Background Nephroureterectomy alone fails to adequately treat many patients with advanced upper tract urothelial carcinoma (UTUC). Perioperative platinum-based chemotherapy has been proposed but requires adequate renal function. Objective Our aim was to determine whether the ability to deliver platinum-based chemotherapy following nephroureterectomy is affected by postoperative changes in renal function. Design, settings, and participants We retrospectively reviewed data on 388 patients undergoing nephroureterectomy for UTUC between 1991 and 2009. Four institutions were included. Intervention All patients underwent nephroureterectomy. Measurements All patients had serum creatinine measured before and after surgery. The value closest to 3 mo after surgery was taken as the postoperative value (range: 2[en]52 wk). Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation. EGFR values before and after surgery were compared using the paired t test. We chose an eGFR of 45 and 60 ml/min per 1.73 m2 as possible cut-offs for chemotherapy eligibility and compared eligibility before and after surgery using the chi-square test. Results and limitations Our cohort of 388 patients included 233 men (60%) with a median age of 70 yr. Mean eGFR decreased by 24% after surgery. Using a cut-off of 60 ml/min per 1.73 m2, 49% of patients were eligible for chemotherapy before surgery, but only 19% of patients remained eligible postoperatively. Using a cut-off of 45 ml/min per 1.73 m2, 80% of patients were eligible preoperatively, but only 55% remained eligible after surgery. This distribution persisted when we limited the analysis to patients with advanced pathologic stage (T3 or higher). Patients older than the median age of 70 yr were more likely to be ineligible for chemotherapy both pre- and postoperatively by either definition, and they were significantly more likely to have an eGFR <45 ml/min per 1.73 m2 postoperatively, regardless of their starting eGFR. This study is limited by its retrospective nature, and there was some variability in the timing of postoperative serum creatinine measurements. Conclusions EGFR is significantly diminished after nephroureterectomy, particularly in elderly patients. These changes in renal function likely affect eligibility for adjuvant cisplatin-based therapy. Accordingly, we suggest strong consideration of neoadjuvant regimens.

Inhibition of bladder activity by tibial nerve stimulation was investigated in α-chloralose-anesthetized cats with an intact spinal cord. Short-duration (3-5 min) tibial nerve stimulation at both low (5 Hz) and high (30 Hz) frequencies applied repeatedly during rhythmic isovolumetric bladder contractions was effective in inhibiting reflex bladder activity. Both frequencies of stimulation were also effective in inducing inhibition that persisted after the termination of the stimulation. The poststimulation inhibitory effect induced by the short-duration stimulation significantly increased bladder capacity to 181.6 ± 24.36% of the control capacity measured before applying the stimulation. Thirty-minute continuous stimulation induced prolonged poststimulation inhibition of bladder activity, which lasted for more than 2 h and significantly increased bladder capacity to 161.1 ± 2.9% of the control capacity. During the poststimulation periods, 5-Hz stimulation applied during the cystometrogram elicited a further increase (~30% on average) in bladder capacity, but 30-Hz stimulation was ineffective. These results in cats support the clinical observation that tibial nerve neuromodulation induces a long-lasting poststimulation inhibitory effect that is useful in treating overactive bladder symptoms.

Our experience indicates that radiofrequency ablation is safe in high-risk patients with stage I non-small lung cancer, with reasonable results in patients who are not fit for surgical intervention.

Purpose To investigate the effects of tibial nerve stimulation on bladder overactivity induced by acetic acid (AA) irritation. Material and Methods Cystometry was performed in 10 α-chloralose anesthetized female cats by infusing saline or AA through a urethral catheter that was secured by a ligature around the urethra. Intravesical infusion of 0.25% AA was used to irritate the bladder and induce bladder overactivity. Multiple cystometrograms (CMGs) were performed before, during, and after tibial nerve stimulation to determine the inhibitory effect on the micturition reflex. Results Infusion of 0.25% AA irritated the bladder, induced bladder overactivity, and significantly reduced the bladder capacity to about 20% of the control capacity measured during saline infusion. Tibial nerve stimulation at either low (5 Hz) or high (30 Hz) frequency significantly increased bladder capacity to about 40% of the saline control capacity when it was applied during AA infusion CMG. The amplitude of bladder contractions was smaller during AA irritation than during saline distention due to a significantly smaller bladder capacity. Tibial nerve stimulation at 5 Hz not only increased bladder capacity but also increased the amplitude of bladder contractions. Conclusion Activation of somatic afferents in the tibial nerve of cats can partially reverse the bladder overactivity induced by intravesical administration of a chemical irritant that activates C-fiber afferent nerves. These data are consistent with clinical studies showing that tibial nerve neuromodulation is effective in treating overactive bladder symptoms.

