus, BDNF does indeed protect cells drugs that damage DNA. Cisplatin and doxorubicin are used to treat NB. Topotecan is in clinical studies for the treatment of NB. Since these drugs induce DNA damage, we also investigated whether BDNF might afford protection from gamma irradiation. BDNF also induces more than a two fold resistance to gamma irradiation. Since BDNF protects cells from agents with different mechanisms of damaging DNA and resistance, it seems likely that BDNF may alter a common signaling pathway required for cell death initiation by DNA damaging agents.

One or two incisions for nephroureterectomy in transitional cell renal pelvis tumours.

A retrospective study comprising 18 patients with transitional cell renal pelvis tumours (TCPT) was carried out to evaluate the results after two different surgical procedures for nephroureterectomy. The kidney was removed by a flank incision and the lower part of the ureter by either an incision in the lower part of the abdomen or intussusception of the ureter followed by transurethral resection of the ureteral orifice. Eight patients were subjected to nephroureterectomy by means of two incisions and another eight patients underwent a simple nephrectomy followed by ureteral intus-susception and transurethral resection. Two patients received other treatments. After nephroureterectomy with a separate incision for ureterectomy, the average hospital stay was 12 days, compared with 7.5 days in patients operated upon with only one abdominal incision. Recurrence of tumour or survival was not significantly different in the two groups.

Local excision of ureteral tumours.

A retrospective study was carried out on 20 patients with transitional cell ureteral tumours (TCUT). Surgical exploration of the tumour was performed in 17 patients. Biopsies for frozen section were evaluated for decision concerning the extent of operative intervention. If radical excision of the tumour could be done, and if the ureteral defect could be bridged, a conservative procedure was chosen. Thus, segmental resection of the ureter and primary end-to-end closure of the ureter was performed in 5 patients and ureteroneocystostomy in 3 patients. In nine patients local tumour excision was not feasible and nephroureterectomy was done. The survival rate at 3 and 10 years after ureteral resection as well as after nephroureterectomy was the same, 66% and 16%, respectively. Local excision of non-invasive low-grade ureteral tumours could be safely performed in selected patients, based on local findings and frozen section at the time of surgery.

Perforation of continent urinary reservoirs. Scandinavian experience.

In a questionnaire survey of urological departments in Sweden, Denmark, Finland and Norway, 20 episodes of perforation of continent urinary pouches were found to have occurred in 18 patients, representing an incidence of 1.5%. This complication occurred with ileal as well as colonic segments, without predilection. In one case there was perforation of an appendiceal outlet. Noticeable findings were (a) a long delay (median 10h) to treatment and (b) that investigational procedures such as enterocystography and enterocystoscopy were not commonly employed. Treatment of this potentially lethal complication was by oversewing the perforation, and there were no subsequent major complications. This complication should be strongly suspected if a patient with continent urinary reconstruction presents with acute abdominal pain.

Long-term experience of self-injection therapy with prostaglandin E1 for erectile dysfunction.

A total of 42 evaluable patients 36-80 years old were treated with intracavernous injection of prostaglandin E1 for erectile dysfunction. They reported retrospectively via a questionnaire their long-term experience of this method. Twenty-four patients (57%) were after 46.9 months still using the technique, while 18 patients (43%) had abandoned the method after 21.4 months of use. No major complications were observed or reported.

Identification of genes required for pollen-stigma recognition in Arabidopsis thaliana.

In higher plants, cell-cell recognition reactions taking place following pollination allow the selective restriction of self-pollination and/or interspecific pollination. Many of these systems function by regulating the process of water transfer from the cells found at the stigmatic surface to the individual pollen grain. Interspecific pollination studies on the cruciferous weed Arabidopsis thaliana revealed only a broad specificity of pollen recognition such that pollen from all tested members of the crucifer family were recognized, whereas pollen from almost all other species failed to hydrate. Genetic analysis of A. thaliana has identified three genes that are essential for this recognition process. Recessive mutations in any of these genes result in male sterility due to the production of pollen grains that fail to hydrate when placed on the stigma, but that are capable of hydrating and growing a pollen tube in vitro. Results from mixed pollination experiments suggest that the mutant pollen grains specifically lack a functional pollen-stigma recognition system. All three mutations described also result in a defect in the wax layer normally found on stems and leaves, similar to previously described eceriferum (cer) mutations. Genetic complementation and mapping experiments demonstrated that the newly identified mutants are allelic to the previously identified genes cer1, cer3 and cer6. TEM analysis of the ultrastructure of the pollen coating revealed that all of the mutant pollen grains bear coatings of normal thickness and that tryphine lipid droplets are missing in cer1-147, are reduced in size in cer6-2654 and appear normal in cer3-2186.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin synthetase inhibition of renal pelvic smooth muscle in the rabbit.

