The dendritic cell vaccine DC-Ad-GM·CAIX is an active, specific immunotherapy with the potential of providing a safe and effective therapy against renal cell carcinoma (RCC). Using immunocompetent ...Balb/c mouse models we tested the efficacy and mechanism of the vaccine to prevent and treat the growth of a syngeneic RCC (RENCA) engineered to overexpress the human TAA carbonic anhydrase IX (NPR-IX). In a prevention model, NPR-IX tumor development was specifically and significantly delayed by 13 days in DC-Ad-GM·CAIX-treated mice (P < 0.001), tumor volumes were 79% smaller (day 24, P < 0.007), and body weight was maintained at study termination compared with the controls. Six of these mice remained tumor-free for > 1 year. In a treatment model, NPR-IX tumors remained smaller in DC-Ad-GM·CAIX-treated mice for 8 days (P < 0.002), achieving a 60% growth inhibition at termination. No vaccine-related organ toxicity was observed in either model. The critical mechanistic parameter separating responsive from nonresponsive tumors was hCAIX protein expression, demonstrated by aggressive growth of tumors that did not express hCAIX protein and in sham-treated mice (DC-Ad-Null). No murine serum anti-hCAIX antibodies were detected. Moreover, altered mechanisms of immunoediting as a means for immune evasion were suggested by differential gene expression (Ccl1, Hmgb1, Fgl2, Cd209a, and Klra2) and therapy evasion miRNAs (miR-1186, miR-98, miR-5097, miR-1942, and miR-708) in tumors that evaded DC-Ad-GM·CAIX immunotherapy. This is the first study in immunocompetent mice that provides a proof of concept for the specificity, efficacy, safety, and activity of the DC-Ad-GM·CAIX immunotherapy, forming the basis for a first-in-human phase I trial in RCC patients.
Abstract Background Continent catheterizable ileal pouches require regular irrigations to reduce the risk of bacteriuria and urinary tract infections (UTIs). Objective Our aim was to compare the UTI ...rate, patient friendliness, and costs of standard sterile irrigation versus irrigation with tap water. Design, setting, and participants Twenty-three patients participated in a prospective randomized two-arm crossover single-center trial. Aseptic intermittent self-catheterization (ISC) combined with sterile sodium chloride (NaCl) 0.9% irrigation was compared with clean ISC and irrigation with tap water (H2 O) during two study periods of 90 d each. Intervention Patients underwent daily pouch irrigations with NaCl 0.9% solution or tap water. Measurements Urine nitrite dipstick tests were evaluated daily; urine culture (UC) and patient friendliness were evaluated monthly. Costs were documented. Results and limitations A total of 3916 study days with nitrite testing and irrigation were analyzed, 1876 (48%) in the NaCl arm and 2040 (52%) in the H2 O arm. In the NaCl arm, 418 study days (22%) with nitrite-positive dipsticks were recorded, 219 d (11%) in the H2 O arm, significantly fewer ( p = 0.01). Of the 149 UCs, 96 (64%) were positive, 48 in each arm, revealing a total of 16 different germs. All patients preferred the H2 O method. Monthly costs were up to 20 times lower in the H2 O arm. Conclusions Pouch irrigation with sterile NaCl 0.9% solution and tap water had comparable rates of positive UC. Irrigation with tap water significantly lowered the incidence of nitrite-positive study days and was substantially less costly and more patient friendly than NaCl irrigation. We therefore recommend the use of tap water (or bottled water) instead of sterile NaCl 0.9% solution for daily irrigation of continent catheterizable ileal pouches. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12610000618055, http://www.ANZCTR.org.au/ACTRN12610000618055.aspx.
To analyze the outcomes of patients with metastatic renal cell carcinoma treated with salvage-targeted therapy after progressing on high-dose interleukin (IL)-2 immunotherapy in a tertiary referral ...center.
A retrospective nonrandomized cohort consisting of 286 patients with metastatic renal cell carcinoma treated from 2003 to 2010 was analyzed from the University of California, Los Angeles (UCLA) Kidney Cancer database. All patients underwent cytoreductive nephrectomy, and 21 patients received salvage-targeted therapy after progression on high-dose IL-2, whereas 111 patients received targeted therapy alone. The remaining 154 patients had other treatment combinations or experimental targeted therapy agents only. Since 2003, selection of patients for high-dose IL-2 was increasingly based on clinical, pathologic, and molecular criteria (UCLA CPM criteria). Disease-specific survival was calculated from diagnosis of metastatic renal cell carcinoma.
Patients selected according to UCLA CPM criteria and treated with salvage-targeted therapy after progressing on high-dose IL-2 experienced a significantly greater disease-specific survival (median not reached) than those treated with targeted therapy alone (30 months; P = 0.004). Since 2006, all high-dose IL-2 patients met the UCLA CPM criteria and were able to receive salvage-targeted therapy upon progression. Disease-specific survival calculated from initiation of targeted therapy was comparable for patients treated with salvage-targeted therapy after progression on high-dose IL-2 (34 months) versus first-line targeted therapy (26 months; P = 0.175).
