Diagnosing and Managing Delirium in Cancer Patients.

Delirium is frequently encountered when caring for cancer patients, from initial diagnosis to the advanced stages of the disease; however, it is often missed. Oncologists need to be familiar with the various defining features of the condition, and should be able to identify common underlying causes. We present a systematic approach to the workup, as well as pharmacologic and nonpharmacologic approaches to management. We discuss the common practice of treatment with neuroleptics, as well as recent controversy surrounding their use.

Cancer-related cognitive impairment in older adults.

PURPOSE OF REVIEW: Cancer, aging, and cognition form a complicated interface that can challenge patients, caretakers, and healthcare professionals. Although the typical aging process allows for compensatory mechanisms to help maintain daily functioning, cancer and cancer treatments can remove the fail-safes and exacerbate cognitive decline. As a result, older cancer patients can experience increased morbidity and mortality. The goal of this article is to provide additional assessment strategies, diagnostic considerations, and treatment options for providers taking care of this growing population. RECENT FINDINGS: In this review, we will discuss current areas of research with regard to epidemiology and our current understanding of cancer-related cognitive impairment in the older patient, while reinforcing the importance of the Comprehensive Geriatric Assessment in assessment, prognosis, and treatment guidance. SUMMARY: Although cognitive impairment in the older cancer patient may be an increasing cause of concern with several gaps in research, there are opportunities to take a methodical treatment approach.

The effect of argon gas pressure on ice ball size and rate of formation.

INTRODUCTION: Contemporary cryoablation technology utilizes the Joule-Thomson effect, defined as a change in temperature that results from expansion of a nonideal gas through an orifice or other restriction. We evaluated the effect of initial gas tank pressures on freezing dynamics in a single-probe model and in a multiprobe model using contemporary cryoablation technology. MATERIALS AND METHODS: Cryoablation trials were performed in a standardized system of transparent gelatin molds at 25°C. Two sets of trials were performed. The first trial evaluated temperature and ice ball size for a given tank pressure when a single needle was deployed. The second trial recorded ice ball temperatures for each probe when multiple probes were fired simultaneously. RESULTS: Trial 1: The rate of temperature change is directly related to the initial pressure of the gas being released, and the group with the highest starting pressures reached the lowest mean temperature and had the largest mean ice ball size (p < 0.01). Trail 2: Multiple-probe ablation did not affect the rate of temperature change or final temperature compared with firing a single probe (p > 0.7). CONCLUSIONS: In accordance with the Joule-Thomson effect, higher initial gas pressures used for cryoablation in a transparent gel model demonstrate statistically significant lower temperatures, faster decreases in temperature, and formation of larger ice balls than lower gas pressures do. With contemporary technology, multiple simultaneous cryoprobe deployment does not compromise individual probe efficacy. The use of higher initial tank pressures will theoretically help future cryoprobes be more effective, creating a greater volume of cell necrosis and a smaller indeterminate zone.

Evaluation of a novel temperature-sensitive polymer for temporary ureteral occlusion.

PURPOSE: Proximal stone migration during ureteroscopic procedures increases operative time and risk. This study was designed to evaluate the ability of a new temperature-sensitive polymer to prevent proximal stone migration during ureteroscopic procedures. MATERIALS AND METHODS: Porcine urinary systems were harvested en bloc. The volume of gel needed to occlude the ureter, time to achieve a solid state, length of ureter filled, and pressure needed to dislodge the gel from the ureter were recorded. Radio opacity of the polymer was evaluated. Endoscopic laser lithotripsy was the performed after deploying the urologic polymer, and, after gel application and stone manipulation, all ureters were examined for histologic changes. RESULTS: At 36.7 degrees C, 0.5 mL and 1 mL of polymer sufficiently occluded the ureter. Both amounts solidified in 25 to 40 seconds. The mean length of ureter occluded was 56.3 mm, and the mean pressure needed to dislodge the polymer was 159.2 mm Hg. The polymer was radiopaque and did not cause histologic alterations in the ureter. Proximal migration of stone fragments was not observed during any of the procedures performed. CONCLUSIONS: Our in vitro study indicates that this radiopaque, thermosensitive polymer is able to transiently occlude the ureter without damaging the urothelium while withstanding the pressure of ureteroscopic irrigation, stone motion, and laser energy.