The prostaglandin synthetase inhibitors diclofenac and indomethacin relieve pain in renal colic probably by decreasing renal pelvic pressure. Decreased diuresis and effects on the oedema around the obstructing stone are plausible explanations. In the present study on rabbit renal pelvic tissue strips it was found that both indomethacin and diclofenac decreased the spontaneous phasic activity of the strips. ED50 was 5.4 +/- 0.7 X 10(-5) M for indomethacin and 2.4 +/- 0.5 X 10(-5) M for diclofenac (P less than 0.001). With the prostaglandin synthetase inhibitors still in the tissue bath the activity was regained when either prostaglandin E2 or F2 alpha was added, prostaglandin E2 being more potent in this respect. It was concluded that prostaglandin synthetase inhibitors seem to reduce smooth muscle activity in the renal pelvis, a mechanism which might contribute to the pain-relieving ability of these drugs in renal colic.

Surgical alleviation of ureteric obstruction in idiopathic retroperitoneal fibrosis. An analysis of 9 cases.

Nine patients with retroperitoneal fibrosis were reviewed. All patients had idiopathic disease, bilateral in eight patients. An IVP on admission was normal in only one of 17 kidneys with delayed excretion in seven. The upper urinary tract was dilated in eight kidneys and no excretion of contrast medium was seen in four; another four kidneys were not examined by IVP because of uremia. Surgical alleviation of ureteric obstruction was carried out by ureterolysis alone (2 ureters), ureterolysis and lateral displacement of the ureter (2 ureters), ureterolysis and neoimplantation into the bladder (2 ureters), ureterolysis and intraperitonealization (2 ureters), and ureterolysis and omental wrap (7 ureters). After surgery, an IVP showed normal excretion in six of the seven kidneys with delayed excretion preoperatively. Two of the four preoperatively nonfunctioning kidneys also showed normal excretion at IVP. Of the four kidneys not preoperatively examined by IVP because of uremia two showed a normal excretion on postoperative IVP. Two ureters developed recurrent obstruction and required additional surgery whereas 10 ureters remained unobstructed in the follow-up period of 26-89 months. Our experience suggests that complete and extensive ureterolysis combined with omental wrapping gives the best results on a long-term basis.

The effect of intraduodenal installation of oleic acid on plasma neurotensin-like immunoreactivity and on gastric acid secretion stimulated by betazole and sham feeding in man.

Intraduodenal administration of oleic acid has previously been shown to inhibit gastric acid secretion induced by pentagastrin in man. This inhibition was dose-dependent and significantly correlated to a rise in plasma concentration of neurotensin-like immunoractivity (NTLI). Maximal inhibition occurred with a volume of oleic acid of 20 ml. In the present study intraduodenal instillation of 20 ml. of oleic acid inhibited acid secretion evoked by sham feeding in healthy subjects but did not significantly inhibit the near-maximal acid secretion stimulated by the histamine analogue betazole. The inhibition of acid secretion induced by sham feeding was the same (about 45%) as the inhibition of pentagastrin-stimulated secretion. Plasma NTLI rose significantly in both the sham feeding and betazole experiments and peaked at about 145 pM. The results are in agreement with the inhibitory characteristics of neurotensin and support the hypothesis that the inhibition of gastric acid secretion by small amounts of intestinal fat is at least partly mediated by neurotensin.

Uretero-neocystostomy in the treatment of postoperative uretero-vaginal fistula.

Nine patients with unilateral uretero-vaginal fistula afer hysterectomy were seen over a 9-year period. In 5 patients radical pelvic surgery combined with radiotherapy had been carried out because of carcinoma of the cervix. In one patient the fistula developed following total hysterectomy 18 years after radiotherapy because of a cervical carcinoma. In 3 patients hysterectomy had been performed for benign disease, uterine fibroids or fibroids combined with endometriosis. In one patient the fistula was successfully treated with an indwelling ureteral catheter for 7 days. In the other 8 patients uretero-neocystostomy was successful as regards vaginal urine leakage; following this procedure one kidney was lost in the follow-up period. It is concluded that in patients with uretero-vaginal fistula, uretero-neocystostomy can be performed with satisfactory results even when the patient has been treated for a cervical carcinoma by radiotherapy and radical surgery.

Urethrovaginal and vesicovaginal fistula. A review of 29 patients.

During an 11-year period 29 women were treated for 6 urethrovaginal and 24 vesicovaginal fistulae. In all patients the urethrovaginal fistula was preceded by an operation for a benign lesion. Of the 24 patients with vesicovaginal fistulae 11 had a benign and 13 a malignant primary disease. Endoscopy, vaginal examination and IVP provided in most cases sufficient information with which to establish a diagnosis. The urethrovaginal fistulae were operated on either by a vaginal approach (3 patients); two recurrences occurred but healed after reoperation. Of the 24 patients with vesicovaginal fistulae, 14 underwent a combined operation usually including omentum interposition, while 10 underwent primary diversion. Primary cure ensued after 9 of 14 combined operations; recurrences were operated on by a combined approach in 2 patients, vaginal in one and with fibrin occlusion in one. Eight of the 10 patients who underwent urinary diversion had a malignant disease. A vaginal approach in recommended at the primary reconstruction of urethrovaginal fistulae, whereas a combined suprapubic and vaginal approach is recommended in vesicovaginal fistulae as well as in recurrent urethrovaginal fistulae.