Patients selected for high-dose IL-2 based on UCLA CPM criteria and treated with salvage-targeted therapy upon progression have achieved outstanding disease-specific survival. Our data suggest a new algorithm for carefully selected patients with metastatic renal cell carcinoma based on UCLA CPM criteria to receive first-line high-dose IL-2 while reserving their option for salvage-targeted therapy with uncompromised efficacy upon progression.
Postoperative readmission rates following radical cystectomy remain significant. Early identification of emerging complications could potentially allow for immediate institution of therapy.
To ...intensify postoperative patient-physician communication via a cellphone-based health care application (CHA) and to evaluate its potential for early detection of complications.
This was a pilot study involving 18 radical cystectomy patients. During the first 30 d, patients received a push cellphone notification twice a week requesting data input into the CHA. This was reduced to once a week from day 31 to day 90. De-identified recorded data were reviewed by the surgeon involved. If deemed necessary, patients were contacted by the surgeon via telephone to obtain more detailed clinical information.
Descriptive statistics were used.
Of the 18 patients enrolled, all completed the 90-d reporting period. On two occasions, interventions were necessary on the basis of data recorded on the CHA. One neobladder patient was given antibiotic therapy for pyelonephritis. Another patient reported weight loss and nausea with clinical suspicion of metabolic acidosis, and his sodium bicarbonate and fluid intake were increased. Limitations include the small number of cases from a single low-volume center.
CHA-based monitoring of clinical parameters within the crucial 90-d postoperative period following radical cystectomy provides meaningful information. In this pilot study, two potential readmissions were possibly avoided on the basis of recorded basic vital signs and early intervention.
Besides regular clinic follow-up visits after radical cystectomy, additional aids such as a cellphone-based health care application can provide treating physicians with relevant clinical information and may help to identify imminent deviations from normal postoperative recovery at an early stage.
Besides regular clinical follow-up after radical cystectomy, an additional aid such as a health care app can provide relevant clinical information and may help in identifying imminent deviations from the normal postoperative course at an early stage.
Abstract A 52-yr-old man presented with hematuria and clot retention. He had undergone simultaneous pancreas–kidney transplantation with exocrine pancreas bladder drainage 16 yr ago. The patient ...suffered from progressive transplant kidney failure with gradually decreasing urine output and needed hemodialysis every other day. Gross hematuria persisted after removal of all blood clots. Cystoscopy showed multiple small, flat ulcers of the bladder mucosa. Some bled discretely and were coagulated cautiously. However, hematuria was refractory to multiple urological interventions, which eventually necessitated an enteric diversion of the exocrine pancreas. Hematuria ceased following an uneventful postoperative course.
What's known on the subject? and What does the study add?
The
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ndo
S
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prototype was first tested in a porcine model several years ago. The investigators found it both simple to master and ...reliable, its greatest advantage being a 2.4‐fold time saving compared with straight laparoscopic suturing. In addition to that publication, there is a single case report describing the performance of an open EndoSew
®
suture to close parts (16 cm) of an ileal neobladder. The time for suturing the 16 cm ileum was 25 min, which is in line with our experience. The knowledge on this subject is limited to these two publications.
We report on the first consecutive series of ileal conduits performed in humans using the novel prototype sewing device
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ndo
S
ew
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. The study shows that the beginning and the end of the suture process represent the critical procedural steps. It also shows that, overall, the prototype sewing machine has the potential to facilitate the intracorporeal suturing required in reconstructive urology for construction of urinary diversions.
Objective
To evaluate the feasibility and safety of the novel prototype sewing device
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in placing an extracorporeal resorbable running suture for ileal conduits.
Patients and Methods
We conducted a prospective single‐centre pilot study of 10 consecutive patients undergoing ileal conduit, in whom the proximal end of the ileal conduit was closed extracorporeally using an
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running suture.
The primary endpoint was the safety of the device and the feasibility of the sewing procedure which was defined as a complete watertight running suture line accomplished by EndoSew
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only
.
Watertightness was assessed using methylene blue intraoperatively and by loopography on postoperative days 7 and 14.
Secondary endpoints were the time requirements and complications ≤30 days after surgery.
Results
A complete EndoSew
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running suture was feasible in nine patients; the suture had to be abandoned in one patient because of mechanical failure.
In three patients, two additional single freehand stitches were needed to anchor the thread and to seal tiny leaks. Consequently, all suture lines in 6/10 patients were watertight with EndoSew
®
suturing alone and in 10/10 patients after additional freehand stitches.
The median (range) sewing time was 5.5 (3–10) min and the median (range) suture length was 4.5 (2–5.5) cm.
There were no suture‐related complications.
Conclusions
The EndoSew
®
procedure is both feasible and safe.
After additional freehand stitches in four patients all sutures were watertight.
With further technical refinements,
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ndo
S
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has the potential to facilitate the intracorporeal construction of urinary diversions.
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