Evolution reversed: the ability to bind iron restored to the N-lobe of the murine inhibitor of carbonic anhydrase by strategic mutagenesis.

The murine inhibitor of carbonic anhydrase (mICA) is a member of the superfamily related to the bilobal iron transport protein transferrin (TF), which binds a ferric ion within a cleft in each lobe. Although the gene encoding ICA in humans is classified as a pseudogene, an apparently functional ICA gene has been annotated in mice, rats, cows, pigs, and dogs. All ICAs lack one (or more) of the amino acid ligands in each lobe essential for high-affinity coordination of iron and the requisite synergistic anion, carbonate. The reason why ICA family members have lost the ability to bind iron is potentially related to acquiring a new function(s), one of which is inhibition of certain carbonic anhydrase (CA) isoforms. A recombinant mutant of the mICA (W124R/S188Y) was created with the goal of restoring the ligands required for both anion (Arg124) and iron (Tyr188) binding in the N-lobe. Absorption and fluorescence spectra definitively show that the mutant binds ferric iron in the N-lobe. Electrospray ionization mass spectrometry confirms the presence of both ferric iron and carbonate. At the putative endosomal pH of 5.6, iron is released by two slow processes indicative of high-affinity coordination. Induction of specific iron binding implies that (1) the structure of mICA resembles those of other TF family members and (2) the N-lobe can adopt a conformation in which the cleft closes when iron binds. Because the conformational change in the N-lobe indicated by metal binding does not impact the inhibitory activity of mICA, inhibition of CA was tentatively assigned to the C-lobe. Proof of this assignment is provided by limited trypsin proteolysis of porcine ICA.

Survival advantage of neonatal CNS gene transfer for late infantile neuronal ceroid lipofuscinosis.

Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal autosomal recessive neurodegenerative lysosomal storage disorder of childhood, is caused by mutations in the CLN2 gene, resulting in deficiency of the protein tripeptidyl peptidase I (TPP-I). We have previously shown that direct CNS administration of AAVrh.10hCLN2 to adult CLN2 knockout mice, a serotype rh.10 adeno-associated virus expressing the wild-type CLN2 cDNA, will partially improve neurological function and survival. In this study, we explore the hypothesis that administration of AAVrh.10hCLN2 to the neonatal brain will significantly improve the results of AAVrh.10hCLN2 therapy. To assess this concept, AAVrh.10hCLN2 vector was administered directly to the CNS of CLN2 knockout mice at 2 days, 3 wk and 7 wk of age. While all treatment groups show a marked increase in total TPP-I activity over wild-type mice, neonatally treated mice displayed high levels of TPP-I activity in the CNS 1 yr after administration which was spread throughout the brain. Using behavioral markers, 2 day-treated mice demonstrate marked improvement over 3 wk, 7 wk or untreated mice. Finally, neonatal administration of AAVrh.10hCLN2 was associated with markedly enhanced survival, with a median time of death 376 days for neonatal treated mice, 277 days for 3 wk-treated mice, 168 days for 7 wk-treated mice, and 121 days for untreated mice. These data suggest that neonatal treatment offers many unique advantages, and that early detection and treatment may be essential for maximal gene therapy for childhood lysosomal storage disorders affecting the CNS.

Risk factors associated with renal parenchymal fracture during laparoscopic cryoablation.