Reimplantation of the ureter in prostatic carcinoma associated with bilateral ureteric obstruction.

Bilateral ureteric obstruction from prostatic carcinoma is not uncommon. A number of techniques for urinary diversion have been used in selected patients when uraemia develops. Reimplantation of the ureter(s) as an alternative to urinary diversion has been carried out in 21 patients over a 7-year period. In 6 of these patients bilateral reimplantation was done. In another 6 patients reimplantation of the ureter was not possible and cutaneous ureterostomy was carried out. The overall survival time was 10.6 months. In 13 patients living more than 6 months post-operatively, survival time was 1.8 years. Most patients had severe uraemia and advanced (clinical stage III or IV) prostatic carcinoma. The immediate management of these patients is outlined and the importance should be considered is stress. It is concluded that, whenever possible, ureteric reimplantation should be considered for relieving ureteric obstruction in patients selected for active treatment.

Inhibition of pentagastrin-stimulated gastric acid secretion by graded intraduodenal administration of oleic acid in man.

The inhibitory effect of intraduodenally administered oleic acid in volumes of 5--40 ml on pentagastrin-stimulated gastric acid secretion was determined in healthy volunteers. In the control experiments, corresponding volumes of saline were given. Five and 10 ml oleic acid brought about a significant inhibition of gastric acid secretion of 29% and 32%, respectively. After 20 ml of oleic acid the inhibition was 46%, a significantly stronger inhibition than after 5 or 10 ml. Forty milliliters of oleic acid did not further increase the inhibition. Maximal inhibition appeared 30--60 min after the administration of oleic acid. In seven duodenal ulcer patients 20 ml oleic acid evoked an inhibition of gastric acid secretion of 20%, which was significantly less than the inhibition produced in healthy subjects after the same volume of oleic acid. The results suggest that the intraduodenal administration of relatively small volumes of oleic acid elicits a dose-dependent inhibition of pentagastrin-stimulated gastric acid secretion in man and that maximal inhibition is obtained by 20 ml of oleic acid. The results also indicate that duodenal ulcer patients may have a defective fat inhibitory mechanism.

Thigh adductor contraction during transurethral resection of bladder tumours: evaluation of inactive electrode placement and obturator nerve topography.

Thigh adductor contraction occurred in 17 of 160 patients during transurethral resection of newly diagnosed bladder tumours. In 13 of the 17 patients contractions were abolished by changing the site of the inactive electrode from the buttocks to the thigh. The topographic relationship between the obturator nerve and the bladder wall studied radiographically and at autopsy showed that the distance between the bladder and the nerve considerably diminished with increasing bladder volume. Thus, when obturator nerve stimulation occurs during transurethral resection transposition of the inactive electrode from the buttocks to the thigh should be tried first to prevent further stimulation. Moreover, TUR at low bladder volume may reduce the frequency of obturator nerve stimulation.

Fat inhibition of gastric acid secretion in man and plasma concentrations of neurotensin-like immunoreactivity.

The effects of intraduodenal administration of oleic acid (5, 10, 20, and 40 ml) on gastric acid secretion stimulated by a submaximal intravenous pentagastrin infusion and on plasma concentrations on neurotensin-like plasma immunoreactivity (NTLI) were studied in 18 healthy subjects. Each volume of oleic acid or saline (controls) was tested in six subjects except the volume of 20 ml, which was given to ten subjects. Gastric acid secretion was studied for a 2-h period at 15-min intervals after intraduodenal infusion. Five milliliters oleic acid evoked a significant inhibition (29%) of gastric acid secretion. Maximal inhibition by oleic acid appeared after 20 ml (43%), which was significantly greater than after 10 ml. In seven duodenal ulcer (DU) patients 20 ml oleic acid evoked an inhibition of 20%, which was significantly lower than in the healthy subjects. Proximal gastric vagotomy (PGV) abolished the fat inhibition in DU patients. Basal and peak NTLI concentrations after 20 ml oleic acid were significantly lower in DU patients than in health subjects. In DU patients there was no significant difference in the integrated response of NTLI before and after PGV. The 2-h integrated NTLI response was dependent on the administered volume of oleic acid in healthy subjects. There was a correlation between acid inhibition and the integrated response ot NTLI in healthy subjects. This suggests that immunoreactive neurotensin may be involved in the oleic-acid-induced inhibition of gastric acid secretion. Neurotensin, or a neurotensin metabolite, apparently exerts its inhibitory effect at a synaptic level, which explains the finding that oleic acid did not inhibit gastric acid secretion after PGV. Neurotensin may have a physiological role as a hormone with enterogastrone functions.