Bladder reflexes evoked by stimulation of pudendal afferent nerves (PudA-to-Bladder reflex) were studied in normal and chronic spinal cord injured (SCI) adult cats to examine the reflex plasticity. Physiological activation of pudendal afferent nerves by tactile stimulation of the perigenital skin elicits an inhibitory PudA-to-Bladder reflex in normal cats, but activates an excitatory reflex in chronic SCI cats. However, in both normal and chronic SCI cats electrical stimulation applied to the perigenital skin or directly to the pudendal nerve induces either inhibitory or excitatory PudA-to-Bladder reflexes depending on stimulation frequency. An inhibitory response occurs at 3–10 Hz stimulation, but becomes excitatory at 20–30 Hz. The inhibitory reflex activated by electrical stimulation significantly (P<0.05) increases the bladder capacity to about 180% of control capacity in normal and chronic SCI cats. The excitatory reflex significantly (P<0.05) reduces bladder capacity to about 40% of control capacity in chronic SCI cats, but does not change bladder capacity in normal cats. Electrical stimulation of pudendal afferent nerves during slow bladder filling elicits a large amplitude bladder contraction comparable to the contraction induced by distension alone. A bladder volume about 60% of bladder capacity was required to elicit this excitatory reflex in normal cats; however, in chronic SCI cats a volume less than 20% of bladder capacity was sufficient to unmask an excitatory response. This study revealed the co-existence of both inhibitory and excitatory PudA-to-Bladder reflex pathways in cats before and after chronic SCI. However our data combined with published electrophysiological data strongly indicates that the spinal circuitry for both the excitatory and inhibitory PudA-to-Bladder reflexes undergoes a marked reorganization after SCI.

Objective To investigate the possibility of suppressing bladder overactivity by electrical activation of somatic afferent nerves in the foot. Materials and Methods Cats with intact spinal cord were studied under α-chloralose anesthesia. Bladder pressure was recorded via a urethral catheter. Foot stimulation was applied via surface pad electrodes attached to the skin of the front or hind foot. Results Reflex micturition was inhibited by electrical stimulation of the hind foot at either low (5 Hz) or high (20 Hz) frequencies, but stimulation of the front foot was not effective. On average bladder capacity during a saline infusion cystometrogram (CMG) was significantly (P<0.05) increased to 153.2±18.2% and 136.9±14.3% of the control bladder capacity by stimulation at frequencies of 5 Hz and 20 Hz, respectively. Intravesical infusion of 0.25% acetic acid (AA) induced bladder overactivity and reduced bladder capacity to 20.3±8.9% of the control capacity measured during saline infusion. Foot stimulation inhibited the AA-induced bladder overactivity recorded under isovolumetric conditions, and significantly (P<0.05) increased bladder capacity during acetic acid infusion. However, it only restored the small bladder capacity caused by AA irritation to about 40-50% of the control bladder capacity measured during saline infusion. The effect of foot stimulation did not persist after termination of stimulation during repeated CMG tests. Conclusions This study demonstrated the potential of non-invasive transcutaneous electrical stimulation of somatic nerves in the foot to inhibit reflex bladder activity and treat overactive bladder symptoms.

Preliminary experience indicates that stereotactic radiosurgery (median dose 20 Gy) is safe in this high-risk group; however, it was associated with significant local progression. Further prospective studies with multiple fractions are needed to evaluate its efficacy in this population.

The incidence of esophageal cancer has increased dramatically in the Western population in the last two decades. Many of these patients tend to present late in the disease course with symptoms of dysphagia and malnutrition. Thus a majority of patients at presentation may require palliation of their symptoms. Lung cancer is the most common cause of cancer related mortality in the United States. Similar to esophageal cancer, many patients present in advanced stages where surgical resection for cure may not be an option. Endobronchial obstruction from both primary and metastatic neoplasm causes significant morbidity. The modalities, which are currently available for palliation of symptoms include surgery, photodynamic therapy, dilation, external beam radiation, stents, Nd:YAG laser therapy, and brachytherapy. Each of these modalities has their specific advantages and drawbacks. In this article, we discuss the role of photodynamic therapy in the palliation of esophageal and lung cancer.