OBJECTIVE: To assess the risk factors for haemorrhage and renal fracture associated with renal cryoablation. MATERIALS AND METHODS: In a porcine model, 120 cryoablations were administered in 26 pigs, with five groups of 24 ice-balls each; in groups 1 and 2 asynchronous cryoprobe activation was evaluated for the 1.47- and 3.4-mm cryoprobes (IceRods, Galil Medical, Plymouth Meeting, PA, USA), respectively; in group 3, three-3.4 mm cryoprobes were used to examine synchronous probe activation; in group 4 the 1.47-mm cryoprobe was used to examine single-probe activation with premature cryoprobe extraction; and in group 5 we used a new 'guillotine' technique for upper-pole renal cryoablation. Ice-ball fractures and haemorrhage were characterized by the location, length and depth of each fracture, was well as the degree of bleeding. RESULTS: In all, 26 domestic pigs successfully had renal cryoablation procedures. In group 1 and 4 there were no episodes of renal fracture; in group 2 renal fracture occurred in 10 (42%) trials. Group 3 had 22 (92%) renal fractures during the freeze/thaw cycle. Group 5 had 13 (54%) renal fractures during the freeze/thaw cycle, and there was an additional ice-ball fracture during probe removal once in 24 times. CONCLUSIONS: Renal fracture is most common with the application of larger 3.4-mm cryoprobes in the synchronous and asynchronous setting. Under standard application, smaller (1.47-mm) cryoprobes result in little renal fracture or bleeding. The use of the guillotine technique is associated with a greater risk of renal fracture.

Comparison of the histologic accuracy of needle biopsy before and after renal cryoablation: laboratory and initial clinical experience.

OBJECTIVES: To minimize the risk of needle biopsy, including tumor seeding and hemorrhage, we examined the feasibility of needle biopsy after renal cryoablation. METHODS: Four cryolesions were created bilaterally on normal porcine renal tissue with an 8-minute double-freeze cycle using a single 17-gauge cryoprobe. Biopsies were obtained with a 16G biopsy needle before and after cryoablation under direct vision. Each biopsy specimen was evaluated for the number of glomeruli and arterioles. We used a two-sample t-test to analyze the data. Subsequently, 10 patients with small renal masses underwent laparoscopic cryoablation using a standard double freeze-thaw cycle. We used an 18G biopsy needle to sample the renal mass with a single core taken before and after cryoablation. A blinded pathologist evaluated the specimens for the histologic accuracy of the two sampling techniques. We used chi-square statistic to determine an association between the diagnostic quality of the core specimens. RESULTS: Two hundred biopsies were obtained from porcine renal tissue. The average number of glomeruli for the pre- and postcryoablation sample was 9.6, and 7.8, respectively (P = 0.04). The average number of arterioles for the pre- and postcryoablation group was 2.3 and 1.9, respectively (P = 0.04). During clinical application, seven of 10 precryoablation and seven of 10 postcryoablation biopsies were diagnostic (P = 0.639). Histopathology was established in all 10 cases. There was no significant bleeding from any needle biopsy. CONCLUSIONS: The porcine model established the feasibility of histologic diagnosis after cryoablation. Our preliminary clinical experience demonstrates that postcryoablation biopsy has similar diagnostic yields to precryoablation biopsy.

Transurethral bladder cryoablation in the porcine model.

OBJECTIVES: To examine the feasibility of transurethral, focal, full-thickness bladder wall cryoablation in the porcine model using a novel 38-cm cryoablation probe. METHODS: A total of 18 pigs were divided into three groups. Groups 1 (n = 6) and 2 (n = 6) underwent transurethral bladder wall cryoablation in a saline environment with two freeze-thaw cycles. The pigs in groups 1 and 2 were killed after 1 and 3 weeks, respectively. The pigs in group 3 (n = 6) underwent transurethral cryoablation after the bladder had been insufflated with carbon dioxide gas. The pigs in group 3 were killed after 1 week. In all groups, laparoscopic access was obtained to protect the abdominal contents from the transmural cryoablation process. Bladder integrity was evaluated with cystography and laparoscopic visualization, and each cryolesion was excised en bloc for extensive histopathologic evaluation. RESULTS: All 18 pigs successfully underwent bladder wall cryoablation. For all groups, the preoperative, postoperative, and sacrifice cystograms were without evidence of extravasation. No urinomas, hematomas, or adhesions were present in groups 1 and 2. Minimal adhesions were identified in 3 (50%) of 6 pigs in group 3. For groups 1, and 2, the mean length and width of the area of complete necrosis on histopathologic evaluation was 6.5 and 3.0 mm and 2.3 and 1.3 mm, respectively. For group 3, the mean diameter of the cryolesion was 8.2 mm. Full-thickness necrosis was confirmed in all groups. CONCLUSIONS: The results of our study have shown that, in this model, complete full-thickness transurethral bladder wall cryoablation, with maintenance of bladder wall integrity, is feasible.